Microwave assisted Pictet-Spengler and Bischler-Napieralski reactions

Article abstract of DOI:10.1081/SCC-120021516

Pictet-Spengler and Bischler-Napieralski reaction products have been prepared-using microwave irradiation on silicagel support under solvent free condition. Microwave assisted reactions have resulted in better yields of the desired products than prepared

Full text of DOI:10.1081/SCC-120021516

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Microwave Assisted Pictet–Spengler and
Bischler–Napieralski Reactions
Bikash Pal a , Parasuraman Jaisankar a & Venkatachalam S. Giri a
a Department of Medicinal Chemistry, Indian Institute of Chemical Biology, Calcutta, West
Bengal, India
Version of record first published: 17 Aug 2006.
To cite this article: Bikash Pal , Parasuraman Jaisankar & Venkatachalam S. Giri (2003): Microwave Assisted Pictet–Spengler
and Bischler–Napieralski Reactions, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 33:13, 2339-2348
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 13, pp. 2339–2348, 2003
Microwave Assisted Pictet–Spengler and
Bischler–Napieralski Reactions
Bikash Pal, Parasuraman Jaisankar, and
*
Venkatachalam S. Giri
Department of Medicinal Chemistry, Indian Institute of
Chemical Biology, Calcutta, West Bengal, India
ABSTRACT
Pictet–Spengler and Bischler–Napieralski reaction products have
been prepared–using microwave irradiation on silicagel support
under solvent free condition. Microwave assisted reactions have
resulted in better yields of the desired products than prepared
under conventional conditions.
Key Words: Microwave; Indole; Isoquinoline; b-carboline; Pictet–
Spengler; Bischler–Napieralski.
*Correspondence: Venkatachalam S. Giri, Department of Medicinal Chemistry,
Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta,
700032, India; Fax: þ91-33-24735197/24730284; E-mail: vsgiri@iicb.res.in.
2339
DOI: 10.1081/SCC-120021516
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2340
Pal, Jaisankar, and Giri
Pictet–Spengler,[1] Bischler–Napieralski[2] are the two most widely
used reactions in the synthesis of b-carboline and isoquinoline backbones
of the indole and isoquinoline alkaloids respectively. The reactions are
well known but it has been observed that sometimes these reactions
become hazardous resulting in poor yields of the products. In order to
overcome this problem it was decided to study the above reactions using
microwave irradiation under solvent free condition.
Microwave heating has been employed as a frequent resource for
improvementof classical reacitons. The use of such non-convenitonal
reaction conditions reveals several features like a short reaction time
compared to conventional eating, ease of isolation of the products after
easy work-up and better selectivity.[3] Ithas also been observed htat
sometimes the intermediate tetrahydro or dihydro products undergo
dehydrogenation resulting in isoquinolines or b-carbolines.
Microwave assisted Pictet–Spengler reaction of tryptamine (1) with
Para-nitrobenzaldehyde (2) afforded the expected tetrahydro (3) and the
dihydro-b-carbolines (3a) whereas ortho-nitrobenzaldehyde (4) with
tryptamine (1) yielded not only the tetrahydro (5) and the dihydro
b-carbolines (5a) but also the fully aromatized product 1-(2-nitrophenyl)-
b-carboline (5b) (Sch. 1). Similar irradiation of meta-Nitro-benzaldehyde
(6) wit h 1gave only the tetrahydro-b-carboline product( 7) (Table 1). On
the other hand, para-fluorobenzaldehyde (8) with tryptamine (1) afforded
both the tetrahydro (9) and the dihydro-b-carbolines (9a).
The microwave assisted Pictet–Spengler reaction has also been
performed with chiral substrates. Thus, tryptamine (1) with the sugar
derivative 10[4] under microwave irradiation gave the chiral b-carboline
compounds (11)[5] and (11a) respectively (Table 1a). Expectedly L and D
tryptophan methyl esters (12) and (14) under the same irradiation
condition gave the corresponding carbomethoxy substituted chiral
b-carbolines 13 and 15 respectively. On the other hand, b-phenylethyl-
amine (16) with the same sugar derivative, di-(1,2)-O-cyclo
Scheme 1.

