Benzazoles 5*. synthesis and arylsulfonylation of 1-hydroxymethylbenzimidazole

Article abstract of DOI:10.1007/s10593-012-1015-1

1-Hydroxymethylbenzimidazole was synthesized by the reaction of benzimidazole with formaldehyde. Arylsulfonylation of the former in the presence of triethylamine occurred anomalously with deformylation to give 1-arylsulfonylbenzimidazoles in place of the

Full text of DOI:10.1007/s10593-012-1015-1

Chemistry of Heterocyclic Compounds, Vol. 48, No. 3, June, 2012 (Russian Original Vol. 48, No. 3, March, 2012)
BENZAZOLES
5*. SYNTHESIS AND ARYLSULFONYLATION
OF 1-HYDROXYMETHYLBENZIMIDAZOLE
K. B. Abdireimov1, N. S. Mukhamedov1**,
M. Zh. Aiymbetov1, and Kh. M. Shakhidoyatov1
1-Hydroxymethylbenzimidazole was synthesized by the reaction of benzimidazole with formaldehyde.
Arylsulfonylation of the former in the presence of triethylamine occurred anomalously with
deformylation to give 1-arylsulfonylbenzimidazoles in place of the expected 1-arylsulfonyloxymethyl-
benzimidazoles.
Keywords: 1-arylsulfonylbenzimidazoles, 1-hydroxymethylbenzimidazole, arylsulfonylation, hydroxy-
methylation, deformylation.
The increased interest in benzimidazole derivatives is explained by their high biological activity and a
broad spectrum of effects [2-7]. In this series, pharmacologically active substances were discovered [2-4] as
well as fungicides, herbicides, and plant growth regulators [5-7].
We have previously studied the interaction of 2-alkylbenzimidazoles with arylsulfonyl chlorides to give
1-arylsulfonylbenzimidazoles [8]. The present work is devoted to the synthesis and arylsulfonylation of
1-hydroxymethylbenzimidazole.
1-Hydroxymethylbenzimidazole (2) was synthesized by the reaction of benzimidazole (1) with
formaldehyde. The reaction of compound 2 with arylsulfonyl chlorides 3a-j in the presence of triethylamine
gave the 1-arylsulfonylbenzimidazoles 5a-j instead of the expected 1-arylsulfonyloxymethylbenzimidazoles
4a-j.
Compounds 5a-j may be formed by two routes (A, B). In route A, the starting compound 2 underwent
deformylation to give compound 1 which reacted with the arylsulfonyl chlorides 3a-j to produce compounds
5a-j. To test the possibility of this decomposition we have studied the behavior of compound 2 in the absence of
arylsulfonyl chlorides. However, in all cases, compound 2 was recovered unchanged. This shows that the
reaction of compound 2 with arylsulfonyl chlorides by route A does not occur and the reaction evidently goes
via route B.
_______
*For Communication 4, see [1]
**To whom correspondence should be addressed, e-mail: nasirxon@rambler.ru.
1S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, 77 Mirzo
Ulugbek Ave., Tashkent 100170, Uzbekistan.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, 488-491, March, 2012. Original
article submitted February 8, 2011. Revision submitted June 27, 2011.
458
0009-3122/12/4803-0458©2012 Springer Science+Business Media, Inc.

O
O
OH
Ar
S
Et3N
N
N
N
ArSO2Cl
3a–j
O
+
Route B
N
2
4a–j
Route А
– CH2O
– CH2O
O
CH2O
H
N
Ar
O
S
Et3N
N
N
3a–j
+
N
1
5a–j
[
3–5 a Ar = Ph, b Ar = 4-MeC6H4, c Ar = 4-MeOC6H4, d Ar = 4-(t-Bu)C6H4,
e Ar = 4-ClC6H4, f Ar = 3-O2NC6H4, g Ar = 4-MeCONHC6H4,
h Ar = 2,4-Me2C6H3, i Ar = 3,4-Me2C6H3, j Ar = 2,4,6-Me3C6H2
It should be noted that in the reaction of 3-hydroxymethylbenzoxazolin-2-ones with 3,4,5-trimethoxy-
benzoyl chloroanhydride, acylation occurs "normally", i.e., at the hydroxyl group [9]. Therefore it can be
proposed that in the case of compounds 4a-j a O→N rearrangement with simultaneous splitting off the formyl
group is possible. This anomalous behavior of compound 2 requires further investigation.
Compounds 5a-j were also prepared by counter synthesis from compound 1 and the arylsulfonyl
chlorides in the presence of triethylamine.
1
The structures of the synthesized compounds 5a-j were confirmed by IR, H NMR, and mass
spectroscopy and counter synthesis. The Table 1 contains the yields of compounds 5a-g,i,j obtained via method
B, their physicochemical properties, and literature data for these substances prepared by other methods
[8, 10-14].
TABLE 1. Physicochemical Characteristics of Compounds 5a-g,i,j,
synthesized by method B.
Com-
pound
Empirical
formula
Found, N %
Calculated, N %
——————
Mp*, °С
Yield, %
C13H10N2O2S
C14H12N2O2S
C14H12N2O3S
C17H18N2O2S
C13H9ClN2O2S
C13H9N3O4S
C15H13N3O3S
C15H14N2O2S
C16H16N2O2S
11.03
10.85
10.02
10.29
10.01
9.72
9.13
8.91
9.73
9.57
14.09
13.85
13.61
13.32
9.68
9.78
104-106 (105-106 [10-12])
86-88 (86-88 [8, 11])
92-94 (92-94 [8])
53
62
54
53
63
72
56
51
61
5a
5b
5c
5d
5e
5f
127-128 (127-128 [8])
126-128 (125-127 [8])
158-160 (159-160 [13, 14])
200-202 (196-198 [14])
115-117 (115-117 [8])
117-119 (120-122 [8])
5g
5i
8.98
9.33
5j
_______
* Recrystallization solvents: ethanol (compounds 5a-f,i,j), 40% aqueous
ethanol (compound 5g).
459

