Vinylacidic Acid in the Reaction of Aza-Michael with 1-Ethylpyrazole

Article abstract of DOI:10.1134/S1070428020080229

Abstract: Commercial vinylacetic acid is a mixture of isomers of but-3-enoic andbut-2-enoic acids. It was shown that but-3-enoic acid undergoes isomerization inthe presence of a catalytic amount of 1-ethylpyrazole. The resulting Z- and E-isomersof but-2-enoic acid enter the aza-Michael reaction with pyrazole. The¹H NMR analysis showed that by the end of theexperiment the ratio of unreacted Z- andE-isomers of but-2-enoic acid in thereaction mixture decreased by half (to 3 : 1), which pointed to a higherreactivity of the Z-isomer.

Full text of DOI:10.1134/S1070428020080229

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 8, pp. 1488–1490. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 8, pp. 1292–1295.
SHORT
COMMUNICATIONS
Vinylacidic Acid in the Reaction
of Aza-Michael with 1-Ethylpyrazole
a,
b
a
H. N. Khachatryan *, A. G. Shahkhatuni , A. M. Arzumanyan ,
a,c
a,c
G. G. Danagulyan , and H. S. Attaryan
a
Scientific Technological Center of Organic and Pharmaceutical Chemistry, National Academy of Science of Armenia,
Yerevan, 0014 Armenia
b
Molecular Structure Research Center, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Science of Armenia, Yerevan, 0014 Armenia
c
Russian-Armenian (Slavonic) University, Yerevan, 0051 Armenia
*e-mail: hovelenatt@mail.ru
Received March 5, 2020; revised March 14, 2020; accepted March 19, 2020
Abstract—Commercial vinylacetic acid is a mixture of isomers of but-3-enoic and but-2-enoic acids. It was
shown that but-3-enoic acid undergoes isomerization in the presence of a catalytic amount of 1-ethylpyrazole.
1
The resulting Z- and E-isomers of but-2-enoic acid enter the aza-Michael reaction with pyrazole. The H NMR
analysis showed that by the end of the experiment the ratio of unreacted Z- and E-isomers of but-2-enoic acid in
the reaction mixture decreased by half (to 3 : 1), which pointed to a higher reactivity of the Z-isomer.
Keywords: vinylacetic acid, isomerization, ethylpyrazole, aza-Michael reaction, Z/E-isomers
DOI: 10.1134/S1070428020080229
1
We have shown in [1] that electrophilic alkenes,
in which the double bond is isolated by a methylene
group, allyl cyanides in particular, should undergo
isomerization of the double bond before aza-Michael
reaction with pyrazoles. Such isomerization readily
occurs in the presence of basic catalysts or at increased
temperatures, as well as an appropriate basicity of the
nucleophiles [1, 2].
According to the H NMR data, the initial 1 : 2 ratio
was 19 : 1, respectively (Scheme 1).
In view of the fact that commetcial acetic acid is
generally a mixture of isomers 1 and 2 [3], we studied
their properties under heating and in the presence of a
catalytic amount of 1-ethylpyrazole (3). We expected
that in the presence of pyrazole 3 (as a base) compound
1
would convert into compound 2 (Scheme 2).
The dependence of the degree of isomerization of
vinylacetic acid (1) from time (at 130°C) was studied
by H NMR spectroscopy (Fig. 1).
The present work is similar to that our previous work
1
[1], except that we now focused on vinylacetic acid (1)
instead of allyl cyanide. Unlike the latter, vinyl acetic
acid we dealt with in the present work was, according
to H NMR, was a mixture of isomeric vinylacetic acid
As seen from the Fig. 1, the degree of conversion of
compound 1 into compound 2 was about 63% within
2 h and about 85% within 4 h. After 4 h, the ratio of
compounds 1 and 2 no longer changes.
1
(but-3-enoic acid, 1) and but-2-enoic acid (2).
Scheme 1.
Scheme 2.
O
O
OH
OH
1
2
1
488