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Pictet–Spengler and Bischler–Napieralski Reactions
Table 1. Pictet–Spengler reaction products.
Substrate Products (yield)
2341
Entry
1
2
3
4
0
hexylidene-a-D-xylo-pentodialdofuranose-5-hydrate)-5,5 :30,5-dianhydride
(10) gave an inseparable diastereomeric mixture (1:1) of the chiral
isoquinolines 17.
Microwave assisted Bischler–Napieralski reaction of N-formyltryp-
tamine (18) and N-acetyltryptamine (20) gave the expected dihydro-
b-carboline (19) and 1 methyl-3,4-dihydro-b-carboline (21) respectively
in very good yield (Table 2). Interestingly, N-formyltryptophan
methyl ester (22) under similar condition afforded apart from the expected
3-carbomethoxy-b-carboline (23), also a dimeric b-carboline 23a. The
dimmer 23a could not be obtained under classical reaction condition.

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2342
Pal, Jaisankar, and Giri
Table 1a. Chiral reaction products.
Substrate Products (yield)
Entry
1
2
3
4
N-acetyltryptophan methyl ester (24) under microwave irradiation gave
only 1-methyl-3-carbomethoxy-b-carboline (25) (Sch. 2).
All the compounds have been characterized using physical data
mainly NMR and compared with those prepared by classical methods.
In conclusion, the method described above could be used to synthe-
size in a convenientmanner both isoquinoline and b-carboline derivatives
as an alternate to the classical methods employed.

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Pictet–Spengler and Bischler–Napieralski Reactions
Table 2. Bischler–Napieralski reaction products.
Substrate Products (yield)
2343
Entry
1
2
3
4
Scheme 2.

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2344
Pal, Jaisankar, and Giri
EXPERIMENTAL
Melting points were determined in open capillaries and are uncor-
rected. Infra red spectra were recorded in FT/IR 410 JASCO spectro-
photometer. 1H NMR and 13C NMR spectra were measured in a
300 MHz BRUKER 300 DPX spectrometer using TMS as internal stan-
dard. The mass spectra were run on a JEOL AX–500 spectrometer at
70 eV. Optical rotations were. recorded at 25ꢀC in P–1020 JASCO
polarimeter. Petroleum ether refers to the fraction boiling in the range
60–80ꢀC. Solvents like petroleum ether, chloroform, methanol, ether,
THF, DMF, and DMSO were purified and dried before use. Column
chromatography was carried out on silica gel of 60–120 mesh. TLC
was done on standard Merck TLC aluminium sheets. Unless otherwise
mentioned the compounds have been crystallized from either petroleum
ether–CHCl3 mixture or MeOH.
Typical procedure for Pictet–Spengler condensation. Ten gram silica-
gel (60–120 mesh) was initially activated irradiating in a microwave
(Domestic oven; AEG, Micromat) oven for 5 min. at 850 W. A mixture
of 1 mmol of the amine and 1 mmol of the aldehyde in 1 mL of glacial
HOAc was adsorbed over activated silica gel. It was then irradiated at
600 W initially for 5 min, then for another 5 min, and finally for 2 more
min. i.e., for a total of 12 min. The reaction was monitored at the end of
each irradiation. The silica gel was then soaked in a mixture of CHCl3
and MeOH (7:3) and filtered. Filtrate was concentrated, diluted with
water, neutralized with NaHCO3 and extracted with CHCl3. The extract
was concentrated and the residue chromatographed over silica gel to
yield the products.
