2484 Bull. Chem. Soc. Jpn., 75, No. 11 (2002)
o-Quinonimines in N-Heterocyclic Synthesis
× 9H, 2s, C(CH3)3), 2.58 (2H, s, CH2-), 3.84 (3H, s, OCH3), 6.24,
6.79 (2 × 1H, 2d, JHH = 4.2 Hz, Ar-H); 13C NMR δ 28.3 (CH2-),
31.4, 32.8 (2 × C(CH3)3], 34.3, 35.5 (2 × C(CH3)3), 54.5 (s,
OCH3), 123.4, 125.4 (C-5 & C-7), 129.8 (C-4a), 133.3 (C-3),
141.8 (C-6), 146.4 (C-8), 150.8 (C-8a), 161.5 (C(O), ester), 173.6
(C-2-(O)); MS m/z (%) 331 (M+, 48), 316 (4), 300 (17), 272 (27),
271 (100), 246 (20), 186 (8).
Elution with hexane/CHCl3 (8:2, v/v) afforded yellow leaflets
of 3H-indol-3-one 11 (195 mg, 22%), mp 155–157 °C (benzene),
and were shown to be identical to material prepared as described
above by using 2a.
(C) A reaction between equimolar amounts of 1b and 2a or 2b
in CHCl3 was carried out, and the reaction mixture was worked up
according to the above-described procedure for 2a,b. The product
mixture gave (with 2a) 9a (21%) and 11 (18%) and (with 2b) 9b
(20%) and 11 (14%). Unreacted oxime 1b was also isolated
(~25%) in each case.
(D) A reaction between 1b and 2 molar amounts of 2a,b was
repeated in dry toluene. The reaction mixture was heated under
reflux for 40 h and afforded, after the usual working up, com-
pounds 9a,b (~28%) and 11 (~17), respectively.
ꢁ. Reactions of 1b with Keto Ylides 12a,b: Preparation of
13a,b and 14a,b: A mixture of 1b (0.8 g, 3.4 mmol) and benzoyl-
12a or acetyl-12b methylenetriphenylphosphorane (4 mmol) in
dry toluene (20 mL) was refluxed for 40 h. The product mixture
was chromatographed on silica gel using hexane/chloroform (8:2,
v/v) as the eluent to give 13a or 13b, respectively.
2-Benzoyl-5,7-di-tert-butyl-2,3-dihydrobenzoxazole (13a) was
obtained as pale-yellow flakes (722 mg, 63%), mp 118–120 °C
(cyclohexane); Anal. Found: C, 78.35; H, 8.14; N, 4.20%. Calcd
for C22H27NO2 (337.46): C, 78.30; H, 8.06; N, 4.15%; IR (KBr)
3345 (NH), 1666 cm−1 C(O)Ph; 1H NMR (CDCl3) δ 1.23, 1.26 (2
× 9H, 2s, C(CH3)3], 3.68 (C-2-H), 6.23 (1H, d, JHH = 4.2 Hz, C-
4-H), 6.81 (1H, d, JHH = 4.2 Hz, C-6-H), 7.35–7.77 (5H, m, Ph-
H), 11.3 (1H, s, NH, exchangeable with D2O); 13C NMR δ 31.2,
32.6 (2 × C(CH3)3), 34.1, 35.5 (2 × C(CH3)3), 51.3 (C-2), 123.4,
124.4 (C-4 & C-6), 142.7 (C-5), 147.4 (C-7), 195.5 (C(O), ben-
zoyl); MS m/z (%) 337 (M+, 33), 335 (55), 307 (10), 232 (29), 230
(100), 186 (6).
2-Acetyl 5,7-di-tert-butyl-2,3-dihydrobenzoxazole (13b) was
obtained as pale yellow needles (475 mg, 51%), mp 108–109 °C
(pentane); Anal. Found: C, 74.23; H, 9.09; N, 5.18%. Calcd for
C17H25NO2 (275.39): C, 74.14; H, 9.15; N, 5.08%; IR (KBr) 3330
(NH), 1675 cm−1 (C(O)CH3); 1H NMR (CDCl3) δ 1.24, 1.26 (2 ×
9H, 2s, C(CH3)3), 2.55 (3H, s, (O)CH3), 3.88 (C-2-H), 6.22 (1H, d,
JHH = 4.2 Hz, C-4-H), 6.76 (1H, d, JHH = 4.2 Hz, C-6-H), 10.68
(1H, s, NH, exchangeable with D2O); 13C NMR δ 30.8, 31.3, 32.8
(C(O)CH3 & 2 × C(CH3)3), 34.6, 35.2 (2 × C(CH3)3), 48.8 (C-
2),123.8, 125.9 (C-4 & C-6), 142.3 (C-5), 146.4 (C-7), 192.5
(C(O), acetyl); MS m/z (%) 275 (M+, 22), 273 (38), 258 (11), 245
(9), 230 (100), 186 (8).
Conversion of 13a,b to 14a,b: N-Bromosuccinimide (NBS)
(54 mg, 0.3 mmol) and benzoyl peroxide (7 mg, 0.04 mmol) were
added to a solution of 13a (100 mg, 0.3 mmol) or 13b (82 mg, 0.3
mmol) in 20 mL of dry CCl4. The mixture was refluxed for 2 h
and filtered while hot. Evaporation of the solvent left a residue,
which was triturated with a small amount of light petroleum to
give the dehydrogenated derivative, 14a or 14b.
