Poly(N,N'-dibromo-N-ethyl-benzene-1,3-disulfonamide), N,N,N',N'- tetrabromobenzene-1,3-disulfonamide as new reagents for conjugate addition of indole, pyrrole with a,b-unsaturated ketones

Article abstract of DOI:10.1007/s13738-012-0087-2

Poly(N,N'-dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] and N,N,N',N'-tetrabromobenzene-1,3- disulfonamide[TBBDA] were used as efficient reagents for conjugate addition of indole and pyrrole with a,b-unsaturated ketones and also, double-conjugate 1,4-

Full text of DOI:10.1007/s13738-012-0087-2

J IRAN CHEM SOC (2012) 9:655–660
DOI 10.1007/s13738-012-0087-2
ORIGINAL PAPER
Poly(N,N0-dibromo-N-ethyl-benzene-1,3-disulfonamide),
N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide as new reagents
for conjugate addition of indole, pyrrole with a,b-unsaturated
ketones
•
R. Ghorbani-Vaghei S. Hajinazari
•
M. Engashte
Received: 31 August 2011 / Accepted: 14 January 2012 / Published online: 4 May 2012
Ó Iranian Chemical Society 2012
Abstract Poly(N,N0-dibromo-N-ethyl-benzene-1,3-disul-
fonamide) [PBBS] and N,N,N0,N0-tetrabromobenzene-1,3-
disulfonamide[TBBDA] were used as efficient reagents for
conjugate addition of indole and pyrrole with a,b-unsatu-
rated ketones and also, double-conjugate 1,4-addition of
indoles to dibenzylidenacetones.
many pharmacologically and biologically active com-
pounds. The C-3 position of indole is the preferred site for
electrophilic substitution reaction and 3-substituted indoles
are versatile compounds. b-Indol ketones have received
more attention as important building blocks for the syn-
thesis of many natural products and other biologically
active compounds. However, the acid-catalyzed conjugate
addition of indoles requires meticulous control of acidity to
prevent side reactions such as dimerization or polymeri-
zation [2, 3]. Thus, a number of milder reagents and Lewis-
acid catalysts such as Al2O3 [4], K2CO3 [5], rhodium
complex [6], ruthenium complex [7], clay-supported
nickel bromide [8], quaternary ammonium salt [9], InBr3
[10], InCl3 [11], Bi(NO3)3 [12], I2 [13], Bi(NO3)3
[14], HClO4/SiO2 [15], GaI3 [16], PTSA [17], sulfamic
acid [18], Ru(III) [19], NH4Cl [20], and N-phenyl-
tris(dimethylamino)iminophosphorane immobilized on
polystyrene resin [21], have been developed over the past
few years.
Keywords Micheal reaction ꢀ a,b-Unsaturated
compounds ꢀ Indole ꢀ Pyrrole ꢀ PBBS ꢀ TBBDA
Introduction
Micheal reaction is one of the most important reactions in
organic chemistry. The conjugate addition of nucleophilic
species to a,b-unsaturated systems is a fundamental con-
cept in organic chemistry and is considered as one of the
most versatile methods in organic synthesis [1]. This type
of conjugate addition of nucleophiles to acceptor-substi-
tuted double-bond belongs to the classical carbon–carbon
bond forming reaction. Indole is a privilege heterocyclic
ring. The synthesis and reaction of indoles have received
much interest for more than a century. Due to their bio-
logical activity, indole and many of its derivatives occur in
Unfortunately, a number of these procedures have one or
more disadvantages such as longer reaction time, use of
excessive expensive catalyst, harsh reaction conditions,
failure to provide additional product and tedious experi-
mental procedure. Consequently, an efficient method is
needed for these transformations, which might work under
mild and more economical conditions.
Further to our interest in the application of poly(N,N0-
dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS], N,
N,N0,N0-tetrabromobenzene-1,3-disulfonamide [TBBDA],
in organic synthesis [22–31], now we report a conve-
nient method for conjugate addition of indole and pyrrole
to a,b-unsaturated ketones using reagents poly(N,N0-
dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS],
N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide [TBBDA]
(Scheme 1).
R. Ghorbani-Vaghei (&)
Department of Organic Chemistry, Faculty of Chemistry,
Bu-Ali Sina University, 65174 Hamedan, Iran
e-mail: rgvaghei@yahoo.com
S. Hajinazari ꢀ M. Engashte
Payame Noor University, Hamedan, Iran
123

