Aromatic and heteroaromatic annelation studies on 3-[bis(methylthio)methylene]-1-methyloxindole: Synthesis of carbazoles and an efficient route to pyrido[2,3-b]indoles

Article abstract of DOI:10.1016/S0040-4020(00)01054-1

The 3-[bis(methylthio)methylene]-1-methyloxindole (2) is shown to undergo cycloaromatization with allyl and methallyl magnesium chlorides to afford substituted carbazoles. A novel route to 2-substituted-3-cyano-4-methylthio/aminopyrido[2,3-b]indoles has been developed via heteroaromatic annelation of 2 with in situ generated 2-lithioamino-2-substituted acrylonitriles.

Full text of DOI:10.1016/S0040-4020(00)01054-1

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 781±789
Aromatic and heteroaromatic annelation studies on
3-[bis(methylthio)methylene]-1-methyloxindole: synthesis of
carbazoles and an ef®cient route to pyrido[2,3-b]indoles
J. R. Suresh, U. K. Syam Kumar, H. Ilap and H. Junjappap
Department of Chemistry, Indian Institute of Technology, Kanpur, 208 016, UP, India
Received 31 July 2000; revised 18 October 2000; accepted 2 November 2000
AbstractÐThe 3-[bis(methylthio)methylene]-1-methyloxindole (2) is shown to undergo cycloaromatization with allyl and methallyl
magnesium chlorides to afford substituted carbazoles. A novel route to 2-substituted-3-cyano-4-methylthio/aminopyrido[2,3-b]indoles
has been developed via heteroaromatic annelation of 2 with in situ generated 2-lithioamino-2-substituted acrylonitriles. q 2001 Elsevier
Science Ltd. All rights reserved.
1. Introduction
and its cyclic derivatives 3a±b for the preparation of substi-
tuted indoles, carbazoles and indolo[b]-fused heterocycles.
In the present paper we report the results of these investi-
gations.
The synthesis of substituted carbazoles1,2 and heterocyclo-
[b]-fused indoles such as pyrido[2,3-b, 4,3-b, 3,4-b]-
indoles3±8 has attracted considerable attention in recent
years as this class of compounds constitute structural frame-
works of several naturally occurring compounds displaying
a wide range of biological activity. Many elegant
approaches have been developed for the synthesis of
benzo and heterocyclo-fused carbazoles,9±11 indoles3±8 and
related natural products involving [b] annulation of indoles.
Our own interest in the synthesis of these compounds relies
upon application of our aromatic and heteroaromatic anne-
lation methodology involving novel (or known) a-oxo-
ketene dithioacetals as three carbon synthons for
developing ef®cient synthetic methods for a wide variety
of aromatic and heterocyclic compounds of biological
importance. We have recently reported a novel and ef®cient
route to functionalized/annulated carbazoles12 and
pyrido[2,3-b]indoles3 based upon these strategies. Also in
a recent publication, we have described the ®rst synthesis of
2-[bis(methylthio)methylene]-3-oxoindole 1 and demon-
strated its utility as a versatile building block for the
construction of substituted benzo-, heterocyclo-fused carba-
zoles and indoles such as pyrido[3,4-b]-, pyrido[3,2-b]-
indoles and indolo[3,2-b]quinolizinium ring system.13
These studies and our continued interest in the development
of new general methods for biologically important hetero-
cycles14 prompted us to examine reactivity and synthetic
application of 3-[bis(methylthio)methylene]-2-oxoindole 2
2. Results and discussion
The ketene dithioacetal 2 derived from 1-methyloxindole is
already known in the literature, ®rst prepared by Kobayashi
and co-workers15a,b by reaction of 1-methyloxindole with
carbon disul®de in the presence of sodium hydride in THF
followed by alkylation with dimethyl sulfate. They have
further reacted 2 with several primary and secondary
amines, diamines, hydrazine and amidines to afford respec-
tive N,S- and N,N-acetals as potential antibacterial and anti-
viral agents.15 Similarly stabilized carbanions derived from
diethyl malonate,16a,b ethyl cyanoacetate16c±e and phenyl-
acetonitrile16f are shown to undergo conjugate displacement
on 2 to give 1,4-adducts which are found to exhibit anti-
fungal and anti-in¯ammatory activities. However no cyclo-
condensation reactions involving the amide group of 2
Keywords: a-oxoketene dithioacetals; aromatic annelation; carbazoles;
pyrido[2,3-b]-indoles.
* Corresponding authors. Tel.: 191-0512-590260; fax: 191-0512-597426;
e-mail: hila@iitk.ac.in
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01054-1

782
J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
Scheme 1.
were reported by these authors with a sole exception of the
formation of anti-in¯ammatory pyrano[2,3-b]indole deriva-
tives when the 1,4-adducts from diethyl malonate and ethyl
acetoacetate with 2 were subjected to thermal or acid
induced cyclization.16d We thus became interested in
exploring reactivity of 2 as potential three carbon 1,3-
dielectrophilic synthon in our [313] aromatic and hetero-
aromatic annelation protocol leading to indolo[b]-fused
carbocycles and heterocycles.
methyl 1,2-dimethylindole-3-carboxylate (5a) in 58%
yield. Similarly the addition of 2 with isopropyl magnesium
chloride followed by methanolysis under identical con-
ditions afforded the corresponding methyl 2-isopropyl-1-
methylindole-3-carboxylate (5b) in moderate (52%) yield.
Interestingly, the t-butyl Grignard reagent also underwent
preferential 1,2-addition with 2 yielding t-butyl ketone 6c as
major product (59%) which is apparently formed by ring
opening of initial carbinol 4c (Scheme 1).
We ®rst examined the addition and cycloaromatization of 2
and its cyclic analogs 3 with allyl and methallyl Grignard
reagents (Scheme 2). The ketene dithioacetals 2 and 3 differ
from other oxoketene dithioacetals, in that they possess a
less electrophilic amide carbonyl group which may resist
charge controlled 1,2-addition of allyl anions. We therefore
reacted 2 ®rst with alkyl magnesium halides with a view to
examine its reactivity towards Grignard reagents. Thus,
when 2 was reacted with methylmagnesium iodide
(1.2 equiv.) it was transformed to the carbinol 4a which
on methanolysis in the presence of BF3´Et2O afforded
The ketene dithioacetal 2 was next reacted with methallyl
magnesium chloride which gave the carbinol adduct 7a in
nearly quantitative yield as monitored by tlc (Scheme 2).
