Cyanoethylation of pyrazoles under conditions of phase-transfer catalysis and hydrogenation of the cyanoethylation products

Article abstract of DOI:10.1134/S1070363206070218

Cyanoethylation of pyrazoles with acrylonitrile was studied under conditions of phase-transfer catalysis. The ease of the process depends on the acidity of pyrazoles. Cyanoethylpyrazoles can be converted into the corresponding aminopropylpyrazoles via reduction of the cyano group. The reduction with lithium tetrahydridoaluminate is accompanied by β-elimination of the cyanoethyl group. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206070218

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 7, pp. 1131 1133.
Original Russian Text O.S. Attaryan, A.O. Baltayan, K.S. Badalyan, G.G. Minasyan, S.G. Matsoyan, 2006, published in Zhurnal Obshchei Khimii,
006, Vol. 76, No. 7, pp. 1180 1182.
Pleiades Publishing, Inc., 2006.
2
Cyanoethylation of Pyrazoles under Conditions
of Phase-Transfer Catalysis and Hydrogenation
of the Cyanoethylation Products
O. S. Attaryan, A. O. Baltayan, K. S. Badalyan, G. G. Minasyan, and S. G. Matsoyan
Institute of Organic Chemistry, National Academy of Science of Armenia,
ul. Zakariya Sarkavaga 167a, Erevan, 375091 Armenia
Received September 15, 2005
Abstract Cyanoethylation of pyrazoles with acrylonitrile was studied under conditions of phase-transfer
catalysis. The ease of the process depends on the acidity of pyrazoles. Cyanoethylpyrazoles can be converted
into the corresponding aminopropylpyrazoles via reduction of the cyano group. The reduction with lithium
tetrahydridoaluminate is accompanied by -elimination of the cyanoethyl group.
DOI: 10.1134/S1070363206070218
Cyanoethylation of pyrazoles is performed in the
talysis and obtained the corresponding 1-(2-cyano-
ethyl)pyrazoles IV VI. The reaction can be carried
out in a liquid liquid system (water NaOH) using
benzyltriethylammonium chloride as phase-transfer
catalyst. The yields of cyanoethylpyrazoles IV VI
ranged from 80 to 90%.
absence of a catalyst under pressure at 140 160 C [1].
It is also known that pyrazoles smoothly take up
acrylonitrile at 70 120 C in the presence of acid and
alkaline catalysts [2]. We succeeded in effecting
cyanoethylation of pyrazoles I III at room tempera-
ture 20 30 C under conditions of phase-transfer ca-
R
R
N
+ CH2=CH C N
N
R
R
N
N
H
CH2CH2C N
I III
IV VI
I, IV, R = R = H, III, VI, R = R = CH ; II, V, R = CH , R = H (a), R = H, R = CH (b).
3
3
3
The reaction time strongly depends on the substrate
acidity. The reaction with unsubstituted pyrazole (I,
data, the isomer ratio was 3:2. We succeeded in se-
parating and identifying isomers Va and Vb. Their
structure was determined on the basis of chemical
shifts of protons in the ring and methyl groups in the
pK 20.4) was complete in 1.5 h, whereas cyano-
a
ethylation of 3,5-dimethylpyrazole (III, pK 22.0)
a
required 5 h, 3(5)-methylpyrazole (pK 21.0) occupies
spectra recorded from solutions in DMSO-d and
benzene [5]. The signal of the 3-H proton in the H
a
6
1
an intermediate place in this series. Obviously, intro-
duction of electron-donor methyl groups into the
pyrazole ring hampers generation of pyrazolate ion,
and the cyanoethylation process slows down.
NMR spectrum of isomer Vb in DMSO-d was lo-
6
cated in a stronger field ( 7.28 ppm, d, 1H), while
the signal from the methyl group appeared in a weaker
field ( 2.35 ppm, s, 3H, 5-CH ); in going to benzene,
3
As might be expected, the reaction with 3(5)-me-
the CH signal was displaced upfield ( 1.93 ppm, s,
3
thylpyrazole (II) gave a mixture of isomeric 3- and
3H, 5-CH ). By contrast, no analogous shift of the
3
5
-methyl1-cyanomelthylpyrazoles Va and Vb in an
overall yield of 90% [3, 4]. According to the H NMR
CH proton signal in going from DMSO-d to benzene
3
6
1
was observed for isomer Va.
1131

