Holzer et al.
C
16H13N3O2 (279.30): C 68.81, H 4.69, N 15.04. Found:
C
7.18 (m, 2 H, Ph H-2,6), 10.61, 11.99 and 16.60 (br s, 2 H, OH,
NH). 13C NMR (DMSO-d6): isomer X δ 16.2 (5-Me, 1J ) 127.6
Hz), 17.1 (Me of R,4 1J ) 130.6 Hz), 47.9 (CH2, 1J ) 139.1 Hz),
94.0 (pyrazole C-4), 127.1 (Ph C-4), 127.4 (Ph C-2,6), 128.3 (Ph
C-3,5), 137.8 (Ph C-1), 145.9 (pyrazole C-5, 2J (C-5,5-Me) ) 6.7
Hz), 151.5 (C-N), 160.6 (pyrazole C-3); isomer Y δ 12.6 (Me of
R4), 14.5 (5-Me), 97.7 (very br, pyrazole C-4), 127.2 (Ph C-4),
127.3 (Ph C-2,6), 128.4 (Ph C-3,5), 137.6 (Ph C-1), 144.2
(pyrazole C-5, 2J (C-5,5-Me) ) 6.7 Hz), 152.5 (br, C-N). MS:
m/z (%) ) 245 (M+, 12), 91 (100), 80 (11), 67 (10), 65 (29), 51
(10), 43 (17), 42 (17). Anal. Calcd for C13H15N3O2 (245.28): C
63.66, H 6.16, N 17.13. Found: C 63.63, H 6.13, N 17.04.
68.91, H 4.92, N 15.10.
(Z)-2,4-Dih yd r o-4-[(h yd r oxya m in o)m e t h ylid e n e ]-5-
m eth yl-2-p h en yl-3H-p yr a zol-3-on e (3d ). Yield 88% (method
b), yellowish crystals of mp 171 °C (diisopropyl ether) (lit. mp
173 °C).42 1H NMR (DMSO-d6): (isomers X:Y ) 5:1), isomer X
δ 2.15 (s, 3 H, 5-Me), 7.16 (m, 1 H, Ph H-4), 7.39 (m, 2 H, Ph
H-3,5), 7.75 (s, 1 H, N-CH), 7.86 (m, 2 H, Ph H-2,6), 10.68,
12.55 and 16.25 (br s, OH, NH); isomer Y δ 2.27 (s, 3 H, 5-Me),
7.21 (m, 1 H, Ph H-4), 7.42 (m, 2 H, Ph H-3,5), 7.74 (m, 2 H,
Ph H-2,6), 8.05 (s, 1 H, N-CH), 10.68, 12.55 and 16.25 (br s,
OH, NH). 13C NMR (DMSO-d6): isomer X δ 12.5 (5-Me, J )
1
128.0 Hz), 94.9 (pyrazole C-4), 119.0 (Ph C-2,6), 124.6 (Ph C-4),
128.7 (Ph C-3,5), 138.7 (Ph C-1), 139.1 (N-CH, 1J ) 174.7 Hz),
149.0 (pyrazole C-5, 2J (C-5,5-Me) ) 6.8 Hz, 3J (C-5,N-CH) )
2.8 Hz), 161.7 (pyrazole C-3); isomer Y δ 14.2 (br, 5-Me), 120.1
(Z)-2-Ben zyl-2,4-Dih yd r o-4-[(h yd r oxya m in o)p h en yl-
m eth ylen e]-5-m eth yl-3H-p yr a zol-3-on e (3h ). Yield 92%
(method a), colorless needles of mp 154-156 °C (EtOH). 1H
NMR (DMSO-d6): δ 1.55 (s, 3 H, 5-Me), 4.98 (s, 2 H, CH2),
7.23 (m, 2 H, Bzl H-2,6), 7.26 (m, 1 H, Bzl H-4), 7.34 (m, 2 H,
Bzl H-3,5), 7.47 (m, 2 H, dCPh H-2,6), 7.40-7.53 (m, 3 H, d
CPh H-3,4,5), 12.36 (br s, 2 H, OH, NH). 13C NMR (DMSO-
1
(Ph C-2,6), 125.1 (Ph C-4), 128.8 (Ph C-3,5), 142.5 (N-CH, J
) 163.1 Hz), 146.6. (pyrazole C-5, 2J (C-5,5-Me) ) 6.8 Hz, 3J (C-
5,N-CH) ) 5.2 Hz). MS: m/z (%) ) 217 (M+, 33), 199 (18), 198
(30), 132 (12), 131 (41), 103 (29), 92 (11), 91 (100), 78 (12), 77
(88), 69 (20), 68 (15), 67 (32), 66 (24), 65 (16), 64 (15), 57 (22),
55 (21), 53 (19), 52 (17), 51 (58), 50 (13), 45 (12), 43 (38), 42
(18), 41 (43).
