Synthesis of α-methyl-β-(3-methylpyrazol-1-yl)- and α-methyl-β-(5-methylpyrazol-1-yl)propionic acids and their esterification with vinyl acetate

Article abstract of DOI:10.1134/S107036320702017X

α-Methyl-β-(3-methylpyrazol-1-yl)-and α-methyl-β-(5- methylpyrazol-1-yl)propionic acids were synthesized by reaction of 3(5)-methylpyrazole with methyl methacrylate, followed by separation of the resulting isomeric esters and their hydrolysis. Esterification of the title acids was performed via vinyl exchange reaction with vinyl acetate in the catalytic system mercury acetate-trifluoroacetic acid.

Full text of DOI:10.1134/S107036320702017X

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 2, pp. 297 300.
Pleiades Publishing, Ltd., 2007.
Original Russian Text O.S. Attaryan, A.O. Baltayan, S.G. Matsoyan, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 2, pp. 325 328.
Synthesis of -Methyl- -(3-methylpyrazol-1-yl)-
and -Methyl- -(5-Methylpyrazol-1-yl)propionic Acids
and Their Esterification with Vinyl Acetate
O. S. Attaryan, A. O. Baltayan, and S. G. Matsoyan
Institute of Organic Chemistry, National Academy of Science of Armenia,
ul. Zakariya Sarkavaga 167a, Erevan, 375091 Armeniya
e-mail: angelabaltayan@mail.ru
Received August 3, 2006
Abstract
-Methyl- -(3-methylpyrazol-1-yl)- and -methyl- -(5-methylpyrazol-1-yl)propionic acids were
synthesized by reaction of 3(5)-methylpyrazole with methyl methacrylate, followed by separation of the result-
ing isomeric esters and their hydrolysis. Esterification of the title acids was performed via vinyl exchange
reaction with vinyl acetate in the catalytic system mercury acetate trifluoroacetic acid.
DOI: 10.1134/S107036320702017X
It is known that 3(5)-methylpyrazole (I) readily
adds to acrylic acid at 80 90 C with formation of 1-
carboxyethyl-3(5)-methylpyrazole [1]. We have found
that 3(5)-methylpyrazole reacts with methacrylic acid
in a similar way to give a mixture of isomeric acids
II and III which are difficult to separate.
CH3
CH3
N
+
N
+ CH2=C COOH
CH3
N
H3C
N
N
N
H
CH2 CH COOH
CH2 CH COOH
CH3
CH3
I
II
III
With a view to obtain individual isomers II
and III, i.e., -methyl- -(3-methylpyrazol-1-yl)-
and -methyl- -(5-methylpyrazol-1-yl)propionic
acids, we propose the following scheme which
includes separation of intermediate esters V and
VI.
CH3
N
II
N
CH2 CH COOH3
CH3
CH3
V
N
+ CH2=C COOH3
CH3
I
N
CH2 CH COOH3
N
III
CH3
H3C
N
IV
CH2 CH COOH
CH3
VI
297

298
ATTARYAN et al.
due to stretching vibrations of the acid carbonyl group;
According to published data [2], methyl methacry-
1
late reacts with 3,5-dimethylpyrazole at 200 C under
pressure. We succeeded in obtaining addition product
IV by heating the reactants in an open vessel for 20 h
at 160 170 C. The yield of methyl -methyl- -[3(5)-
methylpyrazol-1-yl]propionate (IV) was 80%.
Hydrolysis of esters V and VI in the presence of
sodium hydroxide gave the corresponding sodium
salts, and acidification of the latter afforded target
acids II and III.
absorption bands at 1510 1520 and 3300 3500 cm
were assigned to vibrations of the pyrazole ring and
hydroxy group, respectively. According to the 1H
NMR data, the ring proton in isomer III resonates in
a stronger field, at 7.19 ppm (d, 1H, 3-H), and the
methyl proton signal is located in a weaker field, at
2.29 ppm (s, 3H, 5-CH3), as compared to the cor-
responding signals of isomer II. The positions of the
1
4-H signals in the H NMR spectra of isomeric acids
II and III are almost similar ( 5.86 5.87 ppm).