1
132
ATTARYAN et al.
The cyano group in pyrazoles Va and Vb was
The IR spectrua of cyanoethylpyrazoles IV VI
contained a strong absorption band at 2250 cm 1 due
reduced to amino by treatment with lithium tetrahyd-
ridoaluminate; however, the yields of the correspond-
ing aminopropylpyrazoles VIIa and VIIb were 30 and
to stretching vibrations of the cyano group, and ab-
sorption bands in the region 1510 1530 cm 1 were
assigned to vibrations of the pyrazole ring.
36%, respectively, owing to concurrent -elimination
of the cyanoethyl group [6 9].
R
N
R
N
R
CH CH CH NH
2
VIIa, VIIb
2
2
2
N
R
LiAlH4
N
CH CH C N
R
2
2
Va, Vb
N + CH2=CH C N
R
N
H
II
EXPERIMENTAL
(V) was synthesized in a similar way from 8.2 g of
(5)-methylpyrazole (I). Yield 12.6 g (94%), bp 105
3
2
0
20
The IR spectra were recorded on a UR-20 spec-
trometer from samples prepared as thin films or KBr
pellets. The H NMR spectra were measured on a
125 C (2 mm), n 1.4910, d4 1.0847. Found, %: C
D
62.09; H 6.31; N 31.30. C H N . Calculated, %: C
7
9
3
1
62.22; H 6.67; N 31.11. The isomers were separated
by rectification through a 30 4-cm column charged
with a metal packing (column head temperature 110
120 C, still temperature 180 C, pressure 3 mm, reflux
number R 10). Separation of 100 g of a 3:2 isomer
mixture gave 40 g of 3-(3-methyl-1H-pyrazol-1-yl)-
propanenitrile (Va) and 20 g of 3-(5-methyl-1H-
pyrazol-1-yl)propanenitrile (Vb).
Varian Mercury-300 instrument in (CD ) SO using
3
2
HMDS as internal reference. GLC analysis was per-
formed on an LKhM-8MD chromatograph equipped
with a 1-m column packed with 10% of Carbowax-
2
0M on Inerton AW-HMDS; carrier gas helium, flow
1
rate 40 ml min ; detector temperature 220 C.
3
-(1H-Pyrazol-1-yl)propanenitrile (IV). Acrylo-
Isomer Va. bp 108 C (2 mm), n2 1.4890, d 42 0
0
nitrile, 8 g, was added dropwise to a mixture of 6.8 g
of pyrazole I, 1.36 g of sodium hydroxide, 50 ml of
water, and 1 g of benzyltriethylammonium chloride
under stirring at room temperature. The mixture was
stirred for 1.5 h and extracted with chloroform. The
D
1
1
.0830. IR spectrum, , cm : 1520 (ring), 2250 (CN);
1
H NMR spectrum (DMSO-d , 300 MHz), , ppm
6
(
6
J, Hz): 2.20 s (3H, 3-CH ), 2.92 t (2H, CH CN, J
3
2
.6), 4.29 t (2H, CH N, J 6.6), 5.93 d (1H, 4-N, J 2.2),
2
extract was dried over MgSO , the solvent and excess
4
7.49 d (1H, 5-H, J 2.2).
acrylonitrile were distilled off, and the residue was
distilled under reduced pressure. Yield 10.4 g (86%),
Isomer Vb. bp 115 C (2 mm), n2 1.4960, d 24 0
0
D
2
0
20
1
bp 105 110 C (1 mm), n 1.4920, d4 1.0800. IR
1.0865. IR spectrum, , cm : 1520 (ring), 2250 (CN);
H NMR spectrum (DMSO-d , 300 MHz), , ppm
D
1
1
1
spectrum, , cm : 1520 (ring), 2250 (CN). H NMR
6
spectrum (DMSO-d , 300 MHz), , ppm (J, Hz):
(J, Hz): 2.35 s (3H, 5-CH ), 2.94 t (2H, CH CN, J
6
3
2
2
6
1
5
5
.97 t (2H, CH CH , J 6.6), 4.40 t (2H, CH CH , J
6.5), 4.28 t (2H, CH N, J 6.5), 5.95 d (1H, 4-H, J 1.9),
2
2
2
2
2
.6), 6.19 d.d (1H, 4-H, J 2.3, 1.9), 7.41 d (1H, 3-H, J
.9), 7.66 d (1H, 5-H, J 2.3). Found, %: C 59.38; H
.48; N 34.34. C H N . Calculated, %: C 59.50; H
7.28 d (1H, 3-H, J 1.9).
3
-(3,5-Dimethyl-1H-pyrazol-1-yl)propanenitrile
VI) was synthesized as described above for com-
pound IV from 9.6 g of 3,5-dimethyl-1H-pyrazole
6
7
3
(
.79; N 34.71.
2
0
3
-[3(5)-Methyl-1H-pyrazol-1-yl]propanenitrile
(III). Yield 12.5 g (84%), bp 123 125 C (1 mm), nD
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

