Unexpected formation of 4-aryl-3-cyano-6-phenylpyridine-2(1H)-thiones from the reaction of arylmethylenecyanothioacetamides with benzoyl-1,1,1- trifluoroacetone

Article abstract of DOI:10.1007/s10593-006-0027-0

4-Aryl-3-cyano-6-phenylpyridine-2(1H)-thiones, used in the synthesis of substituted 2-alkylthiopyridines, thieno[2,3-b]pyridines, and 1,4-di(pyridin-2-ylthio)butane, have been synthesized by the condensation of arylmethylenecyanothioacetamides with benzoyl-1,1,1-trifluoroacetone. The reaction path includes the formation of the Michael adduct which undergoes loss of the acyl group. The structure of 3-cyano-2-methylthio-4-(1-naphthyl)-6- phenylpyridine has been studied by X-ray crystallography. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0027-0

Chemistry of Heterocyclic Compounds, Vol. 41, No. 12, 2005
UNEXPECTED FORMATION OF 4-ARYL-3-CYANO-
6-PHENYLPYRIDINE-2(1H)-THIONES FROM THE REACTION
OF ARYLMETHYLENECYANOTHIOACETAMIDES
WITH BENZOYL-1,1,1-TRIFLUOROACETONE
V. D. Dyachenko1 and A. N. Chernega2
4-Aryl-3-cyano-6-phenylpyridine-2(1H)-thiones, used in the synthesis of substituted 2-alkylthiopyridines,
thieno[2,3-b]pyridines, and 1,4-di(pyridin-2-ylthio)butane, have been synthesized by the condensation of
arylmethylenecyanothioacetamides with benzoyl-1,1,1-trifluoroacetone. The reaction path includes the
formation of the Michael adduct which undergoes loss of the acyl group. The structure of 3-cyano-
2-methylthio-4-(1-naphthyl)-6-phenylpyridine has been studied by X-ray crystallography.
Keywords: Michael adducts, 2-alkylthiopyridines, arylmethylenecyanothioacetamides, 4-aryl-3-cyano-
6-phenylpyridine-2(1H)-thiones,
benzoyl-1,1,1-trifluoroacetones,
1,4-di(pyridin-2-ylthio)butane,
alkylation, acyl cleavage, X-ray crystallography.
Benzoyl-1,1,1-trifluoroacetone has previously used successfully for the synthesis of substituted
6-trifluoromethylpyridinechalcogenones by the Michael reaction both as donor [1,2] and as acceptor (as the
ethoxymethylene derivative) [3]. Absolute ethanol was used as the solvent and secondary or tertiary amines as
the catalyst. Our invesigations have shown that carrying out the Michael reaction by the interaction of benzoyl-
1,1,1-trifluoroacetone 1 with arylmethylenecyanothioacetamides 2 in ethanol in the presence of a two-fold
excess of N-methylmorpholine gave rise to 4-aryl-3-cyano-6-phenylpyridine-2(1H)-thiones 3 which are
potentially biologically active compounds (method A). In particular 4-(1-naphthyl)-substituted pyridine-2(1H)-
chalcogenones appear to have antiasthmatic activity [4].
The reaction pathway apparently includes formation of the Michael adducts 4. The latter undergo acyl
cleavage [5] on the addition of water or ethanol as result of which products 5 are probably formed which then
undergo heterocyclization into the substituted pyridine-2(1H)-thiones 3. We note that fluorine-containing
β-diketones have a tendency to acyl cleavage [6]. For example, 2-thienoyltrifluoroacetone reacts with
arylmethylenemalononitrile in ethanol in the presence of morpholine to give 2-aryl-1,1-dicyano-3-(2-
thienoyl)propanes and trifluoroacetic acid [7]. However acyl cleavage of benzoyl-1,1,1-trifluoroacetone in
conditions of the Michael reaction is unknown.
__________________________________________________________________________________________
1
Taras Shevchenko Lugansk State Pedagogical University, Lugansk 91011, Ukraine; e-mail:
dvd_lug@online.lg.ua. 2 Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev 02094,
Ukraine; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, 1821-1828, December 2005.
