Synthesis of pyrazolopyrano fused …shodhganga.inflibnet.ac.in/bitstream/10603/29329/12/12...aldehyde 2 (0.05 mol, 9.45 of 2-mercapto-quinoline-3-carbaldehyde or 11.2 its 7-chloro

214

Synthesis of pyrazolopyrano―fused thiochromeno[2,3-b]quinolines inglycerol, and their biological studies

In present section, the syntheses of pyrazolopyrano―fused thiochromeno quinoline scaffolds have been achieved via DKHDA reaction, described new combination of thiopyranoquinoline―based olefin―tethered aldehyde substrates with pyrazolones in glycerol. The stereochemistry of all the compounds was confirmed by various 2D NMR experiments; DQF―COSY and NOESY, and single crystal X―Ray diffraction data.5.4 Introduction 5.4.1 Quinoline

Quinoline, also known as 1-azanaphthalene or benzo[b]pyridine, is an aromatic nitrogen compound existing in a solid―ring structure that contains a benzene ring fused with pyridine via two adjacent carbons. Pyridine is nitrogencontaining six-membered aromatic ring with five carbon atoms.

Runge,1 in 1834, isolated quinoline a stable base from coal―tar distillate,in impure state. Gerhardt2 obtained it, probably tainted by lepidine, from distilling cinchonine and quinine with caustic alkali, who gave it a name quinoleine that Berzelius transformed into quinoline afterward. The basic unit offers a wide spectrum of properties useful in the fields of pharmaceuticals, dyes, catalysis, food colorants etc. having potential antimalarial properties, they act as fungicides, biocides, rubber chemicals and flavoring agents. Therapeutic values of quinolines include antiseptic, analgesic, trypanocidal, germicidal, amoebicidal, antitubercular, anthelmintic, pyroplasmosis, schistomiasis, antiserotonin, cytokinin and antispasmodic.3 They are best tolerated amoebicides known so far.4 Most effective ones are with a methoxy or a methyl at its 8th position. Quinaldine and 2-methylquinoline are precursors to antimalarial drugs, besides oil soluble dyes, food colorants, pH indicators and other organic compounds. Quinaldic acid with a carboxyl function at 2nd position is a catabolite

Section 2 Chapter 5 215

of tryptophan (aromatic side chain amino acid). Quinazoline is used as a chemical intermediate to prepare medicines and other organic compounds. Furthermore, it is also a core structure of antihypertensive agents such as prazosin and doxazosin which are peripheral vasodilator. Quinoxaline, 1,4-diaza-naphthalene is also used as a chemical intermediate for creating fungicides and other agrochemicals. 5.4.2 Quinoline―based alkaloids

Alkaloids are the most valuable among the naturally occurring plant and animal species. Specifically, quinoline-based alkaloids, with remarkable proficiency and physiological properties, have received a considerable attention of synthetic organic and biochemists. Quinine5 is a well-known alkaloid, isolated from S. rufochromogenes and S. echinatus. Naturally occurring white crystalline with bitter taste, it is a stereoisomer of quinidine and has antimalarial, anti―inflammatory, antipyretic, and analgesic activities. It was the first therapeutic agent appeared in the 17th century, effective in treatment of malaria caused by plasmodium falciparum. Raheem,6 Stork7 and others reported its preparation first via stereoselective route.

Rao and Cullen,8 in 1959, isolated unnamed dark―brown metabolite of Streptomyces flocculus, with a striking activity against several animal tumors.9Subsequently, the same was isolated from S. rufochromogenes and S. echinatus. Streptonigrin10 found to be an active agent of all Streptomyces and Actinomycesspecies. Since then, the effort was undertaken towards isolation of this bioactive compound with a variety of frameworks.11 Two closely related antibiotics; streptonigrone12 and lavendamycin, were also isolated. The synthetic work has extensively been studied, reported and discussed in the literature.13

Michael, J. P. isolated a large number of quinolone―based alkaloids from the Rutaceae family, 14 say atanine, the angular alkaloid araliopsine and linear


alkaloid isoplatydesmine, with a variety of pharmacological significances;antimicrobial,15 antiviral,16 mutagenic,17 and cytotoxic18 activities. Natural quinoline―based alkaloids exhibit activities such as antileishmanial,19 calcium channel blocker,20 antimalarial and cytotoxic activities,21 antioxidant,22 cardiac,23anticancer,24 antimalarial25 etc.

Synthetically, many routes are known to prepare quinoline derivatives such as skraup synthesis,26 Doebner―Von Miller synthesis,27 Beyer’s modification of the Doebner―Von Miller synthesis,28 Friedlaender synthesis,29Pfitzinger reaction,30 Doebner Synthesis,31 Combes method,32 Conrad―Limpach Knorr synthesis33 etc.5.4.3 Chromeno―fused quinolines

Chromenes are the unique among oxygenated heterocycles, which are resulted from a fusion of benzene with six member pyran ring, commonly known as benzopyran. Orientation of the fusion of these rings results into two isomers;1-benzopyran(chromene) and 2-benzopyran(isochromene). In chromene, oxygen is at its 1-position with double bond either in between 3rd and 4th (2H-1-chromene) or 2nd and 3rd (4H-1-chromene) carbons.

Many chromene―based structural frameworks and analogous hetero―fused systems exist in a plethora of natural products, exhibiting a variety of known inhibitors for a broad range of receptors.34 On the other hand, a fused―quinoline system has attracted more attention because of a wide―range of its biological applications.35 Examples include chromeno―, pyrazolo―, imidazolo―, furo―, indeno―, pyrimido―, and pyrano―fused quinolines.Chromeno―fused quinoline with powerful bacteriostatic and anti―inflammatory activities,36 acts as glucocorticoid.37 Found effective in the treatment of Alzheimer’s disease,38 these heterocycles are also estrogen receptor β―selective legands.39 With a desirable tissue―selecting profile in a rodent, dihydrochromenoquinoline are also known as robust pharmacophore for selective progesterone receptor modulators (SPRMS) with progestational


activity.40 More recently, Maalej, E. et al. repoted a class of these scaffolds as a selective, potent and mixed type EeAChE inhibitors.41

Further, the bioisosterism is of a notable interest due to its potential application in rational modification of lead compounds into safer and more clinically effective agents. The practice is a rapidly emerging area in the field of medicinal chemistry.42 The thiopyran is bioisiostere of pyran ring, so with increased liophilicity, thiopyranoquinoline is anticipated with interesting biological activity, in addition to anti―proliferative activity that its bioisostere pyranoquinoline scaffolds reveal.43,44,45 For example, thioflavone is as a bioisostere of flavone, exhibiting a potent vasorelexant effect.46 3’,4’-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) 1, which showed extremely potent inhibitory activity against HIV―1 replication in H9 lymphocytic cells.47 Lee, K. H.et al. designed a new series of analogs 2 by replacing the oxygen atom in ring C (pyran ring) of DCK with a sulfur atom and evaluated for anti―HIV activity (Fig.5.8).48

Figure 5.8 Thiopyran as a bioisostere of pyran.Itzstein, M. et al.42d described synthesis and biological evaluation of sulfur

isosteres 4 of the potent influenza virus sialidase inhibitors 4-amino-4-deoxy-and 4-deoxy-4- guanidino-Neu5Ac2en 3 (Fig. 5.8).

