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Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
1
2.1. Introduction
The ever-increasing demand for novel biologically-active compounds and the laborious
process of lead discovery and optimization have resulted in the continuous search for
simple and efficient methods for generating libraries for biological screening. Last
decades have witnessed increasing effort for developing new antifungal drugs that are
capable to inhibit various diseases related to Candida albicans species, considered to be
responsible for the most common type of human pathogenic fungi. Fungal infections are
reported to cause a lot of morbidity and mortality despite recent advances in antifungal
chemotherapeutic regimen.1 This is due to greater use of immunosuppressive drugs,
prolonged use of broad-spectrum of antibiotics for various conditions including cancer
patients and organ transplants.
2.2. Antifungal agents
Fungi are insidious pathogens because they are eukaryotic microorganisms: they are
more closely related to human cells, and are thus more difficult to target with antifungal
chemotherapy. Fungal infections (mycoses) can further be divided into superficial and
systemic types. The first group includes cosmetically unpleasant but less serious
infections of the skin, nails and hair shafts caused by dermatophytes or yeast. On the
other hand, systemic infections such as torulosis and aspergillosis are potentially fatal,
and are a growing danger for human health.2,3
They occur more frequently in individuals
with compromised immune system (AIDS patients, transplant patients, cancer patients).
The most common pathogenic agents that cause invasive fungal infections are Candida
and Aspergillus.4,5
It is, therefore, imperative to diagnose these infections at an early
stage and treat them effectively. The drugs derived from natural sources or prepared
synthetically are available for treating the fungal infections; however none of these drugs
is ideal. For many years, the only available antifungal was amphotericin B 16 or its
combination with nystatin 2,7 which are considered to be the drugs of choice at present
and remain effective therapeutic agent in severe conditions of invasive mycosis but have
been found to be highly toxic and immunosuppressive.8 ,9
The non-availability of an
absorbable oral form of amphotericin B for long maintenance therapy in
immunocompromised patients is another important drawback of this drug.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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Amphotericin B (1)
Nystatin (2)
Antifungal are those agents that destroy the growth of pathogenic fungi and are used as a
medication to treat fungal infections such as athlete’s foot, ringworm, candidiasis
(thrush), serious systemic infections such as cryptococcal meningitis and others.
Antifungal drugs target ergosterol (3) or the steps in its synthesis (Table 1, Figure 1).
Ergosterol (3), the functional fungal analogue of cholesterol in animal cells, is found in
the fungal cell membrane, where it has essential roles in the modulation of membrane
fluidity and as a signal for cell division. Because ergosterol has different chemical
properties from cholesterol, it has been exploited as a target for antifungal drugs, which
are incorporated into fungal cell membranes containing ergosterol, but are less readily
incorporated into host cell membranes, which contain cholesterol (4). In addition to
ergosterol itself, there are several enzymatic steps that are unique to ergosterol synthesis
and are also the targets for antifungal drugs; however, apart from ergosterol and its
biosynthesis, there are few other targets that can be exploited in antifungal therapy.10
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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Ergosterol (3) Cholesterol (4)
Figure 1: Sterol molecules present in mammalian and fungal cell membranes
Table 1: Antifungal agents: activities, mode of action and resistance mechanism
Antifungal agents
(Figure 2)
Spectrum of
activity
Mode of action Resistance
mechanism
Polyenes
Amphotericin B (1) Broad activity
against Candida spp.,
except C. lusitaniae;
Cryptococcus
neoformans and
filamentous fungi,
exceptA. terreus and
A. flavus.
Binding to
ergosterol and
destabilization of
cell membrane
functions
Alteration in
specific steps of
ergosterol
biosynthesis
Pyrimidine analogues
5-Fluorocytosine
(5)
Active against
Candida spp. and
Cryptococcus spp.;
however, rapid
emergence of
resistance can
appear when 5-FC
is used as
monotherapy
Impairment of
nucleic acid
biosynthesis by
formation of toxic
fluorinated
pyrimidine
antimetabolites
Decreased uptake of
5-FC; decreased
formation of toxic
antimetabolites.
Azoles
Fluconazole (6) Active against
Candida spp. and
Cryptococcus spp.;
less active against
Inhibition of
cytochrome P450
14α-lanosterol
demethylase
Enhanced efflux by
upregulation of
multidrug.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
4
C. glabrata and no
activity against C.
krusei; no activity
against filamentous
fungi
Itraconazole (7) Like fluconazole,
but enhanced
activity against
filamentous fungi
Inhibition of
cytochrome P450
14α-lanosterol
demethylase
Target alterations by
occurrence of
mutations
Voriconazole (8) Like fluconazole,
but enhanced
activity against
filamentous fungi,
including
Aspergillus and
Fusarium spp.
- Alteration of
specific steps in the
ergosterol
biosynthesis
pathway
Posaconazole (9) Closely related to
itraconazole, but
more active
- -
Allylamines
Terbinafine (10) Active against most
dermatophytes,
poor activity against
Candida spp.
Inhibition of
squalene epoxidase
Unknown
Morpholines
Amorolfine (11) Active against most
dermatophytes,
poor activity against
Candida spp.
Inhibition of sterol
∆14
reductase and
∆7,8
isomerase
Unknown
Echinocandins
Anidulafungin (12) Active against
Candida spp. With
fungicidal activity,
moderately active
against Aspergillus
spp., poor activity
against C.
neoformans
Inhibition of the cell
wall synthesis
enzymeβ-1,3 glucan
synthase
Unknown
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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Figure 2
2.3. Biological properties of 1,2,3-triazoles
Triazole derivatives are known to exhibit various pharmacological properties such as
anti-microbial,11
anti-tubercular,12
anti-cancer,13
anti-convulsant,14
anti-inflammatory,
analgesic15
and anti-viral.16
Triazoles have also been incorporated in a wide variety of
therapeutically interesting drugs including H1/H2 histamine receptor blockers, CNS
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
6
stimulants, anti-anxiety agents and sedatives.17
Potential pharmaceuticals based on 1,2,3-
triazoles include the anticancer compound carboxyamidotriazole (CAI) (13), the
nucleoside derivative non-nucloside reverse transcriptase inhibitor tert-
butyldimethylsilylspiroaminooxathioledioxide known as TSAO (14), β-lactum antibiotic
Tazobactum (15) and the cephalosporine Cefatrizine (16) (Figure 3).Structure activity
relationships have revealed that bioisosteric replacement of a triazole ring leads to
antifungal activity with a higher selectivity of the fungal targets. Triazole antifungal
drugs are used in the treatment of both superficial and deepseated candidiasis.18
Figure 3: Potential pharmaceuticals based on 1,2,3-triazoles.
A series of triazole-containing novobiocin analogues (17) were designed, synthesized,
and their biological activity was determined by Peterson and co-workers.19
The anti-
proliferative effects of these compounds were evaluated against two breast-cancer cell
lines (SKBr-3 and MCF-7) and displayed IC50 values above 50 μm. In this case, triazole
moiety affects biological activity in two ways: the availability of a hydrogen-bond donor
in the amide linkage and the steric bulk of the side chain. HIV-1 protease (HIV-1-Pr) has
been recognized as an important target for inhibition of viral replication. A library of 1,4-
disubstituted-1,2,3-triazoles (18) was synthesized by Whiting et al.20
These compounds
exhibited high binding efficiency to human immunodeficiency virus type-1 protease
(HIV-1-Pr). 1,2,3-Triazole-containing compounds such as 19, has been reported
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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aspotential dual-action HIV-1 protease and non-nucleoside reverse transcriptase
inhibitors.21
Two series of 1,2,3-triazole compounds with anti-mycobacterium profile
were reported by Costa et al.22
The in vitro anti-tubercular activity screening of these
series showed that the triazole-4-carbaldehyde derivatives (20A) were more effective
than the 4-difluoromethyl derivatives (20B). 1-(2,3-Dihydrobenzofuran-2-yl-methyl-
1,2,3-triazoles (21)23
showed antitubercular activity against Mycobacterium tuberculosis
H37Rv with minimum inhibitory concentration (MIC) values ranging from 12.5 to 3.12
μgmL-1
. Novel H37Rv strain inhibitors with fluorine and 1,2,3-triazole containing
benzimidazoles (22) for the treatment of tuberculosis were disclosed by Gill et al24
(Figure 4).
Figure 4
2.3.1. As Antifungal and Antibacterial Agents
Vatmurge et al.25
have reported the synthesis of novel 1,2,3-triazole-linked with β-
lactam–bile acid conjugates (23, Figure 5) which inhibit significant antifungal activity
against different fungal strains such as Candida albicans, Cryptococcusneoformans,
Benjaminiella poitrasii, Yarrowia lipolytica and Fusarium oxysporum. The triazole
derivatives 24 and 25 showed the best antifungal activity against Candida albicans.26
The
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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fluconazole-based novel mimics 2627
and 27 that contained 1,2,3-triazole were found to
be more potent against Candida fungal pathogens than control drugs fluconazole and
amphotericin B with MIC values ranging from 3.12 to 6.25 mg ml-1
. These molecules
were evaluated in vitro against Candida albicans intravenous challenge in Swiss mice,
and antiproliferative activities were tested against human hepatocellular carcinoma
Hep3B cells and human epithelial carcinoma A431 cells. It was found that a compound
with a long alkyl chain resulted in 97.4% reduction in fungal load in mice and did not
show any profound proliferative effect at lower dosage (0.001 mg mL-1
). Triazole
glycosides (28) detected in subsequent bioassays showed promising antifungal activity.28
Figure 5
2.4. Coumarin(Benzopyran-2-one)
Coumarins are phenolic substances made of fused benzene and α-pyrone rings.
Benzopyran-2-ones (coumarins) form an elite class of compounds, which occupy a
special role in nature. Coumarins and their derivatives have been found to exhibit a
variety of biological and pharmacological activities and have raised considerable interest
because of their potential beneficial effects on human health. They have been reported to
possess among others: anti-HIV, anti-coagulant, anti-bacterial, anti-cancer, anti-
inflammatory and anti-oxidant activities. Among all these activities, anti-fungal activity
is of particular interest.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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2.4.1. Coumarin as antifungal
Coumarins are known potential growth inhibitors of bacteria and fungi, where both
natural and synthetic coumarins inhibit growth of common microorganisms Candida
albicans, Escherichia coli and Staphylococcus aureus. Plant coumarins also bear
antimicrobial potential and have been reported to stimulate macrophages which could
have an indirect negative effect on infections. Hydroxycoumarin scopoletin 29 was
isolated from seed kernels of Melia azedarach29
reported to be antifungal against
Fusarium verticillioides. Deng and Nicholson30
reported the antifungal properties of
surangin B 30, a coumarin from Mammea longifolia. Phytoalexins, which are
hydroxylated derivatives of coumarins, are produced in carrots in response to fungal
infection and can be presumed to have antifungal activity31
. A coumarin namely, 6,7-
dimethoxycoumarin 31, isolated from P. digitatum-infected Valencia fruit confers
resistance against the mycotoxigenic fungi A. parasiticus32
. Clausenidin 32, dentatin, nor-
dentatin, and carbazole alkaloid clauszoline J 33 isolated from Clausena excavata
showed antimycotic activity (MIC 50 μg/mL). Angelicin, 34 a naturally occurring
furanocoumarin, which showed antifungal activity, was considered as a lead structure for
a group of synthetic coumarins.33
In many of the synthesized coumarins and angular
furanocoumarins, the free 6-OH was found to be important for antifungal activity.In a
series of 6,7,8 tri-substituted coumarin derivatives compound 35 has the strongest and
broadest spectrum of activity. This compound is also the only one in this group with a
free 6-OH, which probably contributes to its potency. Substitution of an alkyl group at C-
8 position of 35 results in the increase of antifungal properties compared to 36 (Figure
6). Prenylated coumarin isolated from leaf extract of Baccharis pedunculata have been
identified as active against some human pathogenic fungi.34
Some synthetic coumarin
derivatives have also been reported to be active against the yeast C. albicans.35
Herniarin
(7-methoxycoumrin) has shown activity against Aspergillus glaucus and Aspergillus
flavus.36
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
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Figure 6
2.5. Past work on Synthesis of Coumarin-triazole derivatives
The electron-donating properties of the triazole ring formed in the azide-alkyne ligation
reaction can be effectively utilized for the design of a chemoselective fluorogenic probe
that may find a range of applications in biology, analytical chemistry, or material science.
Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction was applied for linking azide
unit 38 to coumarin derivative with terminal alkyne functionality 37 to synthesize a new
fluorescent probe 39, that takes advantage of the electronic structure changes associated
with the triazole ring (Scheme 1).37
Scheme 1
Several of the coumarin-based fluorophore showed substantial increase in brightness
upon triazole formation, and could prove useful as biological probes. Key et al.38
have
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
11
reported the triazole-substituted coumarin fluorophores 43 and 47 through CuAAC
reaction of coumarinyl alkyne (42, 46) and benzylazide. They also evaluated changes in
the photo-physical properties upon conversion from alkyne to triazole forms. Ethynyl-
coumarin structures showed increases in quantum yield (ca. 1.2 to 9 fold) and
bathochromic shifts (up to 23 nm) after triazole formation. Substitution of coumarin
fluorophores with azide or alkyne groups is known to induce changes in fluorescence
properties. Conjugation of an electron-donating triazole ring to the coumarin backbone at
one of the 3- or 7- positions causes an increase in quantum yield and a bathochromic shift
in emission relative to the starting alkyne.
Scheme 2
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
12
Majumdar and Mandal39
have reported 1,2,3-triazolyl coumarin and quinolone
derivatives 50 through click reaction of coumarinyl on quinolone azide (48) with p-
substituted alkyne 49 by using CuI in DMSO (Scheme 3) and studied their fluorescence
properties. Coumarin and quinolone derivatives show good photo physical effects and
have a stable fluorescence property. Interestingly compounds 48 showed no fluorescence
property due to the quenching effect from electron-rich α- nitrogen of the azide group and
the compounds 50 exhibited high fluorescence due to elimination of the quenching
through the formation of the triazole ring.
Scheme 3
New fluorescent coumarin dyes were reported by Sivakumar et. al.40
Compound 54 was
synthesized with an azido group attached to the 3-position and then with catalytic
amount of Cu(I), the azide 54 reacted smoothly with phenylacetylene in a mixed solution
of ethanol and water (1:1) to afford cycloaddition products 55 at room temperature in
quantitative yield (Scheme 4). The fluorescent signals are triggered by the formation of
triazole ring, which has the potential to be used as probes for imaging or as reporters to
monitor the ligation efficiency. Compound 55 show fluorescence at 478 nm due to the
elimination of the quenching through the formation of the triazole ring. The quantum
yield of 55 is 0.30 in comparison to 0.0 of the starting materials 54.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
13
Scheme 4
Gullapalli Kumaraswamy41
developed a novel and practical procedure for the synthesis
of small molecules possessing α-hydroxy or N-tosylamino 1,2,3-triazole motif 57a-e by
azidation of epoxides 56a-e or N-tosylaziridines with sodium azide followed by “click
reaction” using PEG-400 as a reaction medium in the presence of 5 mol % of CuI
(Scheme 5).
Scheme 5
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
14
2.6. Present Work
Harmful infections caused by various fungal species, such as Aspergillus and Candida,
have been increasing throughout the world.42
Due to the increase in the number of
immune-compromised patients, such as cancer and HIV patients, primary and
opportunistic fungal infections are also mounting rapidly. Furthermore, resistance to the
existing antifungal agents is a growing problem. Almost all major classes of commercial
antibiotics have encountered resistance in clinical applications, even though the
pharmaceutical industry has produced a number of new antibiotics.43
Therefore, the need
for novel therapeutic agents with potency, a wide therapeutic window, and broad-
spectrum activity is critical.
The first generation of azoles antifungal inhibitors of CYP51, have revolutionized
treatment of some serious fungal infections. Triazoles have been the leading agents for
the control of fungal diseases of humans and animals for over last 20 years.44
According
to this, azole derivatives are currently the most widely studied class of antifungal agents.
The 1,2,3-triazole scaffold is very important in the field of medicinal chemistry and has
received much attention in the last few decades due to its chemotherapeutic value.45
1,2,3-Triazole and its derivatives are known to be potent anti-malarial,46
anticonvulsant,47
anti-bacterial,48
anti-fungal49
and anti-HIV agents.50
1,2,3-Triazole derivatives as GABA
receptor antagonists and potassium channel activators have also been demonstrated.51
Therefore, an investigation of the antimicrobial activity of another 1,2,3-triazole
derivative and an explanation of the structure-activity relationships for searching
clinically more valuable compounds would be worthwhile.
Coumarins (Benzopyran-2-ones) form an elite class of compounds, which occupy a
special role in nature and have been known both from synthetic and natural sources. It
was found to be crucial for a variety of pharmacological effects such as inhibition of
platelet aggregation52
, anti-inflammatory53
, anti-convulsant54
, anti-viral55
, anti-HIV56
,
anti-coagulant57
, anti-oxidant58
, anti-bacterial59
, anti-tubercular60
, anti-carcinogenic61
and
anti-fungal.62
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
15
Discovery of efficient, scalable, ecological as well as economical synthesis for the
production of a library of clinical candidates is gaining importance. Copper (I) catalyzed
1,3-dipolar addition of azides to alkyne is one such chemical process which has placed
itself in a class of its own and has enabled many novel applications because of its
robustness.63
Using this clickable method for the synthesis of hybrid drugs is a promising
idea.
Therefore, in continuation of our longstanding interest in synthesis of new coumarin as
well as triazole derivatives, we have been prompted to synthesize new and possibly more
potential pharmacologically active compounds.The potential of triazole containing
coumarin derivatives as antifungal agents have not been studied yet. Therefore, the
current study was undertaken to synthesize a new series of triazolyl derivatives
containing a coumarin backbone with diversity at the 3- and 7- positions via. Huisgen
1,3-dipolar cycloaddition reaction. These compounds contain different alkyl chain at the
C-3 position of the coumarin ring and different aryl ethers at the C-4 position of
1,2,3,triazole ring. The antifungal potential of the synthesized compounds has been
investigated using Aspergillis as model pathogens.
A new series of 1,2,3-triazole substituted 3-alkyl-7-hydroxy-4-
methylcoumarinderivativeshave been synthesized via Cu(I)-catalyzed click chemistry on
7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarin with alkynes. The
synthesis of desired product was achieved starting from C-3 alkyl coumarins 62 and 63
which were synthesized via Pechman condensation of ethyl 2-ethylacetoacetate 60a and
ethyl 2-hexyl acetoacetate 60b with resorcinol (61) in 78 to 80 % yields (Scheme 7). The
2-ethyl/hexyl ethylacetoacetate in turn were prepared from ethyl acetoacetate (58) using
alkyl bromide 59a and 59b in THF in the presence of sodium hydride in 50 to 53 % yield,
respectively (Scheme 6). The C-3 alkyl substituted coumarins were condensed with
epichlorohydrin using 0.6 M NaOH solution in methanol to yield the corresponding
epoxides, 64 and 65 in 70 % yields. Further, the opening of the epoxy ring in compounds
64 and 65 using sodium azide in the presence of ammonium chloride in a methanol:water
(4:1) solution afforded 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarins 66
and 67 in 85 and 90 % yields (Scheme 7).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
16
Scheme 6: Alkylation of ethyl acetoacetate
Scheme 7: Synthesis of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-
methylcoumarins
Traditionally, the triazole forming 1,3-dipolar cycloaddition between azide and alkyne is
performed at high temperature & long duration that usually results in a mixture of two
isomers 1,4-disubstituted and 1,5-disubstituted 1,2,3-triazoles.64
Huisgen-Sharpless 1,3-
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
17
dipolar cycloaddition to form regioselectively 1, 4-disubstituted 1,2,3-triazole bridges is a
very popular and useful reaction for the bioconjugation.65
The reaction is regioselective
only in the presence of Cu (I) salts as a catalyst, because Cu (I) as a catalyst strongly
activated the terminal acetylenes towards 1,3-dipole in azide, to give the desired 1, 4-
disubstituted 1,2,3-triazole.
In the literature, Cu (I) catalysed cycloaddition was studied with various concentration of
CuSO4 in the presence of sodium ascorbate. And the reaction temperature along with
nature of solvent also influenced the CuAAC reaction. Using 0.05 molar equiv of CuSO4
in preliminary experiments, we observed the incomplete reaction. The reaction at 25-30
°C resulted in longer reaction time and moderate yields, while performing the reaction at
50 °C resulted in shorter reaction time and good yields. Hence, 50 °C was the optimum
temperature for the reaction. The yields of the desired 1,4-disubstituted 1,2,3-triazoles
were generally not significantly affected by the steric and electronic properties of the
groups attached to the alkynes reactive centers. So the best results were obtained by using
0.15 molar equiv. of CuSO4.5H2O in t-BuOH:H2O:THF in (1:1:1) ratio compared to t-
BuOH:H2O.
Thus, the Cu (I)-catalyzed process allowed the 1,3-dipolar cycloaddition of 7-(3-azido-2-
hydroxypropyloxy)-3-ethyl-hexyl-4-methylcoumarins 66/67 with commercially available
alkynes i. e. phenyl acetylene (68a), pent-4-ynioc acid (68b), 5-Chloro-1-pentyne (68c)
and propargyl alcohol (68e) in the presence of catalytic amount of copper sulphate and
sodium ascorbate in t-BuOH/H2O/THF (1:1:1) at 50 °C to afford 7-(3-(4-phenyl/alkyl-
1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarins 69a-d and
70a-d in 80 to 92 % yield (Schemes 8).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
18
Scheme 8: Synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-triazol-1-yl)propyloxy)-3-
ethyl-hexyl-4-methylcoumarins
Similarly, 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarins 66 and 67
were condensed with propargyl aryl ethers 72a-u in the presence of catalytic amount of
copper sulphate and sodium ascorbate in t-BuOH/H2O/THF (1:1:1) at 50 °C to afford
triazole containing coumarins 73a-u and 74a-u in 90 to 95 % yields (Schemes 9).
Propargyl aryl ethers 72a-u were prepared in excellent yield by heating substituted
phenols 71a-u with propargyl bromide and K2CO3 in acetone at 60 °C for 12 hr (Scheme
9).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
19
Scheme 9: Synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-triazol-1-yl)propyloxy)-3-
ethyl/hexyl-4-methylcoumarins.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
20
Thus, a series of fifty triazole containing coumarins 69a-d, 70a-d, 73a-u and 74a-u have
been synthesized together with the coumarin precursors 62, 63, 64, 65, 66 and 67. The
antifungal activity of fifty-two compounds, i. e. coumarins 66, 67, 69a-d, 70a-d, 73 a-u
and 74 a-u were evaluated against A. fumigatus, A. niger and A. flavus. The structures of
synthesized coumarin derivatives 62, 63, 64, 65, 66, 67, 69a-d, 70a-d, 73a-u and 74a-u
were unambiguously established by analysis of their spectral data (1H NMR,
13C NMR,
IR, HRMS spectra).Copies of the 1H- and
13C NMR spectrum of selected compounds are
given in the Results and Discussion section.
