7.1 Introduction - INFLIBNETshodhganga.inflibnet.ac.in/bitstream/10603/20742/15/14_chapter - 7.pdf · applications of microwave (MW) technology as nonconventional heating source

Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst

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7.1 Introduction

Indole and its derivatives have occupied a unique place in the chemistry

of nitrogen heterocyclic compounds.1 The indole derivatives were known for

their dying properties. Many compounds of indole derivatives having the

structural resemblance to the ancient dye indigo are known in the literature. A

large number of naturally occurring compounds, like alkaloids, were found to

possess indole nucleus. The recognition of the plant growth hormone,

heteroauxin2, the important amino acids, tryptamine3 & tryptophan4, anti-

inflammatory drug, indomethacine5 and anticancer drug, isatin derivative6 are

the important derivatives of indole which have added stimulus to this research

work. The following are the potent derivatives -

Indole Heteroauxin Tryptamine Tryptophan

Indomethacine Isatin derivative

Isatin (1H-indole-2,3-dione) was first obtained by Erdman and Laurent

in 1841 as a product from the oxidation of indigo by nitric and chromic acids.

Isatin, possessing an indole nucleus containing both the keto and lactam moiety


Chapter 7

220

has aroused tremendous curiosity due to its diverse biological and

pharmacological studies7 and also for the synthesis of numerous heterocyclic

compounds.

In nature, isatin is found in plants of the genus Isatis8, in Calanthe

discolor9 and in Couroupita guianensis10, and has also been found as a

component of the secretion from the parotid gland of Bufo frogs11, and in

humans as it is a metabolic derivative of adrenaline.12-14 Substituted isatins are

also found in plants, for example the melosatin alkaloids (methoxy

phenylpentyl isatins) obtained from the Caribbean tumorigenic plant Melochia

Tomentosa15-17 as well as from fungi: 6-(3'-methylbuten-2'-yl)isatin was

isolated from Streptomyces albus18 and 5-(3'-methylbuten-2'-yl)isatin from

Chaetomium globosum.19 Isatin has also been found to be a component of coal

tar.20

The synthetic versatility of isatin has led to the extensive use of this

compound in organic synthesis. Three reviews have been published regarding

the chemistry of this compound: the first by Sumpter, in 1954,21 a second by

Popp in 1975,22 and the third on the utility of isatin as a precursor for the

synthesis of other heterocyclic compounds.23 The synthetic versatility of isatin

has stemmed from the interest in the biological and pharmacological properties

of its derivatives.


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221

From literature survey it is well known that isatin heterocycles exhibit

manifold importance in the field of medicinal chemistry as a potent

chemotherapeutic agent. Recently Islam24,25 and others in collaboration with

National Cancer Institute (NCI) of USA, have observed and reported that

acylated ∆2-1,3,4 thiadiazoline derivatives of isatin which have shown effective

anticancer activity against a number of cancer cells especially for breast

cancer.

In the last decade, microwave assisted organic synthesis (MAOS) have

become a new and quickly growing area in the synthetic organic chemistry.26,27

This synthetic technique is based on the empirical observation that some

organic reactions proceed much faster and with higher yields under microwave

irradiation as compared to conventional heating. In many cases reactions that

normally require many hours at reflux temperature under classical conditions

can be completed within several minutes or even seconds in a microwave oven.

Recent simplifications of MORE (microwave organic reaction

enhancement) technique have increased safety and practical utility of the

microwave oven for their use in organic laboratories without any modification.

An eco-friendly method is an important salient feature of MORE chemistry,

since it requires no solvent (dry media synthesis) or very little solvent as

energy transfer medium.28

The focal point of chemical research in recent years is the development

of resource and environmentally benign processes in terms of sustainable

chemistry. In this regard development of new eco-friendly reactions,29,30


Chapter 7

222

applications of microwave (MW) technology as nonconventional heating

source are gaining considerable interest in the scientific community and

pharmaceutical industry.31,32 Similarly, chemical processes with high atom

economy have received growing interest from a green chemistry point of view.

