Synthesis and properties of 3-cyano-3-hetaryl-ylidene-2-oxopropyl ethanethioates and 4-cyano-4-hetarylylidene-3-oxobutyl ethanethioates

Article abstract of DOI:10.1007/s10593-010-0598-7

Acylation of hetarylacetonitriles and hetarylylideneacetonitriles with acetylmercaptoacetyl chloride gave 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates. 2-Amino-3-hetaryl-4(5H)oxothio-phenes or 2-hetarylylidene-3-oxo- 4-sulfanylbutanenitriles were obtained on treating them with bases. Acylation of hetarylacetonitriles with 3-acetylmercaptopropionyl chloride gave 4-cyano-4-hetaryl-ylidene-3-oxobutyl ethanethioates, deacetylation of which gave 2-hetarylylidene-3-oxo-5-sulfanyl-pentanenitriles.

Full text of DOI:10.1007/s10593-010-0598-7

Chemistry of Heterocyclic Compounds, Vol. 46, No. 7, 2010
SYNTHESIS AND PROPERTIES OF 3-CYANO-3-HETARYL-
YLIDENE-2-OXOPROPYL ETHANETHIOATES AND 4-CYANO-
4-HETARYLYLIDENE-3-OXOBUTYL ETHANETHIOATES
A. V. Dobridnev1*, T. A. Volovnenko1, A. V. Turov1, and Yu. M. Volovenko1
Acylation of hetarylacetonitriles and hetarylylideneacetonitriles with acetylmercaptoacetyl
chloride gave 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates. 2-Amino-3-hetaryl-4(5H)oxothio-
phenes or 2-hetarylylidene-3-oxo-4-sulfanylbutanenitriles were obtained on treating them with bases.
Acylation of hetarylacetonitriles with 3-acetylmercaptopropionyl chloride gave 4-cyano-4-hetaryl-
ylidene-3-oxobutyl ethanethioates, deacetylation of which gave 2-hetarylylidene-3-oxo-5-sulfanyl-
pentanenitriles.
Keywords: acetylmercaptoacetyl chloride, 3-acetylmercaptopropionyl chloride, 2-amino-3-hetaryl-
4(5H)oxothiophene, 4-cyano-4-hetarylylidene-3-oxobutyl ethanethioates, 3-cyano-3-hetarylylidene-2-oxo-
propyl ethanethioates, hetarylacetonitriles, hetarylideneacetonitriles, 2-hetarylylidene-3-oxo-4-sulfanyl-
butanenitriles, 2-hetarylylidene-3-oxo-5-sulfanylpentanenitriles, lanthanide shift reagents, stereo-
selective synthesis.
Previously we carried out the interaction of hetarylacetonitriles 1a,b with acetylmercaptoacetyl chloride
(2) and studied the spectroscopic properties of the 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates 3a,b
obtained. In the present work we have broadened the series acylated substrates; in the reactions we have
involved hetarylacetonitriles 1c-e (Scheme 1) and also hetarylideneacetonitriles 4a-f (Table 1) obtained by
alkylation of compounds 1a-c,f with dialkyl sulfates with subsequent treatment with aqueous NaOH solution
(Scheme 2). Compounds 4a,c,d were previously obtained by a method described elsewhere [4-6].
Scheme 1
O
R1
R
O
R1
R
X
X
DMF
S
+
SAc
Cl
Ac
CN
N
CN
3a–e
N
H
1a–e
2
1–3 a–c R + R1 = CH=CH–CH=CH; 1,3 a X = NMe, b X = S, c X = NCHF2;
d R + R1 = CH=C(Me)–C(Me)=CH, X = NMe, e R = R1 = H, X = NCH2Ph
_______
* To whom correspondence should be addressed, e-mail: pierrot@gala.net.
1Taras Shevchenko Kiev National University, Kiev 01033, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, 1097-1106, July, 2010. Original
article submitted April 17, 2009.
0009-3122/10/4607-0887©2010 Springer Science+Business Media, Inc.
887

The electronegativity of the substituents on the nitrogen atoms and in the aromatic ring, and also the
nature of the heteroatom in X affected the ratio of the (Z)- and (E)-isomers formed.