Original article submitted July 15, 2003.
0009-3122/05/4112-1499©2005 Springer Science+Business Media, Inc.
1499

Ar
O
O
Ar
O
NMe
A
/ EtOH
CN
S
CN
S
F3C
F3C
+
Ph
O
Ph
O
H2N
2a–d
H2N
1
4
Ar
O
NH
–ROH
OR
ROH
CN
S,
CN
B
Ph
O
Ar
6a–d
Ar
HO
CN
CN
S
F3C
..
H2N
–CF3COOR,
–H2O, –2[H]
N
S
Ph
Ph
O
H
3a–d
5
Ph
NH2
Cl
Hal
Z/KOH
O
7
OMe
8a–r
KOH,
DMF
Ar
Ar
NH2
CN
KOH
DMF
CN
S
Z
Ph
S
Ph
N
Ph
N
S
Z
NH2
N
Ph
10a–w
11a–c
9
O
R = H or Et. 2,3,6 а Ar = naphth-1-yl, b Ar = 4-FC6H4, c Ar = 4-ClC6H4, d Ar = 4-MeOC6H4;
8 a Hal = Cl, b-l Hal = Cl, m-r Hal = Br; a Z = H, b Z = COOCH2Ph, c Z = COOEt, d Z = COOPr,
e Z = Ph, f Z = COOMe, g Z = COO(CH2)8Me, h Z = thiazol-2-ylcarbamoyl, i Z = COO(CH2)7Me, j Z = CONH2,
k Z = 4-BrC6H4NHCO, l Z = CN, m Z = naphth-2-ylcarbonyl, n Z = 4-EtOC6H4CO, o Z = 2-MeC6H4, p Z = 4-BrC6H4CO,
g Z = CH=CH2, r Z = coumarin-3-ylcarbonyl; 10, 11 a Ar = 4-ClC6H4, Z = COOEt, b Ar = 4-MeOC6H4, Z = COOCH2Ph,
c Ar = 4-MeOC6H4, Z = COOMe; 10 d-g Ar = naphth-1-yl, h-j Ar = 4-ClC6H4, k-w Ar = 4-MeOC6H4; d, k Z = H,
e,h Z = COOCH2Ph, f Z = naphth-2-ylcarbonyl, g Z = 4-EtOC6H4CO, i Z = COOPr, j, n Z = Ph, l Z = 2-MeC6H4,
m Z = CONH2, o Z = 4-BrC6H4NHCO, p Z = 4-BrC6H4CO, q Z = CN, r Z = CH=CH2, s Z = coumarin-3-ylcarbonyl,
t Z = COOEt, u Z = COO(CH2)8Me, v Z = thiazol-2-ylcarbamoyl, w Z = COO(CH2)7Me
The structures of compounds 3a-d were shown by physicochemical and spectroscopic methods (Tables 1
and 2), direct synthesis by the interaction of δ-ketodinitriles 6 with elemental sulfur (method B) [8], and also by
chemical transformations. In particular, the pyridinethiones 3 react readily with the alkyl halides 7 and 8 in basic
medium to form the corresponding organic sulfides 9 and 10. Compounds 10a-c underwent intramolecular
Thorpe–Ziegler cyclization under the influence of KOH solution to give substituted thieno-[2,3-b]pyridines 11
which confirmed the presence of the vicinal cyano group [9]. These compounds have potential as intermediates
for creation of medicinal products [10, 11].