1-(4-Nitrophenyl)-1,2,3,4-tetrahydro-b-carboline (3). M.p. 168–170ꢀC;
IR (KBr): 3408, 3229, 1514, 1348. 1H NMR (DMSO-d6): ꢀ 2.72–2.98 (m,
2H), 3.18 (m, 1H), 3.28 (m, 1H), 5.27 (s, 1H), 7.00–7.20 (m, 2H),
7.22–7.27 (m, 1H), 7.51 (d, J ¼ 8.4 Hz, 2H), 7.56 (brd, 1H), 8.19 (d,
J ¼ 8.4 Hz, 2H), 11.02 (s, NH). m/z: 293 (Mþ, 100), 264 (35), 218 (30),
171 (35). Anal. calcd. for C17N3O2H15: C, 69.68; H, 5.16; N, 14.34.
Found: C, 69.58; H, 5.09; N, 14.47.
1-(4-Nitrophenyl)-3,4-dihydro-b-carboline (3a). M.p. 220–222ꢀC. IR
1
(KBr): 3393, 1513, 1350. H NMR (DMSO-d6): ꢀ 2.90 (t, 2H), 3.96 (t,
2H), 7.09 (t, 1H), 7.23 (t, 1H), 7.42 (d, J ¼ 7.5 Hz, 1H), 7.64 (d,
J ¼ 7.2 Hz, 1H), 8.01 (d, J ¼ 6.9 Hz, 2H), 8.38 (t, 2H), 11.21 (s, NH).
m/z: 291 (Mþ, 100), 244 (30), 143 (20). Anal. calcd. for C17N3O2H13:
C, 70.16; H, 4.50; N, 14.44. Found: C, 69.98; H, 4.39; N, 14.58.
1-(2-Nitrophenyl)-1,2,3,4-tetrahydro-b-carboline (5). M.p. 238–240ꢀC.
1
IR (KBr): 3311, 1617, 1539, 1369. H NMR (DMSO-d6): ꢀ 2.95–3.50

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Pictet–Spengler and Bischler–Napieralski Reactions
2345
(m, 3H), 3.55 (m, 1H), 6.42 (s, 1H), 7.07 (t, 1H), 7.15 (t, 1H), 7.28 (m,
1H), 7.34 (d, J ¼ 7.8 Hz, 1H), 7.57 (d, J ¼ 2.5 Hz, 1H), 7.70–7.90 (m, 2 H),
8.31 (m, 1H), 10.72 (s, NH). m/z: 293 (Mþ, 40), 276 (80), 259 (100), 246
(50), 171 (20). Anal. calcd. for C17N3O2HI5: C, 69.68; H, 5.16; N, 14.34.
Found: C, 69.60; H, 5.07; N, 14.43.
1-(2-Nitrophenyl)-3,4-dihydro-b-carboline (5a). M.p. 268–270ꢀC. IR
(KBr): 3150, 1612, 1540, 1373. 1H NMR (DMSO-d6): ꢀ 3.34 (t, 2H),
4.60 (t, 2H), 7.08 (t, 1H), 7.17 (t, 1H), 7.22 (t, 1H), 7.30 (t, 1H),
7.46 (d, J ¼ 7.8 Hz, 1H), 7.56 (brd, 2H), 8.27 (d, J ¼ 6.6 Hz, 1H), 11.7
(s, NH). m/z: 291 (Mþ 100), 171 (20), 117 (10). Anal. calcd. for
C17N3O2HI3: C, 70.16; H, 4.50; N, 14.44. Found. C, 70.02; H, 4.41;
N, 14.58.
1-(2-Nitrophenyl)-b-carboline (5b). M.p. 275–277ꢀC. IR (KBr): 3231,
1530, 1345. 1H NMR (DMSO-d6): ꢀ 7.31 (t, 1H), 7.38 (t, 1H), 7.50 (t, 1H),
7.58 (t, 1H), 7.66 (d, J ¼ 6.9 Hz, 1H), 7.81 (d, J ¼ 6.9 Hz, 1H), 7.93 (d,
J ¼ 8.4 Hz, 1H), 8.10 (d, J ¼ 7.8 Hz, 1H), 8.25 (d, J ¼ 8.1 Hz, 1H), 8.69 (d,
J ¼ 6.9 Hz, 1H), 9.10 (s, NH). m/z: 289 (Mþ, 40), 171 (25), 117 (20), 94
(100). Anal. calcd. for CI7N3O2H11: C, 70.65; H, 3.84; N, 14.54. Found:
C, 70.56; H, 3.78; N, 14.65.