2.7. Results and Discussion
2.7.1 7-(3-Azido-2-hydroxypropyloxy)-3-ethyl-4-methycoumarin (66)
Compound 66 was synthesized by epoxide ring opening of
7-(2,3-epoxypropyloxy)-3-ethyl-4-methylcoumarin 64 with
sodium azide and ammonium chloride in methanol:water
solution at 70 oC and obtained as a white solid in 90 %
yield (Scheme 7). Its high resolution mass spectrum showed [M+Na]+
peak at m/z
326.1099 which confirmed its molecular formula to be C15H17N3O4. The absorption in the
IR spectrum at 2113 cm-1
was assigned to azide group present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH & -OCH2 protons in its 1H NMR
spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.66 (2H, q, J = 7.3 Hz), 3.52-3.61 (2H,
m) and 4.07-4.27 (3H, m), respectively (Figure7). Similarly, in its 13
C NMR spectrum,
the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N3, -OCH2, -CH and CO appeared at
δ 13.03, 20.74, 53.27, 68.96, 69.36 and 161.94, respectively (Figure8). The peaks of all
other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin (66).
2.7.2. 7-(3-Azido-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
21
Compound 67 was synthesized by epoxy ring opening
of 7-(2,3-epoxypropyloxy)-3-hexyl-4-methylcoumarin
65 with sodium azide and ammonium chloride in
methanol:water solution at 70 oC and obtained as a
white solid in 85 % yield (Scheme 7). Its high resolution mass spectrum showed [M+H]+
peak at m/z 360.1900 which confirmed its molecular formula to be C19H25N3O4. The
absorption in the IR spectrum at 2111 cm-1
was assigned to azide group present in the
molecule. The characteristic peak of -(CH2)5CH3, -CH2CH2(CH2)3CH3, -
CH2CH2(CH2)3CH3, -CH2(CH2)4CH3, -CH2N, -CH & -OCH2 protons in its 1H NMR
spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 1.30-1.40 (6H, m), 1.47-1.53 (2H, m),
2.63 (2H, t, J = 7.3 Hz) and 4.06-4.23 (3H, m), respectively (Figure9). Similarly, in its
13C NMR spectrum, the characteristic peaks for -(CH2)5CH3, -CH2(CH2)3CH2CH3, -
CH2CH2(CH2)2CH3, -(CH2)2CH2(CH2)2CH3, -(CH2)3CH2CH2CH3,-CH2N3, -OCH2, -CH
and CO appeared at δ 14.03, 22.57, 27.47, 29.31, 31.63, 53.26, 68.97, 69.35 and 162.07,
respectively (Figure 10). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13CNMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 7-(3-azido-2-
hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67).
2.7.3. 3-Ethyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (69a)
Compound 69a was synthesized by click reaction of 7-(3-
azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin 66
and phenyl acetylene 68a in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbateand copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85
% yield (Scheme 8). Its high resolution mass spectrum showed [M+H]+peak at m/z
406.1751 which confirmed its molecular formula to be C23H23N3O4. The absorption in the
IR spectrum at 3386 and 1708 cm-1
were assigned to OH and CO groups present in the
molecule. The characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
22
and triazole H protons in its 1H NMRspectrum appeared at δ 1.04 (3H, t, J = 7.3 Hz),
2.57 (2H, q, J = 7.3 Hz), 4.08-4.16 (2H, m), 4.31-4.35 (1H, m), 4.48 (1H, dd, J = 10.3 Hz
& J = 7.3 Hz), 4.68 (1H, dd, J = 13.9 Hz & J = 3.7 Hz) and 8.57 (1H, s), respectively
(Figure 11). Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3,-
CH2CH3, -CH2N, -CH, -OCH2, and CO appeared at δ 12.97, 20.21, 52.71, 67.69, 70.09
and 160.75, respectively (Figure 12). The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13CNMR spectra of the compound. Based on the
spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-
hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin(69a).
Figure 7:1H NMR spectrum of compound 66 (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
23
Figure 8:13
C NMR spectrum of compound 66 (100.6 MHz, CDCl3)
Figure 9:1H NMR spectrum of compound 67 (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
24
Figure 10:13
C NMR spectrum of compound 67 (100.6 MHz, CDCl3)
Figure 11:1H NMR spectrum of compound 69a (400 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
25
Figure 12:13
C NMR spectrum of compound 69a (100.6 MHz, DMSO)
2.7.4. 3-Ethyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-
methylcoumarin(69b)
Compound 69b was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin 66 and pent-4-ynoic acid 68b in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium ascorbate
and copper (II) sulfate pentahydrate at 60 oC and
obtained as white solid in 80 % yield (Scheme 8). Its high resolution mass spectrum
showed [M+H]+
peak at m/z 402.1656 which confirmed its molecular formula to be
C20H23N3O6. The absorption in the IR spectrum at 3461 and 1704 cm-1
were assigned to
OH and CO groups present in the molecule. The characteristic peak of -CH2CH3, -
CH2CH3 and -CH2CH2COOH, -CH2CH2COOH, -CH2N, -CH, -OCHα, -OCHβ and triazole
H protons in its 1H NMR spectrum appeared at δ 1.05 (3H, t, J = 7.7 Hz), 2.53-2.60 (4H,
m), 2.85 (2H, t, J = 7.3 Hz), 4.01-4.08 (2H, m), 4.20-4.26 (1H, m), 4.39 (1H, dd, J = 13.9
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
26
& 7.3 Hz), 4.55 (1H, dd, J = 13.9 & 3.6 Hz) and 7.85 (1H, s), respectively (Figure 13).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -
CH2CH2COOH, -CH2CH2COOH, -CH2N, -CH, -OCH2, CO and COOH appeared at δ
12.89, 20.15, 20.60, 33.09, 52.28, 67.65, 70.00, 160.69 and 173.58, respectively (Figure
14). The peaks of all other protons and carbons of the molecule were also present in the
1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-propanoicacid)-
1,2,3-triazol-4-yl)propyoxl)-4-methylcoumarin (69b).
2.7.5. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin (69c)
Compound 69c was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin 66 and 5-Chloro-1-pentyne 68c in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60
oC and obtained as a white solid in 88 % yield (Scheme 8). Its high resolution mass
spectrum showed [M+H]+
peak at m/z 406.1521 which confirmed its molecular formula
to be C20H24ClN3O4. The absorption in the IR spectrum at 3398 and 1713cm-1
were
assigned to OH and CO groups present in the molecule. The characteristic peak of -
CH2CH3, -CH2CH2CH2Cl, -CH2CH3, -CH2CH2CH2Cl, -CH2CH2CH2Cl, -CH2N, -CH, -
OCHα, -OCHβ and triazole H protons in its 1H NMR spectrum appeared at δ 1.05 (3H, t, J
= 7.3 Hz), 2.04 (2H, pentate), 2.56 (2H, q, J = 7.3 Hz), 2.75 (2H, t, J = 7.7 Hz), 3.67 (2H,
t, J = 6.9 Hz), 4.01-4.07 (2H, m), 4.20-4.26 (1H, m), 4.41 (1H, dd, J = 13.9 & 7.4 Hz),
4.56 (1H, dd, J = 13.9 & 3.6 Hz) and 7.89 (1H, s), respectively (Figure 15). Similarly, in
its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2CH2CH2Cl,
-CH2CH2CH2Cl, -CH2CH2CH2Cl, -CH2N, -CH,-OCH2, and CO appeared at δ 12.96,
20.20, 22.12, 31.79, 44.68, 52.34, 67.68, 70.07 and 160.72, respectively (Figure 16). The
peaks of all other protons and carbons of the molecule were also present in the 1H and
13C
NMR spectra of the compound. Based on the spectral data analysis, the structure of the
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
27
compound was established as 7-(3-(4-(3-chloropropyl)-1,2,3-triazol-1-yl)-2-
hydroxypropyloxy)-3-ethyl-4-methylcoumarin (69c).
2.7.6. 3-Ethyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (69d)
Compound 69d was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin 66 and propargyl alcohol 68d in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC
and obtained as a white solid in 87 % yield (Scheme 8). Its high resolution mass
spectrum showed [M+Na]+
peak at m/z 382.1365 which confirmed its molecular formula
to be C18H21N3O5. The absorption in the IR spectrum at 3305 and 1676 cm-1
were
assigned to OH and CO groups present in the molecule. The characteristic peak of -
CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -CH2OH, -OCHβ and triazole H protons in its
1H NMR spectrum appeared at δ 0.96 (3H, t, J = 7.3 Hz), 2.47 (2H, q, J = 7.3 Hz), 3.92-
3.99 (2H, m), 4.13-4.20 (1H, m), 4.36 (1H, dd, J = 13.9 & 8.1 Hz), 4.43 (2H, d, J = 5.1
Hz), 4.49 (1H, dd, J = 13.9 & 3.7 Hz) and 7.86 (1H, s),respectively (Figure 17).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -
CH2N, -CH, -OCH2, and CO appeared at δ 12.99, 20.24, 52.33, 67.75, 70.09 and 160.79,
respectively (Figure 18). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (69d).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
28
Figure 13:1H NMR spectrum of compound 69b (400 MHz, DMSO)
Figure 14:13
C NMR of compound 69b (100.6 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
29
Figure 15:1H NMR spectrum of compound 69c (400 MHz, DMSO)
Figure 16:13
C NMR spectrum of compound 69c (100.6 MHz,DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
30
Figure 17:1H NMR spectrum of compound 69d (400 MHz,DMSO)
Figure 18:13
C NMR spectrum of compound 69d (100.6 MHz,DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
31
2.7.7. 3-Hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (70a)
Compound 70a was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and phenylacetylene 68a in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60
oC and obtained as a white solid in 81 % yield (Scheme 8). Its high resolution mass
spectrum showed [M+H]+
peak at m/z 462.2381 which confirmed its molecular formula
to be C27H31N3O4. The absorption in the IR spectrum at 3386 and 1708 cm-1
were
assigned to OH and CO groups present in the molecule. The characteristic peak of -
(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in its 1H NMR spectrum
appeared at δ 0.86 (3H, t, J = 7.3 Hz), 4.07-4.14 (2H, m), 4.31-4.35 (1H, m), 4.50 (1H,
dd, J = 13.9 & 8.4 Hz), 4.68 (1H, dd, J = 13.9 & 3.6 Hz) and 8.57 (1H, s),respectively.
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -(CH2)5CH3, -CH2N, -CH,
-OCH2 and CO appeared at δ 13.96, 52.70, 67.69, 70.09 and 160.75, respectively. The
peaks of all other protons and carbons of the molecule were also present in the 1H and
13C
NMR spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (70a).
2.7.8. 3-Hexyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-
methylcoumarin (70b)
Compound 70b was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and pent-4-ynoic acid 68b in
t-BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at
60 oC and obtained as a white solid in 79 % yield (Scheme 8). Its high resolution mass
spectrum showed [M+H]+
peak at m/z 458.2284 which confirmed its molecular formula
to be C24H31N3O6. The absorption in the IR spectrum at 3461 and 1704 cm-1
were
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
32
assigned to OH and CO groups present in the molecule. The characteristic peak of -
(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in its1H NMRspectrum
appeared at δ 0.86 (3H, t, J = 7.3 Hz), 3.99-4.07 (2H, m), 4.20-4.23 (1H, m), 4.40 (1H,
dd, J = 13.9 &7.3 Hz), 4.55 (1H, dd, J = 13.9 &3.8 Hz) and 7.84 (1H, s), respectively
(Figure 19). Similarly, in its 13
C NMR spectrum, the characteristic peaks for -(CH2)5CH3,
-CH2N, -CH, -OCH2 and CO appeared at δ 13.96, 52.36, 67.73, 70.09 and
160.93,respectively (Figure 20). The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13C NMR spectra of the compound. Based on
the spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-
hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-methylcoumarin (70b).
2.7.9. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin (70c)
Compound 70c was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-
hexyl-4-methylcoumarin 67 and 5-Chloro-1-
pentyne 68c in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbateand copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 8). Its
high resolution mass spectrum showed [M+H]+peak at m/z 462.2157 which confirmed its
molecular formula to be C24H32ClN3O4. The absorption in the IR spectrum at 3398 and
1713 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in
its1H NMRspectrum appeared at δ 0.84 (3H, t, J = 6.6 Hz), 3.96-4.05 (2H, m), 4.20-4.24
(1H, m), 4.38 (1H, dd, J = 13.9 &7.6 Hz), 4.55 (1H, dd, J = 13.9 &4.4 Hz) and 7.87 (1H,
s), respectively (Figure 21). Similarly, in its 13
C NMR spectrum, the characteristic peaks
for -(CH2)5CH3, -CH2N, -CH, -OCH2 and CO appeared at δ 13.96, 22.08, 22.29, 26.82,
28.20, 28.67, 31.13, 31.81, 44.69, 52.36, 67.71, 70.08 and 160.92,respectively (Figure
22). The peaks of all other protons and carbons of the molecule were also present in the
1H and
13CNMR spectra of the compound. Based on the spectral data analysis, the
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
33
structure of the compound was established as 7-(3-(4-(3-chloropropyl)-1,2,3-triazol-1-
yl)-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (70c).
2.7.10. 3-Hexyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (70d)
Compound 70d was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and propargyl alcohol 68d in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60
oC and obtained as a white solid in 87 % yield (Scheme 8). Its high resolution mass
spectrum showed [M+H]+peak at m/z 416.2176 which confirmed its molecular formula to
be C22H29N3O5. The absorption in the IR spectrum at 3385 and 1717 cm-1
were assigned
to OH and CO groups present in the molecule. The characteristicpeak of -(CH2)5CH3, -
CH2N, -CH, -OCHα, -CH2OH, -OCHβ, and triazole H protons in its1H NMRspectrum
appeared at δ 0.86 (3H, t, J = 6.6 Hz), 3.99-4.07 (2H, m), 4.23-4.26 (1H, m), 4.44 (1H,
dd, J = 13.9 &7.3 Hz), 4.52 (2H, d, J = 5.8 Hz ), 4.58 (1H, dd, J = 13.9 &3.8 Hz) and
7.95 (1H, s),respectively (Figure 23). Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2 and CO appeared at δ 12.99,
52.33, 67.75, 70.09 and 160.79,respectively (Figure 24). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-
4-methylcoumarin (70d).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
34
Figure 19:1H NMR spectrum of compound 70b (400 MHz,DMSO)
Figure 20:13
C NMR of compound 70b (100 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
35
Figure 21:1H NMR spectrum of compound 70c (400 MHz,DMSO)
Figure 22:13
C NMR spectrum of compound 70c (100 MHz,DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
36
Figure 23:1H NMR spectrum of compound 70d (400 MHz,DMSO)
Figure 24:13
C NMR spectrum of compound 70d (100 MHz,DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
37
2.7.11. 3-Ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (73a)
Compound 73a was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin 66 and 3-phenoxyprop-1-yne 72a in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium ascorbate
and copper (II) sulfate pentahydrate at 60 oC and
obtained as a white solid in 85 % yield (Scheme 9). Its high resolution mass spectrum
showed [M+H]+
peak at m/z 436.1858 which confirmed its molecular formula to be
C24H25N3O5. The absorption in the IR spectrum at 3386 and 1717 cm-1
were assigned to
OH and CO groups present in the molecule. The characteristicpeak of -CH2CH3,-
CH2CH3, -CH2N, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ
1.10 (3H, t, J = 7.3 Hz), 2.62 (2H, q, J = 7.3 Hz), 4.01-4.05 (2H, m), 5.14 (2H, s) and
7.78 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the characteristic peaks
for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.03,
20.72, 52.99, 61.59, 68.29, 69.25 and 161.95, respectively. The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (73a).
2.7.12. 3-Ethyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73b)
Compound 73b was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3-ethyl-4-
methylcoumarin 66 and 1-Cl-2-(prope-2-yn-1-
yloxy)benzene 72b in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 92 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 470.1477 which confirmed its
molecular formula to be C24H24ClN3O5. The absorption in the IR spectrum at 3392 and
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
38
1718 cm-1
were assigned to OH and COgroups present in the molecule. The characteristic
peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H
protons in its 1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.7 Hz), 2.65 (2H, q, J =
7.3 Hz), 4.03-4.09 (2H, m), 4.53-4.61 (2H, m), 4.74 (1H, dd, J = 13.9 & 3.8 Hz), 5.25
(2H, s) and 7.86 (1H, s),respectively (Figure 25). Similarly, in its 13
C NMR spectrum,
the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO
appeared at δ 13.03, 20.73, 53.02, 62.97, 68.30, 69.24 and 161.95, respectively (Figure
26). The peaks of all other protons and carbons of the molecule were also present in the
1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(2-
chlorophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73b).
2.7.13. 3-Ethyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73c)
Compound 73c was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-Cl-3-(prope-2-yn-1-
yloxy)benzene 72c in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+peak at m/z 470.1480 which confirmed its
molecular formula to be C24H24ClN3O5. The absorption in the IR spectrum at 3391 and
1706 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its1H NMR spectrum appeared at δ 1.08 (3H, t, J = 7.3 Hz), 2.62
(2H, q, J = 7.3 Hz), 4.01-4.06 (2H, m), 4.50-4.60 (2H, m), 4.71 (1H, dd, J = 13.9 & 3.8
Hz), 5.13 (2H, s) and 7.79 (1H, s), respectively (Figure 27). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.03, 20.74, 53.00, 61.87, 68.32, 69.26 and 161.94,
respectively (Figure 28). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
39
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-((3-chlorophenoxy) methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73c).
2.7.14. 3-Ethyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73d)
Compound 73d was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-Cl-4-(prope-2-yn-1-
yloxy)benzene 72d in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 81 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 470.1474 which confirmed its
molecular formula to be C24H24ClN3O5. The absorption in the IR spectrum at 3392 and
1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.7 Hz), 2.64
(2H, q, J = 7.3 Hz), 4.03-4.11 (2H, m), 4.51-4.60 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.2
Hz), 5.14 (2H, s) and 7.82 (1H, s), respectively (Figure 29). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.02, 20.73, 53.00, 61.89, 68.28, 69.27 and 161.95,
respectively (Figure 30). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C spectra of the compound. Based on the spectral data
analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(4-
chlorophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73d).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
40
Figure 25:1H NMR spectrum of compound 73b (400 MHz, CDCl3)
Figure 26:13
C NMR spectrum of compound 73b (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
41
Figure 27:1H NMR spectrum of compound 73c (400 MHz, CDCl3)
Figure 28:13
C NMR spectrum of compound 73c (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
42
Figure 29:1H NMR spectrum of compound 73d (400 MHz, CDCl3)
Figure 30:13
C NMR spectrum of compound 73d (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
43
2.7.15. 3-Ethyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73e)
Compound 73e was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-Br-2-(prope-2-yn-1-
yloxy)benzene 72e in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 91 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 514.0982 which confirmed its
molecular formula to be C24H24BrN3O5. The absorption in the IR spectrum at 3246 and
1710 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.65
(2H, q, J = 8.1 Hz), 4.03-4.09 (2H, m), 4.51-4.61 (2H, m), 4.73 (1H, dd, J = 13.9 & 2.2
Hz), 5.26 (2H, s) and 7.86 (1H, s), respectively (Figure 31). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.08, 20.79, 52.94, 63.25, 68.48, 69.13 and 161.89,
respectively (Figure 32). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C spectra of the compound. Based on the spectral data
analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(2-
bromophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73e).
2.7.16. 3-Ethyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73f)
Compound 73f was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-Br-4-(prope-2-yn-1-
yloxy)benzene 72f in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
44
resolution mass spectrum showed [M+H]+
peak at m/z 514.0965 which confirmed its
molecular formula to be C24H24BrN3O5. The absorption in the IR spectrum at 3402 and
1717 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.7 Hz), 2.65
(2H, q, J = 7.3 Hz), 4.03-4.10 (2H, m), 4.51-4.60 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.9
Hz), 5.14 (2H, s) and 7.82 (1H, s), respectively (Figure 33). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.03, 20.74, 53.00, 61.82, 68.29, 69.26 and 161.94,
respectively (Figure 34). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73f).
Figure 31:1H NMR spectrum of compound 73e (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
45
Figure 32:13
C NMR spectrum of compound 73e (100.6 MHz, CDCl3)
Figure 33:1H NMR spectrum of compound 73f (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
46
Figure 34:13
C NMR spectrum of compound 73f (100.6 MHz, CDCl3)
2.7.17. 3-Ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73g)
Compound 73g was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-nitro-2-(prope-2-yn-1-
yloxy)benzene 72g in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 481.1711 which confirmed its
molecular formula to be C24H24N4O7. The absorption in the IR spectrum at 3419 and
1689 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.57
(2H, q, J = 7.2 Hz), 4.01-4.10 (2H, m), 4.22-4.28 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
47
Hz), 4.62 (1H, dd, J = 13.9 Hz & J = 3.8 Hz), 5.36 (2H, s) and 8.22 (1H, s), respectively
(Figure 35). Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3,-
CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 12.89, 20.14, 52.49,
62.48, 67.53, 69.98 and 160.69, respectively (Figure 36). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73g).
2.7.18. 3-Ethyl-7-(2-hydroxy-3-(4-(3-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73h)
Compound 73h was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-nitro-3-(prope-2-yn-1-
yloxy)benzene 72h in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 88 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 481.1710 which confirmed its
molecular formula to be C24H24N4O7. The absorption in the IR spectrum at 3210 and
1716 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and-OCHα, -OCHβ, -CH2OPh and
triazole H protons in its1H NMR spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.66
(2H, q, J = 7.3 Hz), 4.00-4.10 (2H, m), 4.50-4.62 (2H, m), 4.75 (1H, dd, J = 13.8 & 3.2
Hz), 5.28 (2H, s) and 7.86 (1H, m), respectively (Figure 37). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph,- CH, -
OCH2, and CO appeared at δ 12.95, 20.21, 52.55, 61.76, 67.61, 70.06 and 160.75,
respectively (Figure 38). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-(3-nitrophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73h).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
48
2.7.19. 3-Ethyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73i)
Compound 73i was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-nitro-4-(prope-2-yn-1-
yloxy)benzene 72i in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 481.1703 which confirmed its
molecular formula to be C24H24N4O7. The absorption in the IR spectrum at 3367 and
1699 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its1H NMR spectrum appeared at δ 1.04 (3H, t, J = 7.3 Hz), 2.55
(2H, q, J = 7.3 Hz), 4.00-4.10 (2H, m), 4.22-4.29 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3
Hz), ), 4.63 (1H, dd, J = 13.9 & 3.8 Hz), 5.33 (2H, s) and 8.27 (1H, s), respectively
(Figure 39). Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3,-
CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 12.88, 20.15, 52.51,
61.83, 67.54, 69.99 and 163.23, respectively (Figure 40). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13CNMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73i).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
49
Figure 35:1H NMR spectrum of compound 73g (400 MHz, DMSO)
Figure 36:13
C NMR spectrum of compound 73g (100.6 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
50
Figure 37:1H NMR spectrum of compound 73h (400 MHz,DMSO)
Figure 38:13
C NMR spectrum of compound 73h (100.6 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
51
Figure 39:1H NMR spectrum of compound 73i (400 MHz, DMSO)
Figure 40:13
C NMR spectrum of compound 73i (100.6 MHz, DMSO)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
52
2.7.20. 3-Ethyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (73j)
Compound 73j was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-methyl-2-(prope-2-yn-1-
yloxy)benzene 72j in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 83 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 450.2010 which confirmed its
molecular formula to be C25H27N3O5. The absorption in the IR spectrum at 3385 and
1716 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 1.15 (3H, t, J =
8.1 Hz), 2.28 (1H, s), 2.63 (2H, q, J = 8.1 Hz), 4.03-4.6 (2H, m), 4.47-4.57 (2H, m), 4.70
(1H, dd, J = 13.9 & 3.8 Hz), 5.14 (2H, s) and 7.77 (1H, s), respectively. Similarly, in its
13C NMR spectrum, the characteristic peaks for -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -
OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.02, 14.48, 20.15, 52.94, 61.99, 68.32,
69.25 and 161.93, respectively. The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13C NMR spectra of the compound. Based on
the spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-
hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73j).
