Reduction of substituted 5-(nitromethyl)-3-phenyl-1,2,4-oxadiazoles

Full text of DOI:10.1023/B:RUJO.0000034958.53324.bc

Russian Journal of Organic Chemistry, Vol. 40, No. 2, 2004, pp. 286-287. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 2, 2004,
pp. 314-315.
Original Russian Text Copyright Ó 2004 by Tyrkov, Usova.
SHORT
COMMUNICATIONS
Reduction of Substituted
5-(Nitromethyl)- 3-phenyl-1,2,4-oxadiazoles
A. G. Tyrkov and A. N. Usova
Astrakhan’ State University, Astrakhan’, 414056 Russia
e-mail: tyrkov@rambler.ru
Received March 27, 2003
Reduction of 3,5-substituted 1,2,4-oxadiazoles are
poorly studied in the literature The catalytic hydrogena-
tion of 5-amino-3-phenyl-1,2,4-oxadiazole on Pd/C is
known to involve the heterocycle rupture at the N–O
bond to give N-carbamoylbenzamidine [1], and the re-
duction of 3,5-diphenyl-1,2,4-oxadiazole with LiAlH4 pro-
ceeds with the cleavage of the azole ring at the C–O
bond affording N-benzylbenzimidoxime [2]. The hydro-
genation of more complex 1,2,4-oxadiazole derivatives is
not mentioned in the literature.
the substituents in position 5 of the heterocycle resulting
in N-glycylbenzamidine IV hydrochloride. Similarly oc-
curred the catalytic hydrogenation of nitroalkane III, but
the trinitromethyl fragment suffered elimination, and the
final product was N-formylbenzamidine V. The reduction
of 1,2,4-oxadiazoles I–III on Pd catalyst was carried out
at atmospheric pressure and 25–30oC in 2–2.5% solution
of hydrochloric acid. The weight of the catalyst was 5%
with respect to the substrate for hydrogenation.
2
Ethyl (nitro)(3-phenyl-1,2,4-oxadiazol-5-yl)-
(chloro)acetate I and its analogs, ethyl (dinitro)(3-phe-
nyl-1,2,4-oxadiazol-5-yl)acetate II and 5-trinitromethyl-
3-phenyl-1,2,4-oxadiazole III contain polyfunctional sub-
stituents in position 5 of the heterocycle and are interest-
ing objects for the study of these transformations. With
the goal to investigate further how the nature of substi-
tuted 5-(nitromethyl)-1,2,4-oxadiazoles affects the direc-
tion of their reduction process we studied the hydrogena-
tion of nitroalkanes I–III effected by various reducing
agents, namely, Pd/C and LiAlH4. We have selected for
the study compounds I–III for the problem is urgent of
developing new synthetic routes involving nitro group re-
duction and ester function hydrolysis and leading to
arylamidine derivatives containing an N-aminomalonic
moiety. The possibility to carry out a process of this sort
was demonstrated formerly [3]. The aminomalonic moi-
ety appears in the structure of a number of pharmaceuti-
cals that are chemical precursors of noradrenaline and
other mediators [4].
1&5
+ ꢀ3Gꢁ&ꢂꢀ+&Oꢂꢀ+ 2
3K&
5
& 12
1 5
1+
,9ꢁꢀ9
2
1
12+
/L$O+ ꢀ(W 2
3K&
3K
B
1+5
9,ꢁꢀ9,,
,ꢀꢀꢀ,,,
R1 = CO2Et, R2 = Cl (I), NO2 (II), R1 = R2 = NO2 (III), R3 =
CH2NH3Cl (IV), H (V), (CH2)2NH2 (VI), Me (VII).
In contrast to catalytic hydrogenation the nitroalkanes
I–III reduction in the presence of LiAlH4 occurred with
heterocycle cleavage at the C–O bond and gave N-(2-
aminoethyl)benzimidoxime VI at the use of compounds I
and II or N-methylbenzimidoxime VII from compound
III. The reduction of the nitromethyl substituents occurred
in the same way as at the catalytic hydrogenation of 1,2,4-
oxadiazoles I–III on Pd catalyst.
We established that hydrogenation of nitroalkanes I
and II on palladium catalyst involved an opening of the
oxadiazole ring at the N–O bond and partial reduction of
Catalytic hydrogenation of 1,2,4-oxadiazoles I–
III on Pd catalyst. Into a flask for hydrogenation was
1070-4280/04/4002-0286Ó2004 MAIK “Nauka/Interperiodica”

