Benzazoles. 3*. Synthesis and arylsulfonylation of 2-substituted benzimidazoles

Article abstract of DOI:10.1007/s10593-010-0606-y

2-Alkylbenzimidazoles have been obtained from o-nitroaniline and aliphatic carboxylic acids by reductive cyclization. Interaction of the former with arenesulfonyl chlorides led to the synthesis of 2-alkyl-1- arylsulfonylbenzimidazoles, the yield of which depended on the structure of the substituent in position 2.

Full text of DOI:10.1007/s10593-010-0606-y

Chemistry of Heterocyclic Compounds, Vol. 46, No. 8, 2010
BENZAZOLES. 3*. SYNTHESIS AND
ARYLSULFONYLATION OF 2-SUBSTITUTED
BENZIMIDAZOLES
K. B. Abdireimov1, N. S. Mukhamedov1**, M. Zh. Aiymbetov1,
and Kh. M. Shakhidoyatov1
2-Alkylbenzimidazoles have been obtained from o-nitroaniline and aliphatic carboxylic acids by
reductive cyclization. Interaction of the former with arenesulfonyl chlorides led to the synthesis of
2-alkyl-1-arylsulfonylbenzimidazoles, the yield of which depended on the structure of the substituent in
position 2.
Keywords: 2-alkyl-1-arylsulfonylbenzimidazoles, 2-alkylbenzimidazoles, arylsulfonylation, reductive
cyclization.
The high biological activity and broad spectrum of action of benzimidazole derivatives [2-8] has caused
increased interest in them. Among 2-substituted benzimidazoles are found substances possessing antitumor,
hypotensive, spasmolytic, neuroleptic, and antibacterial action [2-6], and also herbicidal, fungicidal, and growth
stimulating activity [7, 8].
Communications have appeared recently on the synthesis of 2-cycloalkyl(aralkyl)benzimidazoles and
sulfonylation of the latter with methane- and benzenesulfonyl chlorides [9]. Similar reactions for 2-alkylbenz-
imidazoles have not been studied. Continuing our investigations on the synthesis and conversion of benzazoles
[1], in this work we have synthesized 2-alkylbenzimidazoles 2a-e and have studied their interaction with arene
sulfonyl chlorides.
2-Alkylbenzimidazoles were obtained previously from o-phenylenediamine and the appropriate acids [10].
Compounds 2a-e were synthesized by us from o-nitroaniline (1) and aliphatic acids by reductive
cyclization using iron powder and hydrochloric acid. The interaction of products 2a-e with arene sulfonyl
chlorides in the presence of triethylamine at room temperature led to 2-alkyl-1-arylsulfonyl benzimidazoles 3a-e
and 8a-e (Table 1).
It should be noted that with the lengthening of the substituent R the yields of compounds 3a-e and 8a-e
were reduced. This is probably explained by the action of steric factors. Substitution in Ar did not have a
significant influence on the course of the reaction.
_______
* For Communication 2, see [1].
** To whom correspondence should be addressed, e-mail: nasirxon@rambler.ru.
1
S. Yu. Yunusov Institute of Chemistry of Plant Substances, Academy of Sciences of the Republic of
Uzbekistan, Tashkent 100170, Uzbekistan.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1165-1172, August, 2010.
Original article submitted January 26, 2010.
0009-3122/10/4608-0941©2010 Springer Science+Business Media, Inc.
941

4
7
NO2
NH2
Fe
ArSO2Cl
Et3N
N
N
+
RCOOH
1
HCl
N
R
N
H
R
SO2Ar
3a–e – 8a–e
1
2a–e
2–8 a R = H, b R = Me, c R = Et, d R = Pr, e R = Bu; 3ae Ar = 4-MeC6H4; 4ae Ar = 4-MeOC6H4;
5ae Ar = 4-ClC6H4; 6ae Ar = 4-t-BuC6H4; 7ae Ar = 3,4-Me2C6H3; 8ae Ar = 2,4,6-Me3C6H2
TABLE 1. Physicochemical Characteristics of the Synthesized Compounds
3a-e – 8a-e
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °C*
Yield, %
N
3
1
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
7a
7b
7c
2
4
5
C14H12N2O2S
C15H14N2O2S
C16H16N2O2S
C17H18N2O2S
C18H20N2O2S
C14H12N2O3S
C15H14N2O3S
C16H16N2O3S
C17H18N2O3S
C18H20N2O3S
C14H11ClN2O2S
C15H13ClN2O2S
C16H15ClN2O2S
C17H17ClN2O2S
C18H19ClN2O2S
C17H18N2O2S
C18H20N2O2S
C19H22N2O2S
C20H24N2O2S
C21H26N2O2S
C15H14N2O2S
C16H16N2O2S
C17H18N2O2S
10.58
10.29
10.01
9.79
9.03
9.33
9.26
8.91
8.17
8.53
10.11
9.72
8.83
9.24
9.12
8.86
8.64
8.48
8.51
8.13
9.26
9.58
8.83
9.12
8.38
8.75
8.13
8.38
7.78
8.04
9.25
8.91
8.17
8.53
8.51
8.18
8.09
7.86
7.67
7.56
10.02
9.79
9.12
9.33
9.32
8.91
86-88
86
77
68
54
32
97
85
76
67
62
96
79
68
61
56
76
70
63
58
52
89
80
75
122-124
148-150
102-104
118-120
92-94
132-134
138-140
84-86
86-88
125-127
152-153
172-174
140-142
154-156
127-128
132-134
137-138
111-113
115-116
115-117
82-84
73-75
942

