Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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 & tryptophan 4, antiinflammatory 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
Indomethacine
Tryptophan
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 219
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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.
220
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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,29,30 221
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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.
222
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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-3,40thiopyrano[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[1Hindeno[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.
223
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
Y. Zou37 and others have reported one-pot synthesis of spiro[indoline3,4′-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 en1,4-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
224
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
P.
Diaz40 and
others
have reported
Chapter 7
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 3carbohydrazone 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.
O O
10 mol% I2
+
N H
N H
HN NH
CH2Cl2, R.T
O N H
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
aminobenzimidazole.
225
either
2-aminothiazoline
or
2-
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
Iou-Jiun Kang44 and others have reported a series of isatin-βthiosemicarbazones evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay.
226
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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 belowP. Selvam45 and others have synthesized a series of novel isatinsulphonamide 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)
227
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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. CH3
O N
N
N
N
SCH3
R O N
N
Cl
N-R'
N
H N
H N
N R'
(4)
R''
N S
S
R= H, Cl, Br
O
(5)
N
Cl
O
(3)
R
N
N R
-N-R', R'' =
-N(CH3)2
,
N
N
O
,
N R' R''
S.A. Khan51 and others have reported 1-(phenylaminomethyl)3thiosemicarbazino isatin derivatives and evaluated for analgesic activity. The compound (6) possess analgesic activity
(6)
228
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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'-Furylcis- 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 OMe
activity.
N Cl O N
(9)
229
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
N. Karali57 and others have reported the synthesis, structural determination and primary cytotoxicity evaluation of 5-nitroindole-2,3-dione3-thiosemicarbazone derivatives. The compound (10) showed better activity.
N
H N
H N
CH3
NO2
S O N N
O
(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. Sriram 59 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.
230
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
(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 isatinbenzothiazole 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
N
CH3
S O
N N N N
O
O
(14) 231
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
7.4 Present work The research work carried out pertaining to isatin derivatives which has been described in Scheme-6. The targeted compounds (6a1-6a 3 & 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:
CuPy2Cl2 MW
232
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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.
233
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
7.6 Results and discussion In this research work, it is described CuPy2 Cl2-catalyzed synthesis of reaction of isatin hydrazones with substituted phenyl isocyanate to give 1-(2oxoindolin-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 indoline2,3-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.
234
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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 c
Time to finish the reaction monitored by TLC. 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-2,3dione and 2-(4-fluorophenyl)acetamide under microwave produced the corresponding product 6a. Chiral amine, 2,2-dimethyl-1-phenylpropane-1,3diamine 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
235
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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-3amino-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
methylpyrimidine-1(6H)-amine
indoline-2,3-dione for
the
formation
with of
6-methoxy-43-(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 236
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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
a
Reaction 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.
237
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
Table 3. Influence of different catalyst on the synthesis of indole derivativesa Entry Catalyst Catalyst Time (min)b Yield (%)c (mol %) 1 p-toluene sulfonic 5 65 38 acid 2 NiCl2 5 40 58 3
iodine
5
50
43
4
H3PO4.12WO3.xH2O
5
35
75
5
CuPy2Cl2
5
9
92
a
Reaction 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
13
C-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.
238
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
1-(5-fluoro-2-oxoindolin-3-ylidene)-4-p-tolylsemicardazide (6a1) : Cream color solid: m.p. = 198–199 oC. IR (KBr)
O NH
F
N NH
N H
(vmax/cm-1): 3358, 3297, 1685, 1657, 1585 cm -1;
O
CH 3
1
H 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);
13
C 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)
O NH
F
N NH
N H
O
(vmax/cm-1): 3379, 3266, 2924, 1692, 1643, 1558 Cl
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);
13
C 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; LCMS: 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.
239
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
1-(5-fluoro-2-oxoindolin-3-ylidene)-4-(4-nitrophenyl)semicardazide (6a3) : O NH
F
NO2
Brown color solid: m.p. = 223–224oC. IR (KBr)
N NH
(vmax/cm-1): 3374, 3253, 2918, 1670, 1629, 1572
O
cm -1; 1H NMR (300 MHz, DMSO) δ ppm: 7.10-
N H
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) : F N
Blue color solid: m.p. = 244–246oC. IR (KBr) (vmax/cm-1): 3354, 3309, 2926, 1682, 1637, 1540 cm -1;
NH
1
O N H
H 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, ArH) 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. = 210–212 oC; IR (KBr) (vmax/cm1
H2 N N
N H
): 3469, 3375, 2924, 1689, 1515 cm-1; 1H NMR (300
MHz, DMSO) δ ppm: 1.22 (s, 6H, CH3), 2.95 (d, 2H, O
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. 240
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
Ethyl-3-(2-oxoindolin-3-ylideneamino)-2-naphthoate (6c) : Brown color solid: m.p. = 187–188oC. IR (KBr)
O C 2H5O
(vmax/cm-1): 3424, 2923, 1679, 1629, 1512 cm -1; 1H N
NMR (300 MHz, DMSO) δ ppm: 1.35 (t, 3H, CH3), O N H
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) : O
Cream color solid: m.p. = 217–219 oC; IR (KBr)
CH3
(vmax/cm-1): 3399, 2918, 2879, 1679, cm -1; 1H NMR
N N N H
O
N
CH 3
(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);
13
C 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.
241
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
3-(6-bromo-7H-purin-2-ylimino)-5-fluoroindolin-2-one (6e) : Br N N
N
F O N H
H N N
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.
242
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Spectrum 1: IR Spectrum of compound 6a1
Spectrum 2: 1H NMR Spectrum of compound 6a1 in DMSO
243
Chapter 7
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
Spectrum 3: 13C NMR Spectrum of compound 6a1 in DMSO
Spectrum 4: Mass Spectrum of compound 6a 1
244
Microwave assisted synthesis of Indole derivatives using CuPy2Cl2 as a catalyst
Chapter 7
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