1-(3-Nitrophenyl)-1,2,3,4-tetrahydro-b-carboline (7). M.p. 142–144ꢀC.
IR (KBr): 3310, 1526, 1348. 1H NMR (DMSO-d6): ꢀ 2.72 (m, 2H),
3.02 (m, 2H), 5.26 (s, 1H), 6.90–7.10 (m, 2H), 7.23 (d, J ¼ 7.5 Hz,
1H), 7.43 (d, J ¼ 7.5 Hz, 1H), 7.61 (t, J ¼ 7.5 Hz, 1H), 7.73 (d,
J ¼ 7.5 Hz, 1H), 8.03 (s, 1H), 8.13 (d, J ¼ 7.8 Hz, 1H), 10.51 (s, NH);
m/z: 293 (Mþ, 100), 246 (30), 216 (70), 171 (70), 115 (15). Anal. calcd.
for C17N3O2H15: C, 69.68; H. 5.16; N, 14.34. Found: C, 69.59; H, 5.11;
N, 14.40.
1-(4-Flurophenyl)-1,2,3,4-tetrahydro-b-carboline (9). M.p. 138–140ꢀC.
IR (KBr): 3150, 1506, 1223, 746. 1H NMR (CDC13): ꢀ 2.70–3.00 (m, 2H),
3.01–3.25 (m, 1H), 3.26–3.40 (m, 1H), 5.15 (s, 1H), 7.03 (m, 2H), 7.13 (m,
2H), 7.20–7.34 (m, 4H), 7.40 (brs, NH). 7.54 (m, 1H). m/z: 266 (Mþ, 100),
237 (60). 171 (30). Anal. calcd. for C17N2FH15: C, 76.76; H, 5.68; N,
10.53. Found: C, 76.68; H, 5.60; N, 10.62.
1-(4-Flurophenyl)-3,4-dihydro-b-carboline (9a). M.p. 244–246ꢀC. IR
1
(KBr): 3373, 1537, 1339. H NMR (DMSO-d6): ꢀ 2.89 (t, 2H), 3.89 (t,
2H), 7.08 (t, 1H), 7.22 (t, 1H), 7.30–7.50 (m, 3H), 7.63 (d, J ¼ 7.8 Hz, 1H),
7.77–7.88 (m, 2H), 12.11 (s, NH). m/z: 264 (Mþ, 100), 235 (30), 144 (20),
116 (15). Anal. calcd. for C17N2FH13: C, 77.34; H, 4.96; N, 10.61. Found:
C, 77.27; H, 4.89; N, 10.56.
10,11-O-Cyclohexylidene-12-b-hydroxy-13b-(1-tetrahydro-b-carboli-
nyl)tet rahydro-furan (11). M.p. 200–202ꢀC. [ꢁ]D ¼ ꢁ54.0ꢀ (c ¼ 0.48,
CHC13). IR (KBr): 3454, 3088, 1034, 735. 1H NMR (CDCl3): ꢀ

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2346
Pal, Jaisankar, and Giri
1.40–1.90 (brs, 10H), 2.64–2.84 (m, 2H), 2.90–3.20 (m, 2H), 3.30–3.60 (m,
2H, OH, NH), 4.24 (m, 1H), 4.40–4.60 (m, 3H), 6.04 (d, J ¼ 5.1 Hz, 1H),
7.04–7.60 (m, 4H), 8.44 (brs, NH). 13C NMR (CDCl3): ꢀ 21.89 (t, C-4),
23.4 (t, C-18), 23.76 (t, C-16), 24.75 (t, C-17), 35.23 (t, C-19), 36.22 (t, C-
15), 42.71 (t, C-3), 52.78 (d, C-1), 75.42 (d, C-12), 81.33 (d, C-13), 85.07
(d, C-11), 104.78 (d, C-10), 109.35 (s, C-14), 110.93 (d, C-8), 112.45 (s, C-
4a), 118.01 (d, C-15), 119.18 (d, C-6), 121.63 (d, C-7), 126.90 (s, C-4b),
131.17 (s, C-9a), 136.08 (s, C-8a). m/z: 370 (Mþ, 90), 327 (25),271 (20),
255 (28), 237 (22), 213 (50), 199 (30), 184 (84), 172 (98), 171 (100); Anal.