Pure products in quantitative yields have been reported with the use of

microwave. Low boiling point, toxic and poisonous solvents are often avoided

in microwave synthesis to avoid accidents. The use of microwave for the

synthesis of organic compounds has proved to be efficient, safe and an

environmentally benign technique with shorter reaction time.33

The use of microwave irradiation in organic synthesis has become

increasingly popular within the pharmaceutical and academic areas, because it

is a new enabling technology for drug discovery and development. By taking

advantage of this efficient source of energy, compound libraries for lead

generation and optimization can be assembled in a fraction of the time required

by classical thermal methods. Taking this into consideration, an attempt has

been made to synthesize some isatin derivatives using microwave irradiation

under solvent free condition by employing CuPy2Cl2 as catalyst.


Chapter 7

223

7.2 Methods for the synthesis of indole derivatives

K.C. Majumdar34 and others have developed a green and highly efficient

one-pot three-component approach for the synthesis of spiro[indoline-3,40-

thiopyrano[2,3-b]indole] derivatives by domino reaction of indoline-2-thione,

isatin and ethyl cyanoacetate or malononitrile in ethanol.

K.R. Moghadam and L.Y. Miri35 have reported synthesis of spiro[1H-

indeno[1,2-b]benzoquinolin-13,30-indoline]-7,13-dihydro-12,20-dione

derivatives through three-component reactions between 2H-indene-1,3-dione,

naphthalenamine and isatin derivatives using ionic liquid as catalyst.

Y. Sarrafi36 and others have reported amberlyst 15 can efficiently

catalyzed the electrophilic substitution reaction of indoles with isatin

derivatives to afford 3,3-di(indolyl)oxindoles in water.


Chapter 7

224

Y. Zou37 and others have reported one-pot synthesis of spiro[indoline-

3,4′-pyrano[2,3-c]pyrazole] derivatives by four-component reaction of

hydrazine, β-keto ester, isatin, and malononitrile or ethyl cyanoacetate under

ultrasound irradiation using piperidine as a catalyst.

H.M. Meshram38 and others have described environmentally friendly

synthesis of 3-hydroxy-3-(nitromethyl)indolin-2-one by the reaction of isatins

with nitromethane/nitroethane in the presence of DABCO.

Indole and its derivatives undergo smooth conjugate addition onto en-

1,4-dione derived from isatin and acetophenone, in the presence of a catalytic

amount of molecular iodine in acetonitrile under mild conditions to afford a

novel class of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one

derivatives.39


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225

NH

O

O +NH

10 mol% I2

CH2Cl2, R.T

NH

O

HNNH

P. Diaz40 and others have reported 6-methoxy-N-alkyl Isatin

acylhydrazone derivatives as a novel series of potent selective Cannabinoid

Receptor 2 Inverse Agonists.

Md. Rabiul41 and others have reported the synthesis of isatin 3-

carbohydrazone by reaction of carbohydrazide and isatin in glacial acetic acid.

B.V.S. Reddy42 and others have synthesized novel class of

di(indolyl)indolin-2-one derivatives by the reaction of isatin with indoles in the

presence of a catalytic amount of molecular iodine under mild conditions.

A.T. Taher43 and others have reported a series of new isatin-thiazoline

and isatin-benzimidazole 4a-h derivatives were synthesized via condensation of

isatin Mannich bases 2a-h with either 2-aminothiazoline or 2-

aminobenzimidazole.


Chapter 7

226

Iou-Jiun Kang44 and others have reported a series of isatin-β-

thiosemicarbazones evaluated for antiviral activity against herpes simplex virus

type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay.


Chapter 7

227

7.3 Biologically active Indole derivatives

Isatin (1H-indole-2,3-dione) is a versatile lead molecule for potential

bioactive agents and its derivatives were reported to possess wide spectrum of

activities. A brief review of the literature available on the chemical structure

and the biological activity of indole and its derivatives are given below-

P. Selvam45 and others have synthesized a series of novel isatin-

sulphonamide derivatives evaluated for anti-HIV activity. Investigation showed

that compound (1) was done against HIV-I(III B) in MT-4 cells and HIV

integrase.

