Chemistry of Heterocyclic Compounds 2015, 51(5), 483–490
Et3BnN+Cl– (1.0 g, 5.2 mmol), K2CO3 (27.6 g, 0.2 mol), and
NCH2); 7.55 (1H, s, H-5). Found, %: C 47.61; H 5.65;
N 13.57. C8H11ClN2O2. Calculated, %: C 47.42; H 5.47;
N 13.82.
Me2CO (150 ml) was stirred for 4 h at 50–55°С. The
reaction mixture was then cooled and filtered. Acetone was
removed by evaporation, and the residue was distilled under
vacuum. Yield 11.5 g (76%), colorless liquid, bp 123–130°С
Hydrazide of 1Н-pyrazole-3-carboxylic acid (11). A
solution of methyl 1H-pyrazole-3-carboxylate (2) (1.0 g,
8 mmol) in EtOH (10 ml) was treated with 60% aqueous
hydrazine (1.5 g, 18 mmol), the mixture was heated for 5–
6 h on a water bath. Ethanol and excess hydrazine were
removed by evaporation, the residue was washed with hot
hexane and Et2O. Yield 1.0 g (99%), white crystals, mp
172–174°C (EtOH), Rf 0.1 (2:1 benzene–Me2CO).
1H NMR spectrum, δ, ppm (J, Hz): 4.22 (2H, br. s, NH2);
6.66 (1H, d, J = 2.2, H-4); 7.52 (1H, d, J = 2.2, H-5); 9.03
(1H, br. s, NHNH2); 12.95 (1H, br. s, 1-NH). Found, %:
C 37.89; H 4.83; N 44.51. C4H6N4O. Calculated, %:
C 38.09; H 4.80; N 44.42.
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(3 mmHg) (oil,14,15 bp 145–146°С16), nD 1.4647. IR
spectrum, ν, cm–1: 1500 (ring), 1730 (C=O). 1H NMR
spectrum, δ, ppm (J, Hz): 1.30 (3Н, t, J = 7.1, ОCH2CH3);
4.81 (2Н, q, J = 7.1, ОCH2CH3); 4.94 (2Н, s, NCH2); 7.62
(1Н, s, Н-3); 8.25 (1Н, s, Н-5). Found, %: C 46.28; H 5.99;
N 27.25. C6H9N3O2. Calculated, %: C 46.45; H 5.85;
N 27.08.
Methyl 3-(4-bromo-3-methylpyrazol-1-yl)propionate (7).
mixture of methyl 3-(3-methyl-1H-pyrazol-1-yl)-
A
propionate (26.8 g, 0.16 mol), AcONa (32.0 g, 0.40 mol),
and H2O (112 ml) was charged into a four-necked flask,
stirred at room temperature, and treated by dropwise addition
of a mixture of AcOH (19 ml) and Br2 (10 ml, 31.2 g,
0.20 mol) at such rate that the reaction mixture temperature
did not exceed 20–25°С. The reaction mixture was
neutralized with aqueous Na2CO3, extracted with CHCl3,
and dried over MgSO4. Chloroform was removed by
evaporation and the residue was distilled under vacuum.
Yield 24.1 g (61%), bp 127–128°С (3 mmHg), nD210 1.5082.
IR spectrum, ν, cm–1: 1520 (ring), 1710 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 2.18 (3Н, s, 3-CH3); 2.82 (2Н,
t, J = 6.7, CHCO); 3.65 (3Н, s, OCH3); 4.26 (2Н, t,
J = 6.7, NCH2); 7.56 (1Н, s, H-5). Found, %: C 39.07;
H 4.57; N 11.11. C8H11BrN2O2. Calculated, %: C 38.89;
H 4.49; N 11.34.
Synthesis of hydrazides 12, 13, 15–17 (General
method). A mixture of N2H4·H2O (3.0 g, 0.06 mol) and
ester 3, 5, 7–9 (0.02 mol) was stirred for 10 min at 90–100°С
until complete dissolution. The obtained precipitate was
filtered off after several minutes, washed on filter with a
small amount of Et2O, dried, and recrystallized from EtOH.
Hydrazide of (1Н-pyrazol-1-yl)acetic acid (12). Yield
2.3 g (82%), white crystals, mp 110–112°С, Rf 0.2 (1:1
benzene–Me2CO). 1H NMR spectrum, δ, ppm (J, Hz): 4.23
(2H, br. s, NH2); 4.70 (2H, s, NCH2); 6.18 (1H, dd, J = 2.3,
J = 1.8, H-4); 7.35 (1H, dd, J = 1.8, J = 0.7, H-3); 7.61
(1H, dd, J = 2.3, J = 0.7, H-5); 9.16 (1H, br. s, NH). Found,
%: C 42.65; H 5.49; N 39.79. C5H8N4O. Calculated, %:
C 42.85; H 5.75; N 39.98.
