940
Synthesis of {2-Oxo(thioxo)-3,4-dihydro-2H-1,3-benzoxazin-
4- yl}(thio)ureas and Their Derivatives
M. M. Kurbanova
Baku State University, ul. Z.Khalilova 23, Baku, AZ-1073, Azerbaijan
e-mail: kurbanova1972@rambler.ru
Received May 17, 2012
SHORT
COMMUNICATIONS
Synthesis of natural and biologically active hetero-
cyclic compounds is an important problem of organic
and medicinal chemistry. Oxazine derivatives were
found to be efficient medicines exhibiting high cyto-
static, antibacterial, and antiviral activity [1]; some
compounds showed pronounced fungicidal and hypo-
tensive effects [2]. These findings have stimulated
research in the field of oxazine heterocycles, develop-
ment of efficient methods for their preparation, and
thorough study of their structure and chemical trans-
formations with a view to define their role and place
among other heterocycles. However, some oxazine
derivatives remain poorly studied up to now; in partic-
ular, this applies to {2-oxo(thioxo)-3,4-dihydro-2H-
1,3-benzoxazin-4-yl}(thio)ureas and their derivatives,
though these compounds attract interest from the
viewpoints of synthetic and theoretical chemistry and
design of new efficient medicinal substances.
The condensation of salicylaldehyde with urea in
the presence of HCl was reported to produce
1,1'-[(2-hydroxyphenyl)methylene]diurea [3]. I syn-
thesized (2-oxo-3,4-dihydro-2H-1,3-benzoxazin-4-yl)-
urea (I) by reaction of salicylaldehyde with urea in
acetonitrile. Likewise, (6-bromo-2-oxo-3,4-dihydro-
2H-1,3-benzoxazin-4-yl)urea (II) was synthesized by
analogous condensation of 5-bromosalicylaldehyde
(Scheme 1). Compounds I and II were isolated as
crystalline substances whose structure was confirmed
by NMR and IR spectroscopy and X-ray analysis of
a single crystal of I (see figure) [4]. The ureido substit-
uent in the oxazine ring of I occupies axial position;
the torsion angle C
9
N
2
C
2
N
1
is –64.31(15)°, and the
N
1
C
2
N
2
bond angle is 112.46(11)°]. The N
1
atom
deviates by 0.2674 Å from the plane formed by the
other atoms constituting the oxazine ring, which is due
to formation of intermolecular hydrogen bond between
the N
1
H proton and O
2
of the other molecule. The sum
of the bond angles at the N
1
atom is 352.7°, and the
torsion angle C
2
N
1
O
1
C
1
is 22.4(2)°. Crystalline com-
pound I is a racemate (molecule I possesses one asym-
metric center, C
2
). Molecules I in crystal form zigzag
layers parallel to the 0yz plane via intermolecular
hydrogen bonds involving solvation water molecule
as well.
According to the data of [5], the condensation of
salicylaldehyde with thiourea in methanol yields
(1E,3E)-1,3-bis(2-hydroxybenzylidene)thiourea [5]. I
carried out the reaction with the same reactants in
acetonitrile and obtained (2-thioxo-3,4-dihydro-2H-
1,3-benzoxazin-4-yl)thiourea ( III ). (6-Bromo-2-
ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 6, pp. 940–942. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © M.M. Kurbanova, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 6, pp. 953–955.
DOI: 10.1134/S1070428013060274
I, R = H; II, R = Br.
CHO
OH
(H
2
N)
2
C=O, MeCN
OH
N
H
OH
NH
2
O
(H
2
N)
2
C=O
–H
2
O, –NH
3
O
NH
O
HN NH
2
O
I, II
R R R
Scheme 1.