(1)

T.N. Akhaja and J.P. Raval46 have reported the synthesis and in-vitro

evaluation of tetrahydropyrimidine–isatin hybrids as potential antibacterial,

antifungal and anti-tubercular agents. Compound (2) showed potent activity.

(2)


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228

N

RO

N-R'

NN

NO

SCH3

R

N

N R'

R''

O

N N

N

Cl

CH3

R

NO

N R'

NNH N

H

SS

N

Cl

R''

ONN

R= H, Cl, Br

-N-R', R'' = -N(CH3)2 , ,

S.N. Pandeya47-50 and others have reported some mannich bases of isatin

and screened them for anti-microbial and anti-HIV active showed good

activity. Compounds (3), (4) and (5) showed good activity.

(3) (4) (5)

S.A. Khan51 and others have reported 1-(phenylaminomethyl)3-

thiosemicarbazino isatin derivatives and evaluated for analgesic activity. The

compound (6) possess analgesic activity

(6)


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229

N

ClN

OMe

O

K.M. Khan52 and others have reported bis-schiff’s bases containing

isatin derivatives and screened for anti-glycation activity. The compound (7)

showed an excellent anti-glycation activity better than the standard.

(7)

M.S. Sharma53 and others have synthesized 3'-(p-chlorophenyl) 6'-Furyl-

cis- 5'a, 6'- dihydro spiro [3H-indole 3, 4'-thiazolo(5',1'-c) isoxazolo-2(1H)-

one]. The compound (8) possesses analgesic and anti-inflammatory activity.

(8)

S.K. Sridhar54-56 and others have reported the Schiff’s bases and phenyl

hydrazone of isatin derivatives. The compounds were screened for analgesic,

anti-inflammatory and anti-pyretic activity and compound (9) showed enhanced

activity.

(9)


Chapter 7

230

N. Karali57 and others have reported the synthesis, structural

determination and primary cytotoxicity evaluation of 5-nitroindole-2,3-dione-

3-thiosemicarbazone derivatives. The compound (10) showed better activity.

N

N

O

N O

HN

HN

SNO2CH3

(10)

P. Yogeeswari58 and others have reported the mannich bases of

gatifloxacin isatin derivatives and screened for in vitro against a panel of 58

human tumor cell lines. The compound (11) emerged as a potent anti-cancer

agent being more active than standard DNA topoisomerase II inhibitor.

(11)

D. Sriram59 and others have synthesized mannich bases of isatin

derivatives and evaluated for in vitro and in vivo anti-mycobacterial activity

and compound (12) is considered to be moderately active in reducing bacterial

count in spleen.


Chapter 7

231

(12)

V.A. Muthukumar60 and others have reported some novel Mannich base

isatin derivatives and evaluated for anti-inflammatory and analgesic activity.

The compound (13) showed significant anti-inflammatory and analgesic

activity.

(13)

V.R. Solomon61 and others have reported synthesis of isatin-

benzothiazole analogs. The cytotoxic effect was 10-15 folds higher on cancer

than non-cancer cells and the compound (14) was emerged as the most active

one.165

N

Cl

O

N S

NCH3

N N

N

O

O

(14)


Chapter 7

232

7.4 Present work

The research work carried out pertaining to isatin derivatives which has

been described in Scheme-6. The targeted compounds (6a1-6a3 & 6a-6e) are

synthesized by the reaction of isatin hydrazones with substituted phenyl

isocyanate to give 1-(2-oxoindolin-3-ylidene)-4-phenylsemicarbazide (6a1-6a3)

and reaction of isatin with different anilines to give isatin derivatives (6a-6e)

under microwave irradiation using CuPy2Cl2 as a catalyst. This protocol is

attractive in terms of short reaction time, simple and tolerance of various

anilines, clean reaction profiles and reusability of the catalyst are some of the

important features of this reaction.