1
1
d6): δ 14.3 (5-Me, J ) 127.6 Hz), 48.3 (CH2, J ) 139.0 Hz),
94.3 (pyrazole C-4), 127.2 (Bzl C-4), 127.3 (Bzl C-2,6), 128.3
(dCPh C-2,6), 128.4 (Bzl C-3,5 and dCPh C-3,5), 130.0 (dCPh
C-4), 133.4 (br, dCPh C-1), 137.7 (Bzl C-1), 145.4 (pyrazole
2
C-5, J (C-5,5-Me) ) 6.8 Hz), 151.6 (C-N), 157.0 (br, pyrazole
(Z)-2,4-Dih ydr o-4-[1-(h ydr oxyam in o)eth yliden e]-5-m eth -
yl-2-p h en yl-3H-p yr a zol-3-on e (3e). Yield 82% (method a),
the raw product was washed with diisopropyl ether to afford
colorless crystals of mp 142-144 °C (lit. mp 154-156 °C).26
1H NMR (DMSO-d6): (isomers X:Y ) 2:1), isomer X δ 2.27 (s,
3 H, 5-Me), 2.32 (s, 3 H, Me of R4), 7.17 (m, 1 H, Ph H-4), 7.39
(m, 2 H, Ph H-3,5), 7.89 (m, 2 H, Ph H-2,6), 11.50 and 16.00
(br s, 2 H, OH, NH); isomer Y δ 2.29 (s, 3 H, 5-Me), 2.32 (s, 3
H, Me of R4), 7.14 (m, 1 H, Ph H-4), 7.39 (m, 2 H, Ph H-3,5),
7.89 (m, 2 H, Ph H-2,6), 11.50 and 16.00 (br s, 2 H, NH, OH).
C-3). MS: m/z (%) ) 307 (M+, 6), 288 (11), 212 (12), 142 (15),
91 (100), 77 (29), 65 (29), 51 (17), 42 (19). Anal. Calcd for
C
18H17N3O2 (307.36): C 70.34, H 5.58, N 13.67. Found:
C
70.17, H 5.58, N 13.72.
Gen er a l P r oced u r e for th e Syn th esis of Sp ir o-Com -
p ou n d s 4. Under Ar and with stirring, to a solution of
compound 3 (1 mmol) in 10 mL of anhydrous ether was
dropwise added a solution of trichloroacetyl isocyanate (198
mg, 1.05 mmol) in 10 mL of anhydrous ether. After completion
of the addition, the mixture was stirred for 30 min at room
temperature, then K2CO3 (152 mg, 1.1 mmol) was slowly
added, and the mixture was refluxed for 2 h. After evaporation
of the solvent, 10 mL of water was added, the mixture was
extracted with dichloromethane (3 × 10 mL), and the combined
organic phases were dried over anhydrous Na2SO4 and evapo-
rated in vacuo. The residue was purified by recrystallization
or by chromatographic methods.
