1
hoxy monohydrazones via a novel rearrangement (Scheme
2).8 In this context, and in view of our general interest in
at 1753 and 1769 cm-1. In the H NMR spectrum, the
methoxy protons resonated at δ 3.86 and the methine protons
were discernible at δ 4.93 and 5.21, respectively, as
multiplets. The aromatic proton signal was visible at δ 7.53.
The reaction was found to be general with respect to
various 1,2-benzoquinones, and the dihydro benzoxadiazoles
were obtained in high yields. The results are summarized in
Table 1.
Scheme 2. Phosphine-Mediated Reaction of DEAD with
Benzil
Table 1. Reaction of 1,2-Benzoquinones with Ph3P and
Dialkyl Azodicarboxylate
the reactivity profile of o-benzoquinones,9 we have explored
the reaction of 3 with substituted 3-methoxy-1,2-benzo-
quinones and N-substituted isatins. The preliminary results
of our investigations which expose some novel reactivity
patterns of the zwitterion form the subject of this letter.
In a pilot experiment, a solution of 3-methoxy-4,6-di-tert-
butyl-1,2-benzoquinone and diisopropyl azodicarboxylate
(DIAD) in dry DME under argon atmosphere was treated
with stoichiometric amount of triphenylphosphine at room
temperature. The reaction mixture on usual processing afford-
ed the dihydro-1,2,3-benzoxadiazole derivative 7a10 in 86%
yield as a very pale brown amorphous solid (Scheme 3).11
yield
entry
R1
ethyl
ethyl
ethyl
ethyl
R2
tert-butyl
diphenylmethyl
tert-butyl
R3
tert-butyl
diphenylmethyl
H
4,4′-dichloro-
diphenylmethyl
H
product (%)
1
2
3
4
7b
7c
7d
7e
75
78
91
73
4,4′-dichloro-
diphenylmethyl
5
6
7
isopropyl tert-butyl
isopropyl diphenylmethyl
isopropyl 4,4′-dichloro-
diphenylmethyl
7f
7g
7h
94
85
64
diphenylmethyl
4,4′-dichloro-
diphenylmethyl
dimethyl-
8
isopropyl dimethyl-
7i
85
phenylmethyl
phenylmethyl
Scheme 3. Reaction of 1,2-Benzoquinone with DIAD and
Ph3P
The following mechanistic postulate may be invoked to
rationalize the reaction. The Huisgen zwitterion 3 formed
from triphenylphosphine and azoester adds to quinone
carbonyl to give a tetrahedral intermediate 8 which gives
the spirooxadiazoline 9 presumably by the elimination of
triphenylphosphine oxide via a process resembling the Wittig
reaction. The spirooxadiazoline undergoes aromatization by
ring fragmentation to deliver 10. The latter undergoes another
ring closure to give the final product (Scheme 4).
The product was characterized by spectroscopic analysis.
In the IR spectrum, the ester carbonyl absorption was seen
(7) Girard, M.; Murphy, P.; Tsou, N. N. Tetrahedron Lett. 2005, 46,
2449.
(8) Nair, V.; Biju, A. T.; Abhilash, K. G.; Menon, R. S.; Suresh, E. Org.
Lett. 2005, 7, 2121.
Scheme 4. Proposed Mechanism for the Reaction
(9) (a) Nair, V.; Kumar, S. Synlett 1996, 1143. (b) Nair, V.; Nair, J. S.;
Vinod, A. U.; Rath, N.; P. J. Chem. Soc., Perkin Trans. 1 1997, 3129. (c)
Nair, V.; Nair, J. S.; Vinod, A. U. Synthesis 2000, 1713. (d) Nair, V.; Vinod,
A. U.; Nair, J. S.; Sreekanth, A. R.; Rath, N. P. Tetrahedron Lett. 2000,
41, 6673. (e) Nair, V.; Bindu, S.; Balagopal, L. Tetrahedron Lett. 2001,
42, 2043. (f) Nair, V.; Sreekanth, A. R.; Biju, A. T.; Rath, N. P. Tetrahedron
Lett. 2003, 44, 729.
(10) To a stirred solution of the 1,2-benzoquinone 6 (133 mg, 0.53 mmol)
in anhydrous DME (10 mL), under argon atmosphere, was added DIAD
(0.13 mL, 0.64 mmol) followed by triphenylphosphine (167 mg, 0.64
mmol).The reaction mixture was stirred at room temperature for 5 h. The
solvent was removed under reduced pressure, and the residue on the silica
gel column chromatography using 3% ethyl acetate-hexane afforded 7a
as a very pale brown amorphous solid (198 mg. 86%). IR (Film) νmax: 2964,
1769, 1753, 1475, 1367, 1259, 1166, 1104 cm-1 1H NMR (300 MHz,
.
CDCl3) δ: 1.37-1.43 (m, 30H), 3.86 (s, 3H), 4.93 (m, J ) 6.30 Hz, 1H),
5.21 (m, J ) 6.30 Hz, 1H), 7.53 (s, 1H). 13C NMR (75 MHz CDCl3) δ:
21.9, 30.6, 35.4, 64.6, 72.4, 73.1, 130.0, 136.1, 137.4, 138.4, 140.5, 152.2,
157.9, 160.9. HRMS for C23H36N2O6: calcd (M + 1+) 437.2605, found
437.2648.
(11) On exposure to air the product developed a brown color, presumably
due to air oxidation. The extent of oxidation, however, is insignificant as
no detectable change was observed in the 1H NMR spectra of the compound
after exposure to air.
In all cases only one of the carbonyls participated in the
reaction. This selectivity of the reaction may be attributed
5140
Org. Lett., Vol. 7, No. 23, 2005