The IR spectra of carboxypropylpyrazoles II and
III contained a strong absorption band at 1730 cm
1
CH3
N
N
O
II
CH2 CH C
O
O CH=CH2
CH2=CH O C
CH3
CH3
Hg++, H+
VII
III
N
H3C
N
O
CH2 CH C
O CH=CH2
CH3
VIII
We also examined vinylation of acids II and III
with vinyl acetate in the presence of mercury(II) acetate
and various acids with a view to obtain new vinyl
monomers of the pyrazole series (vinyl esters VII and
VIII). The use of mercury(II) acetate alone [3] was
unsuccessful; in this case, the yield of the target
products was very poor. We succeeded in raising the
yield to 25% using the system Hg(OAc)2 H2SO4 [4].
The catalytic system mercury(II) acetate BF3 Et2O
[5] was also ineffective. Only the system mercury(II)
acetate trifluoroacetic acid [6] enabled us to synthe-
size vinyl pyrazolylpropionates VII and VIII in 45
50% yield.
The double bond in isomer VII (3-CH3) is less
polarized than that in isomer VIII (5-CH3) [7]. Never-
theless, this difference did not affect their radical
homopolymerization: unlike isomeric N-vinylpyrazo-
les [8, 9], vinyl esters VII and VIII exhibited almost
similar reactivities in the polymerization process. It
should also be noted that, in contrast to N-vinylazoles
[10], compounds VII and VIII readily undergo co-
polymerization with vinyl acetate.
EXPERIMENTAL
The IR spectra were recorded on a UR-20 instru-
ment from samples prepared as thin films or KBr
1
pellets. The H NMR spectra were measured on a
Vinyl esters VII and VIII characteristically showed
Varian Mercury-300 spectrometer (300 MHz) from
solutions in DMSO-d6. GLC analysis was performed
on an LKhM-8MD chromatograph equipped with a
1-m column packed with 10% of Carbowax-20M on
Inerton AW-HMDS; carrier gas helium, flow rate
in the IR spectra an absorption band at 1620
1
1630 cm , which corresponds to stretching vibrations
1
of the vinyl group. In the H NMR spectra of these
compounds, protons in the vinyl group gave rise to an
ABX pattern (CHAHB=CHX) with the following
chemical shifts, , ppm: VII: 4.85 (HA), 4.86 (HB),
7.21 (HX); VIII: 4.57 (HA), 4.85 (HB), 7.19 (HX);
JAX 14.0, JBX 6.3, JAB 1.6 Hz.
1
40 ml min ; detector temperature 220 C.
2-Methyl-3-[3(5)-methylpyrazol-1-yl]propionic
acid (II/III) (mixture of isomers). A mixture of 8.2 g
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SYNTHESIS OF -METHYL- -(3-METHYLPYRAZOL-1-YL)
299
1
of 3(5)-methylpyrazole (I), 10 ml of methacrylic acid,
and 0.1 g of hydroquinone was heated for 8 h at 90
100 C under reflux. Excess methacrylic acid was
removed, and the residue was distilled under reduced
pressure. Yield 12.5 g (75%), bp 155 C (1 mm Hg),
white crystals, mp 73 C (from water). IR spectrum, ,
water). IR spectrum, , cm : 1510 (ring), 1710 (CO),
1
3300 3500 (OH). H NMR spectrum, , ppm (J, Hz):
1.08 d (3H, CHCH3, J 7.1), 2.17 s (3H, 3-CH3),
2.89 sextet (1H, CHCH3, J 7.1), 3.95 d d (1H, CH2,
J 13.5, 7.1), 4.27 d.d (1H, CH2, J 13.5, 6.7),
5.86 d (1H, 4-H, J 2.2), 7.30 d (1H, 5-H, J 2.2),
12.01 br.s (1H, COOH). Found, %: C 57.48; H 7.34;
N 16.31. C8H12N2O2. Calculated, %: C 57.14; H 7.14;
N 16.67.