calcd. for C21N2O4H26: C, 68.09; H, 7.07; N, 7.56. Found: C, 67.97; H,
7.14; N, 7.63.
Diastereomer of 11 (11a). M.p. 235–237ꢀC. [ꢁ]D ¼ ꢁ19.70ꢀ (c ¼ 0.58,
1
CHC13); 1R (KBr): 3454, 2936, 1448, 1120, 1016. H NMR (CDCl3):
ꢀ
1.30–1.90 (m, 10H), 2.60–2.90 (m, 2H), 3.01–3.40.(m, 2H),
4.36–4.39 (m, 2H, OH, NH), 4.45–4.55 (m, 2H), 5.98 (d, J ¼ 3.3 Hz,
1H), 7.04–7.20 (m, 3H), 7.47 (d, J ¼ 7.2 Hz, 1H), 8.20 (s, NH).
13C NMR (CDCl3): ꢀ 22.37 (t, C-4), 23.95 (t, C-18), 24.33 (t, C-16),
25.28 (t, C-17), 35.96 (t, C-19), 37.05 (t, C-15), 41.91 (t, C-3), 52.71 (d,
C1), 77.83 (d, C-12), 79.30 (d, C-13), 85.57 (d, C-11), 105 (d, C-10),
110.64 (s, C-4a), 111.40 (d, C-8), 112.78 (s, C-14), 118.51 (d, C-5),
119.84 (d, C-6), 122.36 (d, C-7), 127.78 (s, C-4b), 131.80 (s, C-9a),
136.31 (s, C-8a). m/z: 370 (Mþ, 90), 327 (25),271 (20), 255 (28),
237 (22), 213 (50), 199 (30), 184 (84), 172 (98), 171 (100). Anal. calcd.
for C21N2O4H26: C, 68.09; H, 7.07; N, 7.56. Found: C, 67.94; H, 7.11; N,
7.66.
10,11-O-Cyclohexylidene-12-b-hydroxy-13b-(1-tetrahydro-3b-carbo-
methoxy-b-carbolinyl)tetrahydrofuran (13). M.p. 194–196ꢀC. [ꢁ]D ¼
ꢁ77.6ꢀ (c ¼ 0.39, CHCl3). IR (KBr): 3446, 3378, 1742, 1654, 753.
1H NMR (CDCl3): ꢀ 1.25–1.75 (m, 11H), 2.88 (dd, J ¼ 11:9 Hz, 2.4 Hz,
1H), 3.19 (dd, J ¼ 14.4 Hz, 2.5 Hz, 1H), 3.77 (dd, J ¼ 11.2 Hz, 4.1 Hz, 1H),
3.83 (s, 3H), 4.33 (d, J ¼ 2.8 Hz, 1H), 4.37 (dd, J ¼ 2.8 Hz, 6.7 Hz, 1H),
4.55 (d, J ¼ 3.6 Hz, 1H), 4.64 (d, J ¼ 6.7 Hz, 1H), 4.90 (brs, NH), 6.11
(d, J ¼ 5.0 Hz, 1H), 7.09 (t, J ¼ 7.0 Hz, 1H), 7.19 (t, J ¼ 7.0 Hz, 1H), 7.50
(d, J ¼ 8.0 Hz, 1H), 7.69 (d, J ¼ 8.0 Hz, 1H), 8.51 (brs, NH). 13C NMR
(CDCl3): ꢀ 23.57 (C-18), 23.88 (C-16), 24.84 (C-17), 25.39 (C-4), 35.56
(C-19), 36.44 (C-15), 52.37 (C-1), 55.88 (C-3), 75.34 (C-12), 81.76 (C-13),
84.92 (C-11), 104.97 (C-10), 108.26 (C-14), 111.19 (C-8), 112.68 (C-4a),
118.10 (C-5), 119.60 (C-6), 122.10 (C-7), 126.69 (C-4b), 131.67
(C-9a), 136.28 (C-8a), 172.87 (C-20). m/z: 428 (Mþ, 16), 427 (61), 369
(26), 271 (28), 241 (34), 230 (100), 211 (21), 183 (70), 170 (92), 169 (100);
Anal calcd. for C23N2O6H28: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.61;
H, 6.50; N, 6.60.