Scheme 2
R1
X
1. R2 SO4
2
1a–c,f
2. NaOH
N
R2
CN
R
4a–f
4 a–e R + R1 = CH=CH–CH=CH, a R2 = Me, X = NMe, b R2 = Et,
X = NMe, c R2 = Me, X = S, d R2 = Et, X = S, e R2 = Me, X = NCHF2;
1f, 4f R + R1 = CH=C(Me)–CH=CH, X = NMe; 4f R2 = Me
1
The structures of the isomers and their ratios were determined by H NMR spectra. Thus the products
4c,d were formed exclusively as the (Z)-isomers in which the CN groups are in trans position relative to the NR2
unit. From compound 1a a symmetrical product 4a is formed, while the remaining unsymmetrical nitrogen-
containing hetarylylidene acetonitriles were isolated as mixtures: 4e 1:1.67 (E:Z), 4b 1:1.46 (E:Z), and 4f 1:1.1
(E:Z), in which the isomers with the nitrile trans to the NR2 predominated.
In the IR spectra of compounds 4a-f intense absorption bands are present in the 2175-2150 cm-1 region,
characteristic of a conjugated nitrile group [7], and also stretching bands of a conjugated C=C bond at
1600-1588 cm-1. Sharp singlets of the proton of the =CHCN group were observed in the 3.53-4.15 ppm region in
the 1H NMR spectra, recorded in DMSO-d6.
A single product, either the (Z)- or the (E)-isomer, 5a-f, was obtained by acylation of compounds 4a-f
with the acyl chloride 2 (Scheme 3).
Scheme 3
O
R
X
DMF
SAc
4a–f
2
+
R1
N
CN
5a–f
R2
5a-f X = R-R2, cf. compounds 4a-f respectively (Scheme 2).
The configurations of 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates were established through 1H
NMR spectroscopy using lanthanide shift reagents (LSR).
Thus the use of Eu(FOD)3* showed that in these compounds the CN group is in a trans position relative
to the fragment X (cf. formulas 5a-f in Scheme 3). The similarity in structure of compounds 5b,d and 5c,f
respectively permits the supposition that the latter have similar configurations.
S-acyl derivatives of compounds 3a-e and 5a,b,e,f under influence of bases (alkalis, primary and
secondary amines) undergo deacetylation and the mercaptonitriles formed undergo intramolecular cyclization.
In this way the corresponding substituted oxothiophenes 6a-e were prepared from compounds 3a-e (with
the fragment N(3)H), and in the case of compounds 5a,b,e,f (with the fragment N(3)R2) the products of
cyclization 7a-d were isolated as salts.
_______
* FOD is 2,3-dimethyl-6,6,7,7,8,8,8-heptafluoroocta-3,5-dione.
888

TABLE 1. Characteristics of Compounds Synthesized
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °С*
Yield, %*2
N
S
3с
3d
3e
C14H11F2N3O2S
C16H17N3O2S
C16H15N3O2S
C12H13N3
12.97
13.00
13.40
13.32
13.30
13.41
21.03
21.09
19.06
19.00
20.98
21.09
13.89
13.94
13.31
13.32
9.14
9.20
8.73
8.80
12.40
12.46
13.27
13.32
14.94
14.94
15.31
15.37
15.54
15.49
14.30
14.21
13.52
13.56
12.59
12.67
13.49
13.56
10.60
10.68
10.24
10.14
9.80
9.65
13.99
13.94
9.40
9.39
10.02
9.92
10.13
10.17
10.22
10.23
—
—
—
206
80
239-240
143-145
90-92
72
30
4b
4e
76
C11H9F2N3
142-143
158-160
142
59
4f
C12H13N3
80
5a
5b
5c
C15H15N3O2S
C16H17N3O2S
C14H12N2O2S2
C15H14N2O2S2
C15H13F2N3O2S
C16H17N3O2S
C12H9F2N3OS
C14H15N3OS
C14H13N3OS
C13H14ClN3OS
C14H16ClN3OS
C13H12ClF2N3OS
C14H16ClN3OS
C12H10N2OS2
C13H12N2OS2
C14H14N2OS2
C15H15N3O2S
C16H14N2O2S
C13H13N3OS
C14H12N2OS
10.61
10.64
10.06
10.17
21.11
21.07
20.10
20.14
9.58
9.50
10.15
10.17
11.35
11.40
11.80
11.73
11.70
11.82
10.91
10.84
10.27
10.35
9.60
9.66
10.41
10.35
24.37
24.44
22.08
23.20
22.00
22.08
60 (72)
80 (67)
75 (70)
79 (65)
78
144
225
5d
5e
184-185
154
5f
140-142
240-241 (dec.)
