Synthesis of alkyl-substituted pyrroles by three-component coupling of carbonyl compound, amine and nitro-alkane/alkene on a solid surface of silica gel/alumina under microwave irradiation

Article abstract of DOI:10.1016/S0040-4020(01)00400-8

Efficient synthesis of highly substituted alkylpyrroles and fused pyrroles has been achieved by a three-component coupling of (a) α,β-unsaturated aldehyde/ketone, amine and nitroalkane and (b) α,β-unsaturated nitroalkene, aldehyde/ketone and amine on the surface of silica gel and alumina without any solvent under microwave irradiation.

Full text of DOI:10.1016/S0040-4020(01)00400-8

TETRAHEDRON
Pergamon
Tetrahedron 57 )2001) 4767±4773
Synthesis of alkyl-substituted pyrroles by three-component
coupling of carbonyl compound, amine and nitro-alkane/alkene
on a solid surface of silica gel/alumina under
microwave irradiation
Brindaban C. Ranup and Alakananda Hajra
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India.
Received 20 December 2000; revised 14 March 2001; accepted 30 March 2001
AbstractÐEf®cient synthesis of highly substituted alkylpyrroles and fused pyrroles has been achieved by a three-component coupling of
)a) a,b-unsaturated aldehyde/ketone, amine and nitroalkane and )b) a,b-unsaturated nitroalkene, aldehyde/ketone and amine on the surface
of silica gel and alumina without any solvent under microwave irradiation. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
ef®cient microwave-assisted one-pot synthesis of pyrroles
by two alternative routes: )a) coupling of an a,b-unsaturated
carbonyl compound, an amine and a nitroalkane on the
surface of silica gel8 )Scheme 1) and )b) coupling of a
carbonyl compound, an amine and an a,b-unsaturated
nitroalkene on the surface of alumina )Scheme 2).
The synthesis of pyrroles has remained an extremely attrac-
tive domain in heterocyclic chemistry as they constitute the
core unit of many natural products1 and serve as the building
blocks for porphyrin synthesis.2 Several alkylpyrrole
derivatives have also been shown to possess remarkable
biological activity.3 Although there are quite a number of
methods available for the synthesis of pyrroles,4 most of
them involve multistep synthetic operations which lower
the overall yield. Recently, a few one-step procedures5
have been reported; however these are not very satisfactory
with regard to reaction conditions )long reaction period),
yield, generality and scope of substitution at the ring.
Thus, there is a need for a simple, ef®cient and more general
method for the synthesis of this useful heterocyclic nucleus.
2. Results and discussion
In a typical general procedure for route a, a mixture of a,b-
unsaturated aldehyde or ketone, an amine and nitroalkane
adsorbed on the surface of silica gel was irradiated by
microwave in a domestic microwave oven for a certain
period of time as required to complete the reaction. Elution
of the reaction mixture with ether followed by evaporation
of solvent furnished the crude product which was puri®ed by
column chromatography. The reaction delineated in route b
is also carried out under similar conditions however on the
surface of alumina. Although, either silica gel or alumina
can be used as a surface for these transformations, silica gel
for route a and alumina for route b are chosen for better
performance with regard to yield in respective cases.
The art of performing ef®cient chemical transformation
coupling three or more components in a single operation
by a reusable catalyst avoiding toxic reagents, large amount
of solvents and expensive puri®cation techniques, repre-
sents a fundamental target of the modern organic synthesis.6
As a part of our program to achieve this goal utilising
surface mediated reactions,7 we wish to report here an
Scheme 1.
Keywords: pyrrole; microwave; silica gel; alumina.
Corresponding author. Tel.: 191-33-473-4971; fax: 191-33-473-2805; e-mail: ocbcr@mahendra.iacs.res.in
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020)01)00400-8

4768
B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
Scheme 2.
Table 1. Synthesis of pyrroles from coupling of conjugated carbonyl compounds, amines and nitroalkanes
Entry
R1
R2
R3
R4
R5
Time )min)
Yield )%)a
1
2
3Ph
4
5
Ph
Ph
H
H
Ph
H
H
H
H
H
PhCH
Me
Me
Me
PhCH2
PhCH2
Me
Et
Me
Me
Et
5
8
10
8
10
5
60
62
65
64
66
60
H
2
Ph
Ph
H
PhCH2
PhCH2
PhCH2
6
Me
7
H
H
Me
Me
5
60
8
Ph
H
H
Me
5
62
9
Ph
Ph
H
Me
Me
10
66
10
11
H
H
H
Me2CH
Me2CH
Me
Me
5
5
64
68
Me
12
13
H
H
Me
Me
PhCH2
Me
Et
5
72
68
n-Bu
10
14
15
n-Pr
n-Pr
Et
Et
H
H
PhCH2
Me
Me
5
5
60
65
16
17
18
19
Ph
Ph
Ph
H
H
H
H
H
Me
Me
n-Pr
Me
Me
Me
Me
10
8
10
8
62
61
65
65
n-Bu
n-Bu
n-Bu
± )CH2)4±
a
Yields refer to those of pure isolated products
Table 2. Synthesis of pyrroles from coupling of aldehydes, amines and a,b-
unsaturated nitroalkenes
A wide range of structurally varied a,b-unsaturated
aldehydes and ketones including aromatic, aliphatic and
heterocyclic units were coupled with a variety of aliphatic
and aromatic amines and nitroalkane by this procedure
through a single step operation to produce the corresponding
alkyl substituted pyrroles as summarized in Table 1. The
reaction with nitromethane does not proceed at all; however
higher homologues like nitroethane and nitropropane under-
went smooth reactions. This procedure can put the desired
alkyl substituents at any selected position of the pyrrole ring
with proper choice of coupling components and thus this
route provides easy access to alkyl-substituted pyrroles. A
chiral amine has also been used to furnish pyrrole deriva-
tives )entries 8,9) attached with a chiral moiety which can be
of much importance for further manipulation.
Entry R1
R2
R3
R4
Time )min) Yield )%)a
1
2
Me n-Pr
Me n-Bu
2CH
Me PhCH2
Ph
Ph
Ph
Ph
Me 15
Me 15
Me 15
Me 1375
74
71
78
3Me Me
4
5
Me
Ph
Me 1375
6
7
Et
Et
n-Pr
n-Bu
Ph
Ph
Me 15
Me 15
72
71
8
9
10
11
12
Me n-Bu
p-ClC6H4 Me 1376
p-ClC6H4 Me 1378
p-ClC6H4 Me 1380
Me PhCH2
Me Me2CH
Me Me2CH
Me n-Bu
In the alternative route coupling of an aldehyde with an
amine and a,b-unsaturated nitroalkene on the surface of
alumina under microwave irradiation produced 1,3,4,5-
alkyl-substituted pyrroles. The results are presented in
p-ClC6H4 Et
p-ClC6H4 Et
15
15
81
77
a
Yields refer to those of pure isolated products

B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
4769
Table 3. Synthesis of pyrroles from coupling of ketone, amines and a,b-
unsaturated nitroalkenes
on the pyrrole ring; )e) general applicability and )f) above
all, green synthesis avoiding toxic reagents and solvents.
