PAPER
Ene Reactions of Arylmethylenedihydropyrazoles with 4-Phenyl-3H-1,2,4-triazole-3,5(4H)-dione
1895
1H NMR: = 1.43 (m, 1 H, CH2), 1.57 (m, 1 H, CH2), 1.80 (m, 1 H,
CH2), 1.98 (m, 1 H, CH2), 2.48 (m, 1 H, CH2), 2.88 (m, 1 H, CH2),
3.00 (m, 1 H, CH, J = 10.2 Hz), 4.35 (d, 1 H, CH, J = 10.2 Hz), 7.19
(d, 1 H, CH, J = 1.8 Hz), 7.24–7.49 (m, 10 H, 2 C6H5).
1H NMR: = 2.27 (s, 3 H, CH3), 2.42 (s, 3 H, CH3), 2.74 (dd, 1 H,
CH2, J = 6.0, 10.2 Hz), 2.86 (dd, 1 H, CH2, J = 2.54, 10.2 Hz), 3.64
(m, 2 H, CH2, J = 1.5 Hz), 3.78 (s, 3 H, CH3), 3.83 (s, 3 H, CH3),
3.90 (dm, 1 H, CH, J = 11.2 Hz), 5.63 (d, 1 H, CH, J = 11.2 Hz),
6.82–7.25 (m, 8 H, 2 C6H4), 7.34 (br, 1 H,CH=).
MS: m/z = 228 [M]+.
IR: 1024, 1150, 1609, 1628, 1679, 2846, 2894 cm–1.
9b
UV (CHCl3): max = 313 nm.
MS: m/z = 405 [M]+.
Colorless powder; yield: 72%; mp 94–95 °C (Lit.5 mp 93–95 °C).
1H NMR: = 1.47 (m, 1 H, CH2), 1.69 (m, 1 H, CH2), 1.97 (m, 1 H,
CH2), 2.21 (m, 1 H, CH2), 2.56 (m, 1 H, CH2), 2.91 (m, 1 H,CH2),
2.99 (m, 1 H, CH, J = 10.3 Hz),3.77 (s, 3 H, CH3), 4.54 (d, CH,
J = 10.3 Hz), 6.92 (m, 4 H, C6H5), 7.12 (d, 1 H, CH, J = 2.3), 7.21
(m, 4 H, C6H5), 8.61 (s, 1 H, NH).
Anal. Calcd for C24H27N3O3: C, 71.09; H, 6.71; N 10.36. Found: C,
70.93; H, 6.89; N, 10.47.
Methylidenecyclohexanols 11a,b
These compounds were prepared according to the standard proce-
dure by reacting the ketones 8a–c with MeLi in Et2O.
MS: m/z = 316 [M]+.
9c
1-Methyl-2,6-bis(phenylmethylidene)cyclohexanol (11a)
Pale yellow powder; yield: 68%; mp 120–121 °C (Lit.5 mp 121–
122 °C).
1H NMR: = 1.27–1.60 (m, 1 H, CH2), 1.64 (m, 3 H, CH3), 1.72–
1.88 (m, 1 H, CH2), 1.88 (s, 1 H, OH), 2.15–2.31 (m, 2 H, CH3),
2.90–3.02 (m, 2 H, CH2), 7.16–7.36 (m, 10 H, C6H5), 7.79 (2
H,CH=).
Colorless crystals; yield: 67%; mp 169–171 °C.
1H NMR: = 2.25 (s, 3 H, CH3), 2.70 (dd, 1 H, CH2, J = 5.7, 9.8
Hz), 2.88 (dd, 1 H, CH2, J = 2.6, 9.8 Hz), 3.59 (m, 2 H, CH2), 3.77
(s, 3 H, CH3), 3.82 (s, 3 H, CH3), 3.86 (d, 1 H, CH, J = 11.3 Hz),
5.59 (d, 1 H, CH, J = 11.3 Hz), 6.78–7.20 (m, 8 H, 2 C6H5), 7.33 (s,
1 H, CH=), 9.60 (s, 1 H, NH).
Anal. Calcd for C22H25N3O2: C, 72.70; H, 6.93; N, 11.56. Found: C,
72.58; H, 7.09; N, 11.43.
MS: m/z = 363 [M]+.
13C NMR: = 18.5 (CH3), 22.9 (CH2), 28.3 (2 CH2). 128.2 (2 CH=),
128.5, 130.2, 136.8 (2 C6H5), 135.8, 136.10 (2 Cipso), 141.3 (C–O).
1-Methyl-2,6-bis(4-methoxyphenyl)methylidenecyclohexanol
(11b)
N-Acetyldihydropyrazoles 10a–c
These compounds were obtained by treatment of anhyd compounds
9a–c with Ac2O according to a standard procedure and purified by
recrystallization from EtOH.
Pale yellow powder; yield 65%; mp 153–154 °C (Lit.5 mp 155 °C).
1H NMR: = 1.72–1.85 (m, 2 H, CH2), 1.61 (m, 3 H, CH3), 1.73–
1.84 (m, 1 H, CH2), 2.15–2.33 (m, 2 H, CH3), 2.61 (s, 1 H, OH),
7.26–7.48 (m, 10 H, C6H5), 7.79 (2 H, CH=).
13C NMR: = 19.6 (CH3), 22.9 (CH2), 28.9 (2 CH2), 50.6 (2 CH3),
113.8 (2 CH=), 132.1, 136.4 (2 C6H4), 128.6 (2 C), 134.2 (2 Cipso),
137.8 (2 C–O).