>300
40
6c
86
6d
6e
80
122-124
>300
65
7a
7b
7c
85
>300
75
245-246 (dec.)
256-257 (dec.)
180-182 (dec.)
177
42
7d
8a
8b
9
78
75
80
165-166
201-202
142
71
12a
12b
13a
13b
10.57
10.64
10.82
10.75
12.48
12.36
12.46
12.51
60 (50)
57 (52)
82
16.24
16.20
10.87
10.93
198-199
153
78
______
* Solvents for recrystallization: n-BuOH (compounds 3b,d, 5d, 6c,d);
2-PrOH (compounds 3e, 4b,e,f, 5a,b,e,f, 6e, 8a,b, 9, 12a,b, 13a,b); HOAc
(compound 5c); aqueous 2-PrOH (compounds 7a-d).
*2 The yields in brackets are for samples obtained from compounds
synthesized in this paper – acylation of compounds 8a,b and 13a,b and
alkylation of compound 3a.
889

TABLE 2. Spectral Characteristics of the Compounds Synthesized
Mass
spectrum,
m/z
Com-
pound*
IR cpectrum,
1Н NMR spectrum, δ, ppm (J, Hz)
ν, сm-1
[M+Н]+
1
2
3
4
3с
3131.65 (N-H);
2196.07 (C≡N);
1683.91 (C=O)SAc,
1630.76 (C=O)
2.38 (3H, s, COCH3); 4.09 (2H, s, CH2);
7.34 (2H, m, Н-5,6); 7.62 (1Н, m, Н-4);
7.72-7.74 (1Н, m, Н-7);
324.0
8.28 (1Н, t, 2J = 57.6, CHF2); 13.63 (1H, br. s, NH)
3d
3e
4b
3187.67 (N-H);
2190.47 (C≡N);
1700.69 (C=O)SAc,
1586.01 (C=O)
2.32 (3Н, s, 6-СН3); 2.35 (3Н, s, 5-СН3);
2.37 (3Н, s, COCH3); 3.93 (3Н, s, NCH3);
4.04 (2Н, s, СН2); 7.32 (1Н, s, Н-7);
7.37 (1Н, s, Н-4); 13.08 (1Н, s, NH)
316.0
314.0
200.0
3215.68 (N-H);
2179.27 (C≡N);
1692.30 (C=O)SAc,
1580.41 (C=O)
2.33 (3H, s, COCH3); 3.94 (2H, s, CH2);
5.49 (2Н, s, NCH2); 7.08-7.37 (7H, m, C6H5, H-4,5);
13.05 (1Н, br. s, NH)
2150.61 (CN)
2173.66 (CN)
2156.24 (CN)
2173.66 (CN)
2151.26 (CN)
(E)-Isomer 1.13 (3Н, t, J = 6.8, CH2CH3);
3.62 (1H, s, CHCN); 3.69 (3H, s, NCH3);
3.84 (2H, q, J = 6.8, NCH2); 7.05 (2Н, m, Н-4,7);
7.17 (2Н, m, Н-5,6)
(Z)-Isomer 1.29 (3Н, t, J = 6.8, CH2CH3);
3.28 (3H, s, NCH3); 3.53 (1H, s, CHCN);
4.25 (2H, q, J = 6.8, NCH2); 7.05 (2Н, m, Н-4,7);
7.17 (2Н, m, Н-5,6)
4e
(E)-Isomer 3.32 (3H, s, NCH3);
222.0
3.88 (1H, s, CHCN); 7.05 (1H, m, Н-4);
7.17 (2Н, m, Н-5,6); 7.31 (1H, m, Н-7);
8.03 (1Н, t, 2J =58.0, CHF2)
