Synthesis of 5-r-benzyl-2-iminoselenazolidin-4-ones

Full text of DOI:10.1023/A:1026119009906

Chemistry of Heterocyclic Compounds, Vol. 39, No. 7, 2003
SYNTHESIS OF 5-R-BENZYL-
2
-IMINOSELENAZOLIDIN-4-ONES
V. S. Matiichuk, N. D. Obushak, and V. M. Tsyalkovskii
Keywords: selenazolidin-4-ones, seleazoles, selenourea, arylation, cyclization.
Interest in the synthesis of selenazole derivatives is related largely to the biological activity of these
compounds [1-3]. A convenient method for the synthesis of substituted selenazoles involves the reaction of
α-halo ketones with compounds containing the selenamide fragment, H
given to the reaction of the latter with α-halo carboxylic acids and their derivatives to give selenazolidin-4-ones
4, 5].
2
NC(Se)R [1]. Less attention has been
[
We have developed a simple method for the synthesis of such compounds using acrylates 2a-c, which
are obtained from the bromoarylation of arenediazonium salts 1a-c. Acrylates 2a-c react with selenourea upon
brief heating at reflux in ethanol in the presence of pyridine to give iminoselenazolidinones 3a-c.
Dehydrobromination of α-bromo esters 2a-c does not occur and 3a-c were obtained in high yield. This method
yields 2-iminoselenazolidin-4-one derivatives containing benzyl substituents at C(5), which opens the pathway
for the synthesis of selenium analogs of 5-R-benzyl-2,4-thiazolidinediones, some of which have antidiabetic
activity [6].
O
O
_
o
1
CuBr, 20–25 C
R C H N +Br
6
4
2
+
1
OEt
R C H
OEt
a–c
6
4
H O–Me CO
1
a–c
2
2
Br
2
NH2
NH2
O
H
N
R1
Se
NH
Se
3
a–c
1
-3 a R = H; b R = 4-Me; c R = 2-Cl
1
The H NMR spectra were taken in DMSO-d at 500 MHz.
6
5
-Benzyl-2-iminoselenazolidin-4-one (3a). A solution of benzenediazonium bromide 1a obtained by
the diazotization of aniline (100 mmol) was added dropwise with stirring to a mixture of ethyl acrylate (10 ml)
and CuBr (1.5 g) in acetone (50 ml). The reaction was continued until nitrogen was no longer liberated. Then,
water (200 ml) was added and the organic layer was separated. Distillation in vacuum gave 10.3 g (40%) ethyl
2
0
ester of 2-bromo-3-phenylpropanoic acid 2a; bp 115-117°C (2 mm Hg), n
D
1.5330. A sample of 2a (1.0 g,
4
.1 mmol) and selenourea (0.5 g, 4.1 mmol) were dissolved in ethanol (15 ml). Then, pyridine (0.4 ml) was
_
_________________________________________________________________________________________
Ivan Franko Lvov National University, Lvov 79005, Ukraine; e-mail: obushak@in.lviv.ua. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1115-1116, July, 2003. Original article submitted
September 8, 2002.
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72
0009-3122/03/3907-0972$25.00©2003 Plenum Publishing Corporation

added and the mixture was heated at reflux for 30 min. The precipitate formed was recrystallized from 1:1
1
ethanol–DMF to give 0.83 g (80%) 3a; mp 202-203°C. H NMR spectrum, δ, ppm,(J, Hz): 2.95 (1H, dd,
2
3
2
3
3
3
J = 14.0, J = 11.0, CH
2
); 3.64 (1H, dd, J = 14.0, J = 3.7, CH ); 4.67 (1H, dd, J = 11.0, J = 3.7, CH);
2
7
C
.16-7.28 (5H, m, C
6
H ); 8.53 (1H, s, NH); 8.92 (1H, s, NH). Found, %: C 47.38; H 3.82; N 10.94.
5
10
H
10
N
2
OSe. Calculated, %: C 47.44; H 3.98; N 11.07.
-Iminoselenazolidin-4-ones 3b and 3c were obtained analogously.
2
2
1
-Imino-5-(4-methylbenzyl)selenazolidin-4-one (3b) was obtained in 73% yield; mp 207°C. H NMR
2
3
2
spectrum, δ, ppm (J, Hz): 2.31 (3H, s, CH
3
); 2.91 (1H, dd, J = 14.1, J = 10.8, CH
); 4.64 (1H, dd, J = 10.8, J = 3.9, CH); 7.05 (2H, d, C
.90 (1H, s, NH). Found, %: C 49.33; H 4.45; N 10.36. C11
-(2-Chlorobenzyl)-2-iminoselenazolidin-4-one (3c) was obtained in 83% yield; mp 193-194°C.
2
); 3.60 (1H, dd, J = 14.1,
3
3
3
J = 3.9, CH
2
H
6 4
); 7.10 (2H, d, C
6
H ); 8.52 (1H, s, NH);
4
8
H
12
N OSe. Calculated, %: C 49.45; H 4.53; N 10.48.
2
5
1
2
3
2
3
H NMR spectrum, δ, ppm (J, Hz): 3.07 (1H, dd, J = 14.4, J = 10.5, CH
2
); 3.80 (1H, dd, J = 14.4, J = 3.6,
); 7.31 (1H, m, C ); 7.35 (1H, m, C );
ClN OSe.
3
3
CH
7
2
); 4.78 (1H, dd, J = 10.5, J = 3.6, CH); 7.18-7.26 (2H, m, C
.35 (1H, m, C
H
6 4
6
H
4
H
6 4
6
H
4
); 8.60 (1H, s, NH); 9.02 (1H, s, NH). Found, %: C 41.63; H 3.02; N 9.52. C10
H
9
2
Calculated, %: C 41.76; H 3.15; N 9.74.
REFERENCES
1.
2.
3.
4.
5.
6.
V. P. Litvinov and V. D. Dyachenko, Usp. Khim., 66, 1025 (1997).
Y. Kumar, R. Green, D. S. Wise, L. L. Wotring, and L. B. Townsend, J. Med. Chem., 36, 3843 (1993).
Y. Kumar, R. Green, D. S. Wise, L. L. Wotring, and L. B. Townsend, J. Med. Chem., 36, 3849 (1993).
A. M. Comrie, D. Dingwall, and J. B. Stenlake, J. Chem. Soc., 5713 (1963).
M. Koketsu, Y. Takenaka, and H. Ishihara, Synthesis, 731 (2001).
B. B. Lohray, V. Bhushan, A. S. Reddy, P. B. Rao, N. J. Reddy, P. Harikishore, N. Haritha,
R. K. Vikramadityan, R. Chakrabarti, R. Rajagopalan, and K. Katneni, J. Med. Chem., 42, 2569 (1999).
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