Thus, it provides a better and more practical alternative to
the existing methodologies3,4 for the synthesis of pyrroles
and we believe, our procedure will ®nd important
applications in the synthesis of pyrroles to cater the needs
of academia as well as pharmaceutical industries.
Entry
n
R1
R2
R3
Time )min) Yield )%)a
1
2
1
2
n-Bu
n-Bu
Ph
Ph
Ph
Me 15
Me 15
Me 15
78
84
81
4. Experimental
4.1. General
32 PhCH
2
4
2
Ph
Me 1379
5
6
7
8
9
3
4
1
2
2
n-Bu
n-Bu
PhCH2
Me2CH
PhCH2
Ph
Ph
Me 15
Me 1374
78
Melting points were determined on a glass disk with an
electrical bath and are uncorrected. H NMR )300 MHz)
1
p-ClC6H4 Me 15
p-ClC6H4 Me 15
p-ClC6H4 Me 15
78
85
82
and 13C NMR )75 MHz) spectra were run in CDCl3 solu-
tions. IR spectra were taken as KBr plates for solids and as
neat for liquids. Elemental analyses were done by a Perkin
Elmer autoanalyzer. Silica gel )HF 254, E-Merck, India)
was used as available. Alumina )neutral, Brockmann
activity 1 for column chromatography) was activated by
heating at 1808C for 4 h under vacuum )0.05 mm of Hg)
before use. The starting materials are all commercially
available and were distilled before use. A domestic micro-
wave oven )BPL-Sanyo, India; multipower; power source;
230V, 50 Hz; microwave frequency: 2450 MHz) was used
for all reactions.
10
2
p-ClC6H4 Me 15
80
11
12
2
1
n-Bu
PhCH2
p-ClC6H4 Me 1378
p-ClC6H4 Et
p-ClC6H4 Et
p-ClC6H4 Et
1379
15
1386
132 PhCH
14
15
82
82
2
2
2
Me2CH
PhCH2
p-FC6H4
Me 15
a
Yields refer to those of pure isolated products
Table 2. In this synthesis substitution at the a-position of
nitroalkene is essential without which the reaction takes a
different course which is being investigated separately and
will be disclosed in the future. Open-chain ketones in place
of aldehydes also lead to different products the identities of
which are yet to be established. However, very interestingly
cyclic ketones under similar treatment provided fused
pyrroles. The results are reported in Table 3.
4.2. General procedure for the synthesis of pyrroles.
Route a
4.2.1. N-Benzyl-2-methyl-3-phenylpyrrole *entry 1,
Table 1).
A mixture of cinnamaldehyde )264 mg,
2 mmol), benzyl amine )214 mg, 2 mmol) and nitroethane
)450 mg, 6 mmol) was uniformly adsorbed on the surface of
silica gel )3g) stirring for ®ve minutes in a pyrex round
bottomed ¯ask at room temperature under moisture guard
of anhydrous CaCl2. The ¯ask was then placed on a bed of
silica gel in a porcelain basin and irradiated by microwave
in a domestic microwave oven at 120 W for ®ve minutes
)TLC). The reaction mass was eluted with ether and the
ether extract was evaporated to leave the crude product
which was puri®ed by column chromatography over silica
gel )hexane±ether 98:2) to afford the pure product )296 mg,
60%) as a colourless oil, IR 3058, 3030, 1701, 1602,
In general, the reactions are very fast and clean. The yields
are reasonably good for a three-component coupling reac-
tion. None of these operations involves any strong acid, base
and solvent. Moreover, silica gel and alumina used can be
recycled after being washed with methanol and dried.
Conventional heating in dry media in place of microwave
leads to messy product with formation of tarry material.
However, prolonged re¯ux in THF solution in presence of
silica gel or alumina affords the corresponding pyrroles in
much lower yields.
1550 cm21 1H NMR d 7.41±7.01 )m, 8H), 7.00 )d,
;
Presumably, the imine formed by the initial reaction of a
carbonyl compound and amine on the surface of silica gel or
alumina9 undergoes coupling with nitroalkane leading to
pyrrole nucleus following the course outlined by Ishii in a
similar synthesis.5a,c
Jˆ7.2 Hz, 2H), 6.64 )d, Jˆ2.7 Hz, 1H), 6.32 )d,
Jˆ2.7 Hz, 1H), 4.99 )s, 2H), 2.22 )s, 3H); 13C NMR d
138.7, 138.1, 129.3 )2), 128.9 )2), 128.5 )2), 127.9 )2),
125.7 )2), 125.6, 123.1, 121.2, 108.3, 51.2, 11.4. Anal.
Calcd for C18H17N: C, 87.41; H, 6.93; N, 5.66. Found: C,
87.32; H, 6.85; N, 5.54.
3. Conclusion
This procedure is followed for the synthesis of all pyrroles
listed in Table 1. The known compounds )entries 14, 17, 18,
19) have been identi®ed by comparison of spectral data and
mp with those reported.5a The mp, spectral and analytical
data of all new compounds are presented below in order of
their entries.
In conclusion, the present microwave-assisted one-pot
procedure on the surface of silica gel and alumina provides
an ef®cient methodology for the synthesis of alkyl-
substituted pyrroles and fused pyrroles from easily available
starting materials by a simple three-component coupling
reaction. The notable advantages of this procedure are:
)a) reasonably good yields; )b) fast reaction; )c) mild
reaction conditions; )d) choice of appropriate substituents
4.2.2. N-Benzyl-2-ethyl-3-phenylpyrrole *entry 2).
Colourless oil; IR )neat) 3030, 2966, 2931, 1600, 1498,
1
1454, 1353, 1249, 727 cm21; H NMR d 7.42±7.17 )m,

4770
B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
8H), 7.00 )d, Jˆ6.9 Hz, 2H), 6.57 )d, Jˆ3.0 Hz, 1H), 6.29
)d, Jˆ3.0 Hz, 1H), 5.05 )s, 2H), 2.65 )q, Jˆ7.5 Hz, 2H),
1.12 )t, Jˆ7.5 Hz, 3H); 13C NMR d 139.0, 138.1, 131.6,
129.2 )2), 128.8 )2), 128.3)2), 127.9, 126.8, 125.7, 122.6
)2), 121.1, 108.6, 50.8, 18.4, 15.7. Anal. Calcd for C19H19N:
C, 87.31; H, 7.33; N, 5.36. Found: C, 87.21; H, 7.26; N,
5.31.
C19H19N: C, 87.31; H, 7.33; N, 5.36. Found: C, 87.19; H,
7.26; N, 5.27.
4.2.9. 2,5-Dimethyl-N-*a)-methylbenzyl-3-phenylpyrrole
*entry 9). Colourless cubic crystal, mp 46±488C; IR )KBr)
1
2991, 2912, 1658, 1436, 1406, 1056, 1029, 702 cm21; H
NMR d 7.39±7.07 )m, 10H), 6.03 )s, 1H), 5.54 )q,
Jˆ7.2 Hz, 1H), 2.19 )s, 3H), 2.11 )s, 3H), 1.95 )d,
Jˆ7.2 Hz, 3H); 13C NMR d 142.2, 137.6, 128.4 )2), 128.1
)2), 127.8 )2), 126.8, 125.9, 125.6, 124.7, 124.6, 124.5,
121.2, 107.0, 52.6, 19.3, 13.6, 12.2. Anal. Calcd for
C20H21N: C, 87.23; H, 7.69; N, 5.09. Found: C, 87.11; H,
7.61; N, 4.99.