Scheme-6:

Cu Py

2 Cl2

MW


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233

7.5 Experimental procedure

Synthesis of substituted 3-hydrazonoindolin-2-one62 The preparation of 5-fluoro-3-hydrazonoindolin-2-one was carried out

by refluxing a mixture of 5-fluoroindoline-2,3-dione (1 g) and hydrazine

hydrate (10 mL) in methanol on water bath for 3-4h and cooled. The solid that

separated was filtered and recrystallized from methanol.

Synthesis of 1-(2-oxoindolin-3-ylidene)-4-phenylsemicarbazide(6a1-6a3 & 6a-6e)

A mixture of substituted 3-hydrazonoindolin-2-one (1 mmol) with

substituted phenyl isocyanate (1 mmol) and/or substituted anilines using

CuPy2Cl2 (5 mol %) in ethanol (2 mL) was added drop wise in a reaction

vessel. The mixture was placed on the center of the turn-table in a domestic

microwave oven (IFB-20PG3S, 800 W, 2.45 GHz). The mixture was then

irradiated at the specified power for the prescribed time. After the microwave

was switched off, the reactions were followed by thin layer chromatography

(TLC) using hexane/ethyl acetate (3:1) as an eluents. After completion of the

reaction, the products were cooled at room temperature and the solvent was

evaporated under vacuum. The residue was washed with water and extracted

with CH2Cl2 and the organic layers were dried on Na2SO4 and evaporated

under vacuum. The crude product was recrystallized from ethanol to afford

indole derivatives.


Chapter 7

234

7.6 Results and discussion

In this research work, it is described CuPy2Cl2-catalyzed synthesis of

reaction of isatin hydrazones with substituted phenyl isocyanate to give 1-(2-

oxoindolin-3-ylidene)-4-phenylsemicarbazide (6a1-6a3) and reaction of isatin

with different anilines to give isatin derivatives (6a-6e) under microwave using

CuPy2Cl2 as catalyst (Scheme 1, Table 1).

The synthesis was started from 5-fluoro-3-hydrazonoindolin-2-one62,

which is a very important intermediate in the synthesis of indole derivatives.

The 5-fluoro-3-hydrazonoindolin-2-one was successively irradiated with

substituted isocyanate in ethanol under microwave for 12–15mins using

CuPy2Cl2 as a catalyst to give 1-(5-fluoro-2-oxoindolin-3-ylidene)-4-phenyl

semicarbazide derivatives (6a1-6a3) in good yield (Scheme-6, Table-1).

The same reaction carried out by conventional heating for 12 min, which

is proceeded by only a trace amount and required 19 h with yield 59%. In

microwave reaction, it is required less reaction time with the case of the

conventional heating to yield 1-(5-fluoro-2-oxoindolin-3-ylidene)-4-p-

tolylsemicardazide.Therefore, microwave reaction is advantageous with quick

reaction time and neat reaction conditions. Meanwhile, substituted indoline-

2,3-dione was condensed with different anilines in ethanol under microwave

irradiation using CuPy2Cl2 to give novel indole derivatives (6a1-6a3 & 6a-6e)

(Scheme-6, Table-1). The reaction was completed in 9–14 min and the

products were isolated without any side product in good to excellent yield.


Chapter 7

235

Table - 1. Microwave assisted synthesis of isatin derivatives

Entry

Reactant 1 Reactant 2 Product Time in minsb

Yield (%)c

1

6a1

14

84

2

6a2

12

79

3

6a3

15

75

4

6a

11

90

5

6b

14

64

6

6c

10

88

7

6d

9

92

8

6e

13

71

b Time to finish the reaction monitored by TLC. c Yield refer to isolated products.

A variety of aromatic, chiral and heterocyclic amines were chosen to

modify the substituent on the product formation. The reaction of indoline-2,3-

dione and 2-(4-fluorophenyl)acetamide under microwave produced the

corresponding product 6a. Chiral amine, 2,2-dimethyl-1-phenylpropane-1,3-

diamine was used in order to probe the influence of the stereochemistry on the

product formation. The reaction between indoline-2,3-dione and chiral amine


Chapter 7

236

under microwave, yielded the product 6b (Table 1, entry 5). When the reaction

with this amine was carried under microwave, the corresponding product 6b is

produced in moderate yield (64%). However, when the reaction was performed

in refluxing ethanol, the product is obtained in low yield (45%). This indicates

that the congestion of the chiral moiety on amine affects product formation.