2.7.21. 3-Ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-
4-methylcoumarin (73k)
Compound 73k was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-methyl-3-(prope-2-yn-
1-yloxy)benzene 72k in t-BuOH/H2O/THF (3
mL, 1/1/1) using sodium ascorbate and copper
(II) sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 9).
Its high resolution mass spectrum showed [M+H]+
peak at m/z 450.2023 which confirmed
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
53
its molecular formula to be C25H27N3O5. The absorption in the IR spectrum at 3511 and
1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its1H NMR spectrum appeared at δ 1.12 (3H, t, J = 7.4
Hz), 2.17 (1H, s), 2.64 (2H, q, J = 8.1 Hz), 4.0-4.08 (2H, m), 4.48-4.60 (2H, m), 4.72
(1H, dd, J = 13.9 & 3.8 Hz), 5.18 (2H, s) and 7.75 (1H, s), respectively (Figure 41).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, Ph-
CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.02, 20.72, 21.42, 53.00,
61.58, 68.31, 69.27 and 161.93, respectively (Figure 42). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73k).
2.7.22. 3-Ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-3-
ethyl-4-methylcoumarin (73l)
Compound 73l was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-methyl-4-(prope-2-yn-1-
yloxy)benzene 72l in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 84 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 450.2026 which confirmed its
molecular formula to be C25H27N3O5. The absorption in the IR spectrum at 3386 and
1721 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 1.12 (3H, t, J =
7.3 Hz), 2.26 (1H, s), 2.64 (2H, q, J = 7.3 Hz), 4.01-4.08 (2H, m), 4.51-4.57 (2H, m),
4.72 (1H, dd, J = 13.9 &3.7 Hz), 5.13 (2H, s) and 7.78 (1H, s), respectively (Figure 43).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, Ph-
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
54
CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.08, 20.45, 20.79, 52.91,
61.89, 68.51, 69.17 and 162.21, respectively (Figure 44). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin(73l).
Figure 41:1H NMR spectrum of compound 73k (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
55
Figure 42:13
C NMR spectrum of compound 73k (100.6 MHz, CDCl3)
Figure 43:1H NMR spectrum of compound 73l (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
56
Figure 44:13
C NMR spectrum of compound 73l (100.6 MHz, CDCl3)
2.7.23. 3-Ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73m)
Compound 73m was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-methoxy-2-(prope-2-yn-1-
yloxy)benzene 72m in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 83 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 466.1978 which confirmed its
molecular formula to be C25H27N3O6. The absorption in the IR spectrum at 3401 and
1674 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 1.11 (3H, t, J =
7.7 Hz), 2.62 (2H, q, J = 8.1 Hz), 3.80 (1H, m), 4.01-4.05 (2H, m), 4.45-4.54 (2H, m),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
57
4.68 (1H, dd, J = 11.9 & 2.9 Hz), 5.23 (2H, s) and 7.80 (1H, s), respectively (Figure 45).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -
CH2N, Ph-OCH3, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.03, 20.74, 52.94,
55.72, 62.82, 68.36, 69.22 and 161.91, respectively (Figure 46). The peaks of all other
protons and carbons of the molecule were also present in the 1H and
13C NMR spectra of
the compound. Based on the spectral data analysis, the structure of the compound was
established as 3-ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73m).
2.7.24. 3-Ethyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73n)
Compound 73n was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-methoxy-3-(prope-2-
yn-1-yloxy)benzene 72n in t-BuOH/H2O/THF (3
mL, 1/1/1) using sodium ascorbate and copper
(II) sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 9).
Its high resolution mass spectrum showed [M+H]+
peak at m/z 466.1975 which confirmed
its molecular formula to be C25H27N3O6. The absorption in the IR spectrum at 3228 and
1708 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 1.13 (3H, t, J =
7.32 Hz), 2.65 (2H, q, J = 7.32 Hz), 3.77 (1H, m), 4.03-4.10 (2H, m), 4.50-4.59 (2H, m),
4.72 (1H, dd, J = 12.4 & 2.2 Hz), 5.16 (2H, s) and 7.80 (1H, s), respectively (Figure 47).
Similarly, in its 13
C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -
CH2N, Ph-OCH3, -CH, -OCH2 and CO appeared at δ 13.04, 20.75, 52.98, 55.21, 68.36,
69.25 and 161.94, respectively (Figure 48). The peaks of all other protons and carbons of
the molecule were also present in the 1H and
13C NMR spectra of the compound. Based
on the spectral data analysis, the structure of the compound was established as 3-ethyl-7-
(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (73n).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
58
2.7.25. 3-Ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73o)
Compound 73o was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-iodo-2-(prope-2-yn-1-
yloxy)benzene 72o in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 83 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 562.0842 which confirmed its
molecular formula to be C24H24IN3O5. The absorption in the IR spectrum at 3273 and
1711 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.3 Hz), 2.64
(2H, q, J = 7.3 Hz), 4.03-4.08 (2H, m), 4.52-4.63 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9
Hz), 5.25 (2H, s) and 7.89 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO
appeared at δ 13.05, 20.77, 53.00, 63.39, 68.39, 69.19 and 161.92, respectively. The
peaks of all the protons and carbons of the molecule were also present in the 1H and
13C
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxy methyl)-1,2,3-
triazol-1-yl)propyloxy)-4-methylcoumarin (73o).
2.7.26. 3-Ethyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73p)
Compound 73p was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-iodo-4-(prope-2-yn-1-
yloxy)benzene 72p in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 562.0839 which confirmed its
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
59
molecular formula to be C24H24IN3O5. The absorption in the IR spectrum at 3384 and
1715 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.11 (3H, t, J = 7.3 Hz), 2.62
(2H, q, J = 7.3 Hz), 4.00-4.08 (2H, m), 4.49-4.57 (2H, m), 4.71 (1H, dd, J = 13.2 & 3.7
Hz), 5.11 (2H, s) and 7.78 (1H, s), respectively (Figure 49). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.05, 20.76, 53.00, 61.72, 68.32, 69.27 and 161.94,
respectively (Figure 50). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-(4-iodophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73p).
Figure 45:1H NMR spectrum of compound 73m (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
60
Figure 46:13
C NMR spectrum of compound 73m (100.6 MHz, CDCl3)
Figure 47:1H NMR spectrum of compound 73n (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
61
Figure 48:13
C NMR spectrum of compound 73n (100.6 MHz, CDCl3)
Figure 49:1H NMR spectrum of compound 73p (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
62
Figure 50:13
C NMR spectrum of compound 73p (100.6 MHz, CDCl3)
2.7.27. 3-Ethyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73q)
Compound 73q was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-fluoro-3-(prope-2-yn-1-
yloxy)benzene 72q in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 87 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 454.1773 which confirmed its
molecular formula to be C24H24FN3O5. The absorption in the IR spectrum at 3392 and
1706 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.11 (3H, t, J = 7.7 Hz), 2.62
(2H, q, J = 7.3 Hz), 4.00-4.07 (2H, m), 4.48-4.58 (2H, m), 4.71 (1H, dd, J = 13.2 & 2.9
Hz), 5.14 (2H, s) and 7.79 (1H, s), respectively (Figure 51). Similarly, in its 13
C NMR
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
63
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.02, 20.73, 53.01, 61.89, 68.31, 69.27 and 164.65,
respectively (Figure 52). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-
(4-(3-fluorophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73q).
2.7.28. 3-Ethyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73r)
Compound 73r was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-fluoro-3-(prope-2-yn-1-
yloxy)benzene 72r in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 454.1783 which confirmed its
molecular formula to be C24H24FN3O5. The absorption in the IR spectrum at 3384 and
1705 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.4 Hz), 2.65
(2H, q, J = 7.4 Hz), 4.02-4.10 (2H, m), 4.52-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9
Hz), 5.15 (2H, s) and 7.80 (1H, s), respectively (Figure 53). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -
OCH2, and CO appeared at δ 13.02, 20.74, 52.98, 62.31, 68.33, 69.28 and 161.95,
respectively (Figure 54). The peaks of all the protons and carbons of the molecule were
also present in the 1H and
13C spectra of the compound. Based on the spectral data
analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(4-
fluorophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73r).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
64
Figure 51:1H NMR spectrum of compound 73q (400 MHz, CDCl3)
Figure 52:13
C NMR spectrum of compound 73q (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
65
Figure 53:1H NMR spectrum of compound 73r (400 MHz, CDCl3)
Figure 54:13
C NMR spectrum of compound 73r (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
66
2.7.29. 3-Ethyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73s)
Compound 73s was synthesized by click reaction of 7-
(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 4-(prope-2-yn-1-yloxy)-1,1'-
biphenyl 72s in t-BuOH/H2O/THF (3 mL, 1/1/1) using
sodium ascorbate and copper (II) sulfate pentahydrate
at 60 oC and obtained as a white solid in 89 % yield (Scheme 9). Its high resolution mass
spectrum showed [M+H]+
peak at m/z 512.2171 which confirmed its molecular formula
to be C30H29N3O5. The absorption in the IR spectrum at 3421 and 1707 cm-1
were
assigned to OH and CO groups present in the molecule. The characteristic peak of -
CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H protons in
its 1H NMR spectrum appeared at δ 1.10 (3H, t, J = 7.6 Hz), 2.62 (2H, q, J = 7.3 Hz),
4.00-4.08 (2H, m), 4.50-4.58 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.21 (2H, s) and
7.80 (1H, s), respectively (Figure 55). Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO
appeared at δ 13.02, 20.72, 53.03, 61.75, 68.31, 69.28 and 161.93, respectively (Figure
56). The peaks of all other protons and carbons of the molecule were also present in the
1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(4-
phenylphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73s).
2.7.30. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73t)
Compound 73t was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 2-(prope-2-yn-1-
yloxy)naphthalene 72t in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 89 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 486.2021 which confirmed its
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
67
molecular formula to be C28H27N3O5. The absorption in the IR spectrum at 3161 and
1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMRspectrum appeared at δ 1.11 (3H, t, J = 7.3 Hz), 2.62
(2H, q, J = 7.3 Hz), 4.00-4.07 (2H, m), 4.48-4.57 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8
Hz), 5.28 (2H, s) and 7.81 (1H, s), respectively (Figure 57). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -CH,-OCH2, -OCH2Ph
and CO appeared at δ 13.02, 20.72, 53.03, 61.66, 68.31, 69.27 and 161.93,respectively
(Figure 58). The peaks of all other protons and carbons of the molecule were also present
in the 1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-
yloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73t).
Figure 55:1H NMR spectrum of compound 73s (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
68
Figure 56:13
C NMR spectrum of compound 73s (100.6 MHz, CDCl3)
Figure 57:1H NMR spectrum of compound 73t (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
69
Figure 58:13
C NMR spectrum of compound 73t (100.6 MHz, CDCl3)
2.7.31. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73u)
Compound 73u was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 66 and 1-(prope-2-yn-1-
yloxy)naphthalene 72u in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 90 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 486.2018 which confirmed its
molecular formula to be C28H27N3O5. The absorption in the IR spectrum at 3374 and
1698 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and
triazole H protons in its 1H NMR spectrum appeared at δ 1.11 (3H, t, J = 7.3 Hz), 2.62
(2H, q, J = 7.3 Hz), 3.99-4.06 (2H, m), 4.52-4.57 (2H, m), 4.70 (1H, dd, J = 13.9 &3.7
Hz), 5.30 (2H, s) and 7.83 (1H, s), respectively (Figure 59). Similarly, in its 13
C NMR
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
70
spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -CH, -OCH2, -OCH2Ph
and CO appeared at δ 13.02, 20.72, 53.01, 62.07, 68.32, 69.25 and 161.95, respectively
(Figure 60). The peaks of all other protons and carbons of the molecule were also present
in the 1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-
yloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73u).
2.7.32. 3-Hexyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (74a)
Compound 74a was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 3-phenoxyprop-1-yne 72a
in t-BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at
60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high resolution mass
spectrum showed [M+H]+
peak at m/z 492.2493 which confirmed its molecular formula
to be C28H33N3O5. The absorption in the IR spectrum at 3385 and 1717 cm-1
were
assigned to OH and CO groups present in the molecule. The characteristic peak of -
(CH2)5CH3, -CH2N, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at
δ 0.89 (3H, t, J = 7.3 Hz), 4.02-4.09 (2H, m), 5.19 (2H, s), and 7.79 (1H, s), respectively
(Figure 61). Similarly, in its 13
C NMR spectrum, the characteristic peaks for -(CH2)5CH3,
-CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 13.96, 52.99, 61.59, 68.29, 69.24
and 161.95, respectively (Figure 62). The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13C NMR spectra of the compound. Based on
the spectral data analysis, the structure of the compound was established as 3-hexyl-7-(2-
hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74a).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
71
Figure 59:1H NMR spectrum of compound 73u (400 MHz, CDCl3)
Figure 60:13
C NMR spectrum of compound 73u (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
72
Figure 61:1H NMR spectrum of compound 74a (400 MHz, CDCl3)
Figure 62:13
C NMR spectrum of compound 74a (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
73
2.7.33. 3-Hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74b)
Compound 74b was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-Cl-2-(prope-2-yn-1-
yloxy)benzene 72b in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 92 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 526.2109 which confirmed its
molecular formula to be C28H32ClN3O5. The absorption in the IR spectrum at 3392 and
1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.89 (3H, t, J = 7.3 Hz), 4.01-4.09 (2H,
m), 4.52-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.2 Hz), 5.26 (2H, s), and 7.85 (1H, s),
respectively (Figure 63). Similarly, in its 13
C NMR spectrum, the characteristic peaks for
-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 12.99, 53.02, 62.97,
68.30, 69.24 and 161.95, respectively (Figure 64). The peaks of all other protons and
carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74b).
2.7.34. 3-Hexyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74c)
Compound 74c was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-
hexyl-4-methylcoumarin 67 and 1-Cl-3-(prope-
2-yn-1-yloxy)benzene 72c in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as a white solid in 85
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
74
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+
peak at m/z
526.2106 which confirmed its molecular formula to be C28H32ClN3O5. The absorption in
the IR spectrum at 3393 and 1705 cm-1
were assigned to OH and CO groups present in
the molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.89 (3H, t, J =
6.6 Hz), 4.03-4.09 (2H, m), 4.53-4.60 (2H, m), 4.73 (1H, dd, J = 13.9 & 3.7 Hz), 5.16
(2H, s), and 7.81 (1H, s), respectively (Figure 65). Similarly, in its 13
C NMR spectrum,
the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared
at δ 12.99, 53.00, 61.87, 68.32, 69.26 and 161.94, respectively (Figure 66). The peaks of
all other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-
1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74c).
2.7.35. 3-Hexyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74d)
Compound 74d was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-Cl-4-(prope-2-yn-1-
yloxy)benzene 72d in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 81 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 526.2103 which confirmed its
molecular formula to be C28H32ClN3O5. The absorption in the IR spectrum at 3392 and
1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.02-4.10 (2H,
m), 4.51-4.60 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.2 Hz), 5.15 (2H, s), and 7.80 (1H, s),
respectively (Figure 67). Similarly, in its 13
C NMR spectrum, the characteristic peaks for
-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 12.99, 53.00, 61.89,
68.28, 69.27 and 161.95, respectively (Figure 68). The peaks of all other protons and
carbons of the molecule were also present in the 1H and
13C NMR spectra of the
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
75
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74d).
Figure 63:1H NMR spectrum of compound 74b (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
76
Figure 64:13
C NMR spectrum of compound 74b (100.6 MHz, CDCl3)
Figure 65:1H NMR spectrum of compound 74c (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
77
Figure 66:13
C NMR spectrum of compound 74c (100.6 MHz, CDCl3)
Figure 67:1H NMR spectrum of compound 74d (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
78
Figure 68:13
C NMR spectrum of compound 74d (100.6 MHz, CDCl3)
2.7.36. 3-Hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74e)
Compound 74e was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-Br-2-(prope-2-yn-1-
yloxy)benzene 72e in t-BuOH/H2O/THF (3 mL,
1/1/1, v/v/v) using sodium ascorbate and copper
(II) sulfate pentahydrate at 60oC and obtained as a white solid in 91% yield (Scheme 9).
Its high resolution mass spectrum showed [M+H]+
peak at m/z 570.1603 which confirmed
its molecular formula to be C28H32BrN3O5. The absorption in the IR spectrum at 3232
and 1718 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.89 (3H, t, J = 7.3 Hz), 4.03-4.09 (2H,
m), 4.53-4.61 (2H, m), 4.72 (1H, dd, J = 13.2 & 2.9 Hz), 5.26 (2H, s), and 7.86 (1H, s),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
79
respectively (Figure 69). Similarly, in its 13
C NMR spectrum, the characteristic peaks for
-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.04, 53.00, 63.18,
68.36, 69.19 and 161.89, respectively (Figure 70). The peaks of all other protons and
carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74e).
2.7.37. 3-Hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74f)
Compound 74f was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-Br-4-(prope-2-yn-1-
yloxy)benzene 72f in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 570.1598 which confirmed its
molecular formula to be C28H32BrN3O5. The absorption in the IR spectrum at 3402 and
1717 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristicpeak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its1H NMR spectrum appeared at δ 0.89 (3H, t, J = 7.3 Hz), 4.02-4.09 (2H,
m), 4.50-4.59 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.9 Hz), 5.15 (2H, s), and 7.80 (1H, s)
,respectively (Figure 71). Similarly, in its 13
C NMR spectrum, the characteristic peaks
for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.03, 53.01,
61.83, 68.29, 69.27 and 161.94, respectively (Figure 72). The peaks of all other protons
and carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74f).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
80
Figure 69:1H NMR spectrum of compound 74e (400 MHz, CDCl3)
Figure 70:13
C NMR spectrum of compound 74e (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
81
Figure 71:1H NMR spectrum of compound 74f (400 MHz, CDCl3)
Figure 72: 13
C NMR spectrumof compound 74f(100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
82
2.7.38. 3-Hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74g)
Compound 74g was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-nitro-2-(prope-2-yn-1-
yloxy)benzene 72g in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/ z 537.2346 which confirmed
its molecular formula to be C28H32N4O7. The absorption in the IR spectrum at 3419 and
1716 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and triazole H
protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz), 4.01-4.10 (2H,
m), 4.22-4.30 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3 Hz), 4.60 (1H, dd, J = 13.9 & 3.7
Hz), 5.35 (2H, s), and 8.21 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at
δ 14.01, 52.49, 62.58, 67.67, 70.10 and 160.67,respectively. The peaks of all other
protons and carbons of the molecule were also present in the 1H and
13C NMR spectra of
the compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74g).
2.7.39. 3-Hexyl-7-(2-hydroxy-3-(4-(3-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74h)
Compound 74h was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-
hexyl-4-methylcoumarin 67 and 1-nitro-3-
(prope-2-yn-1-yloxy)benzene 72h in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as a white solid in 88
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
83
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+peak at m/z
537.2336 which confirmed its molecular formula to be C28H32N4O7. The absorption in the
IR spectrum at 3222 and 1717 cm-1
were assigned to OH and CO groups present in the
molecule. The characteristicpeak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh
and triazole H protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz),
3.99-4.07 (2H, m), 4.21-4.28 (1H, m), 4.45 (1H, dd, J = 13.2 & 3.7 Hz), 4.61 (1H, dd, J =
13.8 & 3.2 Hz), 5.29 (2H, s), and 8.25 (1H, s), respectively. Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2 -CH2OPh and CO
appeared at δ 14.62, 52.54, 61.76, 67.61, 70.06 and 160.67,respectively. The peaks of all
other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-nitrophenoxymethyl)-1,2,3-
triazol-1-yl)propyloxy)-4-methylcoumarin (74h).
2.7.40. 3-Hexyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74i)
Compound 74i was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-nitro-4-(prope-2-yn-1-
yloxy)benzene 72i in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 86 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 537.2341 which confirmed its
molecular formula to be C28H32N4O7. The absorption in the IR spectrum at 3367 and
1699 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and triazole H
protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz), 4.00-4.07 (2H,
m), 4.22-4.28 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3 Hz), 4.63 (1H, dd, J = 13.9 & 3.7
Hz), 5.32 (2H, s), and 8.27 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ
13.95, 52.58, 61.91, 67.61, 70.07 and 163.23, respectively. The peaks of all the protons
and carbons of the molecule were also present in the 1H and
13C spectra of the compound.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
84
Based on the spectral data analysis, the structure of the compound was established as 3-
hexyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (74i).
2.7.41. 3-Hexyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (74j)
Compound 74j was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-hexyl-4-
methylcoumarin 67 and 1-methyl-2-(prope-2-yn-
1-yloxy)benzene 72j in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 83 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 506.2653 which confirmed its
molecular formula to be C29H35N3O5. The absorption in the IR spectrum at 3385 and
1716 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh
and triazole H protons in its 1H NMR spectrum appeared at δ 0.86 (3H, t, J = 7.3 Hz),
2.18 (1H, s), 4.05-4.09 (2H, m), 4.54-4.60 (2H, m), 4.71 (1H, dd, J = 13.9 & 3.7 Hz),
5.19 (2H, s), and 7.78 (1H, s), respectively (Figure 73). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -
CH2OPh and CO appeared at δ 14.04, 52.94, 62.03, 68.32, 69.26 and 161.93,respectively
(Figure 74). The peaks of all other protons and carbons of the molecule were also present
in the 1H and
13C NMR spectra of the compound. Based on the spectral data analysis, the
structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(o-
tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74j).
2.7.42. 3-Hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-
4-methylcoumarin (74k)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
85
Compound 74k was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-
methylcoumarin 67 and 1-methyl-3-(prope-2-yn-1-
yloxy)benzene 72k in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 86 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 506.2651 which confirmed its
molecular formula to be C29H35N3O5. The absorption in the IR spectrum at 3511 and
1718 cm-1
were assigned to OH and CO group present in the molecule. The characteristic
peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H
protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 2.31 (1H, s), 4.03-
4.09 (2H, m), 4.53-4.58 (2H, m), 4.72 (1H, dd, J = 13.9 & 3.7 Hz), 5.16 (2H, s), and 7.79
(1H, s), respectively (Figure 75). Similarly, in its 13
C NMR spectrum, the characteristic
peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ
14.03, 21.44, 53.01, 61.59, 68.32, 69.26 and 161.93, respectively (Figure 76). The peaks
of all other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-
triazol-1-yl)propyloxy)-4-methylcoumarin (74k).
2.7.43. 3-Hexyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (74l)
Compound 74l was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-methyl-4-(prope-2-yn-1-
yloxy)benzene 72l in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 84 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 506.2647 which confirmed its
molecular formula to be C29H35N3O5. The absorption in the IR spectrum at 3386 and
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
86
1721 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh
and triazole H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz),
2.27 (1H, s), 4.03-4.10 (2H, m), 4.49-4.58 (2H, m), 4.72 (1H, dd, J = 13.9 & 3.7 Hz),
5.14 (2H, s) and 7.79 (1H, s), respectively (Figure 77). Similarly, in its 13
C NMR
spectrum, the characteristic peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -
CH2OPh and CO appeared at δ 14.04, 20.41, 52.97, 61.85, 68.39, 69.25 and 162.21,
respectively (Figure 78). The peaks of all other protons and carbons of the molecule
were also present in the 1H and
13C NMR spectra of the compound. Based on the spectral
data analysis, the structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-
(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74l).
