G Model
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5
CH), 5.49 (d, J = 11.3 Hz, 1H, CH), 7.15 (d, J = 8.0 Hz, 2H, Ar),
7.37 (d, J = 8.0 Hz, 2H, Ar), 11.04 (br s, 1H).
(100), 208 (5), 186 (24), 159 (19), 109 (16), 68 (43), 59 (48);
IR(KBr):n = 3474, 3397,2960, 2240,1747,1609, 1516, 1306,
1030, 809 cmÀ1; Anal calcd for C16H17N3O4 (%): C, 60.94; H,
5.43; N, 13.33; Found (%): C, 60.72; H, 5.52; N, 13.20.
4.2.4. [(4-Chlorophenyl)(5-hydroxy-3-methyl-1H-pyrazol-
4-yl)methyl]malononitrile (4d)
White solid (2.77 g, yield 97%); mp 229–230 8C (lit [31]
4.2.10. Methyl 2-cyano-3-(5-hydroxy-3-methyl-1H-pyrazol-
4-yl)-3-(4-methylphenyl)propanoate (4j)
mp 229–230 8C); 1H NMR (300 MHz, DMSO-d6):
d (ppm)
2.10 (s, 3H, CH3), 4.70 (d, J = 11.3 Hz, 1H, CH), 5.53 (d,
J = 11.3 Hz, 1H, CH), 7.43 (d, J = 8.5 Hz, 2H, Ar), 7.52 (d,
J = 8.5 Hz, 2H, Ar), 10.98 (br s, 1H).
White solid, mixture of two diastereoisomers (1:1),
(2.63 g, yield 88%), mp 180–181 8C; 1H NMR (300 MHz,
DMSO-d6, double set of signals):
d (ppm) 1.94 (s, 3H, CH3),
2.02 (s, 3H, CH3), 2.23 (s, 3H, CH3), 2.26 (s, 3H, CH3), 3.52 (s,
3H, OCH3), 3.61 (s, 3H, OCH3), 4.28–4.34 (m, 2H, 2CH), 4.74–
4.79 (m, 2H, 2CH), 7.07–7.14 (m, 4H, Ar), 7.21–7.24 (m, 2H,
Ar), 7.34–7.36 (m, 2H, Ar), 10.88 (br s, 2H); 13C NMR
4.2.5. [(3-Bromophenyl)(5-hydroxy-3-methyl-1H-pyrazol-
4-yl)methyl]malononitrile (4e)
White solid (3.26 g, yield 99%); mp 216–217 8C (lit [31]
mp 216–217 8C); 1H NMR (300 MHz, DMSO-d6):
d
(ppm)
(75 MHz, DMSO-d6, double set of signals): d (ppm) 9.9, 10.0,
2.11 (s, 3H, CH3), 4.70 (d, J = 11.4 Hz, 1H, CH), 5.57 (d,
J = 11.4 Hz, 1H, CH), 7.33 (t, J = 7.8 Hz, 1H, Ar), 7.46–7.54 (m,
2H, Ar), 7.74 (s, 1H, Ar), 11.03 (br s, 1 H).
20.6 (2C), 40.7, 41.0, 41.4 (2C), 53.0, 53.2, 99.4, 99.8, 116.8
(2C), 127.3 (2C), 127.7 (2C), 129.0 (4C), 136.2 (2C), 137.3,
137.4, 137.5 (2 C), 159.1, 159.3, 165.9, 166.0; MS (m/z,
relative intensity %): 299 ([M]+, 7), 267 (6), 208 (5), 202 (5),
201 (49), 185 (28), 180 (100), 128 (16), 109 (22), 77 (50); IR
4.2.6. [(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-
yl)(phenyl)methyl]malononitrile (4f)
White solid (2.72 g, yield 83%); mp 171–172 8C (lit [29]
mp 173–174 8C); 1H NMR (300 MHz, DMSO-d6): 2.20 (s,
3H, CH3), 4.73 (d, J = 10.8 Hz, 1H, CH), 5.92 (d, J = 10.8 Hz,
1H, CH), 7.15–7.74 (m, 10H, Ar), 11.60 (br s, 1H).
(KBr):
n = 3401, 2960, 2245, 1749, 1600, 1516, 1432, 1357,
1297, 1163 cmÀ1; Anal calcd forC16H17N3O3 (%): C, 64.20; H,
5.72; N, 14.04; Found (%): C, 64.03; H, 5.84; N, 13.91.
4.2.11. Methyl 3-(4-chlorophenyl)-2-cyano-3-(5-hydroxy-3-
methyl-1H-pyrazol-4-yl)-propanoate (4k)
4.2.7. Methyl 2-cyano-3-(5-hydroxy-3-methyl-1H-pyrazol-
4-yl)-3-phenylpropanoate (4g)
White solid, mixture of two diastereoisomers (1:1),
(2.74 g, yield 86%); mp 155–156 8C; 1H NMR (300 MHz,
White solid, mixture of two diastereoisomers (1:1),
(2.57 g, yield 90%); mp 172–173 8C (lit [31] mp 172–
173 8C); 1H NMR (300 MHz, DMSO-d6, double set of
DMSO-d6, double set of signals): d (ppm) 1.98 (s, 3H, CH3),
2.04 (s, 3H, CH3), 3.52 (s, 3H, OCH3), 3.61 (s, 3H, OCH3),
4.35–4.42 (m, 2H, 2CH), 4.78–4.82 (m, 2H, 2CH), 7.31–7.39
(m, 6H, Ar), 7.50–7.53 (m, 2H, Ar), 10.81 (br s, 2H); 13C NMR
signals):
d (ppm) 1.98 (s, 3H, CH3), 2.06 (s, 3H, CH3),
3.52 (s, 3H, OCH3), 3.64 (s, 3H, OCH3), 4.35–4.41 (m, 2H,
2CH), 4.79–4.84 (m, 2H, 2CH), 7.19–7.39 (m, 8H, Ar), 7.48–
7.51 (m, 2H, Ar), 10.75 (br s, 2H).