The reactions of indoline-2,3-dione with the more congested amines, ethyl-3-

amino-2-naphthoate and 6-methoxy-4-methylpyrimidine-1(6H)-amine still

provided products 6c and 6d respectively. No chiral induction was recorded in

this case, and the reactions (Table-1, entries 6 and 7) gave the corresponding

products 6c and 6d in high yields. This indicated that the ethoxy group and

methoxy group of amines do not affect the product formation.

This reaction proceeded sluggishly in the absence of CuPy2Cl2 catalyst

under microwave and offered only 32% yield of the product (Table-2, entry

5). The yield was greatly affected by the amount of catalyst loaded. When 1, 3,

5 and 10 mol% of the catalyst was used, the yields varied from 49, 71, 92 and

92% respectively (Table 2, entries 6–9). Therefore, 5 mol% of CuPy2Cl2 was

sufficient and use of excessive catalyst had no impact either on the rate of the

reaction or on the compound yield.

To improve the yields further and to make the process environmentally

friendly, the reaction of indoline-2,3-dione with 6-methoxy-4-

methylpyrimidine-1(6H)-amine for the formation of 3-(6-methoxy-4-

methylpyrimidin-1(2H)-ylimino)indolin-2-one (6d) was run in different

solvents (Table-2). It was found that the reaction was complete in just 9 min

and gave 92% yield in ethanol under neat conditions. Thus, it was established


Chapter 7

237

that 5 mol% of CuPy2Cl2 and 9 min of microwave irradiation under ethanol are

the optimized conditions for the effective completion of this reaction. Similar

optimization study was also carried out with 6d in the presence of various

catalysts under microwave in ethanol. Initially, p-toluene sulfonic acid was

chosen as the catalyst to carry out this reaction. As a result, long reaction times

were needed and low yield was observed (Table-3, entry 1). Attempts with

different catalysts under microwave irradiation in ethanol were performed and

the results are listed in Table-3. Best yield of the desired product 6d within a

short span of reaction time was achieved with CuPy2Cl2 (5 mol %) in ethanol.

On the basis of these promising results with CuPy2Cl2 as a catalyst and ethanol

as the reaction medium, we had performed a library synthesis of several

fluorine containing indole derivatives.

Table-2. Influence of catalyst loading on the synthesis of indole derivativesa

Entry Solventsa

CuPy2Cl2 (mol %)

Time (min)b

Yield (%)c

1 DMF 5 35 42

2 1,4 dioxane 5 42 38

3 DMSO 5 40 22 4 CH3CN 5 30 58

5 EtOH 0 21 32 6 EtOH 1 9 49

7 EtOH 3 9 71 8 EtOH 5 9 92

9 EtOH 10 9 92 aReaction of 6d under microwave irradiation using CuPy2Cl2 as catalyst in different solvents.

b Time to finish the reaction monitored by TLC. c Yield refer to isolated products.


Chapter 7

238

Table 3. Influence of different catalyst on the synthesis of indole derivativesa

Entry Catalyst

Catalyst (mol %)

Time (min)b Yield (%)c

1 p-toluene sulfonic acid

5 65 38

2 NiCl2

5 40 58

3 iodine

5 50 43

4 H3PO4.12WO3.xH2O

5 35 75

5

CuPy2Cl2 5 9 92

aReaction of 6d under microwave irradiation in ethanol under different catalysts as catalyst in different solvents under reflux. b Time to finish the reaction monitored by TLC. c Yield refer to isolated products.

The structures of these compounds were elucidated through their IR, 1H

NMR, 13C NMR, Mass spectra and elemental analysis. In the IR spectra, these

compounds exhibited an absorption around 3300cm-1 and 3200 cm-1

characteristic of the NH stretching modes, in addition to a strong absorption

around 1700 cm-1 and 1600 cm-1 assigned to the C=O stretching. The 1H-NMR

and 13C-NMR spectra were consistent with the assigned structures; the NH

proton appeared in the range of 10 ppm and the C=O appeared in the range

160-170 ppm, and the assignment of the remaining carbon and proton signals

in each case were straightforward. The mass spectra of all compounds have

showed molecular ion peak, which is in agreement with the molecular formula.


