Cycloaddition with nitriles of an active methylene group to substituted 1,2,4-thiadiazol-5(2H)-imines [4]

Full text of DOI:10.1023/A:1020821006025

Russian Journal of General Chemistry, Vol. 72, No. 8, 2002, pp. 1317 1318. Translated from Zhurnal Obshchei Khimii, Vol. 72, No. 8, 2002,
pp. 1402 1403.
Original Russian Text Copyright
2002 by Zyabrev, Renskii, Drach.
LETTERS
TO THE EDITOR
Cycloaddition with Nitriles of an Active Methylene Group
to Substituted 1,2,4-Thiadiazol-5(2H)-imines
V. S. Zyabrev, M. A. Renskii, and B. S. Drach
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received October 9, 2001
An important property of substituted 1,2,4-thiadi-
azol-5(2H)-imines (I) is their ability to participate in
in [3+2]-cycloaddition reactions as 1,3 dipoles [1 4].
Heating on acetonitrile results in directed addition of
the C N group to the N=C S triad with heteroring
cleavage [1].
The structure of recyclization products IV was
proved by H NMR and IR spectra. Moreover, the
presence of the enaminonitrile fragment in compound
IVe and its analogs was proved by annelation reac-
tions which will be described in further publications.
1
Ethyl [5-(4-methyl-N-phenylbenzimidoyl)imino-
4-phenyl-4,5-dihydro-1,2,4-thiadiazol-3-yl]acetate
(IIIa). A solution of 2.5 mmol of compound Ia and
2.5 mmol of ethyl cyanoacetate in 10 ml of CH2Cl2
was allowed to stand at 20 25 C for 24 h. The solvent
was removed in a vacuum, the residue was treated
with ethanol, and the precipitate that formed was fil-
tered off. Yield 75%, mp 148 C. IR spectrum
We performed reactions of accessible reagents I
[1, 5] with substituted acetonitriles II containing an
active methylene group and revealed an unusual reac-
tion direction, since expected cycloaddition products
III underwent rearrangement into thiazol derivatives
IV.
Ar
1
1
N
(CH2Cl2), , cm : 1740 (C=O). H NMR spectrum
(CDCl3), , ppm: 1.18 t (CH3CH2), 2.24 s (CH3C6H4),
3.67 s (CH2CO), 4.08 q (CH3CH2), 6.85 7.60 m
(2C6H5, C6H4). Found, %: N 12.38; S 7.10. C26H24
N4O2S. Calculated, %: N 12.27; S 7.02.
X
NR2
+
R1N
N
S
Ia Id
IIa IIe
R2
N
R2
X
N
NH2
X
Ar
Ar
N
Ethyl 4-amino-2-(4-methyl-N-phenylbenzimido-
yl)imino-3-phenyl-2,3-dihydrothiazol-5-carboxylate
(IVa). A solution of 0.5 mmol of compound IIIa in
15 ml of ethanol was heated under reflux for 25 h and
then allowed to stand at 20 25 C for 48 h. The pre-
cipitate that formed was filtered off. Yield 69%, mp
R1N
R1N
N
N
S
S
IIIa IIIe
IVa IVe
R1 = Ph (a, b, e), PhCH2 (c), 4-MeC6H4 (d); R2 = Ph
(a c, e), Me (d); Ar = 4-MeC6H4 (a, e), 4-MeOC6H4 (b),
Ph (c, d); X = CO2Et (a), NO2 (b), P(O)Ph2 (c), Ts (d),
CN (e).
1
182 C (EtOH). IR spectrum (CH2Cl2), , cm : 1660
(C=O), 3350, 3460 (NH2). 1H NMR spectrum (CDCl3;
stereoisomeric mixture), , ppm: 1.33 t (CH3CH2),
2.21 s, 2.38 s (6:1, CH3C6H4), 4.26 q (CH3CH2),
5.71 s (NH2), 6.80 7.76 m (2C6H5, C6H4). Found, %:
N 12.41; S 7.12. C26H24N4O2S. Calculated, %: N
12.27; S 7.02.
The yields of compounds IV are much dependent
on the nature of substituent X in reagents II. Thus, if
nitriles contain strong electron-acceptor groups X
(NO2, Ts, or CN), cycloadducts IIIb, IIId, and IIIe
cannot be isolated, and the yields of recyclization
products are mostly high. At the same time, the major
products of the reaction of compounds Ia and Ic with
N1-[4-Amino-5-nitro-3-phenylthiazol-2(3H)-
ylidene]-4-methoxy-N2-phenylbenzamidine (IVb).
Nitroacetonitrile, 5 mmol, was added to a solution
cyanoacetic ester and diphenylphosphinoylacetonitrile of 5 mmol of compound Ib in 10 ml of CH2Cl2. A
at room temperature are compounds IIIa and IIIc,
which can be converted into corresponding com-
pounds IV by heating.
precipitate formed immediately and was filtered off.
Yield 49%, mp 218 C (decomp.) (ClCH2CH2Cl). IR
1
spectrum (KBr), , cm : 3160 3390 (NH2). 1H NMR
1070-3632/02/7208-1317$27.00 2002 MAIK Nauka/Interperiodica

