Ammonium sulphate-magnesium selective reduction of N-2-nitrophenylimidates: Synthesis of 2-substituted benzimidazoles

Article abstract of DOI:10.1081/SCC-120002122

Various N-2-nitrophenylimidates were selectively reduced by (NH₄)₂SO₄-Mg to the non-isolated N-2-aminophenylimidates which cyclise to the corresponding 2-substituted benzimidazoles.

Full text of DOI:10.1081/SCC-120002122

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AMMONIUM SULPHATE- MAGNESIUM SELECTIVE
REDUCTION OF N-2-NITROPHENYLIMIDATES:
SYNTHESIS OF 2-SUBSTITUTED BENZIMIDAZOLES
Abdallah Harizi a & Hédi Zantour b
a Département de Chimie , Faculté des Sciences de Monastir , Monastir, 5019, Tunisia
b Département de Chimie , Faculté des Sciences de Tunis , Campus Universitaire, Tunis,
1060, Tunisia
Published online: 16 Aug 2006.
To cite this article: Abdallah Harizi & Hédi Zantour (2002) AMMONIUM SULPHATE- MAGNESIUM SELECTIVE REDUCTION OF
N-2-NITROPHENYLIMIDATES: SYNTHESIS OF 2-SUBSTITUTED BENZIMIDAZOLES, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:3, 387-392
To link to this article: http://dx.doi.org/10.1081/SCC-120002122
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SYNTHETIC COMMUNICATIONS, 32(3), 387–392 (2002)
AMMONIUM SULPHATE-
MAGNESIUM SELECTIVE
REDUCTION OF N-2-
NITROPHENYLIMIDATES:
SYNTHESIS OF 2-SUBSTITUTED
BENZIMIDAZOLES
Abdallah Harizi1, and Hedi Zantour2
*
1Departement de Chimie, Faculte des Sciences
de Monastir, 5019, Monastir, Tunisia
2Departement de Chimie, Faculte des Sciences
de Tunis, Campus Universitaire, 1060, Tunis, Tunisia
ABSTRACT
Various N-2-nitrophenylimidates were selectively reduced
by (NH4)2SO4-Mg to the non-isolated N-2-aminophenyl-
imidates which cyclise to the corresponding 2-substituted
benzimidazoles.
INTRODUCTION
Benzimidazoles derivatives are an important class of heterocyclic com-
pounds which have biological activities1–3 and interesting pharmacological
*Corresponding author. E-mail: aharizifr@yahoo.fr
387
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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HARIZI AND ZANTOUR
properties.4,5 In general, 2-substituted benzimidazoles depicted in Scheme 1
were prepared by the condensation of o-phenylenediamine with carbonyl-
containing compounds, such as carboxylic acids, esters or amides.6-8
Scheme 1.
As a part of our continuing studies on N-substituted imidates,9–12
we report in the present investigation the synthesis of some 2-substituted
benzimidazoles, in a single step and under very mild conditions, by using
N-2-nitrophenylimidates as starting materials.
RESULTS AND DISCUSSION
Treatment of N-2-nitrophenylimidates 1a–h with the reducing system
(NH4)2SO4-Mg described by Prajapati and Al.,13 using methanol and water
as solvent and heating at 60ꢀC during 0.5 h gives respectively benzimidazoles
2a–h in good yield (table). The formation of compounds 2 proceeds
Table. Reduction of N-2-nitrophenylimidates by (NH4)2SO4-Mg and Formation of
Benzimidazoles 2
Yield
(%)
M.P.
(ꢀC)
Reported
(M.P.)14
Product
R
X
2a
2b
2c
2d
2e
2f
CH3
C2H5
Ph
H
H
H
92
88
168–170
177–179
265–267
169–171
178–180
266–269
85
–10876106
H
H
108–110
CH3
C2H5
Ph
CH3
CH3
CH3
CH3
86198–200
280–301
82
85
78
216–218
231–233
121–122
218–220
232–234
119–121
2g
2h
H

