Synthesis of some new spirothiopyran derivatives from the reaction of 4-thiopyrylidenemalononitriles with bidentate and active methylene reagents

Article abstract of DOI:10.1080/10426500307794

2,6-Diphenyl and 2-phenyl-6-p-tolyl-4-thiopyrylidenemalomonitriles have been synthesized as α, β-unsaturated nitriles from the condensation of 2,6-diphenyl and 2-phenyl-6-p-tolyl-4H-thiopyran-4-thiones with malononitrile. Treatment of 4-thiopyrylidenemalo

Full text of DOI:10.1080/10426500307794

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Synthesis of Some New Spirothiopyran Derivatives from
the Reaction of 4-Thiopyrylidenemalononitriles with
Bidentate and Active Methylene Reagents
Abdel Moneim El-Ghanam a
a Alexandria University, Alexandria, Egypt
Version of record first published: 27 Oct 2010
To cite this article: Abdel Moneim El-Ghanam (2003): Synthesis of Some New Spirothiopyran Derivatives from the Reaction of
4-Thiopyrylidenemalononitriles with Bidentate and Active Methylene Reagents, Phosphorus, Sulfur, and Silicon and the Related
Elements, 178:4, 863-868
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:863–868
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1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390198020
SYNTHESIS OF SOME NEW SPIROTHIOPYRAN
DERIVATIVES FROM THE REACTION OF
4-THIOPYRYLIDENEMALONONITRILES WITH
BIDENTATE AND ACTIVE METHYLENE REAGENTS
Abdel Moneim El-Ghanam
Alexandria University, Alexandria, Egypt
(Received June 26, 2002; accepted September 21, 2002)
2,6-Diphenyl and 2-phenyl-6-p-tolyl-4-thiopyrylidenemalomonitriles
have been synthesized as , -unsaturated nitriles from the conden-
sation of 2,6-diphenyl and 2-phenyl-6-p-tolyl-4H-thiopyran-4-thiones
with malononitrile. Treatment of 4-thiopyrylidenemalononitriles with
hydrazine hydrate, hydroxylamine hydrochloride, thiourea, thiosemi-
carbazide, or guanidine hydrochloride afforded the corresponding
spirothiopyran derivatives of pyrazole, isoxazole, 1,3-thiazine or
pyrimidine, respectively, while treatment with acetylacetone gave the
corresponding spirothiopyran derivatives of pyran.
Keywords: 4-Thiopyrylidenemalononitriles; IR spectra; mass spectra;
NMR spectra; spirothiopyran
The importance of thiopyran derivatives because of their importance
as intermediates in the synthesis of pyrylium dyes1 as well as their
biological activities2 promoted the present investigation.
, -Unsaturated nitriles have attracted much attention as potential
starting materials for the synthesis of many heterocyclic compounds.3–6
In this investigation, 4-thiopyrylidenemalononitriles are synthesized
as , -unsaturated nitrile to study their reactivity toward some
bidendate and active methylene reagents.
The author thanks Kink Fahd University of Petroleum and Minerals (Saudi Arabia)
Chemistry Department for helping completing this work while working as a Research
Associate in the department.
Address correspondence to Abdel Moneim El-Ghanam, Chemistry Department,
Faculty of Science, Alexandria University, Ibrahimia PO Box 426, Alexandria 21321,
Egypt. E-mail: deghanam@yahoo.com
863