1500

TABLE 1. Characteristics of the Compounds Synthesized, 9, 10a-w, 11a-c, 12
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С*
Yield, %
C
H
N
9
C27H21N3O2S
C22H17ClN2O2S
C28H22N2O3S
C28H18N2O3S
C23H16N2S
71.70
71.82
4.58
4.69
9.20
9.31
303-305
(DMF)
191-193
(BuOH)
132-134
(EtOH)
148-151
(MeOH)
150-152
(AcOH)
176-177
(AcOH)
114-116
(AcOH)
165-166
(AcOH)
195-198
(EtOH)
175-178
(i-PrOH)
194-196
(AcOH)
144-146
(BuOH)
163-165
(BuOH)
251-253
(BuOH)
169-172
(AcOH)
227-228
(BuOH)
229-231
(BuOH)
161-163
(BuOH)
110-111
(BuOH)
235-237
(DMF)
191-193
(BuOH)
122-124
(EtOH)
239-241
(AcOH)
133-134
(i-PrOH)
274-276
(BuOH)
248-250
(AcOH)
215-217
(AcOH)
118-124
(BuOH)
84
71
69
78
77
87
84
78
65
70
63
66
71
78
69
70
82
85
67
73
80
64
77
68
69
75
66
67
10a
10b
10c
10d
10e
10f
10g
10h
10i
64.50
64.62
3.95
4.19
6.74
6.85
71.86
72.08
4.60
4.75
6.14
6.00
67.73
67.68
4.51
4.65
7.02
7.17
78.21
78.38
4.40
4.58
8.11
7.95
C31H22N2O2S
C34H22N2OS
C32H24N2O2S
C27H19ClN2O2S
C23H19ClN2O2S
C25H17ClN2S
C20H16N2OS
C27H22N2OS
C21H17N3O2S
C26H20N2OS
C27H20BrN3O2S
C27H19BrN2O2S
C21H15N3OS
C22H18N2OS
C30H20N2O4S
C23H20N2O3S
C30H34N2O3S
C24H18N4O2S2
C29H32N2O3S
C22H17ClN2O2S
C28H22N2O3S
C22H18N2O3S
C42H34N4O2S2
76.39
76.52
4.42
4.56
5.68
5.76
80.79
80.61
4.21
4.38
5.42
5.53
76.63
76.78
4.70
4.83
5.52
5.60
68.91
68.86
3.84
4.07
6.14
5.95
65.19
65.32
4.61
4.53
6.50
6.62
10j
10k
10l
72.50
72.72
4.02
4.15
6.85
6.78
72.11
72.26
4.70
4.85
8.55
8.43
76.60
76.75
5.32
5.25
6.54
6.63
10m
10n
10o
10p
10q
10r
10s
10t
10u
10v
10w
11a
11b
11c
12
66.95
67.18
4.62
4.56
11.02
11.19
76.32
76.44
5.11
4.93
6.70
6.86
60.96
61.14
3.75
3.80
8.07
7.92
63.02
62.92
3.60
3.72
5.29
5.44
70.42
70.57
4.11
4.23
11.85
11.76
73.58
73.72
4.92
5.06
7.90
7.81
71.20
71.41
4.12
3.99
5.38
5.55
68.14
68.30
4.80
4.98
6.72
6.93
71.50
71.68
6.74
6.82
5.40
5.57
62.71
62.86
4.12
3.96
12.05
12.22
71.12
71.28
6.72
6.60
5.59
5.73
64.40
64.62
3.95
4.19
7.02
6.85
71.85
72.08
4.60
4.75
5.84
6.00
67.74
67.68
4.42
4.65
7.02
7.17
73.18
73.02
5.15
4.96
7.90
8.11
_______
* Solvent for crystallization in brackets.
