Fused Heterocyclic systems derived from 2,6-diaryl-3,5- dibenzylidenetetrahydro-4H-thiopyran-4-ones

Article abstract of DOI:10.1080/10426500500328905

The reaction of 2,6-diphenyl and 2,6-di-p-tolyltetrahydro-4H-thiopyran-4- ones with benzaldehyde afforded 2,6-diphenyl and 2,6-di-p-tolyl-3,5-dibenzy- lidene-tetrahydro-4H-thiopyran-4-ones, which, on treatment with hydroxylamine hydrochloride, hydrazine h

Full text of DOI:10.1080/10426500500328905

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Fused Heterocyclic Systems
Derived from 2,6-Diaryl-3,5-
dibenzylidenetetrahydro-4H-
thiopyran-4-ones
Abdel Moneim El-Ghanam a
a Chemistry Department, Alexandria University,
Alexandria, Egypt
Published online: 01 Feb 2007.
To cite this article: Abdel Moneim El-Ghanam (2006): Fused Heterocyclic Systems
Derived from 2,6-Diaryl-3,5-dibenzylidenetetrahydro-4H-thiopyran-4-ones,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:6, 1419-1425
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Phosphorus, Sulfur, and Silicon, 181:1419–1425, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500328905
Fused Heterocyclic Systems Derived from 2,6-Diaryl-3,5-
dibenzylidenetetrahydro-4H-thiopyran-4-ones
Abdel Moneim El-Ghanam
Chemistry Department, Alexandria University, Alexandria, Egypt
The reaction of 2,6-diphenyl and 2,6-di-p-tolyltetrahydro-4H-thiopyran-4-ones
with benzaldehyde afforded 2,6-diphenyl and 2,6-di-p-tolyl-3,5-dibenzy-lidene-
tetrahydro-4H-thiopyran-4-ones, which, on treatment with hydroxylamine hy-
drochloride, hydrazine hydrate and thiourea, gave thiopyrano[4,3-c]isoxazole,
thiopyrano[4,3-c]pyrazole and thiopyrano[4,3-d]pyrimidine derivatives, respec-
tively. Also, the reaction of dibenzylidenetetrahydrothiopyran-4-ones with malonon-
itrile in piperidine and malononitrile in ammonim acetate afforded thiopyrano[4,3-
b]pyran and thiopyrano[4,3-b]pyridine derivatives, respectively, while treatment
with ethyl acetoacetate gave acetyl thiopyrano[4,3-b]pyran derivatives. On the other
hand, treatment of 2,6-diphenyl and 2,6-di-p-tolyltetrahydro-4H-thiopyran-4-ones
with elemental sulfur and malononitrile in the presence of diethylamine gave
thieno[2,3-c]thiopyran derivatives. Structures of all compounds were confirmed
from their spectral and analytical data.
Keywords Dibenzylidenetetrahydrothiopyrones; thiopyrano[4,3-b]pyridine; thiopy-
rano[4,3-c]isoxazole; thiopyrano[4,3-c]pyrazole; thieno[2,3-c]thiopyran derivatives;
thiopyrano[4,3-d]pyrimidine
A wide spectrum of biological activities as well as industrial impor-
tance associated with thiopyrans and their condensed derivatives. Sev-
eral thetrahydro-4H-thiopyran-4-ones are known to possess significant
antibacterial, parasitic, sedative, and anti-inflammatory activities.1
Also, superior bleaching compounds for textile and porcelain contained
tetrahydrothiopyran-4-one-S,S-dioxides.2 They are also important in-
termediates in the synthesis of pyrylium dyes.3,4 Moreover, tetrahy-
drothiopyrones are precursors of the difficulty available 4H-thiopyran-
4-ones5 which are used in the preparation of organic conductors.6 On the
basis of the previously discussed facts, new fused thiopyran derivatives
Received June 6, 2005; accepted July 28, 2005.
I would like to thank Dr. M. A. Morsy and King Fahd University of Petroleum
and Minerals, Saudi Arabia, for helping measuring spectral properties of some of the
compounds.
Address correspondence to Abdel Moneim El-Ghanam, Alexandria University, Chem-
istry Department, Faculty of Science, Ibrahimia, PO Box 426, Alexandria 21321, Egypt.
E-mail: delghanam@yahoo.com
1419