REDUCTION OF SUBSTITUTED 5-(NITROMETHYL)- 3-PHENYL-1,2,4-OXADIAZOLES
287
charged 3.2 g of activated carbon of OUB grade, 0.16 g
of PdCl2, 2.7 ml of concn. HCl, and 40 ml of water. The
catalyst was hydrogenated till complete saturation with
hydrogen. Then 5 mmol of compound I-III [5–7] was
charged, and the reduction was carried out at 25–30oC
till consumed amount of hydrogen reached the value
calculated according to the number of nitro groups. The
catalyst was filtered off and washed with several portions
of warm water by decanting. The total volume of filtrate
(100 ml) was evaporated at reduced pressure, and the
residues after reaction with compounds I and II were
recrystallized from ethanol. The residue after reaction
with compound III was subjected to chromatography on
50 ml of anhydrous ethyl ether was added at stirring a
solution of 5 mmol of nitroalkane I-III in 20 ml of ether
with a rate sufficient to keep the reaction mixture at weak
boiling. The reaction mixture was stirred for 4 h at 25oC,
then cooled to 5oC, and a minimal amount of ice water
was added till the hydrogen liberation stopped. The pre-
cipitate was filtered off and washed with 15 ml of ether.
The combined ether solution was dried with NaOH and
evaporated at reduced pressure. The residue was sub-
jected to chromatography, as described above. Eluent for
compounds VI and VII chloroform
N-(2-Aminoethyl)benzimidoxime (VI). Yield 70%,
–1
mp 76–78oC. IR spectrum, n, cm : 3540 (OH), 3450–
a column 250´10 mm packed with activated silica gel of
the grade Silicagel 100/400 m, eluent for compound V
ethanol.
3300 (NH2). 1H NMR spectrum, d, ppm: 7.76 m (5H,
H arom), 6.55 br.s (1H, NH), 3.56–3.52 m (4H, CH2),
1.62 br.s (2H, NH2). Found, %: C 60.05; H 6.97; N 23.13.
C9H13N3O. Calculated, %: C 60.34; H 7.26; N 23.46.
2-Amino-N-[amino(phenyl)methylene]acetamide
hydrochloride (IV). Yield 74%, mp 175–178oC. IR spec-
trum, n, cm : 3360–3250 (NH2), 3200–2600 (NH3+),
–1
N-Methylbenzimidoxime (VII). Yield 72%, mp 46–
–1
1720–1710 (C=O). Found, %: C 50.37; H 5.43; N 19.42.
C9H11N3O3×HCl. Calculated, %: C 50.59; H 5.62;
N 19.67.
48oC. IR spectrum, n, cm : 3550 (OH), 3340 (NH).
1H NMR spectrum, d, ppm: 7.75 m (5H, H arom),
6.50 br.s (1H, NH), 3.12 d (3H, CH3). Found, %: C 63.82;
H 6.45; N 18.48. C8H10N2O. Calculated, %: C 64.00;
H 6.67; N 18.67.
N-Formylbenzamidine (V) . Yield 67%, mp 112–
–1
113oC. IR spectrum, n, cm : 3360–3250 (NH2), 1710
1
(C=O). H NMR spectrum, d, ppm: 10.15 s (1H, CH),
IR spectra were recorded on spectrophotometer IKS-
29 from pellets with KBr (compounds IV and V) and
from solutions in chloroform (compounds VI and VII).
1H NMR spectra were registered on spectrometer Tesla
BS-487C (80 MHz) in acetone-d6 , internal reference
HMDS.
7.74 m (5H, H arom), 6.82 br.s (2H, NH2). Found, %:
C 64.61; H 5.24; N 18.73. C8H8N2O. Calculated, %:
C 64.86; H 5.41; N 18.92.
Reduction of 1,2,4-oxadiazoles I–III with lithium
aluminum hydride. To a solution of 1.8 g of LiAlH4 in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004