(335.45): C, 78.77; H, 7.51; N, 4.17%; IR (KBr) 1667 (C(O)Ph),
1
1605 cm−1 (CwN); H NMR (CDCl3) δ 1.23, 1.25 (2 × 9H, 2s,
C(CH3)3], 6.23, 6.83 (2 × 1H, 2d, JHH = 4.2 Hz, C-4-H & C-6-H),
7.35–7.77 (5H, m, Ph-H); MS m/z (%) 335 (M+, 28), 307 (13),
231 (66), 230 (100), 185 (3).
2-Acetyl-5,7-di-tert-butylbenzoxazole (14b) was obtained as
yellow crystals (57 mg, 70%), mp 89–90 °C (light petroleum);
Anal. Found: C, 74.62; H, 8.58; N, 5.06%. Calcd for C17H23NO2
(273.38): C, 74.69; H, 8.48; N, 5.12%; IR (KBr) 1675 (C(O)Me),
1
1598 cm−1 (CwN); H NMR (CDCl3) δ 1.22, 1.24 [2 × 9H, 2s,
C(CH3)3], 2.57 (3H, s, (O)CH3), 6.22, 6.79 (2 × 1H, 2d, JHH = 4.2
Hz, C-4-H & C-6-H); MS m/z (%) 273 (M+, 43), 258 (14), 245
(8), 230 (100), 186 (8).
ꢂ. Reaction of Monoxime 1b with Allylidenetriphenylphos-
phorane (16): Preparation of 19: A solution of allyltriphen-
ylphosphonium bromide (1.4 g, 3.6 mmol) and the monoxime 1b
(0.8 g, 3.4 mmol) in chloroform (40 mL) was stirred by a magnet-
ic stirrer. Freshly prepared aqueous lithium hydroxide (0.5 M, 15
mL, 1 M = 1 mol dm−3) was added in one portion to the mixture,
and the two- phase system was stirred at room temperature for 1 h,
then refluxed for 4 h. The product mixture was then extracted
with CHCl3 (2 × 50 mL) and dried; the solvent was removed un-
der reduced pressure. The residue was chromatographed on silica
gel using hexane/CHCl3 7:3, v/v to give 6,8-di-tert-butyl-2-meth-
yl-2H-1,4-benzoxazine (19) (425 mg, 48%), mp 174–175 °C (ace-
tonitrile); Anal. Found: C, 78.77; H, 9.67; N, 5.32%. Calcd for
C17H25NO (259.39): C, 78.71; H, 9.71; N, 5.40%; IR (KBr) 1600
cm−1 (CwN); 1H NMR (CDCl3) δ 1.24, 1.28 (2 × 9H, 2s,
C(CH3)3), 1.68 (3H, d, JHH = 8.2 Hz, C-2-CH3), 3.84 (1H, d of q,
JHH = 5.8 Hz, C-2-H), 6.25 (1H, d, JHH = 2.4 Hz, C-5-H), 6.87–
6.95 (2H, m, C-3-H & C-7-H); 13C NMR δ 22.2 (C-2-CH3), 31.1,
32.4 (2 × C(CH3)3), 34.3, 35.3 (2 × C(CH3)3), 44.7 (C-2), 122.6,
123.3, 125.2 (C-3, C-5 & C-7), 129.8 (C-4a), 142.4 (C-6), 146.6
(C-8), 150.4 (C-8a); MS m/z (%) 259 (M+, 57), 244 (100), 228
(21), 226 (11), 199 (7), 186 (10).
In the next fractions several polymeric unidentified products
with mp > 300 °C were eluted.
References
1
W. M. Abdou, M. R. Mahran, T. S. Hafez, and M. M.
Sidky, Phosphorus, Sulfur, Silicon, Relat. Elem., 27, 345 (1986).
a) W. M. Abdou, N. A. F. Ganoub, and N. M. Abdel-
2
Rahman, Phosphorus, Sulfur, Silicon, Relat. Elem., 61, 91 (1991).
b) W. M. Abdou, Phosphorus, Sulfur, Silicon, Relat. Elem., 66,
285 (1992). c) W. M. Abdou, and N. A. F. Ganoub, Synth. Com-
mun., 28, 3579 (1998).
3
For recent accounts see references a–g: a) W. M. Abdou,
Phosphorus, Sulfur, Relat. Elem., 177, 325 (2002). b) W. M.
Abdou, A. F. M. Fahmy, and A. A. Kamel, Heteroat. Chem., 13,
357 (2002). c) W. M. Abdou, N. A. F. Ganoub, and A. M. Shaddy,
Phosphorus, Sulfur, Silicon, Relat. Elem., 165, 171 (2000). d) W.
M. Abdou, N. A. F. Ganoub, and A. M. Shaddy, Tetrahedron, 54,
9079 (1998). e) W. A. Abdou, M. A. I. Salem, and A. A. Sediek,
Tetrahedron, 53, 13945 (1997). f) W. M. Abdou, N. A. F. Ganoub,
and A. M. Shaddy, Heterocycl. Commun., 3, 57 (1997). g) W. M.
Abdou, Synth. Commun., 27, 3599 (1997).
4
W. Flitsh, “Comprehensive Heterocyclic Chemistry,” ed by
2-Benzoyl-5,7-di-tert-butylbenzoxazole (14a) was obtained as
a pale-yellow substance (72 mg, 72%), mp 105–107 °C (pentane);
Anal. Found: C, 78.65; H, 7.45; N, 4.07%. Calcd for C22H25NO2
A. R. Katritzky, and C. W. Rees, Pergamon, London (1984), Vol 3,
pp. 443-470; A. Kleemann and J. Engel, “Pharmazeutishe Wirkst-
off Synthesen,” Patente, 2nd ed, Anwendungen, Thieme Verlage,