4.2.3. N-Benzyl-3,5-diphenyl-2-methylpyrrole *entry 3).
Colourless cubic crystal, mp 103±1058C; IR )KBr) 3039,
2927, 1600, 1448, 1348, 758, 700 cm21; 1H NMR d 7.47 )d,
Jˆ7.1 Hz, 2H), 7.36±7.24 )m, 11H), 7.00 )d, Jˆ7.1 Hz,
2H), 6.45 )s, 1H), 5.20 )s, 2H), 2.27 )s, 3H); 13C NMR d
138.8, 137.1, 134.3, 133.4, 128.9, 128.8 )2), 128.7 )2), 128.4
)2), 128.3, 128.0, 127.6, 127.0, 126.9, 126.6 )2), 125.6,
125.2, 122.4, 108.5, 47.9, 11.3. Anal. Calcd for C24H21N:
C, 89.13; H, 6.54; N, 4.33. Found: C, 89.01; H, 6.45; N,
4.21.
4.2.10. N-Isopropyl-2-methyl-3-phenylpyrrole *entry
10). Colourless cubic crystal, mp 74±768C; IR )KBr)
2976, 2931, 1598, 1552, 1496, 1452, 1342, 1234, 763,
700 cm21 1H NMR d 7.40±7.17 )m, 5H), 6.74 )d,
;
Jˆ2.9 Hz, 1H), 6.28 )d, Jˆ2.9 Hz, 1H), 4.35±4.26 )m,
1H), 2.35 )s, 3H), 1.43 )d, Jˆ6.7 Hz, 6H); 13C NMR d
137.6, 128.2 )2), 124.9 )2), 124.2, 121.7, 114.8 )2), 107.5,
47.1, 23.6 )2), 10.8. Anal. Calcd. For C14H17N: C, 84.37; H,
8.60; N, 7.03. Found: C, 84.25; H, 8.52; N, 6.91.
4.2.4. N-Benzyl-2,5-dimethyl-3-phenylpyrrole *entry 4).
Colourless cubic crystal, mp 52±548C; IR )KBr) 3035,
1
2931, 1604, 1456, 1346, 748, 702 cm21; H NMR d 7.43±
7.21 )m, 8H), 6.78 )d, Jˆ7.4 Hz, 2H), 6.10 )s, 1H), 5.05 )s,
2H), 2.25 )s, 3H), 2.18 )s, 3H); 13C NMR d 138.8, 138.1,
129.2 )2), 128.8 )2), 128.7 )2), 128.4, 128.3)2), 126.1,
125.4, 124.8, 121.4, 106.9, 47.4, 12.8, 11.6. Anal. Calcd
for C19H19N; C, 87.31; H, 7.33; N, 5.36. Found: C, 87.20;
H, 7.29; N, 5.29.
4.2.11. N-Isopropyl-3-*2-furfuryl)-2,5-dimethylpyrrole
*entry 11). Colourless oil; IR )neat) 2974, 2933, 1622,
1311, 1199, 910, 731 cm21 1H NMR d 7.46 )s, 1H),
;
6.52±6.50 )m, 1H), 6.27 )d, Jˆ3.2 Hz, 1H), 6.17 )s, 1H),
5.54 )m, 1H), 2.51 )s, 3H), 2.41 )s, 3H), 1.59 )d, Jˆ6.2 Hz,
6H); 13C NMR d 153.0, 140.1, 128.1, 125.1, 112.1, 111.3,
106.1, 103.2, 47.7, 22.6 )2), 14.5, 12.9. Anal. Calcd for
C13H17NO: C, 76.81; H, 8.43; N, 6.89. Found: C, 76.70;
H, 8.32; N, 6.80.
4.2.5. N-Benzyl-2-ethyl-5-methyl-3-phenylpyrrole *entry
5). Colourless oil; IR )neat) 2966, 2931, 1602, 1527, 1452,
1
1350, 761, 727, 698 cm21; H NMR d 7.42±6.88 )m, 8H),
6.86 )d, Jˆ6.9 Hz, 2H), 6.08 )s, 1H), 5.04 )s, 2H), 2.63)q,
Jˆ7.5 Hz, 2H), 2.10 )s, 3H), 1.12 )t, Jˆ7.5 Hz, 3H); 13C
NMR d 139.2, 138.2, 131.0, 129.2 )2), 128.8 )2), 128.3 )2),
127.6, 126.0 )2), 125.2, 124.9, 121.3, 107.4, 47.3, 18.8,
16.3, 12.8. Anal. Calcd for C20H21N: C, 87.23; H, 7.69; N,
5.09. Found: C, 87.11; H, 7.61; N, 4.99.
4.2.12. N-Benzyl-3-*2-furfuryl)-2,5-dimethylpyrrole *entry
12). Colourless oil; IR )neat) 2976, 2918, 1624, 1452, 1338,
1
908, 727 cm21; H NMR d 7.35±7.24 )m, 5H), 6.91 )d,
Jˆ6.9 Hz, 1H), 6.40±6.39 )m, 1H), 6.19±6.16 )m, 2H),
5.03 )s, 2H), 2.31 )s, 3H), 2.16 )s, 3H); 13C NMR d 152.8,
140.0, 138.4, 129.2 )2), 128.5, 128.1, 127.5, 126.0, 125.2,
112.0, 111.3, 104.9, 102.8, 47.1, 12.6, 11.7. Anal. Calcd for
C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 81.12; H,
6.71; N, 5.51.
4.2.6. N-Benzyl-2,5-dimethylpyrrole *entry 6). Colourless
oil; IR )neat) 2995, 2912, 1652, 1434, 1406, 1056, 1029,
731 cm21 1H NMR d 7.31±7.20 )m, 3H), 6.88 )d,
;
Jˆ6.9 Hz, 2H), 5.85 )s, 2H), 4.85 )s, 2H), 2.13)s, 6H);
13C NMR d 139.0, 129.1 )2), 128.4, 127.4, 126.9, 126.1
)2), 105.8 )2), 47.1, 12.9 )2). Anal. Calcd for C13H15N: C,
84.28; H, 8.16; N, 7.54. Found: C, 84.14; H, 8.05; N, 7.42.
4.2.13. N-Butyl-2-ethyl-3-*2-furfuryl)-5-methylpyrrole
*entry 13). Colourless oil; IR )neat) 2962, 2871, 1620,
1
1463, 1340, 910, 779, 732 cm21; H NMR d 7.42 )s, 1H),
4.2.7. N-Cyclohexyl-2,5-dimethylpyrrole *entry 7).
Colourless oil; IR )neat) 2985, 2044, 1620, 1326, 1187,
6.48±6.47 )m, 1H), 6.24 )d, Jˆ3.0 Hz, 1H), 6.17 )s, 1H),
3.84 )t, Jˆ7.8 Hz, 2H), 2.91 )q, Jˆ7.5 Hz, 2H), 2.32 )s, 3H),
1.76±1.67 )m, 2H), 1.52±1.45 )m, 2H), 1.31 )t, Jˆ7.5 Hz,
3H), 1.07 )t, Jˆ7.8 Hz, 3H); 13C NMR d 152.9, 139.9,
130.9, 127.6, 111.3, 111.0, 104.9, 102.3, 43.7, 34.1,
20.6, 19.2, 15.4, 14.3, 12.8. Anal. Calcd for C15H21NO: C,
77.88; H, 9.15; N, 6.05. Found: C, 77.79; H, 9.09; N,
5.99.