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J IRAN CHEM SOC (2012) 9:655–660
O
R1
O
2a
N
R2
3a
N
O
R1
H
R1
R1
R1
TBBDA or PBBS
CH3CN
TBBDA or PBBS
CH3CN
NH
R1
1a
r.t.
HN
r.t.
3b
2b
Br
N
Br
N
Br
Br
N
R1: alkyl, aryl
CH2
Br
N
Br
S
S
CH2
S
S
O
O
O
n
O
R2: H, Me
O
O
O
O
PBBS
TBBDA
Scheme 1 Conjugate addition of indole and pyrrole to a,b-unsaturated ketones
Experimental section
Table 1 Screening for optimum reaction conditions
Entry
Conditions
Time (h)
Yield (%)
General
1
2
3
4
5
6
7
8
EtOH
4
90
80
45
97
70
85
85
40
CHCl3
CCl4
6
Substrates, solvents and other chemicals were purchased from
Fluka, Merck and Aldrich chemical companies. The progress
of the reaction was monitored by (TLC SiO2-n-hexane:
acetone). IR spectra (KBr) were recorded on a Perkin Elmer
GX FT-IR spectrophotometer and the nuclear magnetic res-
onance (NMR) spectra were obtained on a Jeol 90 MHz
FT-NMR spectrometer using TMS as the internal standard.
5
CH3CN
THF
3
6.5
4
CH2Cl2
MeOH
Solvent-free
3.5
1
The Michael addition of indole or pyrrole to
a,b-unsaturated carbonyl compounds: general
procedure
was attempted by different solvents such as EtOH, MeOH,
CHCl3, and CCl4, the yield was found to be better in
acetonitrile (Table 1).
Electron-deficient olefins, such as methyl vinyl ketone,
chalcon and dibenzylidenacetone afford the product in
good to excellent yields. The results are summarized in
(Table 2). Based on the obtained results, the reaction was
extended to pyrrole, and found that the reaction of pyr-
role (3a) with different a,b-unsaturated ketones (1a),
affording 2-substituted pyrrole derivatives (3b) with
comparable yields (Table 2, entries 16–18). We found
that TBBDA and PBBS promoted the reaction of indoles
and dibenzylidenacetones leading to two c–c bonds in
one-pot under solvent conditions, affording the desired
adducts in high yields (Scheme 2). Treatment of indoles
(1 mmol) with dibenzylidenacetone (0.5 mmol) in the
presence of TBBDA or PBBS (0.1 g) in acetonitrile
(3 mmol) at room temperature gave the correspond-
ing 1,5-di(3-indolyl)-1,5-diphenyl-penran-3-one (Table 2,
entries 13–15).
To a mixture of indole or pyrrole (1 mmol), a,b-unsatu-
rated ketone (1 mmol), in CH3CN (5 mmol), TBBDA
(0.1 g, 0.2 mmol) or PBBS (0.1 g) was added and the
mixture was stirred at room temperature for the appropriate
time in (Table 2). After completion of reaction (TLC
analysis), CH2Cl2 cold (20 mL) was added and the pre-
cipitated sulfonamide was removed by filtration. Then, the
organic phase separated and dried. Removal of the solvent
under reduced-pressure gave the crude product. Further
purification was achieved by recrystallized from ethanol.
Results and discussion
In a preliminary experiment, treatment of indole (2a) with
1,3-diphenylpropenone (1a) in CH3CN, using [TBBDA]
and [PBBS] as reagents at room temperature for 3 h,
afforded the 3-substituted indole adduct 2b in high yield
after recrystallization by ethanol. The product 2b was
characterized by spectroscopic analysis. Encouraged by
this result, we decided to study the effect of solvent and
reaction conditions on the Michael addition for the syn-
thesis of 3-substituted indoles (2b) (Table 1). The reaction
N-methylindoles were studied, and the desired products
were obtained in good yields (Table 2, entries 19–21). a,b-
Unsaturated nitriles and aldehydes did not produce any
products (Table 2, entries 22 and 23).
To compare poly (N-bromo-N-ethyl-benzene-1,3-di-
sulfonamide) [PBBS] and N,N,N0,N0-tetrabromobenzene-
123