1420
A. M. El-Ghanam
have been synthesized from 2,6-diphenyl (2a) and 2,6-di-p-tolyl (2b)
3,5-dibenzylidenetetrahydro-4H-thiopyran-4-ones (Scheme 1).
SCHEME 1
RESULTS AND DISCUSSION
The reaction of one molar amount of 2,6-diphenyl (1a) and 2,6-di-p-
tolyl (1b)-tetrahydro-4H-thiopyran-4-ones, prepared according to the
literature method,7 with two molar amount of benzaldehyde in the pres-
ence of piperidine under reflux conditions afforded the corresponding
2,6-diphenyl (2a) and 2,6-di-p-tolyl (2b)-3,5-dibenzylidenetetrahydro-
4H-thiopyran-4-ones in moderate yields, respectively (Scheme 1). The

Fused Heterocyclic Systems
1421
structures of 2a,b were established from their spectral and analyti-
cal data (see Experimental section). The IR spectra showed a mod-
erately carbonyl absorption in the range of 1692–1686 cm−1, while
1
their H-NMR spectra showed, beside other characteristics, a singlet
at δ 4.28–4.22 for benzylic protons on C-2 and C-6 and a singlet at
δ 7.24–7.16 for the ylidene protons on C-3 and C-5 of a thiopyran
ring. On the other hand, the reaction of 3,5-dibenzylidenetetrahydro-
4H-thiopyran-4-ones 2a,b with bidentate reagents, hydroxylamine hy-
drochloride, hydrazine hydrate, and thiourea gave the fused rings
thiopyrano[4,3-c]isoxazole 3a,b, thiopyrano[4,3-c]pyrazole 4a,b, and
thiopyrano[4,3-d]pyrimidine 5a,b derivatives, respectively (Scheme 1).
The IR spectra of the fused heterocyclic systems 3a,b–5a,b showed
bands at 1640–1628 cm−1 for C N and a disappearance of car-
1
bonyl absorptions. The H-NMR spectra showed a singlet at δ 4.28–
4.18 for one of the benzylic protons of a thiopyran ring, a dou-
blet at δ 4.46–4.32 for other benzylic protons, a doublet of a dou-
blet at δ 3.46–3.24, and a doublet at δ 4.70–4.52 (see Experimental
section).
This investigation was extended to include the reactivity of
2a,b with some active methylene compounds as nucleophiles. Thus,
when 2a,b were refluxed with malononitrile in the presence of
ethanol/piperidine,8 it gave 2-amino-5,7-diaryl-8-benzylidene-3-cyano-
4-phenylthiopyrano[4,3-b]pyran 6a,b in good yields (Scheme 1). The
IR spectra showed a moderate absorption at 2190–2182 cm−1 for C N
and a NH2 absorption at 3368–3354 cm−1 and 3262–3256 cm−1. The
1H-NMR spectra showed, beside other characteristics, a singlet at δ
4.38–4.26 for thiopyran ring protons and a singlet at δ 4.82–4.76 for a
pyran proton (see Experimental section). On the other hand, the reac-
tion of 2a,b with malononitrile in the presence of an ethanol/ammonium
acetate8 mixture under a reflux condition afforded 2-amino-5,7-
diaryl-8-benzylidene-3-cyano-4-phenylthiopyrano[4,3-b]pyridine 7a,b
(Scheme 1). The structures of 7a,b were confirmed from their spectral
and analytical data (see Experimental section).
Finally, the reaction of 2a,b with ethyl acetoacetate9 in ethanol in the
presence of triethylamine gave 3-acetyl-5,7-diaryl-8-benzylidene-2-oxo-
4-phenylthiopyrano[4,3-b]pyran 8a,b in moderate yields (Scheme 1).
The 1H-NMR spectra exhibited the presence of a COCH3 singlet at
δ 2.38–2.36 and the absence of OC2H5 fragment. Also, the reaction
of 2,6-diphenyl 1a and 2,6-di-p-tolyl 1b-tetrahydro-4H-thiopyran-4-
ones with malononitrile in the presence of sulfur and diethyl amine
gave 2-amino-3-cyano-5,7-diarylthieno[2,3-c]thiopyran 9a,b. The ele-
mental analyses and spectral data were in agreement with structures
9a,b.