Figure 73:1H NMR spectrum of compound 74j (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
87
Figure 74:13
C NMR spectrum of compound 74j (100.6 MHz, CDCl3)
Figure 75:1H NMR spectrum of compound 74k (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
88
Figure 76:13
C NMR spectrum of compound 74k (100.6 MHz, CDCl3)
Figure 77:1H NMR spectrum of compound 74l (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
89
Figure 78:13
C NMR spectrum of compound 74l (100.6 MHz, CDCl3)
2.7.44. 3-Hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74m)
Compound 74m was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-
hexyl-4-methylcoumarin 67 and 1-methoxy-2-
(prope-2-yn-1-yloxy)benzene 72m in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as white solid in 83
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+
peak at m/z
522.2596 which confirmed its molecular formula to be C29H35N3O6. The absorption in the
IR spectrum at 3411 and 1694 cm-1
were assigned to OH and CO groups present in the
molecule. The characteristicpeak of -(CH2)5CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -
OCHβ, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.89 (3H,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
90
t, J = 7.3 Hz), 4.00-4.05 (2H, m), 4.45-4.55 (2H, m), 4.69 (1H, dd, J = 11.9 & 2.9 Hz),
5.26 (2H, s), and 7.83 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -(CH2)5CH3, -CH2N, Ph-OCH3, -CH, -OCH2, -CH2OPh and CO
appeared at δ 14.05, 52.94, 55.75, 62.87, 68.40, 69.22 and 161.91, respectively. The
peaks of all other protons and carbons of the molecule were also present in the 1H and
13C
NMR spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-
1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74m).
2.7.45. 3-Hexyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74n)
Compound 74n was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-
hexyl-4-methylcoumarin 67 and 1-methoxy-3-
(prope-2-yn-1-yloxy)benzene 72n in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as white solid in 86
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+
peak at m/z
522.2593 which confirmed its molecular formula to be C29H35N3O6. The absorption in the
IR spectrum at 3222 and 1715 cm-1
were assigned to OH and CO group present in the
molecule. The characteristic peak of -(CH2)5CH3, Ph-OCH3 -CH2N, -CH and -OCHα, -
OCHβ, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.88 (3H,
t, J = 7.3 Hz), 4.03-4.10 (2H, m), 4.53-4.59 (2H, m), 4.72 (1H, dd, J = 12.4 & 2.2 Hz),
5.16 (2H, s) and 7.80 (1H, s), respectively. Similarly, in its 13
C NMR spectrum, the
characteristic peaks for -(CH2)5CH3, -CH2N, Ph-OCH3, -CH, -OCH2, -CH2OPh and CO
appeared at δ 14.03, 52.98, 55.20, 61.89, 68.34, 69.24 and 161.94, respectively. The
peaks of all other protons and carbons of the molecule were also present in the 1H and
13C
NMR spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-
1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74n).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
91
2.7.46. 3-Hexyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74o)
Compound 74o was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-iodo-2-(prope-2-yn-1-
yloxy)benzene 72o in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 83 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+peak at m/z 618.1475 which confirmed its
molecular formula to be C28H32IN3O5. The absorption in the IR spectrum at 3285 and
1717 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.03-4.08 (2H,
m), 4.54-4.63 (2H, m), 4.72 (1H, dd, J = 13.2 & 2.9 Hz), 5.24 (2H, s) and 7.89 (1H, s),
respectively (Figure 79). Similarly, in its 13
C NMR spectrum, the characteristic peaks for
-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.06, 52.97, 63.40,
68.39, 69.15 and 161.94 ,respectively (Figure 80). The peaks of all other protons and
carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74o).
2.7.47. 3-Hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin 714p)
Compound 74p was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-iodo-4-(prope-2-yn-1-
yloxy)benzene 72p in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as white solid in 85 % yield (Scheme 9). Its high
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
92
resolution mass spectrum showed [M+H]+
peak at m/z 618.1459 which confirmed its
molecular formula to be C28H32IN3O5. The absorption in the IR spectrum at 3384 and
1715 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.02-4.09 (2H,
m), 4.53-4.59 (2H, m), 4.71 (1H, dd, J = 13.2 & 3.7 Hz), 5.14 (2H, s), and 7.80 (1H, s),
respectively (Figure 81). Similarly, in its 13
C NMR spectrum, the characteristic peaks for
-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.05, 53.01, 61.69,
68.29, 69.26 and 161.94, respectively (Figure 82). The peaks of all other protons and
carbons of the molecule were also present in the 1H and
13C NMR spectra of the
compound. Based on the spectral data analysis, the structure of the compound was
established as 3-hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74p).
Figure 79:1H NMR spectrum of compound 74o (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
93
Figure 80:13
C NMR spectrum of compound 74o (100.6 MHz, CDCl3)
Figure 81:1H NMR spectrum of compound 74p (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
94
Figure 82:13
C NMR spectrum of compound 74p (100.6 MHz, CDCl3)
2.7.48. 3-Hexyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74q)
Compound 74q was synthesized by click reaction
of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-flouro-3-(prope-2-yn-1-
yloxy)benzene 72q in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II)
sulfate pentahydrate at 60 oC and obtained as white solid in 87 % yield (Scheme 9). Its
high resolution mass spectrum showed [M+H]+
peak at m/z 510.2393 which confirmed its
molecular formula to be C28H32FN3O5. The absorption in the IR spectrum at 3404 and
1702 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.00-4.07 (2H,
m), 4.48-4.58 (2H, m), 4.71 (1H, dd, J = 13.2 & 2.9 Hz), 5.16 (2H, s) and 7.82 (1H,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
95
s),respectively. Similarly, in its 13
C NMR spectrum, the characteristic peaks for -
(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.05, 52.97, 61.96,
68.39, 69.23 and 164.65, respectively. The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13C NMR spectra of the compound. Based on
the spectral data analysis, the structure of the compound was established as 3-hexyl-7-(2-
hydroxy-3-(4-(3-flourophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin
(74q).
2.7.49. 3-Hexyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74r)
Compound 74r was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 1-flouro-4-(prope-2-yn-1-
yloxy)benzene 72r in t-BuOH/H2O/THF (3 mL,
1/1/1) using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as white solid in 85 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 510.2399 which confirmed its
molecular formula to be C28H32FN3O5. The absorption in the IR spectrum at 3413 and
1702 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.03-4.10 (2H,
m), 4.50-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9 Hz), 5.14 (2H, s) and 7.81 (1H, s),
respectively. Similarly, in its 13
C NMR spectrum, the characteristic peaks for -(CH2)5CH3,
-CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.02, 52.99, 62.26, 68.29, 69.25
and 161.97, respectively. The peaks of all other protons and carbons of the molecule were
also present in the 1H and
13C NMR spectra of the compound. Based on the spectral data
analysis, the structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(4-
flourophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74r).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
96
2.7.50. 3-Hexyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74s)
Compound 74s was synthesized by click reaction of
7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin 67 and 4-(prope-2-yn-1-yloxy)-1,1'-
biphenyl 72s in t-BuOH/H2O/THF (3 mL, 1/1/1)
using sodium ascorbate and copper (II) sulfate
pentahydrate at 60 oC and obtained as white solid in 89 % yield (Scheme 9). Its high
resolution mass spectrum showed [M+H]+
peak at m/z 568.2804 which confirmed its
molecular formula to be C34H37N3O5. The absorption in the IR spectrum at 3421 and
1707 cm-1
were assigned to OH and CO groups present in the molecule. The
characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole
H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.0 Hz), 4.02-4.09 (2H,
m), 4.48-4.58 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.29 (2H, s), and 7.83 (1H,
s),respectively. Similarly, in its 13
C NMR spectrum, the characteristic peaks for -
(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.03, 53.03, 61.65,
68.29, 69.27 and 161.93,r espectively. The peaks of all other protons and carbons of the
molecule were also present in the 1H and
13C NMR spectra of the compound. Based on
the spectral data analysis, the structure of the compound was established as 3-hexyl-7-(2-
hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin
(74s).
2.7.51. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74t)
Compound 74t was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-
3-hexyl-4-methylcoumarin 67 and 4-(prope-2-
yn-1-yloxy)-1,1'-biphenyl 72t in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as white solid in 89
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
97
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+peak at m/z
542.2649 which confirmed its molecular formula to be C34H37N3O5. The absorption in the
IR spectrum at 3161 and 1718 cm-1
were assigned to OH and CO groups present in the
molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J =
7.3 Hz), 4.02-4.09 (2H, m), 4.51-4.57 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.23
(2H, s), and 7.83 (1H, s), respectively (Figure 83). Similarly, in its 13
C NMR spectrum,
the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared
at δ 14.03, 53.02, 61.78, 68.34, 69.27 and 161.93, respectively (Figure 84). The peaks of
all other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as3-hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-
1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74t).
2.7.52. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74u)
Compound 74u was synthesized by click
reaction of 7-(3-azido-2-hydroxypropyloxy)-
3-hexyl-4-methylcoumarin 67 and 4-(prope-
1-yn-1-yloxy)-1,1'-biphenyl 72u in t-
BuOH/H2O/THF (3 mL, 1/1/1) using sodium
ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as white solid in 90
% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+
peak at m/z
542.2652 which confirmed its molecular formula to be C32H35N3O5. The absorption in the
IR spectrum at 3384 and 1716 cm-1
were assigned to OH and CO groups present in the
molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -
CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J =
7.3 Hz), 4.01-4.08 (2H, m), 4.52-4.59 (2H, m), 4.70 (1H, dd, J = 13.9 & 3.7 Hz), 5.36
(2H, s), and 7.86 (1H, s), respectively (Figure 85). Similarly, in its 13
C NMR spectrum,
the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
98
at δ 14.05, 53.01, 62.12, 68.36, 69.25 and 161.95, respectively (Figure 86). The peaks of
all other protons and carbons of the molecule were also present in the 1H and
13C NMR
spectra of the compound. Based on the spectral data analysis, the structure of the
compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-
1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74u).
Figure 83:1H NMR spectrum of compound 74t (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
99
Figure 84:13
C NMR spectrum of compound 74t (100.6 MHz, CDCl3)
Figure 85:1H NMR spectrum of compound 74u (400 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
100
Figure 86:13
C NMR spectrum of compound 74u (100.6 MHz, CDCl3)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
101
2.8. BIOLOGICAL ACTIVITY
The synthesized coumarin derivatives 66, 67, 69a-d, 70a-d, 73a-u and 74a-u were
evaluated for the antifungal inhibition. The detailed results of antifungal activity
evaluation on these compounds are shown in Table 2.
Table 2: Antifungal inhibitory activity of (22, 23, 25a-d, 26a-d, 29a-u and 30 a-u)
Comp. A. fumigatus
MIC
A. niger
MIC
A. flavus
MIC
μg/ml
(MDA)
μg/disc
(DDA)
μg/ml
(MDA)
μg/disc
(DDA)
μg/ml
(MDA)
μg/disc
(DDA)
66 15.62 3.91 62.50 15.62 125.00 31.25
67 62.50 15.62 62.50 31.25 250.00 62.50
69a 500.00 125.00 500.00 250.00 - -
69b 62.50 31.25 125.00 31.25 - -
69c 62.50 15.62 62.50 31.25 125.00 31.25
69d 125.00 31.25 125.00 31.25 250.00 62.50
70a 500.00 125.00 - - - -
70b 125.00 31.25 - - - -
70c 250.00 62.50 - - 500.00 125.00
70d 31.25 7.81 31.25 15.62 125.00 31.25
73a 500.00 125.00 250.00 62.50 500.00 125.00
73b 500.00 250.00 500.00 125.00 - -
73c 250.00 62.50 125.00 62.50 250.00 62.50
73d 125.00 31.25 125.00 31.25 250.00 125.00
73e - - - - - -
73f 500.00 125.00 500.00 250.00 - -
73g 500.00 125.00 500.00 250.00 - -
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
102
73h 500.00 125.00 250.00 125.00 - -
73i 62.50 15.62 125.00 31.25 125.00 31.25
73j - - - - - -
73k - - - - - -
73l - - 250.00 62.50 - -
73m - - - - - -
73n - - - - - -
73o - - - - - -
73p 500.00 250.00 500.00 125.00 - -
73q 500.00 125.00 - - - -
73r 62.50 15.62 62.50 31.25 250.00 62.50
73s - - - - - -
73t - - - - - -
73u - - - - - -
74a - - - - - -
74b - - - - - -
74c 500.00 250.00 500.00 125.00 - -
74d 500.00 125.00 250.00 62.50 - -
74e - - - - - -
74f 125.00 31.25 62.50 31.25 - -
74g - - - - - -
74h - - - - - -
74i 125.00 62.50 125.00 31.25 - -
74j - - - - - -
74k - - - - - -
74l - - - - - -
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
103
74m - - - - - -
74n - - - - - -
74o - - - - - -
74p 500.00 125.00 - - 500.00 125.00
74q 500.00 250.00 500.00 250.00 - -
74r 250.00 125.00 500.00 250.00 500.00 250.00
74s - - - - - -
74t - - - - - -
74u - - - - - -
‘-’ These compounds did not show any activity even at the highest tested concentration.
These results clearly show that among all the tested azido-coumarin and 1,2,3-triazole
containing coumarins, 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin 66
inhibited A. fumigatus at lowest concentration i. e. 3.91 μg/disc in disc diffusion (DDA)
and 15.62 μg/ml in microbroth dilution assays (DDA). In case of A. niger it showed
activity at 15.62 μg/disc in DDA and 62.50 μg/ml in MDA. While in case of A. flavus it
inhibited at 31.25 μg/disc in DDA and 125.00 μg/ml in MDA, 7-(2-hydroxy-3-(4-
hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-3-hexyl-4-methylcoumarin (70d) inhibited
at low concentration 7.81 μg/disc in DDA and 31.25 μg/ml in MDA in case of A.
fumigatus. In case of A. niger it showed activity at 15.62 μg/disc in DDA and 31.25
μg/ml in MDA. While in case of A. flavus it inhibited at 31.25 μg/disc in DDA and
125.00 μg/ml in MDA. Compounds 67, 69b, 69c, 69d, 69b, 73d, 73i, 73r, 74f and 74i
exhibited moderate to good antifungal activity whereas remaining compounds i. e. 69a,
70a, 70c, 73a, 73b, 73c, 73e, 73f, 73g, 73h, 73l, 73p, 73q, 73c, 74d, 74p, 74q and 74r
did not show any appreciable activity. And the rest are inactive as evident from the data
presented in the (Table 1).
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
104
2.9. CONCLUSION
Herein, we have reported the synthesis of a series of fifty two azido- and 1,2,3-
triazole containing coumarin derivatives 66, 67, 69a-d, 70a-d, 74a-u and 74a-u
(having C2 and C6 alkyl chain) and various alkynes by using Click reaction, and
all these synthesized compounds are novel and synthesized for the first time. All
these are well characterized from their spectral data (1H,
13C NMR, IR and HRMS
spectrometry).
Out of two azido coumarinyl derivatives the compound having C2 alkyl chain at
C-3 position of coumarin, i. e. 66 exhibited the best antifungal activity than
similar derivative having C6 alkyl chain 67. So, in case of azido derivatives it has
been observed that, with the increase in aliphatic chain length at the C-3 position
of coumarin, the antifungal activity decreases considerably.
The same pattern of activity was seen in all 1,2,3-triazolylcoumarin derivatives,
but surprisingly, one of the C6 derivative 70d shows superior activity than their C2
derivative and all the other 1,2,3-triazolylcoumarin derivatives.
We have compared all the aryl ethers linked 1,2,3-triazolylcoumarins by varying
the position (o-, m- and p-) and substituent on aryl ethers. The structure activity
relationship suggests that antifungal activity of 1,2,3-triazolylcoumarin
derivatives was in the order : p- >m- >o-. Also the increasing order of
electronegative substituent also increases the antifungal activity, while the
electron donating substituents are found almost inactive.
It has been observed that more electronegative group at p-position of aryl ethers
are responsible for better activity trend in 1,2,3-triazolylcoumarins.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
105
2.10. EXPERIMENTAL
Melting points were determined on Buchi M-560 instrument and are uncorrected. The IR
spectra were recorded on a Perkin-Elmer model 2000 FT-IR spectrometer by making KBr
disc for solid samples and thin film for oils. The 1H- and
13C NMR spectra were recorded
on a Jeol alpha-400 spectrometer at 400 and 100.6 MHz, respectively, using TMS as
internal standard. The chemical shift values are on scale and the coupling constants (J)
are in Hz. Signals from OH groups in 1H NMR spectra recorded in CDCl3 were verified
by removing them by D2O exchange method. The mass spectra analyses were done on
microTOF-Q instrument from Bruker Daltonics, Bremen and were run in ESI positive
mode. Reactions were conducted under an atmosphere of nitrogen when anhydrous
solvents were used. Analytical TLCs were performed on precoated Merck silica-gel
60F254 plates; the spots were detected under UV light. Silica gel (100-200 mesh) was
used for column chromatography. Chemicals were obtained from commercial suppliers
and were used without any further purification unless otherwise noted.
2.10.1. General procedure for the synthesis of 3-alkyl-7-(2,3-epoxypropyloxy)-4-
methylcoumarins (64 and 65)
This is two steps synthesis. The first step was synthesis of C-3 substituted coumarin, via.
Pechmann condensation of resorcinol (1.0 g, 9 mmol) and alkylated ethyl acetoacetate
(60a,1.63 mL, 15.43 mmol) or (60b, 3.22 mL, 15.43 mmol) in concentrated sulfuric acid
(5 mL, dropwise) at 0 oC. The mixture was stirred at room temperature for 3-4 h. On
completion of the reaction, 100 mL ice/water was added. The crude solid so obtained was
then filtered, washed with water, dried and crystallized from ethanol to give the
coumarins (62, 78 %) / (63, 80 %) as pale yellow coloured crystals. In second step, 3-
alkyl-7-hydroxy-4-methylcoumarin (62 and 63, 5.68mmol) was added into a 50 mL 0.6
M NaOH solution in methanol with constant stirring at 0 °C. To this solution
epichlorohydrin (8.52 mmol) was added dropwise and the reaction was stirred for 24 hr at
room temperature. The progress of the reaction was monitored on TLC. After completion
of the reaction, methanol was completely evaporated under reduced pressure and the
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
106
residue thus obtained was extracted with chloroform (4 x 50 mL) and washed with brine
(2 x 20 mL). Organic layer was separated and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure and the crude product, thus obtained was purified
by column chromatography on silica gel using EtOAc:petroleum ether (2:8) as an eluent
to obtain pure product 64/65.
2.10.1.1. 3-Ethyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (64)
It was obtained as white solid in 70 % yield; m. p 103-105 °C;IR (cm-1
, KBr):, 2859,
1720, 1607, 1389, 1281, 1151, 1069, and 841 cm-1
; 1H NMR (400 MHz, CDCl3): δ 1.14
(3H, t, J = 8.1 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.66 ( 2H, q, J = 7.3 Hz, -CH2CH3),
2.79 (1H, dd, J = 5.1 & 2.9 Hz, -CHα), 2.94 (1H, t, J = 5.1 Hz, -CHβ), 3.39 (1H, m, -CH),
3.96 (1H, dd, J = 11 & 5.9 Hz, -OCHα), 4.33 (1H, dd, J = 11 & 2.9 Hz, -OCHβ), 6.80
(1H, d, J = 2.2 Hz, C-8H), 6.89 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 7.51 (1H, d, J = 8.8
Hz, C-5H); 13
C NMR (100.6 MHZ, CDCl3): δ 13.04 (-CH2CH3), 14.48 (C-4 CH3), 20.74
(-CH2CH3), 44.49 (-CH2), 49.77 (-CH), 69.02 (-OCH2), 101.21 (C-8), 112.23 (C-6),
114.63 (C-10), 125.11 (C-3), 125.43 (C-5), 145.67 (C-9), 153.42 (C-4), 160.21 (C-7),
161.81 (CO); HR-ESI-TOF-MS m/z 261.1115 ([M+H]+), calcd for [C15H16O4+H]
+
261.1121.
2.10.1.2. 3-Hexyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (65)
It was obtained as white solid in 70 % yield; m. p 104-105 °C;IR (cm-1
, KBr):, 2851,
1718, 1610, 1389, 1277, 1121, 1060, and 844 cm-1
; 1H NMR (400 MHz, CDCl3): δ 0.89
(3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.28-1.41 (6H, m, -CH2CH2(CH2)3CH3), 1.48-1.55 (2H,
m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3), 2.62 ( 2H, t, J = 7.3 Hz, -
CH2(CH2)4CH3), 2.79 (1H, dd, J = 4.4 & 2.2 Hz, -CHα), 2.94 (1H, t, J = 5.1 Hz, -CHβ),
3.39 (1H, m, -CH), 3.96 (1H, dd, J = 11 & 5.9 Hz, -OCHα), 4.33 (1H, dd, J = 10.9 & 2.9
Hz, -OCHβ), 6.80 (1H, d, J = 2.2 Hz, C-8H), 6.89 (1H, dd, J = 9.5 and 2.9 Hz, C-6H),
7.51 (1H, d, J = 8.8 Hz, C-5H); 13
C NMR (100.6 MHZ, CDCl3): δ 13.04 (-(CH2)5CH3),
14.48 (C-4CH3), 20.74 (-CH2(CH2)3CH2CH3), 25.40 (-CH2CH2(CH2)3CH3), 27.40 (-
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
107
(CH2)2CH2(CH2)2CH3), 29.9 (-(CH2)3CH2CH2CH3), 44.51 (-CH2), 49.78 (-CH), 69.03 (-
OCH2), 101.21 (C-8), 112.24 (C-6), 114.67 (C-10), 124.03 (C-3), 125.44 (C-5), 145.84
(C-4), 153.44 (C-9), 160.19 (C-7), 161.95 (CO); HR-ESI-TOF-MS m/z 317.1743
([M+H]+), calcd for [C19H24O4+H]
+ 317.1747.
2.10.2. Synthesis of 3-alkyl-7-(3-azido-2-hydroxypropyloxy)-4-methylcoumarin (66
and 67)
3-Alkyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (43.10 mmol), sodium azide (215.51
mmol) and ammonium chloride (103.44 mmol) were added to a 50 mL methanol-water
(4:1 v/v) solution. The reaction was carried out at 70 °C and the conversion and synthesis
of the product was monitored by TLC. Upon completion of the reaction, the methanol
was evaporated, 50 mL of water was added to the residue and the product extracted with
CHCl3 (3 x 30 mL). The organic layers were combined and dried over Na2SO4. The
alcohol 66 and 67 was purified by column chromatography using EtOAc : petroleum
ether (1:9) as an eluent to obtain pure product 66 and 67.