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SELECTIVE REDUCTION OF N-2-NITROPHENYLIMIDATES
389
presumably by selective reduction of the functional group -NO2 and forma-
tion of the non-isolated intermediary N-2-aminophenylimidates which
undergo cyclization (Scheme 2).
Scheme 2.
The structures of compounds 2a–h have been unambiguously charac-
terized on the basis of their IR, NMR (1H, 13C) and mass spectra.
The IR spectra show the characteristic bands of NH, C¼N and C¼C
1
aromatic, the H and 13C NMR spectra display the characteristic signals of
protons and carbons of all the substituents (aromatics, R and X), their
spectral data are presented in the experimental part. It is noteworthy that
the EI-MS spectra of the compounds 2 record the existence of the molecular
ion peaks as the base peaks indicating that the heterocycle skeletons are
stable under the EI-MS conditions.
In conclusion, these results demonstrated a versatile and selective
reducing system for N-2-nitrophenylimidates; the N-2-aminophenylimidates
were not isolated and the reaction afforded directly the corresponding
2-substituted benzimidazoles 2 in good yield.
EXPERIMENTAL
The uncorrected melting points were determined by a Buchi 510 appa-
ratus. IR spectra were recorded on a Perkin-Elmer 681 and band positions
were reported in wave numbers (cmÀ1) (KBr pellet). NMR spectra of
compounds 2 (1H at 300 MHz (CDCl3) and 13C at 75 MHz (CDCl3)) were
carried out on a VARIAN unity spectrometer using tetramethylsilane as the

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HARIZI AND ZANTOUR
internal standard. Mass spectra were recorded on a HP micromass 5890A
instrument.
Synthesis of N-2-Nitrophenylimidates 1a–h: The N-2-nitrophenylimi-
dates 1 were obtained according to the literature16,17 by the following pro-
cedure: A solution of 2-nitroaniline (1.38 g, 10 mmol) in triethylorthoacetate
(30 mL) was refluxed until TLC (ethyl acetate : hexane : 1 : 1) indicated that
the starting material was converted. Excess of orthoacetate was removed
in vacuo, and the resultant nearly pure 1a obtained on more than 80% was
used without further purification.
Synthesis of 2-Substituted Benzimidazoles 2a–h: General procedure: A
solution of the N-2-nitrophenylimidate 1a (5.12 g, 20 mmol) was added to a
mixture of magnesium (2.19 g, 120 mmol) and ammonium sulphate (26.40 g,
200 mmol dissolved in 6ml of water) in methanol (50 mL). The reaction
mixture was stirred at 60ꢀC for about 30 min and then quenched by addition
of water and ether. The product was extracted with ether (3 Â 50 mL),
washed with water and dried over Na2SO4. After evaporation of the solvent
the residual oily material was chromatographed on a silica gel 60 (Fluka)
(ether : ethylacetate : 70 : 30) to yield 2-substituted benzimidazoles 2a as a
solid recrystallized from ethanol.
Spectroscopic data (IR: n (cmÀ1), 1H-NMR: d (ppm), J (Hz),
13C-NMR: d (ppm), MS: (m/z (%)) of benzimidazoles 2a–h are given here:
1
2a: IR: 3360 (NH), 1630 (C¼N), 1580 (C¼C); H-NMR 3.0 (s, 3H),
7.4–7.8 (m, 4H), 9.6(s, 1H, NH); 13C-NMR 149.5 (C1), 136.8 (C2), 131.6
(C7), 18.9 (C8), 114.5–126.4 (other C. arom.); MS: 132 (Mþ, 100), 131 (79),
104 (12), 133 (12), 77 (8).
1
2b: IR: 3350 (NH), 1635 (C¼N), 1560 (C¼C); H-NMR: 1.1 (t, 3H,
J ¼ 7.5), 3.1 (q, 2H, J ¼ 7.5), 7.3–7.9 (m, 4H), 9.0 (s, 1H, NH); 13C-NMR:
149.3 (C1), 137.4 (C2), 130.2 (C7), 20.0 (C9), 54.5 (C8), 115.5–124.5 (other
C. arom.); MS: 146(M þ, 100), 145 (95), 147 (10), 77 (6), 56 (10).
1
2c: IR: 3370 (NH), 1640 (C¼N), 1560 (C¼C); H-NMR: 7.2–8.1 (m,
9H), 9.5 (s, 1H, NH); 13C-NMR: 149.7 (C1), 136.8 (C2), 131.6 (C7), 118.8–
128.2 (other C. arom.); MS: 194 (Mþ, 100), 193 (92), 166 (9), 77 (8), 104 (12).