J IRAN CHEM SOC (2012) 9:655–660
657
Table 2 Michael addition of indole, pyrrole to a,b-unsaturated ketones by TBBDA and PBBS
TBBDA
Time
(h)
PBBS
Time
(h)
Entry Nucleophile Electrophile
Products
References
[14]
Yield
(%)
Yield (%)
85
O
O
1
3
90
7
N
H
HN
O
O
2
3
4.5
80
9
75
90
[14]
[17]
N
H
HN
O
O
3
97
95
7.5
8.5
N
H
HN
HN
HN
HN
Me
OMe
Cl
O
O
O
O
4
5
6
3.5
92
85
87
[17]
[17]
[17]
N
H
Me
MeO
Cl
O
3.5
3
95
97
8
N
H
O
6.5
N
H
O
O
7
8
9
3.5
4
95
92
95
8
8
6
90
85
92
N
H
[17]
[32]
Me
Br
HN
Me
Br
O
O
N
H
HN
Cl
O
O
O
3
–
–
N
H
Br
Cl
HN
Br
OMe
O
10
11
3.5
3.5
96
97
6
9
90
92
N
H
Br
MeO
HN
Br
Me
O
O
–
N
H
Me
Me
HN
Me
O
O
OMe
12
13
4
3
85
90
8.5
7.5
80
85
[14]
[19]
N
H
OMe
HN
O
O
O
N
H
NH
HN
Cl
Cl
O
14
3.5
90
7.5
90
[19]
N
H
Cl
Cl
NH
HN
123

658
J IRAN CHEM SOC (2012) 9:655–660
Table 2 continued
TBBDA
Time
(h)
PBBS
Time
(h)
Entry Nucleophile Electrophile
Products
References
[19]
Yield
(%)
Yield (%)
80
OMe
OMe
O
15
O
O
3.5
80
8.5
N
OMe
H
MeO
NH
HN
O
16
17
0.75
0.25
80
90
2
86
80
–
N
H
Br
NH
Br
O
O
1.5
[32]
N
H
NH
OMe
O
O
18
19
0.5
2.5
85
95
2
6
80
85
[32]
[10]
N
H
MeO
NH
O
O
N
Me
N
Me
Cl
O
O
20
21
3
90
95
8
85
90
[16]
N
Cl
Me
N
Me
Me
O
O
2.5
6.5
–
N
Me
Me
N
Me
O
H
22
23
NR
NR
24
24
–
–
24
24
–
–
–
–
N
H
CN
N
H
a
Products were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic method
NR no reaction
R2
R2
O
O
TBBDA or PBBS
+
R2
R2
CH3CN
r.t.
N
H
N
H
N
H
R2: aryl
Scheme 2 One-pot addition of indole to dibenzylidenacetones
1,3-disulfonamide [TBBDA] with previously published
methods for conjugate addition of indole with a,b-unsatu-
rated ketones, we carried out the following studies, as
shown in Table 3. This clearly demonstrates that poly (N-
bromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] and
N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide [TBBDA]
are good reagents for conjugate addition of indole with
a,b-unsaturated ketones.
123