1501

TABLE 2. Spectroscopic Characteristics of Compounds 9, 10a-w, 11a-c, 12
1Н NMR spectrum, δ, ppm (J,Hz)
IR
spectrum,
ν, cm-1
(C≡N,
C(5)H, s,
SCH2, s,
or
Com-
pound
others signals
4
C=O)
NH2, br. s
1
2
3
9
2218,
1664
7.86,
5.84
3.86 (3H, s, CH3O); 7.07 and 8.32 (2H each, both d,
J = 8.0, C6H4); 7.37-7.72 [11H, m, (C6H5)2 and NH2],
8.06 (1H, br. s, NH2)
10a
10b
10c
2224,
1714
7.95,
4.27
1.18 (3H, t, J = 6.7, CH2CH3); 4.10 (2H, q, CH2CH3);
7.58 (3H, m, C6H5); 7.65 and 7.81 (2H each, both d, J = 8.7,
C6H4); 8.22 (2H, m, C6H5)
2221,
1705
7.89,
4.37
3.83 (3H, s, CH3O); 5.15 (2H, s, OCH2); 7.15 and 7.75 (2H each,
both d, J = 8.1, C6H4); 7.29 (5H, s, C6H5); 7.49 (3H, m, C6H5);
8.21 (2H, m, C6H5)
2214,
1709
7.90,
4.27
3.67 (3H, s, COOCH3); 3.86 (3H, s, OCH3);
7.15 and 7.77 (2H each, both d, J = 7.8, C6H4);
7.53 (3H, m, C6H5); 8.21 (2H, m, C6H5)
10d
10e
10f
10g
2224
7.99,
3.35
7.35-7.78 (8H, m, Harom,); 8.10 (2H, m, Harom,); 8.33 (2H, m, Harom,)
2225,
1716
7.82,
4.32
5.16 (2H, s, OCH2); 7.25-7.69 (13H, m, Harom,); 8.05 (4H, m, Harom,)
2234,
1700
—*,
5.13
6.99 (2H, t, J = 7.9, Harom,); 7.21 (1H, m, Harom,);
7.51-8.14 (16H, m, Harom,)*; 8.88 (1H, s, C(1)H naphthyl)
2210,
1675
7.76,
4.95
1.46 (3H, t, J = 6.7, CH3); 4.17 (2H, q, CH2);
7.04 and 7.87 (2H each, both d, J = 8.1, C6H4); 7.22 (2H, m, Harom,);
7.35 (1H, m, Harom,); 7.59 (5H, m, Harom,); 8.09 (4H, m, Harom,
)
10h
10i
2225,
1698
7.95,
4.27
5.14 (2H, s, CH2); 7.48-7.60 (8H, m, Harom,); 7.64
and 7.80 (2H each, both d, J = 8.10, C6H4); 8.24 (2H, m, Harom,
)
2217,
1695
7.98,
4.25
0.81 (3H, t, J = 8.4, CH3); 1.55 (2H, m, CH2); 4.08 (2H, t,
J = 7.9, OCH2); 7.54 (3H, m, C6H5); 7.67 and 7.79 (2H each,
both d, J = 8.5, C6H4); 8.24 (2H, m, C6H5)
10j
2220
2218
2215
7.93,
4.72
7.30-7.54 (8H, m, Harom,); 7.65 and 7.80 (2H each, both d,
J = 8.5, C6H4); 8.28 (2H, m, Harom,
)
10k
10l
7.78,
2.73
3.84 (3H, s, OCH3); 7.70 and 8.25 (2H each, both d, J = 8.4, C6H4);
7.60 (5H, m, C6H5)
7.81,
4.72
2.42 (3H, s, CH3); 3.85 (3H, m, OCH3); 7.08 and 8.27 (2H each,
both d, J = 8.5, C6H4); 7.20 (2H, m, Harom,); 7.38-7.74 (7H, m, Harom,
)
10m
10n
10o
10p
10q
10r
2224,
1670
7.88,
4.08
3.85 (3H, s, OCH3); 7.05 and 8.29 (2H each, both d, J = 8.5, C6H4);
7.25 (1H, br. s, NH2); 7.52-7.79 (6H, m, C6H5 and NH2)
2221
7.85,
4.70
3.31 (3H, s, OCH3); 7.11 and 7.71 (2H each, both d, J = 8.5, C6H4);
