Ring opening-ring closure of 4-phenyl-1,2-dithiole-3-thione: Convenient route to novel thiinethione derivatives by the reaction with active methylene nitriles

Article abstract of DOI:10.1080/17415993.2010.499942

4-Phenyl-1,2-dithiole-3-thione (1) reacts with active methylene nitriles in the presence of triethylamine to afford fused and isolated thiine derivatives, mainly from initial nucleophilic attack of methylene group at C-5 of the dithiole ring.

Full text of DOI:10.1080/17415993.2010.499942

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Ring opening–ring closure of 4-
phenyl-1,2-dithiole-3-thione:
convenient route to novel thiinethione
derivatives by the reaction with active
methylene nitriles
Magda A. Barsy a & Eman A. El Rady a
a Chemistry Department, Faculty of Science, South Valley
University, Aswan, 81528, Egypt
Available online: 12 Aug 2010
To cite this article: Magda A. Barsy & Eman A. El Rady (2010): Ring opening–ring closure of 4-
phenyl-1,2-dithiole-3-thione: convenient route to novel thiinethione derivatives by the reaction
with active methylene nitriles, Journal of Sulfur Chemistry, 31:4, 255-261
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Journal of Sulfur Chemistry
Vol. 31, No. 4, August 2010, 255–261
Ring opening–ring closure of 4-phenyl-1,2-dithiole-3-thione:
convenient route to novel thiinethione derivatives by the
reaction with active methylene nitriles
Magda A. Barsy* and Eman A. El Rady
Chemistry Department, Faculty of Science, South Valley University, Aswan 81528, Egypt
(Received 17 April 2010; final version received 5 June 2010)
4-Phenyl-1,2-dithiole-3-thione (1) reacts with active methylene nitriles in the presence of triethylamine to
afford fused and isolated thiine derivatives, mainly from initial nucleophilic attack of methylene group at
C-5 of the dithiole ring.
Keywords: 4-phenyl-1,2-dithiole-3-thione; 2-amino-1,1-dicyano-3-ethoxycarbonyl-1-propene; 2-cyano-
methylbenzimidazole; thiino[2,3-b]pyran-2-thione; thiinethione
1. Introduction
The reactivity of 1,2-dithiole-3-thiones has been extensively investigated (1–11). Its utility as a
precursor of new sulfur compounds was reported (12–16), while the mechanistic pathway of its
reactions has received additional concern (17–20). In the previous work, we reported that the
reaction of 4-phenyl-1,2-dithiol-3-thione (1) with some selected α, β-unsaturated nitriles does in
fact take place on the C-5 of the dithiole ring as the preferential site of nucleophilic attack (21,
22); here, we wish to report our investigations on the reactivity of (1) toward active methylene
nitriles.
2. Results and discussion
The reaction of (1) with 2-amino-1,1-dicyano-3-ethoxycarbonyl-1-propene (2a, X = CN) in
refluxing ethanol in the presence of triethylamine as a catalyst afforded thiino[2,3-b]pyrane (6) in
a good yield. The structure of (6) was established based on its spectral and analytical data. Its mass
spectrum indicated molecular ion at m/z 311 (M+). The IR showed absorption bands at ν 3350,
3110 and 2218 cm−1 corresponding to the spectra of amino, imino and cyano groups, respectively.
The 1H-NMR spectrum of the product revealed the presence of a singlet at δ = 6.2 ppm for NH2,
*Corresponding author. Email: magdabarsy@hotmail.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415993.2010.499942
http://www.informaworld.com

256 M.A. Barsy and E.A. El Rady
a multiplet at δ = 7.1–7.9 ppm for aromatic protons and a singlet at δ = 12.1 for NH. As detailed
in Section 3, 13C-NMR spectra showed all expected signals of compound (6), but did not include
the signals due to the ethoxy group, such data agree with the structure (6). It is difficult to explain
the formation of (6) on the basis of initial nucleophilic attack at C-3 or at ring sulfur, but readily
in terms of initial attack at C-5, as this position has been reported to readily undergo nucleophilic
attack (23). The most likely scheme for the formation of (6) would involve deprotonation by base
to form the Michael adduct (3) which looses a sulfur atom probably from a –S-SH group (23, 24)
released during the ring opening of (3) to generate (4) which could be subsequently recyclized to
(5) via ethanol elimination, followed by a heterocyclization to afford the final product (6). Neither
prolonged treatment of (1) with (2b, X = COOEt) under the same reaction condition nor fusion
at 150 ◦C resulted in a product possibly because of steric hindrance (Scheme 1).
S
S
H2N
EtOOC
CN
X
+
S
Ph
2 a, X = CN
1
b, X = COOEt
X = CN
X = COOEt
No Reaction
S
S
EtOOC
NC
S
Ph
NH2
NC
3
-S
SH
O
S
S
EtOOC
NC
-EtOH
S
NC
NC
Ph
Ph
NH2
NH2
CN
4
5
HN
NC
O
S
S
Ph
NH2
6
Scheme 1. Reaction conditions, EtOH, TEA, reflux, 3 h or heating above the melting point.
When compound (1) reacted with 2-cyanomethylbenzimidazole (7a, X = NH) in refluxing
ethanol in the presence of catalytic amounts of triethylamine, the thiinethione derivative (10a,
X = NH) was obtained, suggesting that the position of initial nucleophilic attack is also at C-5
of the dithiole ring, the reaction proceeds through intermediate (8). Under basic conditions, the
S–S bond is ruptured, leading to ring opening, followed by loss of one sulfur atom, as discussed

