Reactions of 3-aminoisoxazolo[4,5-c]coumarin with benzoyl chloride: The first example of a preparative 1,2,4-oxadiazole-oxazole rearrangement

Article abstract of DOI:10.1016/j.mencom.2011.03.019

Depending on conditions, reaction of 3-amino-4H-chromeno[3,4-d]isoxazol-4- one with benzoyl chloride gives 4-hydroxy- and/or 4-benzoyloxy-3-(5-phenyl-1,2, 4-oxadiazol-3-yl)coumarins, which are rearranged into 2-benzamido-4H-chromeno[3, 4-d]oxazol-4-one by

Full text of DOI:10.1016/j.mencom.2011.03.019

Mendeleev
Communications
Mendeleev Commun., 2011, 21, 110–111
Reactions of 3-aminoisoxazolo[4,5-c]coumarin with benzoyl chloride:
the first example of a preparative 1,2,4-oxadiazole–oxazole rearrangement
Vyacheslav Ya. Sosnovskikh,*a Vladimir S. Moshkin,a Mikhail Yu. Korneva and Mikhail I. Kodessb
a Department of Chemistry, A. M. Gorky Ural State University, 620083 Ekaterinburg, Russian Federation.
Fax: +7 343 261 5978; e-mail: vyacheslav.sosnovskikh@usu.ru
b I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
620990 Ekaterinburg, Russian Federation
DOI: 10.1016/j.mencom.2011.03.019
Depending on conditions, reaction of 3-amino-4H-chromeno[3,4-d]isoxazol-4-one with benzoyl chloride gives 4-hydroxy- and/or
4-benzoyloxy-3-(5-phenyl-1,2,4-oxadiazol-3-yl)coumarins, which are rearranged into 2-benzamido-4H-chromeno[3,4-d]oxazol-4-one
by heating in DMSO.
Unlike the reaction of 3-amino-5-methylisoxazole with aroyl
chlorides giving the expected 3-aroylamino-5-methylisoxazoles,1
information on the reactions of 3-aminobenzisoxazole with benzoyl
chloride is rather contradictory. It has been reported previously2
(without the procedure details) that this reaction gives 3-benzoyl-
aminobenzisoxazole 1 in 65% yield; in the presence of bases, such
as sodium ethoxide or sodium hydroxide, compound 1 exists in
equilibrium with 3-(2-hydroxyphenyl)-5-phenyl-1,2,4-oxadiazole
2 (the Boulton–Katritzky rearrangement3). On the other hand, it
was recently4 shown that treatment of 3-aminobenzisoxazole with
benzoyl chloride in the presence of triethylamine in dichloro-
methane afforded compound 1 in only 2% yield, whereas diben-
zoylated derivatives 3 (38%) and 4 (17%) were the major products
(Scheme 1).
and furnished individual compound 7 (30 min, yield 51%). If
sulfuric acid is replaced by pyridine, deeper benzoylation occurs
to give 4-benzoyloxy-3-(5-phenyl-1,2,4-oxadiazol-3-yl)coumarin
8 (yield 76%).† Compounds 7 and 8 are rearranged almost quan-
titatively on heating in DMSO (90°C, 3–4 h) to produce 2-ben-
zoylamino-4H-chromeno[3,4-d]oxazol-4-one 9 (Scheme 2).‡
It is important to note that the 7(8) ® 9 transformation is the
first example of preparative 1,2,4-oxadiazole–oxazole rearrange-
ment, since the previously studied 3-acetonyl-5-aryl-1,2,4-oxa-
diazoles are characterised by the Boulton–Katritzky rearrangement
into 3-aroylamino-5-methylisoxazoles, whereas 2-aroylamino-
5-methyloxazoles were formed in insignificant amounts.5 Although
the rearrangement of the isoxazole 5 N-acetyl derivative, 3-acetyl-
amino-4H-chromeno[3,4-d]isoxazol-4-one, into 2-acetylamino-
4H-chromeno[3,4-d]oxazol-4-one recently discovered by us occurs
via 4-hydroxy-3-(5-methyl-1,2,4-oxadiazol-3-yl)coumarin, we
failed to isolate it in pure form due to its lower stability.6 We
obtained the parent compound of this series, 2-amino-4H-chro-
meno[3,4-d]oxazol-4-one, from a trifluoroacetyl derivative of
isoxazole 5 by the isoxazole–oxazole rearrangement,6 the mech-
anism of which has been studied in detail.5 Based on the data
reported in ref. 5, it may be assumed that DMSO acts as the Lewis
base in the 7 ® 9 conversion by deprotonating the 4-hydroxy-
coumarin ring to the anionic form, which then undergoes re-
cyclisation via azirin and carbodiimide to give fused oxazole 9
(Scheme 3).