7.29 (2H, m, Harom,); 7.56 (6H, m, Harom,); 8.25 (2H, m, Harom,
)
2218,
1674
2227,
1705
7.82,
4.31
7.90,
5.00
3.78 (3H, s, OCH3); 6.81 and 8.19 (2H each, both d, J = 8.0, C6H4);
7.46-7.70 (9H, m, Harom,); 10.61 (1H, br. s, NH)
3.81 (3H, s, OCH3); 6.75 and 8.05 (2H each, both d, J = 8.5, C6H4);
7.52-7.80 (9H, m, Harom,
)
2252,
2217
7.93,
4.50
3.84 (3H, s, OCH3); 7.08 and 8.34 (2H each, both d, J = 8.5, C6H4);
7.50-7.78 (5H, m, C6H5)
2218
7.82,
4.08
3.83 (3H, s, OCH3); 5.16 (1H, d, Jcis = 9.1, =CH2);
5.37 (1H, d, Jtrans = 16.9, =CH2); 6.05 (1H, m, CH=);
(d, J = 6.9), 7.04 and 8.25 (2H each, both d, J = 8.0, C6H4); 7.61 (5H, m, C6H5)
10s
10t
2220,
1698
7.95,
4.98
3.69 (3H, s, OCH3); 6.77 and 8.04 (2H each, both d, J = 8.0, C6H4);
7.32-7.78 (9H, m, Harom,); 8.61 (1H, s, H(3) coumarinyl)
2214,
1717
7.84,
4.24
1.19 (3H, s, J = 6.9, CH2CH3); 3.85 (3H, s, OCH3);
4.13 (2H, q, OCH2); 7.07 and 8.20 (2H each, both d, J = 8.2, C6H4);
6.61 (5H, m, C6H5)
10u
2206,
1690
7.75,
4.14
0.82 (3H, t, J = 4.02, CH3); 1.19 [12H, m, (CH2)6], 1.55 (2H, m,
CH2); 3.88 (3H, s, OCH3); 4.06 (2H, t, J = 6.66, OCH2);
7.08 and 7.69 (2H each, both d, J = 8.7, C6H4); 7.50 (3H, m,C6H5);
8.13 (2H, m, C6H5)
1502

TABLE 2 (continued)
1
2
3
4
10v
2216,
1660
7.70,
4.33
3.89 (3H, s, OCH3); 7.02 and 7.39 (1H each, both d, J = 3.54, H(5)
and H(4) thiazolyl); 7.10 and 7.69 (2H each, both d, J = 8.0, C6H4);
7.32 (3H, m, C6H5); 8.05 (2H, d, J = 7.04, C6H5);
12.51 (1H, br. s, NH)
10w
2220,
1704
7.75,
4.12
0.83 (3H, t, J = 4.02, CH3); 1.20 [10H, m, (CH2)5], 1.56 (2H, m,
CH2); 3.89 (3H, s, OCH3); 4.05 (2H, t, J = 4.98, OCH2);
7.08 and 7.65 (2H each, both d, J = 6.76, C6H4); 7.46 (3H, m, C6H5);
8.14 (2H, m, C6H5)
11a
11b
11c
12
1713
1705
1714
2219
7.80,
5.86
1.30 (3H, t, J = 6.7, CH2CH3); 4.27 (2H, q, CH2CH3);
7.53 (3H, m, C6H5); 7.66 (4H, s, C6H4); 8.21 (2H, m, C6H5)
7.72,
5.84
3.82 (3H, s, OCH3); 5.31 (2H, s, CH2); 7.04 and 8.18 (2H each,
both d, J = 8.1, C6H4); 7.40 (5H, s, C6H5); 7.59 (5H, s, C6H5)
7.74,
5.79
7.70,
3.78 (3H, s, COOCH3); 3.83 (3H, s, OCH3); 7.04 and 8.18 (2H each,
both d, J = 8.0, C6H4); 7.60 (5H, s, C6H5)
2.00 [4H, m, (CH2)2], 3.75 [6H, s, (OCH3)2], 6.94 and 8.13 [4H each,
3.45 (m,) both d, J = 8.0, (C6H4)2], 7.59 [10H, m, (C6H5)2]
_______
* Signals are overlapped.
Alkylation of the pyridinethione 3d with 1,4-dichlorobutane with a reagent ratio of 2:1 gave
1,4-di(pyridin-2-ylthio)butane 12.