2.10.2.1. 7-(3-Azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin (66)
It was obtained as white solid in 90 % yield; m. p 88-90 °C;IR (cm-1
, KBr):, 2858, 2113,
1714, 1617, 1392, 1288, 1156, 1078, and 746 cm-1
; 1H NMR (400 MHz, CDCl3): δ 1.14
(3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.66 (2H, q, J = 7.3 Hz, -CH2CH3),
3.52-3.61 (2H, m, -CH2N), 4.07-4.27 (3H, m, -CH & -OCH2), 6.80 ( 1H, d, J = 2.2 Hz,
C-8H), 6.86 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 7.50 (d, 1H, J = 8.8 Hz, C-5H); 13
C NMR
(100.6 MHZ, CDCl3): δ 13.03 (-CH2CH3), 14.49 (C-4 CH3), 20.74 (-CH2CH3), 53.27 (-
CH2N3), 68.96 (-OCH2), 69.36 (-CH), 101.29 (C-8), 112.06 (C-6), 114.74 (C-10), 125.16
(C-3H), 125.47 (C-5), 145.82 (C-9), 153.36 (C-4), 160.07 (C-7), 161.94 (CO); HR-ESI-
TOF-MS m/z 326.1099 ([M+Na]+), calcd for [C15H17N3O4+Na]
+ 326.1111.
2.10.2.2. 7-(3-Azido-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
108
It was obtained as white solid in 85 % yield; m. p 84-86 °C;IR (cm-1
, KBr):, 2860, 2111,
1710, 1614, 1389, 1279, 1183, 1092, and 747 cm-1
; 1H NMR (400 MHz, CDCl3): δ 0.88
(3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.30-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.47-1.53 (2H,
m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3), 2.63 (2H, t, J = 7.3 Hz, -
CH2(CH2)4CH3), 3.52-3.60 (2H, m, -CH2N), 4.06-4.23 (3H, m, -CH & -OCH2), 6.79 (
1H, d, J = 2.2 Hz, C-8H), 6.86 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 7.51 (d, 1H, J = 8.8 Hz,
C-5H); 13
C NMR (100.6 MHZ, CDCl3): δ 14.03 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.57 (-
CH2(CH2)3CH2CH3), 27.47 (-CH2CH2(CH2)2CH3), 29.31 (-(CH2)2CH2(CH2)2CH3), 31.63
(-(CH2)3CH2CH2CH3), 53.26 (-CH2N3), 68.97 (-OCH2), 69.35 (-CH), 101.28 (C-8),
112.03 (C-6), 114.76 (C-10), 124.06 (C-3H), 125.47 (C-5), 145.98 (C-9), 153.36 (C-4),
160.03 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 360.1900 ([M+Na]+), calcd for
[C19H25N3O4+Na]+
360.1918.
2.10.3. General procedure for the synthesis of propargyl ethers of substituted
phenols 72a-u
To a stirred solution of substituted phenols (50 mmol) in acetone, equimolar amount of
propargyl bromide and K2CO3 were added. The reaction mixture was refluxed at 60 °C
for 12 hr.On completion of the reaction as indicated by the TLC, the solution was
evaporated at reduced pressure and then water (30 mL) was added. Subsequently, the
mixture was extracted with chloroform (3 x 30 mL), and organic phases were combined,
dried over anhydrous Na2SO4 and then evaporated under reduced pressure to produce
propargyl ethers 72a-u. The propargyl ethers of substituted phenols were used in the
following reactions without further purification.
2.10.4. General procedure for the synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-
triazol-1-yl)propyloxy)-3-alkyl-4-methylcoumarins 69a-d, 70a-d, 73a-u and
74a-u
To a solution of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarin
(66/67, 3.60 mmol) and commercially available alkynes 68a-d (4.32 mmol) or propargyl
ethers of substituted phenols 72a-u (4.32 mmol) in t-BuOH/H2O/THF (3 mL, 1/1/1,
v/v/v), was added sodium ascorbate(1.29 mmol) and copper (II) sulfate pentahydrate
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
109
(0.54 mmol). Thereafter the reaction mixture was stirred at 60 °C and the reaction was
monitored by TLC. On completion of the reaction the solvent was evaporated under
reduced pressure and the crude product thus obtained was purified by silica gel column
chromatography using methanol/chloroform as eluting solution to afford the desired
products 69a-d, 70a-d, 73a-uand 74a-u.
2.10.4.1.1. 3-Ethyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (69a)
It was obtained as white solid in 85 % yield; m. p 140-143 °C; IR (cm-1
, KBr): 3386,
2925, 2854, 1708, 1610, 1387, 1253, 1172, 1093 and 766 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 1.04 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H,s, C-4 CH3), 2.57 (2H, q, J =
7.3 Hz, -CH2CH3), 4.08-4.16 (2H, m, -CH2N), 4.31-4.35 (1H, m, -CH), 4.48 (1H, dd, J =
10.3 & 7.3 Hz, -OCHα), 4.68 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.70 (1H, d, J = 5.8
Hz, OH), 6.97-7.00 (2H, m, C-6H, C-8H), 7.31 (1H, t, J = 7.4 Hz, ArH), 7.42-7.47 (2H,
m, ArH), 7.71 (1H, d, J = 9.5 Hz, C-5H), 7.85-7.86 (2H, m, ArH), 8.57 (1H, s, triazole
H); 13
C NMR (100.6 MHZ, DMSO-d6): δ 12.97 (-CH2CH3), 14.32 (C-4 CH3), 20.21 (-
CH2CH3), 52.71 (-CH2N), 67.69 (-CH), 70.09 (-OCH2), 101.06 (C-8), 112.31 (C-6),
113.87 (C-10), 122.45 (C-3), 123.81 (CH=C), 125.10 (2-ArC), 126.32 (C-5), 127.75,
128.88, 130.86 (4-ArC), 146.09 (CH=C), 156.39 (C-9), 153.04 (C-4), 160.43 (C-7),
160.75 (CO); HR-ESI-TOF-MS m/z 406.1751 ([M+H]+), calcd for [C23H23N3O4+H]
+
406.1761.
2.10.4.1.2. 3-Ethyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-
methylcoumarin(69b)
It was obtained as white solid in 80 % yield; m. p 123-126 °C; IR (cm-1
, KBr): 3461,
2920, 2859, 1704, 1617, 1303, 1211, 1159, 1089 and 865 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 1.05 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.53-2.60 (4H,
m, -CH2CH3 and -CH2CH2COOH), 2.85 (2H, t, J = 7.3 Hz, -CH2CH2COOH), 4.01-4.08
(2H, m, -CH2N), 4.20-4.26 (1H, m, -CH), 4.39 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.55
(1H, dd, J = 13.9 & 3.6 Hz, -OCHβ), 5.61 (1H, brs, OH), 6.95-6.97 (2H, m, C-6H, C-8H),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
110
7.70 (1H, d, J = 8.7 Hz, C-5H), 7.85 (1H, s, triazole H), 12.17 (1H, s, -CH2CH2COOH);
13C NMR (100.6 MHZ, DMSO-d6): δ 12.89 (-CH2CH3), 14.25 (C-4 CH3), 20.15 (-
CH2CH3), 20.60 (-CH2CH2COOH), 33.09 (-CH2CH2COOH), 52.28 (-CH2N), 67.65 (-
CH), 70.00 (-OCH2), 100.95 (C-8), 112.23 (C-6), 113.79 (C-10), 122.92 (C-3), 123.75
(CH=C), 126.24 (C-5), 145.36 (CH=C), 146.33 (C-9), 152.96 (C-4), 160.35 (C-7), 160.69
(CO), 173.58 (COOH); HR-ESI-TOF-MS m/z 402.1656 ([M+H]+), calcd for
[C20H23N3O6+H]+
402.1660.
2.10.4.1.3. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl-
4-methylcoumarin (69c)
It was obtained as white solid in 88 % yield; m. p 104-108 °C; IR (cm-1
, KBr): 3398,
2922, 2854, 1713, 1609, 1387, 1281, 1181, 1093 and 822 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 1.05 (3H, t, J = 7.3 Hz, -CH2CH3), 2.04 (2H, pentate, -CH2CH2CH2Cl),
2.39 (3H, s, C-4 CH3), 2.56 (2H, q, J = 7.3 Hz, -CH2CH3), 2.75 (2H, t, J = 7.7 Hz, -
CH2CH2CH2Cl), 3.67 (2H, t, J = 6.9 Hz, -CH2CH2CH2Cl), 4.01-4.07 (2H, m, -CH2N),
4.21-4.26 (1H, m, -CH), 4.41 (1H, dd, J = 13.9 & 7.4 Hz, -OCHα), 4.56 (1H, dd, J = 13.9
& 3.6 Hz, -OCHβ), 5.62 (1H, d, J = 5.1 Hz, OH), 6.95-6.98 (2H, m, C-6H & C-8H), 7.70
(1H, d, J = 8.7 Hz, C-5H), 7.89 (1H, s, triazole H); 13
C NMR (100.6 MHZ, DMSO-d6): δ
12.96 (-CH2CH3), 14.32 (C-4 CH3), 20.20 (-CH2CH3), 22.28 (-CH2CH2CH2Cl), 31.79 (-
CH2CH2CH2Cl), 44.68 (-CH2CH2CH2Cl), 52.34 (-CH2N), 67.68 (-CH), 70.07 (-OCH2),
101.00 (C-8), 112.29 (C-6), 113.85 (C-10), 123.14 (C-3), 123.80 (CH=C), 126.31 (C-5),
145.17 (CH=C), 146.39 (C-9), 153.03 (C-4), 160.42 (C-7), 160.74 (CO); HR-ESI-TOF-
MS m/z 406.1521 ([M+H]+), calcd for [C20H24ClN3O4+H]
+ 406.1528.
2.10.4.1.4. 3-Ethyl-7-(2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (69d)
It was obtained as white solid in 92 % yield; m. p 101-103 °C; IR (cm-1
, KBr): 3305,
2922, 2854, 1676, 1617, 1307, 1230, 1163, 1098 and 828 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.96 (3H, t, J = 7.3 Hz, -CH2CH3), 2.31 (3H, s, C-4 CH3), 2.47 (2H, q, J =
7.3 Hz, -CH2CH3), 3.92-3.99 (2H, m, -CH2N), 4.13-4.20 (1H, m, -CH), 4.36 (1H, dd, J =
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
111
13.9 & 8.1 Hz, -OCHα), 4.43 (2H, d, J = 5.1 Hz, -CH2OH), 4.49 (1H, dd, J = 13.9 & 3.7
Hz, -OCHβ), 5.10 (1H, t, J = 5.5 Hz, -CH2OH), 5.54 (1H, d, J = 5.8 Hz, OH), 6.88-6.90
(2H, m, C-6H, C-8H), 7.63 (1H, d, J = 9.6 Hz, C-5H), 7.86 (1H, s, triazole H); 13
C NMR
(100.6 MHz, DMSO-d6): δ 12.99 (-CH2CH3), 14.36 (C-4 CH3), 20.24 (-CH2CH3), 52.33
(-CH2N), 55.08 (-CH=C-CH2), 67.75 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.33 (C-6),
113.89 (C-10), 123.73 (C-3), 123.84 (-CH=C), 126.36 (C-5), 146.45 (-CH=C), 147.75
(C-9), 153.05 (C-4), 160.45 (C-7), 160.79 (CO); HR-ESI-TOF-MS m/z 382.1365
([M+Na]+), calcd for [C18H21N3O5+Na]
+ 382.1373.
2.10.4.1.5. 3-Hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (70a)
It was obtained as white solid in 84 % yield; m. p 136-139 °C; IR (cm-1
, KBr): 3386,
2925, 2854, 1708, 1610, 1387, 1253, 1172, 1093 and 766 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.86 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.27-1.33 (6H, m, -
CH2CH2(CH2)3CH3), 1.39-1.43 (2H, m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3),
2.53 (2H, q, J = 7.3 Hz, -CH2(CH2)4CH3), 4.06-4.14 (2H, m, -CH2N), 4.31-4.35 (1H, m, -
CH), 4.50 (1H, dd, J = 13.9 & 8.4 Hz, -OCHα), 4.68 (1H, dd, J = 13.9 & 3.6 Hz, -OCHβ),
5.70 (1H, d, J = 5.1 Hz, OH), 6.96-6.99 (2H, m, C-6H & C-8H), 7.33 (1H, t, J = 7.4 Hz,
ArH), 7.45 (2H, t, J = 7.7 Hz, ArH), 7.70 (1H, d, J = 9.6 Hz, C-5H), 7.86 (2H, d, J = 7.3
Hz, ArH), 8.57 (1H, s, triazole H); 13
C NMR (100.6 MHZ, DMSO-d6): δ 13.96 (-
(CH2)5CH3), 14.63 (C-4 CH3), 22.70 (-CH2(CH2)3CH2CH3), 27.40 (-CH2CH2(CH2)3CH3),
29.4 (-(CH2)2CH2(CH2)2CH3), 31.90 (-(CH2)3CH2CH2CH3), 52.70 (-CH2N), 67.69 (-CH),
70.09 (-OCH2), 101.05 (C-8), 112.30 (C-6), 113.86 (C-10), 122.45 (C-3), 123.81
(CH=C), 125.10 (2-ArC), 126.32 (C-5), 127.75,128.87, 130.86 (4-ArC), 146.08 (CH=C),
156.39 (C-9), 153.04 (C-4), 160.42 (C-7), 160.75 (CO); HR-ESI-TOF-MS m/z 462.2381
([M+H]+), calcd for [C27H31N3O4+H]
+ 462.2387.
2.10.4.2. 3-Hexyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-
methylcoumarin(70b)
It was obtained as white solid in 82 % yield; m. p 118-120 °C; IR (cm-1
, KBr): 3461,
2920, 2859, 1704, 1617, 1303, 1211, 1159, 1084 and 865 cm-1
; 1H NMR (400 MHz,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
112
DMSO-d6): δ 0.86 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.24-1.35 (6H, m, -
CH2CH2(CH2)3CH3), 1.39-1.43 (2H, m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3),
2.53-2.67 (4H, m, -CH2(CH2)4CH3 and -CH2CH2COOH), 2.85 (2H, t, J = 7.3 Hz, -
CH2CH2COOH), 3.99-4.07 (2H, m, -CH2N), 4.20-4.23 (1H, m, -CH), 4.40 (1H, dd, J =
13.9 & 7.3 Hz, -OCHα), 4.55 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.61 (1H, d, J = 5.1
Hz, OH), 6.95-6.98 (2H, m, C-6H & C-8H), 7.69 (1H, d, J = 9.5 Hz, C-5H), 7.84 (1H, s,
triazole H), 12.17 (1H, d, -CH2CH2COOH); 13
C NMR (100.6 MHZ, DMSO-d6): δ 13.96
(-(CH2)5CH3, C-4 CH3), 14.63 (-CH2(CH2)3CH2CH3), 20.69 (-CH2CH2COOH), 22.07 (-
CH2CH2(CH2)CH3), 28.20 (-(CH2)2CH2(CH2)2CH3), 31.12 (-(CH2)3CH2CH2CH3), 33.17
(-CH2CH2COOH), 52.36 (-CH2N), 67.73 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.32
(C-6), 113.87 (C-10), 122.61 (C-3), 123.00 (CH=C), 126.34 (C-5), 145.45 (CH=C),
146.67 (C-9), 153.05 (C-4), 160.44 (C-7), 160.93 (CO), 173.66 (COOH); HR-ESI-TOF-
MS m/z 458.2284 ([M+H]+), calcd for [C24H31N3O6+H]
+ 458.2286.
2.10.4.3. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-hexyl-4-
methylcoumarin (70c)
It was obtained as white solid in 86 % yield; m. p 99-102 °C; IR (cm-1
, KBr): 3398, 2922,
2854, 1713, 1609, 1387, 1252, 1181, 1093 and 779 cm-1
; 1H NMR (400 MHz, DMSO-
d6): δ 0.84 (3H, t, J = 6.6 Hz, -(CH2)5CH3), 1.23-1.34 (6H, m, -CH2CH2(CH2)3CH3),
1.37-1.44 (2H, m, -CH2CH2(CH2)3CH3), 2.02 (2H, pentate, -CH2CH2CH2Cl), 2.36 (3H, s,
C-4 CH3), 2.48-2.52 (2H, m, -CH2(CH2)4CH3), 2.73 (2H, t, J = 7.4 Hz, -CH2CH2CH2Cl),
3.65 (2H, t, J = 6.9 Hz, -CH2CH2CH2Cl), 3.96-4.05 (2H, m, -CH2N), 4.20-4.24 (1H, m, -
CH), 4.38 (1H, dd, J = 13.9 & 7.6 Hz, -OCHα), 4.55 (1H, dd, J = 13.9 & 4.4 Hz, -OCHβ),
5.61 (1H, d, J = 5.8 Hz, OH), 6.92-6.95 (2H, m, C-6H, C-8H), 7.67 (1H, d, J = 8.8 Hz, C-
5H), 7.87 (1H, s, triazole H); 13
C NMR (100.6 MHZ, DMSO-d6): δ 13.96 (-(CH2)5CH3),
14.63 (C-4 CH3), 22.08 (-CH2CH2(CH2)3CH3), 22.29 (-(CH2)4CH2CH3), 26.82 (-
CH2CH2CH2Cl), 28.20 (-CH2CH2(CH2)3CH3), 28.67 (-(CH2)2CH2(CH2)2CH3), 31.13 (-
(CH2)3CH2CH2CH3), 31.82 (-CH2CH2CH2Cl), 44.69 (-CH2CH2CH2Cl), 52.36 (-CH2N),
67.71 (-CH), 70.08 (-OCH2), 101.01 (C-8), 112.29 (C-6), 113.86 (C-10), 122.60 (C-3),
123.16 (CH=C), 126.33 (C-5), 145.20 (CH=C), 146.65 (C-9), 153.04 (C-4), 160.42 (C-7),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
113
160.92 (CO); HR-ESI-TOF-MS m/z 462.2157 ([M+H]+), calcd for [C24H32ClN3O4+H]
+
462.2154.
2.10.4.4. 3-Hexyl-7-(2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (70d)
It was obtained as white solid in 92 % yield; m. p 106-108 °C; IR (cm-1
, KBr): 3305,
2922, 2854, 1676, 1617, 1307, 1230, 1163, 1013 and 828 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.86 (3H, t, J = 6.6 Hz, -(CH2)5CH3), 1.23-1.36 (6H, m, -
CH2CH2(CH2)3CH3), 1.37-1.46 (2H, m, -CH2CH2(CH2)3CH3), 2.39 (3H, s, C-4 CH3),
2.50-2.55 (2H, m, -CH2(CH2)4CH3), 4.00-4.05 (2H, m, -CH2N), 4.23-4.26 (1H, m, -CH),
4.44 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.52 (2H, d, J = 5.8 Hz, -CH2OH), 4.58 (1H,
dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.18 (1H, t, J = 5.9 Hz, -CH2OH) 5.62 (1H, d, J = 5.9 Hz,
OH), 6.96-6.98 (2H, m, C-6H, C-8H), 7.70 (1H, d, J = 9.5 Hz, C-5H), 7.95 (1H, s,
triazole H); 13
C NMR (100.6 MHz, DMSO-d6): δ 12.99 (-(CH2)5CH3), 14.36 (C-4 CH3),
22.50 (-CH2(CH2)3CH2CH3), 27.40 (-CH2CH2(CH2)3CH3), 31.90 (-(CH2)3CH2CH2CH3),
52.33 (-CH2N), 55.07 (-CH=C-CH2), 67.75 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.33
(C-6), 113.88 (C-10), 123.72 (C-3), 123.84 (-CH=C), 126.36 (C-5), 145.75 (-CH=C),
147.29 (C-9), 153.05 (C-4), 160.45 (C-7), 160.79 (CO); HR-ESI-TOF-MS m/z 416.2176
([M+H]+), calcd for [C22H29N3O5+H]
+ 416.2180.
2.10.4.4.1. 3-Ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-
methylcoumarin (73a)
It was obtained as white solid in 85 % yield; m. p 128-130 °C; IR (cm-1
, KBr): 3386,
2925, 2854, 1717, 1610, 1387, 1253, 1172, 1093, and 766 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.10 (3H, t, J = 7.1 Hz, -CH2CH3), 2.34 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3
Hz, -CH2CH3), 3.45 (1H, brs, OH), 4.01-4.05 (2H, m, -CH2N), 4.47-4.56 (2H, m, -CH &
-OCHα), 4.69 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh), 6.72-6.73 (1H,
m, C-8H), 6.80 (1H, dd, J = 8.7 & 2.3 Hz, C-6H), 6.90 (3H, m, ArH), 7.24 (2H, t, J = 7.3
Hz, ArH), 7.44 (1H, d, J = 8.8 Hz, C-5H), 7.78 (1H, s, triazole H); 13
C NMR (100.6
MHz, CDCl3): δ 13.03 (-CH2CH3), 14.48 (C-4 CH3), 20.72 (-CH2CH3), 52.99 (-CH2N),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
114
61.59 (-OCH2Ph), 68.29 (-CH), 69.25 (-OCH2), 101.28 (C-8), 112.15 (C-6), 114.60 (C-
10), 114.71 (2-ArC), 121.21 (C-3), 124.59 (CH=C), 125.05 (ArC), 125.48 (C-5), 129.46
(2-ArC), 143.88 (CH=C), 145.91 (C-9), 153.26 (C-4), 158.02 (C-7), 159.93 (ArC),
161.95 (CO); HR-ESI-TOF-MS m/z 436.1858 ([M+H]+), calcd for [C24H25N3O5+H]
+
436.1867.
2.10.4.5. 3-Ethyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73b)
It was obtained as white solid in 92 % yield; m. p 136-139 °C; IR (cm-1
, KBr): 3392,
2926, 2367, 1718, 1617, 1458, 1251, 1170, 1087, and 759 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.13 (3H, t, J = 7.7 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.65 (2H, q, J = 7.3
Hz, -CH2CH3), 3.81 (1H, brs, OH), 4.03-4.09 (2H, m, -CH2N), 4.53-4.61 (2H, m, -CH &
-OCHα), 4.74 (1H, dd, J = 13.2 & 2.2 Hz, -OCHβ), 5.25 (2H, s, -CH2OPh), 6.76 (1H, d, J
= 2.9 Hz, C-8H), 6.83 (1H, dd, J = 5.8 & 2.9 Hz, C-6H), 6.87-6.91 (1H, m, ArH), 7.05-
7.21 (2H, m, ArH), 7.31-7.33 (1H, m, ArH), 7.48 (1H, d, J = 9.5 Hz, C-5H), 7.86 (1H, s,
triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.03 (-CH2CH3), 14.48 (C-4CH3), 20.73
(-CH2CH3), 53.02 (-CH2N), 62.97 (-OCH2Ph), 68.30 (-CH), 69.24 (-OCH2), 101.24 (C-
8), 112.16 (C-6), 114.06 (C-3), 114.71 (C-10), 122.02 (2-ArC), 122.91 (CH=C), 124.69
(ArC), 125.06 (C-5), 127.74, 130.24 (2-ArC), 143.62 (CH=C), 145.91 (C-9), 153.27 (C-
4), 153.54 (C-7), 159.92 (ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 470.1477 ([M+H]+),
calcd for [C24H24ClN3O5+H]+
470.1477.