J IRAN CHEM SOC (2012) 9:655–660
659
Table 3 Reaction times and
yield for the previously
published methods
Entry Electrophile
1
Condition
Time (h) Yield (%) References
O
TBBDA (0.1 g), room temperature, CH3CN
3
97
85
80
70
85
80
This work
This work
[34]
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O
O
O
O
O
2
3
4
5
6
PBBS (0.1 g), room temperature, CH3CN
PDA, room temperature, MeOH
(Zn-HAP), reflux, CH3CN
7
24
24
6
[35]
SmI3, reflux, CH3CN
[33]
RuCl3.nH2O, reflux, MeOH
3
[19]
O
O
7
8
TBBDA (0.1 g), room temperature, CH3CN
RuCl3.nH2O, reflux, MeOH
3
3
90
77
This work
[19]
Ph
Ph
Ph
Ph
Poly(N,N0-dibromo-N-ethyl-benzene-1,3-disulfonamide)
[PBBS] and N,N,N0,N0-tetrabromobenzene-1,3-disulfona-
mide [TBBDA] are inexpensive and non-hazardous
reagents. They react under heterogeneous conditions, are
conveniently handled, and can be removed from the reac-
tion mixture by simple filtration.
3H), 2.25 (s, 3H). MS (EI): Anal. Calcd. for C24H23BrNO2:
C, 66.37; H, 4.64; N, 3.22. Found: C, 66.42; H, 4.52; N,
3.26: m/z = 353.
Spectra data of 11(2a) solid; mp 157–158 °C. IR (KBr):
3,435, 3,063, 1,673, 1,576, 1,510, 1,335, 1,247, 1,129,
.
1,024, 818, 746 cm-1 1H NMR (FT-90 MHz, CDCl3):
d = 7.96 (s, NH, 1H), 7.19–7.87 (m, ArH, 12H), 6.75 (s,
indole ring, 1H), 4.96 (t, j = 7.2 Hz, CH, 1H), 3.73 (s, 3H),
3.72–3.76 (m, CH2, 2 H). Anal. Calcd. for C25H23NO: C,
84.95; H, 6.56; N, 3.96. Found: C, 83.91; H, 6.51; N, 4.12.
MS (EI): m/z = 434.
Conclusion
In conclusion, we have developed efficient and cost-
effective method for Michael addition of indole, pyrrole to
Michael acceptors and double-conjugate 1,4-addition of
indoles to symmetric enones, using TBBDA and PBBS at
room temperature. The method has advantages of mild
reaction condition, high yield of products, cleaner reaction
and novel method for synthesis of important 3-substituted
indole and 2-substituted pyrrole derivatives.
Spectra data of 16(3b) solid, mp 125–127 °C. IR (KBr):
3,395, 1,690, 1,420, 1,275, 1,041 cm-1 1H NMR (FT-
.
90 MHz, CDCl3): d = 8.25 (brs, NH, 1H), 6.50–8.12 (m,
ArH, 12H), 5.10 (t, j = 8.0 Hz, CH, 1H), 3.52–3.61 (m,
CH2, 2 H). Anal. Calcd. for C19H16BrNO: C, 64.42; H,
4.55; N, 3.95. Found: C, 64.35; H, 4.34; N, 3.64. MS (EI):
m/z = 354.
Spectra data of 21(2a) solid; mp 158–159 °C. IR (KBr):
3,043, 1,680, 1,596, 1,493, 1,247, 1,129, 1,024, 818,
Acknowledgments We are thankful to Bu-Ali Sina University,
Center of Excellence and Development of Chemical Methods
(CEDCM) for financial support.
1
746 cm-1. H NMR (FT-90 MHz, CDCl3): 7.01–7.87 (m,
ArH, 13H), 6.80 (s, indole ring, 1H), 5.00 (t, j = 7.2 Hz,
CH, 1H), 3.72 (s, 3H), 3.69–3.76 (m, CH2, 2 H), 2.25 (s,
3H). Anal. Calcd. for C25H23NO: C, 84.95; H, 6.56; N,
3.96. Found: C, 84.19; H, 6.67; N, 3.98. MS (EI):
m/z = 434.
Characterisation of the selected data
Spectra data of 9(2a) solid; mp 130–132 °C. IR (KBr):
3,398, 3,084, 3,056, 3,026, 1,681, 1,596, 1,579, 1,489, 820,
.
768, 746, 689 cm-1 1H NMR (FT-90 MHz, CDCl3):
References
d = 8.04 (s, NH, 1H), 7.19–7.87 (m, ArH, 12H), 7.01 (s,
indole ring, 1H), 4.97 (t, j = 7.2 Hz, CH, 1H), 3.71–3.85
(m, CH2, 2 H). Anal. Calcd. for C23H17BrClNO: C, 62.96;
H, 3.91; N, 3.19. Found: C, 62.52; H, 3.75; N, 3.06. MS
(EI): m/z = 438.
1. E. Lewandowska, Tetrahedron 63, 2107 (2007)
2. N. Krause, A. Hoffman-Roder, Synthesis 171 (2001)
3. H. Firouzabadi, N. Iranpoor, A. Jafari, J. Mol. Catal. A. Chem.
244, 168 (2006)
4. B.C. Ranu, S. Bhar, D.C. Sarkar, Tetrahedron Lett. 32, 2811
(1991)
5. Z. Zhang, Y.W. Dong, G.W. Wang, K. Komatsu, Synlett. 61
(2004)
6. S. Paganelli, A. Schionato, C. Botteghi, Tetrahedron Lett. 32,
2807 (1991)
Spectra data of 10(2a) solid; mp 167–168 °C. IR (KBr):
1
3,434, 3,060, 1,669, 1,588,809, 738, 578 cm-1. H NMR
(FT-90 MHz, CDCl3): d = 7.98 (s, NH, 1H), 7.19–7.87
(m, ArH, 12H), 6.75 (s, indole ring, 1H), 5.00 (t,
j = 7.2 Hz, CH, 1H), 3.73–3.62 (m, CH2, 2 H), 2.37 (s,
123

