Spiro-Fused (C5)-Isoxazolino-(C4)-pyrazolones
J . Org. Chem., Vol. 67, No. 3, 2002 881
3-(2-Ch lor op h e n yl)-9-m e t h yl-7-p h e n yl-1-oxa -2,7,8-
tr ia za sp ir o[4.4]n on a -2,8-d ien -6-on e (6). Following general
method B, 4a (624 mg, 2.22 mmol) and phenylhydrazine (229
µL, 2.33 mmol) gave 6 (483 mg, 64%): mp 103-104 °C; IR 3064,
2999, 2921, 1705, 1595, 1497, 1433, 1367, 1306 cm-1; 1H NMR
δ 2.23 (s, 3H), 3.86 (s, 2H), 7.20 (t, J ) 7.5 Hz, 1H), 7.38 (m,
5H), 7.68 (dd, J ) 7.9 and 1.8 Hz, 1H), 7.88 (d, J ) 7.5 Hz,
2H); 13C NMR δ 12.7, 44.3, 87.0, 118.5, 125.4, 126.9, 127.2,
128.8, 130.6, 131.0, 131.7, 132.8, 137.4, 155.4, 157.9, 169.2.
Anal. Calcd for C18H14ClN3O2: C, 63.63; H, 4.15; N, 12.37.
Found: C, 63.52; H, 4.07; N, 12.23.
4c (202 mg, 650 µmol), methylhydrazine (140 µL, 2.6 mmol),
and TiCl4 (500 µmol) gave 12 (193 mg, 97%): mp 146-147 °C;
IR 3067, 2929, 1715, 1582, 1469, 1359, 886, 774, 694 cm-1; 1H
NMR δ 3.45 (s, 3H), 3.93 (s, 2H), 7.37 (m, 4H), 7.71 (dd, J )
7.5 and 1.8 Hz, 2H), 7.79 (td, J ) 7.5 and 1.8 Hz, 1H), 8.13 (d,
J ) 7.9 Hz, 1H), 8.58 (dt, J ) 4.8 and 0.9 Hz, 1H); 13C NMR
δ 31.8, 43.9, 85.3, 122.3, 124.8, 125.8, 128.5, 128.9, 130.7, 136.5,
147.6, 149.3, 155.2, 157.9, 171.7. Anal. Calcd for C17H14N4O2:
C, 66.66; H, 4.61; N, 18.29. Found: C, 66.96; H, 4.80; N, 18.16.
7,9-Dip h en yl-3-(2-p yr id yl)-1-oxa -2,7,8-tr ia za sp ir o[4.4]-
n on a -2,8-d ien -6-on e (13). Following general method C, 4c
(600 mg, 1.9 mmol), phenylhydrazine (230 µL, 2.3 mmol), and
TiCl4 (1.4 mmol) gave the corresponding hydrazone (205 mg,
27%) [mp 141-142 °C; IR 3206, 3059, 2949, 1757, 1600, 1584,
9-E t h yl-3-(4-m e t h oxyp h e n yl)-7-m e t h yl-1-oxa -2,7,8-
tr ia za sp ir o[4.4]n on a -2,8-d ien -6-on e (7). Following general
method C, 4b (231 mg, 790 µmol), methylhydrazine (170 µL,
3.2 mmol), and TiCl4 (500 µmol) gave 7 (265 mg, 87%): mp
74-75 °C; IR 3052, 2976, 2941, 2839, 1716, 1606, 1253, 897,
1
1494, 1249, 911, 698 cm-1; H NMR δ 3.82 (s, 3H), 4.03 (d, J
) 18 Hz, 1H), 4.22 (d, J ) 18 Hz, 1H), 6.83 (td, J ) 7.6 and
0.9 Hz, 1H), 6.95 (d, 2H), 7.19 (t, J ) 7.6 Hz, 2H), 7.27 (ddd,
J ) 7.6, 4.8 and 0.9 Hz, 1H), 7.46 (m, 5H), 7.57 (br s, 1H),
7.68 (td, J ) 7.6 and 1.8 Hz, 1H), 7.95 (d, J ) 7.6 Hz, 1H),
8.57 (dt, J ) 4.8 and 0.9 Hz, 1H); 13C NMR δ 41.1, 52.9, 92.7,
112.9, 120.6, 121.7, 124.4, 129.0, 129.1, 129.5, 129.7, 136.3,
139.0, 143.6, 148.4, 149.2, 158.5, 170.9, 172.8] as well as 13
(308 mg, 44%) [mp 124-126 °C; IR 3065, 1725, 1585, 1493,
1324, 1131, 750, 671 cm-1; 1H NMR δ 4.02 (d, J ) 18 Hz, 1H),
4.08 (d, J ) 18 Hz, 1H), 7.26 (td, J ) 6.9 and 0.9 Hz, 2H), 7.42
(m, 5H), 7.82(m, 3H), 8.01 (d, J ) 7.9 Hz, 2H), 8.16 (dd, J )
7.9 and 0.9 Hz, 1H), 8.60 (dd, J ) 5.3 and 0.9 Hz, 1H); 13C
NMR δ 44.5, 86.5, 118.7, 122.4, 125.0, 125.6, 126.3, 128.5,
128.9, 129.1, 131.1, 136.6, 137.5, 147.6, 149.5, 155.7, 158.0,
170.2].