The carbinol 7a was found to be unstable and used as such
for further transformation without characterization. Thus 7a
underwent smooth cycloaromatization in the presence of
BF3´Et2O in benzene to give 2,9-dimethyl-4-(methylthio)-
carbazole 8a in 67% yield. Similarly the corresponding
9-methyl-4-(methylthio)carbazole 8b was obtained in
moderate yield (46%) under identical conditions from
allyl magnesium chloride. Both the carbazoles 8a±b
Scheme 2.

J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
783
Scheme 3.
underwent smooth dethiomethylation in the presence of
Raney Ni (W2) to give sulfur free compounds 9a±b in
excellent yields. Interestingly, cycloaromatization of cyclic
ketenedithioacetal 3b with methallylmagnesium chloride
under the above described conditions yielded novel 2,9-
dimethyl-4-(3-mercaptopropylthio)carbazole 10 which is
apparently formed by opening of 1,3-dithiane ring during
BF3´Et2O induced cyclization (Scheme 2). However
addition of methallylmagnesium chloride to the correspond-
ing dithiolan derivative 3a gave only an intractable mixture
of several products under identical conditions. Thus both
intermediates 2 and 3 have been found to be useful pre-
cursors for the synthesis of functionalized indoles and carba-
zoles.
We next examined conjugate addition of stabilized car-
banions derived from aryl and heteroaryl acetonitriles on
2 and subsequent cyclization of the resulting 1,4-adducts
with a view to synthesize benzo[a]- and heterocyclo[a]-
fused carbazoles. As model examples we examined conju-
gate addition-displacement of 3,4-dimethoxyphenylaceto-
nitrile 11 and 1-benzylindole-3-acetonitrile 12 with 2 in
the presence of sodium hydride which afforded the corre-
sponding adducts 13 and 14 in high yields. We were par-
ticularly interested in cyclocondensation of the adduct 14
from indole-3-acetonitrile 12 to give the indolo[2,3-a]-
carbazole derivative 16 possessing the basic framework
present in naturally occurring indolocarbazole alkaloids
staurosporine17 and rebeccamycin.18 However our all
attempts to cyclize either 13 or 14 to the desired 15 or 16
in the presence of various condensation agents (POCl3,
H3PO4, TfOH, Tf2O, BF3´Et2O) or under thermal conditions
did not meet with any success and only gave an intractable
mixture of products.
We next focussed our attention on heterocyclization of
ketene dithioacetal 2 with lithioacetonitrile and substituted
b-(lithioamino)acrylonitriles with a view to the construction
of carboline frameworks following our earlier reported
methods.19 Interestingly, reaction of 2 with lithioacetonitrile
(1 equiv.) gave exclusively the adduct 18 formed by 1,4-
addition-displacement instead of 1,2-addition product as
observed earlier (Scheme 3).19 Attempted cyclization of
18 to a pyrido[2,3-b]indole derivative in the presence of
H3PO4 or ammonium acetate did not yield any identi®able
product. However when 2 was reacted with lithioamino-
crotonitrile 19a [generated in situ from acetonitrile
(2 equiv.) and butyl lithium (1 equiv.)], work-up of the reac-
tion mixture afforded only one product (71%) which was
characterized as 3-cyano-2,9-dimethyl-4-(methylthio)pyrido-
[2,3-b]indole (21a) on the basis of its spectral and analytical
data (Scheme 4). The reaction was found to be general and
other 2-alkyl/aryl/heteroaryl-3-cyano-4-(methylthio)pyrido-
[2,3-b]indoles 21b±g were obtained smoothly in 60±76%
Scheme 4.

784
J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
Scheme 5.
overall yields by reacting 2a with various in situ generated
2-substituted lithioaminoacrylonitriles 19b±g derived from
the respective nitriles (Scheme 4). Compound 21b was
subjected to Raney nickel (W2) desulfurization to afford
sulfur free 22b (80%) in which the cyano group is trans-
formed into the diethylaminomethyl functionality. Simi-
larly, in another experiment, the pyridoindole 21g was
reacted with W4 Raney nickel under identical conditions
to afford 4-dethiomethylated 3-methyl derivative 23g with
complete reduction of 3-cyano group. To further examine
the scope of the methodology, the N,S-acetal 24 prepared
from 2 and pyrrolidine, was reacted with lithioaminoacrylo-
nitrile 19e under similar conditions to afford the corre-
sponding 3-cyano-2-(4-methoxyphenyl)-4-(N-pyrrolidino)-
pyrido[2,3-b]indole 25e in 45% yield (Scheme 5).
ACF-300 and Jeol LA-400 spectrometers. Chemical shifts
are reported in d (ppm) relative to tetramethylsilane. Mass
spectra were obtained on a Jeol D-300 mass spectrometer.
Elemental analyses were carried out on a Heraeus CHN-O
Rapid analyzer.
All reactions were conducted in oven-dried (1208C) glass-
ware under a dry argon/nitrogen atmosphere. All reactions
were monitored by TLC on a glass plates coated with silica
gel (Acme) containing 13% calcium sulfate as binder and
visualization of compounds was accomplished by exposure
to iodine vapour or by spraying with acidic potassium per-
manganate solution. Column chromatography was carried
out using Acme silica gel (60±120 mesh). THF was distilled
over sodium benzophenone ketyl prior to use. DMF was
distilled over CaH2 and stored over molecular sieves.
n-BuLi was purchased from Aldrich.
3-Bis(methylthio)methylene-2,3-dihydro-1-methyl-2-oxo-
indole (2) was prepared by a literature procedure.15a,b The
corresponding cyclic ketene dithioacetals 3a±b were
prepared by a similar procedure and the analytical and spec-
tral data of all these ketene dithioacetals are given below.
In summary, we have demonstrated that 3-[bis(methylthio)-
methylene]-1-methyloxindole 2 is a useful precursor for
functionalized indoles and carbazoles, whereas its reaction
with 3-substituted-3-lithioaminoacrylonitriles provides a
new and ef®cient route to a variety of 2-substituted-3-
cyano-4-methylthio/aminopyrido[2,3-b]indoles. It should
be noted that pyrido[2,3-b]indoles are important targets
for synthetic organic chemists because of the presence of
this framework in marine alkaloids Grassularine 1 and 220
and Mescengricin21 displaying a broad spectrum of bio-
logical activity. Most of the synthetic approaches for these
compounds described in the literature involve construction
of pyridine ring from 2-amino-3-substituted indole deriva-
tives22 which are not easily accessible or via construction of
pyrrole ring involving cross coupling between an appro-
priately substituted pyridine and substituted aniline pre-
cursor.23 The present method along with our recently
reported method3 provides a facile access to a wide variety
of pyrido[2,3-b]indoles from easily available starting
materials. Our efforts to utilize 2 and 3 in further cyclo-
condensation processes are in progress.