1
cm : 1510 (ring), 1700 (CO), 3300 3500 (OH).
Isomer ratio 3:2.
Methyl 2-methyl-3-[3(5)-methylpyrazol-1-yl]-
propionate (IV) (mixture of isomers). Methyl metha-
crylate, 6.5 ml, was added dropwise to 4.1 g of 3(5)-
methylpyrazole (I) heated to 160 170 C. The mixture
was heated for 20 h at the boiling point, excess me-
thyl methacrylate was distilled off, and the residue
was distilled under reduced pressure. Yield 7.3 g
(80%), bp 81 86 C (1 mm Hg), n2D0 1.4778, d420
2-Methyl-3-(5-methylpyrazol-1-yl)propionic
acid (III) was synthesized in a similar way from ester
VI. Yield 12.6 g (75%), white crystals, mp 101
102 C (from water). IR spectrum, , cm : 1520 (ring),
1720 (CO), 3300 3500 (OH). H NMR spectrum, ,
ppm (J, Hz): 1.10 d (3H, CHCH3, J 7.1), 2.29 s (3H,
5-CH3), 2.98 sextet (1H, CHCH3, J 7.1), 3.90 d.d
(1H, CH2, J 13.6, 7.4), 4.25 d.d (1H, CH2, J 13.6,
6.9), 5.87 br.d (1H, 4-H, J 1.8), 7.19 d (1H, 3-H,
J 1.8), 11.95 br.s (1H, COOH). Found, %: C 57.37;
H 7.42; N 16.21. C8H12N2O2. Calculated, %: C 57.14;
H 7.14; N 16.67.
1
1
1
1.0633. IR spectrum, , cm : 1520 (ring), 1720 (CO).
Isomeric esters V and VI were separated by frac-
tional distillation through a 30 4-cm column packed
with a metal filling. The upper part of the column was
heated at 110 120 C; still temperature 180 C; reflux
number R 10; pressure 5 mm. Fractionation of
100 g of isomer mixture IV (isomer ratio 3:2) gave
40 g of V and 20 g of VI.
General procedure for vinylation of 2-methyl-3-
(3-methylpyrazol-1-yl)- and 2-methyl-3-(5-methyl-
pyrazol-1-yl)propionic acids II and III. A mixture
of 0.1 mol of acid II or III, 50 ml of vinyl acetate,
4.0 g of mercury(II) acetate, 2 ml of trifluoroacetic
acid, and 0.1 g of hydroquinone was heated for 20 h
at 70 80 C. Sodium acetate, 8.0 g, was then added
to decompose mercury catalyst. After 2 h, the pre-
cipitate was filtered off, and the filtrate was neautrali-
zed with a 2 N solution of sodium carbonate and ex-
tracted with diethyl ether. The extract was dried over
magnesium sulfate, the solvent was distilled off, and
the residue was distilled under reduced pressure.
Methyl 2-methyl-3-(3-methylpyrazol-1-yl)pro-
pionate (V). bp 85 C (1 mm Hg), n2D0 1.4778, d420
1
1.0640. IR spectrum, , cm : 1510 (ring), 1720 (CO).
1H NMR spectrum, , ppm (J, Hz): 1.10 d (3H,
CHCH3, J 7.1), 2.18 s (3H, 3-CH3), 3.00 sextet (1H,
CHCH3, J 7.1), 3.64 s (3H, OCH3), 4.02 d.d (1H,
CH2, J 13.6, 6.9), 4.26 d.d (1H, CH2, J 13.6, 7.1),
5.87 d (1H, 4-H, J 2.2), 7.29 d (1H, 5-H, J 2.2).
Found, %: C 59.57; H 7.83; N 15.21. C9H14N2O2.
