202
H. Maruoka, F. Okabe, K. Yamagata
Vol 44
122.1, 131.2, 157.5 (C aryl), 164.6 (C-2); ms: m/z 217 [M+H]+.
Anal. Calcd. for C12H12N2O2 (MW 216.2): C, 66.65; H, 5.59; N,
12.95. Found: C, 66.65; H, 5.59; N, 12.93.
with primary arylamines (aniline, 4-methylaniline, 4-
methoxyaniline, 4-chloroaniline and 4-bromoaniline) in
refluxing ethanol gave the corresponding 1-aryl-2-imino-3-
pyrrolidinecarbonitriles 5a-e in fair to good yields.
Probably, these reaction take place through the malono-
nitrile derivatives C. The 1H nmr spectra of 5a-e in deuterio-
chloroform indicate that 5a-e consist of a tautomeric
mixture of the imine D and the enamine E forms.
1-(4-Chlorophenyl)-2-oxo-3-pyrrolidinecarbonitrile (3d).
This compound was obtained as colorless needles (2.51 g, 57%),
mp 120-121° (acetone-petroleum ether); ir (potassium bromide):
1
ꢀ 2250, (CN), 1701 cm-1 (C=O); H nmr (deuteriochloroform):
ꢁ, ppm 2.45-2.55 (m, 1H, 4-H), 2.60-2.67 (m, 1H, 4-H), 3.74 (t,
J = 9.2 Hz, 1H, 3-H), 3.85-3.95 (m, 2H, 5-H), 7.30-7.40 (m, 2H,
aryl H), 7.50-7.60 (m, 2H, aryl H); 13C nmr (deuteriochloro-
form): ꢁ, ppm 23.5 (C-4), 35.1 (C-3), 46.7 (C-5), 116.4 (CN),
121.3, 129.2, 131.1, 136.7 (C aryl), 164.9 (C-2); ms: m/z 221
[M+H]+. Anal. Calcd. for C11H9ClN2O (MW 220.7): C, 59.88;
H, 4.11; N, 12.70. Found: C, 59.96; H, 4.15; N, 12.66.
However, the reaction of 2 with 2-nitroaniline, 3-
nitroaniline or 4-nitroaniline failed, and 2 was recovered
unchanged.
EXPERIMENTAL
1-(4-Bromophenyl)-2-oxo-3-pyrrolidinecarbonitrile (3e).
This compound was obtained as colorless scales (2.99 g, 56%),
mp 133-134° (acetone-petroleum ether); ir (potassium bromide):
ꢀ 2251 (CN), 1700 cm-1 (C=O); 1H nmr (deuteriochloroform): ꢁ,
ppm 2.45-2.55 (m, 1H, 4-H), 2.60-2.67 (m, 1H, 4-H), 3.73 (t, J =
9.2 Hz, 1H, 3-H), 3.85-3.95 (m, 2H, 5-H), 7.40-7.50 (m, 4H,
aryl H); 13C nmr (deuteriochloroform): ꢁ, ppm 23.4 (C-4), 35.1
(C-3), 46.6 (C-5), 116.4 (CN), 118.8, 121.6, 132.1, 137.2 (C
aryl), 164.9 (C-2); ms: m/z 265 [M+H]+. Anal. Calcd. for
C11H9BrN2O (MW 265.1): C, 49.84; H, 3.42; N, 10.57. Found:
C, 49.87; H, 3.40; N, 10.53.
General Procedure for the Preparation of 5. A solution of
2 (0.92 g, 10 mmoles) and the arylamine (20 mmoles) in ethanol
(5 ml) was refluxed for 2 hours (in the case of aniline, 4-
methylaniline and 4-methoxyaniline) or 4 hours (4-chloroaniline
and 4-bromoaniline). After removal of the solvent in vacuo, the
residue was purified by column chromatography on silica gel
with dichloromethane-acetone (4:1) as the eluent to give 5.
All melting points are uncorrected. Ir spectra were recorded
1
on a JASCO FT/IR-230 spectrometer. The H nmr and 13C nmr
spectra were measured with a JEOL JNM-A500 instrument
(500.00 MHz for 1H, 125.65 MHz for 13C) with TMS as internal
standard. 13C signal assignments were confirmed by the DEPT
techniques. FAB mass spectra were taken with a JEOL JMS-
HX100 instrument at 70 eV. Elemental analyses were performed
using a YANACO MT-6 elemental analyzer.
General Procedure for the Preparation of 3. A mixture of
methyl 1-cyanocyclopropanecarboxylate (2.50 g 20 mmoles)
and the arylamine (20 mmoles) was heated at 140° for 4 hours
(in the case of aniline, 4-methylaniline and 4-methoxyaniline) or
8 hours (4-chloroaniline and 4-bromoaniline). After cooling, the
reaction mixture was purified by column chromatography on
silica gel with dichloromethane as the eluent to give 3.
2-Oxo-1-phenyl-3-pyrrolidinecarbonitrile (3a). This
compound was obtained as colorless columns (2.76 g, 74%), mp
121-122° (acetone-petroleum ether); ir (potassium bromide):
2-Imino-1-phenyl-3-pyrrolidinecarbonitrile (5a).
compound was obtained as pale yellow prisms (1.07 g, 58%),
This
1
ꢀ 2250 (CN), 1695 cm-1(C=O); H nmr (deuteriochloroform): ꢁ,
mp 91-92° (acetone-petroleum ether); ir (potassium bromide): ꢀ
1
3435, 3347, 3200 (NH), 2149 cm-1 (CN); H nmr (deuterio-
ppm 2.45-2.52 (m, 1H, 4-H), 2.58-2.65 (m, 1H, 4-H), 3.72 (t, J =
9.2 Hz, 1H, 3-H), 3.88-3.96 (m, 2H, 5-H), 7.20-7.60 (m, 5H,
aryl H); 13C nmr (deuteriochloroform): ꢁ, ppm 23.6 (C-4), 35.1
(C-3), 46.8 (C-5), 116.7 (CN), 120.2, 125.7, 129.1, 138.1 (C
aryl), 164.8 (C-2); ms: m/z 187 [M+H]+. Anal. Calcd. for
C11H10N2O (MW 186.2): C, 70.95; H, 5.41; N, 15.04. Found: C,
71.07; H, 5.57; N, 14.94.