3.1. 3-Bis(methylthio)methylene-2,3-dihydro-1-methyl-
2-oxoindole (2)
Yellow crystals (chloroform±hexane); mp 83±848C; lit.15a,b
mp 85±888C; Yield 75%; IR (KBr): 2923, 1670, 1605,
1518 cm21 1H NMR (300 MHz, CDCl3): 2.49 (s, 3H,
;
SCH3), 2.62 (s, 3H, SCH3), 3.27 (s, 3H, NCH3), 6.81 (d,
1H, Jˆ7.8 Hz, ArH), 7.05 (td, 1H, Jˆ7.8, 1.1 Hz, ArH),
7.23 (td, 1H, Jˆ7.8, 1.2 Hz, ArH), 8.16 (dd, 1H, Jˆ7.8,
1 Hz, ArH); 13C NMR (75 MHz, CDCl3): 19.17, 19.37,
25.92, 107.55, 121.55, 122.67, 123.35, 123.41, 127.60,
141.55, 158.02, 165.06; Anal. Calcd for C12H13NOS2
(251.37): C, 57.34; H, 5.21; N, 5.57%. Found: C, 57.53;
H, 5.14; N, 5.68%.
3.2. 3-(Ethylenedithio)methylene-2,3-dihydro-1-methyl-
2-oxoindole (3a)
Yellow crystals (chloroform±hexane); mp 112±1138C;
1
Yield 68%; IR (KBr): 1627, 1571, 1452 cm21; H NMR
3. Experimental
(400 MHz, CDCl3): 3.30 (s, 3H, NCH3), 3.48±3.57 (m,
4H, ±(CH2)2±), 6.83 (d, 1H, Jˆ 7.6 Hz, ArH), 7.07 (t, 1H,
Jˆ7.6 Hz, ArH), 7.20 (t, 1H, Jˆ7.6 Hz, ArH), 7.62 (d, 1H,
Jˆ7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3): 25.98,
37.70, 37.74, 107.47, 113.50, 121.48, 121.52, 122.82,
126.39, 140.55, 158.06, 165.91; MS: m/z (%): 249 (M1,
Melting points were obtained on Thomas Hoover and Mel-
Temp capillary melting point apparatus. IR spectra were
recorded on a Perkin±Elmer-983 and Perkin±Elmer-1320
spectrophotometers. NMR spectra were recorded on Bruker

J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
785
100); Anal. Calcd for C12H11NOS2 (249.37): C, 57.80; H,
4.45; N, 5.62%. Found: C, 57.78; H, 4.49; N, 5.71%.
ArH), 7.03 (dd, 1H, Jˆ7.6, 1.7 Hz, ArH), 7.12±7.17 (m, 1H,
ArH); 13C NMR (100 MHz, CDCl3): 16.61, 18.01, 27.47,
30.43, 44.69, 110.16, 115.84, 120.81, 129.93, 130.62,
130.64, 135.36, 146.40, 147.11; MS: m/z (%): 309 (M1,
27), 276 (100); Anal. Calcd for C16H23NOS2 (309.50): C,
62.09; H, 7.49; N, 4.53%. Found: C, 62.35; H, 7.41; N,
4.57%.
3.3. 3-(Trimethylenedithio)methylene-2,3-dihydro-1-
methyl-2-oxoindole (3b)
Yellow crystals (chloroform±hexane); mp 148±1498C;
1
Yield 71%; IR (KBr): 1616, 1590, 1458 cm21; H NMR
(400 MHz, CDCl3): 2.31 (tt, 2H, Jˆ 7.0 Hz, ±CH2±), 3.08
(t, 2H, Jˆ7.0 Hz, ±CH2±), 3.15 (t, 2H, Jˆ7.0 Hz, ±CH2±),
3.27 (s, 3H, NCH3), 6.82 (d, 1H, Jˆ 7.8 Hz, ArH), 7.04 (t,
1H, Jˆ7.7 Hz, ArH), 7.19±7.24 (m, 1H, ArH), 8.05 (d, 1H,
Jˆ7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3): 23.54,
25.70, 28.53, 29.28, 107.33, 120.12, 121.34, 122.83,
122.89, 126.68, 140.81, 158.19, 165.53; Anal. Calcd for
C13H13NOS2 (263.38); C, 59.28; H, 4.97; N, 5.32%.
Found: C, 59.53; H, 5.05; N, 5.25%.
3.5. General procedure for the reaction of allyl and
methallyl Grignard reagents with 2 and 3: synthesis of
carbazoles 8a±b and 10
To an ice cooled solution of appropriate Grignard reagent
(prepared from allyl bromide or methallyl chloride,
10 mmol and magnesium tunings, 0.5 g, 20.8 mmol) in
dry ether (75 mL), a solution of 2 or 3b (5 mmol) in dry
THF (30 mL) was added dropwise and the reaction mixture
was further stirred at room temperature for 2 h. It was then
poured into saturated aqueous NH4Cl solution (200 mL),
extracted with benzene (2£100 mL), the combined benzene
extracts were washed with water, dried (Na2SO4) and evapo-
rated to give crude carbinol as viscous residue which was
dissolved in dry benzene (50 mL) followed by addition of
BF3´Et2O (2 mL). The reaction mixture was then re¯uxed
for 2 h (monitored by tlc), cooled, poured into saturated
aqueous NaHCO3 solution (100 mL), extracted with chloro-
form (2£100 mL), washed with water, dried (Na2SO4) and
the solvent evaporated to give viscous residue which was
puri®ed by silica gel column chromatography using hexane±
ethyl acetate (99:1) as eluent.
3.4. General procedure for the reaction of alkyl
Grignard reagents with 2
To an ice cooled solution of alkyl magnesium halide
[prepared from the respective alkyl halides namely methyl
iodide, i-propyl bromide, t-butylchloride (10 mmol) and
magnesium turnings (0.5 g, 20.8 mmol)] in dry ether
(75 mL), a solution of 2 (1.26 g, 5 mmol) in dry THF
(30 mL) was added dropwise and the reaction mixture was
further stirred at room temperature for 2 h. It was then
poured into saturated aqueous NH4Cl solution (200 mL),
extracted with benzene (2£100 mL) and the combined
benzene extracts were washed with water, dried (Na2SO4)
and evaporated to give carbinol thioacetals 4 as viscous
residue. To a solution of 4 in absolute methanol (50 mL),
BF3´Et2O (2 mL) was added and the reaction mixture was
re¯uxed for 3 h. It was then poured into saturated NaHCO3
solution (100 mL), extracted with chloroform (2£100 mL),
the organic layer washed with water, dried (Na2SO4) and
evaporated to give viscous residue which was puri®ed by
silica gel chromatography using hexane±ethyl acetate
(19:1) as eluent.