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Pictet–Spengler and Bischler–Napieralski Reactions
2347
10,11-O-Cyclohexylidene-12-b-hydroxy-13b-(1-tetrahydro-3a-carbo-
methoxy b-carbolinyl) tetrahydrofuran (15). M.p. 175–177ꢀC.
[ꢁ]D ¼ ꢁ60.17ꢀ (c ¼ 0.339, CHCl3); IR (KBr): 3364, 1740, 1654, 747.
1H NMR (DMSO-d6): ꢀ 1.25–1.90 (m, 11H), 3.00–3.19 (m, 2 H), 3.69 (s,
3 H), 3.98 (t, J ¼ 5.1 Hz, 1H), 4.29 (d, J ¼ 3.0 Hz, 1H), 4.36 (dd, J ¼ 2.7,
13.8 Hz, 1H), 4.53 (d, J ¼ 3.6 Hz, 1H), 4.79 (d, J ¼ 6.6 Hz, 1H), 6.08 (d,
J ¼ 3.3 Hz, 1H), 7.10 (t, J ¼ 6.3 Hz, 1H), 7.13 (t, J ¼ 7.50 Hz, 1H), 7.34 (d,
J ¼ 7.5 Hz, 1H), 7.50 (d, J ¼ 7.5 Hz, 1H), 8.29 (s, NH). 13C NMR (DMSO-
d6): ꢀ 24.83 (C-4), 23.61 (C-18), 23.68 (C-16), 23.89 (C-17), 36.04 (C-19),
36.79 (C-15), 55.64 (C-3), 51.78 (C-1), 78.50 (C-12), 81.83 (C-13), 83.62 (C-
11), 105.63 (C-10), 105.42 (C-14), 111.13 (C-8), 113.08 (C-4a), 118.16 (C-
5), 119.19 (C-6), 120.02 (C-7), 126.76 (C-4b), 131.70 (C-9a), 136.35 (C-8a),
172.37 (C-20). m/z: 428 (Mþ, 17), 427 (59), 369 (26), 271 (48), 241 (30), 230
(100), 211(20), 183 (62), 170 (90), 169 (100). Anal. calcd. for C23N2O6H28:
C, 64.47; H, 6.59; N, 6.54. Found: C, 64.65; H, 6.52; N, 6.63.
9,10-O-Cyclohexylidene-11-b-hydroxy-12b-(1,2,3,4-tetrahydroisoqui-
nolinyl) tetra-hydrofuran (17). IR (KBr): 3328, 1495, 1102. 1H NMR
(CDC13): ꢀ 1.35–2.50 (m, 20H), 2.64–2.90 (m, 8H), 3.10–3.35 (m, 2H),
3.89 (brs, 2H), 4.24 (brd, 1H), 4.30 (brd, 2H), 4.58 (d, J ¼ 3.6 Hz, 1H),
5.75 (d, J ¼ 4.8 Hz, 1H), 5.97 (d, J ¼ 3.6 Hz, IH), 7.00–7.40 (m, 8H).