1
906, 733 cm21; H NMR d 5.73)s, 2H), 3.91 )m, 1H),
2.29 )s, 6H), 1.95±1.21 )m, 10H); 13C NMR d 128.3)2),
106.4 )2), 56.8, 32.8 )2), 27.1 )2), 26.1 )2), 14.9. Anal. Calcd
for C12H19N: C, 81.30; H, 10.80; N, 7.90. Found: C, 81.16;
H, 10.72; N, 7.79.
4.2.8. 2-Methyl-N-*a)-methylbenzyl-3-phenylpyrrole
*entry 8). Colourless oil; IR )neat) 3028, 2979, 1600,
4.2.14. N-Cyclohexyl-4-ethyl-2-methyl-3-propylpyrrole
*entry 15). Colourless oil; IR )neat) 3011, 2981, 1629,
1
1496, 1448, 1309, 975, 761, 700 cm21; H NMR d 7.41±
7.27 )m, 8H), 7.02 )d, Jˆ8.2 Hz, 2H), 6.61 )d, Jˆ3.0 Hz,
1H), 6.35 )d, Jˆ3.0 Hz, 1H), 5.33 )q, Jˆ7.0 Hz, 1H), 2.20
)s, 3H), 1.83 )d, Jˆ7.0 Hz, 3H); 13C NMR d 144.0, 137.9,
130.9, 129.4 )2), 128.6, 128.5, 127.9, 127.6 )2),126.1, 125.8,
122.8, 122.6, 117.1, 107.9, 55.6, 22.9, 11.3. Anal. Calcd for
1497, 1301, 970, 711 cm21 1H NMR d 6.33 )s, 1H),
;
3.94±3.85 )m, 1H), 2.39 )q, Jˆ7.5 Hz, 2H), 2.31 )t,
Jˆ7.3Hz, 2H), 2.24 )s, 3H), 1.95±1.21 )m, 12H), 1.12 )t,
Jˆ7.5 Hz, 3H), 6.94 )t, Jˆ2.4 Hz, 3H); 13C NMR d 128.1,
127.6, 118.9, 115.5, 56.7, 31.8 )2), 26.2 )2), 25.1, 24.6, 23.5,

B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
4771
22.5, 14.2, 13.8, 11.7. Anal. Calcd for C16H27N: C, 82.34; H,
11.66; N, 6.00. Found: C, 82.21; H, 11.57; N, 5.92.
4.2.20. 2,4-Dimethyl-N-*a)-methylbenzyl-3-phenylpyrrole
*entry 5). Colourless oil; IR )neat) 2973, 2940, 1701, 1482,
1369, 1082, 731 cm21; 1H NMR d 7.42±7.22 )m, 8H), 7.09
)d, Jˆ7.2 Hz, 2H), 6.70 )s, 1H), 5.32 )q, Jˆ7.2 Hz, 1H),
2.20 )s, 3H), 2.12 )s, 3H), 1.85 )d, Jˆ7.2 Hz, 3H); 13C
NMR d 143.7, 136.7, 129.9 )2), 128.9 )2), 128.5 )2),
127.8 )2), 127.0, 125.8, 125.1 )2), 124.9, 116.0, 114.6,
54.8, 22.3, 11.2, 10.7. Anal. Calcd for C20H21N: C, 87.23;
H, 7.69; N, 5.09. Found: C, 87.04; H, 7.58; N, 4.97.
4.2.15. 2-Methyl-3-phenyl-N-propylpyrrole *entry 16).
Colourless oil; IR )neat) 2973, 2932, 1699, 1687, 1362,
1
1190, 713cm 21; H NMR d 7.40±7.17 )m, 5H), 6.64 )d,
Jˆ3.0 Hz, 1H), 6.26 )d, Jˆ3.0 Hz, 1H), 3.85 )t, Jˆ7.4 Hz,
2H), 2.33 )s, 3H), 1.92±1.86 )m, 2H), 1.07 )t, Jˆ7.4 Hz,
3H); 13C NMR d 137.6, 130.4 )2), 129.2 )2), 128.2, 125.6,
122.2, 118.1, 116.3, 47.6, 25.2, 11.4, 10.8. Anal. Calcd for
C14H17N: C, 84.37; H, 8.60; N, 7.03. Found: C, 84.21; H,
5.51; N, 6.92.
4.2.21. 4-Ethyl-2-methyl-3-phenyl-N-propylpyrrole *entry
6). Colourless oil; IR )neat) 3029, 2952, 1665, 1482, 1089,
731 cm21; 1H NMR d 7.37±7.18 )m, 5H), 6.48 )s, 1H), 3.84
)t, Jˆ7.3Hz, 2H), 2.48 )q, Jˆ7.5 Hz, 2H), 2.17 )s, 3H),
1.91±1.82 )m, 2H), 1.07 )t, Jˆ7.4 Hz, 3H), 0.95 )t,
Jˆ7.5 Hz, 3H); 13C NMR d 137.5, 130.4 )2), 128.2 )2),
125.3, 125.1, 123.4, 121.3, 117.1, 47.4, 24.9, 21.5, 20.1,
11.4, 11.0. Anal. Calcd for C16H21N: C, 84.53; H, 9.31; N,
6.16. Found: C, 84.42; H, 9.22; N, 6.09.
4.2.16. N-Benzyl-2,4-dimethyl-3-phenylpyrrole *route b)
*entry 4, Table 2). A mixture of propionaldehyde )116 mg,
2 mmol), benzyl amine )214 mg, 2 mmol) and a solution of
a-methyl-b-nitrostyrene )326 mg, 2 mmol) in THF )2 mL)
was uniformly adsorbed on the surface of alumina by stir-
ring for ®ve minutes and then THF was removed completely
under reduced pressure. The residual solid mass was then
irradiated by microwave as described in the previous experi-
ment for 13minutes. Usual work and puri®cation provided
the pure pyrrole )392 mg, 75%) as a colourless oil, IR 2930,
4.2.22. N-Butyl-4-ethyl-2-methyl-3-phenylpyrrole *entry
7). Colourless oil; IR )neat) 3030, 2926, 1625, 1476, 1091,
731 cm21; 1H NMR d 7.38±7.18 )m, 5H), 6.45 )s, 1H), 3.78
)t, Jˆ7.5 Hz, 2H), 2.48 )q, Jˆ7.5 Hz, 2H), 2.17 )s, 3H),
1.75±1.67 )m, 2H), 1.43±1.37 )m, 2H), 1.10 )t, Jˆ7.5 Hz,
3H), 0.96 )t, Jˆ7.5 Hz, 3H); 13C NMR d 137.5, 130.5 )2),
128.1 )2), 125.6, 125.5, 123.7, 121.5, 116.8, 46.9, 33.9,
20.5, 19.3, 15.2, 14.2, 10.8. Anal. Calcd for C17H23N: C,
84.59; H, 9.60; N, 5.80. Found: C, 84.43; H, 9.51; N, 5.72.