Recently, Zhon, W. et al.49 investigated an acid―promoted intramolecular Friedel―Crafts reaction of the Morita―Baylis―Hillman adducts 5 derived from 2-arylthioquinolin-3-carbaldehyde. The substrates with an electron―donating groups on aromatic ring afforded six membered fused―ring system 12H-thiochromeno[2,3-b]quinolines 6 in good yield, while those with electron―withdrawing groups, eight―membered fused―ring 5H-benzo[7,8]


thiocino[2,3-b]quinolines 7 in moderate yields. Using triflic acid instead of sulfuric acid, only product 6 was obtained under the similar reaction condition.

OH

SR1

R2

EWG H2SO4

CH2Cl2

N S

EWG

R2R1

N S

EWG

R1

R2

and/or

5

6

7

The substrates 4-(2-bromobenzylsulfanyl)-1-alkyl-1H-quinolin-2-ones 8were heated in dry degassed benzene under a nitrogen atmosphere with nBu3SnH in the presence of a catalytic amount of AIBN for 1 h to give the cyclic [6,6]thiopyranoquinoline-2-ones 9 as a major products along with small amount of the β-scission products.50

Yang, G. et al.51 described synthesis and antifungal activity of some 6H-thiochromeno[4,3-b]quinolines. Reaction of 4-chloro-2H-thiochromene-3-carbaldehydes 10 with 2-aminophenols 11 in DMF gives 6H-thiochromeno[4,3-b]quinolines 12.

Gong, P. et al.52 described the synthesis and in vitro anti―hepatitis B virus activity of benzothiopyrano[4,3-b]quinolines 16. Reaction of 2-aminobenzaldehyde 13 derived from benzaldehyde, with benzothiopyran-4-one 14 from thiophenol in alkaline condition, followed by hydrolysis and Mannich reaction produced desired products.


Junjappa, H. et al.53 synthesized thiochromeno[2,3-b]quinolines 19 by cyclization reaction of quinoline 18 derived from anilinoacetals 17.

5.5 Present workIn the present wok, a glycerol mediated DKHDA reaction has been

demonstrated, for the first time, to afford polyheterocycles, incorporating a potential bioactive thiochromeno[2,3-b]quinoline unit. The products were characterized by elemental analysis, mass, FT―IR, 1H NMR, and 13C NMR spectral data. For investigating into stereochemical aspects of all the compounds, the 2D NMR experiment NOESY and the single crystal X―Ray diffraction data of model compounds HBC65 and HBC66 were also taken. Finally, all were screened for their antimicrobial, anti-tubercular and antioxidant activities.

5.5.1 Experimental5.5.1.1 Synthesis(A) Synthesis of pyrazolo[4’’,3’’:5’,6’]pyrano[4’,3’:5,6]thiochromeno[2,3-

b]quinolines HBC68―85.All title compounds were synthesized via following steps:a) Preparation of thiopyrano[2,3-b]quinoline-3-carbaldehydes HBC65―67.(i) 2-Chloroquinoline-3-carbaldehydes.


(ii) 2-Mercaptoquinoline-3-carbaldehydes.(iii) Thiopyrano[2,3-b]quinoline-3-carbaldehydes HBC65―67.b) Optimization of the reaction conditions.c) Synthesis of pyrazolo[4’’,3’’:5’,6’]pyrano[4’,3’:5,6]thiochromeno[2,3-b]

quinolines HBC68―85.a) Preparation of thiopyrano[2,3-b]quinoline-3-carbaldehydes HBC65―67.(i) Preparation of 2-chloro quinoline-3-carbaldehydes.

All 2-chloroquinoline-3-carbaldehydes were obtained by methodsdescribed earlier as (ii) of (A) under 2.2.1. Experimental in Chapter-2, takingacetanilide, 3-chloroaniline and o-toludine [page No. 48].(ii) Preparation of 2-mercaptoquinoline-3-carbaldehyde.

Scheme 5.8 Reagents and conditions: (i) Na2S, DMF, rt.General procedure: Fused flakes of sodium sulfide (0.15 mol; 11.70 g) were added to a solution of a respective qunoline-3-carbaldehyde (0.1 mol; 19.15 g ofits 2-chloro derivative or 22.6 g of its 2,7-dichlo derivative or 20.56 g of its 8-methyl-2-chloro derivative) in dry DMF (100 mL). The resulted mixture was stirred for 1―2 h at rt. After completion of the reaction, confirmed by TLC, it was poured into ice―cooled water followed by the acidification with acetic acid. The solid mass left after filtering, washing (with water) and drying the acidified content was pure enough to use for the next step.(iii) Thiopyrano[2,3-b]quinoline-3-carbaldehydes HBC65―67.

Scheme 5.9 Reagents and conditions: (i) EDDA, Xylene, reflux, 3-3.5 h.General procedure: Catalyst EDDA was added to a stirred mixture of respective aldehyde 2 (0.05 mol, 9.45 of 2-mercapto-quinoline-3-carbaldehyde or 11.2 its 7-chloro derivative or 10 g of its 8-methyl-derivative) with citral (0.06 mol, 9.12


g, 10.4 mL) in xylene (20 mL) at rt. It was then refluxed for 3―3.5 h and cooled to rt. Removal of solvent under reduced pressure left oily products HBC65―67 as yellow residues, which were finally purified by silica gel column chromatography using a 10:1 n-hexane―ethyl acetate mixture. The yields were in the 68―73 % range.Table 5.5 Physical data of thiopyrano[2,3-b]quinoline-3-carbaldehydes HBC65―67.Product R1 R2 Time (h) Yield % mp ℃aHBC65 H H 3 72 70―72HBC66 Cl H 3.5 68 86―88HBC67 H Me 3 73 66―68a uncorrectedb) Optimization of the reaction conditions

A spectrum of various experimental setups (displayed in Table 5.5) was tested to optimize the DKHDA reaction. A combination of HBC65 with 1-phenyl-3-methyl-5-pyrazolone was taken as model reaction (scheme 5.10).

Scheme 5.10 A combination used in optimizing the reaction conditions.Table 5.6 Optimization of reaction conditions.