TABLE 1 (continued)
1
2
3
4
5
7d
C18H20N2O2S
C19H22N2O2S
8.26
8.53
8.42
8.18
8.98
9.33
9.17
8.91
8.81
8.53
7.86
8.18
8.19
7.86
86-88
64
58
72
64
58
53
47
7e
98-100
120-122
121-122
126-127
96-98
8a
8b
C16H16N2O2S
C17H18N2O2S
8c
8d
8e
C18H20N2O2S
C19H20N2O2S
C20H20N2O2S
66-68
_______
* Solvents for recrystallization: ethanol (compounds 3a-e, 4a-e, 5a,b,d,e,
6e, 7a,c-e, 8a-e), aqueous ethanol (compound 5c), benzene (compounds
6a-d), petroleum ether (compound 7b).
The composition and structure of the synthesized compounds 3a-e and 8a-e were confirmed by the
results of elemental analysis, data of IR, mass, and 1H NMR spectra.
There were characteristic absorption bands in the IR spectra of compounds 3-8 for the asymmetric and
symmetric stretching vibrations of the SO2 group in the 1100-1400 cm-1 region (Table 2).
Peaks were observed in the mass spectra of compounds 3a-e to 8a-e for molecular ions and fragments
confirming completely the structures proposed. The direction of fragmentation of the molecular ions of
compounds 3a-e to 8a-e depended on the nature of the substituent R and did not depend on the character of the
substitution in Ar. The mass spectra of compounds 3a-c to 8a-c showed a single type of fragmentation with
cleavage of the ArSO2-Het bond, leading to [M-ArSO2]+ and [M-Het]+ fragments with the former possessing
maximal intensity. In the mass spectra of compounds 3d,e to 8d,e (R = Pr, Bu) cleavage of the substituent
R occurs first and then ArSO2.
3a–c – 8a–c
.
+
+
+
N
N
3d,e – 8d,e
N
N
R
N
R
N
R
SO2Ar
SO2Ar
SO2Ar
+
M
H
N
+
+
+
N
N
N
N
N
R
m/z 116
SO2Ar
The 1H NMR spectra of compounds 3a-e to 8a-e (Table 2) contain the following signals characteristic of
the benzimidazole fragment: signals of the H-4 and H-7 protons as two doublets (in the 7.55-8.01 ppm region),
multiplet signals of the H-5 and H-6 protons (at 7.22-8.81 ppm), and a low field singlet for the H-2 proton
(8.30-8.61 ppm). There were also signals in the spectra for the HAr protons (6.85-7.45), and for HR protons, and
for alkyl substituents in Ar (0.78-3.74 ppm).
943

944

945

EXPERIMENTAL
The IR spectra of nujol suspensions of compounds were taken on a Perkin-Elmer 2000 Fourier
1
spectrometer, and the H NMR spectra on a Unity 400+ (400 MHz) spectrometer, internal standard was TMS.
The mass spectra were recorded on a Kratos MS-30 instrument with direct insertion of sample into the ion
source (ionization energy 70 eV). A check on the progress of reactions and the homogeneity of the synthesized
compounds was effected by TLC on Silufol UV-254 plates in the solvent system benzene–acetone, 10:1, the
developer was a solution of KMnO4 (1 g) in H2SO4 (4 ml) and H2O (96 ml).
2-Alkylbenzimidazoles 2a-e (General Method). A mixture of compound 1 (1.38 g, 10 mmol), the
appropriate carboxylic acid (60 mmol), iron powder (1.68 g, 30 mmol) and 32% HCl (10 ml) was heated to
70oC. After the end of the vigorous evolution of hydrogen the mixture was maintained at the same temperature
for 1 h, and then at 90-100oC for 2 h. The reaction mixture was cooled, 20% NaOH solution was added to pH
9-10, the precipitated solid was filtered off, and washed with water until neutral reaction. Alcohol (20 ml) was
added to the washed solid, the mixture was boiled for 1 h, and filtered without cooling. Alcohol (~10 ml) was
distilled from the filtrate, the residue was diluted with three volumes of water, the resulting product 2 was
filtered off, and recrystallized from the appropriate solvent. The melting points of the synthesized compounds
2a-e, and of samples of them obtained by cyclization of o-phenylenediamine with carboxylic acids [10],
coincided.
2-Alkyl-1-arylsulfonylbenzimidazoles 3a-e to 8a-e (General Method). A solution of compound 2
(10 mmol) and triethylamine (1.11 g, 11 mmol) in acetone (30 ml) was added dropwise to a solution of the
appropriate arene sulfonyl chloride (11 mmol) in acetone (20 ml). The reaction mixture was stirred at room
temperature for 4 h, the acetone was then distilled, and water (50 ml) was added to the residue. The solid
product obtained of 3a-e to 8a-e was filtered off and recrystallized from the appropriate solvent.
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