BROMINATION OF N,N,-SUBSTITUTED MALONODIAMIDES
1081
labile halogen atom in agreement with the published
data [7].
shifts were presented in
measured on Specord M-80 instrument from KBr
pellets, substance concentration 1%.
scale. IR spectra were
The success of the synthesis can be preliminary
checked by a positive Beilstein,s test and higher
melting point of the product than that of the initial
compound (Table 1).
N,N -Substituted bromomalonodiamides IIa i
(general procedure). To a solution of 0.01 mol of
N,N,-substituted malonodiamide Ia g, methylmalono-
diamide Ih, or bromomalonodiamide Ii in 20 m of
glacial acetic acid was added dropwise while stirring
0.52 ml (0.01 mol) of bromine. The reaction was
started by irradiation with light. After stirring for
1 h the reaction mixture which became colorless was
poured into 100 ml of cold water. The separated
precipitate was filtered off, dried, and recrystallized
from ethanol.
The structures were proved by elemental analyses
and spectral methods.
1
The analysis of H NMR spectra of compounds
synthesized showed that the common signal of proton
from the substituted methylene group in the spectra
of compounds IIa g was shifted downfield as
compared with the spectra of the initial compounds
(Table 2). The displacement originates from the
introduction into the molecule of electronegative
bromine atom which induces paramagnetic shift of the
neighboring protons [8]. The signals from aromatic
and aliphatic substituents in amide groups and from
the methyl attached to the methylene group of the acid
skeleton in IIh compound remain the same as in the
initial compounds [2, 4].
Dibromomalonic acid N,N -dibenzylamide (IIi).
To a solution of 2.8 g (0.01 mol) of malonic acid
,
N,N -dibenzylamide (Ib) in 20 ml of glacial acetic
acid was added dropwise while stirring 1.04 ml
(0.02 mol) of bromine. The reaction was started by
irradiation with light. After stirring for 1 h the reac-
tion mixture that became colorless was poured into
100 ml of cold water. The separated precipitate was
filtered off, dried, and recrystallized from ethanol.
Yield 3.4 g (77%), mp 198 200 C (from water).
Yields, melting points, Rf values, and elemental
analyses for compounds IIa i are listed in Table 1,
In the IR spectra of compounds IIa i the absorp-
tion bands of stretching vibrations of the methylene
group shift to larger wave numbers because of the
halogen atom, and the maxima of these bands appear
1
1
IR and H NMR spectra in Table 2.
in the region over 3000 cm (Table 2) evidencing the
presence of bromine atom in the molecule [9].
REFERENCES
Although the target of our work was the synthesis
of semiproducts for preparation of biologically active
compounds, we tested also their proper pharmaco-
logical effect.
1. Georgiyants, V.A., Fiziologichno aktivni rechovini,
1999, no. 1 (27), pp. 29 32
2. Bezuglii, P.O., Ukrainets, I.V., Georgiyants, V.A.,
Triskach, V.I., Sergienko, M.G., Savchenko, V.M.,
and Turov, O.V., Farmats. Zh., 1990, no. 4,
pp. 35 38.
3. Bezuglyi, P.A., Georgiyants, V.A., Rakhimova, M.V.,
and Kostochka, V.A., Farmakom, 1998, no. 4,
pp. 45 46.
4. Georgiyants, V.A., Rakhimova, M.V., and Gladchen-
ko, O.M., Visnik farmatsii, 1998, no. 1 (17), pp. 11 14.
5. Georgiyants, V.A., Farmats. Zh., 2001, no. 4,
pp. 66 69.
The pharmacological activity of compounds syn-
thesized was investigated by V. N. Savchenko in
Karazin Kharkov National University.
The presence of bromine in the molecules of
organic compounds is known to induce appearance of
sedative properties. Therefore the pharmacological
screening was directed to testing the effect of com-
pounds synthesized on the central nervous system.
The results of the pharmacological screening
revealed weak protective properties of the compounds
obtained against convulsions caused by corazole. As
was expected, all the compounds provide synergistic
soporific effect with phenobarbital.
6. Bezuglyi, P.A.., Georgiyants, V.A., and Rakhimo-
va, M.V., Zh. Org. Khim., 1999, vol. 35, no. 3,
pp. 416 418.
7. Arct, B., Kossovska, B., Lorenz, M., Prelicz, D., and
Sedzik-Hibner, D., J. Env. Sci. Health, 1983, vol. 18,
no. 4 5, pp. 559 568.
8. Kornilov, M.Yu. and Kutrov, G.P., Yadernyi magnit-
nyi rezonans v khimii (NMR in Chemistry), Kiev:
Vishcha shkola, 1985.
9. Brown, D.W., Floyd, A.J., and Sainsbury, M., Organic
Spectroscopy, New York: J. Wiley 1988.
EXPERIMENTAL
1H NMR spectra were registered on spectrometer
Bruker WP-100 SY at operating frequency 100 MHz,
solvent DMSO-d6, internal reference TMS, chemical
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 8 2002