1-(4-Methylphenyl)-2-oxo-3-pyrrolidinecarbonitrile (3b).
This compound was obtained as colorless columns (2.45 g, 61%),
m.p. 135-136° (acetone-petroleum ether); ir (potassium bromide):
ꢀ 2249 (CN), 1700 cm-1 (C=O); 1H nmr (DMSO-d6): ꢁ, ppm 2.29
(s, 3H, CH3), 2.30-2.40 (m, 1H, 4-H), 2.50-2.60 (m, 1H, 4-H),
3.80-3.85 (m, 2H, 5-H), 4.30 (dd, J = 9.2, 10.4 Hz, 1H, 3-H), 7.20-
7.22 (m, 2H, aryl H), 7.50-7.52 (m, 2H, aryl H); 13C nmr (DMSO-
d6): ꢁ, ppm 20.3 (CH3), 22.7 (C-4), 34.6 (C-3), 46.5 (C-5), 118.1
(CN), 120.0, 129.1, 134.1, 136.1 (C aryl), 165.6 (C-2); ms: m/z
201 [M+H]+. Anal. Calcd. for C12H12N2O (MW 200.3): C, 71.98;
H, 6.04; N, 13.99. Found: C, 72.00; H, 6.05; N, 14.00.ꢀ
chloroform): ꢁ, ppm 2.35-2.60 (m, 1H, 4-H), 2.70-2.80 (m, 1H,
4-H), 3.70-3.90 (m, 2.5H, 3-H, 5-H), 4.57 (br. s, 1H, NH2), 7.10-
7.20 (m, 2H, aryl H), 7.30-7.50 (m, 3.5H, NH, aryl H); ms: m/z
186 [M+H]+. Anal. Calcd. for C11H11N3 (MW 185.2): C, 71.33;
H, 5.99; N, 22.69. Found: C, 71.35; H, 6.06; N, 22.71.
2-Imino-1-(4-methylphenyl)-3-pyrrolidinecarbonitrile (5b).
This compound was obtained as colorless prisms (1.02 g, 51%),
mp 129-130° (acetone-petroleum ether); ir (potassium bromide):
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ꢀ 3423, 3334, 3240 (NH), 2156 cm-1 (CN); H nmr (deuterio-
chloroform): ꢁ, ppm 2.34 (s, 3H, CH3), 2.40-2.80 (m, 2H, 4-H),
3.75-3.90 (m, 2.6H, 3-H, 5-H), 4.42 (br. s, 0.8H, NH2), 7.00-
7.40 (m, 4.6H, NH, aryl H); ms: m/z 200 [M+H]+. Anal. Calcd.
for C12H13N3 (MW 199.3): C, 72.33; H, 6.58; N, 21.09. Found:
C, 72.52; H, 6.60; N, 21.02.
2-Imino-1-(4-methoxyphenyl)-3-pyrrolidinecarbonitrile (5c).
This compound was obtained as pale yellow columns (1.32 g,
61%), mp 149-151° (acetone-diethyl ether); ir (potassium
1
bromide): ꢀ 3441, 3275, 3210, 3165 (NH), 2158 cm-1 (CN); H
1-(4-Methoxyphenyl)-2-oxo-3-pyrrolidinecarbonitrile (3c).
This compound was obtained as colorless columns (2.80 g,
65%), mp 135-136° (acetone-petroleum ether); ir (potassium
nmr (deuteriochloroform): ꢁ, ppm 2.35-2.80 (m, 2H, 4-H), 3.81
(s, 3H, CH3), 3.70-3.90 (m, 2.5H, 3-H, 5-H), 4.48 (br. s, 1H,
NH2), 6.90-7.35 (m, 4.5H, NH, aryl H); ms: m/z 216 [M+H]+.
Anal. Calcd. for C12H13N3O (MW 215.3): C, 66.96; H, 6.09; N,
19.52. Found: C, 66.94; H, 6.12; N, 19.57.
1-(4-Chlorophenyl)-2-imino-3-pyrrolidinecarbonitrile (5d).
This compound was obtained as pale yellow prisms (0.60 g,
27%), mp 127-129° (acetone-petroleum ether); ir (potassium
bromide): ꢀ 2252 (CN), 1686 cm-1 (C=O); H nmr (deuterio-
1
chloroform): ꢁ, ppm 2.40-2.50 (m, 1H, 4-H), 2.55-2.65 (m, 1H,
4-H), 3.70 (t, J = 9.2 Hz, 1H, 3-H), 3.80 (s, 3H, OCH3), 3.83-
3.93 (m, 2H, 5-H), 6.88-6.93ꢀ(m, 2H, aryl H), 7.43-7.47 (m, 2H,
aryl H); 13C nmr (deuteriochloroform): ꢁ, ppm 23.6 (C-4), 34.9
(C-3), 47.2 (C-5), 55.5 (O-CH3), 114.3 (C aryl), 116.8 (CN),