2-Acetyl-3-phenyl-7-phenylmethylidene-3,4,5,6,7,9-hexahydro-
2H-indazole (10a)
Colorless crystals; yield: 73%; mp 168–169 °C (Lit.5 mp 168–
169 °C).
1H NMR: = 1.50 (m, 1 H, CH2), 2.38 (s, 3 H, CH3), 3.05 (m, 1 H,
CH, J = 9.3 Hz), 4.93(d, 1 H, CH, J = 9.3 Hz), 7.18 (d, 1 H, CH,
J = 2.0 Hz), 7.24–7.40 (m, 10 H, 2 C6H5).
13C NMR: = 22.2 (CH3), 24.3, 29.0, 30.7 (3 CH2), 57.2, 57.7 (2
CH), 125.5 (CH=), 127.3 (C), 127.5, 127.9, 128.2, 128.7, 129.5,
130.6 (C6H5), 135.9, 141.8 (2 Cipso), 158.6 (C=N), 170.1 (C=O).
N-Methyl Substituted Dihydropyrazoles 12a,b; General Proce-
dure
A mixture of a chalcone 8a or 8b (5 mmol) and methylhydrazine (2
mL) was boiled in MeOH (30 mL) with stirring for 1 h and cooled
to 0 °C. The crystals formed were filtered, washed with aq MeOH,
and purified by recrystallization from MeOH.
MS: m/z = 330 [M]+.
2-Methyl-3-phenyl-7-phenylmethylidene-3,4,5,6,7,9-hexa-
hydro-2H-indazole (12a)
Yellow crystals; yield: 72%; mp 120–121 °C.
2-Acetyl-3-(4-methoxyphenyl)-7-(4-methoxyphenyl)methyl-
idene-3,4,5,6,7,9-hexahydro-2H-indazole (10b)
Colorless crystals; yield: 71%; mp 162–163 °C (Lit.5 mp 162–
163 °C).
1H NMR: = 1.49 (m, 1 H, CH2), 1.63 (m, 1 H, CH2), 1.93 (m, 1 H,
CH2), 2.16 (m, 1 H, CH2), 2.42 (m, 1 H, CH2), 2.97 (m, 1 H, CH2),
2.35 (s, 3 H, CH3), 3.04 (m, 1 H, CH, J = 9.5 Hz), 3.78 (s, 3 H, CH3),
3.83 (s, 3 H, CH3), 4.86 (d, 1 H, CH, J = 9.5 Hz), 6.89 (m, 4 H,
C6H4), 7.14 (d, 1 H, CH, J = 2.6 Hz), 7.22 (m, 4 H, C6H5).
13C NMR: = 22.2 (CH3), 24.3, 29.0, 30.0 (3 CH2), 55.2 (2 CH),
57.2, 67.3 (2 CH), 126.9 (CH=), 127.6 (C), 113.7, 114.2, 131.1 (2
C6H5), 128.8, 144.1 (2 Cipso), 158.8 (2 C–O), 159.1 (C=N), 170.29
(C=O).
1H NMR: = 1.40 (m, 1 H, CH2), 1.52 (m, 1 H, CH2), 1.88 (m, 1 H,
CH2), 2.02 (m, 1 H, CH2), 2.40 (m, 1 H, CH2), 2.86 (m, 1 H, CH2),
2.80 (s, 3 H, CH3), 3.01 (dd, 1 H, CH, J = 13.8 Hz), 3.65 (d, 1 H,
CH, J = 13.8 Hz), 7.20 (d, 1 H, CH=, J = 1.8 Hz), 7.22–7.46 (m, 10
H, C6H5).
13C NMR: = 24.3 (CH2), 26.7 (2 CH2), 42.0 (CH3), 55.2, 81.4 (2
CH), 127.0 (CH=), 127.1 (C), 127.3, 127.7, 128.0, 128.6, 128.6 (2
C6H5), 130.9, 136.6 (2 Cipso), 155.2 (C=N).
Anal. Calcd for C21H22N2: C, 83.41; H, 7.33; N, 9.26. Found: C,
84.53; H, 7.21; N, 9.33.
3-(4-Methoxyphenyl)-7-(4-methoxyphenyl)methylidene-2-
methyl-3,4,5,6,7,9-hexahydro-2H-indazole (12b)
Yellow crystals; yield: 69%; mp 105–106 °C.
1H NMR: = 1.48 (m, 1 H, CH2), 1.88 (m, 1 H, CH2), 1.98 (m, 1 H,
CH2), 2.39 (m, 1 H, CH2), 2.83 (m, 1 H, CH2), 2.87 (m, 1 H, CH2),
2.77 (s, 3 H, CH3), 2.99 (dm, 1 H, CH, J = 14.0 Hz), 3.58 (d, 1 H,
CH, J = 14.0 Hz), 3.81 (s, 3 H, CH3), 3.82 (s, 3 H, CH3), 7.15 (d, 1
MS: m/z = 390 [M]+.
2-Acetyl-3-(4-methoxyphenyl)-7-(4-methoxyphenyl)methyl-
idene-5-methyl-5-aza-3,4,5,6,7,9-hexahydro-2H-indazole (10c)
Colorless crystals; yield: 69%; mp 232–233 °C.
Synthesis 2002, No. 13, 1891–1897 ISSN 0039-7881 © Thieme Stuttgart · New York