3.5.1. 2,9-Dimethyl-4-(methylthio)carbazole (8a). Color-
less crystals (chloroform±hexane); mp 132±1338C; Yield
1
67%; IR (KBr): 2916, 1593, 1469 cm21; H NMR (300
MHz, CDCl3): 2.50 (s, 3H, CH3), 2.59 (s, 3H, SCH3), 3.64
(s, 3H, NCH3), 6.83 (s, 1H, ArH), 6.90 (s, 1H, ArH), 7.20±
7.27 (m, 2H, ArH), 7.37±7.42 (m, 1H, ArH), 8.49 (d, 1H,
Jˆ7.8 Hz, ArH); 13C NMR (75 MHz, CDCl3): 15.39, 22.19,
28.86, 105.69, 107.84, 117.09, 117.75, 118.87, 122.71,
123.10, 124.71, 133.32, 135.80, 140.70, 141.35; MS: m/z
(%): 241 (M1, 100); Anal. Calcd for C15H15NS (241.36):
C, 74.65; H, 6.26; N, 5.80%. Found: C, 74.91; H, 6.33; N,
5.75%.
3.4.1. Methyl 1,2-dimethylindole-3-carboxylate (5a).
Colorless crystals (chloroform±hexane); mp 137±1388C;
lit.24 mp 141±1428C; Yield 58%.
3.5.2. 9-Methyl-4-(methylthio)carbazole (8b). Colorless
crystals (chloroform±hexane); mp 80±818C; Yield 46%;
3.4.2. Methyl 1-methyl-2-(i-propyl)indole-3-carboxylate
(5b). Colorless crystals (chloroform±hexane); mp 92±938C;
1
IR (KBr): 2919, 1579, 1460 cm21; H NMR (300 MHz,
1
Yield 52%; IR (KBr): 2966, 1690, 1528 cm21; H NMR
CDCl3): 2.57 (s, 3H, SCH3), 3.63 (s, 3H, NCH3), 6.98 (d,
1H, Jˆ7.5 Hz, ArH), 7.07 (d, 1H, Jˆ8.0 Hz, ArH), 7.22±
7.44 (m, 4H, ArH), 8.55 (dd, 1H, Jˆ7.6, 1.2 Hz, ArH); 13C
NMR (75 MHz, CDCl3): 15.33, 28.88, 105.19, 107.93,
115.54, 118.94, 119.78, 122.62, 123.52, 125.20, 125.56,
133.85, 140.61, 140.83; MS: m/z (%): 227 (M1, 100);
Anal. Calcd for C14H13NS (227.33): C, 73.97; H, 5.76; N,
6.16%. Found: C, 73.66; H, 5.84; N, 6.25%.
(300 MHz, CDCl3): 1.45 (d, 6H, Jˆ7.3 Hz, (CH3)2), 3.79
(s, 3H, NCH3), 3.92 (s, 3H, OCH3), 4.42 (septet, 1H, Jˆ
7.3 Hz, CH), 7.20±7.30 (m, 3H, ArH), 8.08±8.12 (m, 1H,
ArH); 13C NMR (75 MHz, CDCl3): 20.16, 25.10, 31.49,
50.68, 102.96, 109.05, 121.68, 121.81, 122.13, 126.64,
136.86, 153.57, 166.44; MS: m/z (%): 231 (M1, 100);
Anal. Calcd for C14H17NO2 (231.29): C, 72.70; H, 7.41;
N, 6.06%. Found: C, 72.97; H, 6.32; N, 6.11%.
3.5.3. 2,9-Dimethyl-4-(3-mercaptopropylthio)carbazole
(10). Colorless crystals (Chloroform±hexane); mp 120±
3.4.3. 1,1-Bis(methylthio)-4,4-dimethyl-2-(2-N-methyl-
aminophenyl)-1-penten-3-one (6c). Viscous yellow liquid;
1
1218C; Yield 51%; IR (KBr): 2919, 1595, 1469 cm21; H
1
Yield 59%; IR (CCl4): 2911, 7124, 1420 cm21; H NMR
NMR (400 MHz, CDCl3):1.33 (t, Jˆ8.0 Hz, 1H, SH), 1.93±
2.05 (m, 2H, ±CH2±), 2.53 (s, 3H, CH3), 2.63±2.69 (m, 2H,
±CH2±), 3.17 (t, Jˆ8.0 Hz, 2H, ±CH2±), 3.74 (s, 3H,
NCH3), 7.01 (s, 2H, ArH), 7.20±7.26 (m, 1H, ArH), 7.33
(400 MHz, CDCl3): 1.05 (s, 9H, t-butyl), 2.07 (s, 3H,
SCH3), 2.27 (s, 3H, SCH3), 2.76 (s, 3H, NCH3), 4.58 (brs,
1H, NH), 6.53 (d, Jˆ7.6 Hz, 1H, ArH), 6.58±6.63 (m, 1H,

786
J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
(d, Jˆ8.0 Hz, 1H, ArH), 7.40±7.45 (m, 1H, ArH), 8.60 (d,
Jˆ8.0 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): 22.12,
23.48, 28.98, 31.54, 32.97, 106.90, 107.97, 118.96, 119.36,
121.22, 122.67, 123.19, 125.04, 130.52, 135.72, 140.90,
141.65; MS: m/z (%): 301 (M1, 93) 227 (100); Anal.
Calcd for C17H19NS2 (301.48): C, 67.73; H, 6.35; N,
4.65%. Found: C, 67.97; H, 6.43; N, 4.59%.
3.7. Reaction of lithioacetonitrile with 2
To a stirred solution of freshly distilled acetonitrile (0.6 mL,
11.5 mmol) in dry THF (25 mL), n-BuLi (12 mmol) was
added under nitrogen atmosphere at 2788C and the reaction
mixture was further stirred at the same temperature for
0.5 h. To the resulting suspension of lithioacetonitrile, a
solution of 2 (2.51 g, 10 mmol) in dry THF (40 mL) was
added and the reaction mixture was allowed to warm to
room temperature during 2 h with continuous stirring. It
was then poured into saturated NH4Cl solution (200 mL),
extracted with chloroform (2£100 mL), washed with water
and concentrated to give viscous residue which was puri®ed
by passing through silica gel column using hexane±ethyl
acetate (19:1) as eluent.