Chapter 7

239

1-(5-fluoro-2-oxoindolin-3-ylidene)-4-p-tolylsemicardazide (6a1) :

Cream color solid: m.p. = 198–199oC. IR (KBr)

(vmax/cm-1): 3358, 3297, 1685, 1657, 1585 cm-1;

1H NMR (300 MHz, DMSO) δ ppm: 2.51 (s, 3H,

CH3), 6.98-7.38 (m, 4H, Ar-H), 7.69-7.94 (m, 3H, Ar-H) 10.52 (s, 2H, NH),

10.69 (s, 1H, NH); 13C NMR (100 MHz, DMSO) δ ppm: 25.8, 110.8, 118.3,

122.2, 123.0, 124.7, 126.0, 127.0, 127.9, 133.8, 135.8, 139.4, 140.8, 158.8,

163.6; 167.5 LC-MS: m/z 312 (M+). Anal. calcd for C16H13FN4O2: C, 61.53; H,

4.2; F, 6.08; N, 17.94. Found: C, 61.59; H, 4.17; F, 6.11; N, 17.99.

4-(4-chlorophenyl)-1-(5-fluoro-2-oxoindolin-3-ylidene)semicarbazide (6a2) :

Yellow color solid: m.p. = 205–207oC. IR (KBr)

(vmax/cm-1): 3379, 3266, 2924, 1692, 1643, 1558

cm-1; 1H NMR (300 MHz, DMSO) δ ppm: 6.97-

7.43 (m, 4H, Ar-H), 7.65-7.90 (m, 3H, Ar-H), 10.36 (s, 2H, NH), 10.74 (s, 1H,

NH); 13C NMR (100 MHz, DMSO) δ ppm: 112.3, 114.6, 118.4, 122.6, 123.2,

125.4, 126.1, 127.3, 128.1, 132.5, 135.3, 139.8, 104.3, 157.4, 163.1, 166.4; LC-

MS: m/z 332 (M+). Anal. calcd for C15H10ClFN4O2: C, 54.15; H, 3.03; F, 5.71;

N, 16.84. Found: C, 54.17; H, 3.08; F, 5.75; N, 16.82.

NH

N

O

F NHNH

O

CH3

NH

N

O

F NHNH

O

Cl


Chapter 7

240

1-(5-fluoro-2-oxoindolin-3-ylidene)-4-(4-nitrophenyl)semicardazide (6a3) :

Brown color solid: m.p. = 223–224oC. IR (KBr)

(vmax/cm-1): 3374, 3253, 2918, 1670, 1629, 1572

cm-1; 1H NMR (300 MHz, DMSO) δ ppm: 7.10-

7.32 (m, 3H, Ar-H), 7.68-8.06 (m, 4H, Ar-H) 10.41 (s, 2H, NH), 10.63 (s, 1H,

NH); LC-MS: m/z 343 (M+). Anal. calcd for C15H10FN5O4: C, 52.48; H, 2.94;

F, 5.53; N, 20.40. Found: C, 52.44; H, 2.91; F, 5.59; N, 20.46.

2-(4-fluorophenyl)-N-(2-oxoindolin-3-ylidene)acetimidamide (6a) :

Blue color solid: m.p. = 244–246oC. IR (KBr)

(vmax/cm-1): 3354, 3309, 2926, 1682, 1637, 1540 cm-1;

1H NMR (300 MHz, DMSO) δ ppm: 2.74 (s, 2H,

CH2), 6.95-7.13 (m, 4H, Ar-H), 7.32-7.65 (m, 4H, Ar-

H) 8.56 (s, 1H, NH), 10.81 (s, 1H, NH); LC-MS: m/z 281 (M+). Anal. calcd for

C16H12FN3O2: C, 68.32; H, 4.30; F, 6.75; N, 14.94. Found: C, 68.26; H, 4.34;

F, 6.71; N, 14.87.

