An Improved Procedure for Preparing
2-(2-Hetaryl)imidazolines and Their Analogs
A. A. Aleksandrov and M. M. El’chaninov
South-Russian State Technical University (Novocherkassk Polytechnic Institute), Novocherkassk, Rostov oblast, Russia
Received April 6, 2009
Abstract—Known procedures for preparing 2-R-imidazolines were analyzed. An improved procedure for
preparing a large series of 2-(2-hetaryl)imidazolines and their analogs was suggested. The biological activity of
noble metal salts of 2-(2'-furyl)- and 2-(2'-thienyl)imidazolines was evaluated.
ORGANIC SYNTHESIS AND INDUSTRIAL
ISSN 1070-4272, Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 12, pp. 2161–2165. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.A. Aleksandrov, M.M. El’chaninov, 2009, published in Zhurnal Prikladnoi Khimii, 2009, Vol. 82, No. 12, pp. 2019–2022.
Chemistry of imidazolines is among fields of hetero-
cyclic chemistry attracting increased researchers’
attention. Some of imidazoline derivatives exhibit high
physiological activity . For example, 2-
benzylimidazoline is an active vasodilator, and 2-(α-
naphthylmethyl)imidazoline, on the contrary, behaves
as a vasopressor. Some 2-substituted imidazolines
exhibit antihistamine activity .
Here we suggest an improved procedure for
preparing 2-R-imidazolines. Particular attention is
given to the preparation of 2-hetarylimidazolines, which
are potentially bioactive compounds.
Previously 2-(2-furyl)imidazoline I was syn-
thesized in ~30% yield by the reaction of ethyl pyro-
mucate with ethylenediamine (EDA) in the presence of
KU-2 cation exchanger . Despite large excess of
EDA, significant amounts of a by-product, N,N'-di(2-
furoyl)ethylenediamine, are always formed in this
reaction. This by-product is separated by vacuum
distillation. With the aim to increase the yield of I, we
examined a modification of this procedure, involving
refluxing of appropriate carboxylic acid, 100% EDA,
and EDA dihydrochloride in the presence of p-
toluenesulfonic acid in ethylene glycol .
We found that, in preparation of I by this
procedure, furan-2-carboxylic acid indergoes decarbo-
xylation to significant extent. With commercially
produced 50–70% aqueous EDA solutions taken
instead of 100% EDA, the temperature of the reaction
mixture and thus the extent of decarboxylation and
tarring can be decreased. Apparently, the first step of
the process is formation of N-furoyl-2-ethylene-
diamine. Then, in the course of slow distillation of
aqueous ethylene glycol, it undergoes cyclodehydra-
tion. The latter operation is particularly important,
because without distillation of water, e.g., in the course
of heating in aqueous-alcoholic solutions, imidazolines
are hydrolyzed back to monoacyl EDA derivatives .
By this procedure, along with 2-(2-furyl)imida-
zoline I, we prepared a series of other 2-substituted
imidazolines II–XIII [scheme (1)]. Their yields in
syntheses starting from 100% EDA and 50% aqueous
EDA are given in Table 1.
As can be seen, the use of 50% aqueous EDA
ensures, on the whole, higher yield of 2-R-imida-
R = 2-furyl (I), 2-thienyl (II), 2-selenienyl (III), phenyl
(IV), 2-pyridyl (V), 3-pyridyl (VI), 4-pyridyl (VII), methyl
(VIII), benzyl (IX), p-phenylene (X), 2,5-pyridinediyl (XI),
2,6-naphthylene (XII), and 4,4'-(C