3212
J . Org. Chem. 1996, 61, 3212-3213
Sch em e 1
Oxid a tive Rin g Op en in g of
2-Oxoisoxa zolo[2,3-a ]p yr im id in es.
F or m a tion of P yr im id in -2-yl P h en yl
Keton es
Ph
O
N
R1
+
1
DMSO
N
O–
R2
S+Me2
Gury Zvilichovsky* and Vadim Gurvich
O
Ph
O
N
R1
Department of Organic Chemistry, The Hebrew University of
J erusalem, J erusalem, 91904 Israel
4 + CO2 + Me2S
N
O–
R2
Received December 12, 1995
Sch em e 2
H
O–
O
O
The synthesis of 2-oxo-3-phenylisoxazolo[2,3-a]pyrim-
idines 1 and their rearrangement in nucleophilic solvents
was described recently.1 Upon heating in water or
ethanol, under nitrogen, the isoxazole ring was opened
and a spontaneous decarboxylation led to the formation
of pyrimidinylphenylmethanols 2 and their ethyl ethers
3, respectively.
–C5H5N
R
C
C
RCH
C
+
O–
+NC5H5
O– +NC5H5
H
O
R
C
C
RCH
O
O–
O
+NC5H5
Ph
N
R1
H2O
R1
EtOH
N
Sch em e 3
OH
OEt
O
O
H+
N
N
R1
R2
O + Me2S+
O–
Ph
Ph
Ph2C
C
1
N
N
OH
Ph2C COOH + Me2S + H+
OH
O
Ph2C
H
C
R2
R2
S+Me2
2
3
O
H
In the present work a new rearrangement of the same
isoxazolo[2,3-a]pyrimidines is described. It was observed
that when the reaction was carried out without the
exclusion of air and light traces of an additional product
was observed. It was identified as a 2-benzoylpyrimidine
derivative (4). Upon bubbling oxygen through the heated
aqueous solutions of these isoxazolopyrimidine deriva-
tives 1, these ketones became the major products. One
of these ketones (4a ) was recently described.2 The
presence of a carbonyl group in 4c was demonstrated by
the 13C signal at 192 ppm, a carbonyl stretching vibration
in the IR spectrum at 1690 cm-1, and the condensation
of 4b and 4c with (2,4-dinitrophenyl)hydrazine to produce
the hydrazone derivatives.
This oxidative cleavage in boiling water is completed
in about 10-24 h. Upon heating at 135° in dimethyl
sulfoxide, it takes about 10 min even without bubbling
of oxygen. Presumably the solvent is the oxidizing agent
as is shown in Scheme 1. This mechanism is supported
by the detection of dimethyl sulfide in the reaction
mixture, by gas chromatography and NMR.
An analogous mechanism (Scheme 2) which involves
oxidation with an amine oxide was described earlier by
Cohen3 and in turn is related to that which was proposed
by Lillien4 to account for the production of benzilic acid
in the oxidation of diphenylketene by aqueous dimethyl
sulfide (Scheme 3).
O
N
R1
Ph
Exp er im en ta l Section
N
O2
1
∆
R2
Gen er a l Meth od s. Melting points are uncorrected. Chro-
matographic separation was carried out with silica gel (230-
400 mesh) on a 450 × 20 mm column.
4a: R1 = H, R2 = H
4b: R1 = Me, R2 = H
4c: R1 = Me, R2 = Me
4d: R1 = Me, R2 = Ph
Oxid a tive Rea r r a n gem en t of 2-Oxo-3-p h en ylisoxa zolo-
[2,3-a ]p yr im id in es in Wa ter . 2-Oxo-3-phenylisoxazolo[2,3-a]-
pyrimidine (1, 0.001 mol) was suspended in a mixture of 6:1
water-acetonitrile (100 mL), which was previously saturated
by oxygen. The mixture was refluxed with bubbling of oxygen
for 24 h. The solvent was evaporated under reduced pressure,
and the residue which contained 4 and 2 (5:1) was resolved by
silica gel chromatography. Results and NMR data are sum-
marized in Table 1.
Heating the pyrimidinylphenylmethanols 2 in the
presence of oxygen as above did not bring about any
oxidation of the secondary alcohols to a ketone. This
excluded alcohols being intermediates in the formation
of 4.
(1) Zvilichovsky, G.; Gurvich, V.; Segev, S. J . Org. Chem. 1995, 60,
5251.
(2) Ba´tori, S.; Messmer, A. J . Heterocycl. Chem. 1994, 31, 1041.
(3) Cohen, T.; Song, I. H.; Fager, J . H.; Deets, G. L. J . Am. Chem.
Soc. 1967, 89, 4968.
(4) Lillien, I. J . Org. Chem. 1964, 29, 1631.
S0022-3263(95)02200-6 CCC: $12.00 © 1996 American Chemical Society
Zvilichovsky, Gury
