Asian Journal of Chemistry; Vol. 27, No. 1 (2015), 98-100
ASIAN JOURNAL OF CHEMISTRY
Synthesis of 1-Alkyl-2-chloromethylbenzimidazole Under Green Conditions
*
S. SRINIVAS RAO , CH. VENKATA RAMANA REDDY and P.K. DUBEY
Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad College of Engineering Kukatpally, Hyderabad -500 085, India
*Corresponding author: E-mail: seenu604@gmail.com
Received: 20 November 2013;
Accepted: 27 January 2014;
Published online: 26 December 2014;
AJC-16514
A green approach for the synthesis of 1-alkyl-2-chloromethylbenzimidazoles (3) (R1 = CH3, C2H5, CH2Ph) under, different conditions has
been developed from 2-chloromethylbenzimidazole (2) by reaction with an alkylating agent (i.e. DMS, DES, PhCH2Cl) by physical
grinding or by using green solvent like PEG-600 or by using micro-wave irradiation technique.
Keywords: Green synthesis, Grinding, Microwave, N-alkyl-2-chloromethylbenzimidazole, Benzimidazole.
irradiation were carried out by using the commercially
available CEM Discover Microwave Reactor.
INTRODUCTION
Benzimidazoles are very useful intermediates/subunits for
the development of molecules of pharmaceutical or biological
interest1. Benzimidazoles are an important class of bioactive
molecules in the field of drugs and pharmaceuticals2.
2-Mercaptobenzimidazole derivatives having substitution
either at the nitrogen or sulfur are reported to exhibit a broad
spectrum of biological activity3-8.
Verma et al.9 reported that N-methyl-o-phenylenediamine
on treatment with chloro acetic acid in aq. HCl under reflux for
1 h gave 1-methyl-2-chloromethylbenzimidazole in 80-82 %
yield. Flosi et al.10 described that 1-methyl-1H-benzimidazole-
2-carbaldehyde on treatment with diisobutylaluminium
hydride in THF for 1 h followed by chlorination with SOCl2 in
dichloromethane gave 1-methyl-2-chloromethylbenzimdazole.
In continuation of our earlier studies on alkylation of 2-acetyl-
benzimidazole11 and thiolation of N-methyl-2-chlorobenzi-
midazole12, we now wish to report on alkylation of 2-chloro-
methylbenzimidazole using green methods.
Synthesis of 1-alkyl-2-chloromethylbenzimidazoles (3) (R1
= CH3, C2H5, CH2Ph) from 2-chloromethylbenzimidazole (2)
Physical grinding method:A mixture of 2 (10 mM), alky-
lating agent (10 mM) and K2CO3 (1.38 g, 10 mM) was ground
together for about 10-15 min in a mortar with a pestle at room
temperature to obtain a homogeneous mixture. The completion
of the reaction was monitored by TLC on silica gel-G plates
using samples of the starting material and authentic target
compounds as references. The mixture was then treated with
ice-cold water (about 30-40 mL). The separated solid was
filtered, washed with water (2 × 10 mL) and dried to obtain
crude 3a-c. Recrystallization of the crude product from ethyl
acetate gave pure 3a-c. IR, 1H NMR and LC-MS spectra for
the compounds 3a-c were found to be in agreement with the
structures assigned to them. Yields are shown in Table-1.
In PEG-600: A mixture of 2 (10 mM), alkylating agent
(10 mM) and PEG-600 (20 mL) was heated on a steam-bath
at 100 °C for 3 h. At the end of this period, the mixture was
cooled to room temperature and poured into ice-cold water
(about 50 mL). The separated solid was filtered, washed with
water (2 × 10 mL) and dried. The crude products were purified
by recrystallization from ethyl acetate to obtain pure 3a-c,
identical with the same products obtained above. Yields are
shown in Table-1.
EXPERIMENTAL
Melting points were determined in open capillaries in
sulfuric acid bath and are uncorrected. IR spectra were
1
recorded with Jasca FT-IR 5300. H NMR and spectra were
recorded in CDCl3/DMSO usingVarian 400-MHz instrument.
Mass spectra were recorded on an Agilent LC-MS instrument
giving only M+ values in Q + 1 mode. Thin-layer chromato-
graphy (TLC) analyses were carried out on glass plates coated
with silica gel GF-254 and visualization was achieved using
iodine vapours or UV lamp. Experiments under microwave
Under microwave condition: A mixture of 2 (10 mM)
and alkylating agent (10 mM) was taken in a 10 mL CEM-
reaction tube sealed by rubber stopper and subjected to
microwave irradiation for 2 min in a commercial microwave