Methyl 3-(4-bromo-3,5-dimethylpyrazol-1-yl)propio-
nate (8). A mixture of methyl 3-(3,5-dimethyl-1H-pyrazol-
1-yl)propionate (12.70 g, 70 mmol), AcONa (14.35 g,
175 mmol), and Н2О (49 ml) was charged into a four-
necked flask, stirred at room temperature, and treated by
dropwise addition of a mixture of AcOH (7 ml) and Br2
(4.3 ml, 13.40 g, 84 mmol). Stirring was continued until
complete fading of bromine color, then the reaction
mixture was treated analogously to the procedure described
for compound 7. Yield 13.20 g (72%), colorless liquid, bp
Hydrazide of 3-(1Н-pyrazol-1-yl)propionic acid (13).
Yield 2.8 g (91%), white shiny crystals, mp 63–65°С,
1
Rf 0.2 (1:1 benzene–Me2CO). H NMR spectrum, δ, ppm
(J, Hz): 2.59 (2H, t, J = 6.9, CH2CO); 3.97 (2H, br. s,
NH2); 4.34 (2H, t, J = 6.9, NCH2); 6.11 (1H, dd, J = 2.3,
J = 1.8, H-4); 7.31 (1H, dd, J = 1.8, J = 0.6, H-3); 7.49 (1H,
dd, J = 2.3, J = 0.6, H-5); 8.95 (1H, br. s, NH). Found, %:
С 46.89; Н 6.64; N 36.55. C6H10N4О. Calculated, %:
С 46.74; Н 6.54; N 36.34.
Hydrazide of 3-(4-bromo-3-methyl-1Н-pyrazol-1-yl)-
propionic acid (15). Yield 4.0 g (81%), white crystals, mp
120–122°С, Rf 0.4 (2:1 benzene–Me2CO). 1H NMR
spectrum, δ, ppm (J, Hz): 2.13 (3H, s, CH3); 2.56 (2H, t,
J = 6.8, CH2CO); 3.90 (2H, br. s, NH2); 4.24 (2H, t, J = 6.8,
NCH2); 7.55 (1H, s, H-5); 8.97 (1H, br. s, NH). Found, %:
С 34.28; Н 4.21; N 22.45. C7H11BrN4О. Calculated, %:
С 34.03; Н 4.49; N 22.67.
20
117–119°С (1 mmHg), nD 1.5098. IR spectrum, ν, cm–1:
1
1540 (ring), 1720 (C=O). H NMR spectrum, δ, ppm (J,
Hz): 2.27 (3Н, s, 5-CH3); 2.73 (2Н, t, J = 6.8, CH2CO);
2.75 (3Н, s, 3-CH3); 3.60 (3Н, s, OCH3); 4.12 (2Н, t,
J = 6.8, NCH2). Found, %: C 41.48; H 5.19; N 10.58.
C9H13BrN2O2. Calculated, %: C 41.40; H 5.02; N 10.73.
Methyl 3-(4-chloro-3-methylpyrazol-1-yl)propionate (9).
A mixture of methyl 3-(3-methylpyrazol-1-yl)propionate
(33.6 g, 0.2 mol), AcOH (65 ml), and conc. HCl (27 ml)
was charged into a two-necked flask with a reflux condenser
and thermometer, then treated with 30% H2O2 (73 ml) in one
portion. The reaction mixture was left overnight, diluted
with Н2О, extracted with Et2O, washed with aqueous
Na2CO3, and dried over Na2SO4. Ether was removed at
reduced pressure, the residue was distilled under vacuum,
collecting the fraction with bp 105–120°С (3 mmHg).
Yield 19.7 g (64%), yellowish liquid, nD20 1.4908. 1H NMR
spectrum, δ, ppm (J, Hz): 2.13 (3H, s, 3-CH3); 2.81 (2H, t,
J = 6.7, CH2CO); 3.65 (3H, s, OCH3); 4.24 (2H, t, J = 6.7,
Hydrazide of 3-(4-bromo-3,5-dimethyl-1Н-pyrazol-1-yl)-
propionic acid (16). Yield 4.5 g (86%), white shiny
crystals, mp 153–155°С, Rf 0.2 (1:1 benzene–Me2CO).
1H NMR spectrum, δ, ppm (J, Hz): 2.11 (3H, s, CH3); 2.25
(3H, s, CH3); 2.55 (2H, t, J = 6.9, CH2CO); 3.92 (2H, br. s,
NH2); 4.17 (2H, t, J = 6.9, NCH2); 8.95 (1H, br. s, NH).
Found, %: С 36.58; Н 5.15; N 21.57. C8H13BrN4О.
Calculated, %: С 36.80; Н 5.02; N 21.46.
Hydrazide of 3-(4-chloro-3-methyl-1H-pyrazol-1-yl)-
propionic acid (17). Yield 4.0 g (91%), yellow crystals,
1
mp 105–107°С, Rf 0.3 (1:1 benzene–Me2CO). H NMR
spectrum, δ, ppm (J, Hz): 2.13 (3H, s, CH3); 2.55 (2H, t,
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