1422
A. M. El-Ghanam
Generally, six-member heterocyclic rings are known to be mostly in
the chair conformation.10 Sulfur heterocyclic also demonstrate the chair
conformation for a heterocyclic ring from their conformational studies.11
Assuming the chair conformation for the thiopyran ring, the two aryl
groups (Ar, Ar’) in compounds 3, 4, 5, 6, 7, 8, and 9 expected to occupy
the less-hindered equatorial positions.7
EXPERIMENTAL
Melting points are uncorrected and were measured on a Kofler Block
Infrared spectra were recorded with a Unicam SP 1025 spectropho-
1
tometer for KBr pellets. The H-NMR spectra were recorded on Jeol
Lambada-500 MHz spectrometer using TMS as an internal standard.
Mass spectra were recorded on a Finnigan-Matt 8430 mass spectrom-
eter operating at an ionization potential of 70 eV. Elemental analyses
were carried out at the Microanalytical Center of Cairo University.
Synthesis of 2,6-Diaryl-3,5-dibenzylidenetetrahydro-4H-
thiopyran-4-ones 2a,b
A mixture of 2,6-diaryltetrahydro-4H-thiopyran-4-ones 1a,b (1 mmol)
and benzaldehyde (2 mmol) in 30 mL of absolute ethanol and piperidine
(0.5 mL) was refluxed for 4 h. The reaction mixture then was poured
into ice cold water and acidified with HCl to give 2a,b as solids, which
recrystallized from ethanol.
1
2a: Yield, 66%, m.p. 168◦C; IR (KBr, cm−1) : 3086, 1692; H-NMR
(DMSO-d6, δ) : 4.28 (s, 2H, thiopyran protons), 7.16 (s, 2H, ylidene),
7.26–7.86 (m, 20H, arom.); MS: m/z (M+) 444. anal. calc. for C31H24SO:
C, 83.78; H, 5.41; S, 7.21. Found: C, 83.69; H, 5.28; S, 7.22.
1
2b: Yield, 62%, m.p. 192◦C; IR (KBr, cm−1) : 3082, 2886, 1686; H-
NMR (DMSO-d6, δ): 4.22 (s, 2H, thiopyran protons), 7.24 (s, 2H, yli-
dene), 7.28–7.80 (m, 18H, arom.), 2.42 (s, 6H, 2 CH3); MS: m/z (M+) 472.
anal. calc. for C33H28SO: C, 83.90; H, 5.93; S, 6.78. Found: C, 83.82; H,
5.92; S, 6.80.
Synthesis of Fused Thiopyran Compounds 3a,b–5a,b
A solution of 2,6-diaryl-3,5-dibenzylidenetetrahydro-4H-thiopyran-4-
ones 2a,b (0.02 mmol) in 30 mL of ethanol was treated with an equimo-
lar amount of hydroxylamine hydrochloride, hydrazine hydrate, or
thiourea and a few drops of acetic acid. The reaction mixture was re-
fluxed for 4 h, concentrated, and cold, and the separated compounds
were filtered off and recrystallized from ethanol.