2.10.4.6. 3-Ethyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73c)
It was obtained as white solid in 85 % yield; m. p 111-113 °C; IR (cm-1
, KBr): 3392,
2954, 2853, 1718, 1611, 1493, 1387, 1285, 1169, 1091, and 825 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.08 (3H, t, J = 7.3 Hz, -CH2CH3), 2.35 (3H, s, C-4 CH3), 2.62 (2H, q, J
= 7.4 Hz, -CH2CH3), 3.76 (1H, brs, OH), 4.01-4.06 (2H, m, -CH2N), 4.50-4.60 (2H, m, -
CH& -OCHα), 4.71 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.13 (2H, s, -CH2OPh), 6.74-
6.93 (5H, m, C-6H & C-8H, ArH), 7.15 (1H, t, J = 8.1 Hz, ArH), 7.45 (1H, d, J = 8.8 Hz,
C-5H), 7.79 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.03 (-CH2CH3),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
115
14.50 (C-4 CH3), 20.74 (-CH2CH3), 53.00 (-CH2N), 61.87 (-OCH2Ph), 68.32 (-CH),
69.26 (-OCH2), 101.29 (C-8), 112.13 (C-6), 112.96 (C-3), 114.77 (C-10), 115.22 (2ArC),
121.41 (CH=C), 124.69 (ArC), 125.12 (C-5), 125.51, 130.25 (2-ArC), 143.34 (CH=C),
145.89 (C-9), 153.28 (C-4), 158.74 (C-7), 159.90 (ArC), 161.94 (CO); HR-ESI-TOF-MS
m/z 470.1480 ([M+H]+), calcd for [C24H24ClN3O5+H]
+ 470.1477.
2.10.4.7. 3-Ethyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73d)
It was obtained as white solid in 81 % yield; m. p 127-129 °C; IR (cm-1
, KBr): 3392,
2927, 2859, 1718, 1607, 1389, 1281, 1151, 1069, and 841 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.13 (3H, t, J = 7.7 Hz, -CH2CH3), 2.36 (3H, s, C-4 CH3), 2.64 (2H, q, J = 7.3
Hz, -CH2CH3), 3.94 (1H, brs, OH), 4.03-4.11 (2H, m, -CH2N), 4.51-4.60 (2H, m, -CH &
-OCHα), 4.74 (1H, dd, J = 13.9 & 2.2 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh), 6.74 (1H, d, J
= 2.9 Hz, C-8H), 6.81 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 6.85-6.88 (2H, m, ArH), 7.17-
7.21 (2H, m, ArH), 7.46 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13
C NMR
(100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.49 (C-4 CH3), 20.73 (-CH2CH3), 53.00 (-
CH2N), 61.89 (-OCH2Ph), 68.28 (-CH), 69.27 (-OCH2), 101.23 (C-8), 112.16 (C-6),
114.71 (C-10), 115.94 (2-ArC), 124.70 (C-3), 125.06 (CH=C), 125.49 (ArC), 126.07 (C-
5), 129.28 (2-ArC), 144.45 (CH=C), 145.95 (C-9), 153.23 (C-4), 156.59 (C-7), 159.89
(ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 470.1474 ([M+H]+), calcd for
[C24H24ClN3O5+H]+
470.1477.
2.10.4.8. 3-Ethyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73e)
It was obtained as white solid in 91 % yield; m. p 132-136 °C; IR (cm-1
, KBr): 3246,
2931, 2859, 1710, 1618, 1479, 1384, 1297, 1156, 1069, and 759 cm-1
; 1H NMR (400
MHz, CDCl3): δ δ 1.14 (3H, t, J = 7.3 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.65 (2H, q,
J = 8.1 Hz, -CH2CH3), 3.72 (1H, brs, OH), 4.03-4.09 (2H, m, -CH2N), 4.51-4.61 (2H, m,
-CH & -OCHα), 4.73 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.77
(1H, d, J = 2.9 Hz, C-8H), 6.81-6.86 (2H, m, C-6H & ArH), 7.03 (1H, dd, J = 8.1 & 1.8
Hz, ArH), 7.21-7.27 (1H, m, ArH), 7.47-7.51(2H, m, ArH, C-5H), 7.86 (1H, s, triazole
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
116
H); 13
C NMR (100.6 MHz, CDCl3): δ 13.08 (-CH2CH3), 14.55 (C-4CH3), 20.79 (-
CH2CH3), 52.94 (-CH2N), 63.25 (-OCH2Ph), 68.48 (-CH), 69.13 (-OCH2), 101.39 (C-8),
112.26 (C-6), 113.92 (C-3), 114.91 (C-10), 122.57 (2-ArC), 124.55 (CH=C), 125.30
(ArC), 125.57 (C-5), 128.55, 133.36 (2-ArC), 143.85 (CH=C), 145.76 (C-9), 153.38 (C-
4), 154.43 (C-7), 159.85 (ArC), 161.89 (CO); HR-ESI-TOF-MS m/z 514.0982 ([M+H]+),
calcd for [C24H24BrN3O5+H]+
514.0972.
2.10.4.9. 3-Ethyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73f)
It was obtained as white solid in 85 % yield; m. p 100-102 °C; IR (cm-1
, KBr): 3402,
2922, 2859, 1717, 1610, 1490, 1387, 1251, 1171, 1091 and 823 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.13 (3H, t, J = 7.7 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.65 (2H, q, J
= 7.3 Hz, -CH2CH3), 3.88 (1H, d, J = 4.4 HzOH), 4.03-4.10 (2H, m, -CH2N), 4.51-4.60
(2H, m, -CH & -OCHα), 4.74 (1H, dd, J = 13.9 & 2.9 Hz, -OCHβ), 5.14 (2H, s, -
CH2OPh), 6.75 (1H, d, J = 2.9 Hz, C-8H), 6.80-6.84 (3H, m, C-6H, ArH), 7.32-7.35 (2H,
m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13
C NMR (100.6 MHz,
CDCl3): δ 13.03 (-CH2CH3), 14.51 (C-4 CH3), 20.74 (-CH2CH3), 53.00 (-CH2N), 61.82 (-
OCH2Ph), 68.29 (-CH), 69.26 (-OCH2), 101.24 (C-8), 112.14 (C-6), 113.41 (C-3), 114.73
(C-10), 116.45 (2-ArC), 124.70 (CH=C), 125.08 (ArC), 125.50 (C-5), 132.22 (2-ArC),
143.42 (CH=C), 145.93 (C-9), 153.24 (C-4), 157.10 (C-7), 159.88 (ArC), 161.94 (CO);
HR-ESI-TOF-MS m/z 514.0965 ([M+H]+), calcd for [C24H24BrN3O5+H]
+ 514.0972.
2.10.4.10. 3-Ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73g)
It was obtained as white solid in 85 % yield; m. p 136-139 °C; IR (cm-1
, KBr): 3419,
2924, 2856, 1689, 1612, 1523, 1466, 1347, 1255, 1163, 1090 and 739 cm-1
; 1H NMR
(400 MHz, DMSO-d6): δ 1.14 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.57
(2H, q, J = 7.2 Hz, -CH2CH3), 4.01-4.10 (2H, m, -CH2N), 4.22-4.28 (1H, m, -CH), 4.48
(1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.62 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.36 (2H,
s, -CH2OPh), 5.64 (1H, d, J = 5.1 Hz, OH), 6.94-6.97 (2H, m, C-6H & C-8H), 7.11-7.15
(1H, m, ArH), 7.59-7.72 (3H, m, ArH), 7.85 (1H, d, J = 8.4 Hz, C-5H), 8.22 (1H, s,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
117
triazole H); 13
C NMR (100.6 MHz, DMSO-d6): δ 12.89 (-CH2CH3), 14.25 (C-4 CH3),
20.14 (-CH2CH3), 52.49 (-CH2N), 62.48 (-OCH2Ph), 67.53 (-CH), 69.98 (-OCH2), 100.93
(C-8), 112.24 (C-6), 113.80 (C-10), 115.50 (2-ArC), 120.81 (CH=C), 123.75 (C-3),
124.85 (ArC), 125.84 (C-5), 126.25, 134.21 (2-ArC), 139.66 (CH=C), 146.34 (C-9),
150.54 (C-4), 152.96 (C-7), 160.32 (ArC), 160.69 (CO); HR-ESI-TOF-MS m/z 481.1711
([M+H]+), calcd for [C24H24N4O7+H]
+ 481.1718.
2.10.4.11. 3-Ethyl-7-(2-hydroxy-3-(4-(3-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73h)
It was obtained as white solid in 88 % yield; m. p 136-140 °C; IR (cm-1
, KBr): 3210,
2929, 2869, 1716, 1618, 1527, 1350, 1251, 1163, 1062 and 829 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.14 (3H, t, J = 7.3 Hz, -CH2CH3), 2.38 (3H, s, C-4 CH3), 2.66 (2H, q, J
= 7.3 Hz, -CH2CH3), 3.35 (1H, brs, OH), 4.00-4.10 (2H, m, -CH2N), 4.50-4.62 (2H, m, -
CH& -OCHα), 4.75 (1H, dd, J = 13.8 & 3.2 Hz, -OCHβ), 5.28 (2H, s, -CH2OPh), 6.76
(1H, d, J = 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.7 & 2.8 Hz, C-6H), 7.30-7.51 (3H, m,
ArH), 7.81-7.86 (3H, m, ArH, C-5H & triazole H); 13
C NMR (100.6 MHz, CDCl3): δ
12.95 (-CH2CH3), 14.31 (C-4 CH3), 20.21 (-CH2CH3), 52.55 (-CH2N), 61.76 (-OCH2Ph),
67.61 (-CH), 70.06 (-OCH2), 101.03 (C-8), 109.06 (C-6), 112.29 (C-10), 113.88, 115.76
(2-ArC), 122.17 (CH=C), 123.84 (C-3), 125.91 (ArC), 126.30 (C-5), 130.66 (ArC),
141.68 (ArC), 146.39 (CH=C), 148.70 (C-9), 153.02 (C-4), 158.55 (C-7), 160.38 (ArC),
160.75 (CO); HR-ESI-TOF-MS m/z 481.1710 ([M+H]+), calcd for [C24H24N4O7+H]
+
481.1718.
2.10.4.12. 3-Ethyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73i)
It was obtained as white solid in 86 % yield; m. p 148-150 °C; IR (cm-1
, KBr): 3367,
2929, 2856, 1699, 1610, 1510, 1332, 1256, 1173, 1086 and 834 cm-1
; 1H NMR (400
MHz, DMSO-d6): δ 1.04 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s,C-4 CH3), 2.55 (2H,
q, J = 7.3 Hz, -CH2CH3), 4.00-4.10 (2H, m, -CH2N), 4.22-4.29 (1H, m, -CH), 4.48 (1H,
dd, J = 13.9 & 7.3 Hz, -OCHα), 4.63 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.33 (2H, s, -
CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.95-6.97 (2H, m, C-6H, C-8H), 7.26-7.28 (2H,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
118
m, ArH), 7.70 (1H, d, J = 8.8 Hz, C-5H), 8.18-8.23 (2H, m, ArH), 8.27 (1H, s, triazole
H); 13
C NMR (100 MHz, DMSO-d6): δ 12.88 (-CH2CH3), 14.24 (C-4 CH3), 20.15 (-
CH2CH3), 52.51 (-CH2N), 61.83 (-OCH2Ph), 67.54 (-CH), 69.99 (-OCH2), 100.95 (C-8),
112.20 (C-6), 113.80 (C-10), 115.21 (2ArC), 123.77 (C-3) (CH=C), 125.75, 125.99
(3ArC), 126.23 (C-5), 141.35 (CH=C), 146.32 (C-9), 152.95 (C-4), 160.30 (C-7), 160.68
(ArC), 163.23 (CO); HR-ESI-TOF-MS m/z 481.1703 ([M+H]+), calcd for
[C24H24N4O7+H]+
481.1718.
2.10.4.13. 3-Ethyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73j)
It was obtained as white solid in 83 % yield; m. p 123-126 °C; IR (cm-1
, KBr): 3385,
2922, 2852, 1716, 1611, 1387, 1250, 1121, 1025 and 748 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.15 (3H, t, J = 8.1 Hz, -CH2CH3), 2.28 (Ph-CH3), 2.35 (3H, s, C-4 CH3), 2.63
(2H, q, J = 8.1 Hz, -CH2CH3), 3.85 (1H, d, J = 5.1 Hz, OH), 4.03-4.6 (2H, m, -CH2N),
4.47-4.57 (2H, m, -CH & -OCHα), 4.70 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.14 (2H, s,
-CH2OPh), 6.72-6.85 (5H, m, C-6H, C-8H & 3-ArH), 7.13 (1H, m, ArH), 7.46 (1H, d, J
= 8.7 Hz, C-5H), 7.77 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.02 (-
CH2CH3), 14.48 (Ph-CH3), 16.12 (C-4 CH3), 20.73 (-CH2CH3), 52.94 (-CH2N), 61.99 (-
OCH2Ph), 68.32 (-CH), 69.24 (-OCH2), 101.29 (C-8), 111.35 (C-6), 112.11 (ArC),
114.74 (C-10), 120.93 (ArC, CH=C), 124.30 (ArC), 125.10 (C-3H), 125.49 (ArC),
126.91 (C-5), 130.72 (ArC), 144.43 (CH=C), 145.87 (C-9), 153.29 (C-4), 156.20 (C-7),
159.94 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z 450.2010 ([M+H]+), calcd for
[C25H27N3O5+H]+
450.2023.
2.10.4.14. 3-Ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73k)
It was obtained as white solid in 86 % yield; m. p 121-124 °C; IR (cm-1
, KBr): 3511,
2924, 2852, 1718, 1610, 1458, 1259, 1173, 1085 and 777 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.13 (3H, t, J = 7.4 Hz, -CH2CH3), 2.17 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.64
(2H, q, J = 8.1 Hz, -CH2CH3), 3.57 (d, 1H, J = 5.1 Hz, OH), 4.00-4.08 (2H, m, -CH2N),
4.48-4.60 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.18 (2H, s,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
119
-CH2OPh), 6.76-6.92 (4H, m, C-6H, C-8H & ArH), 7.09-7.14 (2H, m, ArH), 7.47 (1H, d,
J = 8.7 Hz, C-5H), 7.75 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.02 (-
CH2CH3), 14.48 (C-4 CH3), 20.72 (-CH2CH3), 21.42 (Ph-CH3), 53.00 (-CH2N), 61.58 (-
OCH2Ph), 68.31 (-CH), 69.27 (-OCH2), 101.28 (C-8), 111.43 (C-6), 112.13 (C-3, ArC),
114.71 (C-10), 115.46 (ArC), 122.05 (CH=C), 124.53, 125.06 (2ArC), 129.17 (C-5),
139.52 (ArC), 143.99 (CH=C), 145.88 (C-9), 153.28 (C-4), 158.05 (C-7), 159.95 (ArC),
161.93 (CO); HR-ESI-TOF-MS m/z 450.2023 ([M+H]+), calcd for [C25H27N3O5+H]
+
450.2023.
2.10.4.15. 3-Ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73l)
It was obtained as white solid in 84 % yield; m. p 127-130 °C; IR (cm-1
, KBr): 3386,
2920, 2852, 1721, 1610, 1510, 1383, 1247, 1176, 1089 and 831 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.12 (3H, t, J = 7.3 Hz, -CH2CH3), 2.26 (Ph-CH3), 2.36 (3H, s, C-4
CH3), 2.64 (2H, q, J = 7.3 Hz, -CH2CH3), 3.78 (1H, d, J = 5.1 Hz, OH), 4.01-4.08 (2H,
m, -CH2N), 4.51-4.57 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ),
5.13 (2H, s, -CH2OPh), 6.75-6.85 (4H, m, C-6H, C-8H & ArH), 7.03-7.06 (2H, m, Ar′H),
7.46 (1H, d, J = 8.7 Hz, C-5H), 7.78 (1H, s, triazole H); 13
C NMR (100.6 MHZ, CDCl3):
δ 13.08 (-CH2CH3), 14.55 (C-4 CH3), 20.45 (-CH2CH3), 20.79 (Ph-CH3), 52.91 (-CH2N),
61.89 (-OCH2Ph), 68.51 (-CH), 69.17 (-OCH2), 101.46 (C-8), 111.97 (C-6), 114.54 (C-3,
ArC), 114.91 (C-10), 124.44 (ArC), 125.31 (CH=C), 125.57, 129.95 (3ArC), 130.56 (C-
5), 144.30 (CH=C), 145.76 (C-9), 153.38 (C-4), 155.96 (C-7), 159.86 (ArC), 161.91
(CO); HR-ESI-TOF-MS m/z 450.2023 ([M+H]+), calcd for [C25H27N3O5+H]
+ 450.2026.
2.10.4.16. 3-Ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (73m)
It was obtained as white solid in 83 % yield; m. p 130-132 °C; IR (cm-1
, KBr): 3401,
2963, 2859, 1674, 1605, 1508, 1387, 1254, 1122, 1030 and 735 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.11 (3H, t, J = 7.7 Hz, -CH2CH3), 2.35 (3H, s, C-4 CH3), 2.62 (2H, q, J
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
120
= 8.1 Hz, -CH2CH3), 3.80 (2H, m, Ph-OCH3 & OH), 4.01-4.05 (2H, m, -CH2N), 4.45-
4.54 (2H, m, -CH & -OCHα), 4.68 (1H, dd, J = 11.9 & 2.9 Hz, -OCHβ), 5.23 (2H, s, -
CH2OPh), 6.74 (1H, d, J = 2.9 Hz, C-8H), 6.79-6.94 (4H, m, C-6H & ArH), 6.98-7.00
(1H, m, ArH), 7.45 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13
C NMR (100.6
MHz, CDCl3): δ 13.03 (-CH2CH3), 14.49 (C-4 CH3), 20.74 (-CH2CH3), 52.94 (-CH2N),
55.72 (Ph-OCH3), 62.82 (-OCH2Ph), 68.36 (-CH), 69.22 (-OCH2), 101.32 (C-8), 111.77
(C-6), 112.07 (C-3), 114.27 (ArC), 114.75 (C-10), 120.78 (ArC), 121.88 (CH=C),
124.78, 125.12 (2ArC), 125.48 (C-5), 144.02 (ArC), 145.81 (CH=C), 147.42 (C-9),
149.49 (C-4), 153.31 (C-7), 159.92 (ArC), 161.91 (CO); HR-ESI-TOF-MS m/z 466.1978
([M+H]+), calcd for [C25H27N3O6+H]
+ 466.1973.
2.10.4.17. 3-Ethyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (73n)
It was obtained as white solid in 86 % yield; m. p 90-93 °C; IR (cm-1
, KBr): 3228, 2938,
2859, 1708, 1617, 1458, 1295, 1155, 1057 and 841 cm-1
; 1H NMR (400 MHz, CDCl3): δ
1.13 (3H, t, J = 7.32 Hz, -CH2CH3), 2.37 (3H, s,C-4 CH3), 2.65 (2H, q, J = 7.32 Hz, -
CH2CH3), 3.71 ( 1H, brs, OH), 3.77 (1H, s, Ph-OCH3), 4.03-4.10 (m, 2H, -NCH2), 4.50-
4.59 (m, 2H, -CH, -OCHα), 4.72 (dd, 1H, J = 12.44 & 2.20 Hz, -OCHβ), 5.16 (s, 2H, -
CH2OPh), 6.51-6.57 (3H, m, C-6H, C-8H & ArH), 6.77-6.85 (2H, m, ArH), 7.14-7.19
(m, 1H, ArH), 7.48 (d, 1H, J = 8.80 Hz, C-5H), 7.80 (s, 1H, triazole H); 13
C NMR (100.6
MHz, CDCl3): δ 13.04 (-CH2CH3), 14.49 (C-4 CH3), 20.75 (-CH2CH3), 52.98 (-NCH2),
55.21 (Ph-OCH3), 61.76 (-OCH2Ph), 68.36 (-CH), 69.25 (-OCH2), 101.19 (C-8), 106.65
(C-6), 106.84 (C-3, ArC), 112.11 (C-10), 114.77 (ArC), 124.58 (CH=C), 125.13, 125.51
(2-ArC), 129.92 (C-5), 143.84 (ArC), 145.87 (CH=C), 153.31 (C-9), 159.29 (C-4),
159.92 (C-7), 160.74 (ArC), 161.94 (CO); HR-ESI-TOF-MS m/z 466.1975 ([M+H]+),
calcd for [C25H27N3O6+H]+
466.1973.
2.10.4.18. 3-Ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73o)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
121
It was obtained as white solid in 83 % yield; m. p 172-174 °C; IR (cm-1
, KBr): 3273,
2932, 2873, 1711, 1617, 1439, 1297, 1155, 1061 and 760; 1H NMR (400 MHz, CDCl3): δ
1.13 (3H, t, J = 7.3 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.64 (2H, q, J = 7.3 Hz, -
CH2CH3), 3.70 (1H, d, J = 5.2 Hz, OH), 4.03-4.08 (2H, m, -CH2N), 4.52-4.63 (1H, m, -
CH & -OCHα), 4.74 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.25 (2H, s, -CH2OPh), 6.69-
6.96 (4H, m, C-6H, C-8 & ArH), 7.25-7.30 (1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz, C-
5H), 7.72-7.74 (1H, m, ArH), 7.89 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ
13.05 (-CH2CH3), 14.52 (C-4 CH3), 20.77 (-CH2CH3), 53.00 (-CH2N), 63.39 (-OCH2Ph),
68.39 (-CH), 69.19 (-OCH2), 101.36 (C-8), 112.13 (C-6), 112.27 (C-10), 114.48 (2ArC),
123.18 (C-3), 124.64 (CH=C), 125.54 (ArC), 129.55 (C-5), 139.38 (2ArC, CH=C),
145.83 (C-9), 153.33 (C-4), 156.59 (C-7), 159.92 (ArC), 161.92 (CO); HR-ESI-TOF-MS
m/z 562.0839 ([M+H]+), calcd for [C24H24IN3O5+H]
+ 562.0833.
2.10.4.19. 3-Ethyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73p)
It was obtained as white solid in 85 % yield; m. p 162-165 °C; IR (cm-1
, KBr): 3384,
2922, 2852, 1715, 1611, 1487, 1386, 1249, 1175, 1096 and 824 cm-1
; 1H NMR (400
MHz, CDCl3): δ 1.11 (3H, t, J = 7.3 Hz, -CH2CH3), 2.35 (3H, s, C-4 CH3), 2.62 (2H, q, J
= 7.3 Hz, -CH2CH3), 3.78 (1H, brs, OH), 4.00-4.08 (2H, m, -CH2N), 4.49-4.57 (2H, m, -
CH & -OCHα), 4.71 (1H, dd, J = 13.2 & 3.7 Hz, -OCHβ), 5.11 (2H, s, -CH2OPh), 6.68-
6.82 (4H, m, C-6H, C-8H & ArH), 7.44-7.51 (3H, m, ArH, C-5H), 7.78 (1H, s, triazole
H); 13
C NMR (100.6 MHz, CDCl3): δ 13.05 (-CH2CH3), 14.55 (C-4 CH3), 20.76 (-
CH2CH3), 53.00 (-CH2N), 61.72 (-OCH2Ph), 68.32 (-CH), 69.27 (-OCH2), 101.28 (C-8),
112.13 (C-6), 114.78 (C-10), 117.05 (2ArC, C-3), 124.69 (CH=C), 125.14 (ArC), 125.52
(C-5), 138.20 (2ArC, CH=C), 145.91 (C-9), 153.27 (C-4), 157.89 (C-7), 159.87 (ArC),
161.94 (CO);HR-ESI-TOF-MS m/z 562.0839 ([M+H]+), calcd for [C24H24IN3O5+H]
+
562.0833.
