Novel clay-catalysed cyclisation of salicylaldehyde semicarbazones to 2H-benz[e]-1,3-oxazin-2-ones under microwave irradiation

Article abstract of DOI:10.1016/S0040-4039(02)02065-8

A microwave-expediated, high yielding, synthesis of 2H-benz[e]-1,3-oxazin-2-ones (2a-j) involving cyclodehydrazination of salicylaldehyde semicarbazones (1a-j) on montmorillonite K 10 clay in solvent-free conditions is reported.

Full text of DOI:10.1016/S0040-4039(02)02065-8

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TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8551–8553
Novel clay-catalysed cyclisation of salicylaldehyde
semicarbazones to 2H-benz[e]-1,3-oxazin-2-ones under
microwave irradiation
Lal Dhar S. Yadav,* Sarvesh Singh and Amrish Singh
Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Received 27 June 2002; revised 10 September 2002; accepted 19 September 2002
Abstract—A microwave-expediated, high yielding, synthesis of 2H-benz[e]-1,3-oxazin-2-ones (2a–j) involving cyclodehydrazina-
tion of salicylaldehyde semicarbazones (1a–j) on montmorillonite K 10 clay in solvent-free conditions is reported. © 2002
Published by Elsevier Science Ltd.
Efavirenz (sustiva), a benzoxazinone derivative, is
presently in clinical use for the treatment of AIDS.
Recently, various benzoxazinones have been synthe-
sised and evaluated with a view to achieving antiviral
agents of choice.1–3 Most of the methods available for
the construction of the benzoxazinone nucleus often
suffer from one or more drawbacks such as the long
reaction time required to obtain a good yield of the
desired product or the use of expensive and hazardous
reagents and solvents.1–6 Salicylaldehyde has been used
as a bifunctional building block for the synthesis of
various oxygen heterocycles of chemical and biological
interest.7–11
are basic protocols because solvents are often toxic and
are agents that pollute the environment.
Prompted by the above reports and in pursuing our
work on new synthetic routes to potentially bioactive
compounds,11,19–21 we have devised a salicylaldehyde-
based, clay-catalysed, expeditious synthesis of benzox-
azinones
2 using microwaves (Scheme 1). It is
noteworthy that all the benzoxazinones 2 reported
herein are new and not accessible through any of the
known synthetic routes for benzoxazinones.1–6 After
some preliminary experimentation, it was found that
the envisaged dehydrazinative cyclisation (1“2) was
effective with montmorillonite
K 10 clay under
Clay-catalysed organic transformations have generated
considerable interest because of their inexpensive nature
and special catalytic attributes under heterogeneous
reaction conditions.12–14 The use of microwave (MW)
methodology in organic synthesis has attracted much
attention in recent years because it offers several advan-
tages, such as rapid reaction rates and higher yields of
pure products,15–18 as a consequence of the selective
absorption of microwave energy by polar molecules or
polar intermediates formed during the course of the
reaction.18 Furthermore, with increasing environmental
consciousness the development of environmentally
friendly synthetic methods has become desirable. In this
respect organic syntheses under solvent-free conditions
microwave irradiation for the time specified in Table 1
to afford benzoxazinones 2 in 83–94% yield (Table 1).
However, the use of other mineral supports, viz., silica
gel, neutral or basic alumina, was far less effective
resulting in either no cyclisation (in the case of basic
alumina) or relatively very low yields (13–49%) (in the
cases of silica gel and neutral alumina). That the effect
of microwaves may not be purely thermal22 is sup-
ported by the fact that the reaction could not be
completed, e.g., only 60% conversion over 20 h at the
same bulk temperature (90°C) employing conventional
heating in an oil bath. The mechanism shown in
Scheme 1 is supported by the formation of hydrazine
during the reaction.
In conclusion, we have developed an expeditious
method for the synthesis of 2H-benz[e]-1,3-oxazin-2-
ones by cyclodehydrazination of salicylaldehyde semi-
Keywords: benzoxazinones; cyclodehydrazination;
K
10 clay;
microwave-expediated synthesis; salicylaldehyde semicarbazones.
* Corresponding author. Fax: +91532545021; e-mail: lds-yadav@
hclinfinet.com
carbazones on
a clay surface under microwave
irradiation under solvent-free conditions. The applica-
0040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)02065-8

