Acid and alkaline hydrolysis of substituted 5-aryl-1,2-oxazolidine-3,3- dicarbonitriles

Full text of DOI:10.1134/S1070428011120268

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 12, pp. 1908–1910. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.G. Pak, A.G. Tyrkov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 12, pp. 1870–1872.
SHORT
COMMUNICATIONS
Acid and Alkaline Hydrolysis
of Substituted 5-Aryl-1,2-oxazolidine-3,3-dicarbonitriles
I. G. Pak and A. G. Tyrkov
Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia
e-mail: tyrkov@rambler.ru
Received April 1, 2011
DOI: 10.1134/S1070428011120268
There are no published data on chemical trans-
formations of 2,5-substituted 1,2-oxazolidine-3,3-di-
carbonitriles. With a view to elucidate the direction of
hydrolysis of substituted 5-aryl-1,2-oxazolidine-3,3-di-
carbonitriles we examined the reaction of 2-(2-nitro-1-
phenylethoxy)-5-phenyl-1,2-oxazolidine-3,3-dicarbo-
nitrile (I) with dilute (1:1) hydrochloric acid. As
a result, we obtained cinnamic acid III and benzoic
acid (IV) which were formed, respectively, from the
isoxazolidine fragment and side chain of compound I.
It was reasonable to presume that substituted
4,5-dihydro-1,2-oxazole-3-carbonitriles V and IX and
the corresponding nitroethenes VI and X are formed as
intermediate products in the acid hydrolysis of
1,2-oxazoles I and II under severe conditions. In fact,
by heating compound V in dilute hydrochloric acid we
obtained cinnamic acid (III), while the hydrolysis of
nitroethene VI under similar conditions gave benzoic
acid (IV).
The reaction of compound I with an alcoholic
solution of alkali under mild conditions afforded
2-(2-hydroxy-2-phenylethyl)propane-1,3-dinitrile
potassium salt (XI), (1-ethoxy-2-nitroethyl)benzene
(XII), and (1-ethoxy-2,4-dinitrobutan-1,3-diyl)diben-
zene (XIII) (Scheme 2). The formation of compounds
XII and XIII suggests initial generation of interme-
diates A and B, followed by stabilization of the latter
via addition of ethanol molecule with formation of
ethoxy derivative XII. Intermediate A is likely to
undergo cleavage of the isoxazole ring at the N2–C3
bond to produce compound XI through carbanion C.
Presumably, the process involves both cleavage of
the isoxazolidine ring at the N2–C3 and O1–C5 bonds
and decomposition of the 2-nitro-1-phenylethoxy sub-
stituent. Our attempt to perform hydrolysis of the
cyano group in I under mild conditions (in acetic acid)
resulted in the formation of 5-phenyl-4,5-dihydro-1,2-
oxazole-3-carbonitrile 2-oxide (V) and 2-nitroethenyl-
benzene (VI). Analogous transformations occurred in
acid hydrolysis of 5-(4-methylphenyl)-2-[2-nitro-1-(4-
methylphenyl)ethoxy]-1,2-oxazolidine-3,3-dicarboni-
trile (II) (Scheme 1).
Scheme 1.
CN
CN
CN
O
C6H4R-4
NO2
AcOH, Δ
NO2
+
4-RC6H4
VI, X
HCl (dilute), Δ
N
N
4-RC6H4
4-RC6H4
O
O
O
I, II
V, IX
HCl (dilute), Δ
HCl (dilute), Δ
COOH
4-RC6H4COOH
IV, VIII
4-RC6H4
III, VII
I, III–VI, R = H; II, VII–X, R = Me.
1908