VINYLACIDIC ACID IN THE REACTION OF AZA-MICHAEL WITH 1-ETHYLPYRAZOLE
1489
By the end of the process, compound 2 was a mixture
of the Z- and E-isomers in a 6 : 1 ratio (Scheme 3).
To obtain further evidence for our results, we
have studied the reaction of unsubstituted pyrazole
4
with vinylacetic acid (1) in the absence of catalyst
(Scheme 4).
1
The progress of this reaction was monitored by H
NMR spectroscopy and GC–MS. It was found that
within 5 h at 130°C the conversion of pyrazole was
about 85%. And the Z- and E-isomers of but-2-enoic
acid (2) formed during isomerization undergo aza-
Michael reaction with pyrazole to form 3-(1H-pyrazol-
Fig. 1. Isomerization of acid 1 into acid 2.
1
1
-yl)butanoic acid (5). Taking into account that by the
(
E)-But-2-enoicacid(2). HNMRspectrum, δ, ppm:
end of the reaction the ratio of the unreacted Z- and
E-isomers was 3 : 1 instead of the expected 6 : 1, we
can suggest that the Z-isomer much easier reacts with
pyrazole 4 than the E-isomer.
2
=
.08 d.d (3H, CH , J 7.2, J 1.8 Hz), 5.68 d.q (1H,
3 1 2
CH, J 11.4, J 1.8 Hz), 6.23 d.q (1H, =CH, J 11.4, J
1 2 1 2
7
.2 Hz), 11.84 m (1H, COOH).
-(1H-Pyrazol-1-yl)butanoic acid (5). A mixture of
.68 g (10 mmol) of pyrazole 4 and 1.72 g (20 mmol)
3
Conversion of but-3-enoic acid (1) into (E)-but-
0
2
-enoic acid (2). But-3-enoic acid (1), 5 g (60 mmol),
was added at room temperature to 0.5 g (4.5 mmol) of
-ethyl-3-methylpyrazole (3), and immediately after
of but-3-enoic acid (1) was heated at 140°C for 5 h.
The solvent was then removed, and the residue was
distilled in a vacuum. Yield 1 g (65%), bp 156–157°C
1
that the first sample of the reaction mixture was taken
for analysis. The mixture was heated under reflux for
–1
(1 mmHg), mp 59–60°C. IR spectrum, ν, cm : 3200–
1
3
400 (COOH), 1690 (C=O), 1530 (ring). Н NMR
spectrum, δ, ppm: 1.50 d (3H, C–CH3, J 6.8 Hz),
.64 d.d (1H, CH–CH , J 16.1, 6.7 Hz), 2.84 d.d (1H,
4
h, during which 4 more samples were taken. The
1
reaction progress was monitored by H NMR (Fig. 1).
2
2
1
But-3-enoic acid (1). H NMR spectrum, δ, ppm:
CH–CH , J 16.1, 7.2 Hz), 4.66–4.78 m (1H, CH–CH ),
6.11 d.d (1H, 4-CH, J 2.3, 1.7 Hz), 7.33 d.d (1H, 3-CH,
J 1.7, 0.7 Hz), 7.51 d.d (1H, 5-CH, J 2.3, 0.7 Hz),
2
3
2
.96 d.t (2H, CH , J 6.9, J 1.5 Hz), 5.06 d.d.t (1H,
2 1 2
=
CH , J 10.2, J 1.8, J 1.4 Hz), 5.10 d.d.t (1H, =CH ,
2 2 2 3 2
J 17.1, J 1.8, J 1.7 Hz), 5.87 d.d.t (1H, =CH, J 17.1,
1
2
3
1
11.44 br.s (1H, COOH). Found, %: C 54.76; H 6.22;
J 10.2, J 6.9 Hz), 11.84 m (1H, COOH).
2
3
N 18.31. C H N O . Calculated, %: C 54.54; H 6.54;
N 18.17.
7
10
2
2
1
(
Z)-But-2-enoic acid (2). H NMR spectrum, δ, ppm:
1
=
.87 d.d (3H, CH , J 6.9, J 1.7 Hz), 5.71 d.q (1H,
3
1
2
Vinylacetic acid was purchased from ARIAK
Armenia), pyrazol was obtained from Sigma-Aldrich,
CH, J 15.71, J 1.7 Hz), 6.80 d.q (1H, =CH, J 15.5,
1 2 1
(
J2 6.9 Hz), 11.84 m (1H, COOH).
and 1-ethylpyrazole was prepared by the procedure in
4].
Scheme 3.
[
O
O
The IR spectra were measured on a Thermo
1
Nicoletion Nexus spectrometer in mineral oil. The H
NMR spectra were recorded on a Bruker AVANCE
NEO 400 MHz spectrometer at 30°C.
OH
OH
Z
E
Scheme 4.
FUNDING
The work was funded by the Ministry for Education
and Science through the subsidy allocated to the Russian–
Armenian University for research, as well as by the State
Committee for Science, Ministry for Education and Science
of the Republic of Armenia (project no. 18T-2E151).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 8 2020

1490
KHACHATRYAN et al.
https://doi.org/10.1134/S1070363215040404
CONFLICT OF INTEREST
The authors declare no conflict of interest.
3. Lynn, J.W., Roberts, R.L., and Kilsheimer, J.R., J. Org.
Chem., 1961, vol. 26, p. 4300.
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