864
A. M. El-Ghanam
RESULTS AND DISCUSSION
2,6-Diphenyl and 2-phenyl-6-p-tolyl-4-thiopyrylidenemalononitriles
2a,b are synthesized from the reaction of 2,6-diphenyl and 2-phenyl-
6-p-tolyl-4H-thiopyran-4-thiones 1a,b, and prepared according to the
literature method,7 with malononitrile in refluxing ethanol in the
presence of triethylamine as a catalyst (Eq. 1).
(1)
The structure of 4-thiopyrylidenemalononitriles 2a,b are confirmed
from their spectral and analytical data (Tables I and II). The IR spectra
1
showed a moderately C N absorption in the range 2192–2196 cm
,
while their 1H-NMR spectra showed beside other characteristics, a
singlet at 6.76–6.82 for H-3 and H-4 protons of thiopyran ring.
Treatment of 2a,b with hydrazine hydrate, hydroxylamine hy-
drochloride, thiourea, thiosemicarbazide, or guanidine hydrochloride
in ethanol in the presence of pipredine afforded the corresponding
spirothiopyran derivatives of pyrazole, isoxazole, 1,3-thiazine or prim-
idine 3a,b–7a,b (Scheme 1). The reaction involve the addition of the
amino or mercapto groups at the ethylenic double bond and then nu-
cleophilic attack of the amino or imino group to give the cyclized spiro
compounds.
Also, the reaction of 4-thiopyrylidenemalononitriles 2a,b with active
methylene compounds, acetylacetone, in ethanol in the presence of
pipredine gave the corresponding spirothiopyran derivatives 8a,b
(Scheme 1).
A carbanion formation is assumed in these reactions followed
by nucleophilic addition at the ethylenic bond and cyclization
to give the spiro compounds 8a,b. All spirothiopyran derivatives
3a,b–8a,b were confirmed from their spectral and analytical data
(Tables I and II).
EXPERIMENTAL
Elemental analysis were preformed on a Perkin-Elmer 240 microanaly-
zer. Melting points were recorded on a Kofler Block and are uncorrected.

Synthesis of Some New Spirothiopyran Derivatives
865
SCHEME 1
Infrared spectra were measured with a Unicam SP 1025 spectropho-
tometer for KBr pellets. The 1H NMR spectra were recorded on a Varian
EM-390 MHz spectrometer using TMS as internal standard. Mass spec-
tra were recorded at 70 eV with an AEI MS-9 spectrometer coupled to
a DS-50 Data System using a direct insertion probe for introduction of
samples.