2.10.4.20. 3-Ethyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73q)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
122
It was obtained as white solid in 87 % yield; m. p 120-122 °C; IR (cm-1
, KBr): 3392,
2935, 2875, 1706, 1616, 1490, 1298, 1160, 1070 and 840 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.11 (3H, t, J = 7.7 Hz, -CH2CH3), 2.35 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3
Hz, -CH2CH3), 3.64 (1H, d, J = 5.1 Hz, OH), 4.00-4.07 (2H, m, -CH2N), 4.48-4.58 (2H,
m, -CH & -OCHα), 4.71 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh),
6.62-6.82 (5H, m, C-6H, C-8H & ArH), 7.16-7.21 (1H, m, ArH), 7.46 (1H, d, J = 8.8 Hz,
C-5H), 7.79 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3),
14.48 (C-4 CH3), 20.73 (-CH2CH3), 53.01 (-CH2N), 61.89 (-OCH2Ph), 68.31 (-CH),
69.27 (-OCH2), 101.27 (C-8), 102.41 (C-6), 102.66 (C-3), 107.96 (C-10), 108.17, 110.26
(2ArC), 112.16 (CH=C), 114.74 (ArC), 124.71 (C-5), 125.50, 130.21 (2ArC), 145.95
(CH=C), 153.26 (C-9), 159.30 (C-4), 159.92 (C-7), 161.97 (ArC), 164.65 (CO); HR-ESI-
TOF-MS m/z 454.1773 ([M+H]+), calcd for [C24H24FN3O5+H]
+ 454.1773.
2.10.4.21. 3-Ethyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73r)
It was obtained as white solid in 85 % yield; m. p 126-129 °C; IR (cm-1
, KBr): 3384,
2963, 2873, 1705, 1616, 1510, 1298, 1159, 1095 and 822 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.13 (3H, t, J = 7.4 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.65 (2H, q, J = 7.4
Hz, -CH2CH3), 3.67 (1H, d, J = 4.4 Hz, OH), 4.02-4.10 (2H, m, -CH2N), 4.52-4.60 (2H,
m, -CH & -OCHα), 4.74 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.15 (2H, s, -CH2OPh),
6.76-6.97 (6H, m, C-6H, C-8H & ArH), 7.48 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s,
triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.48 (C-4 CH3), 20.74
(-CH2CH3), 52.98 (-CH2N), 62.31 (-OCH2Ph), 68.33 (-CH), 69.28 (-OCH2), 101.29 (C-
8), 112.15 (C-6), 114.77 (C-3), 115.70 (C-10), 115.74, 115.82 (2ArC), 115.93 (CH=C),
125.13 (ArC), 125.50 (C-5), 143.72, 145.91 (2ArC), 153.28 (CH=C), 154.13 (C-9),
156.23 (C-4), 158.62 (C-7), 159.91 (ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 454.1783
([M+H]+), calcd for [C24H24FN3O5+H]
+ 454.1773.
2.10.4.22. 3-Ethyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (73s)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
123
It was obtained as white solid in 89 % yield; m. p 128-131 °C; IR (cm-1
, KBr): 3421,
2925, 2856, 1707, 1609, 1387, 1251, 1177, 1085 and 761 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.10 (3H, t, J = 7.6 Hz, -CH2CH3), 2.33 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3
Hz, -CH2CH3), 3.61 (1H, d, J = 4.5 Hz, OH), 4.00-4.08 (2H, m, -CH2N), 4.50-4.58 (2H,
m, -CH & -OCHα), 4.70 (1H, dd, J = 13.7 & 2.8 Hz, -OCHβ), 5.21 (2H, s, -CH2OPh),
6.75 (1H, d, J = 2.3 Hz, C-8H), 6.80 (1H, dd, J = 2.8 & 8.7 Hz, C-6H), 6.99-7.02 (2H, m,
ArH), 7.26-7.52 (8H, m, C-5H, ArH), 7.80 (1H, s, triazole H); 13
C NMR (100.6 MHZ,
CDCl3): δ 13.02 (-CH2CH3), 14.45 (C-4 CH3), 20.72 (-CH2CH3), 53.03 (-CH2N), 61.75
(-OCH2Ph), 68.31 (-CH), 69.28 (-OCH2), 101.28 (C-8), 112.11 (C-6), 114.71 (C-10),
114.93 (2ArC), 124.66 (C-3), 125.47 (CH=C), 126.57 (C-5), 126.70 (3ArC), 128.05
(3ArC), 128.67 (2-ArC), 140.39 (ArC), 143.79 (CH=C), 145.89 (C-9), 153.26 (C-4),
157.58 (C-7), 159.91 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z 512.2171 ([M+H]+),
calcd for [C30H29N3O5+H]+ 512.2180.
2.10.4.23. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (73t)
It was obtained as white solid in 89 % yield; m. p 142-146 °C; IR (cm-1
, KBr): 3161,
2925, 2856, 1718, 1621, 1466, 1294, 1182, 1084 and 845 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.11 (3H, t, J = 7.3 Hz, -CH2CH3), 2.33 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3
Hz, -CH2CH3), 3.62 (1H, d, J = 5.12 Hz, OH), 4.00-4.07 (2H, m, -CH2N), 4.48-4.57 (2H,
m, -CH & -OCHα), 4.70 (1H, dd, J = 13.7 & 2.8 Hz, -OCHβ), 5.28 (2H, s, -CH2OPh),
6.74 (1H, d, J = 2.2 Hz, C-8H), 6.79 (1H, dd, J = 2.2 & 8.8 Hz, C-8H), 7.10-7.22 (2H,
m, ArH), 7.29-7.73 (6H, m, C-5H, ArH), 7.81 (1H, s, triazole H); 13
C NMR (100.6 MHz,
CDCl3): δ 13.02 (-CH2CH3), 14.43 (C-4 CH3), 20.72 (-CH2CH3), 53.03 (-CH2N), 61.66 (-
OCH2Ph), 68.31 (-CH), 69.27 (-OCH2), 101.24 (C-8), 107.02 (ArC), 112.08 (C-6),
114.67 (C-10), 118.59 (ArC), 123.82 (C-3), 124.70 (ArC), 125.44 (CH=C), 127.52
(ArC), 129.46 (ArC), 143.71 (ArC), 145.88 (CH=C), 153.23 (C-4), 155.94 (C-9), 159.89
(C-7), 161.93 (CO); HR-ESI-TOF-MS m/z 486.2021 ([M+H]+), calcd for
[C28H27N3O5+H]+
486.2023.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
124
2.10.4.24. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (73u)
It was obtained as white solid in 90 % yield; m. p 110-113 °C; IR (cm-1
, KBr): 3374,
2932, 2872, 1698, 1608, 1389, 1268, 1151, 1097 and 771 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 1.11 (3H, t, J = 7.3 Hz, -CH2CH3), 2.31 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3
Hz, -CH2CH3), 3.76 (1H, brs, OH), 3.99-4.06 (2H, m, -CH2N), 4.52-4.58 (1H, m, -CH &
-OCHα), 4.70 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.30 (2H, s, -CH2OPh), 6.72 (1H, d, J
= 2.9 Hz, C-8H), 6.78 (1H, dd, J = 2.2 & 8.8 Hz, C-6H), 6.89 (1H, d, J = 7.3 Hz, ArH),
7.28-7.46 (5H, m, ArH), 7.75 (1H, d, J = 8.1 Hz, C-5H), 7.83 (1H, s, Triazole), 8.15 (1H,
d, J = 8.8 Hz, ArH); 13
C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.43 (C-4
CH3), 20.72 (-CH2CH3), 53.01 (-CH2N), 62.07 (-CH), 68.32 (-OCH2), 69.25 (-OCH2Ph),
101.23 (C-8), 105.20 (ArC), 112.08 (C-6), 114.68 (C-10), 120.79 (C-3), 121.81, 124.56,
125.04 (3ArC), 125.19 (C-5), 125.04, 125.40, 125.46 (3ArC), 126.38 (CH=C), 127.39,
134.38 (2-ArC), 143.99 (CH=C), 145.89 (C-4), 153.23 (C-9), 153.72 (ArC), 159.88 (C-
7), 161.95 (CO); HR-ESI-TOF-MS m/z 486.2018 ([M+H]+), calcd for [C28H27N3O5+H]
+
486.2023.
2.10.4.25. 3-Hexyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74a)
It was obtained as white solid in 85 % yield; m. p 101-104 °C; IR (cm-1
, KBr): 3385,
2920, 2851, 1717, 1611, 1387, 1260, 1172, 1026 and 770 cm-1
cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.89 (3H, t, J = 7.0 Hz, -(CH2)5CH3), 1.25-1.40 (6H, m, -CH2CH2(CH2)3CH3),
1.46-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 7.3 Hz, -
CH2(CH2)4CH3), 4.02-4.09 (2H, m, -CH2N), 4.47-4.59 (2H, m, -CH & -OCHα), 4.72 (1H,
dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.19 (2H, s, -CH2OPh), 6.78 (1H, d, J = 2.9 Hz, C-8H),
6.83 (1H, dd, J = 8.8 & 1.5 Hz, C-6H), 6.94-6.96 (3H, m, ArH), 7.25-7.30 (2H, t, J = 8.8
Hz, ArH), 7.47 (1H, d, J = 8.7 Hz, C-5H), 7.79 (1H, s, triazole H); 13
C NMR (100.6
MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.79 (C-4 CH3), 21.46 (-CH2(CH2)3CH2CH3),
22.59 (-CH2(CH2)3CH2CH3), 28.74 (-CH2CH2(CH2)3CH3), 29.35 (-CH2CH2(CH2)3CH3),
31.66 (-(CH2)3CH2CH2CH3), 53.00 (-CH2N), 61.66 (-CH), 68.38 (-OCH2), 69.27 (-
OCH2Ph), 101.35 (C-8), 111.48 (C-6,C-10), 112.11 (2ArC), 115.52 (ArC), 122.09 (C-3),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
125
124.52 (C-5), 125.52 (CH=C), 129.21 (2ArC), 139.59 (CH=C), 146.02 (C-4), 153.33 (C-
9), 158.09 (ArC), 159.92 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 492.2493 ([M+H]+),
calcd for [C28H33N3O5+H]+
492.2493.
2.10.4.26. 3-Hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74b)
It was obtained as white solid in 92 % yield; m. p 134-138 °C; IR (cm-1
, KBr): 3392,
2926, 2872, 1718, 1617, 1458, 1280, 1170, 1087 and 759 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.89 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.40 (6H, m, -CH2CH2(CH2)3CH3),
1.45-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, d, J = 7.3 Hz, -
CH2(CH2)4CH3), 3.75 (1H, brs, OH), 4.04-4.09 (2H, m, -CH2N), 4.53-4.60 (2H, m, -CH
& -OCHα), 4.74 (1H, dd, J = 13.2 & 2.2 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.76 (1H, d,
J = 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 6.87-7.34 (4H, m, ArH), 7.47
(1H, d, J = 8.8 Hz, C-5H), 7.85 (1H, s, triazole H); 13
C NMR (100.6MHz, CDCl3): δ
14.03 (-(CH2)5CH3), 14.77 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.46 (-
CH2(CH2)3CH2CH3), 28.69 (-CH2CH2(CH2)3CH3), 29.32 (-(CH2)2CH2(CH2)2CH3), 31.62
(-(CH2)3CH2CH2CH3), 53.03 (-CH2N), 62.97 (-CH), 68.29 (-OCH2), 69.23 (-OCH2Ph),
101.23 (C-8), 112.13 (C-6), 114.07 (C-10), 114.73, 122.03, 122.92 (3ArC), 123.97 (C-3),
124.70 (C-5), 125.48 (CH=C), 127.74 (2ArC), 130.24 (CH=C), 146.06 (C-4), 153.27 (C-
9), 153.54 (ArC), 159.92 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 526.2109 ([M+H]+),
calcd for [C28H32ClN3O5+H]+
526.2103.
2.10.4.27. 3-Hexyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74c)
It was obtained as white solid in 85 % yield; m. p 100-102 °C; IR (cm-1
, KBr): 3393,
2927, 2855, 1705, 1616, 1383, 1298, 1159, 1087 and 768 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.89 (3H, t, J = 6.6 Hz, -(CH2)5CH3), 1.26-1.38 (6H, m, -CH2CH2(CH2)3CH3),
1.46-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, d, J = 7.7 Hz, -
CH2(CH2)4CH3), 3.75 (1H, brs, OH), 4.03-4.09 (2H, m, -CH2N), 4.53-4.60 (2H, m, -CH
& -OCHα), 4.73 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.16 (2H, s, -CH2OPh), 6.76-6.95
(5H, m, C-6H, C-8H & ArH), 7.15 (1H, t,J = 8.1 Hz, ArH), 7.48 (1H, d, J = 8.8 Hz, C-
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
126
5H), 7.81 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3),
14.81 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.49 (-CH2(CH2)3CH2CH3), 28.72 (-
CH2CH2(CH2)3CH3), 29.34 (-(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.99
(-CH2N), 61.89 (-CH), 68.37 (-OCH2), 69.24 (-OCH2Ph), 101.31 (C-8), 112.08 (C-6),
114.03 (C-10), 112.97, 115.24, 121.44 (3ArC), 124.10 (C-3), 124.65 (C-5), 125.53
(CH=C), 130.26, 134.84 (2ArC), 143.39 (CH=C), 146.01 (C-4), 153.31 (C-9), 158.75 (C-
7), 159.85 (ArC), 162.06 (CO); HR-ESI-TOF-MS m/z 526.2106 ([M+H]+), calcd for
[C28H32ClN3O5+H]+
526.2103.
2.10.4.28. 3-Hexyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74d)
It was obtained as white solid in 81 % yield; m. p 122-126 °C; IR (cm-1
, KBr): 3392,
2922, 2853, 1718, 1611, 1387, 1250, 1091 and 825 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.45-1.54
(2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 7.3 Hz, -
CH2(CH2)4CH3), 3.71 (1H, brs, OH), 4.02-4.10 (2H, m, -CH2N), 4.51-4.60 (2H, m, -CH
& -OCHα), 4.74 (1H, dd, J = 13.9 & 2.2 Hz, -OCHβ), 5.15 (2H, s, -CH2OPh), 6.75 (1H, d,
J = 2.9 Hz, C-8H), 6.81 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 6.85-6.89 (2H, m, ArH), 7.17-
7.21 (2H, m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13
C NMR
(100.5 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.81 (C-4 CH3), 22.59 (-
CH2(CH2)3CH2CH3), 27.49 (-CH2(CH2)3CH2CH3), 28.72 (-CH2CH2(CH2)3CH3), 29.35 (-
(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.98 (-CH2N), 61.96 (-CH), 68.36
(-OCH2), 69.26 (-OCH2Ph), 101.31 (C-8), 112.08 (C-6), 114.84 (C-10), 115.99, 124.12
(3ArC), 124.62 (C-3), 125.53 (C-5), 126.13 (CH=C), 129.33 (2ArC), 143.56 (CH=C),
146.02 (ArC), 153.31 (C-4), 156.63 (C-9), 159.84 (C-7), 162.06 (CO); HR-ESI-TOF-MS
m/z 526.2103 ([M+H]+), calcd for [C28H32ClN3O5+H]
+ 526.2103.
2.10.4.29. 3-Hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74e)
It was obtained as white solid in 91 % yield; m. p 129-133 °C; IR (cm-1
, KBr): 3232,
2925, 2853, 1718, 1621, 1487, 1297, 1170, 1087 and 757 cm-1
; 1H NMR (400 MHz,
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
127
CDCl3): δ 0.89 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.40 (6H, m, -CH2CH2(CH2)3CH3),
1.46-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1 Hz, -
CH2(CH2)4CH3), 3.80 (1H, brs, OH), 4.03-4.09 (2H, m, -CH2N), 4.53-4.61 (2H, m, -CH
& -OCHα), 4.73 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.77 (1H,
d, J = 2.9 Hz, C-8H), 6.81-6.86 (2H, m, C-6H, ArH), 7.03 (1H, dd, J = 8.1 & 1.5 Hz,
ArH), 7.21-7.27 (1H, m, ArH), 7.46-7.51(2H, m, ArH and C-5H), 7.86 (1H, s triazole H);
13C NMR (100.6 MHz, CDCl3): δ 14.04 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.58 (-
CH2(CH2)3CH2CH3), 27.49 (-CH2CH2(CH2)3CH3), 29.33 (-(CH2)2CH2(CH2)2CH3), 31.64
(-(CH2)3CH2CH2CH3), 53.00 (-CH2N), 63.18 (-CH), 68.36 (-OCH2), 69.19 (-OCH2Ph),
101.30 (C-8), 112.09 (C-6, ArC), 112.23 (C-10), 113.89 (ArC), 114.81 (C-3), 122.54
(ArC), 124.08 (C-5), 124.61 (CH=C), 125.52, 128.52 (2ArC), 133.32 (CH=C), 145.99
(C-4), 153.32 (C-9), 154.40 (ArC), 159.87 (C-7), 162.04 (CO); HR-ESI-TOF-MS m/z
570.1603 ([M+H]+), calcd for [C28H32BrN3O5+H]
+ 570.1598.
2.10.4.30. 3-Hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74f)
It was obtained as white solid in 85 % yield; m. p 99-101 °C; IR (cm-1
, KBr): 3402, 2922,
2855, 1717, 1610, 1387, 1251, 1171, 1091 and 823 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.89 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.44 (6H, m, -CH2CH2(CH2)3CH3), 1.48-1.54
(2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1 Hz, -
CH2(CH2)4CH3), 3.76 (1H, d, J = 4.4 Hz,OH), 4.02-4.09 (2H, m, -CH2N), 4.50-4.59 (2H,
m, -CH & -OCHα), 4.74 (1H, dd, J = 13.9 & 2.9 Hz, -OCHβ), 5.15 (2H, s, -CH2OPh),
6.75 (1H, d, J = 2.9 Hz, C-8H), 6.80-6.85 (3H, m, C-6H, ArH), 7.33-7.36 (2H, m, ArH),
7.47 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3):
δ 14.03 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.46 (-
CH2CH2(CH2)3CH3), 29.32 (-(CH2)2CH2(CH2)2CH3), 31.62 (-(CH2)3CH2CH2CH3), 53.01
(-CH2N), 61.83 (-CH), 68.29 (-OCH2), 69.27 (-OCH2Ph), 101.23 (C-8), 112.13 (C-6),
113.42 (C-10), 114.76, 116.46 (3ArC), 123.99 (C-3), 124.70 (C-5), 125.50 (CH=C),
132.22 (2ArC), 143.41 (CH=C), 146.09 (C-4), 153.24 (C-9), 157.10 (ArC), 159.86 (C-7),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
128
162.08 (CO); HR-ESI-TOF-MS m/z 570.1598 ([M+H]+), calcd for [C28H32BrN3O5+H]
+
570.1598.
2.10.4.31. 3-Hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74g)
It was obtained as white solid in 85 % yield; m. p 130-133 °C; IR (cm-1
, KBr): 3419,
2924, 2856, 1689, 1612, 1347, 1255, 1163, 1090 and 739 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.84 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -
CH2CH2(CH2)3CH3), 1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3),
2.61 (2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 4.01-4.10 (2H, m, -CH2N), 4.22-4.30 (1H, m, -
CH), 4.48 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.60 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ),
5.35 (2H, s, -CH2OPh), 5.64 (1H, d, J = 5.12 Hz, OH), 6.93-6.96 (2H, m, C-6H, C-8H),
7.09-7.14 (1H, m, ArH), 7.57-7.70 (3H, m, ArH), 7.85 (1H, d, J = 8.1 Hz, C-5H), 8.21
(1H, s, triazole H); 13
C NMR (100.6 MHz, DMSO-d6): δ 14.01 (-(CH2)5CH3), 14.68 (C-4
CH3), 22.13 (-CH2(CH2)3CH2CH3), 26.86 (-CH2CH2(CH2)3CH3), 28.71 (-
(CH2)2CH2(CH2)2CH3), 31.67 (-(CH2)3CH2CH2CH3), 52.61 (-CH2N), 62.58 (-CH), 67.67
(-OCH2), 70.10 (-OCH2Ph), 101.04 (C-8), 112.38 (C-6), 113.92 (C-10), 115.61, 120.95
(2ArC), 122.65 (C-3), 124.99 (C-5), 125.99 (ArC), 126.39 (CH=C), 134.38, 139.77
(2ArC), 141.56 (CH=C), 146.76 (C-4), 150.66 (C-9), 153.08 (ArC), 160.44 (C-7), 161.01
(CO); HR-ESI-TOF-MS m/z 537.2346 ([M+H]+), calcd for [C28H32N4O7+H]
+ 537.2344.
2.10.4.32. 3-Hexyl-7-(2-hydroxy-3-(4-(3-nitrophenoxy)methyl)-1,2,3-triazol-1-
yl)propoxy)-4-methylcoumarin (74h)
It was obtained as white solid in 88 % yield; m. p 136-140 °C; IR (cm-1
, KBr): 3222,
2928, 2858, 1717, 1618, 1349, 1252, 1162, 1083 and 826 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.84 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.26-1.33 (6H, m, -
CH2CH2(CH2)3CH3), 1.38-1.43 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3),
2.49-2.54 (2H, m, -CH2(CH2)4CH3), 3.99-4.07 (2H, m, -CH2N), 4.21-4.28 (2H, m, -CH),
4.45 (1H, dd, J = 13.2 & 3.7 Hz, -OCHα), 4.61 (1H, dd, J = 13.8 & 3.2 Hz, -OCHβ), 5.29
(2H, s, -CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.93-6.96 (2H, m, C-8H, C-6H), 7.49-
7.69 (3H, m, ArH), 7.80-7.87 (2H, m, ArH, C-5H), 8.25 (1H, s, triazole H); 13
C NMR
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
129
(100.6 MHz, DMSO-d6): δ 13.94 (-(CH2)5CH3), 14.62 (C-4 CH3), 22.05 (-
CH2(CH2)3CH2CH3), 26.79 (-CH2CH2(CH2)3CH3), 28.64 (-(CH2)2CH2(CH2)2CH3), 31.00
(-(CH2)3CH2CH2CH3), 52.54 (-CH2N), 61.76 (-CH), 67.61 (-OCH2), 70.06 (-OCH2Ph),
101.01 (C-8), 109.06 (C-6), 112.18 (C-10), 113.87, 115.76, 122.17 (3ArC), 122.61 (C-3),
125.91 (C-5), 126.31 (CH=C), 130.66 (ArC), 141.68 (CH=C), 146.64 (C-4), 148.69
(ArC), 153.02 (C-9), 158.55 (C-7), 160.37 (ArC), 160.90 (CO); HR-ESI-TOF-MS m/z
537.2336 ([M+H]+), calcd for [C28H32N4O7+H]
+ 537.2344.