3.5.4. 2,9-Dimethylcarbazole (9a) and 9-methylcarbazole
(9b). To a solution of 8a or 8b (2 mmol) in ethanol (25 mL),
Raney nickel (W2, 5 times by weight) was added and the
suspension was re¯uxed with stirring for 3 h (monitored by
tlc). The reaction mixture was then cooled, ®ltered through a
sintered funnel and the residue was washed with ethanol.
The ®ltrate was evaporated under vacuum and the residue
was dissolved in chloroform (50 mL), washed with water,
dried (Na2SO4) and concentrated to give crude 9a or 9b
which was puri®ed by passing through a small silica gel
column using hexane as eluent.
3.7.1. 3-[2-Cyano-1-(methylthio)ethylidene]-2,3-dihydro-
1-methyl-2-oxoindole (18). Yellow crystals (chloroform±
hexane); mp 155±1568C; yield 80%; IR (KBr): 1615, 1516,
1473 cm21; 1H NMR (400 MHz, CDCl3): 2.72 (s, 3H, SCH3),
3.23 (s, 3H, NCH3), 4.78 (s, 2H, CH2), 6.80 (d, 1H, Jˆ7.8 Hz,
ArH), 7.05±7.09 (m, 1H, ArH), 7.26±7.31 (m, 1H, ArH),
7.97 (d, 1H, Jˆ7.8 Hz, ArH); 13C NMR (100 MHz,
CDCl3): 14.06, 17.59, 25.85, 107.61, 116.12, 122.06,
122.67, 122.89, 125.16, 128.89, 141.85, 144.35, 165.53;
Anal. Calcd for C13H12N2OS (244.32): C, 63.91; H, 4.95;
N, 11.47%. Found: C, 64.13; H, 4.91; N, 11.56%.
3.5.5. 2,9-Dimethylcarbazole (9a). Colorless crystals
(hexane); mp 82±838C; lit.25 mp 85±878C; Yield 82%.
3.5.6. 9-Methylcarbazole (9b). Colorless crystals (hexane);
mp 878C; lit.26 mp 87±888C; Yield 86%.
3.6. General procedure for the reaction of 3,4-dimeth-
oxyphenylacetonitrile and 1-benzylindole-3-acetonitrile
with 2
3.7.2. Procedure for the generation of lithio-
aminocrotononitrile (19a) and its reaction with 2: synthe-
sis of 3-Cyano-2,9-dimethyl-4-(methylthio)pyrido[2,3-b]-
indole (21a). To a stirred solution of acetonitrile (0.8 mL,
15.3 mmol) in dry THF (25 mL), n-BuLi (7.5 mmol) was
added under nitrogen atmosphere at 2788C and the reaction
mixture was stirred for 0.5 h at the same temperature. To the
resulting light reddish suspension of b-lithioaminocrotono-
nitrile, a solution of 2 (1.26 g, 5 mmol) in dry THF (25 mL)
was added dropwise and the reaction mixture was further
stirred at re¯uxing temperature for 48 h. It was then cooled
and poured into saturated NH4Cl solution, extracted with
chloroform (2£100 mL), combined organic phase was
washed with water, dried (Na2SO4) and concentrated to
give crude 21a which was puri®ed by column chroma-
tography over silica gel using hexane±ethyl acetate (19:1)
as eluent.
To a stirred suspension of NaH (10 mmol) in DMF (10 mL)
at 08C, a solution of 3,4-(dimethoxyphenyl)acetonitrile or
1-benzylindole-3-acetonitrile (5 mmol) in DMF (10 mL)
was added dropwise. After 20 min, a solution of 2 (1.26 g,
5 mmol) in DMF (10 mL) was slowly added and the reac-
tion mixture was brought to room temperature and further
stirred for 7±10 h (monitored tlc). It was then poured into
saturated NH4Cl solution (200 mL) and the solid obtained
was ®ltered, dried and recrystallized.
3.6.1. 3-[2-Cyano-2-(3,4-dimethoxyphenyl)-1-methylthio]-
ethylidine-2,3-dihydro-1-methyl-2-oxoindole (13). Yellow
crystals (methanol); mp 135±1368C; Yield 92%; IR (KBr):
1
2930, 2240, 1684, 1608, 1513 cm21; H NMR (400 MHz,
CDCl3): 2.42 (s, 3H, SCH3), 3.28 (s, 3H, NCH3), 3.88 (s,
3H, OCH3), 3.92 (s, 3H, OCH3), 4.96 (s, 1H, CHCN),
6.84±6.92 (m, 2H, ArH), 6.98±7.18 (m, 3H, ArH), 7.26±
7.41 (m, 2H, ArH); MS: m/z (%): 380 (M1, 92), 332 (100);
Anal. Calcd for C21H20N2O3S (380.47): C, 66.30; H, 5.30; N,
7.36%. Found: C, 66.56; H, 5.24; N, 7.47%.
21a: Colorless crystals (ether±hexane); mp 162±1638C;
1
Yield 71%; IR (KBr): 2200, 1540, 1458 cm21; H NMR
(400 MHz, CDCl3): 2.73 (s, 3H, CH3), 2.81 (s, 3H, SCH3),
3.86 (s, 3H, NCH3), 7.31±7.39 (m, 2H, ArH), 7.51±7.56 (m,
1H, ArH), 8.50 (d, 1H, Jˆ7.8 Hz, ArH); 13C NMR
(100 MHz, CDCl3): 18.17, 24.26, 27.72, 102.94, 109.14,
114.28, 118.03, 119.79, 121.20, 123.89, 127.34, 140.30,
145.24, 150.96, 159.58; MS: m/z (%): 267 (M1, 100);
Anal. Calcd for C15H13N3S (267.35): C, 67.39; H, 4.90; N,
15.72%. Found: C, 67.67; H, 4.81; N, 15.56%.
3.6.2. 3-[2-(N-Benzylindol-3-yl)-2-cyano-1-methylthio]-
ethylidine-2,3-dihydro-1-methyl-2-oxoindole (14). Light
yellow crystals (methanol); mp 136±1378C; Yield 90%;
;
IR (KBr): 2923, 2210, 1697, 1608 cm21 1H NMR
(400 MHz, CDCl3): 2.37 (s, 3H, SCH3), 3.26 (s, 3H,
NCH3), 5.13 (s, 1H, CHCN), 5.32 (s, 2H, CH2Ph), 6.85 (d,
Jˆ7.6 Hz, 1H, ArH), 7.00±7.35 (m, 11H, ArH), 7.91 (s,
1H, ArH), 8.00±8.02 (m, 1H, ArH); MS: m/z (%): 449
(M1, 25), 91 (100); Anal. Calcd for C28H23N3OS (449.58):
C, 74.81; H, 5.16; N, 9.35%. Found: C, 74.48; H, 5.31; N,
9.54%.