Entry Solvent Catalysta Temp (˚C) Time (h) Yield (%)1 MeCN ― RT 48 trace2 Toluene ― Reflux 18 153 MeCN EDDA Reflux 20 304 Xylene EDDA Reflux 9 655 Xylene TBA―HS Reflux 7 706 Xylene ZnO Reflux 10 607 Water Piperidine RT 15 trace8 ― ― 100 10 609 ― TBA―HS 100 4 7510 ― ZnO 120 4 8011 TEAA ― 120 5 8312 Glycerol ― 100 4 8513 Glycerol ― 120 3 91acatalyst used 20 mol%


As could be seen, from the above (Table 5.6), the reaction proceeds with improved yields (91%) and time (3h) in glycerol at 120 oC (entry 13). c) Synthesis of pyrazolo[4’’,3’’:5’,6’]pyrano[4’,3’:5,6]thiochromeno[2,3-

b]quinolines HBC68―85.

Scheme 5.11 Reagents and conditions: (i) Glycerol, 120 oC.General procedure: Some 3 mL glycerol were added to a mixture of equimolar quantity (0.002 mol) of thiopyrano[2,3-b]quinoline-3-carbaldehyde HBC65―67(0.65 g of HBC65 or 0.72 g of HBC66 or 0.67 g of HBC67) and corresponding 3-methyl-5-pyrazolone [0.35 g of its 1-Ph derivative or 0.38 g of its 1-(4-MePh) derivative or 0.42 g of its 1-(3-ClPh) derivative or 0.49 g of its 1-(2,5-Cl2Ph) derivative or 0.44 g of its 1-(4-NO2Ph) derivative or 0.47 g of 1,3-diphenyl-5-pyrazolone] in a 50 mL round―bottomed flask connected to a reflux condenser, and it was stirred at 120 °C. After completion of the reaction, as monitored by TLC with a 1:4 EtOAc―n-hexane mixture as an eluent, some 5 mL warm water were added and the precipitates were isolated simply by filtration. The filtrate after being heated (for water removal) under reduced pressure at 100 °C gave glycerol back. This recovered glycerol was reused at least five times without loss of its activity and efficiency. All the compounds HBC68―85 were received quantitatively with an excellent purity.Table 5.7 Physical data of pyrazolopyrano―fused thiochromeno[2,3-b]quinoline HBC68―85.Entry Products R1 R2 R3 R4 Yielda (%) M.P. °Cb

1 HBC68 H H Ph Me 91 260―2622 HBC69 H H 4-MePh Me 90 228―2303 HBC70 H H 3-ClPh Me 88 254―2564 HBC71 H H Ph Ph 91 234―2365 HBC72 H H 2,5-Cl2Ph Me 89 248―2506 HBC73 H H 4-NO2Ph Me 85 224―226


7 HBC74 Cl H Ph Me 91 136―1388 HBC75 Cl H 4-MePh Me 87 150―1529 HBC76 Cl H 3-ClPh Me 90 170―17210 HBC77 Cl H Ph Ph 86 144―14611 HBC78 Cl H 2,5-Cl2Ph Me 90 138―14012 HBC79 Cl H 4-NO2Ph Me 82 162―16413 HBC80 H Me Ph Me 93 146―15014 HBC81 H Me 4-MePh Me 89 236―23815 HBC82 H Me 3-ClPh Me 90 210―21216 HBC83 H Me Ph Ph 88 188―19017 HBC84 H Me 2,5-Cl2Ph Me 91 214―21618 HBC85 H Me 4-NO2Ph Me 86 248―250aReaction time 3 h in each case, buncorrected5.5.1.2 Biological screening test methods used

Identical methods (2.2.1.2), described earlier under Experimental part in Chapter 2, were used to screen compounds for their bioactivity [page No. 53].5.6 Results and discussion5.6.1 Optimization and plausible general mechanism

NN N

N

OH HO

R4 R4

R3 R3

R

R

N N

OH H

O

R3

R4

H O O H

NN

H

OR3

R4O

H O O H

OH

H

NN

O

R4

R3H

OOH

OH

O NN

R4

R3

HBC65-67 I II

HBC68-85

+ I

- I

III

IV

Figure 5.9 Plausible mechanism of DKHDA reaction in glycerol.Table 5.6 displays a spectrum of various conditions tested for DKHDA

reaction. In glycerol however, it gave improved results. A plausible mechanism is


outlined in Fig. 5.9. It shows the Knoevenagel alkene intermediate II formed under influence of OH of glycerol (on aldehyde and 5-pyrazolone protons) undergoes a hetero-Diels―Alder cyclization HBC68―85 in the subsequent next step via a minor Michael adduct III formation (as confirmed at 80 oC).

Possible orientations of dienophile towards alkene (Knoevenagel intermediate) result in four exo―E―anti, endo―E―syn, exo―Z―syn and endo―Z―anti transition states. Since anti attack are ruled out due to angle strain, only two geometries are expected from syn attacks. In present work, the cis relation between both ring junction Ha and Hb protons that has been confirmed based on the single crystal X―ray data in all major products favors the endo―E―syn state. Identification of trans-relationship between these protons in minor cycloadducts also favors exo―Z―syn transition state.5.6.2 Spectroscopic data Aldehyde substrate HBC65―67.

N SR1

HBC65-67

R2

O

Figure 5.10 General structural features of compounds HBC65―67.Two characteristic IR bands appeared in the 1670―1700 cm-1 and

2740―2850 cm-1 ranges are due to ν C=O and ν C―H of aldehyde, respectively. At around 1600 cm-1 the band appeared is assigned to ν C=C of alkenes, and the other in the 1177―1000 cm-1 range to ν C―O of ether. A band in the 650―710 cm-1 range in all compounds is due to the ν C―S of thiopyran ring.

Both the peaks; a singlet in the δ 9.53―9.75 ppm range in 1H NMR and at around δ 192.0 ppm in 13C NMR, confirm the presence of aldehyde. A singlet in the range δ 2.35―2.52 ppm is due to (CH―4) thiopyran ring proton. Multiplets in the δ 1.69―1.81 ppm and δ 1.96―2.39 ppm ranges are attributed to two ―CH2 of a side chain. Negative peaks appeared in the δ 20―42 ppm range in APT confirms the same.


Domino products HBC68―85The spectroscopic data of all the domino products HBC68―85 are in good

agreement with their proposed structures (Fig 5.11). The FT―IR for ν sp2 C―H and ν sp3 C―H appeared in the 3050―3010 cm-1 and the 3000―2850 cm-1ranges. A band in the ν 1105―1138 cm-1 range indicates C―O―C linkage of pyran ring. Similarly, a band in the ν 650―710 cm-1 range confirms C―S―C of thiopyran unit.