13C NMR (CDC13): ꢀ 23.39, 23.49, 23.59, 23.74, 23.90, 24.90, 35.65,
36.07, 36.21, 36.47, 36.75, 36.96 (C-4, C-14, C-15, C-16, C-17, C-18),
46.66, 46.93 (C-3), 56.56 (C-1), 72.41, 77.90 (C-11), 79.05, 83.53
(C-12), 89.25, 89.69 (C-10), 104.11, 104.42 (C-9), 112.18, 113.24 (C-13),
125.95, 126.45, 128.27, 128.45, 128.50, 128.51, 128.55, 128.62, 128.63,
128.64 (C-4a, C-5, C-6, C-7, C-8), 139.65, 140.30 (C-8a). m/z: 331 (Mþ,
20), 284 (90), 240 (20), 174 (50), 132 (30), 86 (100).
Typical Procedure for Bischler–Napieralski Condensation. Ten gram
silicagel (60–120 mesh) was initially activated by irradiating in a microwave
(Domestic oven: AEG, Micromat) oven for 5 min. at 850 W. A mixture of
1 mmol of the amide and 0.5 mL of POC13 was adsorbed over activated
silica gel. It was then irradiated at 600 W initially for 5 min, then for
another 2 min and finally for 2 more min. i.e., for a total of 9 min. The
reaction was monitored at the end of each irradiation. The silica gel was
then processed as has been described for Pictet–Spengler condensation and
the products purified by column chromatography over silica gel.
3,4-dihydro-b-carboline (19). M.p. 86ꢀC and then at 175–177ꢀC (Lit.[6]
m.p. 87ꢀC and then at 175–176ꢀC) crystallized from ether.
1-methyl 3,4-dihydro-b-carboline (21). M.p. 236–238ꢀC (Lit.[7]
235–237ꢀC).
3-carbomethoxy b-carboline (23). M.p. 242–244ꢀC. IR (KBr): 3263,
1725, 1434, 1247. 1H NMR (CDC13): ꢀ 4.07 (s, 3H), 7.38 (m, 1H),

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2348
Pal, Jaisankar, and Giri
7.45–7.65 (m, 2H), 8.22 (d, J ¼ 8.1 Hz, 1H), 8.90 (s, 1H), 8.95 (brs, 1H),
9.03(s,1H).m/z:226(Mþ,100).195(30),171(40),140(100).Anal.calcd. for
C13N2O2H10:C, 69.08;H,4.46;N,12.40. Found:C,69.12;H,4.38;N, 12.58.
1-(3-carbomethoxy-1,2,3,4-tetrahydro-b-carbolinyl)-3-carbomethoxy-
b-carboline (23a). M.p. 208–210ꢀC. IR (KBr): 3349, 3293, 1739,
1673, 1223. 1H NMR (CDC13): ꢀ 2.85 (m, 1H), 4.65 (m, 2H), 3.84
(s, 3H), 4.05 (s, 3H), 6.04 (s, 1H), 6.72–7.50 (m, 6H), 7.52–7.82 (m, 2H),
8.78 (s, 1H), 9.50 (s, NH), 10.93 (s, 1H). m/z: 454 (Mþ,100), 395 (24), 366
(36), 333 (37), 307 (40), 229 (30), 169 (65).
1-methyl,3-carbomethoxy-b-carboline (25). M.p. 168–170ꢀC. IR (KBr):
1
3331, 1717, 1352, 1256. H NMR (CDCl3): ꢀ 2.89 (s, 3H), 4.05 (s, 3H),
7.37 (m, 1H), 7.45–7.65 (m, 2H), 8.18 (d, J ¼ 7.8 Hz, 1H), 8.68 (brs, 1H),
8.79 (s, NH). m/z: 240 (Mþ, 100), 181 (85), 170 (90). Anal. calcd. for
C14N2O2H12: C, 70.06; H, 5.04; N, 11.67. Found: C, 69.89; H, 5.15;
N, 11.54.
REFERENCES
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Govindachari, T.R. Synthesis of Tetrahydroisoquinolines and
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Received in the Netherlands October 14, 2002