3.8. General procedure for the generation of
2-substituted 2-lithioaminoacrylonitriles 13b±g and
their reaction with 2: synthesis of 2-substituted-3-cyano-
4-(methylthio)-pyrido[2,3-b]indoles 21b±g
To a stirred solution of acetonitrile (0.4 mL, 7.6 mmol) in

J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
787
1
dry THF (25 mL), n-BuLi (7.5 mmol) was added under
nitrogen atmosphere at 2788C and the reaction mixture
was stirred for 0.5 h at the same temperature. To the result-
ing white suspension of lithioacetonitrile, a solution of
alkyl/aryl or heteroarylnitrile (7.5 mmol) in dry THF
(10 mL) was added dropwise and the reaction mixture was
further stirred at the same temperature for 0.5 h to obtain a
light reddish solution of 2-substituted 2-lithioaminoacrylo-
nitrile. To this in situ generated 2-lithioaminoacrylonitrile
19, a solution of 2 (1.26 g, 5 mmol) in dry THF (25 mL) was
added dropwise and the reaction mixture was further stirred
at re¯uxing temperature for 40±48 h (monitored by tlc). It
was then cooled and poured into saturated NH4Cl solution,
extracted with chloroform (2£100 mL), combined organic
phase was washed with water, dried (Na2SO4) and concen-
trated to give crude 21 which was puri®ed by column
chromatography over silica gel using hexane±ethyl acetate
(19:1) as eluent.
1596, 1460 cm21; H NMR (400 MHz, CDCl3): 2.82 (s,
3H, SCH3), 3.90 (s, 3H, NCH3), 4.00 (s, 3H, OCH3),
7.05±7.08 (m, 2H, ArH), 7.39±7.43 (m, 1H, ArH), 7.49
(d, 1H, Jˆ8 Hz, ArH), 7.59±7.64 (m, 1H, ArH), 7.98±
8.02 (m, 2H, ArH), 8.70 (d, 1H, Jˆ8 Hz, ArH); MS: m/z
(%): 359 (M1, 100); Anal. Calcd for C21H17N3OS (359.45):
C,70.17; H, 4.77; N, 11.69%. Found: C, 70.41; H, 4.68; N,
11.61%.
3.8.5. 3-Cyano-9-methyl-4-methylthio-2-(2-thienyl)pyr-
ido[2,3-b]indole (21f). Colorless crystals (ether±hexane);
mp 228±2298C; Yield 60%; IR (KBr): 2202, 1550,
1490 cm21 1H NMR (400 MHz, CDCl3): 2.77 (s, 3H,
,
SCH3), 3.97 (s, 3H, NCH3), 7.17±7.20 (m, 1H, ArH),
7.36±7.41 (m, 1H, ArH), 7.45 (d, 1H, Jˆ8.3 Hz, ArH),
7.53 (dd, 1H, Jˆ5.1, 1 Hz, ArH), 7.57±7.62 (m, 1H,
ArH), 8.34 (dd, 1H, Jˆ3.7, 1 Hz, ArH), 8.64 (d, 1H,
Jˆ8 Hz, ArH); 13C NMR (100 MHz, CDCl3): 18.64,
27.97, 99.64, 109.38, 115.74, 118.71, 120,09, 121.66,
124.29, 128.03, 128.52, 129.03, 129.88, 141.33, 142.77,
146.76, 151.06, 151.61; MS: m/z (%): 335 (M1, 100);
Anal. Calcd for C18H13N3S2 (335.45): C, 65.45; H, 3.91;
N, 12.53%. Found: C, 64.69; H, 4.02; N, 12.41%.
3.8.1. 3-Cyano-2-ethyl-9-methyl-4-(methylthio)pyrido[2,3-
b]indole (21b). Colorless crystals (ether±hexane); mp 151±
1528C; Yield 68%; IR (KBr): 2924, 2213, 1560, 1396 cm21
;
1H NMR (400 MHz, CDCl3): 1.45 (t, 3H, Jˆ7.6 Hz,
CH2CH3), 2.77 (s, 3H, SCH3), 3.19 (q, 2H, Jˆ7.6 Hz,
CH2CH3), 3.95 (s, 3H, NCH3), 7.35±7.39 (m, 1H, ArH),
7.45 (d, 1H, Jˆ8.4 Hz, ArH), 7.55±7.60 (m, 1H, ArH), 8.61
(d, 1H, Jˆ7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3): 13.41,
18.36, 27.86, 30.83, 102.74, 109.28, 114.71, 118.04, 120.10,
121.28, 124.14, 127.47, 140.67, 145.58, 151.54, 164.74; MS:
m/z (%): 281 (M1, 100), 248 (54); Anal. Calcd for C16H15N3S
(281.38): C, 68.30; H, 5.37; N, 14.93%. Found: C, 68.57; H,
5.28; N, 15.04%.
3.8.6. 3-Cyano-9-methyl-2-(N-methyl-3-indolyl)-4-(methyl-
thio)pyrido[2,3-b]indole (21g). Colorless crystals (ether±
hexane); mp 219±2208C; Yield 70%; IR (KBr): 2200, 1554,
1505 cm21 1H NMR (400 MHz, CDCl3): 2.76 (s, 3H,
;
SCH3), 3.88 (s, 3H, NCH3), 4.01 (s, 3H, NCH3), 7.28±
7.45 (m, 5H, ArH), 7.54±7.58 (m, 1H, ArH), 8.28 (s, 1H,
ArH), 8.60±8.67 (m, 2H, ArH); 13C NMR (100 MHz,
CDCl3): 18.63, 28.10, 33.44, 100.28, 109.17, 109.61,
109.65, 113.02, 113.86, 119.99, 120.40, 121.21, 121.30,
122.68, 122.77, 123.93, 127.28, 132.05, 137.33, 140.99,
146.47, 151.85, 154.97; MS: m/z (%): 382 (M1, 100);
Anal. Calcd for C23H18N4S (382.49): C, 72.23; H, 4.74; N,
14.65%. Found: C, 72.06; H, 4.78; N 14.77%.