CYANOETHYLATION OF PYRAZOLES UNDER CONDITIONS
1133
1
1
(
3
.4880, mp 45 47 C. IR spectrum, , cm : 1520
pyrazole Vb. Yield 4 g (36%), bp 100 105 C (5 mm),
1
20
D
20
1
ring), 2250 (CN). H NMR spectrum (DMSO-d ,
00 MHz), , ppm (J, Hz): 2.15 s (3H, 3-CH ), 2.30 s
n
1.5065, d4 1.0424. IR spectrum, , cm : 1520
(ring), 3350 3400 (NH ). H NMR spectrum (DMSO-
6
1
3
2
(
3H, 5-CH ), 2.98 t (2H, CH CN, J 6.6), 4.20 t (2H,
d , 300 MHz), , ppm (J, Hz): 1.85 q (2H, CH , J 7.4,
3
2
6
2
CH N, J 6.6), 5.72 s (1H, 4-H). Found, %: C 64.64;
7.0), 1.85 br.s (2H, NH ), 2.60 t (2H, CH NH , J 7.4),
2
2 2 2
H 7.13; N 28.36. C H N . Calculated, %: C 64.43;
H 7.38; N 28.19.
4.15 t (2H, CH N, J 7.0), 5.95 d (1H, 4-H, J 1.9),
7.28 d (1H, 3-H, J 1.9). Found, %: C 60.18; H 9.09;
8
11
3
2
N 30.46. C H N . Calculated, %: C 60.43; H 9.35;
N 30.22.
7
13
3
3
-(3-Methyl-1H-pyrazol-1-yl)propan-1-amine
(
VIIa). A solution of 10 g of cyanoethylpyrazole Va
in 150 ml of anhydrous diethyl ether was added drop-
wise under stirring to a mixture of 7 g of lithium
tetrahydridoaluminate and 100 ml of anhydrous di-
ethyl ether at such a rate that the mixture evenly
boiled. The mixture was heated for 3 h under reflux
and cooled to room temperature, 25 ml of water was
carefully added in a dropwise fashion, and 30 ml of a
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1
2
3
4
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1
1
. Auwers, K. and Schmidt, W., Chem. Ber., 1925,
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3
0% solution of sodium hydroxide was added. The
organic phase was separated, the residue was washed
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0
20
7
8 83 C (1 mm), n 1.5000, d 1.0319. IR spectrum,
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D
4
1
1
,
cm : 1520 (ring), 3350 3400 (NH ). H NMR
2
6. Wiedeman, O.F. and Montgomery, W.H., J. Am. Chem.
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6
1
2
4
.85 q (2H, CH , J 7.4, 7.0), 2.20 s (3H, 3-CH ),
2
3
7
8
9
. Buckle, F.J. and Saunders, B.C., J. Chem. Soc., 1949,
no. 11, p. 2774.
.58 t (2H, CH NH , J 7.4), 4.08 t (2H, CH N, J 7.0),
2
2
2
.08 br (2H, NH ), 5.88 d (1H, 4-H, J 2.2), 7.31 d
2
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C H N . Calculated, %: C 60.43; H 9.35; N 30.22.
7
13
3
. Shostakovskii, M.F., Atavin, A.S., Vodbol’skaya, B.A.,
Gusarova, N.K., and Lavrov, V.I., Dokl. Akad. Nauk
SSSR, 1966, vol. 166, no. 9, p. 1381.
3
-(5-Methyl-1H-pyrazol-1-yl)propan-1-amine
(VIIb) was obtained in a similar way from 10 g of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006