2.10.4.33. 3-Hexyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74i)
It was obtained as white solid in 86 % yield; m. p 136-140 °C; IR (cm-1
, KBr): 3367,
2929, 2856, 1699, 1610, 1382, 1256, 1173, 1003 and 834 cm-1
; 1H NMR (400 MHz,
DMSO-d6): δ 0.84 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.26-1.33 (6H, m, -
CH2CH2(CH2)3CH3), 1.38-1.45 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3),
2.50-2.54 (2H, m, -CH2(CH2)4CH3), 4.00-4.07 (2H, m, -CH2N), 4.22-4.28 (1H, m, -CH),
4.48 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.63 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.32
(2H, s, -CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.93-6.96 (2H, m, C-6H, C-8H), 7.24-
7.27 (2H, m, ArH), 7.67 (1H, d, J = 8.8 Hz, C-5H), 8.18-8.22 (2H, m, ArH), 8.27 (1H, s,
triazole H); 13
C NMR (100.6 MHz, DMSO-d6): δ 13.95 (-(CH2)5CH3), 14.61 (C-4 CH3),
22.07 (-CH2(CH2)3CH2CH3), 26.81 (-CH2CH2(CH2)3CH3), 28.66 (-
(CH2)2CH2(CH2)2CH3), 31.10 (-(CH2)3CH2CH2CH3), 52.58 (-CH2N), 61.91 (-CH), 67.61
(-OCH2), 70.07 (-OCH2Ph), 101.02 (C-8), 112.28 (C-6), 113.88 (C-10), 115.20 (2ArC),
122.62 (C-3), 125.83 (2ArC), 126.05 (C-5), 126.32 (CH=C), 140.99 (ArC), 141.43
(CH=C), 146.65 (C-4), 153.02 (C-9), 160.38 (C-7), 160.92 (ArC), 163.31 (CO); HR-ESI-
TOF-MS m/z 537.2341 ([M+H]+), calcd for [C28H32N4O7+H]
+ 537.2344.
2.10.4.34. 3-Hexyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74j)
It was obtained as white solid in 83 % yield; m. p 120-122 °C; IR (cm-1
, KBr): 3385,
2922, 2852, 1716, 1611, 1387, 1250, 1121, 1025 and 748 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.86 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -CH2CH2(CH2)3CH3),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
130
1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.18 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.61
(2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 3.87 (1H, d, J = 5.1 Hz, OH), 4.05-4.09 (2H, m, -
CH2N), 4.54-4.60 (2H, m, -CH & -OCHα), 4.71 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.19
(2H, s, -CH2OPh), 6.75-6.92 (4H, m, C-6H, C-8H & ArH), 7.10-7.15 (2H, m, ArH), 7.47
(1H, d, J = 8.7 Hz, C-5H), 7.78 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ
14.04 (-(CH2)5CH3), 14.79 (Ph-CH3), 16.19 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3),
27.49 (-CH2CH2(CH2)3CH3), 28.66 (-(CH2)2CH2(CH2)2CH3), 31.65 (-
(CH2)3CH2CH2CH3), 53.00 (-CH2N), 61.59 (-CH), 68.32 (-OCH2), 69.26 (-OCH2Ph),
101.29 (C-8), 111.44 (C-6), 112.66 (ArC), 114.82 (C-10), 120.95 (ArC), 124.09 (C-3),
124.28 (C-5), 125.52, 126.87(2ArC), 126.87 (CH=C), 130.75 (ArC), 144.49 (CH=C),
146.00 (C-4), 153.32 (C-9), 156.22 (ArC), 159.89 (C-7), 162.06 (CO); HR-ESI-TOF-MS
m/z 506.2653 ([M+H]+), calcd for [C29H35N3O5+H]
+ 506.2649.
2.10.4.35. 3-Hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74k)
It was obtained as white solid in 86 % yield; m. p 99-102 °C; IR (cm-1
, KBr): 3511, 2924,
2852, 1718, 1610, 1385, 1259, 1173, 1085 and 777 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.30-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.45-1.52
(2H, m, -CH2CH2(CH2)3CH3), 2.31 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1
Hz -CH2(CH2)4CH3), 3.77 (d, 1H, J = 5.1 Hz, OH), 4.03-4.09 (2H, m, -CH2N), 4.53-4.58
(2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.16 (2H, s, -
CH2OPh), 6.74-6.85 (5H, m, C-6H, C-8H, ArH), 7.11-7.16 (1H, m, ArH), 7.47 (1H, d, J
= 8.7 Hz, C-5H), 7.79 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.03 (-
(CH2)5CH3), 14.78 (C-4 CH3), 21.44 (Ph-CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.47 (-
CH2CH2(CH2)3CH3), 29.32 (-(CH2)2CH2(CH2)2CH3), 31.63 (-(CH2)3CH2CH2CH3), 53.01
(-CH2N), 61.59 (-CH), 68.32 (-OCH2), 69.26 (-OCH2Ph), 101.29 (C-8), 111.44 (C-6),
112.11 (ArC), 114.75 (C-10), 115.48, 122.07 (2ArC), 123.99 (C-3), 124.54 (C-5), 125.48
(CH=C), 129.18, 139.55 (2ArC), 144.01 (CH=C), 146.04 (C-4), 153.29 (C-9), 158.06 (C-
7), 159.91 (ArC), 162.07 (CO); HR-ESI-TOF-MS m/z 506.2651 ([M+H]+), calcd for
[C28H35N3O5+H]+
506.2649.
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
131
2.10.4.41. 3-hexyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74l)
It was obtained as white solid in 84 % yield; m. p 130-134 °C; IR (cm-1
, KBr): 3386,
2920, 2852, 1721, 1610, 1383, 1247, 1176, 1089 and 831 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.44 (6H, m, -CH2CH2(CH2)3CH3),
1.45-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.27 (3H, s, Ph-CH3) 2.36 (3H, s, C-4 CH3),
2.61 (2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 3.85 (1H, d, J = 5.1 Hz, OH), 4.03-4.10 (2H,
m, -CH2N), 4.49-4.58 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ),
5.14 (2H, s, -CH2OPh), 6.75-6.86 (4H, m, C-6H, C-8H & ArH), 7.03-7.07 (2H, m, ArH),
7.47 (1H, d, J = 8.7 Hz, C-5H), 7.79 (1H, s, triazole H); 13
C NMR (100.6 MHZ, CDCl3):
δ 14.04 (-(CH2)5CH3), 14.79 (C-4 CH3), 20.41 (Ph-CH3), 22.59 (-CH2(CH2)3CH2CH3),
27.50 (-CH2CH2(CH2)3CH3), 29.34 (-(CH2)2CH2(CH2)2CH3), 31.65 (-
(CH2)3CH2CH2CH3), 52.97 (-CH2N), 61.85 (-CH), 68.39 (-OCH2), 69.25 (-OCH2Ph),
101.36 (C-8), 112.07 (C-6), 114.53 (2ArC), 114.81 (C-10), 124.08 (C-3), 124.49 (C-5),
125.51 (CH=C), 129.91, 130.52 (3ArC), 144.15 (CH=C), 145.98 (C-4), 153.33 (C-9),
155.96 (ArC), 159.89 (C-7), 162.05 (CO); HR-ESI-TOF-MS m/z 506.2647 ([M+H]+),
calcd for [C29H35N3O5+H]+
506.2649.
2.10.4.36. 3-Hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (74m)
It was obtained as white solid in 83 % yield; m. p 86-90 °C; IR (cm-1
, KBr): 3411, 2924,
2854, 1694, 1608, 1385, 1255, 1124, 1087 and 736 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.89 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.45-1.52
(2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1 Hz, -
CH2(CH2)4CH3), 3.83 (4H, m, Ph-OCH3, OH), 4.01-4.05 (2H, m, -CH2N), 4.45-4.55 (2H,
m, -CH & -OCHα), 4.69 (1H, dd, J = 11.9 & 2.9 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh),
6.76-7.04 (6H, m, C-8H, C-6H & ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.83 (1H, s,
triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.80 (C-4 CH3),
22.59 (-CH2(CH2)3CH2CH3), 27.49 (-CH2CH2(CH2)3CH3), 29.34 (-
(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.94 (-CH2N), 55.75 (Ph-OCH3),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
132
62.87 (-CH), 68.40 (-OCH2), 69.22 (-OCH2Ph), 101.35 (C-8), 112.04 (C-6, ArC), 114.31
(C-10), 114.80, 120.81, 121.89 (3ArC), 124.08 (C-3), 124.76 (C-5), 125.50 (CH=C),
144.08 (CH=C), 145.95 (C-4), 147.45, 149.52 (2ArC), 153.33 (C-9), 159.89 (C-7),
162.02 (CO); HR-ESI-TOF-MS m/z 522.2596 ([M+H]+), calcd for [C29H35N3O6+H]
+
522.2599.
2.10.4.37. 3-Hexyl-7-(2-hydroxy-3-(4-((3-methoxyphenoxy)methyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (74n)
It was obtained as white solid in 86 % yield; m. p 89-92 °C; IR (cm-1
, KBr): 3222, 2923,
2853, 1715, 1609, 1301, 1201, 1160, 1051 and 783 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.42 (6H, m, -CH2CH2(CH2)3CH3), 1.46-1.54
(2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.76-3.79 ( 4H, m, OH, Ph-OCH3), 4.03-4.10 (2H, m, -CH2N), 4.53-
4.59 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 12.4 & 2.2 Hz, -OCHβ), 5.16 (2H, s, -
CH2OPh), 6.51-6.57 (3H, m, C-6H, C-8H & ArH), 6.76-6.85 (2H, m, ArH), 7.13-7.18
(1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13
C NMR (100.6
MHz, CDCl3): δ 14.03 (-(CH2)5CH3), 14.78 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3),
27.47 (-CH2CH2(CH2)3CH3), 29.32 (-(CH2)2CH2(CH2)2CH3), 31.64 (-
(CH2)3CH2CH2CH3), 52.98 (-CH2N), 55.20 (Ph-OCH3), 61.69 (-CH), 68.34 (-OCH2),
69.24 (-OCH2Ph), 101.19 (ArC), 106.65 (C-8), 106.83, 112.08 (2ArC), 114.77 (C-6),
124.02 (C-10), 124.59 (C-3), 125.49 (C-5), 129.91 (CH=C), 143.81 (ArC), 146.03
(CH=C), 153.29 (C-4), 159.27 (C-9), 159.88 (C-7), 160.72 (2ArC), 162.07 (CO); HR-
ESI-TOF-MS m/z 522.2593 ([M+H]+), calcd for [C29H35N3O6+H]
+ 522.2599.
2.10.4.38. 3-Hexyl-7-(2-hydroxy-3-(4-((2-iodophenoxy)methyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74o)
It was obtained as white solid in 83 % yeld; m. p 168-173 °C; IR (cm-1
, KBr): 3285,
2924, 2855, 1717, 1618, 1333, 1297, 1169, 1086 and 761 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.25-1.42 (6H, m, -CH2CH2(CH2)3CH3),
1.48-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
133
CH2(CH2)4CH3), 3.78 (1H, d, J = 5.2 Hz, OH), 4.03-4.08 (2H, m, -CH2N), 4.54-4.63 (1H,
m, -CH & -OCHα), 4.72 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.24 (2H, s, -CH2OPh),
6.69-6.96 (4H, m, C-6H, C-8H & ArH), 7.25-7.30 (1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz,
C-5H), 7.71-7.73 (1H, m, ArH), 7.89 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3):
δ 14.06 (-(CH2)5CH3), 14.82 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.51 (-
CH2CH2(CH2)3CH3), 29.34 (-(CH2)2CH2(CH2)2CH3), 31.66 (-(CH2)3CH2CH2CH3), 52.97
(-CH2N), 63.40 (-CH), 68.39 (-OCH2), 69.15 (-OCH2Ph), 86.60 (ArC), 101.35 (C-8),
112.09 (C-6), 112.73 (C-10), 114.85, 123.18 (2ArC), 124.13 (C-3), 124.62 (C-5), 129.55
(CH=C), 125.55, 139.38 (2ArC), 143.96 (CH=C), 145.97 (C-4), 153.34 (C-9), 156.59
(C-7), 159.87 (ArC), 161.03 (CO); HR-ESI-TOF-MS m/z 618.1475 ([M+H]+), calcd for
[C28H32IN3O5+H]+
1459.
2.10.4.39. 3-Hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxy)methyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74p)
It was obtained as white solid in 85 % yield; m. p 158-163 °C; IR (cm-1
, KBr): 3384,
2922, 2852, 1717, 1611, 1386, 1249, 1175, 1096 and 841 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.26-1.42 (6H, m, -CH2CH2(CH2)3CH3),
1.46-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.77 (1H, brs, OH), 4.02-4.09 (2H, m, -CH2N), 4.53-4.59 (2H, m, -CH
& -OCHα), 4.71 (1H, dd, J = 13.2 & 3.7 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh), 6.71-6.83
(4H, m, C-6H, C-8H & ArH), 7.46-7.53 (3H, m, ArH, C-5H), 7.80 (1H, s, triazole H);
13C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.83 (C-4 CH3), 22.58 (-
CH2(CH2)3CH2CH3), 27.48 (-CH2CH2(CH2)3CH3), 29.33 (-(CH2)2CH2(CH2)2CH3), 31.63
(-(CH2)3CH2CH2CH3), 53.01 (-CH2N), 61.69 (-CH), 68.29 (-OCH2), 69.26 (-OCH2Ph),
83.45 (ArC), 101.24 (C-8), 112.12 (C-6), 112.77 (C-10), 117.03 (2ArC), 124.02 (C-3),
124.70 (C-5), 125.51 (CH=C), 138.19 (2ArC), 143.39 (CH=C), 146.09 (C-4), 153.24 (C-
9), 157.87 (ArC), 159.85 (C-7), 162.08 (CO);HR-ESI-TOF-MS m/z 618.1459 ([M+H]+),
calcd for [C28H32IN3O5+H]+
618.1459.
2.10.4.40. 3-Hexyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74q)
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
134
It was obtained as white solid in 87 % yield; m. p 120-122 °C; IR (cm-1
, KBr): 3404,
2931, 2858, 1702, 1615, 1335, 1287, 1158, 1087 and 844 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -CH2CH2(CH2)3CH3),
1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.78 (1H, d, J = 5.12 Hz, OH), 4.00-4.07 (2H, m, -CH2N), 4.48-4.58
(2H, m, -CH & -OCHα), 4.71 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.16 (2H, s, -
CH2OPh), 6.61-6.84 (5H, m, C-6H, C-8H & ArH), 7.16-7.23 (1H, m, ArH), 7.47 (1H, d,
J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.05 (-
(CH2)5CH3), 14.79 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.51 (-CH2CH2(CH2)3CH3),
29.35 (-(CH2)2CH2(CH2)2CH3), 31.63 (-(CH2)3CH2CH2CH3), 52.97 (-CH2N), 61.96 (-
CH), 68.39 (-OCH2), 69.23 (-OCH2Ph), 101.34 (ArC), 102.46 (C-8), 102.71, 107.99
(2ArC), 108.21 (C-6), 110.29 (C-10), 112.06 (C-3), 114.87 (C-5), 124.14 (CH=C),
124.63 (ArC), 125.54 (CH=C), 130.33 (C-4), 143.49 (C-9), 145.99 (C-7), 153.33, 159.85
(2ArC), 162.05 (CO); HR-ESI-TOF-MS m/z 510.2393 ([M+H]+), calcd for
[C28H32FN3O5+H]+
510.2399.
2.10.4.41. 3-Hexyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74r)
It was obtained as white solid in 85 % yield; m. p 126-129 °C; IR (cm-1
, KBr): 3413,
2932, 2859, 1702, 1615, 1355, 1216, 1158, 1087 and 829 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.30-1.42 (6H, m, -CH2CH2(CH2)3CH3),
1.46-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.84 (1H, d, J = 4.4 Hz, OH), 4.03-4.10 (2H, m, -CH2N), 4.50-4.60
(2H, m, -CH & -OCHα), 4.74 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.14 (2H, s, -
CH2OPh), 6.75-6.97 (6H, m, C-6H, C-8H & ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.81
(1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.02 (-(CH2)5CH3), 14.77 (C-4
CH3), 22.56 (-CH2(CH2)3CH2CH3), 27.45 (-CH2CH2(CH2)3CH3), 29.31 (-
(CH2)2CH2(CH2)2CH3), 31.62 (-(CH2)3CH2CH2CH3), 52.99 (-CH2N), 62.26 (-CH), 68.29
(-OCH2), 69.25 (-OCH2Ph), 101.23 (C-8), 112.12 (C-6), 114.75 (C-10), 115.69, 115.78,
115.92 (4ArC), 123.99 (C-3), 124.64 (C-5), 125.49 (CH=C), 143.67 (CH=C), 146.09 (C-
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
135
4), 153.25 (C-9), 154.09, 156.21 (2ArC), 159.87 (C-7), 162.09 (CO); HR-ESI-TOF-MS
m/z 510.2399 ([M+H]+), calcd for [C28H32FN3O5+H]
+ 510.2399.
2.10.4.42. 3-Hexyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-
yl)propyloxy)-4-methylcoumarin (74s)
It was obtained as white solid in 89 % yield; m. p 126-129 °C; IR (cm-1
, KBr): 3421,
2925, 2856, 1707, 1609, 1387, 1251, 1085 and 761 cm-1
; 1H NMR (400 MHz, CDCl3): δ
0.88 (3H, t, J = 7.0 Hz, -(CH2)5CH3), 1.26-1.44 (6H, m, -CH2CH2(CH2)3CH3), 1.46-1.54
(2H, m, -CH2CH2(CH2)3CH3), 2.34 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1 Hz, -
CH2(CH2)4CH3), 3.79 (1H, brs, OH), 4.02-4.09 (2H, m, -CH2N), 4.51-4.57 (2H, m, -CH
& -OCHα), 4.70 (1H, dd, J = 13.7 & 2.8 Hz, -OCHβ), 5.23 (2H, s, -CH2OPh), 6.76-6.83
(2H, m, C-6H, C-8H), 7.01-7.04 (2H, m, ArH), 7.29-7.53 (8H, m, C-5H, ArH), 7.83 (1H,
s, triazole H); 13
C NMR (100.6 MHZ, CDCl3): δ 14.03 (-(CH2)5CH3), 14.74 (C-4CH3),
22.58 (-CH2(CH2)3CH2CH3), 27.47 (-CH2CH2(CH2)3CH3), 29.33 (-
(CH2)2CH2(CH2)2CH3), 31.64 (-(CH2)3CH2CH2CH3), 53.02 (-CH2N), 61.78 (-CH), 68.34
(-OCH2), 69.27 (-OCH2Ph), 101.30 (C-8), 112.06 (C-6), 114.78 (C-10), 114.95, 124.02
(3ArC), 124.02 (C-3), 124.64 (C-5), 125.49, 126.59 (3ArC), 126.71 (CH=C), 128.08,
128.67, 134.22, 140.41 (6ArC), 143.85 (CH=C), 146.02 (C-4), 153.29 (C-9), 157.59
(ArC), 159.88 (C-7), 162.06 (CO); HR-ESI-TOF-MS m/z 568.2804 ([M+H]+), calcd for
[C34H37N3O5+H]+ 568.2806.
2.10.4.43. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (74t)
It was obtained as white solid in 89 % yield; m. p 139-140 °C; IR (cm-1
, KBr): 3161,
2925, 2856, 1718, 1621, 1390, 1294, 1161, 1084 and 845 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.26-1.42 (6H, m, -CH2CH2(CH2)3CH3),
1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.34 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.77 (1H, brs, OH), 4.02-4.09 (2H, m, -CH2N), 4.48-4.58 (2H, m, -CH
& -OCHα), 4.70 (1H, dd, J = 13.7 & 2.8 Hz, -OCHβ), 5.29 (2H, s, -CH2OPh), 6.73-6.82
(2H, m, C-6H, C-8H), 7.12-7.23 (2H, m, ArH), 7.32-7.75 (6H, m, C-5H, ArH), 7.83 (1H,
s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.03 (-(CH2)5CH3), 14.71 (C-4 CH3),
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
136
22.57 (-CH2(CH2)3CH2CH3), 27.45 (-CH2CH2(CH2)3CH3), 29.32 (-
(CH2)2CH2(CH2)2CH3), 31.62 (-(CH2)3CH2CH2CH3), 53.03 (-CH2N), 61.65 (-CH), 68.29
(-OCH2), 69.27 (-OCH2Ph), 101.23 (C-8), 107.02 (ArC), 112.05 (C-6), 114.69 (C-10),
118.59 (ArC), 123.81 (C-3), 123.81, 123.93 (3ArC), 124.69 (C-5), 125.44, 126.38,
126.78 (3ArC), 127.51 (CH=C), 129.03, 129.45, 134.25 (3ArC), 143.70 (CH=C), 146.02
(C-4), 153.23 (C-9), 155.93 (ArC), 159.87 (C-7), 162.05 (CO); HR-ESI-TOF-MS m/z
542.2649 ([M+H]+), calcd for [C32H35N3O5+H]
+ 542.2649.
2.10.4.44. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-
1-yl)propyloxy)-4-methylcoumarin (74u)
It was obtained as white solid in 90 % yield; m. p 109-101 °C; IR (cm-1
, KBr): 3384,
2923, 2853, 1716, 1610, 1395, 1271, 1104, 1021 and 766 cm-1
; 1H NMR (400 MHz,
CDCl3): δ 0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -CH2CH2(CH2)3CH3),
1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.33 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.0 Hz, -
CH2(CH2)4CH3), 3.89 (1H, brs, OH), 4.01-4.08 (2H, m, -CH2N), 4.52-4.59 (2H, m, -CH
& -OCHα), 4.70 (1H, dd, J = 13.7 & 2.8 Hz, -OCHβ), 5.36 (2H, s, -CH2OPh), 6.75-6.81
(2H, m, C-6H, C-8H), 6.91 (1H, d, J = 7.3 Hz, ArH), 7.31-7.48 (5H, m, ArH), 7.76 (1H,
d, J = 8.1 Hz, C-5H), 7.86 (1H, s, triazole H); 13
C NMR (100.6 MHz, CDCl3): δ 14.05 (-
(CH2)5CH3), 14.75 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.49 (-CH2CH2(CH2)3CH3),
29.34 (-(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 53.00 (-CH2N), 62.12 (-
CH), 68.36 (-OCH2), 69.25 (-OCH2Ph), 101.28 (C-8), 105.24 (ArC), 112.04 (C-6),
114.77 (C-10), 120.82 (ArC), 121.83 (C-3), 124.03, 124.52 (2ArC), 125.21 (C-5),
125.45, 125.48, 125.70 (3ArC), 126.39 (CH=C), 127.42, 134.42 (2ArC), 144.67 (CH=C),
146.00 (C-4), 153.29 (C-9), 155.75 (ArC), 159.86 (C-7), 162.05 (CO);HR-ESI-TOF-MS
m/z 542.2652 ([M+H]+), calcd for [C32H35N3O5+H]
+542.2649
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
137
2.11. Experimental details of antifungal activity
Antifungal activity assay
The anti-A. fumigatus, A. niger and A. flavus activity of all the compounds was studied by
disc diffusion and microbroth dilution assays.66
Anti Aspergillus activity assays
Disc diffusion assay
The disc diffusion test was performedin radiation sterilized Petri plates of 10.0
cmdiameter (Tarsons, Kolkata, India). Different concentrations ranging from 750 to 1.46
μg of the test compounds were impregnated on the sterilized disc (5.0 mm in diameter) of
Whatman filter paper No. 1. The discs were placed on the surface of the agar plates
already inoculated with A. fumigates, A. niger or A. flavus spores. The plates were
incubated at 37 oC and examined at 24, 48 and 96 h for zone of inhibition, if any, around
the disc. The concentration, which developed the zone of inhibition of at least 6.0 mm
diameter, was considered as minimum inhibitory concentration.
Microbroth dilution assay
The test was performed in 96 well culture plates (Nunc, Nunclon). Various
concentrations of synthetic compounds in the range of 1000-3.1μg/ml were prepared in
the wells by two-fold dilution method. Amphotericin B (1) was used as a standard drug
for comparison. Assay was performed as per standard method described by Dabur et al.67
Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins
138
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Recommended