1
2878, 1701, 1531 cm21; H NMR d 7.39±7.04 )m, 10H),
6.47 )s, 1H), 5.0 )s, 2H), 2.13 )s, 3H), 2.02 )s, 3H); 13C NMR
d 138.3, 136.8, 130.4, 130.0, 129.8 )2), 128.8 )2), 128.1 )2),
127.9, 125.3)2), 122.3, 118.4, 116.4, 50.3, 11.0, 10.5. Anal.
Calcd for C19H19N: C, 87.31; H, 7.33; N, 5.36. Found: C,
87.20; H, 7.26; N, 5.22.
This procedure is followed for the synthesis of all pyrroles
listed in Table 2. The mp, spectral and analytical data of all
new compounds are summarized below in order of their
entries.
4.2.23. N-Butyl-3-*4-chlorophenyl)-2,4-dimethylpyrrole
*entry 8). Colourless oil; IR )neat) 2957, 2931, 1647,
1605, 1382, 702 cm21
;
1H NMR d 7.43)d, Jˆ8.4 Hz,
2H), 7.23)d, Jˆ8.4 Hz, 2H), 6.47 )s, 1H), 3.80 )t,
Jˆ7.3 Hz, 2H), 2.21 )s, 3H), 2.03 )s, 3H), 1.73±1.68 )m,
2H), 1.42±1.36 )m, 2H), 0.94 )t, Jˆ7.3Hz, 3H); 13C NMR d
135.9, 132.1, 131.1 )2), 130.3 )2), 129.3, 125.6, 118.2,
116.1, 46.8, 33.8, 20.4, 13.3, 11.3, 10.9. Anal. Calcd for
C16H20NCl: C, 73.41; H, 7.70; N, 5.35. Found: C, 73.29;
H, 7.59; N, 5.29.
4.2.17. 2,4-Dimethyl-3-phenyl-N-propylpyrrole *entry
1). Colourless oil; IR )neat) 2972, 2930, 1709, 1685,
1
1192, 732 cm21; H NMR d 7.52±7.33 )m, 5H), 6.57 )s,
1H), 3.86 )t, Jˆ7.3 Hz, 2H), 2.33 )s, 3H), 2.25 )s, 3H),
1.92±1.84 )m, 2H), 1.07 )t, Jˆ7.4 Hz, 3H); 13C NMR d
137.5, 130.4 )2), 129.1, 128.4 )2), 125.6, 122.2, 118.1,
116.3, 48.8, 25.1, 11.9, 11.4, 11.0. Anal. Calcd for
C15H19N: C, 84.86; H, 8.98; N, 6.57. Found: C, 84.72; H,
8.92; N, 6.51.
4.2.24. N-Benzyl-3-*4-chlorophenyl)-2,4-dimethylpyrrole
*entry 9). Colourless oil; IR )neat) 3030, 2961, 2927,
1
1670, 1488, 1091, 731 cm21; H NMR d 7.39±7.10 )m,
9H), 6.51 )s, 1H), 5.04 )s, 2H), 2.16 )s, 3H), 2.06 )s, 3H);
13C NMR d 135.8, 131.5, 131.2 )2), 128.9 )2), 128.8, 128.7
)2), 128.6, 128.3, 127.8 )2), 125.7, 125.3, 116.7, 50.8, 11.4,
11.0. Anal. Calcd for C19H18NCl: C, 77.15; H, 6.13; N, 4.74.
Found: C, 77.01; H, 6.02; N, 4.63.
4.2.18. N-Butyl-2,4-dimethyl-3-phenylpyrrole *entry 2).
Colourless oil; IR )neat) 2971, 2959, 1526, 1352, 1081,
1
831 cm21; H NMR d 7.39±7.18 )m, 5H), 6.44 )s, 1H),
3.74 )t, Jˆ7.2 Hz, 2H), 2.04 )s, 3H), 1.73 )s, 3H), 1.73±
1.70 )m, 2H), 1.42±1.37 )m, 2H), 0.95 )t, Jˆ7.5 Hz, 3H);
13C NMR d 136.9, 130.1 )2), 130.0, 128.4, 127.8 )2), 125.1,
116.1, 115.8, 46.3, 33.4, 20.0, 13.7, 11.7, 10.3. Anal. Calcd
for C16H21N: C, 84.53; H, 9.31; N, 6.16. Found: C, 84.41; H,
9.25; N, 6.04.
4.2.25.
3-*4-Chlorophenyl)-N-isopropyl-2,4-dimethyl-
pyrrole *entry 10). Colourless oil; IR )neat): 2974, 2931,
1705, 1487, 1363, 1098, 835, 732 cm21; 1H NMR d 7.30 )d,
Jˆ8.4 Hz, 2H), 7.17 )d, Jˆ8.4 Hz, 2H), 6.51 )s, 1H), 4.25
)m, 1H), 2.15 )s, 3H), 2.03 )s, 3H), 1.40 )d, Jˆ6.6 Hz, 6H);
13C NMR d 135.9, 131.6 )2), 131.3 )2), 129.2, 128.5, 125.2,
116.4, 113.5, 47.2, 24.5 )2), 11.5, 10.9. Anal. Calcd for
C15H18NCl: C, 72.72; H, 7.32; N, 5.65. Found: C, 72.62;
H, 7.22; N, 5.52.
4.2.19. 2,4-Dimethyl-N-isopropyl-3-phenylpyrrole *entry
3). Colourless oil; IR )neat) 2974, 2931, 1685, 1363, 1193,
759 cm21; 1H NMR d 7.41±7.18 )m, 5H), 6.53)s, 1H), 4.26
)m, 1H), 2.21 )s, 3H), 2.10 )s, 3H), 1.41 )d, Jˆ6.6 Hz, 6H);
13C NMR d 137.4, 130.9 )2), 130.7, 130.5, 130.4, 129.2 )2),
125.2, 116.5, 47.2, 24.0 )2), 12.8, 11.6. Anal. Calcd for
C15H19N: C, 84.46; H, 8.98; N, 6.57. Found: C, 84.35; H,
8.92; N, 6.51.
4.2.26. 3-*4-Chlorophenyl)-2-ethyl-N-isopropyl-4-methyl-
pyrrole *entry 11). Colourless cubic crystal, mp 62±
648C; IR )KBr) 2981, 2964, 1527, 1365, 1085, 837 cm21
;

4772
B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
1H NMR d 7.42 )d, Jˆ8.4 Hz, 2H), 7.30 )d, Jˆ8.4 Hz, 2H),
6.60 )s, 1H), 4.38 )m, 1H), 2.67 )q, Jˆ7.5 Hz, 2H), 2.12 )s,
3H), 1.54 )d, Jˆ6.6 Hz, 6H), 1.24 )t, Jˆ7.5 Hz, 3H); 13C
NMR d 136.1, 131.6 )2), 131.5, 131.2, 128.5 )2), 120.2,
116.8, 113.5, 46.9, 24.6 )2), 18.2, 16.3, 11.5. Anal. Calcd
for C16H20NCl: C, 73.45; H, 7.30; N, 5.35. Found: C, 73.31;
H, 7.21; N, 5.29.