Figure 5.11 general structural features of compounds HBC68―85.The 1H NMR showed a two singlet in the δ 1.26―1.53 ppm range that

indicates protons of CH3 attached to C-5, and a singlet in the δ 1.63―1.68 ppm range due to protons of CH3 attached to C-7a. Doublet in the δ 3.70―4.10 ppm range with coupling constant J = 6.8―8.8 Hz is attributed to Ha proton, and multiplets in the δ 2.38―2.59 ppm range Hb proton. Singlet in the δ 6.30―6.40range is assigned to 15―CH proton.

13C NMR was intended to explain the peak responsible for each carbon atom. APT experiments indicate positive peaks for CH3 and CH, while negative for CH2 and quaternary type carbon.

Figure 5.12 Characteristic COSY and NOE’s of HBC68.


The correlation between the different kinds of protons in the molecule HBC68 can be confirmed by 2D NMR experiment NOESY spectra. A strong NOE between Ha and Hb protons in HBC68 suggests their cis relationship. Further, protons of methyl attached to ring junction has a strong NOE with Ha and Hb, indicating all three kinds of protons are lying in the same face of the molecule (Fig. 5.12).

The structure of some representative compounds was also supported by their mass spectral studies. For example, in the mass spectra of compoundsHBC68, HBC76 and HBC85 (MF = C30H29N3OS, C30H27Cl2N3OS and C31H20N4O3Srespectively), molecular ion peaks (in m/z); 479.7 M+1, 547.9 M+1 and 538.7 M+1 are fully agreed with their calculated molecular weights (479.2, 547.13 and 538.20 m/z) Besides, the C H N elemental analysis also agrees with their theoretical values.5.6.3 Single crystal X―Ray data

The stereochemistry was further confirmed by single crystal X―Ray diffraction analysis. Single crystals of both the compounds HBC68 was developedin ethyl acetate as recrystallizing solvent following a slow evaporation method.5.6.3.1 Single crystal X―Ray data analysis of compound HBC68.

The crystallographic data are summarized in Table 5.7. An ORTEP view of the title compound HBC68 with atomic labeling is shown as Figure 5.13. Table 5.8 Crystal and experimental data of HBC68.

HBC68CCDC No 914747Crystal description yellow blockCrystal size 0.30 x 0.20 x 0.20 mmEmpirical formula C30 H29N3OSFormula weight 479.62Radiation, Wavelength Mo Kα, 0.71073 ÅUnit cell dimensions a=10.3294(2), b= 14.8602(4), c=19.1562(4) Å, β=122.631(1) º Crystal system Monoclinic Space group P 21/cUnit cell volume 2476.30(10) Å3No. of molecules per unit cell, Z 4Absorption coefficient(µ) 0.159 mm-1F (000) 1016θ range for entire data collection 3.38 < θ < 26.00Reflections collected / unique 74367 / 4863


Reflections observed [I > 2σ (I)] 3823No. of parameters refined 320 Final R 0.0436wR(F2) 0.0979Goodness-of-fit 1.040(Δ/σ)max in the final cycle 0.001 Final residual electron density -0.227< Δρ < 0.222 eÅ-3

Figure 5.13 ORTEP view of the molecule (HBC68). Figure 5.14 The packing arrangement of molecules (HBC68) viewed down the c-axis.5.6.4 Biological evaluation

All biological screening test results were evaluated in comparison with that of standard drugs listed under biological evaluation (2.3.3)― the results and discussion section of Chapter 2 [page No. 59].

Antimicrobial screening test results of all thiochromeno-fused heterocycles HBC65—85 are displayed in Table 5.9. With MIC values, against Gram +ve and –ve bacteria, in general, which are closed to standard drug Ampicillin, a majority of compounds have good activity. Compound HBC69, against most of Gram +ve and –ve bacteria, and compounds HBC73 and HBC81, only against Gram +ve bacteria, were good antibacterial agents. Among the tested candidates, a few of them against some selected bacteria, have even more potency than Ampicillin. The examples include HBC65,68,70,74,75,76 and HBC84, against Gram +ve Bacillussubtilis bacteria, that resemble standard drug Norfloxacin in the potency. On the other hand compounds HBC69 and HBC82, against all these bacteria, showed same potency but they resemble standard drugs; Chloramphinicol and Ciprofloxacin. Resembling these standard drugs in MIC value, compound HBC66, against Gram


+ve Streptococcus pneumoniae bacteria, have same potency. The candidates,against Gram +ve Clostridium tetani bacteria, that resembles only Ciprofloxacin in MIC include HBC69,70,72,73,76,80 and HBC81. Compound HBC85, against Gram –ve Vibrio cholerae bacteria, is also close to the same standard. Finally, compound HBC66, against Gram +ve Bacillus subtilis bacteria, reveals MIC that is close to that of standard Norfloxacin. Although antifungal screening test results are poor against Aspergillus fumigatus, most of them have MIC, against Candida albicansfungi that is close to Grisofulvin drug.

Out of compounds tested for their anti-tuberculosis activity, two compounds HBC79 and HBC85, against M. tuberculosis H37Rv bacteria, were found with the percent growth inhibition, laying in the 90—100 % range. Compounds HBC71 and HBC76 have percent growth inhibition in the 80―90 % range.

Ferric reducing antioxidant power of all the compounds was measured in mM per 100 g of sample (equivalent of ascorbic acid). The FRAP value of all wereobserved in the 102—70 mmol/100 g range, indicating that the compounds are moderate in the anti-oxidant activity.

Antibacterial activity of all the compounds tested might be varied with the different pyrazolones used in the synthesizing the polyheterocycles. For example, compounds HBC68,74,80 derived from simple 5-pyrazolone (1-phenyl-3-methyl) and HBC69,75,81 from its 1-(4-MePh)-3-methyl derivative, against all bacteria showed good activity, resembling standard Ampicillin drug in bioactivity. Compounds HBC70,76,82 from its 1-(3-ClPh)-3-methyl derivative, against Gram +ve Bacillus subtilis and Clostridium tetani bacteria, also showed a remarkable potency.