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8552
L. D. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 8551–8553
Scheme 1.
Table 1. Benzoxazinones 2 prepared on clay under microwave irradiation
Product
Time (min)
Yielda (%)
Mp (°C)
Mol. form.b,c
(wt.)
1H NMR l, J (Hz)
MS m/z (M+
)
2a
2b
3.0
2.5
84
86
138–139
161–163
C8H5NO2
(147.13)
C8H4BrNO2
(226.03)
7.19–7.90 (m, 4H, Ar-H), 8.51 (s, 1H, 4-H)
147
7.30 (d, J 9.0, 1H, 8-H), 7.92 (dd, J 9.0, 2.4, 225
1H, 7-H), 8.24 (d, J 2.4, 1H, 5-H), 8.58 (s,
1H, 4-H)
2c
2d
2.0
2.5
87
90
181–183
151–152
C8H3Br2NO2
(304.92)
C8H4ClNO2
(181.58)
7.87 (d, J 2.5, 1H, 7-H), 8.19 (d, J 2.5, 1H,
5-H), 8.62 (s, 1H, 4-H)
7.32 (d, J 9.2, 1H, 8-H), 7.97 (dd, J 9.2, 2.6, 181
1H, 7-H), 8.27 (d, J 2.6, 1H, 5-H), 8.61 (s,
1H, 4-H)
305
2e
2f
2.0
2.0
94
91
157–159
145–146
C8H3Cl2NO2
(216.02)
C8H4FNO2
(165.12)
7.89 (d, J 2.5, 1H, 7-H), 8.22 (d, J 2.5, 1H,
5-H), 8.65 (s, 1H, 4-H)
7.66 (dd, J 9.4, 2.4, 1H, 5-H), 7.75 (dd, J 9.5, 165
9.4, 1H, 6-H), 7.95 (dd, J 9.5, 2.4, 1H, 7-H),
8.54 (s, 1H, 4-H)
215
2g
2h
3.0
2.0
88
90
148–149
192–194
C9H7NO3
(177.16)
4.01 (s, 3H, MeO), 7.63 (dd, J 9.3, 2.5, 1H,
5-H), 7.70 (dd, J 9.4, 9.3, 1H, 6-H), 7.82 (dd,
J 9.4, 2.5, 1H, 7-H), 8.53 (s, 1H, 4-H)
7.35 (d, J 9.1, 1H, 8-H), 7.99 (dd, J 9.1, 2.5, 192
1H, 7-H), 8.29 (d, J 2.5, 1H, 5-H), 8.63 (s,
1H, 4-H)
177
C8H4N2O4
(192.13)
2i
2j
1.5
3.0
93
83
208–211
177–180
C8H3N3O6
(237.13)
C8H3I2NO2
(398.92)
7.92 (d, J 2.4, 1H, 7-H), 8.26 (d, J 2.4, 1H,
5-H), 8.67 (s, 1H, 4-H)
7.85 (d, J 2.4, 1H, 7-H), 8.17 (d, J 2.4, 1H,
5-H), 8.61 (s, 1H, 4-H)
237
399
a Yield of purified and isolated product.
b All compounds gave C, H and N analyses within 0.30%.
c All compounds exhibited IR bands due to wCꢀO in the region 1725–1735 cm−1
.

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L. D. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 8551–8553
8553
tion of this method to the synthesis of aglycon-modified
potentially antiviral nucleosides is at present ongoing in
our laboratory.
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2H-Benz[e]-1,3-oxazin-2-ones 2. General procedure: To
a solution of salicylaldehyde semicarbazone 1 (2.0 mmol)
in a small amount of dichloromethane (3 mL) was added
montmorillonite K 10 clay (3.0 g), mixed thoroughly and
dried. The contents were taken in a Pyrex test tube, placed
in an alumina bath inside the microwave oven and
irradiated for the time specified in Table 1. After comple-
tion of the reaction as indicated by TLC (hexane:AcOEt,
8:2, v/v), the product was extracted with dichloromethane
(3×30 mL) and the extract was dried under reduced
pressure to leave the crude product which was recrys-
tallised from ethanol to obtain an analytical sample of
benzoxazinone 2 (Table 1).
Acknowledgements
We sincerely thank RSIC, Lucknow, India, for providing
microanalyses and spectra.