Hydroxymethylation with formaldehyde of substituted 3-(4-methoxyphenyl)-5-nitromethyl-1,2,4-oxadiazoles

Full text of DOI:10.1023/A:1020986517798

Russian Journal of Organic Chemistry, Vol. 38, No. 8, 2002, pp. 1220 1221. From Zhurnal Organicheskoi Khimii, Vol. 38, No. 8, 2002,
pp. 1271 1272.
Original English Text Copyright
2002 by Tyrkov.
SHORT
COMMUNICATIONS
Hydroxymethylation with Formaldehyde of Substituted
3-(4-Methoxyphenyl)-5-nitromethyl-1,2,4-oxadiazoles
A. G. Tyrkov
Astrakhan State Pedagogical University, Astrakhan, 414056 Russia
Received December 20, 2000
Halopolynitromethanes and tetranitromethane in
reaction with formaldehyde undergo substitution of
one or two functional groups by a hydroxymethyl
function [1, 2]. However no published data exist
describing reaction between formaldehyde and ana-
logous derivatives of 1,2,4-oxadiazoles. We carried
out reaction of formaldehyde with a series of sub-
stituted
3-(4-methoxyphenyl)-5-nitromethyl-1,2,4-
oxadiazoles and obtained as a result various hydr-
oxymethylation products of oxadizoles V and VI. The
R = NO2, R = CO2Et (I, V); R = R = NO2 (II); R = NO2, R = Cl (III); R = CO2Et, R = Cl (IV).
reactions occur more readily than with halonitro-
methanes presumably because of higher acceptor
quality of the 1,2,4-oxadiazole ring.
formaldehyde along Henri reaction [4] to furnish
alcohols V, VI. The direction of hydroxymethylation
is governed presumably by the electrophilicity of the
substituent in the 5 position of the oxadiazole.
Hydroxymethylation of ester I or trinitroalkane II
proceeds under mild conditions and is completed by
elimination of the ethoxycarbonyl or nitro groups
yielding compound V. Dinitrochloroalkane III and
ester IV do not react with formaldehyde under mild
conditions. The reaction occurs at heating, with a
loss of substituents in 5 position of the heterocycle,
and provides as a result hydroxymethyloxadiazole VI.
The nature of products V, VI suggests that these
processes follow the mechanism assumed for form-
aldehyde reaction with polynitromethanes [3]. In the
course of electrophilic attack of nitroalkanes on the
carbonyl oxygen of formaldehyde compounds I IV
are reduced to the corresponding intermediates A and
B. The latter undergo condensation with excess
1-Hydroxy-2-[3-(4-methoxyphenyl)-1,2,4-oxadi-
azol-5-yl]-2,2-dinitroethane (V). To 6 mmol of com-
pound I or II [5] was added 40 ml of formalin, and
the mixture was stirred 300 h at 25 C. Then the
products were extracted into ether (2 10 ml), the
extract was evaporated, the residue was subjected to
chromatography on a column (250 10 mm) packed
with activated Silicagel 100/400 , eluent benzene.
1
Yield 53%, mp 107 108 C. IR spectrum, , cm :
1
3560 (OH); 1570, 1330 (NO2). H NMR spectrum, ,
ppm: 7.80 6.82 m (C6H4); 5.54 t (OH); 4.86 d
(CH2); 3.81 c (CH3O). Found, %: C 42.47; H 3.14;
N 17.95. C11H10N4O7. Calculated, %: C 42.58;
H 3.23; N 18.07.
1070-4280/02/3808-1220$27.00 2002 MAIK Nauka/Interperiodica

HYDROXYMETHYLATION WITH FORMALDEHYDE
5-Hydroxymethyl-3-(4-methoxyphenyl)-1,2,4- REFERENCES
1221
oxadiazole (VI). To 6 mmol of compound III or IV
[5] was added 40 ml of formalin, and the mixture was
boiled for 15 min, cooled, and extracted with ether
(2 10 ml), the solvent was evaporated, and the
residue was subjected to chromatography under
similar conditions (eluent ethyl ether). Yield 67%,
1. Zendin, L. and Schechter, H., J. Am. Chem. Soc.,
1957, vol. 79, no. 16, pp. 4708 4716.
2. Fridman, A.L., Ivshina, T.N., and Ivshin, V.P., Zh.
Org. Khim., 1969, vol. 39, no. 5, p. 1181.
3. Fridman, A.L., Ivshina, T.N., and Ivshin, V.P.,
Zh. Org. Khim., 1968, vol. 5, no. 6, pp. 980 985.
4. Shvekhgeimer, G.A., Pyatakov, N.F., and Novi-
1
mp 131 C. IR spectrum, , cm : 3580 (OH).
1H NMR spectrum, , ppm: 7.74 6.80 m (C6H4);
5.51 t (OH); 4.68 d (CH2); 3.80 s (CH3O). Found,
%: C 58.14; H 4.78; N 13.47. C10H10N2O3. Cal-
culated, %: C 58.25; H 4.85; N 13.59.
kov, S.S., Usp. Khim.,
1959, vol. 28, no. 4,
pp. 484 518.
5. Ladyzhnikova, T.D., Altukhov, K.V., Solov,ev, N.A.,
Zh. Org. Khim., 1986, vol. 22, no. 12, pp. 2618 2619.
6. Tyrkov, A.G. and Resnyanskii, V.V., Izv. Vuzov, Ser.
Khim. i Khim. Tekhnol., 1994, vol. 37, no. 10 12,
pp. 131 132.
IR spectra were recorded on spectrophotometer
IKS-29 from solutions in chloroform. 1H NMR
spectra were registered on spectrometer Tesla
BS-487C (80 MHz) in acetone-d6, internal reference
HMDS.
7. Tyrkov, A.G. and Suikhanova, B.G., Zh. Org. Khim.,
1999, vol. 35, no. 9, pp. 1330 1331.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 8 2002