3.8.2. 3-Cyano-2-methoxymethyl-9-methyl-4-(methylthio)-
pyrido[2,3-b]indole (21c). Colorless crystals (ether±hexane);
mp 180±1818C; Yield 75%; IR (KBr): 2202, 1600,
1541 cm21; 1H NMR (400 MHz, CDCl3): 2.79 (s, 3H,
SCH3), 3.59 (s, 3H, NCH3), 3.97 (s, 3H, CH2OCH3), 4.85
(s, 2H, CH2OCH3), 7.37±7.42 (m, 1H, ArH), 7.48 (d, 1H,
Jˆ 8.3 Hz, ArH), 7.59±7.63 (m, 1H, ArH), 8.63 (d, 1H, Jˆ
7.8 Hz, ArH); 13C NMR (100 MHz, CDCl3): 18.36, 28.10,
59.38, 74.64, 103.30, 109.45, 115.90, 117.18, 119.84,
121.54, 124.45, 127.98, 140.90, 146.03, 151.09, 158.02;
MS: m/z (%): 297 (M1, 27), 267 (100); Anal. Calcd for
C16H15N3OS (297.38): C, 64.62; H, 5.08; N, 14.13%.
Found: C, 64.35; H, 5.17; N, 14.29%.
3.9. General procedure for the reaction of 15b and 15g
with Raney nickel
To a solution of 21b or 21g (2 mmol) in ethanol (25 mL),
Raney nickel (W2 or W4, 5 times by weight) was added and
the suspension was re¯uxed with stirring for 3±4 h
(monitored by tlc). The reaction mixture was then cooled,
®ltered through sintered funnel and the residue was washed
with ethanol. The ®ltrate was evaporated under vacuum and
the residue was dissolved in chloroform (50 mL), washed
with water, dried (Na2SO4) and concentrated to give crude
products which were puri®ed by passing through a small
silica gel column using hexane as eluent.
3.8.3. 3-Cyano-9-methyl-4-methylthio-2-phenylpyrido[2,3-
b]indole (21d). Colorless crystals (ether±hexane); mp 171±
1
1728C; Yield 66%; IR (KBr): 2210, 1546, 1460 cm21; H
NMR (400 MHz, CDCl3): 2.83 (s, 3H, SCH3), 4.00 (s, 3H,
NCH3), 7.40±7.44 (m, 1H, ArH), 7.49±7.57 (m, 4H, ArH),
7.60±7.65 (m, 1H, ArH), 7.98±8.01 (m, 2H, ArH), 8.71 (d,
1H, Jˆ7.8 Hz, ArH); 13C NMR (100 MHz, CDCl3): 18.57,
28.02, 102.52, 109.41, 115.65, 118.60, 120.01, 121.60,
124.52, 128.00, 128.42, 128.49, 129.54, 129.81, 138.33,
141.22, 146.76, 159.70; MS: m/z (%): 329 (M1, 100);
Anal. Calcd for C20H15N3S (329.43): C, 72.92; H, 4.59; N,
12.76%. Found C, 73.18; H, 4.65; N, 12.63%.
3.9.1. 3-(Diethylamino)methyl-2-ethyl-9-methylpyrido[2,3-
b]indole (22b). Colorless crystals (hexane±chloroform);
mp 109±1108C; Yield 76%; IR (KBr): 2968, 2788, 1597,
1472 cm21
;
1H NMR (400 MHz, CDCl3): 1.06 (t, Jˆ
7.1 Hz, 6H, (CH2CH3)2), 1.38 (t, Jˆ7.6 Hz, 3H, CH2CH3),
2.57 (q, 4H, Jˆ7.1 Hz, (CH2CH3)2), 3.05 (q, Jˆ7.6 Hz, 2H,
CH2CH3), 3.69 (s, 2H, CH2), 3.94 (s, 3H, NCH3), 7.21±7.25
(m, 1H, ArH), 7.39 (d, Jˆ8 Hz, 1H, ArH), 7.44±7.48 (m,
1H, ArH), 8.03 (d, Jˆ7.8 Hz, 1H, ArH), 8.25 (s, 1H, ArH);
13C NMR (100 MHz, CDCl3): 11.73, 13.81, 27.55, 28.43,
46.70, 55.21, 108.79, 113.20, 119.33, 120.65, 123.57,
3.8.4. 3-Cyano-2-(4-methoxyphenyl)-9-methyl-4-(methyl-
thio)pyrido[2,3-b]ndole (21e). Colorless crystals (ether±
hexane); mp 209±2108C; Yield 76%; IR (KBr): 2200,

788
J. R. Suresh et al. / Tetrahedron 57 (2001) 781±789
Moody, C. J.; JAI: Greenwich (CT), 1995; Vol. 1, pp 173. (d)
Bergman, J.; Pelcman, B. Pure Appl. Chem. 1990, 62, 1967±
1976. (e) Pindur, U. Chimia 1990, 44, 406±409.
125.72, 125.78, 129.86, 140.27, 150.92, 159.61; MS: m/z
(%): 295 (M1, 41), 221 (100); Anal. Calcd for C19H25N3
(295.43): C, 77.25; H, 8.53; N, 14.22%. Found: C, 77.51;
H, 8.42; N, 14.31%.
2. Katritzky, A. R.; Xie, L. J. Org. Chem. 1995, 60, 3707±3710
(and references cited therein).
3.9.2. 3,9-Dimethyl-2-(1-methyl-2-indolyl)pyrido[2,3-b]-
indole (23g). Colorless crystals (ether±hexane); mp 151±
3. Barun, O.; Patra, P. K.; Ila, H.; Junjappa, H. Tetrahedron Lett.
1999, 40, 3797±3800.
1
1528C; Yield 70%; IR (KBr): 2924, 1599, 1477 cm21; H
4. (a) Merlic, C. A.; Motamed, S.; Quinn, B. J. Org. Chem. 1995,
60, 3365±3369. (b) Malapel-Andrieu, B.; Merour, J.-Y.
Tetrahedron 1998, 54, 11095±11110.
NMR (400 MHz, CDCl3): 2.63 (s, 3H, CH3), 3.89 (s, 3H,
NCH3), 4.01 (s, 3H, NCH3), 7.21±7.52 (m, 7H, ArH), 8.03±
8.06 (m, 1H, ArH), 8.21 (s, 1H, ArH), 8.29 (d, Jˆ7.8 Hz,
1H, ArH); MS: m/z (%): 325 (M1, 100); Anal. Calcd for
C22H19N3 (325.41): C, 81.20; H, 5.88; N, 12.91%. Found: C,
81.47; H, 5.81; N, 13.03%.
5. Radchenko, O. S.; Novikov, V.; Elyakov, G. B. Tetrahedron
Lett. 1997, 38, 5339±5342.
6. (a) Abouabdellah, A.; Dodd, R. H. Tetrahedron Lett. 1998, 39,
2119±2122. (b) Abas, S. A.; Hossain, M. B.; van der Helm, D.;
Schmitz, F. J. J. Org. Chem. 1996, 61, 2709±2712.