4.2.31. N-*a)-methylbenzyl-7-methyl-6-phenyl-2,3,4,5-
tetrahydroindole *entry 4). Colourless oil; IR )neat)
1
2970, 2931, 1701, 1457, 1347, 1049, 732 cm21; H NMR
d 7.40±7.15 )m, 10H), 5.56 )q, Jˆ7.2 Hz, 1H), 2.60±2.48
)m, 4H), 2.22 )s, 3H), 1.85 )d, Jˆ7.2 Hz, 3H), 1.82±1.76
)m, 4H); 13C NMR d 143.0, 137.4, 130.4, 130.3 )2), 130.1,
129.2 )2), 129.0, 128.9 )2), 126.6 )2), 124.5, 111.5, 53.1,
24.4, 22.9, 23.2, 22.9, 22.5, 12.4. Anal. Calcd for C23H25N: C,
87.57; H, 7.99; N, 4.44. Found: C, 87.42; H, 7.89; N, 4.32.
4.2.27. N-Butyl-3-*4-chlorophenyl)-2-ethyl-4-methylpyr-
role *entry 12). Colourless oil; IR )neat) 2931, 2871, 1706,
1529, 1365, 1091, 823 cm21; 1H NMR d 7.45 )d, Jˆ8.4 Hz,
2H), 7.33 )d, Jˆ8.4 Hz, 2H), 6.56 )s, 1H), 3.90 )t, Jˆ7.5 Hz,
2H), 2.68 )q, Jˆ7.5 Hz, 2H), 2.14 )s, 3H), 1.92±1.87 )m,
2H), 1.53±1.48 )m, 2H), 1.25 )q, Jˆ7.5 Hz, 3H), 1.07 )t,
Jˆ7.5 Hz, 3H); 13C NMR d 136.1, 131.8, 131.6 )2), 128.6
)2), 120.6, 119.5, 118.0, 116.5, 46.5, 34.3, 20.7, 18.2, 15.9,
14.3, 11.3. Anal. Calcd for C17H22NCl: C, 74.03; H, 8.04; N,
5.08. Found: C, 73.92; H, 8.01; N, 4.97.
4.2.32. N-Butyl-2-methyl-3-phenylcyclohepta[b]pyrrole
*entry 5). Colourless oil; IR )neat) 2956, 2922, 1647,
1
1602, 1384, 702 cm21; H NMR d 7.50±7.30 )m, 5H),
3.91 )t, Jˆ7.5 Hz, 2H), 2.85 )t, Jˆ4.8 Hz, 2H), 2.69 )t,
Jˆ5.1 Hz, 2H), 2.34 )s, 3H), 2.00±2.71 )m, 8H), 1.59±
1.49 )m, 2H), 1.11 )t, Jˆ7.2 Hz, 3H); 13C NMR d 137.1,
130.9, 130.4 )2), 127.9 )2), 121.9, 120.8, 119.7, 117.6, 43.3,
33.8, 32.2, 28.9, 27.7, 25.7, 24.9, 20.2, 13.9, 10.8. Anal.
Calcd for C20H27N: C, 85.35; H, 9.67; N, 4.98. Found: C,
85.25; H, 9.61; N, 4.87.
4.2.28. N-Benzyl-7-methyl-6-phenyl-2,3,4,5-tetrahydro-
indole *route b) *entry 3, Table 3). A mixture of cyclo-
hexanone )196 mg, 2 mmol), benzyl amine )214 mg,
2 mmol) and a-methyl-b-nitrostyrene )326 mg, 2 mmol)
was treated in the same way as in previous experiment to
afford a pure product )488 mg, 81%) as a colourless oil, IR
4.2.33. N-Butyl-2-methyl-3-phenylcycloocta[b]pyrrole
*entry 6). Colourless oil; IR )neat) 2970, 1645, 1444,
1
1601, 1127, 700 cm21; H NMR d 7.38±7.14 )m, 5H),
3.47 )t, Jˆ7.5 Hz, 2H), 2.73)t, Jˆ5.1 Hz, 2H), 2.46 )t,
Jˆ5.1 Hz, 2H), 2.18 )s, 3H), 1.72±1.37 )m, 12H), 0.94 )t,
Jˆ7.2 Hz, 3H); 13C NMR d 137.2, 130.7, 130.6 )2), 128.0
)2), 127.9, 127.0, 119.2, 117.5, 43.8, 31.6, 29.5, 28.3, 26.2,
25.8, 24.2, 23.4, 20.2, 13.8, 10.7. Anal. Calcd for C21H29N:
C, 85.37; H, 9.89; N, 4.74. Found: C, 85.31; H, 9.81; N,
4.62.
1
2974, 2934, 1652, 1557 cm21; H NMR d 7.46±7.02 )m,
10H), 5.03)s, 2H), 2.61 )t, Jˆ6 Hz, 2H), 2.25 )t, Jˆ6 Hz,
2H), 2.23)s, 3H), 1.92±1.76 )m, 4H); 13C NMR d 139.1,
137.3, 130.2, 129.2 )2), 129.1 )2), 129.0, 128.9 )2), 127.4,
125.3 )2), 119.2, 115.8, 109.6, 47.1, 25.0, 24.4, 23.5, 22.3,
11.1. Anal. Calcd for C22H23N: C, 87.66; H, 7.69; N, 4.65.
Found: C, 87.52; H, 7.58; N, 4.56.
4.2.34. N-Benzyl-3-*4-chlorophenyl)-2-methylcyclohepta-
[b]pyrrole *entry 7). Colourless cubic crystal, mp 83±
858C; IR )KBr) 2937, 2842, 1525, 1382, 1089, 831,
This procedure is followed for the synthesis of all pyrroles
listed in Table 3. The mp, spectral and analytical data of all
new compounds are presented below in order of their
entries.
731 cm21 1H NMR d 7.25±7.16 )m, 8H), 6.96 )d,
;
Jˆ7.0 Hz, 2H), 4.90 )s, 2H), 2.68 )t, Jˆ6.8 Hz, 2H), 2.54
)t, Jˆ6.7 Hz, 2H), 2.37±2.28 )m, 2H), 2.13 )s, 3H); 13C
NMR d138.6, 137.7, 136.3, 131.2, 130.6 )2), 129.5 )2),
129.1 )2), 127.7, 127.1, 124.6, 124.5 )2), 116.7, 49.2,
28.9, 26.4, 25.3, 12.0. Anal. Calcd for C21H21N: C, 87.76;
H, 7.36; N, 4.87. Found: C, 87.62; H, 7.26; N, 4.81.
Although the experimental procedures were based on mmol
scale reactions, gram-scale reactions also afforded the corre-
sponding products in analogously good yields.
4.2.29. N-Butyl-2-methyl-3-phenylcyclopenta[b]pyrrole
*entry 1). Colourless oil; IR )neat) 3036, 2929, 1602,
4.2.35. 6-*4-Chlorophenyl)-7-methyl-N-isopropyl-2,3,4,5-
tetrahydroindole *entry 8). Colourless oil; IR )neat)
1
1458, 1126, 748, 700 cm21; H NMR d 7.41±7.13)m,
1
5H), 3.73 )t, Jˆ7.5 Hz, 2H), 2.76±2.67 )m, 4H), 2.46±
2.38 )m, 2H), 2.32 )s, 3H), 1.73±1.61 )m, 2H), 1.42±1.30
)m, 2H), 0.88 )t, Jˆ7.2 Hz, 3H); 13C NMR d 137.5, 136.5,
128.5, 128.2 )2), 127.8 )2), 125.9, 123.8, 116.7, 45.1, 33.5,
28.5, 25.8, 20.2, 19.8, 13.8, 11.3. Anal. Calcd for C18H23N:
C, 85.32; H, 9.15; N, 5.53. Found: C, 85.19; H, 9.09; N,
5.42.