OMe
OMe
Cl
/ KOH
Cl
3d
NC
S
CN
S
DMF
N
Ph
N
Ph
12
TABLE 3. Mass Spectra of Compounds 10d-g, 10u-w
Compound
m/z (Irel, %)
352 [M]+ (58), 351 [M−1]+ (100), 305 (6), 277 (8), 77 (4)
10d
10e
486 [M]+ (65), 485 [M−1]+ (45), 441 (12), 351 (52), 337 (28), 318 (13), 277 (14),
239 (6), 91 (100), 77 (8), 65 (7)
10f
10g
10u
506 [M]+ (10), 351 (18), 296 (7), 155 (100), 127 (64), 77 (3)
500 [M]+ (8), 351 (7), 149 (100), 121 (39), 77 (4), 65 (6)
502 [M]+ (47), 501 [M−1]+ (88), 487 (21), 469 (13), 331 (100), 317 (16), 300 (8),
288 (12), 242 (15), 77 (6), 69 (14), 55 (26), 43 (65), 41 (39)
10v
458 [M]+ (14), 457 [M−1]+ (6), 385 (10), 359 (52), 331 (100), 317 (24), 303 (7),
288 (17), 242 (23), 214 (13), 127 (76), 100 (19), 77 (18), 55 (16), 45 (18)
10w
488 [M]+ (49), 487 [M−1]+ (77), 473 (18), 331 (100), 317 (16), 300 (10), 288 (14),
242 (15), 214 (10), 77 (8), 69 (12), 55 (22), 43 (57)
1503

C22
C16
C17
C21
C15
C14
C20
C18
C19
C13
C3
N2
C2
C1
C23
C4
C12
C7
C11
C10
C5
S1
N1
C8
C6
C9
Fig. 1. General view of the molecule 10d with numbering of the atoms (H atoms are not shown).
Principal bond lengths and angles: S(1)–C(5) 1.754(5), S(1)–C(6) 1.781(6), N(1)–C(1) 1.349(6), N(1)–C(5) 1.331(5) Å;
C(5)–S(1)–C(6) 101.3(3), C(1)–N(1)–C(5) 118.4(4) deg. The remaining bond lengths and angles
are comparable with standard values [12].
To establish unambiguously the structure of the products of the interaction of benzoyl-1,1,1-
trifluoroacetone with arylmethylencyanothioacetamides under the conditions of the Michael reaction and the
regioselectivity of their alkylation compound 10d (Fig. 1) was studied by X-ray crystallography. The benzene
ring C(7-12) and the C(13-22) group form dihedral angles of 25.5 and 60.0° with the central pyridine ring N(1)C(1-5)
.
The S–Me substituent is practically coplanar with the pyridine ring – the torsion angle N(1)–C(5)–S(1)–C(6) is only
11.6°.
So condensation of benzoyl-1,1,1-trifluoroacetone with arylmethylencyanothioacetamides include acyl
cleavage from the Michael adducts to give substituted 4-aryl-3-cyano-6-phenylpyridine-2(1H)-thiones.
EXPERIMENTAL
A monocrystal of compound 10d was initially rolled into a sphere of diameter 0.19 mm.
X-ray Crystallography was carried out at room temperature on an automatic four circle Enraf-Nonius
CAD-4 diffractometer (CuKα radiation, λ = 1.54178 A, with relative scanning rate 2θ/ω = 1.2, θmax = 60°,
segment of the sphere 0 ≤ h ≤ 9, 0 ≤ k ≤ 15, 0 ≤ l ≤ 16). A total of 1592 reflexions were collected. Crystalls of
compound 10d are rhombic, a = 8.849(2), b = 14.795(3), c = 14.004(5) Å; V = 1833.5(9) Å3; M = 352.45; Z = 4;
dcalc = 1.28 g/cm3; µ = 15.72 cm-1; F(000) = 739.0; space group Pna21 (No. 33). The structures was refined by
the direct method by least squares analysis in the complete matrix anisotropic approximation using the
CRYSTALS suite of programs [13]. In the refinement 1415 reflexions with I > 1.5σ(I) (235 calculated
parameters with 6.0 reflexions per parameter). About half the hydrogen atoms were found from electron density
difference syntheses, while the rest were placed in calculated positions. All the hydrogen atoms were included in
the refinement at fixed positions with fixed thermal parameters. Absorption by the crystal was calculated with
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the help of azimuthal scanning [14]. The Chebyshev weighting scheme [15] with five parameters: 0.92, 0.12,
0.80, 0.01, and 0.25, was used in the refinement. The final values of the residual factors were R = 0.038 and Rw =
0.036, GOF = 1.217. Coordinates of the non-hydrogen atoms may be obtained from the authors.