1
13C NMR (DMSO-d6): isomer X δ 16.4 (5-Me, J ) 128.0 Hz),
17.3 (Me of R,4 1J ) 130.8 Hz), 95.5 (pyrazole C-4), 119.3 (Ph
C-2,6), 124.6 (Ph C-4), 128.7 (Ph C-3,5), 138.7 (Ph C-1), 147.7
(pyrazole C-5, 2J (C-5,5-Me) ) 6.8 Hz), 152.8 (C-N), 161.3
(pyrazole C-3); isomer Y δ 12.8 (Me of R,4 1J ) 130.1 Hz), 15.5
(br, 5-Me, 1J ) 127.7 Hz), 96.5 (br, pyrazole C-4), 118.8 (Ph
C-2,6), 124.3 (Ph C-4), 128.7 (Ph C-3,5), 138.7 (Ph C-1), 146.5
2
(pyrazole C-5, J (C-5,5-Me) ) 6.8 Hz), 157.3 (br, C-N), 160.7
(pyrazole C-3). MS: m/z (%) ) 231 (M+, 64), 215 (12), 212 (30),
199 (12), 92 (12), 91 (61), 82 (11), 81 (12), 80 (28), 78 (12), 77
(100), 69 (14), 67 (31), 66 (24), 65 (20), 64 (17), 63 (13), 54 (11),
53 (12), 52 (16), 51 (73), 50 (16), 43 (14), 42 (54), 41 (14).
(Z)-2,4-Dih yd r o-4-[(h yd r oxya m in o)p h en ylm eth ylen e]-
5-m eth yl-2-ph en yl-3H-pyr azol-3-on e (3f). Yield 76% (method
a), recrystallization from ethanol afforded cream colored
crystals of mp 162-170 °C (dec) (lit. mp 166 °C45 or 168-172
°C26). 1H NMR (DMSO-d6): δ 1.61 (s, 3 H, 5-Me), 7.21 (m, 1
H, 2-Ph H-4), 7.44 (m, 2 H, 2-Ph H-3,5), 7.52 (m, 2 H, C-Ph
H-3,5), 7.53 (m, 1 H, C-Ph H-4), 7.57 (m, 2 H, C-Ph H-2,6),
7.89 (m, 2 H, 2-Ph H-2,6), 12.90 (br s, 2 H, OH, NH). 13C NMR
5,7-Dim eth yl-2-p h en yl-1,5,6-tr ia za sp ir o[2.4]h ep ta -1,6-
d ien -4-on e (4a ). The crude product was purified by prepara-
tive TLC (dichloromethane/ethyl acetate 1:10) to afford a
colorless oil which solidified on standing (mp 66 °C), yield 61%.
1H NMR (CDCl3): δ 1.80 (s, 3 H, 7-Me), 3.42 (s, 3 H, 5-Me),
7.58 (m, 2 H, Ph H-3,5), 7.69 (m, 1 H, Ph H-4), 7.81 (m, 2 H,
Ph H-2,6). 13C NMR (CDCl3): δ 12.9 (7-Me, 1J ) 129.3 Hz),
32.2 (5-Me, J ) 139.8 Hz), 45.0 (C-3, J (C-3,7-Me) ) 3.2 Hz),
120.1 (Ph C-1), 129.6 (Ph C-3,5), 131.0 (Ph C-2,6), 135.0 (Ph
C-4), 156.5 (C-7, 2J (C-7,7-Me) ) 7.6 Hz), 157.9 (C-2, 3J (C-2,
Ph H-2,6) ) 5.5 Hz), 170.4 (C-4, 3J (C-4,5-Me) ) 2.2 Hz). IR
(KBr): ν 1780 (CdN), 1704 (CdO) cm-1. MS: m/z (%) ) 213
(M+, 55), 142 (23), 118 (16), 105 (100), 77 (31), 76 (16), 67 (90),
56 (11), 52 (11), 51 (46), 50 (22), 43 (29), 42 (10). Anal. Calcd
for C12H11N3O (213.24): C 67.59, H 5.20, N 19.71. Found: C
67.66, H 5.34, N 19.62.