1
819 cm-1; H NMR δ 1.23 (t, J ) 7.3 Hz, 3H), 2.43 (m, 2H),
3.32 (s, 3H), 3.49 (d, J ) 17 Hz, 1H), 3.70 (d, J ) 17 Hz, 1H),
3.86 (s, 3H), 6.94 (d, J ) 8.8 Hz, 2H), 7.60 (d, J ) 8.8 Hz, 2H);
13C NMR δ 9.1, 20.1, 31.3, 42.1, 55.2, 84.9, 114.1, 120.0, 128.5,
154.9, 161.4, 171.4. Anal. Calcd for C15H17N3O3: C, 62.71; H,
5.96; N, 14.63. Found: C, 62.38; H, 5.89; N, 14.46.
9-E t h yl-3-(4-m e t h oxyp h e n yl)-7-p h e n yl-1-oxa -2,7,8-
tr ia za sp ir o[4.4]n on a -2,8-d ien -6-on e (8). Following general
method A, 4b (150 mg, 515 µmol) and phenylhydrazine (101
µL, 1.03 mmol) in xylene gave 8 (130 mg, 72%): mp 119-120
°C; IR 3036, 2976, 1715, 1596, 1499, 1347, 1252, 819, 754 cm-1
;
1H NMR δ 1.27 (t, J ) 7.5 Hz, 3H), 2.48 (m, 2H), 3.57 (d, J )
17 Hz, 1H), 3.75 (d, J ) 17 Hz, 1H), 3.79 (s, 3H), 6.89 (d, J )
8.8 Hz, 2H), 7.17 (t, J ) 7.5 Hz, 1H), 7.38 (t, J ) 7.5 Hz, 2H),
7.57 (d, J ) 8.8 Hz, 2H), 7.90 (d, J ) 7.5 Hz, 2H); 13C NMR δ
9.1, 20.3, 42.6, 55.2, 86.3, 114.2, 118.3, 119.9, 125.1, 128.6,
128.7, 137.5, 155.0, 161.5, 162.0, 169.8. Anal. Calcd for
3-(2-Met h oxyp h en yl)-7-m et h yl-9-(4-m et h ylp h en yl)-1-
oxa -2,7,8-tr ia za sp ir o [4.4]n on a -2,8-d ien -6-on e (14). Fol-
lowing general method A, 4d (234 mg, 662 µmol) and meth-
ylhydrazine (53 µL, 1.0 mmol) in toluene gave 14 (166 mg,
72%): mp 156-157 °C; IR 3029, 2939, 2838, 1721, 1670, 1601,
C
20H19N3O3: C, 68.75; H, 5.48; N, 12.03. Found: C, 68.85; H,
5.48; N, 11.97.