(Z)-Isomer 3.73 (3H, s, NCH3);
4.15 (1H, s, CHCN); 7.05 (1H, m, Н-4);
7.17 (2Н, m, Н-5,6); 7.31 (1H, m, Н-7);
7.72 (1Н, t, 2J =57.2, CHF2)
4f
2.36 (3Н, s, 5-СН3); 3.26 (3Н, s, N(3)CH3);
3.34 (1H, s, CHCN); 3.69 (3Н, s, N(1)CH3);
6.81 (1Н, d, J = 8.0, H-4); 6.92 (2H, m, Н-6,7)
200.4
302.0
316.0
5a
5b
2173.66 (C≡N);
1683.91 (C=O)SAc,
1602.79 (C=O)
2.37 (3H, s, COCH3); 3.75 (6Н, s, NCH3);
4.00 (2H, s, CH2); 7.45 (2Н, m, Н-4,7);
7.71 (2Н, m, Н-5,6)
2173.66 (C≡N);
1686.71 (C=O)SAc,
1602.79 (C=O)
1.45 (3Н, t, J = 6.8, CH2CH3);
2.37 (3H, s, COCH3); 3.70 (3H, s, NCH3);
3.99 (2H, s, COCH2);
4.42 (2H, q, J = 6.8, CH2CH3); 7.48 (2Н, m, Н-4,7);
7.78 (2Н, m, Н-5,6)
5c
2184.87 (C≡N);
1695.10 (C=O)SAc,
1613.98 (C=O)
2.39 (3Н, s, COCH3); 4.15 (2Н, s, CH2);
4.19 (3Н, s, NСН3); 7.40 (1Н, t, J = 8.0, Н-5);
7.56 (1Н, t, J = 8.0, Н-6);
305.2
318.8
7.72 (1Н, d, J = 8.0, Н-4); 7.91 (1Н, d, J = 8.0, Н-7)
5d
2190.47 (C≡N);
1681.11 (C=O)SAc,
1613.98 (C=O)
1.54 (3Н, t, J = 7.2, СН2СН3);
2.39 (3Н, s, COCH3); 4.16 (2Н, s, CH2);
4.81 (2Н, q, J = 7.2, СН2СН3);
7.39 (1Н, t, J = 8.0, Н-5); 7.55 (1Н, t, J = 8.0, Н-6);
7.74 (1Н, d, J = 8.0, Н-4); 7.91 (1Н, d, J = 8.0, Н-7)
5e
5f
6c
2184.87 (C≡N);
2.37 (3Н, s, COCH3); 3.85 (3Н, s, NCH3);
4.04 (2Н, s, СН2); 7.51-7.54 (2Н, m, Н-5,6);
7.56 (1Н, t, 2J = 56.5, CHF2);
338.0
316.0
282.0
1695.10 (C=O)SAc,
1605.59 (C=O)
7.74 (1H, d, J = 7.6, Н-4); 7.83 (1H, d, J = 7.4, Н-7)
2168.06 (C≡N);
1686.71 (C=O)SAc,
1602.79 (C=O)
2.37 (3Н, s, COCH3); 2.5 (3Н, s, 5-СН3);
3.72 (3Н, s, N(3)СН3); 3.73 (3Н, s, N(1)СН3);
3.99 (2Н, s, CH2); 7.27 (1Н, d, J = 8.0, Н-6);
7.53 (1Н, s, Н-4); 7.60 (1Н, d, J = 8.0, Н-7)
3187.67 (N-H)аs,
3058.82 (N-H)sim
1588.81 (C=O)
3.79 (2Н, s, СН2); 7.27-7.30 (2Н, m, Н-5,6);
7.61-7.67 (2Н, m, Н-4,7);
,
7.95 (1Н, t, 2J = 58.0, CHF2); 9.31 (1Н, br. s, NH);
9.49 (1Н, br. s, NH)
890

TABLE 2 (continued)
1
2
3
4
6d
6e
3327.73 (N-H)аs,
3254.90 (N-H)sim
1611.18 (C=O)
2.32 (3Н, s, 6-СН3); 2.36 (3Н, s, 5-СН3);