866
A. M. El-Ghanam
TABLE I Spectral Data of the Prepared Compounds 2a,b–8a,b
1
Compd.
IR (KBr) (cm
)
1H-NMR (ppm) CDCl3
2a
3086 (CH, arom), 2192 (C N),
1582 (C C).
7.62 (m, 10H, arom), 6.76 (s, 2H, H-3
and H-5 in thiopyran)
2b
3a
3072 (CH, arom), 2196 (C N),
1579 (C C), 2920 (CH, aliph)
3392, 3326, 3214 (NH2 + NH),
3094 (CH, arom), 2198 (C N),
1632 (C N), 1608 (C C)
3386, 3332, 3220 (NH2 + NH),
3086 (CH, arom); 2920 (CH, aliph)
2196 (C N), 1628 (C N),
1596 (C C)
7.60 (m, 9H, arom), 6.82 (s, 2H, H-3 and
H-5 in thiopyran), 2.38 (s, 3H, CH3)
10.82 (br, 1H, NH), 7.62 (m, 10H, arom),
7.22, 6.88 (s, 2H, H-3 and H-5 in
thiopyran), 5.58 (br, 2H, NH2)
10.90 (br, 1H, NH), 7.58 (m, 9H, arom),
7.18, 6.90 (s, 2H, H-3 and H-5 in
thiopyran), 5.62 (br, 2H, NH2),
2.40 (s, 3H, CH3)
3b
4a
4b
3398, 3322, 3232 (NH2 + NH),
3093 (CH, arom), 2196 (C N),
1608 (C C)
11.22 (br, 1H, NH), 7.58 (m, 10H, arom),
7.20, 6.86 (s, 2H, H-3 and H-5 in
thiopyran), 5.86 (br, 2H, NH2)
11.16 (br, 1H, NH), 7.62 (m, 9H, arom),
7.12, 6.82 (s, 2H, H-3 and H-5 in
thiopyran), 5.86 (br, 2H, NH2),
2.42 (s, 3H, CH3)
3389, 3329, 3226 (NH2 + NH),
3112 (CH, arom), 2920
(CH, aliph), 2206 (C N),
1602 (C C)
5a
5b
6a
6b
3390, 3336 (NH2), 3102 (CH, arom), 7.56 (m, 10H, arom), 5.48–5.82 (br, 4H,
2202 (C N), 1630 (C N),
1608 (C C)
2NH2), 7.22, 6.88 (s, 2H, H-3 and
H-5 in thiopyran)
3394, 3328 (NH2), 3092 (CH, arom), 7.58 (m, 9H arom), 7.26, 6.80 (s, 2H, H-3
2932 (CH, aliph), 2196 (C N),
1632 (C N), 1606 (C C)
3388, 3336, 3240 (NH2 + NH),
3096 (CH, arom), 2204 (C N),
1636 (C N), 1600 (C C)
3404, 3332, 3236 (NH2 + NH),
3092 (CH, arom), 2198 (C N),
2936 (CH, aliph), 1642 (C N),
1606 (C C)
and H-5 in thiopyran), 5.18–5.56
(br, 4H, 2NH2), 2.42 (s, 3H, CH3)
10.82 (br, 1H, NH), 7.62 (m, 10H, arom),
7.26, 6.92 (s, 2H, H-3 and H-5 in
thiopyran), 4.68–5.32 (br, 4H, 2NH2)
10.94 (br, 1H, NH), 7.56 (m, 9H, arom),
7.18, 6.92 (s, 2H, H-3 and H-5 in
thiopyran), 4.56–5.38 (br, 4H, 2NH2),
2.38 (s, 3H, CH3)
7a
7b
3406, 3336, 3240 (NH2 + NH),
3102 (CH, arom), 2192 (C N),
1642 (C N), 1596 (C C)
11.16 (br, 1H, NH2), 7.60 (m, 10H, arom),
7.26, 6.98 (s, 2H, H-3 and H-5 in
thiopyran), 5.16–5.58 (br, 4H, 2NH2)
11.10 (br, 1H, NH), 7.64 (m, 9H, arom),
3396, 3342, 3230 (NH2 + NH),
3112 (CH, arom), 2940 (CH, aliph), 7.64, 6.84 (s, 2H, H-3 and H-5 in
2190 (C N), 1638 (C N),
1602 (C C)
thiopyran), 5.28–5.60 (br, 4H, 2NH2),
2.42 (s, 3H, CH3)
8a
8b
3406, 3350 (NH2), 3110 (CH, arom), 7.58 (m, 10H, arom), 7.22, 6.94 (s, 2H,
2966, 2942 (CH, aliph),
2192 (C N), 1668 (C O),
1608 (C C)
H-3 and H-5 in thiopyran), 5.24 (br, 2H,
NH2), 2.32 (s, 3H, CH3),
2.20 (s, 3H, COCH3)
3396, 3342 (NH2), 3108 (CH, arom), 7.52 (m, 9H, arom), 7.16, 6.82 (s, 2H, H-3
2962, 2938 (CH, aliph),
2188 (C N), 1672 (C O),
1592 (C C)
and H-5 in thiopyran), 5.30 (br, 2H,
NH2), 2.30 (s, 3H, CH3),
2.22 (s, 3H, COCH3)