(3-amino-2,2-dimethyl-3-phenylpropylimino)indolin-2-one (6b) :

Pale yellow solid: m.p. = 210–212oC; IR (KBr) (vmax/cm-

1): 3469, 3375, 2924, 1689, 1515 cm-1; 1H NMR (300

MHz, DMSO) δ ppm: 1.22 (s, 6H, CH3), 2.95 (d, 2H,

NH2), 3.26 (s, 2H, CH2), 4.01 (s, 1H, CH), 7.01-7.24 (m,

5H, Ar-H), 7.33-7.74 (m, 4H, Ar-H) 10.49 (s, 1H, NH); LC-MS: m/z 307 (M+).

Anal. calcd for C19H21N3O: C, 74.24; H, 6.89; N, 13.67. Found: C, 74.17; H,

6.85; N, 13.71.

NH

N

O

F NHNH

ONO2

NH

N

O

NH

F

NH

N

O

H2N


Chapter 7

241

Ethyl-3-(2-oxoindolin-3-ylideneamino)-2-naphthoate (6c) :

Brown color solid: m.p. = 187–188oC. IR (KBr)

(vmax/cm-1): 3424, 2923, 1679, 1629, 1512 cm-1; 1H

NMR (300 MHz, DMSO) δ ppm: 1.35 (t, 3H, CH3),

4.21 (s, 2H, CH2), 7.03-7.39 (m, 3H, Ar-H), 7.43-7.96

(m, 6H, Ar-H) 10.38 (s, 1H, NH); LC-MS: m/z 344 (M+). Anal. calcd for

C21H16N2O3: C, 73.24; H, 4.68; N, 8.13. Found: C, 73.27; H, 4.71; F, 5.21; N,

8.19.

3-(6-methoxy-4-methylpyrimidin-1(2H)-ylimino)indolin-2-one (6d) :

Cream color solid: m.p. = 217–219 oC; IR (KBr)

(vmax/cm-1): 3399, 2918, 2879, 1679, cm-1; 1H NMR

(300 MHz, DMSO) δ ppm: 1.29 (s, 3H, CH3), 2.57

(s, 1H, CH), 3.16 (s, 2H, CH2) 3.82 (s, 3H, OCH3), 7.09-7.49 (m, 4H, Ar-H),

10.24 (s, 1H, NH); 13C NMR (100 MHz, DMSO) δ ppm: 21.9, 51.2, 56.8,

62.8, 119.5, 120.5, 121.7, 122.6, 130.8, 142.9, 151.3, 163.1, 169.4; LC-MS:

m/z 270 (M+). Anal. calcd for C14H14N4O2: C, 62.21; H, 5.22; N, 20.73. Found:

C, 62.25; H, 5.16; N, 20.77.

NH

O

N

C2H5O

O

NH

N

O

N

N CH3

OCH3


Chapter 7

242

3-(6-bromo-7H-purin-2-ylimino)-5-fluoroindolin-2-one (6e) :

Light brown solid: m.p. = 196–198oC; IR (KBr)

(vmax/cm-1): 3458, 3364, 2923, 1665, cm-1; 1H NMR

(300 MHz, DMSO) δ ppm: 7.13-7.66 (m, 3H, Ar-H)

7.89 (s, 1H, Ar-H), 10.49 (s, 1H, NH) 11.54 (s, 1H,

NH); LC-MS: m/z 361 (M+). Anal. calcd for C13H6BrFN6O: C, 43.24; H, 1.67;

F, 5.26; N, 23.27. Found: C, 43.27; H, 1.65; F, 5.29; N, 23.31.

NH

N

OF

N

N

N

HN

Br


Chapter 7

243

Spectrum 1: IR Spectrum of compound 6a1

Spectrum 2: 1H NMR Spectrum of compound 6a1 in DMSO


Chapter 7

244

Spectrum 3: 13C NMR Spectrum of compound 6a1 in DMSO

Spectrum 4: Mass Spectrum of compound 6a1


Chapter 7

245

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