Calculated, %: C 59.34; H 7.69; N 15.39.
Vinyl 2-methyl-3-(3-methylpyrazol-1-yl)pro-
Methyl 2-methyl-3-(5-methylpyrazol-1-yl)pro-
pionate (VII). Yield 47%, bp 88 89 C (1 mm Hg),
pionate (VI). bp 99 100 C (1 mm Hg), n2D0 1.4713,
n2D0 1.4790, d240 1.0545. IR spectrum, , cm :
1
1
d240 1.0567. IR spectrum, , cm : 1530 (ring), 1720
1
1
1510 (ring), 1730 (CO), 1620 (C=C). H NMR spec-
(CO). H NMR spectrum, , ppm (J, Hz): 1.12 d (3H,
trum, , ppm (J, Hz): 1.15 d (3H, CHCH3, J 7.2),
2.17 s (3H, 3-CH3), 3.10 sextet (1H, CHCH3, J 7.0),
4.08 d.d (1H, NCH2, J1 13.6, J2 6.8), 4.30 d.d
(1H, NCH2, J1 = 13.6, J2 6.9), 4.58 d.d (1H, CHAHB,
J1 6.3, J2 1.6), 4.86 d.d (1H, CHAHB, J1 14.0,
J2 1.6), 5.87 d (1H, 4-H, J 2.2), 7.21 d.d (1H,
CH=CH2, J1 14.0, J2 6.3), 7.32 d (1H, 5-H, J
2.2). Found, %: C 61.38; H 7.60; N 14.11. C10H14
N2O2. Calculated, %: C 61.86; H 7.22; N 14.43.
CHCH3, J 7.1), 2.28 s (3H, 5-CH3), 3.08 sextet (1H,
CHCH3, J 7.1), 3.62 s (3H, OCH3), 3.96 d.d (1H,
CH2, J 13.7, 6.9), 4.24 d.d (1H, CH2, J 13.7, 7.4),
5.87 br.d (1H, 4-H), 7.19 d (1H, 3-H, J 1.9). Found,
%: C 59.59; H 7.78; N 15.18. C9H14N2O2. Calculated,
%: C 59.34; H 7.69; N 15.39.
2-Methyl-3-(3-methylpyrazol-1-yl)propionic
acid (II). A mixture of 18.2 g of methyl 2-methyl-3-
(3-methylpyrazol-1-yl)propionate (V), 8 g of sodium
hydroxide, and 50 ml of water was stirred for 3 h at
room temperature. It was then extracted with diethyl
ether, the aqueous phase was neautralized with hydro-
chloric acid, and the precipitate was filtered off. Yield
13.8 g (82%), white crystals, mp 103 104 C (from
Vinyl 2-methyl-3-(5-methylpyrazol-1-yl)pro-
pionate (VIII). Yield 40%, bp 102 105 C (1 mm Hg),
n2D0 1.4846, d240 1.0548. IR spectrum, , cm :
1
1
1530 (ring), 1750 (CO), 1630 (C=C). H NMR spec-
trum, , ppm (J, Hz): 1.19 d (3H, CHCH3, J 7.1),
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ATTARYAN et al.
2.28 s (3H, 5-CH3), 3.19 sextet (1H, CHCH3, J 7.1),
4.03 d.d (1H, NCH2, J1 13.8, J2 6.7), 4.28 d.d (1H,
NCH2, J1 13.8, J2 7.4), 4.57 d.d (1H, CHAHB,
J1 6.3, J2 1.6), 4.85 d.d (1H, CHAHB, J1 14.0,
J2 1.6), 5.88 d (1H, 4-H, J 1.8), 7.19 d.d (1H,
CH=CH2, J1 14.0, J2 6.3), 7.20 d (1H, 3-H, J
1.8). Found, %: C 61.35; H 7.81; N 14.85. C10H14
N2O2. Calculated, %: C 61.86; H 7.22; N 14.43.
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