2974, 2931, 1552, 1488, 1460, 1344, 1089, 736 cm21; H
NMR d 7.27 )d, Jˆ8.4 Hz, 2H), 7.10 )d, Jˆ8.4 Hz, 2H),
4.35 )m, 1H), 2.62 )d, Jˆ6.0 Hz, 2H), 2.36 )d, Jˆ6.0 Hz,
2H), 2.18 )s, 3H), 1.79±1.75 )m, 2H), 1.63±1.60 )m, 2H),
1.42 )d, Jˆ7.2 Hz, 6H); 13C NMR d 135.7, 131.6 )2), 128.9
)2), 126.7, 121.2, 119.7, 115.9, 111.5, 47.6, 24.0, 23.4, 22.8
)2), 22.0, 12.2. Anal. Calcd for C18H22NCl: C, 75.11; H,
7.70; N, 4.87. Found: C, 75.01; H, 7.59; N, 4.82.
4.2.30. N-Butyl-7-methyl-6-phenyl-2,3,4,5-tetrahydro-
indole *entry 2). Colourless oil; IR )neat) 2973, 2930,
4.2.36. N-Benzyl-6-*4-chlorophenyl)-7-methyl-2,3,4,5-tetra-
hydroindole *entry 9). Colourless cubic crystal, mp 95±
1547, 1487, 1462, 1339, 1087, 733 cm21 1H NMR d
;
7.38±7.15 )m, 5H), 3.73 )t, Jˆ7.8 Hz, 2H), 2.59 )t,
Jˆ6.0 Hz, 2H), 2.51 )t, Jˆ6.0 Hz, 2H), 2.27 )s, 3H),
1.80±1.62 )m, 6H), 1.41±1.36 )m, 2H), 0.97 )t, Jˆ7.2 Hz,
3H); 13C NMR d 136.8, 130.2, 129.5 )2), 128.0, 127.9 )2),
124.7, 119.3, 114.5, 43.2, 33.2, 23.8, 23.4, 22.6, 22.0, 20.2,
13.8, 10.5. Anal. Calcd for C19H25N: C, 85.34; H, 9.42; N,
5.24. Found: C, 85.24; H, 9.30; N, 5.21.
978C; IR )KBr) 2937, 2931, 1536, 1381, 1079, 700 cm21
;
1H NMR d 7.47±7.32 )m, 7H), 7.09 )d, Jˆ7.2 Hz, 2H), 5.13
)s, 2H), 2.67±2.60 )m, 4H), 2.30 )s, 3H), 1.99±1.81 )m, 4H);
13C NMR d 138.9, 135.9, 131.1 )2), 129.2, 129.1 )2), 128.7
)2), 127.7, 127.6, 126.5, 126.4, 124.5, 119.3, 115.8, 47.1,
25.2, 24.4, 23.2, 22.5, 11.1. Anal. Calcd for C22H22NCl: C,
78.67; H, 6.60; N, 4.17. Found: C, 78.52; H, 6.53; N, 4.09.

B.C.Ranu, A.Hajra / Tetrahedron 57 *2001) 4767±4773
4773
4.2.37. 6-*4-Chlorophenyl)-7-methyl-N-*a)-methylben-
zyl-2,3,4,5-tetrahydroindole *entry 10). Colourless oil,
IR )neat) 2929, 2848, 1645, 1535, 1450, 1371, 1089,
Acknowledgements
This investigation has enjoyed ®nancial support from CSIR,
New Delhi. A. H. is also thankful to CSIR for his fellowship.
698 cm21
;
1H NMR d 7.47±7.26 )m, 9H), 5.65 )q,
Jˆ7.2 Hz, 1H), 2.67±2.55 )m, 4H), 2.29 )s, 3H), 2.05 )d,
Jˆ7.2 Hz, 3H), 1.86±1.75 )m, 4H); 13C NMR d 142.9,
136.0, 131.4, 131.2 )2), 129.3, 129.0, 128.6 )2), 127.5 )2),
126.6 )2), 124.6, 119.8, 116.1, 53.0, 25.5, 24.2, 24.1, 23.4,
20.1, 12.2. Anal. Calcd for C23H24NCl: C, 78.95; H, 6.91; N,
4.00. Found: C, 78.81; H, 6.89; N, 3.91.
References
1. )a) Anderson, R. J.; Faukner, D. J.; Cun-heng, H.; Van Duyne,
1985, 107, 5492.
G. D.; Clardy, J. J.Am.Chem.Soc.
)b) Yoshida, W. Y.; Lee, K. K.; Carrol, A. R.; Scheuer, P. J.
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4.2.38. N-Butyl-6-*4-chlorophenyl)-7-methyl-2,3,4,5-tetra-
hydroindole *entry 11). Colourless oil; IR )neat) 2929,
1
2956, 1647, 1595, 1488, 1089, 1014, 821 cm21; H NMR
d 7.49 )d, Jˆ8.4 Hz, 2H), 7.24 )d, Jˆ8.4 Hz, 2H), 3.74 )t,
Jˆ7.8 Hz, 2H), 2.60 )t, Jˆ6.0 Hz, 2H), 2.50 )t, Jˆ6.0 Hz,
2H), 2.27 )s, 3H), 1.89±1.67 )m, 6H), 1.47±1.42 )m, 2H),
0.97 )t, Jˆ7.2 Hz, 3H); 13C NMR d 136.7, 135.2, 131.0 )2),
129.8, 129.2 )2), 126.9, 123.8, 115.3, 43.7, 33.7, 24.3, 23.8,
22.5, 20.8, 20.6, 14.2, 10.9. Anal. Calcd for C19H24NCl: C,
75.60; H, 8.01; N, 4.64. Found: C, 75.51; H, 7.96; N, 4.61.
2. Nonn, A. Angew.Chem.Int.Ed.Engl.
references cited therein.
1995, 34, 1795 and
3. Meanwell, N. A.; Romine, J. L.; Rosenfeld, M. J.; Martin, S. W.;
Trehan, A. K.; Wright, J. J. K.; Malley, M. F.; Goughoutas, J. Z.;
Brassard, C. L.; Buchanan, J. O.; Federici, M. E.; Fleming, J. S.;
Gamberdella, M.; Hartl, K. S.; Zavoico, G. B.; Seiler, S. M.
J.Med.Chem. 1993, 36, 3884.
4. )a) Fischer, H. Organic Syntheses, Wiley: New York, 1943;
Coll. Vol. II, pp 202. )b) Cooney, J. V.; McEwen, W. E.