3.69 (5Н, s, NCH3, CH2); 7.14 (1Н, s, Н-7);
7.28 (1Н, s, Н-4); 8.98 (2Н, br. s, NH2)
274.2
,
,
3372.54 (N-H)аs,
3249.29 (N-H)sim
1611.18 (C=O)
3.61 (2Н, s, SСН2); 5.31 (2Н, s, NСН2);
6.95-7.04 (4Н, m, 4,5-H, CH2C6H5-3,5);
7.20-7.25 (3Н, m, CH2C6H5-2,4,6);
272.2
8.55 (1Н, br. s, NH); 8.72 (1Н, br. s, NH)
7a
7b
3512.60 (N-H)аs,
3260.50 (N-H)sim
1622.37 (C=O)
3.90 (6Н, s, 2NCH3); 3.96 (2Н, s, СН2);
7.66 (2Н, m, J = 3.2, H-4,7);
7.99 (2Н, m, J = 3.2, H-5,6)
260.0
274.0
,
,
3422.96 (N-H)аs,
3109.24 (N-H)sim
1641.95 (C=O)
1.42 (3Н, t, J = 6.8, NCH2CH3);
3.86 (3H, s, NCH3); 3.92 (2H, s, SCH2);
4.42 (2H, m, NCH2); 7.63 (2Н, m, Н-4,7);
8.01 (2Н, m, Н-5,6); 9.59 (1H, s, NH);
9.77 (1H, s, NH)
7c
3428.57 (N-H)аs,
3126.05 (N-H)sim
1630.76 (C=O)
3.95 (3H, s, NCH3); 3.96 (2H, s, CH2);
7.74 (2Н, m, Н-4,7); 7.89 (1Н, t, 2J = 55.6, CHF2);
7.96 (1Н, m, Н-5); 8.09 (1Н, m, Н-6);
9.76 (1Н, s, NH); 9.98 (1Н, s, NH)
296.0
,
7d
3434.17 (N-H)аs,
3204.48 (N-H)сиm
1639.16 (C=O)
2.58 (3Н, s, 5-СН3); 3.82 (3Н, s, N(3)СН3);
3.83 (3Н, s, N(1)СН3); 3.93 (2Н, s, CH2);
7.45 (1Н, d, J = 8.0, Н-6); 7.76 (1Н, s, Н-4);
7.83 (1Н, d, J = 8.0, Н-7); 9.38 (1H, s, NH);
9.61 (1H, br. s, NH)
274.13
,
8a
8b
2565.82 (S-H);
2190.47 (C≡N);
1616.78 (C=O)
2.55 (1Н, t, J = 8.0, SH); 3.65 (2Н, d, J = 8.0, CH2S);
4.20 (3Н, s, NСН3); 7.40 (1Н, t, J = 8.0, Н-5);
7.55 (1Н, t, J = 8.0, Н-6);
263.0
277.5
7.73 (1Н, d, J = 8.0, Н-4); 7.93 (1Н, d, J = 8.0, Н-7)
2565.82 (S-H);
2196.07 (C≡N);
1630.76 (C=O)
1.53 (3Н, t, J = 7.2, СН2СН3); 2.59 (1Н, t, J = 8.0, SH);
3.65 (2Н, d, J = 8.0, CH2S);
4.80 (2Н, q, J = 7.2, NСН2СН3);
7.40 (1Н, t, J = 8.0, Н-5); 7.56 (1Н, t, J = 8.0, Н-6);
7.75 (1Н, d, J = 8.0, Н-4); 7.93 (1Н, d, J = 8.0, Н-7)
9
2184.87 (C≡N);
1.25 (3Н, t, J = 7.2, СН2СН3);
291.2
1616.78 (C=O)
2.59 (2Н, q, J = 7.2, СН2СН3); 3.55 (2Н, s, CH2S);
4.17 (3Н, s, NСН3); 7.37 (1Н, t, J = 8.0, Н-5);
7.53 (1Н, t, J = 8.0, Н-6); 7.69 (1Н, d, J = 8.0, Н-4);
7.88 (1Н, d, J = 8.0, Н-7)
12a
12b
3193.27 (N-H);
2190.47 (C≡N);
