Cascade synthesis of pyrimido-[4,3-b][1,3,5] selenadiazine derivatives

Full text of DOI:10.1007/s10593-009-0257-z

Chemistry of Heterocyclic Compounds, Vol. 45, No. 2, 2009
CASCADE SYNTHESIS OF PYRIMIDO-
[
4,3-b][1,3,5] SELENADIAZINE DERIVATIVES
1
1
1
2
K. A. Frolov , S. G. Krivokolysko , V. V. Dotsenko **, and V. P. Litvinov *
Keywords: 2-thienylmethylidenecyanoselenoacetamide, cascade synthesis, Mannich reaction.
The interest in the chemistry of selenium heterocycles is largely due to the broad spectrum of their
biological activity [1, 2]. Derivatives of 1,3,5-selenadiazine form a relatively little studied class of heterocyclic
compounds. The methods reported for preparation of the 1,3,5-selenadiazine ring have been based on the
reaction of 1,3-dichloro-1,3-bis(dimethylamino)-2-azapropenylium chlorides with selenamides or selenoureas
[3, 4], the multicomponent reaction of benzylamine, sodium hydroselenide, and formaldehyde with aryl
selenoisocyanates in acid media [5], the recyclization of 1,3,5-oxaselenazine [6, 7], and the reaction of
dialkyl(1-aryl-1-chloro-2-aza-1-propenylidene)immonium perchlorate with N-acylselenoureas [8]. Butler and
Fox [9] have described the preparation of a selenadiazine derivative as the result of recyclization of a
1
,2,4-selenadiazolium salt. Condensed derivatives of 1,3,5-selenadiazines have not been described in the
literature.
N
S
N
1
Se
NH2
8
9
RNH (3), HCHO
2
2
3
S
7
Se
N
N
5
N
EtOH, ∆
R
R
4
6
2
1
1
, 3 a R = 4-MeC H , b R = CH Ph
6
4
2
We have developed a one-pot cascade method for the preparation of derivatives of
pyrimido[4,3-b][1,3,5]selenadiazine (1) starting from (2-thienyl)methylidenecyanoselenoacetamide (2) [10, 11].
Selenamide 2 readily undergoes the Mannich reaction with primary amines 3 and excess formaldehyde upon
brief heating at reflux to give 1a and 1b in 38-50% yield.
_
*
*
______
Deceased.
* To whom correspondence should be addressed, e-mail: ksg@lep.lg.ua, Victor_Dotsenko@bigmir.net
1
Vladimir Dal' East-Ukrainian National University, Lugansk 91034, Ukraine.
N. D. Zelinsky Institute of Organic Chemistry, Moscow 117913, Russia.
2
_
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 313-315, February, 2009. Original
article submitted October 14, 2008.
009-3122/09/4502-0255©2009 Springer Science+Business Media, Inc.
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255

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The H NMR spectra were taken on a Bruker Avance II 400 spectrometer at 400 MHz in DMSO-d with
TMS as the internal standard. The IR spectra were taken on an IKS-29 spectrometer in vaseline mull. The
elemental analyses were carried out on a Perkin-Elmer C,H,N-analyzer. The reaction course and purity of the
products were monitored by thin-layer chromatography on Silufol UV-254 plates using 3:5 acetone–hexane as
the eluent. The plates were developed with iodine vapor. The melting points were determined on a Koefler
block.
Pyrimido[4,3-b][1,3,5]selenadiazines 1 (General Method). A mixture of selenoamide 2 (0.6 g,
2
.5 mmol), amine 3 (5.2 mmol), and 37% formalin (1.0 ml, 12.5 mmol) in ethanol (30 ml) was heated at reflux
for about 2-3 min in an argon atmosphere until the starting reagents were dissolved, rapidly filtered through
filter paper, and left for 24 h at room temperature in an argon atmosphere. The precipitate formed was filtered
off and washed with ethanol and hexane.
3
,7-Di(4-methylphenyl)-8-(2-thienyl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[4,3-b][1,3,5]selenadiazine-
-
1
9
(
-carbonitrile (1a) was obtained in 50% yield (0.61 g); mp 173-175°C (acetone). IR spectrum, ν, cm : 1605
C=C); 2165 (C≡N). H NMR spectrum, δ, ppm (J, Hz): 7.31 (1H, m, H-5 thienyl); 6.86-7.01 (10H, m, 2Ar,
H-3 thienyl, H-4 thienyl); 5.27 (2H, d, J = 10.9, NCH Se); 5.13 (1H, s, H-8), 4.83 (2H, br. pseudo-s, NCH N);
.46 (2H, d, J = 12.8, NCH N); 2.30, 2.31 (3H each, both s, 2CH ). Found, %: C 60.12; H 4.87; N 11.53.
1
2
2
2
2
4
2
3
C H N SSe. Calculated, %: C 61.09; H 4.92; N 11.40.
25
24
4
3
,7-Dibenzyl-8-(2-thienyl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[4,3-b][1,3,5]selenadiazine-9-carbo-
-
1
nitrile (1b) was obtained in 38% yield (0.47 g); mp 127-130°C. IR spectrum, ν, cm : 1605 (C=C); 2175 (C≡N).
H NMR spectrum, δ, ppm (J, Hz): 7.24-7.36 (11H, m, 2Ar, H-5 thienyl); 6.96-7.03 (2H, m, H-3 thienyl,
H-4 thienyl); 4.83 (2H, d, J = 10.2, NCH Se); 4.35 (1H, s, H-8); 3.98 (2H, br. s, NCH C H ); 3.89 (2H, br. s,
1
2
2
2
6
5
2
NCH C H ); 3.82 (2H, d, J = 12.6, NCH N). Found, %: C 60.59; H 4.83; N 11.57. C H N SSe. Calculated,
2
6
5
2
25 24
4
%: C 61.09; H 4.92; N 11.40.
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