ACID AND ALKALINE HYDROLYSIS OF SUBSTITUTED 5-ARYL-1,2-OXAZOLIDINE-...
1909
Scheme 2.
CN
CN
O
KOH, EtOH
NO2
+
I
Ph
N
Ph
O
A
B
EtOH
CN
OEt
OEt Ph
OH
CN
K+
+
NO2
NO2
CN
O
Ph
Ph
Ph
CN
N
Ph
NO2
O
XI
C
XII
XIII
of concentrated hydrochloric acid, and 10 ml of water
was heated for 2 h under reflux. The mixture was
cooled, and the precipitate was filtered off. Yield of
cinnamic acid (III) 0.414 g (56%), mp 132°C [1];
yield of compound VII 0.470 g (58%), mp 198°C [2].
The filtrate was evaporated to isolate 0.122 g (20%) of
benzoic acid (IV), mp 122°C [3], or 0.150 g (22%) of
p-toluic acid (VIII), mp 178°C [4].
Hydrolysis of 5-aryl-1,2-oxazolidine-3,3-dicarbo-
nitriles I and II in acetic acid (general procedure).
A mixture of 5 mmol of compound I or II, 40 ml of
acetic acid, and 10 ml of water was heated under reflux
until nitrogen dioxide no longer evolved (~1 h). The
mixture was evaporated, and the residue was subjected
to chromatography using benzene (compounds V and
IX) or hexane (VI, X) as eluent.
5-Phenyl-4,5-dihydro-1,2-oxazole-3-carbonitrile
2-oxide (V). Yield 0.658 g (70%), mp 90°C (from
ethanol) [5].
2-Nitroethenylbenzene (VI). Yield 0.387 g (52%),
mp 58°C (from ethanol) [6].
5-(4-Methylphenyl)-4,5-dihydro-1,2-oxazole-
3-carbonitrile 2-oxide (IX). Yield 0.737 g (73%),
mp 76°C (from ethanol) [5].
Alkaline hydrolysis of isoxazole I under severe condi-
tions resulted in the formation of a tarry product which
was not identified.
Compounds III–X, XII, and XIII showed no de-
pression of the melting point on mixing with authentic
samples.
5-Aryl-1,2-oxazolidine-3,3-dicarbonitriles I and
II (general procedure). A solution of 5 mmol of
2,2-dinitromalononitrile in 10 ml of anhydrous diethyl
ether was cooled to 0±5°C, a solution of 10 mmol of
ethenylbenzene or 4-ethenyltoluene in diethyl ether
was added, and the mixture was kept for 10 days at
25°C. The mixture was evaporated, and the residue
was subjected to chromatography in a 10×500-mm
column charged with activated silica gel (100–400 μm)
using CHCl3 (compound I) or benzene (II) as eluent.
2-(2-Nitro-1-phenylethoxy)-5-phenyl-1,2-oxazoli-
dine-3,3-dicarbonitrile (I). Yield 0.464 g (25%),
mp 115°C. IR spectrum, ν, cm–1: 2245 (C≡N); 1550,
1380 (NO2); 1070–1030 (ONO). 1H NMR spectrum, δ,
ppm: 3.14 d (2H, CH2), 4.28 d (2H, CH2), 5.46 t (1H,
CH), 5.82 t (1H, CH), 7.53–7.62 m (10H, C6H5).
Found, %: C 62.46; H 4.22; N 15.18. C19H16N4O4. Cal-
culated, %: C 62.64; H 4.40; N 15.38.
1-Methyl-4-(2-nitroethenyl)benzene (X). Yield
0.489 g (60%), mp 97°C (from ethanol) [7].
5-(4-Methylphenyl)-2-[1-(4-methylphenyl)-2-
nitroethoxy]-1,2-oxazolidine-3,3-dicarbonitrile (II).
Yield 0.529 g (27%), mp 144°C. IR spectrum, ν, cm–1:
2245 (C≡N); 1550, 1380 (NO2); 1070–1030 (ONO).
1H NMR spectrum, δ, ppm: 2.31 s (3H, CH3), 3.10 d
(2H, CH2), 4.30 d (2H, CH2), 5.42 t (1H, CH), 5.80 t
(1H, CH), 7.15–7.53 m (8H, C6H4). Found, %:
C 64.11; H 4.91; N 14.08. C21H20N4O4. Calculated, %:
C 64.29; H 5.10; N 14.29.
Hydrolysis of 5-aryl-4,5-dihydro-1,2-oxazole-3-
carbonitrile 2-oxides V and IX in hydrochloric acid
(general procedure). A mixture of 3 mmol of com-
pound V or IX, 10 ml of concentrated hydrochloric
acid, and 5 ml of water was heated for 1.5 h under
reflux. The mixture was cooled, and the precipitate
was filtered off. Yield of III 0.198 g (45%), mp 132°C
[1]; yield of VII 0.230 g (48%), mp 198°C [2].
Hydrolysis of 5-aryl-1,2-oxazolidine-3,3-dicarbo-
nitriles I and II in hydrochloric acid (general proce-
dure). A mixture of 5 mmol of compound I or II, 30 ml
Hydrolysis of (2-nitroethenyl)benzenes VI and X
in hydrochloric acid (general procedure). A mixture
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 12 2011

PAK, TYRKOV
1910
of 3 mmol of compound VI or X, 10 ml of concentrat-
ed hydrochloric acid, and 5 ml of water was heated for
2 h under reflux. After cooling, 0.135 g (41%) of IV,
mp 122°C [3], or 0.181 g (43%) of VIII, mp 178°C
[4], was isolated.
The IR spectra were recorded in KBr on an IKS-29
spectrometer. The H NMR spectra were obtained on
1
a Tesla BS-487C spectrometer (80 MHz) from solu-
tions in D2O using hexamethyldisiloxane as internal
reference. The progress of reactions and the purity of
products were monitored by TLC on Silufol UV-254
plates using acetone–hexane (2:3) as eluent; develop-
ment with iodine vapor.
Alkaline hydrolysis of 2-(2-nitro-1-phenyl-
ethoxy)-5-phenyl-1,2-oxazolidine-3,3-dicarbonitrile
(I). A solution of 5 mmol of potassium hydroxide in
20 ml of ethanol was slowly added under stirring to
5 mmol of compound I. The mixture was heated for
3 h on a water bath, and the precipitate was filtered off.
Yield of compound XI 0.717 g (64%), decomposition
point 194–196°C (from methanol). IR spectrum, ν,
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1
cm–1: 3545 (OH), 2230 (C≡N). H NMR spectrum, δ,
ppm: 3.52 d (2H, CH2), 5.03 d (1H, OH), 5.28 q (1H,
CH), 7.51 m (5H, C6H5). Found, %: C 58.74; H 3.82;
N 12.34. C11H9N2KO. Calculated, %: C 58.93; H 4.02;
N 12.50.
The filtrate was evaporated, the residue was diluted
with diethyl ether, and the mixture was acidified with
dilute hydrochloric acid to pH 4 (litmus). The organic
layer was separated, dried over Na2SO4, and evaporat-
ed, and the residue was subjected to chromatographic
separation. Elution with carbon tetrachloride gave
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subsequent elution with chloroform afforded 0.086 g
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 12 2011