(75 MHz, DMSO-d6, double set of signals): d (ppm) 9.8, 9.9,
40.5, 40.7, 40.9, 41.3, 53.1, 53.2, 98.8, 99.3, 116.6, 116.7,
128.4 (4C), 129.4 (2C), 129.8 (2C), 131.7, 131.8, 137.5,
137.7, 139.5, 139.6, 159.0, 159.2, 165.7, 165.8; MS (m/z,
relative intensity %): 319 ([M]+, 4), 221 (100), 185 (15), 163
(7), 128 (21), 109 (45), 75 (6), 68 (18), 59 (35), 51 (6); IR
4.2.8. Ethyl 2-cyano-3-(5-hydroxy-3-methyl-1H-pyrazol-4-
yl)-3-phenylpropanoate (4h)
White solid, mixture of two diastereoisomers (1:1),
(2.72 g, yield 91%); mp 182–183 8C (lit [3] mp 182–183 8C);
(KBr): n = 3424, 2960, 2248, 1748, 1604, 1532, 1520, 1496,
1300, 1096 cmÀ1; Anal calcd for C15H14ClN3O3 (%): C,
56.35; H, 4.41; Cl, 11.09; N, 13.14; Found (%): C, 56.14; H,
4.52; Cl, 10.93; N, 12.96.
1H NMR (300 MHz, DMSO-d6, double set of signals):
d
(ppm) 0.88 (t, J = 7.1 Hz, 3H, CH3), 1.00 (t, J = 7.1 Hz, 3H,
CH3), 1.98 (s, 3H, CH3), 2.05 (s, 3H, CH3), 3.88–3.96 (m, 2H,
OCH2), 4.00–4.12 (m, 2H, OCH2), 4.29–4.37 (m, 2H, 2CH),
4.75–4.79 (m, 2H, 2CH), 7.15–7.38 (m, 8H, Ar), 7.48–7.51
(m, 2H, Ar), 10.95 (br s, 2H).
4.2.12. 6-Amino-3-methyl-4-phenyl-1,4-dihydro[2,3-
c]pyrazole-5-carbonitrile (5a)
White solid, (2.17 g, yield 86%); mp 244–245 8C (lit [28]
mp 244–245 8C); 1H NMR (300 MHz, DMSO-d6):
d (ppm)
4.2.9. Methyl 2-cyano-3-(5-hydroxy-3-methyl-1H-pyrazol-
4-yl)-3-(4-methoxyphenyl)propanoate (4i)
1.79 (s, 3H, CH3), 4.60 (s, 1H, CH), 6.83 (s, 2H, NH2), 7.16–
7.34 (m, 5H, Ar), 12.09 (s, 1H, NH).
Yellowish solid, mixture of two diastereoisomers (1:1),
(2.87 g, yield 91%); mp 159–160 8C; 1H NMR (300 MHz,
4.2.13. (4-Methoxybenzylidene)malononitrile (6)
DMSO-d6, double set of signals):
d
(ppm) 1.97 (s, 3H, CH3),
Yellow solid, (1.80 g, yield 98%); mp 113–114 8C (lit [32]
2.05 (s, 3H, CH3), 3.53 (s, 3H, OCH3), 3.62 (s, 3H, OCH3), 3.70
(s, 3H, OCH3), 3.72 (s, 3H, OCH3), 4.29–4.36 (m, 2H, 2CH),
4.72–4.79(m, 2H, 2CH), 6.83–6.90(m, 4H, Ar), 7.27–7.30(m,
2H, Ar), 7.40–7.43 (m, 2H, Ar), 10.78 (br s, 2H); 13C NMR
mp 113–114 8C); 1H NMR (300 MHz, CDCl3):
d (ppm) 3.92
(s, 3H, OCH3), 7.02 (d, J = 8.7 Hz, 2H, Ar), 7.65 (s, 1H, CH),
7.91 (d, J = 8.7 Hz, 2H, Ar)
Acknowledgments
(75 MHz, DMSO-d6, double set of signals): d (ppm) 9.9, 10.0,
40.3, 40.6, 41.0, 41.1, 41.6, 53.0, 53.2, 55.0 (2C), 99.5, 99.9,
113.8 (4C), 116.9, 128.6 (2C), 129.0 (2C), 132.5, 132.6, 137.3,
137.5, 158.2, 158.3, 159.1, 159.2, 166.0, 166.1; MS (m/z,
relative intensity %): 315 ([M]+, 8), 283 (3), 218 (9), 216
The authors gratefully acknowledge the financial
support of the Russian Foundation for Basic Research
(Project No. 12-03-00135a).
Please cite this article in press as: Elinson MN, et al. Sodium acetate catalyzed tandem Knoevenagel–Michael
multicomponent reaction of aldehydes, 2-pyrazolin-5-ones, and cyano-functionalized C–H acids: Facile and efficient way