5.6.5 CharacterizationHBC65 2-methyl-2-(4-methylpent-3-en-1-yl)-2H-thiopyrano[2,3-b]quinoline-3-carbaldehydeM.F. C20H21NOSM.P. 70―72 oCM.W. (g/mole) 323.13 Element. Anal. C H NCal 74.27 6.54 4.33Obs 74.05 6.46 4.391H NMR δ ppm(CDCl3)

1.53 (s, 3H, CH3), 1.63 (s, 3H, CH3), 1.69―1.79 (m, 2H, CH2), 1.83 (s, 3H, 2―CH3), 1.96―2.28 (m, 2H, CH2), 2.35 (s, 1H, 4―H), 5.04 (t, 1H, J = 6.8 Hz, CH=CMe2), 7.45―7.95 (m, 5H, Ar―H), 9.63 (s, 1H, CHO)13C NMR δ ppm(CDCl3)

24.46, 25.55, 29.19, 41.86, 51.33, 123.18, 123.73, 126.26, 128.05, 128.55, 131.56, 136.82, 137.01, 141.33, 145.46, 145.76, 149.28, 158.74, 191.33FT―IR max cm-1(KBr) 741, 920, 1094, 1177, 1374, 1553, 1608, 1683, 2852, 2900, 2973, 3054

HBC66 8-chloro-2-methyl-2-(4-methylpent-3-en-1-yl)-2H-thiopyrano[2,3-b] quinoline-3-carbaldehydeM.F. C20H20NOSM.P. 86―88 oCM.W. (g/mole) 357.10Element. Anal. C H NCal 67.12 5.63 3.91Obs 67.01 5.70 3.8551H NMR δ ppm(CDCl3)

1.56 (s, 3H, CH3), 1.68 (s, 3H, CH3), 1.70―1.81 (m, 2H, CH2), 1.90 (s, 3H, 2―CH3), 2.01―2.32 (m, 2H, CH2), 2.42 (s, 1H, 4―H), 5.10 (t, 1H, J = 6.0 Hz, CH=CMe2), 7.52―8.12 (m, 4H, Ar―H), 9.75 (s, 1H, CHO)13C NMR δ ppm(CDCl3)

24.52, 25.45, 29.09, 41.85, 51.45, 123.23, 123.87, 126.32, 128.15, 128.25, 128.65, 131.55, 132.44, 136.78, 137.25, 141.33, 145.67, 149.30, 158.64, 192.13FT―IR max cm-1(KBr) 580, 741, 920, 1094, 1177, 1374, 1553, 1608, 1691, 2910, 2922, 3054


HBC67 2,9-dimethyl-2-(4-methylpent-3-en-1-yl)-2H-thiopyrano[2,3-b]quinoline-3-carbaldehydeM.F. C21H23NOSM.P. 66―68 oCM.W. (g/mole) 337.15Element. Anal. C H NCal 74.74 6.87 4.15Obs 74.61 6.73 4.251H NMR δ ppm(CDCl3)

1.61 (s, 3H, CH3), 1.65 (s, 3H, CH3), 1.70―1.79 (m, 2H, CH2), 1.89 (s, 3H, 2―CH3), 2.11―2.39 (m, 2H, CH2), 2.52 (s, 1H, 4―H), 2.71 (s, 3H, 8―CH3), 5.45 (t, 1H, J = 6.4 Hz, CH=CMe2), 7.33―8.22 (m, 4H, Ar―H), 9.53 (s, 1H, CHO)13C NMR δ ppm(CDCl3)

23.98, 25.22, 26.41, 28.89, 42.18, 51.34, 123.28, 124.08, 126.15, 127.95, 128.55, 131.47, 136.67, 137.37, 141.61, 145.82, 146.18, 149.30, 159.21, 193.01FT―IR max cm-1(KBr) 578, 157, 950, 1088, 1177, 1375, 1560, 1610, 1689, 2915, 3058

HBC68(5aR,15bS)1,5,5,7a-tetramethyl-3-phenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C30H29N3OSM.P. 260―262 oCM.W. (g/mole) 479.2Element. Anal. C H NCal 72.12 6.09 8.76Obs 71.98 5.98 8.70

1H NMR δ ppm(CDCl3)1.28 (s, 3H, 5―CH3), 1.50 (s, 3H, 5―CH3), 1.64 (s, 3H, 7a―CH3), 1.99―2.10 (m, 4H, 6&7―CH2), 2.30 (s, 3H, 1―CH3), 2.40―2.47 (m, 1H, 5a―H), 3.70 (d, 1H, J = 8.4 Hz, 15b―H), 6.40 (s, 1H, 15―H), 7.22―7.97 (m, 10H, Ar―H)

13C NMR δ ppm(CDCl3)13.28, 21.07, 22.08, 28.13, 30.25, 30.86, 31.91, 33.49, 41.02, 48.01, 84.58, 93.99, 120.10, 122.17, 125.33, 125.83, 126.43, 126.76, 127.63, 127.77, 128.85, 129.59, 132.61, 138.92, 143.27, 147.19, 147.34, 150.46, 158.08

FT―IR max cm-1(KBr) 689, 749, 1119, 1390, 1510, 1598, 1648, 2917, 2946, 2979, 3059


HBC69 (5aR,15bS)1,5,5,7a-tetramethyl-3-(p-tolyl)-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno [2,3-b]quinolineM.F. C31H31N3OSM.P. 228―230 oCM.W. (g/mole) 493.66Element. Anal. C H NCal 75.42 6.33 8.51Obs 75.29 6.43 8.44

1H NMR δ ppm(CDCl3)1.27 (s, 3H, 5―CH3), 1.48 (s, 3H, 5―CH3), 1.64 (s, 3H, 7a―CH3), 1.82―2.07 (m, 4H, 6&7―CH2), 2.29 (s, 3H, 1―CH3), 2.39 (s, 3H, p―CH3), 2.41―2.44 (m, 1H, 5a―H), 3.70 (d, 1H, J = 8.4 Hz, 15b―H), 6.40 (s, 1H, 15―H), 7.23―7.96 (m, 9H, Ar―H)

13C NMR δ ppm(CDCl3)13.35, 20.71, 20.94, 22.13, 28.31, 30.29, 31.96, 33.57, 41.13, 41.35, 47.99, 69.80, 84.26, 120.28, 122.17, 125.87, 126.45, 126.80, 127.57, 129.50, 132.21, 132.49, 135.05, 136.47, 143.25, 143.97, 147.02FT―IR max cm-1

(KBr) 749, 818, 1100, 1391, 1517, 1581, 1605, 2921, 3034

HBC70(5aR,15bS)3-(3-chlorophenyl)-1,5,5,7a-tetramethyl-5,5a,6,7,7a,15b-hexahydro-3H pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C30H28ClN3OSM.P. 254―256 oCM.W. (g/mole) 513.16Element. Anal. C H NCal 70.09 5.49 8.17Obs 69.91 5.53 8.05

1H NMR δ ppm(CDCl3)1.32 (s, 3H, 5―CH3), 1.47 (s, 3H, 5―CH3), 1.68 (s, 3H, 7a―CH3), 1.77―2.11 (m, 4H, 6 & 7―CH2), 2.38 (s, 3H, 1― CH3), 2.41―2.52 (m, 1H, 5a―H), 4.02 (d, 1H, J = 7.2 Hz, 15b―H), 6.56 (s, 1H, 15―H), 7.22―7.94 (m, 9H, Ar―H)

