SYNTHESIS, PHYSICOCHEMICAL AND PHARMACOLOGICAL PROPERTIES
477
reaction (reaction with unsaturated compounds). This
specific behavior of paraform is apparently due to the
higher accessibility of the methylene group in the
ylidene derivative III for the carbanion formed from
the second dianilide molecule. We studied the effect
of the reaction medium, base catalyst, temperature,
and reaction duration on the rate of the corresponding
reaction. Sufficient yields were obtained in reaction
carried out in DMF solution. The presence of base
catalysts did not affect significantly the reaction rate.
The yield was not increased at higher temperature
because of tarring, but at low temperature yields
were reduced.
1H NMR spectra were registered on Varian WXR-
400 instrument in DMSO-d6 + CCl4 at operating
frequency 100 MHz, chemical shifts were presented
in the
scale from TMS as internal reference.
N, N , N , N -substituted tetraamides of
1,1,3,3-propanetetracarboxylic (IV XIV). General
procedure. (a) In 70 ml of anhydrous methanol was
dissolved 0.46 g (2 mmol) of metal sodium. To the
solution was added 2 mmol of symmetrical malonic
acid diamide, and the mixture was heated for 1 h.
Then to the reaction mixture was added several
crystals of phenolphthalein and 5 ml of dichloro-
methane. The reaction mixture was heated at reflux
till the solution became colorless (38 h). On cooling
the excess dichloromethane was distilled off, the re-
action mixture was poured into water acidified to
pH 5 with hydrochloric acid. The separated pre-
cipitate was filtered off and recrystallized from a
mixture of 2-propanol and DMF. Melting points and
1H NMR spectra of compounds synthesized are listed
in Tables 1, 2.
The mixed sample of compounds prepared by
procedures a and b melted without depression of the
melting point.
Sufficiently high yields of target products obtained
by procedure b (Table 1) show its advantages and
promising features for the synthesis of potential
medicines. The structures, composition, and purity
of compounds synthesized were confirmed by spectral
methods (Table 2) and elemental analyses.
(b) To a solution of 2 mmol of symmetrical
malonic acid diamide in 10 ml of DMF was added
0.06 g (2 mmol) of paraform, and the mixture was
heated at reflux for 18 h, the reaction mixture was
poured into water acidified to pH 5 with hydrochloric
acid. The separated precipitate was filtered off and re-
crystallized from a mixture of 2-propanol and DMF.
IR spectra of all compounds obtained contain a
band of stretching vibrations belonging to carbonyl
group (amide-I).
1H NMR spectra of compounds synthesized
contain a general set of proton signals: The singlet in
the region 9.29 9.80 ppm corresponds to the amide
group proton of the anilide moiety, the multiplet at
6.75 7.85 ppm belongs to aromatic protons (com-
pounds V XIV), the triplet at 4.20 4.45 ppm cor-
responds to the free methylene group, and the triplet
at 3.00 3.35 ppm arises because of the presence of
methine group proton (Table 2).
REFERENCES
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Amides of 1.1..3-propanetetracarboxylic acid
obtained were subjected to primary pharmacological
screening with respect to anticonvulsant activity. It
was established that almost all compounds synthesiz-
ed possessed a pronounced anticonvulsant activity
combined with low toxicity. The anticonvulsant
activity of the compounds was compared with that of
the drugs most often used in medical practice to stop
the convulsions, namely, with Phenobarbital and
Diphenin. All compounds prevented convulsions
induced by Corazol and electroshock. The pharmaco-
logical activity was found to depend on the structure
of the respective molecule.
6. Georgyants, V.A., Rakhimova, M.V., and Gladchen-
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EXPERIMENTAL
IR spectra of compounds obtained were recorded
on spectrometer Specord M-80 from samples pelletiz-
ed with KBr, concentration of compound studied 1%.
9. Lewis, D.E., Organic Chemistry. A Modern Perspec-
tive, 1996, p. 678.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 4 2003