Heterocyclizations based on products of cycloaddition of malononitrile to substituted 1,2,4-thiadiazol-5(2H)-imines [4]

Full text of DOI:10.1023/A:1023322103478

Russian Journal of General Chemistry, Vol. 72, No. 11, 2002, pp. 1826 1827. Translated from Zhurnal Obshchei Khimii, Vol. 72, No. 11, 2002,
pp. 1931 1932.
Original Russian Text Copyright
2002 by Renskii, Zyabrev, Drach.
LETTERS
TO THE EDITOR
Heterocyclizations Based on Products of Cycloaddition
of Malononitrile to Substituted 1,2,4-Thiadiazol-5(2H)-imines
M. A. Renskii, V. S. Zyabrev, and B. S. Drach
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received December 22, 2001
Substituted 1,2,4-thiadiazol-5(2H)-imines I react
heterocycle [1]. We found that such a reaction of com-
with acetonitrile to give [3+2]-cycloaddition products. pounds I with malononitrile gives an unexpected
The reaction occurs quite regioselectively and in-
volves the N=C S triad, with opening of the initial
result: cycloadducts II with an active methylene group
rearrange into 2,3-dihydrothiazole derivatives III.
Ph
N
N
Ar
N
PhN
Ar
N
+
NPh
N
N
PhN
N
S
S
Ia, Ib
IIa, IIb
Ph
Ph
Ph
NH2
1) PCl5;
2) MeONa
OMe
OMe
MeCOCH2CO2Et,
SnCl4
Ar
Ar
Ar
N
N
N
Me
O
N
N
P
N
N
N
PhN
PhN
N
PhN
OEt
N
S
S
S
OMe
NH2
IV
IIIa, IIIb
V
PhCOCl, Py
Ph
Ph
Ar
N
O
N
Ph
NH
H2O, H+
N
O
N
Ph
NH
N
PhN
O
S
S
VI
VII
Ar = 4-MeC6H4 (Ia IIIa, VI), 4-MeOC6H4 (Ib IIIb, IV, V).
Recyclization produts III appeared to be suitable
for preparing new fused heterocyclic compounds IV
enamino nitriles [4]. Therefore, the structure of V was
proved by single crystal X-ray diffraction. The fea-
tures of the molecular structure of V and its analogs
will be discussed later.
VII. Annelations similar to cyclizations III
IV and
III VI were studied previously with certain carbo-
and heterocyclic compounds containing CN and NH2
groups [2, 3]. At the same time, the transformation
N1-[4-Amino-3-phenyl-5-cyanothiazol-2(3H)-yli-
dene]-4-methyl(methoxy)-N2-phenylbenzamidines
III
V has an analog only in the series of acyclic
1070-3632/02/7211-1826$27.00 2002 MAIK Nauka/Interperiodica