13C NMR δ ppm(CDCl3)13.52, 20.88, 21.96, 28.47, 30.22, 31.98, 33.62, 41.15, 48.19, 85.09, 117.91, 120.09, 122.12, 125.23, 125.65, 126.22, 126.78, 127.19, 128.65, 130.15, 132.35, 134.85, 135.23, 143.50, 147.67, 147.98, 159.69

FT―IR max cm-1(KBr) 670, 752, 1125, 1392, 1515, 1598, 1652, 2926, 2950, 2979, 3062


HBC71 (5aR,15bS)5,5,7a-trimethyl-1,3-diphenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C35H31N3OSM.P. 234―236 oCM.W. (g/mole) 541.71Element. Anal. C H NCal 77.60 5.77 7.76Obs 77.81 5.68 7.84

1H NMR δ ppm(CDCl3)1.32 (s, 3H, 5―CH3), 1.53 (s, 3H, 5―CH3), 1.68 (s, 3H, 7a―CH3), 1.88―2.17 (m, 4H, 6&7―CH2), 2.52―2.59 (m, 1H, 5a―H), 4.09 (d, 1H, J = 8.4 Hz, 15b―H), 6.30 (s, 1H, 15―H), 7.31―7.99 (m, 15H, Ar―H)

13C NMR δ ppm(CDCl3)18.95, 23.03, 25.16, 29.23, 35.36, 36.86, 50.57, 60.66, 74.83, 105.40, 116.65, 117.14, 120.71, 124.48, 125.43, 127.03, 127.41, 127.42, 128.02, 128.46, 128.80, 136.66, 138.50, 139.13, 141.07, 148.41, 149.95, 152.58, 157.22

FT―IR max cm-1(KBr) 691, 752, 1070, 1136, 1386, 1484, 1509, 1596, 2856, 2931, 3052

HBC72(5aR,15bS)3-(2,5-dichlorophenyl)-1,5,5,7a-tetramethyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C30H27ClN3OSM.P. 248―250 oCM.W. (g/mole) 547.13Element. Anal. C H NCal 65.69 4.96 7.66Obs 65.79 5.05 7.53

1H NMR δ ppm(CDCl3)1.28 (s, 3H, 5―CH3), 1.44 (s, 3H, 5―CH3), 1.59 (s, 3H, 7a―CH3), 1.81―2.11 (m, 4H, 6 & 7―CH2), 2.32 (s, 3H, 1―CH3), 2.38―2.43 (m, 1H, 5a―H), 3.88 (d, 1H, J = 8.4 Hz, 15b―H), 6.54 (s, 1H, 15―H), 7.49―8.12 (m, 8H, Ar―H)


(KBr) 689, 772, 1080, 1142, 1397, 1489, 1510, 1603, 2856, 2931, 3067


HBC73(5aR,15bS)1,5,5,7a-tetramethyl-3-(4-nitrophenyl)-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C30H28N4O3S

N S

O

NN

NO2M.P. 224―226 oCM.W. (g/mole) 524.63Element. Anal. C H NCal 68.68 5.38 10.68Obs 68.79 5.44 10.59


13C NMR δ ppm(CDCl3)13.35, 18.02, 19.32, 20.88, 22.12, 28.77, 30.54, 31.89, 33.57, 41.22, 47.89, 49.23, 86.08, 95.22, 117.64, 118.75, 122.55, 124.75, 124.97, 125.25, 125.77, 126.62, 133.03, 135.89, 142.44, 144.26, 144.68, 146.22, 149.78FT―IR max cm-1

(KBr) 678, 792, 1078, 1152, 1385, 1492, 1525, 1610, 2858, 2942, 3060

HBC74(5aR,15bS)11-chloro-1,5,5,7a-tetramethyl-3-phenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C30H28ClN3OSM.P. 136―138 oCM.W. (g/mole) 513.16Element. Anal. C H NCal 70.09 5.49 8.16Obs 69.89 5.56 8.08

1H NMR δ ppm(CDCl3)1.19 (s, 3H, 5―CH3), 1.48 (s, 3H, 5―CH3), 1.58 (s, 3H, 7a―CH3), 2.09―2.16 (m, 4H, 6&7―CH2), 2.41 (s, 4H, 1―CH3), 2.45―2.49 (m, 1H, 5a―H), 3.85 (d, 1H, J = 8.4 Hz, 15b―H), 6.36 (s, 1H, 15―H), 7.11―7.89 (m, 9H, Ar―H)

13C NMR δ ppm(CDCl3)12.88, 21.12, 22.28, 28.34, 30.22, 30.98, 32.01, 33.62, 39.89, 48.11, 84.65, 94.09, 120.25, 122.10, 125.13, 125.98, 126.54, 126.80, 127.36, 127.67, 128.58, 132.46, 138.89, 143.32, 147.31, 147.63, 150.64, 158.10FT―IR max cm-1

(KBr) 753, 776, 895, 932, 1075, 1128, 1397, 1489, 1516, 1603, 1616, 2862, 2935, 3065


HBC75(5aR,15bS)11-chloro-1,5,5,7a-tetramethyl-3-(p-tolyl)-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C31H30ClN3OSM.P. 150―152 oCM.W. (g/mole) 527.18Element. Anal. C H NCal 70.50 5.73 7.96Obs 70.36 5.80 8.01

1H NMR δ ppm(CDCl3)1.29 (s, 3H, 5―CH3), 1.50 (s, 3H, 5―CH3), 1.63 (s, 3H, 7a―CH3), 1.79―2.10 (m, 4H, 6&7―CH2), 2.32 (s, 3H, 1―CH3), 2.35 (s, 3H, p―CH3), 2.41―2.49 (m, 1H, 5a―H), 3.75 (d, 1H, J = 8.4 Hz, 15b―H), 6.51 (s, 1H, 15―H), 7.20―7.95 (m, 8H, Ar―H)

13C NMR δ ppm(CDCl3)13.33, 20.61, 21.09, 22.23, 28.45, 30.13, 31.89, 33.63, 41.18, 41.40, 48.10, 69.92, 84.26, 120.28, 122.17, 125.93, 126.52, 126.80, 129.68, 132.22, 132.67, 135.05, 136.47, 143.25, 144.15, 147.22FT―IR max cm-1

(KBr) 758, 777, 892, 935, 1082, 1120, 1392, 1497, 1515, 1598, 1610, 2858, 2926, 3069

HBC76(5aR,15bS)11-chloro-3-(3-chlorophenyl)-1,5,5,7a-tetramethyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6] thiochromeno[2,3-b]quinolineM.F. C30H27Cl2N3OSM.P. 170―172 oCM.W. (g/mole) 547.13Element. Anal. C H NCal 65.69 4.96 7.66Obs 65.78 5.03 7.53



(KBr) 751, 774, 881, 927, 1078, 1119, 1387, 1478, 1505, 1593, 1607, 2856, 2929, 3071