IR spectra of nujol mulls of the synthesized compounds were recorded with an IKS-29 instrument.
1H NMR spectra of DMSO-d6 solutions with Me4Si as internal standard were recorded with the following
instruments: Bruker WP-100 SY (100 MHz) (compounds 9, 10a-c, h-t), Gemini -200 (200 MHz) (compounds
10e-g, v), Bruker WM-250 (250 MHz) (compound 3a), Varian Mercury-400 (400 MHz) (compound 10d) and
Bruker DR 500 (500 MHz) (compounds 10u,w). Mass spectra were taken with a Kratos MS-890 machine with
direct introduction of the sample into the ion source (70 eV). Melting points were determined with a Kofler
block. The course of reactions and the purity of the compounds obtained were monitored by TLC (Silufol
UV 254, 3:5 acetone–hexane, detection with iodine vapor).
4-Aryl-3-cyano-6-phenylpyridine-2(1H)-thiones
3a-d.
Method
A.
The
corresponding
arylmethylencyanothioacetamide 2 (10 mmol) and N-methylmorpholine (2.2 ml, 10 mmol) were added to a
solution of benzoyl-1,1,1-trifluoroacetone (2.16 g, 10 mmol) in ethanol (25 ml) and the mixture was stirred for
4 h. The mixture was then kept for 1 d, then diluted with 10% hydrochloric acid to pH 5 and kept for 48 h. The
precipitate which formed was separated and washed with water and hexane. Compounds 3a-d were formed and
were crystallized from glacial acetic acid.
3-Cyano-4-(1-naphthyl)-6-phenylpyridine-2(1H)-thione (3a). Yield 2.37 g (70%); mp 228-230°C.
IR spectrum (nujol mull), ν, cm-1: 2212 (C≡N). 1H NMR spectrum, δ, ppm: 7.14 (1H, s, C(5)H); 7.49-8.18 (12H,
m, Harom); 14.23 (1H, br. s, NH). Mass spectrum, m/z, (Irel): 338 [M]+(47), 337 [M-1]+ (100), 277 (9), 177 (18),
175 (25), 169 (47), 77 (20). Found, %: C 77.89; H 4.02; N 8.36. C22H14N2S. Calculated, %: C 78.08; H 4.17;
N 8.28.
3-Cyano-4-(4-fluorophenyl)-6-phenylpyridine-2(1H)-thione (3b). Yield 68%; mp199-204°C
(200-202°C [16]). The spectroscopic characteristics corresponded to those in the literature [16].
4-(4-Chlorophenyl)-3-cyano-6-phenylpyridine-2(1H)-thione (3c). Yield 74%; mp 233-236°C
(233-234°C [8]). The spectroscopic characteristics corresponded to those in the literature [8].
3-Cyano-4-(4-methoxyphenyl)-6-phenylpyridine-2(1H)-thione (3d). Yield 65%; mp 219-224°C
(223-225°C [8]). The spectroscopic characteristics corresponded to those in the literature [8].
Method B was described in the literature [8, 17]. The yields of compounds 3a-d were 75, 60, 79, and
66% respectively.
2-(1-Carbamoyl-1-phenylmethylthio)-3-cyano-4-(4-methoxyphenyl)-6-phenylpyridine (9), 4-Aryl-
3-cyano-2-Z-methyl-6-phenylthiopyridines 10a-w, 6-Amino-4-aryl–6-phenyl-2-Z-thieno[2,3-b]pyridines
11a-c, and 1,4-Di[3-cyano-4-(4-methoxyphenyl)-6-phenylpyrin-2-ylthio]butane (12) were obtained by a
known method [18] (see Tables 1 and 2).
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