1318
ZYABREV et al.
spectrum (DMSO-d6; stereisomeric mixture), , ppm:
3.67 s, 3.81 s (4:1, CH3), 6.69 7.79 m (2C6H5, C6H4),
8.21 br.s (NH2). Found, %: N 15.83; S 7.11. C23H19
N5O3S. Calculated, %: N 15.72; S 7.20.
N2-Benzyl-N1-[3-(diphenylphosphinoyl)methyl-
4-phenyl-1,2,4-tiadiazol-5(4H)-ylidene]benzamidine
(IIIc) and N1-[4-amino-5-diphenylphosphinoyl-3-
phenylthiazol-2(3H)-ylidene]-N2-benzylbenz-
amidine (IVc). a. A solution of 5 mmol of compound
Ic and 5 mmol of diphenylphosphinoylacetonitrile in
10 ml of CH2Cl2 was allowed to stand at room tem-
perature for 72 h. The solvent was removed in a
filtered off. Yield 87%, mp 181 C (decomp.)
1
(MeOH/CHCl3). IR spectrum (CH2Cl2), , cm : 3360,
1
3460 (NH2). H NMR spectrum (DMSO-d6), , ppm:
2.21 s (CH3C), 2.25 s (CH3C), 3.56 s (CH3N), 6.54 d
(2Harom), 6.98 s (NH2), 7.02 d (2Harom), 7.24
7.39 m (7Harom), 7.78 d (2Harom). Found, %: C
62.78; H 5.00; N 11.71; S 13.35. C25H24N4O2S2.
Calculated, %: C 63.00; H 5.08; N 11.76; S 13.45.
N1-[4-Amino-5-cyano-3-phenyltiazol-2(3H)-
ylidene]-4-methyl-N2-phenylbenzamidine (IVe). A
mixture of 20 mmol of compound Ia, 20 mmol of
malonodinitrile, and 10 ml of dioxane was heated
vacuum, the residue was treated with 10 ml of ethanol, under reflux with stirring for 3 h and then cooled to
and the mixture of compounds IIIc and IVc (2.4:1,
by H NMR) was filtered off. Recrystallization of this
mixture from benzene gave pure compound IIIc.
20 C. The precipitate was filtered off and dried in an
oven at 100 C. Yield 76%, mp 215 C (decomp.)
1
1
(MeCN). IR spectrum (KBr), , cm : 2200 (C N),
1
Yield 55%, mp 82 85 C. 1H NMR spectrum (CDCl3),
, ppm: 3.66 d (CH2P, JHP 15 Hz), 4.88 s (CH2N),
7.17 7.73 m (5C6H5). Found, %: C 70.66; H 5.06; N
9.41; S 5.51. C35H29N4OPS. Calculated, %: C 71.90;
H 5.00; N 9.58; S 5.48. The benzene mother liquor
was evaporated in a vacuum, the residue was treated
with ethanol, and compound IVc was filtered off.
Yield 10%, mp 163 C (MeCN). IR spectrum (KBr),
3220 3380 (NH2). H NMR spectrum (DMSO-d6), ,
ppm: 2.18 s (CH3), 6.69 d (2Harom), 6.84 s (NH2),
6.92 7.05
m
(5Harom), 7.17 7.25
m
(2Harom),
7.47 7.60 m (5Harom). Found, %: C 71.48; H 4.80;
N 17.41; S 7.87. C24H19N5S. Calculated, %: C 70.39;
H 4.67; N 17.10; S 7.83.
The IR spectra were recorded on a Specord IR-71
instrument in CH2Cl2 solutions and on a UR-20 in-
1
, cm : 3340, 3400 (NH2). 1H NMR spectrum
1
strument in KBr pellets. The H NMR spectra were
(DMSO-d6; stereisomeric mixture), , ppm: 4.44 s,
4.62 s (1:3, CH2), 6.05 s, 6.26 s (3:1, NH2), 7.19
7.77 m (5C6H5). Found, %: C 71.89; H 4.95; N 9.66;
P 5.35. C35H29N4OPS. Calculated, %: C 71.90; H
5.00; N 9.58; P 5.30.
obtained on Varian VXR-300 (compounds IIIa, IIIc,
and IVa IVd) and Varian Gemini-200 (compound
IVe) spectrometers, internal reference TMS.
REFERENCES
b. A mixture of 0.5 mmol of compound IIIc, 3 ml
of ethanol, and one drop of triethylamine was heated
under reflux for 0.5 h, cooled to 20 C, and compound
IVc was filtered off. Yield 17%.
N1-[4-Amino-3-methyl-5-tosylthiazol-2(3H)-
ylidene]-N2-p-tolylbenzamidine (IVd). A solution
of 5 mmol of triethylamine in 5 ml of ethanol was
added dropwise to a solution of 5 mmol of base Id
hydrobromide and 5 mmol of tosylacetonitrile in
10 ml of CH2Cl2. The mixture was allowed to stand
at 20 25 C for 24 h, the solvent was removed in a
vacuum, and the residue was washed with ethanol and
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002