HBC77(5aR,15bS)11-chloro-5,5,7a-trimethyl-1,3-diphenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno [2,3-b]quinolineM.F. C35H30ClN3OSM.P. 144―146 oCM.W. (g/mole) 575.18Element. Anal. C H NCal 72.96 5.25 7.29Obs 73.10 5.20 7.35

1H NMR δ ppm(CDCl3)1.32 (s, 3H, 5―CH3), 1.48 (s, 3H, 5―CH3), 1.68 (s, 3H, 7a―CH3), 1.77―2.07 (m, 4H, 6 & 7―CH2), 2.41―2.56 (m, 1H, 5a―H), 4.01 (d, 1H, J = 8.4 Hz, 15b―H), 6.56 (s, 1H, 15―H), 6.89―7.99 (m, 14H, Ar―H)

13C NMR δ ppm(CDCl3)14.24, 21.22, 22.56, 28.31, 31.32, 32.15, 33.49, 41.25, 48.17, 85.18, 105.40, 116.85, 117.54, 120.58, 124.87, 125.12, 127.59, 127.89, 127.95, 128.02, 128.22, 128.80, 136.66, 138.50, 140.03, 141.07, 148.41, 150.10, 152.58, 157.47

FT―IR max cm-1(KBr) 762, 780, 896, 945, 1079, 1135, 1394, 1496, 1510, 1603, 1615, 2858, 2925, 3070

HBC78(5aR,15bS)11-chloro-3-(2,5-dichlorophenyl)-1,5,5,7a-tetramethyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6] thiochromeno[2,3-b]quinolineM.F. C30H26Cl3N3OSM.P. 138―140 oCM.W. (g/mole) 581.09Element. Anal. C H NCal 61.81 4.50 7.21Obs 61.75 4.46 7.25

1H NMR δ ppm(CDCl3)1.26 (s, 3H, 5―CH3), 1.38 (s, 3H, 5―CH3), 1.63 (s, 3H, 7a―CH3), 1.81―2.11 (m, 4H, 6 & 7― CH2), 2.28 (s, 3H, 1―CH3), 2.38―2.43 (m, 1H, 5a―H), 3.70 (d, 1H, J = 8.4 Hz, 15b―H), 6.38 (s, 1H, 15―H), 7.33―7.95 (m, 7H, Ar―H)

13C NMR δ ppm(CDCl3)13.44, 20.27, 22.10, 28.33, 30.55, 31.90, 33.57, 40.95, 48.12, 85.02, 117.88, 120.09, 122.08, 125.27, 125.37, 126.65, 126.98, 127.92, 128.70, 130.12, 132.08, 135.55, 143.65, 147.78, 147.98, 160.04FT―IR max cm-1

(KBr) 581, 656, 771, 806, 870, 927, 1092, 1138, 1476, 1512, 1605,2858, 2923, 3070


HBC79(5aR,15bS)11-chloro-1,5,5,7a-tetramethyl-3-(4-nitrophenyl)-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6] thiochromeno[2,3-b]quinolineM.F. C30H27ClN4O3SM.P. 162―164 oCM.W. (g/mole) 603.13Element. Anal. C H NCal 64.45 4.87 10.02Obs 64.35 4.92 9.98

1H NMR δ ppm(CDCl3)1.27 (s, 3H, 5―CH3), 1.47(s, 3H, 5―CH3), 1.63 (s, 3H, 7a―CH3), 2.12―2.18 (m, 4H, 6 & 7―CH2), 2.35 (s, 3H, 1―CH3), 2.38―2.45 (m, 1H, 5a―H), 3.63 (d, 1H, J = 6.8 Hz, 15b―H), 6.42 (s, 1H, 15―H), 7.10―7.82 (m, 8H, Ar―H)

13C NMR δ ppm(CDCl3)13.33, 17.90, 19.22, 20.77, 21.95, 28.58, 30.33 31.91, 33.44, 41.05, 47.88, 49.12, 85.88, 95.65, 117.70, 118.56, 122.41, 124.66, 124.97, 125.80, 125.89, 126.56, 132.89, 135.85, 142.37, 144.55, 146.32, 149.80FT―IR max cm-1

(KBr) 577, 658, 782, 806, 890, 927, 1088, 1145, 1482, 1515, 1610, 2862, 2932, 3064

HBC80(5aR,15bS)1,5,5,7a,10-pentamethyl-3-phenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C31H31N3OS

N S

O

NNM.P. 146―148 oCM.W. (g/mole) 493.22Element. Anal. C H NCal 75.42 6.33 8.51Obs 75.50 6.29 8.56

1H NMR δ ppm(CDCl3)1.32 (s, 3H, 5―CH3), 1.55 (s, 3H, 5―CH3), 1.67 (s, 3H, 7a―CH3), 1.89―2.22 (m, 4H, 6&7―CH2), 2.36 (s, 3H, 1―CH3), 2.45―2.53 (m, 1H, 5a―H), 2.77 (s, 3H, 10―CH3) 3.68 (d, 1H, J = 8.4 Hz, 15b―H), 6.51 (s, 1H, 15―H), 7.32―8.05 (m, 9H, Ar―H)

13C NMR δ ppm(CDCl3)12.88, 20.97, 22.28, 26.25, 28.23, 30.37, 30.89, 31.98, 33.67, 40.92, 47.98, 84.64, 94.09, 120.23, 122.21, 125.22, 125.89, 126.37, 126.89, 127.56, 127.99, 128.80, 129.75, 132.36, 138.89, 143.32, 147.31, 147.43, 150.57, 158.17FT―IR max cm-1

(KBr) 757, 822, 1105, 1335, 1397, 1489, 1610, 2935, 2962, 3042


HBC81(5aR,15bS)1,5,5,7a,10-pentamethyl-3-(p-tolyl)-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C32H33N3OSM.P. 236―238 oCM.W. (g/mole) 507.23Element. Anal. C H NCal 75.70 6.55 8.28Obs 75.62 6.59 8.32

1H NMR δ ppm(CDCl3)1.26 (s, 3H, 5―CH3), 1.48 (s, 3H, 5―CH3), 1.64 (s, 3H, 7a―CH3), 1.98―2.03 (m, 4H, 6&7―CH2), 2.29 (s, 3H, 1―CH3), 2.33 (s, 3H, p―CH3), 2.40 (m, 1H, 5a―H), 2.77 (s, 3H, 10―CH3), 3.70 (d, 1H, J = 8.4 Hz, 15b―H), 6.39 (s, 1H, 15―H), 7.25―7.79 (m, 8H, Ar―H)