Fused Heterocyclic Systems
1423
1
3a: Yield, 71%, m.p. 240◦C; IR (KBr, cm−1): 3018, 1628; H-NMR
(DMSO-d6, δ): 4.42 (d, 1H), 4.28 (s, 1H), 3.24 (dd, 1H), 4.70 (d, 1H),
7.16–7.82 (m, 21H, 20H arom. + 1H ylidene); MS: m/z (M+) 459. anal.
calc. for C31H25NOS: C, 81.05; H, 5.45; N, 3.05; S, 6.97. Found: C, 80.96;
H, 5.50; N, 3.12; S, 6.88.
1
3b: Yield, 68%, m.p. 198◦C; IR (KBr, cm−1): 3186, 3064, 1640; H-
NMR (DMSO-d6, δ): 4.36 (d, 1H), 4.26 (s, 1H), 3.30 (dd, 1H), 4.68 (d,
1H), 7.22–7.86 (m, 19H, 18H arom. + 1H ylidene), 2.46 (s, 6H, 2CH3).
anal. calc. for C33H29NOS: C, 81.31; H, 5.95; N, 2.87. Found: C, 81.42;
H, 5.92; N, 2.98.
1
4a: Yield, 73%, m.p. 166◦C; IR (KBr, cm−1): 3192, 3078, 1632; H-
NMR (DMSO-d6): 11.22 (s, 1H, NH), 4.42 (d, 1H), 4.18 (s,1H), 3.42 (dd,
1H), 4.62 (d, 1H), 7.16–7.82 (m, 21H, 20H arom. + 1H ylidene); MS: m/z
(M+) 458. anal. calc. for C31H26N2S: C, 81.22; H, 5.68; N, 6.11. Found:
C, 81.26; H, 5.58; N, 6.26.
1
4b: Yield, 68%, m.p. 215◦C; IR (KBr, cm−1): 3168, 3058, 1632; H-
NMR (DMSO-d6, δ): 10.98 (s, 1H, NH), 4.40 (d, 1H), 4.26 (s, 1H), 3.46
(dd, 1H), 4.54 (d, 1H) 7.16–7.88 (m, 19H, 18H arom. + 1H ylidene),
2.48 (s, 6H, 2CH3). anal. calc. for C33H30N2S: C, 81.48; H, 6.17, N, 5.76.
Found: C, 81.32; H, 6.08; N, 5.66.
5a: Yield, 76%, m.p. 246◦C; IR (KBr, cm−1): 3166, 3072, 1636, 1454;
1H-NMR (CDCl3, δ): 11.24 (s, 1H, NH), 4.46 (d, 1H), 4.24 (s, 1H), 3.24
(dd, 1H), 4.62 (d, 1H), 7.08–7.86 (m, 21H, 20H arom. + 1H ylidene); MS:
m/z (M+) 502. anal. calc. for C32H26N2S2: C, 76.49; H, 5.18; N, 5.58, S,
12.75. Found: C, 76.32; H, 5.22; N, 5.40; S, 12.81.
5b: Yield, 71%, m.p. 220◦C; IR (KBr, cm−1): 3152, 3066, 1630, 1450;
1H-NMR (CDCl3, δ): 10.86 (s, 1H, NH), 4.32 (d, 1H), 4.28 (s, 1H), 3.36
(dd, 1H), 4.60 (d, 1H), 7.12–7.84 (m, 19H, 18H arom. + 1H ylidene),
2.46 (s, 6H, 2CH3). anal. calc. for C34H30N2S2: C, 76.98; H, 5.66. Found:
C, 76.80; H, 5.80.
Synthesis of Thiopyrano[4,3-b]pyran Derivatives 6a,b
2,6-diaryl-3,5-dibenzylidenetetrahydro-4H-thiopyran-4-ones
2a,b
(0.01 mmol) was added to an equimolar amount of malononitrile in
ethanol (20 mL) and a few drops of piperidine. The reaction mixture was
refluxed for 3 h, concentrated, and cold to give thiopyrano[4,3-b]pyran
derivatives 6a,b in good yields which recrystallized from dioxane.
6a: Yield, 76%, m.p. 256◦C; IR (KBr, cm−1): 3368, 3256, 3062, 2182;
1H-NMR (DMSO-d6, δ): 4.30 (s, 1H), 4.26 (s, 1H), 4.76 (s, 1H), 5.28 (b,
2H, NH2), 7.16–7.88 (m, 21H, 20H arom. + 1H ylidene). MS: m/z (M+)
510. Anal. calc. for C34H26N2OS: C, 80.00; H, 5.10. Found: C, 79.88; H,
5.16.