Thus, arylsulfonylation of 1-hydroxymethylbenzimidazole was accompanied by deformylation, leading
to the formation of 1-arylsulfonylbenzimidazoles in place of the expected 1-arylsulfonyloxymethyl-
benzimidazoles.
EXPERIMENTAL
IR spectra of nujol mulls were recorded with a Perkin-Elmer 2000 spectrometer. 1H NMR spectra were
recorded with a Unity +400 (400 MHz) spectrometer with TMS as internal standard. Mass spectra were
recorded with a Kratos MS 30 instrument with direct injection of the sample into the ion source (ionization
energy 70 eV). The progress of reactions and the purity of the synthesized compounds were monitored by TLC
on Silufol UV-254 plates with 10:1 benzene–acetone eluent and development with 1 g KMnO4 in 4 ml H2SO4
and 96 ml H2O.
1-Hydroxymethylbenzimidazole (2). 33% Formaldehyde (1.5 ml, 15 mmol) was added to a solution of
compound 1 (1.18 g, 10 mmol) in ethanol (20 ml) and heated at 75-85°C on a water bath for 2 h, the solvent was
1
evaporated, and the residue was recrystallized from benzene. Yield 1.15 g (78%); mp 144-146°C. H NMR
spectrum (CD3OD), δ, ppm (J, Hz): 7.99 (1H, s, H-2); 7.54 (2H, m H-4,5); 7.21 (2H, m, H-6,7), 4.61 (2H, s,
CH2), 4.23 (1H, br. s, OH). Found, %: C 65.06; H 5.58; N 19.12. C8H8N2O. Calculated, %: C 64.85; H 5.44;
N 18.91.
1-Arylsulfonylbenzimidazoles 5a-j (General Method). Synthesis from compound 2. A solution of
compound 2 (1.48 g, 10 mmol) and triethylamine (1.11 g, 11 mmol) in acetone (30 ml) was added dropwise to a
solution of arylsulfonyl chloride 3a-j (11 mmol) in acetone (20 ml). The reaction mixture was stirred at room
temperature for 4 h, the acetone was then evaporated and water (50 ml) was added to the residue. The obtained
precipitation of the product 5a-j was filtered off and recrystallized from the corresponding solvent (Table 1).
Compounds 5a-j were also obtained by an analogous method from benzimidazole (1) (1.18 g, 10 mmol)
[8].
Mixed samples of compounds 5a-j obtained from compounds 1 and 2 showed no depression of the
melting points.
1-(2',4'-Dimethylbenzenesulfonyl)benzimidazole (5h). Yield 1,86 g (65%); mp 66-68°C. IR spectrum,
ν, cm-1: 1365 (SO2 asym), 1168 (SO2 sym). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.35 (1H, s, H-2); 7.94
(1H, d, J4,5 = 8.1, H-4); 7.66 (1H, m, H-5); 7.46 (1H, m, H-6); 7.21 (2H, m, H-5',6'); 7.06 (1H, dd, J7,6 = 8.1,
J7,5 = 1.9, H-7); 6.92 (1H, s, H-3'); 2.33 (3H, s, 2'-CH3); 2.19 (3H, s, 4'-CH3). Mass spectrum, m/z (Irel, %): 286
[M]+ (61), 169 (100), 117 (43). Found, %: N 10.06. C15H14N2O2S. Calculated, %: N 9.78.
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