HETEROCYCLIZATIONS BASED ON PRODUCTS OF CYCLOADDITION
1827
IIIa and IIIb. A mixture of 20 mmol of Ia or Ib ob-
tained by the general procedure [1], 20 mmol of ma-
lononitrile, and 10 ml of dioxane was refluxed with
stirring for 3 h and cooled to 20 C; the precipitate was
filtered off, washed with dioxane, and dried at 100 C.
C6H4). Found, %: N 13.03; P 5.53; S 5.91. C27H26
N5O4PS. Calculated, %: N 12.79; P 5.66; S 5.86.
Single crystal X-ray diffraction study showed that the
bicyclic system is almost planar; the deviations of the
atoms from the least-squares plane do not exceed
Yield of IIIa 76%, mp 215 C (dec.) (MeCN). IR spec- 0.092 . Bond lengths (d, ): N1 P2 1.607(4), P2 N3
1
trum (KBr), , cm : 2200 (C N), 3220 3380 (NH2).
1H NMR spectrum, , ppm: 2.18 s (CH3), 6.69 d (2H
arom.), 6.84 s (NH2), 6.92 7.05 m (5H arom.), 7.17
7.25 m (2H arom.), 7.47 7.60 m (5H arom.). Found,
%: C 71.48; H 4.80; N 17.41; S 7.87. C24H19N5S.
Calculated, %: C 70.39; H 4.68; N 17.10; S 7.83.
Yield of IIIb 75%, mp 219 C (dec.) (dioxane). IR
1.602(4), N3 C4 1.324(6), C4 C4a 1.384(6), C4a C7a
1.384(6), N1 C7a 1.339(6).
4-Methyl-N1-{7-oxo-3,5-diphenyl-6,7-dihydro-
thiazolo[4,5-d]pyrimidin-2(3H)ylidene}-N2-phenyl-
benzamidine VI. A mixture of 5 mmol of IIIa,
10 mmol of benzoyl chloride, and 5 ml of pyridine
was refluxed with stirring for 4 h; then the mixture
was cooled to 20 C, and the precipitate was filtered
off and washed with ethanol. Yield 66%, mp 322 C
1
spectrum (KBr), , cm : 2200 (C N), 3220, 3270,
3340, 3460 (NH2). 1H NMR spectrum, , ppm: 3.66 s
(CH3), 6.67 6.73 m (4H arom.), 6.83 s (NH2), 6.95
7.27 m (5H arom.), 7.48 7.62 m (5H arom.). Found,
%: C 66.91; H 4.61; N 16.59; S 7.42. C24H19N5OS.
Calculated, %: C 67.74; H 4.50; N 16.46; S 7.54.
1
(DMF). IR spectrum (KBr), , cm : 1660 (C=O),
3050 (NH). Found, %: N 13.37; S 6.10. C31H23N5OS.
Calculated, %: N 13.64; S 6.24.
Ethyl 7-amino-5-methyl-2-(4-methoxy-N-phenyl-
benzimidoyl)imino-3-phenyl-2,3-dihydrothiazolo-
[4,5-b]pyridine-6-carboxylate IV. A 5-mmol portion
of SnCl4 was added to a mixture of 2.5 mmol of IIIb,
2.5 mmol of ethyl acetoacetate, and 20 ml of 1,2-di-
chloroethane. The mixture was refluxed for 6 h and
then cooled to 20 C and neutralized with 10 ml of
2 M sodium carbonate; the precipitate was filtered off,
and the organic layer was separated, kept over CaCl2,
and evaporated to dryness in a vacuum. Yield 89%,
3,5-Diphenylthiazolo[4,5-d]pyrimidine-2,7(3H,-
6H)-dione VII. A solution of 2 mmol of VI, 10 ml of
acetic acid, and 0.5 ml of concentrated HCl was re-
fluxed for 40 h and then allowed to stand at 20 25 C
for 24 h. The precipitate was filtered off and washed
with ethanol. Yield 54%, mp 325 C (DMF). IR spec-
trum (KBr), , cm : 1680 (C=O), 3060 (NH). Found,
%: C 62.95; H 3.35; N 13.35; S 9.92. C17H11N3O2S.
Calculated, %: C 63.54; H 3.45; N 13.08; S 9.98.
1
mp 189 C (EtOH C6H6). IR spectrum (CH2Cl2),
,
The IR spectra were recorded on Specord IR-71
(CH2Cl2 solutions) and UR-20 (KBr pellets) spec-
trometers. The H NMR spectra were measured on
1
cm : 1670 (C=O), 3340, 3460 (NH2). 1H NMR spec-
trum (mixture of stereoisomers), , ppm: 1.42 t
(CH3CH2), 2.53, 2.62 s (CH3C), 3.72, 3.83 s (CH3O),
4.38 q (CH3CH2), 5.77, 6.13 s (1 : 4, NH2), 6.63
7.87 m (2C6H5, C6H4). Found, %: N 13.20; S 6.01.
C30H27N5O3S. Calculated, %: N 13.03; S 5.96.
1
Varian VXR-300 (300 MHz; IV and V) and Varian
Gemini-200 (200 MHz; IIIa and IIIb) spectrometers;
solvent DMSO-d6, internal reference TMS. X-ray
diffraction study of V was performed with an Enraf
Nonius CAD-4 diffractometer (CuK radiation,
1.54180 ) in cooperation with A.N. Chernega (Insti-
tute of Organic Chemistry, National Academy of Sci-
ences of Ukraine).
4-Methoxy-N1-{2,2,4-trimethoxy-7-phenyl-2,2-
dihydrothiazolo[4,5-d][1,3,2 5]diazaphosphorin-
6(7H)-ylidene}-N2-phenylbenzamidine V. A mixture
of 2 mmol of IIIb, 2.2 mmol of PCl5, and 6 ml of dry
chlorobenzene was refluxed with stirring for 20 min;
then the mixture was cooled to 20 C, and the precip-
itate was filtered off and vacuum-dried. This product
was suspended in 5 ml of dioxane, and 1.9 ml of a
4.3 M solution of sodium methylate in methanol,
diluted with 3 ml of dioxane, was added dropwise.
The mixture was stirred for 2 h, the precipitate of
NaCl was filtered off, the filtrate was vacuum-evap-
orated, and the residue was treated with methanol to
initiate crystallization; the precipitate was filtered off.
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3. Khalil, Z.H., Abdel-Hafez, A.A., Geies, A.A., and El-
Dean, A.M.K., Bull. Chem. Soc. Jpn., 1991, vol. 64,
no. 2, p. 668.
1
Yield 77%, mp 186 C (AcOMe). H NMR spectrum
(mixture of stereoisomers), , ppm: 3.59, 3.63, 3.66,
3.71, 3.83, 3.95 s (4CH3), 6.60 7.87 m (2C6H5,
4. Kornuta, P.P., Kalenskaya, A.I., and Shevchenko, V.I.,
Zh. Obshch. Khim., 1971, vol. 41, no. 5, p. 988.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 11 2002