1424
A. M. El-Ghanam
6b: yield, 75%, m.p. 222◦C; IR (KBr, cm−1): 3354, 3262, 3070, 2190;
1H-NMR (DMSO-d6, δ): 4.38 (s, 1H), 4.26 (s, 1H), 4.82 (s, 1H), 5.26 (b,
2H, NH2), 7.16–7.89 (m, 19H, 18H arom. + 1H ylidene), 2.46 (s, 6H,
2CH3). Anal. calc. for C36H30N2OS: C, 80.30; H, 5.58. Found: C, 80.18;
H, 5.52.
Synthesis of Thiopyrano[4,3-b]pyridine Derivatives 7a,b
A mixture of 2a,b (0.01 mmol) and malononitrile (0.01 mmol) in 20 mL
of ethanol was refluxed for 6 h with ammonium acetate (2 gm). The
solvent was evaporated, and the solid formed was recrystallized from
benzene to give 7a,b.
1
7a: Yield, 69%, m.p. 196◦C; IR (KBr, cm−1): 3400, 3350, 2208; H-
NMR (DMSO-d6, δ): 4.24 (s, 2H, thiopyran), 5.26 (b, 2H, NH2), 7.12–
7.82 (m, 21H, 20H arom. + 1H ylidene). Anal. calc. for C34H25N3S: C,
80.47; H, 4.93; N, 8.28; S, 6.31. Found: C, 80.52; H, 5.12; N, 8.16; S, 6.28.
1
7b: Yield, 66%, m.p. 224◦C, IR (KBr, cm−1): 3412, 3360, 2214; H-
NMR (DMSO-d6, δ): 4.26 (s, 2H, thiopyran), 5.32 (b, 2H, NH2), 7.02–
7.94 (m, 19H, 18H arom + 1H ylidene), 2.42 (s, 6H, 2CH3). Anal. calc.
for C36H29N3S: C, 80.75; H, 5.42; N, 7.85. Found: C, 80.76; H, 5.38; N,
7.88.
Synthesis of 3-Acetylthiopyrano[4,3-b]pyran Derivatives 8a,b
A mixture of 2a,b (0.01 mmol) and ethyl acetoacetate (0.01 mmol) in
absolute ethanol (20 mL) was refluxed for 2 h in the presence of triethy-
lamine (0.5 mL). The reaction mixture was concentrated to give 8a,b,
which recrystallized from benzene.
8a: Yield, 71%, m.p. 245◦C, IR (KBr, cm−1): 3104, 2889,1696, 1668;
1H-NMR (DMSO-d6, δ): 2.38 (s, 3H, COCH3), 4.26 (s, 2H, thiopyran
protons), 7.04–7.82 (m, 21H, 20H arom. + 1H ylidene). Anal. calc. for
C35H26SO3: C, 79.85; H, 4.94; S, 6.08. Found: C, 79.92; H, 4.90; S, 6.12.
8b: Yield, 69%, m.p. 265◦C, IR (KBr, cm−1): 3096, 2908, 1698, 1672;
1H-NMR (DMSO-d6, δ): 2.36 (s, 3H, COCH3), 2.42 (s, 6H, 2CH3), 4.28
(s, 2H, thiopyran protons), 7.10–7.86 (m, 19H, 18H arom. + 1H ylidene).
Anal. calc. for C37H30SO3: C, 80.14; H, 5.42; S, 5.78. Found: C, 80.22; H,
5.48; S, 5.68.
Synthesis of Thieno[2,3-c]thiopyran Derivatives 9a,b
To
a solution of 2,6-diaryltetrahydro-4H-thiopyran-4-ones 1a,b
(0.02 mmol) in 30 mL of THF, elemental sulfur (0.02 mmol), malononi-
trile (0.02 mmol) and a catalytic amount of triethylamine were added.
The reaction mixture was heated at reflux for 4 h and then poured into

Fused Heterocyclic Systems
1425
ice water and acidified with few drops of HCl. The solid product formed
was collected by filtration, washed with water, dried, and recrystallized
from dioxane.
9a: Yield, 68%, m.p. 182◦C, IR (KBr, cm−1): 3389, 3228, 3086, 2966,
2182; 1H-NMR (DMSO-d6, δ): 3.02 (m, 2H), 4.38 (s, 1H), 4.22 (dd, 1H),
7.12-7.90 (m, 10H, arom.), 8.22 (br, 2H, NH2). anal. calc. for C20H16N2S2:
C, 68.97; H, 4.60; N, 8.05. Found: C, 68.82; H, 4.76; N, 8.12.
9b: Yield, 63%, m.p. 194◦C; IR (KBr, cm−1): 3402, 3238, 3092, 2974;
1H-NMR (DMSO-d6, δ): 2.98 (m, 2H), 4.42 (s, 1H), 4.26 (dd, 1H), 7.16-
7.88 (m, 8H, arom.), 8.32 (br, 2H, NH2), 2.48 (s, 6H, 2CH3). anal. calc.
for C22H20N2S2: C, 70.21; H, 5.32. Found: C, 70.18; H, 5.38.
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