Journal of Sulfur Chemistry 257
before, to give intermediate (9), which subsequently cyclized via the nucleophilic addition of thiol
sulfur onto the carbonitrile carbon to yield eventually the thiinethione derivative (10a). Likewise
compound (1) reacted with 2-cyanomethylbenzothiazole (7b, X = S) to give the thiinethione
derivative (10b, X = S). Structure of 10a and 10b was established based on spectral and elemental
data. The IR spectra showed no absorption bands due to nitrile function, whereas sharp bands
were recorded at 3110 and 3120 cm−1 assigned to NH function.
Treatment of (1) with 2-cyanomethy-1,3-thiazolidine-4-thione (11a) and 2-ethoxycarbonyl-
1,3-thiazolidine-4-thione (11b) under the same reaction condition resulted in decomposition. It
seems that in the case of the former reaction, intermediates (8,9) are stabilized by the aromatic ring
(Scheme 2).
S
S
N
N
S
S
+
CN
S
S
X
X
CN
Ph
Ph
1
7 a, X = NH
8
b, X = S
-S
+
N
X
S
S
SH
S
S
HN
NC
N
11 a, X = CN
S
b, X = COOEt
No Reaction
Ph
N
Ph
X
X
10 a, X = NH
9
b, X = S
Scheme 2. Reaction conditions, EtOH, TEA, reflux, 4–6 h.
On the other hand, when compound (1) was heated at 150 ◦C with arylidenecyanoacetamide
derivatives (12a–12d) in a heating mantle in the presence of a few drops of triethylamine, the
corresponding thiinethione derivative (17) was formed as the sole and only product in all cases.The
melting points, the mass spectra and the IR spectra of the resulting products resemble each other.
The mass spectra revealed M+ at m/z 244. In the IR spectra, the absorption band assigned to cyano
group was present. These facts indicate that the cyano group does not participate in the reaction.
Unexpectedly, structure (17) was suggested for reaction product rather than structures (18) and
(19), which could be produced by losing hydrogen sulfide or hydrogen cyanide, respectively.These
data could explain the formation of (17) via initial nucleophilic attack on C-5; this would lead to
ring opening to give acyclic thione (14) which recyclized to a seven-membered ring intermediate
(25) (15) which is not stable and undergoes thiobenzaldehyde extrusion affording intermediate
(16). Recyclization via loss of water molecule would give the final product (17) (Scheme 3).
As an extension of this reaction, compound (1) was allowed to react with N-arylcyanoacetamide
derivatives (20a–20c), the thiine derivatives (23a–23c) were provided. Structures of (23a–23c)
were established based on both spectral and elemental data. The mass spectrum of compound (23a,
Ar = Ph) indicated m/z at 320 (M+), and IR showed absorption bands at 3130 and 2223 cm−1
.
1H-NMR was identical with the structure of compound (23a). It appears that in this case also ring
cleavage is the dominant reaction, possibly by initial nucleophilic attack at C-5 of the thiole ring.
Cyclization occurs by loss of water molecule rather than hydrogen sulfide with the formation of
(23). These results are comparable to other such studies made by us (21, 22) (Scheme 4).

258 M.A. Barsy and E.A. El Rady
S
S
S
S
CN
Ar
B+
-
+
S
S
Ar
CONH2
H2NOC
CN
Ph
Ph
12 a, Ar = C6H5
1
13
b, Ar = C6H4CH3-p
c, Ar = C6H4OCH3-p
d, Ar = C6H4OH-p
-
Ar
+
Ar
S
NC
CONH2
Ph
S
S
H
S
- ArCH S
SH
S
H2NOC
S
H2NOC
S
NC
CN
Ph
Ph
14
15
16
-H2O
NH2
-H2S
-HCN
S
O
H2NOC
NC
NC
NH
S
S
S
S
Ph
19
Ph
18
Ph
17
Scheme 3. Reaction conditions, heating at 150 ◦C in heating mantel, TEA, 1 h.
NC
S
S
S
S
NC
ArHN
+
S
S
ArHN
Ph
O
Ph
O
1
20 a, Ar = C6H5
b, Ar = C6H4OH-p
c, Ar = C6H4CH3-p
21
-S
O
ArHN
NC
S
S
SH
-H2O
ArHN
S
Ph
CN Ph
23 a, Ar = C6H5
b, Ar = C6H4OH-p
c, Ar = C6H4CH3-p
22
Scheme 4. Reaction conditions, EtOH, TEA, reflux, 5 h.
3. Experimental
Melting points were determined on a Gallenkamp electrothermal melting point apparatus and
are uncorrected. The IR spectra were recorded as potassium bromide pellets using an FTIR unit