Ph
N
HN COPh
O
N
N
O
OH
1
2
NH2
N
+
PhCOCl
COPh
COPh
O
N
COPh
COPh
N
+
N
N
1
The structures of compounds 7–9 were confirmed by H
O
O
and 13C NMR spectroscopic data; assignment of all signals was
3
4
Scheme 1
†
4-Hydroxy-3-(5-phenyl-1,2,4-oxadiazol-3-yl)-2H-chromen-2-one 7.
A suspension of 5 (200 mg, 1.0 mmol) in benzoyl chloride (1.8 g, 12.8 mmol)
was heated to dissolve the substance, followed by addition of one drop
of conc. H2SO4. The resulting mixture was kept at room temperature for
30 min and diluted with diethyl ether (8 ml). The solid obtained was
filtered off, washed with diethyl ether, and recrystallized from butanol–
ethanol (8:2). Yield, 150 mg (51%); mp 192–194°C, colourless powder.
4-Benzoyloxy-3-(5-phenyl-1,2,4-oxadiazol-3-yl)-2H-chromen-2-one 8.
To a suspension of 5 (260 mg, 1.3 mmol) in benzoyl chloride (0.9 g,
6.4 mmol), pyridine (240 mg, 3.0 mmol) was added. The resulting reaction
mixture was heated at 90°C for 2 h and diluted with toluene (4 ml). Then,
the mixture was heated for another 6 h and kept at room temperature. The
solid obtained was filtered off, washed with toluene, ethanol, and water.
Yield, 400 mg (76%); mp 228–230°C, colourless powder.
In this work we studied the reaction of 3-amino-4H-chromeno-
[3,4-d]isoxazol-4-one 5 with excess of benzoyl chloride (5.6 equiv.,
90°C, 4 h) in the absence of a solvent and found that the initial
N-benzoylation, which results in 3-benzoylamino-4H-chromeno-
[3,4-d]isoxazol-4-one 6, is accompanied by the Boulton–Katritzky
rearrangement of the isoxazole ring into a 1,2,4-oxadiazole ring
(Scheme 2). The thus forming product is 4-hydroxy-3-(5-phenyl-
1,2,4-oxadiazol-3-yl)coumarin 7, which is more thermodyna-
mically stable than compound 6 due to conjugation with the
phenyl substituent. The rearrangement occurs incompletely under
these conditions, and the products 6 and 7 were isolated as 26:74
mixture (1H NMR spectroscopic data). However, addition of one
drop of concentrated H2SO4 accelerated the process considerably
For spectral characteristics and elemental analyses of compounds 7
and 8, see Online Supplementary Materials.
© 2011 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2011, 21, 110–111
O
NHBz
N
N
OH
4
O
N
O
2'
5
8
Ph
OH
1'
O
N
O
O
4a
8a
N
3'
151.8
9b
6
7
8.03
H
N
3
+
Ph
7.45
7.77
4'
N
N
3a
123.9
2
O
O
O
O
1
O
O
O
O
6
7
7.48
7
9
PhCOCl
N
NHAc
N
OH
O
N
151.2
9b
8.01
7.47
O
Me
7.45
7.77
3a
NH2
PhCOCl
H2SO4
123.8
7
O
O
O
O
O
O
DMSO
O
5
Figure 1 Comparison of the selective 1H and 13C chemical shifts (d/ppm)
of compounds 7 and 9 with the data reported for related molecules.6
HN
2
1'
2'
4'
Py 2 PhCOCl
1 O
9b
N3
3a
9
6
4''
3'
9a
8
7
3''
2''
Although these derivatives could not be isolated in pure form,
they were reliably identified by 1H NMR spectra of mixtures that
contained no other admixtures. This result allows for anticipation
of finding more suitable aroylation conditions.
