Russian Journal of Applied Chemistry, 2007, Vol. 80, No. 12, pp. 2165
Pleiades Publishing, Ltd., 2007.
Original Russian Text ©
S.A. Malin, B.M. Laskin, A.S. Malin, 2007, published in Khimicheskaya Promyshlennost’, 2007, Vol. 84, No. 7, pp. 335
TECHNOLOGY OF ORGANIC
AND INORGANIC SUBSTANCES
α-Bromocarboxylic Acids with Hydrazine
S. A. Malin, B. M. Laskin and A. S. Malin
Russian Scientific center “Applied Chemistry,” St. Petersburg, Russia
Received March 13, 2007
Abstract—Nucleofilic reaction of a series of α-bromocarboxylic acids with hydrazine and dimethylhydrazine is
studied. High reactivity of α-bromocarboxylic acids is revealed and a series of α-hydrazinoarboxylic acids and
N-(1-carboxyalkyl)-N,N-dimethylhydrazinium bromides are synthesized.
α-Bromocarboxylic acids are known as parent
compounds for the synthesis of potentially biologically
active compounds, α-hydrazino- and α-dimethyl-
hydrazinocarboxylic acids, the analogs of aminoacids.
These latter compounds show antiviral and antitumor
activity and can serve as a basis for producing antibiotics,
peptidomimetics and related substances [1−3].
Methods for the synthesis of α-hydrazinocarboxylic
acids have not been sufficiently studied and the known
data are mutually very contradicting in respect both
conditions of carrying out the process and product yields
[4−6]. Therefore we performed search of appropriate
methods for the synthesis of α-hydrazinocarboxylic acids
and study of main regularities of the process.
As the model targeted compounds we choose the
following α-bromocarboxylic acids: α-bromopropanoic
(Ia), α-bromobutyric (Ib), α-bromo-isovaleric (Ic) and
α-bromophenylacetic (Id). These α-bromoacids were
involved to the reaction of nucleophilic substitution with
hydrazine and dimethylhydrazine according to the
We studied influence of the reagents ratio, parameters
of duration and temperature and solvent (medium) nature
on the reaction proceeding and results. We found that
reaction of compounds Ia–d with hydrazine proceeds
smoothly enough at carrying out the process in the med-
ium of aqueous ethanol at the molar ratio I : hydrazine =
1: 4–6, temperature 70–80ºC and reaction dura-tion 6–8
h with high yield (50–70%) of compounds IIa–d.
Reaction conditions of IIa–d are listed in Table 1.
The most smooth process occurs with 40–60%
hydrazine hydrate which provides necessary solvation
of removing anion in the process of nucleophilic
Isolation of α-hydrazinocarboxylic acids was carried
out by concentrating the reaction solution (by 40 –50%)
under vacuum followed by diluting with water and
filtrating the product. The crystals formed were filtered
off and recrystallized from 40% ethanol (α-hydrazino-
propanoic acid or hydrazoalanine), from isopropyl
alcohol (α-hydrazinobutyric acid), water (α-hydrazino-
isovaleric acid) or ethyl acetate (α-hydrazinophenyl-
acetic acid or hydrazinophenylalanine). The α-hy-
drazinocarboxylic acids obtained were characterized by
means of elemental analysus, IR and
IR and NMR spectroscopy data (Table 2) and
elemental analyses (Table 3) confirmed structure and
composition of the obtained compounds.
The high reactivity of the bromine atom in α-bromo-
carboxylic acids in the reactions of nucleophilic sub-
where R is Me (a), Et (b), i-Pr (c) and Ph (d).