1
9-E t h yl-3-(4-m et h oxyp h en yl)-1-oxa -2,7,8-t r ia za sp ir o-
[4.4]n on a -2,8-d ien -6-on e (9). Following general method A,
4b (525 mg, 1.8 mmol) and hydrazine hydrate (350 µL, 7.2
mmol) in toluene at room temperature gave 9 (390 mg, 80%):
mp 170-171 °C; IR 3345, 3223, 3111, 2983, 1715, 1604, 1514,
1253 cm-1; H NMR δ 2.35 (s, 3H), 3.41 (s, 3H), 3.77 (s, 3H),
3.85 (d, J ) 18 Hz, 1H), 3.92 (d, J ) 18 Hz, 1H), 6.93 (d, J )
8 Hz, 1H), 7.01 (td, J ) 8 and 1 Hz, 1H), 7.19 (d, J ) 8 Hz,
2H), 7.42 (td, J ) 8 and 2 Hz, 1H), 7.65 (d, J ) 8 Hz, 2H), 7.89
(dd, J ) 8 and 2 Hz, 1H); 13C NMR δ 21.4, 31.8, 46.7, 55.4,
85.1, 111.4, 116.8, 120.9, 126.0, 129.6, 129.8, 132.1, 141.0,
1
1420, 1249, 1178, 869, 827 cm-1; H NMR δ 1.23 (t, J ) 7.3
Hz, 3H), 2.43 (m, 2H), 3.52 (d, J ) 17 Hz, 1H), 3.72 (d, J ) 17
Hz, 1H), 3.85 (s, 3H), 6.94 (d, J ) 8.8 Hz, 2H), 7.61 (d, J ) 8.8
Hz, 2H), 8.6 (br, 1H); 13C NMR δ 9.2, 19.9, 41.5, 84.3, 114.5,
120.2, 128.9, 155.9, 161.3, 161.5, 174.1.
155.3, 156.0, 157.5, 172.3. Anal. Calcd for
C20H19N3O3‚
0.33H2O: C, 67.59; H, 5.58; N, 11.82. Found: C, 67.48; H, 5.43;
N, 11.76.
3-(2-Met h oxyp h en yl)-7-p h en yl-9-(4-m et h ylp h en yl)-1-
oxa -2,7,8-tr ia za sp ir o [4.4]n on a -2,8-d ien -6-on e (15). Fol-
lowing general method A, 4d (383 mg, 1.08 mmol) and
phenylhydrazine (117 µL, 1.19 mmol) in toluene gave 15 (258
mg, 58%): mp 180-181 °C; IR 3032, 2843, 1722, 1593, 1491,
7-Be n zyl-9-e t h yl-3-(4-m e t h oxyp h e n yl)-1-oxa -2,7,8-
tr ia za sp ir o[4.4]n on a -2,8-d ien -6-on e (10). Following general
method A, 4b (150 mg, 515 µmol), TEA (208 mg, 2.06 mmol),
and benzylhydrazine dihydrochloride (200 mg, 1.03 mmol) in
xylene gave 10 (140 mg, 77%): mp 123-124 °C; IR 3032, 2976,
2930, 1714, 1606, 1412, 1349, 1253 cm-1; 1H NMR δ 1.08 (t, J
) 7.3 Hz, 3H), 2.29 (m, 2H), 3.41 (d, J ) 17 Hz, 1H), 3.60 (d,
J ) 17 Hz, 1H), 3.72 (s, 3H), 4.69 (d, J ) 15 Hz, 1H), 4.76 (d,
J ) 15 Hz, 1H), 6.82 (d, J ) 8.8 Hz, 2H), 7.24 (m, 5H), 7.49 (d,
J ) 8.8 Hz, 2H); 13C NMR δ 9.3, 20.3, 42.3, 48.2, 55.3, 85.2,
114.2, 120.1, 127.7, 128.0, 128.5, 128.6, 135.8, 155.0, 161.5,
161.6, 171.4. Anal. Calcd for C21H21N3O3: C, 69.41; H, 5.82;
N, 11.56. Found: C, 69.24; H, 5.77; N, 11.55.