1686.71 (C=O)SAc,
1591.60 (C=O)
2.31 (3H, s, COCH3); 2.91 (2Н, t, J = 6.8, CH2S);
3.13 (2Н, t, J = 6.8, COCH2); 3.96 (3H, s, NCH3);
7.26 (2Н, m, Н-5,6); 7.51 (1Н, d, J = 8.0, Н-7);
7.66 (1Н, d, J = 8.0, Н-4), 13.32 (1H, br. s, NH)
302.2
299.2
3434.17 (N-H);
2190.47 (C≡N);
1683.91 (C=O)SAc,
1633.56 (C=O)
2.32 (3H, s, COCH3); 2.97 (2Н, t, J = 6.8, CH2S);
3.14 (2Н, t, J = 6.8, COCH2);
7.32 (1Н, d, J = 9.2, Н-3); 7.50 (1Н, t, J = 7.6, Н-6);
7.76 (1Н, t, J = 7.6, Н-7); 7.87 (1Н, d, J = 7.6, Н-8);
7.89 (1Н, d, J = 7.6, Н-5); 8.37 (1Н, d, J = 9.2, Н-4);
15.50 (1H, br. s, NH)
13a
13b
2560.22 (S-H);
2179.27 (C≡N);
1597.20 (C=O)
2.02 (1H, t, J = 8.0, SН); 2.76 (2Н, q, J = 8.0, CH2S);
2.94 (2Н, t, J = 8.0, COCH2); 3.98 (3H, s, NCH3);
7.23 (2Н, m, Н-5,6); 7.52 (1Н, d, J = 8.0, Н-7);
7.66 (1H, d, J = 8.0, Н-4); 13.38 (1H, br. s, NH)
260.0
257.2
2521.00 (S-H);
2196.07 (C≡N);
1630.76 (C=O)
2.11 (1H, t, J = 8.0, SН); 2.82 (2Н, q, J = 8.0, CH2S);
3.14 (2Н, t, J = 8.0, COCH2);
7.32 (1Н, d, J = 9.2, Н-3); 7.50 (1Н, t, J = 7.6, Н-6);
7.76 (1Н, t, J = 7.6, Н-7); 7.87 (1Н, d, J = 7.6, Н-8);
7.89 (1Н, d, J = 7.6, Н-5); 8.37 (1Н, d, J = 9.2, Н-4);
15.59 (1H, br. s, NH)
_______
* Compounds 4b,e,f were isolated as mixtures of (Z)- and (E)-isomers.
*2 Molecular ions have the form [M+H]+ (for compounds 3c-e, 4b,f,e,
5a-f, 6c-e, 8a,b, 9, 12a,b, 13a,b) and [M-Cl]+ (for compounds 7a-d).
891

Scheme 4
H2N
O
R1
R
R1
R
X
CN
B:
X
S
SH
3a–e
DMF
N
N
H
O
6a–e
O
O
R1
R1
R
X
X
B:
HCl
5a,b,e,f
SH
+
N
S
DMF
–
CN
N
R
Cl
R2
R2
NH2
7a–d
6a–e R, R1, X cf. compounds 3a–e (Scheme 1).
7 a–с R + R1 = CH=CH–CH=CH, a R2 = Me, X = NMe, b R2 = Et, X = NMe, c R2 = Me,
X = NCHF2; d R + R1 = CH=C(Me)–CH=CH, R2 = Me, X = NMe
We had prepared compounds 6a and 6b previously [2, 3].
Deacetylation of compounds 5c,d, in contrast to compound 3c, was not accompanied by cyclization. On
acidification of the basic solutions 2-hetarylylidene-3-oxo-4-sulfanylbutanenitriles 8a,b were isolated
(Scheme 5).