Synthesis of Some New Spirothiopyran Derivatives
867
TABLE II Analytical Data of Compounds 2a,b–8a,b
Analysis % calcd. (found)
S
m.p. ( C)
(cryst. solv.)
Compd.
Yield (%)
78
Mol. form.
C
H
N
2a
128 (ethanol)
146 (ethanol)
162 (ethanol)
150 (ethanol)
126 (ethanol)
166 (ethanol)
186 (ethanol)
172 (ethanol)
188 (benzene)
192 (benzene)
182 (ethanol)
196 (ethanol)
216 (benzene)
194 (benzene)
C20H12N2S
76.92 3.84
(76.76 3.94
77.30 4.29
(77.42 4.18
69.77 4.64 16.28
(69.82 4.56 16.36
70.39 5.03 15.64
(70.52 5.22 15.60
69.57 4.35 12.17
(69.64 4.18 12.08
70.19 4.74 11.70
(70.06 4.72 11.62
8.96 10.26
9.12 10.24)
2b
3a
3b
4a
4b
5a
5b
6a
6b
7a
7b
8a
8b
81
62
66
73
60
71
66
81
73
71
66
62
70
C21H14N2S
8.59
8.71
9.82
9.88)
9.30
9.21)
8.94
8.76)
9.28
9.36)
8.91
8.76)
C
20H16N4S
C21H18N4S
C20H15N3OS
C
21H17N3OS
C21H16N4S2
23H20N4S2
C21H17N5S2
64.95 4.12 14.43 16.49
(65.12 4.28 14.30 16.38)
65.67 4.48 13.93 15.92
(65.48 4.56 14.06 15.76)
62.53 4.22 17.37 15.88
(62.42 3.98 17.52 15.82)
63.31 4.56 16.79 15.35
(63.48 4.38 16.88 15.32)
C
C
C
22H19N5S2
21H17N5S
67.92 4.58 18.87
(67.76 4.66 18.72
68.57 4.94 18.18
(68.62 4.78 18.30
8.63
8.48)
8.31
8.29)
7.77
7.76)
7.51
7.38)
C22H19N5S
C
C
25H20N2O2S
26H22N2O2S
72.82 4.85
(72.68 4.96
73.24 5.16
(73.36 5.22
6.80
6.72
6.57
6.70
Synthesis of 4-Thiopyrylidenemalononitriles 2a,b
0.023 mmol of 2,6-diphenyl and 2-phenyl-6-p-tolyl-4H-thiopyran-4-
thiones 1a,b prepared according to the literature method7 was added to
an equimoler amount of malononitrile in 50 ml ethanol and few drops of
triethylamine. The reaction mixture was refluxed for 6 h, concentrated
and cooled to give 2a,b, which was collected by filtration and crystal-
lized from ethanol. MS: m/z (relative abundance) 2a M+ 312 (12), 286
(18), 280 (22), 260 (19), 236 (52), 210 (24), 183 (100), 178 (22), 77 (36).
Synthesis of Spiro Compounds 3a,b--6a,b
General Procedure
A solution of 4-thiopyrylidenemalononitriles 2a,b (0.02 mmol in
40 ml ethanol) was treated with equimolar amount of hydrazine

868
A. M. El-Ghanam
hydrate or hydroxylamine hydrochloride or thiourea or thiosemecar-
bazide or guanidine hydrochloride and few drops of pipridene. The re-
action mixture was refluxed for 4 h, concentrated, cooled, and the sep-
arated compound was filtered off and recrystallized from the suitable
solvent. MS: m/z (relative abundance) 3b M+ 358 (22), 343 (16), 332
(22), 326 (32), 315 (46), 234 (18), 202 (26), 148 (100), 135 (26), 117 (28),
103 (32), 91 (18), 77 (36); 4a M+ 345 (12), 319 (18), 313 (12), 302 (36)
268 (22), 236 (34), 134 (100), 77 (36); 5a M+ 388 (8), 362 (12), 356 (22),
346 (28), 330 (32), 253 (16), 236 (100), 134 (36), 77 (42); 6b M+ 417 (26),
402 (18). 386 (22), 360 (36), 250 (30), 148 (100), 91 (48), 77 (18).
Synthesis of Compounds 8a,b
0.02 mmol of 4-thiopyrylidenemalononitriles 2a,b was added to a
stirred mixture of equimolar amount of acetylacetone in 40 ml ethanol
and few drops of pipredine. The reaction mixture was refluxed for
4 h, concentrated, cooled, and the separated solid was filtered off and
recrystallized from suitable solvent. MS: m/z (relative abundance) 8a
M+ 412 (14), 380 (24), 369 (18), 343 (42), 335 (20), 327 (28), 236 (100),
134 (38), 77 (28).
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[2] A. H. Ingall, Compr. Heterocycl Chem., 3, 885 (1984).
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[4] G. E. H. El-Gemeie and F. A. Abdelaal, Heterocyles, 24, 349 (1986).
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