13C NMR δ ppm(CDCl3)12.88, 13.31, 17.89, 20.68, 20.95, 21.05, 22.09, 28.29, 30.24, 31.85, 33.58, 41.13, 47.87, 84.43, 93.82, 120.31, 121.10, 122.23, 125.58, 126.11, 126.72, 129.43, 129.46, 129.72, 132.88, 135.08, 135.86, 138.17, 142.76, 146.54, 147.09, 156.76FT―IR max cm-1

(KBr) 756, 817, 1105, 1327, 1390, 1490, 1608, 2920, 2950, 3033

HBC82(5aR,15bS)3-(3-chlorophenyl)-1,5,5,7a,10-pentamethyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano [4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C31H30ClN3OSM.P. 210―212 oCM.W. (g/mole) 527.18Element. Anal. C H NCal 70.50 5.73 7.96Obs 70.62 5.68 7.91

1H NMR δ ppm(CDCl3)1.37 (s, 3H, 5―CH3), 1.47 (s, 3H, 5―CH3), 1.66 (s, 3H, 7a―CH3), 1.75―2.05 (m, 4H, 6 & 7―CH2), 2.28 (s, 3H, 1―CH3), 2.38―2.47 (m, 1H, 5a―H), 2.82 (s, 3H, 10―CH3), 3.75 (d, 1H, J = 7.2 Hz, 15b―H), 6.22 (s, 1H, 15―H), 7.35―7.88 (m, 8H, Ar―H)


(KBr) 750, 821, 1115, 1325, 1387, 1497, 1612, 2906, 2956, 3062


HBC83(5aR,15bS)5,5,7a,10-tetramethyl-1,3-diphenyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C36H33N3OSM.P. 188―190 oCM.W. (g/mole) 555.23Element. Anal. C H NCal 77.80 5.99 7.56Obs 77.73 6.03 7.60

1H NMR δ ppm(CDCl3)1.27 (s, 3H, 5―CH3), 1.48 (s, 3H, 5―CH3), 1.61 (s, 3H, 7a―CH3), 1.77―2.11 (m, 4H, 6 & 7―CH2), 2.32 (s, 3H, 1―CH3), 2.40―2.56 (m, 1H, 5a―H), 2.70 (s, 3H, 10―CH3), 3.71 (d, 1H, J= 6.8 Hz, 15b―H), 6.49 (s, 1H, 15―H), 7.13―7.88 (m, 14H, Ar―H)

13C NMR δppm(CDCl3)15.12, 18.56, 21.32, 22.88, 28.31, 31.49, 32.35, 33.98, 41.25, 48.17, 85.58, 107.15, 116.78, 117.54, 120.83, 124.87, 125.46, 127.59, 127.89, 128.15, 128.52, 128.89, 129.10, 136.78, 138.50, 139.93, 141.07, 148.89, 150.10, 152.58, 156.97FT―IR maxcm-1 (KBr) 757, 828, 1125, 1330, 1390, 1495, 1608, 2910, 2963, 3058

HBC84(5aR,15bS)3-(2,5-dichlorophenyl)-1,5,5,7a,10-pentamethyl-5,5a,6,7,7a,15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano [4',3':5,6]thiochromeno[2,3-b]quinolineM.F. C31H29ClN3OSM.P. 214―216 oCM.W. (g/mole) 561.14Element. Anal. C H NCal 66.19 5.20 7.47Obs 66.08 5.26 7.51

1H NMR δ ppm(CDCl3)1.32 (s, 3H, 5―CH3), 1.58 (s, 3H, 5―CH3), 1.65 (s, 3H, 7a―CH3), 1.78―2.08 (m, 4H, 6 & 7―CH2), 2.26 (s, 3H, 1― CH3), 2.32―2.38 (m, 1H, 5a―H), 2.56 (s, 3H, 10―CH3), 3.89 (d, 1H, J = 8.4 Hz, 15b―H), 6.58 (s, 1H, 15―H), 7.21―7.85 (m, 7H, Ar―H)

13C NMR δ ppm(CDCl3)12.89, 20.28, 22.75, 26.58, 28.45, 30.91, 31.92, 33.67, 41.09, 48.26, 85.13, 117.76, 120.19, 121.98, 125.89, 125.98, 126.22, 126.75, 127.71, 128.70, 130.12, 132.08, 135.42, 143.65, 147.87, 147.98, 159.79

FT―IR max cm-1(KBr) 557, 775, 858, 1115, 1345, 1397, 1508, 1598, 2922, 2958, 3128


HBC85(5aR,15bS)1,5,5,7a,10-pentamethyl-3-(4-nitrophenyl)5,5a,6,7,7a, 15b-hexahydro-3H-pyrazolo[4'',3'':5',6']pyrano[4',3':5,6] thiochromeno[2,3-b]quinolineM.F. C31H30N4O3SM.P. 248―250 oCM.W. (g/mole) 538.20Element. Anal. C H NCal 69.12 5.61 10.40Obs 69.05 5.67 10.36

1H NMR δ ppm(CDCl3)1.29 (s, 3H, 5―CH3), 1.57(s, 3H, 5―CH3), 1.65 (s, 3H, 7a―CH3), 2.01―2.06 (m, 4H, 6 & 7―CH2), 2.31 (s, 3H, 1―CH3), 2.40―2.45 (m, 1H, 5a―H), 2.77 (s, 3H, 10―CH3), 3.71 (d, 1H, J = 7.2 Hz, 15b―H), 6.34 (s, 1H, 15―H), 7.28―8.32 (m, 8H, Ar―H)

13C NMR δ ppm(CDCl3)13.41, 17.87, 19.10, 20.85, 22.05, 23.33, 28.38, 30.22, 31.81, 33.54, 40.95, 47.78, 48.96, 85.81, 95.49, 117.68, 118.79, 122.39, 124.76, 125.01, 125.71, 125.87, 126.68, 132.90, 135.91, 142.16, 143.97, 146.31, 149.68

FT―IR max cm-1(KBr) 511, 750, 851, 1106, 1336, 1392, 1511, 1595, 2917, 2947, 3119

1H NMR spectrum of compound HBC65


APT spectrum of compound HBC65

FT-IR spectrum of compound HBC65


1H–1H NOESY spectrum of compound HBC68


1H–1H DQF–COSY spectrum of compound HBC68



13C NMR spectrum of compound HBC68


DEPT―135 spectrum of compound HBC68


N S

O

NN

1

23

4

5

6

78910

11

1213 14 15 15b

5a

7a


ESI―MS of compound HBC68











N S

O

NN

1

23

4

5

6

78910

11

1213 14 15 15b

5a

7a

Cl

Cl


ESI―MS of compound HBC76












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Synthesis of pyrazolopyrano fused …shodhganga.inflibnet.ac.in/bitstream/10603/29329/12/12...aldehyde 2 (0.05 mol, 9.45 of 2-mercapto-quinoline-3-carbaldehyde or 11.2 its 7-chloro