Scheme 5
O
O
R1
R
R1
R
S
S
HCl
MeONa
MeOH
SNa
SH
5c,d
N
N
CN
CN
R2
R2
8a,b
8a,b R + R1 = CH=CH–CH=CH, a R2 = Me, b R2 = Et
These differences are apparently determined by the different spatial dispositions of the CN and SH
groups in the initially formed thiols, which are determined by the nature of the fragment X and the substituent at
the atom N(3). For example with X = NMe or NCHF2 (in the thiols from compounds 5a,b,e,f) this position is
favorable for cyclization, whereas with X = S (in the thiols from compounds 5c,d) it is unfavorable. The ease of
formation of the cyclic products 6a-e from compounds 3a-e with the fragment N(3)H (and with X= S in
compound 3b) shows the decisive influence of this fragment for cyclization, probably because of the production
of a intramolecular hydrogen bond between it and the C=O group, which is possible with the cis position of the
CN fragment relative to the X fragment.
Scheme 6
1. MeONa / MeOH
2. HCl
O
O
S
S
EtI / MeONa
5c,d
8a
SH
S
Et
AcCl / DMF
N
CN
N
Me
CN
R
9
8a,b
892

The structures of compounds 8a,b were confirmed from their spectral characteristics (Table 2). In their
1H NMR spectra are signals of protons of the CH2 group of the thioglycolic group (doublet at 3.65 ppm) and the
proton of the SH group (triplet at 2.55-2.60 ppm). In the IR spectra there are weak stretching vibrations of the
SH group at 2565 cm-1. Also treatment of compounds with acetyl chloride gave acyl derivatives 5c,d, and
treatment of the thiol 8a with ethyl iodide gave the product of alkylation, 9.
Compound 3a is capable of alkylation at the NH group with alkyl halides (MeI, EtI) in DMF in the
presence of K2CO3 to give compounds 5a,b respectively.
Interaction of the hetarylacetonitriles 1a and 10 with 3-acetylmercaptopropionyl chloride 11 gave the
4-cyano- 4-hetarylylidene-3-oxobutyl ethanethioates 12a,b (Scheme 7).
Scheme 7
O
O
X
X
DMF
Cl
+
SAc
CN
N
N
H
CN
SAc
1a, 10
11
12a,b
1a, 12 a X = NMe; 10, 12 b X = CH=CH
Like 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates 3a-e, compounds 12a,b exist in tautomeric
forms with intramolecular hydrogen bonding between the NH fragment of the heterocycle and the conjugated
carbonyl group of the acyl fragment CH2COCH2.
As in the case of compounds 5c,d, deacetylation of compounds 12a,b is not accompanied by cyclization,
1
but 2-hetarylylidene-3-oxo-5-sulfanylpentanenitriles 13a,b are formed (Scheme 8). The H NMR spectra of
compounds 13a,b, like those of compounds 8a,b, contain the characteristic signal of the SH proton (a triplet in
the 2.0-2.1 ppm range), and a weak stretching band of the SH group is observed at 2560 cm-1 in the IR spectra.
Completely analogously, treatment of the mercapto derivatives 13a,b with acetyl chloride in DMF leads to
acetylation of the sulfhydryl group, regenerating the initial structures of compounds 12a,b.
Scheme 8.
MeONa / MeOH
CN
X
2) HCl
SH
12a,b
N
H
13a,b
AcCl / DMF
O
13 a X = NMe, b X = CH=CH
Thus increasing the hydrocarbon chain of the acylating agent with a protected mercapto group in the end
leads to the impossibility of intramolecular cyclization of the thiols produced.
EXPERIMENTAL
Monitoring of the course of experiments and of the purity of the compounds synthesized was carried out
by TLC on Silufol UV-254 plates with 9:1 chloroform–methanol. 1H NMR spectra of DMSO-d6 solutions with
TMS as internal standard were measured with a Varian Mercury 400 (400 MHz) instrument. IR spectra of KBr
893

tablets were obtained with a Perkin-Elmer BX instrument, mass spectra were observed with an Agilent 1100
Series instrument with and Agilent LC/MSD SL detector. Melting points were measured with a small laboratory
Boetius heating plate with a VEB Analytic PNMK 05 observation device.