1
3
1
(DMSO-d6): δ 14.5 (5-Me, J ) 128.0 Hz), 96.0 (br, pyrazole
C-4), 119.5 (2-Ph C-2,6), 124.9 (2-Ph C-4), 128.6 (C-Ph C-3,5),
128.8 (2-Ph C-3,5 and C-Ph C-2,6), 130.7 (C-Ph C-4), 132.1 (br,
C-Ph C-1), 138.5 (2-Ph C-1), 147.5 (pyrazole C-5, 2J (C-5,5-Me)
) 7.0 Hz), 152.9 (br, C-N), 158.8 (br, pyrazole C-3). MS: m/z
(%) ) 293 (M+, 7), 275 (15), 231 (27), 212 (14), 91 (56), 80 (13),
78 (11), 77 (100), 67 (22), 66 (17), 65 (16), 64 (13), 63 (10), 51
(59), 50 (13), 43 (12), 42 (34), 42 (10).
5,7-Dim eth yl-2-(2-th ien yl)-1,5,6-tr ia za sp ir o[2.4]h ep ta -
1,6-d ien -4-on e (4b). The crude product was purified by
preparative TLC (dichloromethane/ethyl acetate 1:1) to afford
yellowish-orange crystals of mp 93 °C, yield 54%. 1H NMR
(CDCl3): δ 1.82 (s, 3 H, 7-Me), 3.42 (s, 3 H, 5-Me), 7.28 (dd,
2J (H-4,H-5) ) 5.0 Hz, 2J (H-4,H-3) ) 3.8 Hz, 1 H, Th H-4), 7.67
(dd, 3J (H-3,H-4) ) 3.8 Hz, 4J (H-3,H-5) ) 1.2 Hz, 1 H, Th H-3),
(Z)-2-Be n zyl-2,4-Dih yd r o-4-[1-(h yd r oxya m in o)e t h -
yliden e]-5-m eth yl-3H-pyr azol-3-on e (3g). Yield 54% (method
a), yellowish crystals of mp 133 °C (diisopropyl ether). 1H NMR
(DMSO-d6): (isomers X:Y ) 2:1), isomer X δ 2.16 (s, 3 H, 5-Me),
2.25 (s, 3 H, Me of R4), 4.86 (s, 2 H, CH2), 7.16-7.34 (m, 3 H,
Ph H-3,4,5), 7.20 (m, 2 H, Ph H-2,6), 10.61, 11.99 and 16.60
(br s, 2 H, OH, NH); isomer Y δ 2.15 (s, 3 H, 5-Me), 2.16 (s, 3
H, Me of R4), 4.93 (s, 2 H, CH2), 7.16-7.34 (m, 3 H, Ph H-3,4,5),
3
4
7.97 (dd, J (H-5,H-4) ) 5.0 Hz, J (H-5,H-3) ) 1.2 Hz, 1 H, Th
H-5). 13C NMR (CDCl3): δ 12.9 (7-Me, 1J ) 129.3 Hz), 32.2
(5-Me, 1J ) 139.8 Hz), 45.6 (C-3, 3J (C-3,7-Me) ) 3.2 Hz), 121.7
(Th C-2, 2J (C-2,H-3) ) 5.9 Hz, 3J (C-2,H-4) ) 10.9 Hz, 3J (C-
1
2
2,H-5) ) 6.5 Hz), 128.9 (Th C-4, J ) 172.4 Hz, J (C-4,H-3) )
2
1
4.8 Hz, J (C-4,H-5) ) 3.9 Hz), 137.1 (Th C-3, J ) 171.6 Hz,
2J (C-3,H-4) ) 5.9 Hz, 3J (C-3,H-5) ) 9.5 Hz), 137.4 (Th C-5, 1J
) 187.8 Hz, 2J (C-5,H-4) ) 7.5 Hz, 3J (C-5,H-3) ) 11.0 Hz), 151.1
(45) Rana, A. K.; Shah, J . R. Indian J . Chem. Sect. A 1981, 20A,
142-144.
7948 J . Org. Chem., Vol. 68, No. 21, 2003