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SELECTIVE REDUCTION OF N-2-NITROPHENYLIMIDATES
391
1
2d: IR: 3350 (NH), 1640 (C¼N), 1550 (C¼C); H-NMR: 6.4 (s, 1H),
7.3–7.7 (m, 4H), 8.5 (s, 1H, NH); 13C-NMR: 150.6(C1), 136.8 (C2), 131.6
(C7), 119.2–127.0 (other C. arom.); MS: 118 (Mþ, 100), 117 (85), 77 (12),
104 (6).
1
2e: IR: 3365 (NH), 1635 (C¼N), 1560 (C¼C); H-NMR: 2.4 (s, 3H),
3.0 (s, 3H), 7.3–7.9 (m, 3H), 10.2 (s, 1H, NH); 13C-NMR: 150.1 (C1), 137.7
(C2), 129.6(C7), 20.2 (C8), 13.8 (C14), 112.5–121.7 (other C. arom.); MS:
146(M þ, 92), 145 (100), 77 (18), 104 (15), 51 (16).
1
2f: IR: 3360 (NH), 1630 (C¼N), 1550 (C¼C); H-NMR 1.1 (t, 3H,
J ¼ 7.2), 3.2 (q, 2H, J ¼ 7.2), 2.5 (s, 3H), 7.2–8.0 (m, 3H), 9.2 (s, 1H, NH);
13C-NMR: 149.8 (C1), 136.8 (2), 128.8 (C7), 19.6 (C8), 57.0 (C9), 14.5 (C14),
120.0–128.5 (other C. arom.); MS: 160 (Mþ, 100), 159 (90), 104 (12), 77 (15).
1
2g: IR: 3340 (NH), 1640 (C¼N), 1560 (C¼C); H-NMR: 2.4 (s, 3H),
7.1–8.0 (m, 8H), 8.5 (s, 1H, NH); 13C-NMR: 150.5 (C1), 135.8 (C2), 130.2
(C7), 13.0 (C14), 118.8–128.2 (other C. arom.); MS: 208 (Mþ, 100), 207 (77),
209 (18), 104 (22), 77 (20).
1
2h: IR: 3355 (NH), 1640 (C¼N), 1550 (C¼C); H-NMR: 2.4 (s, 3H,
6.5 (s, 1H), 7.2–7.7 (m, 3H), 9.0 (s, 1H, NH); 13C-NMR: 150.4 (C1), 136.6
(C2), 130.2 (C7), 13.5 (C14), 122.5–126.0 (other C. arom.); MS: 132
(Mþ, 100), 131 (83), 77 (18), 133 (12), 77 (8).
REFERENCES
1. Joshi, K.; Jain, R.; Dandia, A.; Sharma, K. J. Fluorine Chem.
1992, 56, 1.
2. Parmar, S.S.; Misra, R.S.; Chaudhari, A.; Gupta, T.K. J. Pharm. Sci.
1972, 61, 1322.
3. Antonini, I.; Martelli, S.J. J. Med. Chem. 1988, 31, 260.
4. Kaliszan, R.; Milczarska, B.; Lega, B.; Szefer, P.; Janowiec, M. Pol. J.
Pharmacol. Pharm. 1978, 30(4), 585; Chem. Abstr. 1979, 90, 197398y.
5. Winn, M.; Kyncl, J. U.S. 4.093. 726; Chem. Abstr. 1978, 99, 197600n.
6. Philips, M.A.; J. Chem. Soc. 1928, 2393.
7. Hein, D.W.; Alheim, R.S.; Leavitt, J.J. J. Am. Chem. Soc. 1957, 79, 427.
8. Alcalde, E.; Dinares, I.; Perez-Garcia, L.; Roca, T.; Synthesis 1992,
4, 395.
9. Hajjem, B.; Chihi, A.; Baccar, B. Synth. Commun. 1992, 28, 133.
10. Harizi, A.; Hajjem, B.; Baccar, B. Revue Roumaine de Chimie 1998,
43, 35.
11. Dridi, K.; El Efrit, M.L.; Baccar, B.; Zantour, H. Synth. Commun.
1999, 29(11), 2026.

ORDER
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392
HARIZI AND ZANTOUR
12. Harizi, A.; Hajjem, B.; Zantour, H.; Baccar, B. J. Soc. Chim. Tunisie
1995, 10, 683; Chem. Abstr. 1996, 124, 289482v.
13. Prajapathi, D.; Borah, H.N.; Sandhu, J.S.; Ghosh, A.C. Synth.
Commun. 1995, 25(24), 4025.
14. The products were identified by comparison of M.P. and spectral data
with the literature (15).
15. Pretsch, E.; Cherc, T.; Seibel, J.; Simon, W. Tables of Spectral Data for
Structure Determination of Organic Compound. 13C NMR, 1H NMR,
IR, MS, UV/Vis, (Springer-Verlag, Berlin, 1976).
16. Younes, M.I.; Metwally, S.A.M.; Atta, A.H. Synthesis 1990, 704.
17. Gatta, F.; Giudice, M.R.D.; Borioni, A. J. Het. Chem. 1993, 30(1), 11.
Received in the USA March 19, 2001

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