5a
4
O
O
1''
5
9
O
O
4
N
O
DMSO
2'
5
1'
4a
3'
4'
6
7
O
N
3
N
O
Cl
8a
2
O
O
NH
8
OH
O
O
N
1
8
N
Scheme 2
O
O
Cl
10
O
performed based on results of 2D H–13C HSQC and HMBC
experiments and by comparison of characteristic 1H and 13C shifts
with those of similar atoms in related molecules6 (Figure 1).
The most informative cross-peaks of the 2D HMBC spectrum
in DMSO-d6 for compound 8 are as follows: H(2',6')/OCN,
H(2'',6'')/OCO, H(5)/C(4), H(5)/C(8a), H(5)/C(7), H(7)/C(8a),
H(7)/C(5), H(4'')/C(2'',6''), H(2'',6'')/C(4'').
Unfortunately, to date, all our attempts to extend the scope of
this 1,2,4-oxadiazole–oxazole rearrangement failed. In fact, contrary
to expectations, the stage of isoxazole 5 4-chlorobenzoylation
undersulfuricacidcatalysisprovedtobeslowerthanbenzoylation
and resulted in a mixture of the starting isoxazole 5 (85%) and
4-hydroxy-3-[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]coumarin
11 (15%), whereas the reaction of 5 with 4-chlorobenzoyl chloride
in the presence of pyridine led to a mixture of approximately equal
amounts of compounds 10 (45%) and 11 (55%) (Scheme 4).
1
11
Scheme 4
In summary, benzoylation of 3-amino-4H-chromeno[3,4-d]
isoxazol-4-one 5 on treatment with benzoyl chloride is accom-
panied by a Boulton–Katritzky rearrangement and results in
5-phenyl-1,2,4-oxadiazoles 7 and 8 containing a 4-hydroxy-
coumarin moiety at the 3-position. The nearly quantitative con-
version of these compounds into 2-benzamido-4H-chromeno-
[3,4-d]oxazol-4-one 9 occurs under mild conditions and gives
a first example of a preparative 1,2,4-oxadiazole–oxazole rear-
rangement. In conjuction with the pharmaceutical importance of
oxazolo[4,5-c]coumarins, some of which possess antiallergic,
antiinflammatory and central nerve depressing activities,7 this reac-
tion is noteworthy and will complement the published synthetic
methods for the preparation of fused heterocycles incorporating
a coumarin moiety.
DMSO
7
9
– H+
H+
O
O
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2011.03.019.
N
N
Ph
O
N
O
Ph
N
N
References
O
O
O
O
O
1 S. Buscemi, V. Frenna and N. Vivona, Heterocycles, 1991, 32, 1765.
2 K. Harsányi, J. Heterocycl. Chem., 1973, 10, 957.
3 A. J. Boulton, A. R. Katritzky and A. M. Hamid, J. Chem. Soc. (C), 1967,
2005.
4 L. E. J. Kennis, G. C. P. Vanhoof, J.-P. A. M. Bongartz, M. G. M. Luyckx
and W. E. Minke, Pat. WO 089753, 2005.
5 A. Pace, P. Pierro, S. Buscemi, N. Vivona and G. Barone, J. Org. Chem.,
2009, 74, 351.
6 V.Ya. Sosnovskikh, V. S. Moshkin and M. I. Kodess, Mendeleev Commun.,
NCOPh
O
O
N
C
N
O
Ph
O
O
O
Scheme 3
2010, 20, 209.
‡
2-Benzoylamino-4H-chromeno[3,4-d]oxazol-4-one 9. A solution of 7 or
7 W. Steinschifter, W. Fiala and W. Stadlbauer, J. Heterocycl. Chem., 1994,
31, 1647 and references therein.
8 (0.35 mmol) in DMSO (1.5 ml) was heated at 90°C for 3–4 h. Then, the
reaction mixture was diluted with water (8 ml) and the solid obtained was
filtered off, washed with water, and dried.Yield, 91–98%; mp 276–277°C
(decomp.), colourless crystals.
For spectral characteristics and elemental analysis of compound 9, see
Online Supplementary Materials.
Received: 6th July 2010; Com. 10/3558
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