1392, 1256, 756 cm-1 1H NMR δ 2.39 (s, 3H), 3.80 (s, 3H),
;
3.97 (d, J ) 18 Hz, 1H), 4.04 (d, J ) 18 Hz, 1H), 6.95 (d, J )
7.4 Hz, 1H), 7.05 (t, J ) 7.4 Hz, 1H), 7.23 (m, 3H), 7.45 (m,
3H), 7.78 (d, J ) 8.4 Hz, 2H), 7.93 (dd, J ) 7.9 and 1.8 Hz,
1H), 8.02 (d, J ) 7.9 Hz, 2H); 13C NMR δ 21.5, 47.3, 55.4, 86.3,
111.5, 116.7, 118.7, 121.0, 125.4, 125.8, 126.4, 128.9, 129.7,
129.8, 132.2, 137.7, 141.6, 155.4, 156.4, 157.5, 170.7. Anal.
Calcd for C25H21N3O3: C, 72.98; H, 5.14; N, 10.21. Found: C,
72.86; H, 5.07; N, 10.15.
9 -E t h y l -3 ,7 -b i s (4 -m e t h o x y p h e n y l )-1 -o x a -2 ,7 ,8 -
tr ia za sp ir o[4.4]n on a -2,8-d ien -6-on e (11). Following general
method A, 4b (150 mg, 515 µmol), TEA (104 mg, 1.03 mmol),
and (4-methoxyphenyl)hydrazine hydrochloride (180 mg, 1.03
mmol) in xylene gave 11 (190 mg, 97%): mp 122-123 °C; IR
2976, 2935, 2837, 1711, 1514, 1243 cm-1; 1H NMR δ 1.31 (t, J
) 7.0 Hz, 3H), 2.52 (m, 2H), 3.58 (d, J ) 17 Hz, 1H), 3.81 (d,
J ) 17 Hz, 1H), 3.83 (s, 3H), 3.86 (s, 3H), 6.95 (d, J ) 8.8 Hz,
2H), 6.96 (d, J ) 8.8 Hz, 2H), 7.63 (d, J ) 8.8 Hz, 2H), 7.80 (d,
J ) 8.8 Hz, 2H); 13C NMR δ 9.4, 20.6, 42.8, 55.4, 55.5, 86.4,
114.1, 114.4, 120.3, 120.5, 128.7, 131.0, 155.0, 157.2, 161.7,
162.1, 169.5. Anal. Calcd for C21H21N3O4: C, 66.48; H, 5.58;
N, 11.08. Found: C, 66.27; H, 5.58; N, 11.08.
3-[2-((4-Br om oben zyl)oxy)ph en yl]-9-(4-m eth oxyph en yl)-
7-m e t h yl-1-oxa -2,7,8-t r ia za sp ir o[4.4]n on a -2,8-d ie n -6-
on e (16). Following general method A, 4e (319 mg, 608 µmol)
and methylhydrazine (43 µL, 670 µmol) in toluene gave 16 (142
mg, 45%): mp 116-117 °C; IR 3080, 2954, 1721, 1681, 1601,
1
1258, 1173 cm-1; H NMR δ 3.37 (s, 3H), 3.73 (d, J ) 18 Hz,
1H), 3.82 (s, 3H), 3.88 (d, J ) 18 Hz, 1H), 4.98 (s, 3H), 6.87 (d,
J ) 8.8 Hz, 2H), 6.95 (d, J ) 8.4 Hz, 1H), 7.03 (dd, J ) 7.5
and 0.9 Hz, 1H), 7.09 (d, J ) 8.8 Hz, 2H), 7.31 (d, J ) 8.8 Hz,
2H), 7.40 (ddd, J ) 7.5, 1.8, and 0.9 Hz, 1H), 7.66 (d, J ) 8.8
Hz, 2H), 7.85 (dd, J ) 7.9 and 1.8 Hz, 1H); 13C NMR δ 31.7,
46.5, 55.3, 69.7, 85.1, 112.5, 114.3, 117.3, 121.3, 121.5, 122.0,
127.7, 128.9, 130.3, 131.6, 132.1, 134.7, 155.4, 155.7, 156.3,
161.4, 171.9. Anal. Calcd for C26H22BrN3O4: C, 60.01; H, 4.26;
N, 8.07. Found: C, 59.75; H, 4.33; N, 7.89.
7-Meth yl-9-ph en yl-3-(2-pyr idyl)-1-oxa-2,7,8-tr iazaspir o-
[4.4]n on a -2,8-d ien - 6-on e (12). Following general method C,