(c) Molina, P.; Fresneda, P. M.; Sanz, M. A.; Foces-
Foces, C.; Ramirez de Arellano, M. C. Tetrahedron 1998,
54, 9623±9638.
3.9.3. 2,3-Dihydro-1-methyl-3-[(N-pyrrolidino)(methyl-
thio)methylene]-2-oxoindole (24). A solution of 2 (5 g,
0.02 mol) and pyrrolidine (1.8 mL, 0.021 mol) in ethanol
(150 mL) was re¯uxed for 3.5 h (monitored by tlc) and
then the solvent was removed under vacuum. The residue
obtained was dissolved in chloroform washed with water,
dried and evaporated to obtain the crude 24 which was
puri®ed by recrystallization from chloroform±ether. Yellow
crystals (chloroform±ether); mp 137±1388C; Yield 90%; IR
7. (a) Papamicael, C.; Dupas, G.; Queguiner, G.; Bourguignon, J.
Heterocycles 1998, 47, 991±1004. (b) Kin, J.-S.; Shin-ya, K.;
Furihata, K.; Hayakawa, Y.; Seto, H. Tetrahedron Lett. 1997,
38, 3431±3434. (c) Choshi, T.; Yamada, S.; Sugino, E.;
Kuwada, T.; Hibino, S. Synlett 1995, 147±148.
(d) Molina, P.; Fresneda, P. M.; Sanz, M. A. Tetrahedron
Lett. 1997, 38, 6909±6912.
1
(KBr): 2920, 1631, 1604, 1504 cm21; H NMR (400 MHz,
CDCl3): 2.00±2.04 (m, 4H, CH2CH2), 2.40 (s, 3H, SCH3),
3.34 (s, 3H, NCH3), 3,83 (brs, 4H, CH2±N±CH2), 6.85±6.87
(m, 1H, ArH), 6.96±7.05 (m, 2H, ArH), 7.45 (d, Jˆ7.4 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3): 18.86, 25.29,
25.82, 53.53, 93.48, 106.73, 118.05, 120.07, 121.34,
124.52, 137.50, 163.98, 165.26; Anal. Calcd for
C15H18N2OS (274.39): C, 65.66; H, 6.61; N, 10.21%.
Found: C, 65.92; H, 6.72; N, 10.03%.
8. (a) Desarbre, E.; Merour, J.-Y. Synthesis 1997, 73±78.
(b) Molina, P.; Murcia, F.; Fresneda, P. M. Tetrahedron
Lett. 1994, 35, 1453±1456. (c) Amrein, R.; Leeshman, B.;
Bentzinger, C.; Roncari, G. Medical Toxicology 1987, 2,
411±429. (d) Dubois, C.; Dorey, G.; Potier, P.; Dodd, R. A.
Tetrahedron: Asymmetry 1995, 6, 455±462.
9. Bergman, J. In Stereoselective Synthesis (Part A), Studies in
Natural Product Chemistry, Atta-ur-Rahman, C. J., Ed.;
Elsevier: Amsterdam, 1988; Vol. 1, pp 3.
3.9.4. 3-Cyano-2-(4-methoxyphenyl)-9-methyl-4-(N-pyr-
rolidino)pyrido[2,3-b]indole (25e). Procedure is same as
that of 21e except N,S-acetal 24 was used instead of 2.
Colorless crystals (chloroform±hexane); mp 229±2308C;
10. Gillner, M.; Fernstrom, B.; Gustafsson, J.-A.; Bergman, J.;
Cambillau, C. Chemosphere 1986, 15, 1673±1680.
11. (a) Gribble, G. W. In The Alkaloids, Chemistry and Pharma-
cology, Brossi, A., Ed.; Academic: San Diego, 1990; Vol. 39
(Chapter 7). (b) Pindur, U.; Haber, M.; Sattler, K. J. Chem.
Educ. 1993, 70, 263±272.
1
Yield 45%; IR (KBr): 2823, 2219, 1568, 1444 cm21, H
NMR (300 MHz, CDCl3): 2.01 (brs, 4H, ±CH2±CH2±),
3.28 (s, 3H, NCH3), 3.66 (brs, 4H, ±CH2±N±CH2±), 3.88
(s, 3H, OCH3), 6.99 (d, Jˆ8.4 Hz, 2H, ArH), 7.20±7.48 (m,
5H, ArH) 8.77 (d, Jˆ7.8 Hz, 1H, ArH); MS: m/z (%): 382
(M1, 100), 357 (49); Anal. Calcd for C24H22N4O (382.46):
C, 75.37; H, 5.80; N, 14.65%. Found: C, 75.66; H, 5.87; N,
14.53%.
12. (a) Patra, P. K.; Suresh, J. R.; Ila, H.; Junjappa, H. Tetrahedron
Lett. 1997, 38, 3119±3122. (b) Syam Kumar, U. K.;
Patra, P. K.; Ila, H.; Junjappa, H. Tetrahedron Lett. 1998,
39, 2029±2032. (c) Rao, M. V. B.; Sathyanarayana, J.;
Ila, H.; Junjappa, H. Tetrahedron Lett. 1995, 36, 3385±3388.
13. Rao, M. V. B.; Syam Kumar, U. K.; Ila, H.; Junjappa, H.
Tetrahedron 1999, 55, 11563±11578.
14. (a) Kishore, K.; Reddy, K. R.; Suresh, J. R.; Ila, H.;
Junjappa, H. Tetrahedron 1999, 55, 7645±7652. (b) Roy, A.;
Reddy, K. R.; Ila, H.; Junjappa, H. J. Chem. Soc., Perkin
Acknowledgements
Financial assistance under DST scheme is acknowledged.
H. J., J. R. S., and U. K. S. thanks CSIR for Emeritus
Scientistship, Research Associateship and Senior Research
Fellowship respectively.
Trans.
1 1999, 3001±3004. (c) Barun, O.; Ila, H.;
Junjappa, H.; Singh, O. M. J. Org. Chem. 2000, 65, 1583±
1587.
15. (a) Kobayashi, G.; Furukawa, S.; Matsuda, Y. Yakugaku
Zasshi 1966, 86, 1152±1155; Chem. Abstr. 1967, 67, 3031e.
(b) Teshigawara, T.; Kobayashi, G.; Matsuda, Y. Japan 15543
(1967); Chem. Abstr. 1968, 69, 2869p. (c) Kobayashi, G.;
Matsuda, Y.; Teshigawara, T. Japan 6724899 (1967); Chem.
Abstr. 1968, 69, 43798h. (d) Tominaga, Y.; Takada, S.;
Kohra, S. Heterocycles 1994, 39, 15±18.
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