3-Cyano-3-hetarylylidene-2-oxopropyl Ethanethioates 3a-e, 5a-f, and 4-Cyano-4-hetarylylidene-
3-oxobutyl Ethanethioates 12a,b (General Method). Acetylmercaptoacetyl chloride 2 (5.5 mmol) or 3-acet-
oxymercaptopropionyl chloride 11 (5.5 mmol) was added to a solution of hetarylacetonitrile 1a-e, 10, or
hetarylylideneacetonitrile 4a-f (5 mmol) in DMF (5 ml) at 25°C. The reaction mixture was kept at room
temperature for 12 h, then the precipitate was filtered off, washed with water, dried and recrystallized from a
suitable solvent (Table 1).
Hetarylylideneacetonitriles 4a-f (General Method). A mixture of hetarylacetonitrile 1a-c, f (10 mmol) and
the corresponding dialkyl sulfate (11 mmol) was stirred for 40 min at 70°C. Then the reaction mixture was
poured into water (10 ml) and a solution of NaOH (25 mmol) in water (20 ml) was added with stirring. The
precipitate formed was filtered off, washed with cold water, dried and recrystallized.
2-Amino-3-hetaryl-4(5H)-oxothiophenes 6a-c (General Method). Aqueous ammonia (10 mmol) was
added to a solution of compound 3a-e (5 mmol) in DMF (5 ml) and the mixture was kept at 30-40°C for 24 h.
The precipitate was filtered off, washed with water, dried, and recrystallized.
2-Amino-4(5H)-oxothiophenehetaren-3-ium Chlorides 7a-d (General Method). An aqueous solution
of NaOH (10 mmol) in water (2 ml) was added to a solution of compound 5a,b,e,f (5 mmol) in DMF (10 ml)
and kept at 30-40°C for 24 h. Aqueous HCl was added until the mixture was slightly acidic, evaporated, and the
residue was recrystallized.
2-(3-Alkyl-2,3-dihydro-1,3-benzothiazol-2-ylidene)-3-oxo-4-sulfanylbutanenitriles 8a,b and 2-Het-
arylylidene-3-oxo-5-sulfanylpentanenitriles 13a,b (General Method). MeONa (10 mmol) in MeOH (10 ml)
was added with stirring at 60°C to a suspension of 6e,f or 12a,b (5 mmol) in MeOH (15 ml). After the reaction
mixture had become homogeneous, aqueous HCl was added to an acid reaction, the precipitate was filtered off,
washed with water, dried, and recrystallized.
2-(3-Methyl-2,3-dihydro-1,3-benzothiazol-2-ylidene)-3-oxo-4-ethylsulfanylbutanenitrile (9). MeONa
(10 mmol) in MeOH (10 ml) was added with stirring at 60°C to a suspension of compound 8a (5 mmol) in MeOH
(15 ml). After the reaction mixture was completely homogenized and cooled, ethyl iodide (10 mmol) was added with
stirring. Product 9 precipitated over 8 h, was filtered off, washed with methanol, dried and recrystallized.
Acylation of 2-(3-Alkyl-2,3-dihydro-1,3-benzothiazol-2-ylidene)-3-oxo-4-sulfanylbutanenitriles
8a,b and 2-Hetarylylidene-3-oxo-5-sulfanylpentanenitriles 13a,b (General Method). AcCl (5.5 mmol) was
added to a solution of nitrile 8a,b or 13a,b (5 mmol) in DMF (5 ml). The reaction mixture was kept for 12 h at
room temperature, the precipitate was filtered off, washed with water, dried and recrystallized. Compounds 5c,d
or 12a,b obtained respectively were identical with samples synthesized as described above. No depression of the
melting point was observed with mixed samples.
Alkylation of 3-Cyano-3-(1-methyl-2,3-dihydro-1H-benzoimidazol-2-ylidene)-2-oxopropyl Ethane-
thioate 3a (General Method). Finely dispersed K2CO3 (20 mmol) and the corresponding alkyl iodide
(10 mmol) were added to a solution of compound 3a (5 mmol) in DMF (20 ml). The reaction mixture was
stirred for 12 h at a temperature of 50°C, cooled to room temperature, filtered, the filtrate evaporated, and the
residue was recrystallized. The compounds 5a,b obtained were identical to samples synthesized as described
above. No depressions of mixed melting points were observed.
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894

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