660
J IRAN CHEM SOC (2012) 9:655–660
7. S.G. Alvarez, S. Hasegawa, M. Hirano, S. Komiya, Tetrahedron
Lett. 39, 5209 (1998)
8. P. Laszlo, M.T. Montaufier, S.L. Randriamahefa, Tetrahedron
Lett. 31, 4867 (1990)
21. D. Bensa, T. Constantieux, J. Rodriguez, Synthesis 923 (2004)
22. R. Ghorbani-Vaghei, H. Jalili, Synthesis 1099 (2005)
23. R. Ghorbani-Vaghei, M.A. Zolfigol, M. Chegeny, H. Veisi, Tet-
rahedron Lett. 46, 4505 (2006)
9. D.Y. Kim, S.C. Huh, S.M. Kim, Tetrahedron Lett. 42, 6299
(2001)
24. R. Ghorbani-Vaghei, S. Akbari-Dadamahaleh, Tetrahedron Lett.
50, 1055 (2009)
10. M. Bandini, P.G. Cozzi, M. Giacomini, P. Melchiorre, S. Selva, J.
Org. Chem. 67, 3700 (2002)
25. R. Ghorbani-Vaghei, E. Shahbazee, J. Braz. Chem. Soc. 16, 647
(2005)
11. B. C. Ranu, S.S. Dey, S. Samanta, ARKIVOC 44 (2005)
12. M.M. Khodaei, I. Mohammadpoor-Baltork, H.R. Memarian, A.R.
Khosropour, K. Nikofar, P. Ghanbary, J. Heterocyclic Chem. 45,
1 (2008)
26. R. Ghorbani-Vaghei, M. Chegini, Tetrahedron Lett. 50, 1851
(2009)
27. R. Ghorbani-Vaghei, E. Shahbazee, H. Veisi, Mendeleev Com-
mun. 15, 207 (2005)
13. C. Chu, S. Gao, M.N. Sastry, C. Yao, Tetrahedron Lett. 46, 497
(2005)
14. M.M. Alam, R. Varala, S.R. Adapa, Tetrahedron Lett. 44, 5115
(2003)
15. A. T. Khan, S. Ghosh, L. H. Choudhury, Eur J. Org. Chem. 2226
(2006)
16. Z.H. Huang, J.P. Zou, W.Q. Jiang, Tetrahedron Lett. 47, 7965
(2006)
17. S.J. Ji, S.Y. Wang, Ultrason. Sonochem. 12, 339 (2005)
18. L.T. An, J.P. Zou, L.L. Zhang, Y. Zhang, Tetrahedron Lett. 48,
4297 (2007)
19. K. Tabatabaeian, M. Mamaghani, N.O. Mahmoodi, A. Khorshidi,
J. M. Catal. A. Chem. 270, 112 (2007)
20. W.Y. Chen, L. Shi, Catal. Commun. 9, 1079 (2008)
28. R. Ghorbani-Vaghei, H. Veisi, ARKIVOC 44 (2009)
29. R. Ghorbani-Vaghei, M. Amiri, N. Moshfeghifar, H. Veisi, S.
Akbari Dadamahaleh, J. Iran. Chem. Soc. 6, 754 (2009)
30. R. Ghorbani-Vaghei, H. Veisi, J. Braz. Chem. Soc. 21, 193
(2010)
31. R. Ghorbani-Vaghei, S.M. Malaekehpoor, J. Iran. Chem. Soc. 10,
957 (2010)
32. W. Li, X. F. Lin, J. Wang, G.L. Li, Y.G. Wang, Synlett. 2003
(2005)
33. ZhP Zhang, R. Yang, K. Lang, Tetrahedron Lett. 46, 3859 (2005)
34. L. Zhou, W. Zhou, L. Xu, L. Yang, P.Q. Zhao, ChG Xia, J. Mol.
Catal. A. Chem. 249, 129 (2006)
35. R. Tahir, K. Banert, A. Solhy, Sebti, J. Mol. Catal. A: Chem. 249,
39 (2006)
123