J.Org.Chem. 1981, 46, 2570. )c) Berree, F.; Marchand, E.;
Morel, G. Tetrahedron Lett. 1992, 33, 6155. )d) Furstner, A.;
4.2.39. N-Benzyl-3-*4-chlorophenyl)-2-ethylcyclopenta-
[b]pyrrole *entry 12). Colourless oil; IR )neat) 2964,
1
2931, 1670, 1521, 1452, 1384, 1091, 829 cm21; H NMR
d 7.41±7.24 )m, 7H), 7.05 )d, Jˆ6.6 Hz, 2H), 5.04 )s, 2H),
2.79±2.38 )m, 8H), 1.15 )t, Jˆ7.5 Hz, 3H); 13C NMR d
138.8, 137.8, 136.3, 134.3, 134.1, 130.7 )2), 129.8 )2),
129.3)2), 129.1, 127.7, 116.2, 49.0, 28.7, 26.4, 25.2, 19.0,
15.9. Anal. Calcd for C22H22NCl: C, 78.67; H, 6.60; N, 4.17.
Found: C, 78.57; H, 6.51; N, 4.11.
Weintritt, H.; Hupperts, A. J.Org.Chem.
1995, 60, 6637.
)e) Roskamp, E. J.; Dragovich, P. S.; Hartung Jr, J. B.;
Pederson, S. F. J.Org.Chem. 1989, 54, 4736. )f) Periasamy,
M.; Srinivas, G.; Bharathi, P. J.Org.Chem. 1999, 64, 4204.
)g) Tsutsui, H.; Narasaka, K. Chem.Lett. 1999, 45. )h) Fejes, I.;
Toke, L.; Blasko, G.; Nyerges, M.; Pak, C. S. Tetrahedron
2000, 56, 8545. )i) Grigg, R.; Savie, V. Chem.Comm. 2000,
873. )j) Burley, I.; Bilic, B.; Hewson, A. T.; Newton, J. R. A.
Tetrahedron Lett. 2000, 41, 8969. )k) Liu, J.-H.; Yang, Q.-C.;
Mak, T. C. W.; Wong, H. N. C. J.Org.Chem. 2000, 65, 327 and
references cited therein.
4.2.40. N-Benzyl-6-*4-chlorophenyl)-7-ethyl-2,3,4,5-tetra-
hydroindole *entry 13). Colourless oil; IR )neat) 2929,
2873, 1645, 1531, 1485, 1353, 1095, 1014, 827,
1
732 cm21; H NMR d 7.53±7.11 )m, 9H), 5.14 )s, 2H),
2.70±2.48 )m, 6H), 1.89±1.80 )m, 4H), 1.18 )t, Jˆ7.5 Hz,
3H); 13C NMR d 139.3, 136.0, 131.4 )2), 131.0, 129.2 )2), 129.1
)2), 128.8, 128.6, 127.5, 126.3)2), 126.1, 119.0, 116.0, 47.0,
24.3, 23.8, 23.1, 22.5, 18.3, 16.3. Anal. Calcd for C23H24NCl: C,
78.95; H, 6.91; N, 4.00. Found: C, 78.81; H, 6.82; N, 3.93.
5. )a) Shiraishi, H.; Nishitani, T.; Sakaguchi, S.; Ishii, Y. J.Org.
Chem. 1998, 63, 6234. )b) Danks, T. N. Tetrahedron Lett. 1999,
40, 3957. )c) Shiraishi, H.; Nishitani, T.; Nishihara, T.;
Sakaguchi, S.; Ishii, Y. Tetrahedron 1999, 55, 13957.
6. )a) Dittmer, D. C. Chem.Ind.*London) 1947, 779. )b) Mizuno,
N.; Misono, M. Chem.Rev. 1998, 98, 199.
4.2.41. 6-*4-Chlorophenyl)-7-ethyl-N-isopropyl-2,3,4,5-
tetrahydroindole *entry 14). Colourless oil; IR )neat)
2972, 2933, 1703, 1647, 1488, 1460, 1350, 1091, 1012,
7. )a) Ranu, B. C.; Bhar, S.; Sarkar, D. C. Tetrahedron Lett. 1991,
32, 2811. )b) Ranu, B. C.; Bhar, S.; Chakraborti, R. J.Org.
Chem. 1992, 57, 7349. )c) Ranu, B. C.; Bhar, S. J.Chem.
Soc., Perkin Trans. 1 1992, 365. )d) Ranu, B. C.; Saha, M.;
Bhar, S. Tetrahedron Lett. 1993, 34, 1989. )e) Ranu, B. C.;
1
786 cm21; H NMR d 7.29 )d, Jˆ8.4 Hz, 2H), 7.05 )d,
Jˆ8.4 Hz, 2H), 4.30 )m, 1H), 2.68 )t, Jˆ6.0 Hz, 2H), 2.53
)t, Jˆ7.5 Hz, 2H), 2.34 )t, Jˆ6.0 Hz, 2H), 1.74±1.61 )m,
4H), 1.42 )d, Jˆ6.9 Hz, 6H), 0.94 )t, Jˆ7.5 Hz, 3H); 13C
NMR d 136.1, 131.5, 131.2 )2), 130.3, 129.6 )2), 128.6,
121.2, 116.6, 47.5, 25.1, 24.3, 23.9, 23.1 )2), 23.1, 18.8,
16.7. Anal. Calcd for C19H24NCl: C, 75.60; H, 8.01; N,
4.64. Found: C, 75.48; H, 7.92; N, 4.52.
Saha, M. J.Org.Chem.
1994, 59, 8269. )f) Ranu, B. C.;
Majee, A.; Das, A. R. Synth.Commun. 1995, 25, 363.
)g) Ranu, B. C.; Sarkar, A.; Saha, M.; Bhar, S. Pure Appl.
Chem. 1996, 68, 775. )h) Ranu, B. C.; Ghosh, K.; Jana, U.
J.Org.Chem. 1996, 61, 9545. )i) Ranu, B. C.; Saha, M.;
Bhar, S. Synth.Commun. 1997, 27, 621. )j) Ranu, B. C.;
Saha, M.; Bhar, S. Synth.Commun. 1997, 27, 3065. )k) Ranu,
B. C.; Jana, U.; Majee, A. Green Chemistry 1999, 33. )l) Ranu,
B. C.; Guchhait, S. K.; Ghosh, K.; Patra, A. Green Chemistry
2000, 5. )m) Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett.
2000, 41, 531.
4.2.42.
tetrahydroindole *entry 15). Colourless cubic crystal, mp
71±738C; IR )KBr) 2929, 1639, 1504, 1386, 842, 731 cm21
N-Benzyl-6-*4-¯uorophenyl)-7-methyl-2,3,4,5-
;
1H NMR d 7.35±6.85 )m, 9H), 4.90 )s, 2H), 2.39 )m, 4H),
2.06 )s, 3H), 1.72±1.62 )m, 4H); 13C NMR d 139.0, 133.3,
131.6 )2), 131.2, 131.1, 129.0, 127.8 )2), 127.4, 126.5,
126.3, 124.2, 115.9, 115.1, 109.7, 47.1, 24.4, 23.8, 23.1,
22.4, 11.4. Anal. Calcd for C22H22NF: C, 82.73; H, 6.94;
N, 4.39. Found: C, 82.59; H, 6.88; N, 4.27.
8. A preliminary communication has been made with a part of this
work: Ranu, B. C.; Hajra, A.; Jana, U. Synlett 2000, 75.
9. Ranu, B. C.; Majee, A.; Sarkar, A. J.Org.Chem. 1998, 63, 370.