Journal of Sulfur Chemistry 259
Bruker-vector 22 Spectrophotometer; 1H-NMR and 13C-NMR spectra were obtained in deuter-
ated dimethyl sulfoxide as a solvent at 300 MHz and 75 MHz, respectively, on a Varian Gemini
spectrometer using TMS as the internal standard. Chemical shifts are reported in δ units (ppm).
Mass spectra were recorded on a Hewlett Packard MS-5988 spectrometer at 70 eV. Elemental
analysis was carried out at the Micro Analytical Center of Cairo University, Egypt.
3.1. 5-Amino-6-cyano-7-imino-3-phenylthiino[2,3-b]pyran-2-thione (6)
To a mixture of 4-phenyl-1,2-dithiol-3-thione (26, 27) (1) (2.1 g, 0.01 mmol) and 2-amino-1,1-
dicyano-3-ethoxycarbonyl-1-propene (2a, X = CN) (1.6 g, 0.01 mmol) in ethanol (30 ml), 0.5 ml
of triethylamine was added. The reaction mixture was refluxed for 3 h. The solvent was removed in
vacuo; the solid product so formed was collected by filtration and crystallized from (EtOH/dioxane
3:1) as dark red needles.
Yield: (260 mg), 83%, m.p.: >300 ◦C. IR: (KBr, ν = cm−1) 3350–3320 (NH2), 3110 (NH),
1
=
2218 (CN), 1154 (C S); H-NMR: (DMSO, δ = ppm) 6.23 (s, 2H, NH2), 7.12–7.90 (m, 6H, Ar-
H and thiine γ -proton), 12.14 (s, 1H, NH); 13C-NMR (DMSO-d6,TMS): δ 118.22, 122.27, 127.77,
128.20, 129.11, 129.91, 132.62, 134.33, 135.08, 139.37, 141.88, 143.10, 153.12, 160.65, 205.77;
MS m/z = 311 (M+, 69%), 309 (M-2, 100%), 266 (31%), 66 (24%). Calcd. for C15H9N3OS2
(311.38): C, 57.86; H, 2.91; N, 13.50; S, 20.59; found: C, 57.81; H, 2.86; N, 13.47; S, 20.56.
3.2. 5-(Benzyimidazol-2-yl)-6-imino-3-phenyl-thiine-2-thione (10a)
A mixture of (1) and 2-cyanomethylbenzimidazole (7a, X = NH) (1.6 g, 0.01 mmol) in 30 ml of
ethanol containing catalytic amounts of triethylamine was refluxed for 4–6 h. The solid product
so formed was collected by filtration and crystallized from EtOH/H2O (3:1) as buff powder.
1
Yield: (251 mg), 75%, m.p.: 260–261 ◦C. IR: (KBr, ν = cm−1) 3110 (NH), 1155 (C S); H-
=
NMR: (DMSO, δ = ppm) 6.21 (d, 1H, thiine-H, J = 3.9 Hz), 7.00 (d, 1H, thiine-H, J = 3.8 Hz),
7.33–7.95 (m, 9H, Ar-H), 8.91 (s, 1H, NH), 12.77 (s, 1H, NH); 13C-NMR (DMSO-d6, TMS): δ
118.87, 119.00, 128.16, 128.67, 128.98, 129.15, 129.98, 130.09, 131.14, 132.21, 133.86, 134.18,
134.32, 135.73, 142.00, 149.27, 207.78; MS m/z = 334 (M-1, 100%), 300 (50%), 275 (13%),
257 (11%), 151 (10%), 102 (20%), 77 (10%), 65 (29%). Calcd. for C18H13N3S2 (335.44): C,
64.45; H, 3.91; N, 12.53; S, 19.12; found: C, 64.41; H, 3.88; N, 12.50; S, 19.09.
3.3. 5-(Benzythiazol-2-yl)-6-imino-3-phenyl-thiine-2-thione (10b)
The reaction was performed as previously described except that 2-cyanomethylbenzthiazole (7b,
X = S) was used, crystallized from EtOH/H2O (3:1) as red crystals.
1
Yield: (253 mg), 72%, m.p.: 250–251 ◦C. IR: (KBr, ν = cm−1) 3120 (NH), 1150 (C S); H-
=
NMR: (DMSO, δ = ppm) 6.09 (d, 1H, thiine-H, J = 3.4 Hz), 7.02 (d, 1H, thiine-H, J = 3.6 Hz),
7.31–7.98 (m, 9H,Ar-H), 12.79 (s, 1H, NH). MS m/z = 352 (M+, 100%), 337 (55%), 305 (23%),
275 (12%), 257 (12%), 151 (13%), 102 (25%), 77 (12%), 65 (26%). Calcd. for C18H12N2S3
(352.49): C, 61.33; H, 3.43; N, 7.95; S, 27.29; found: C, 61.30; H, 3.39; N, 7.91; S, 27.26.
3.4. Reaction of 4-phenyl-1,2-dithiole-3-thione (1) with arylidenecyanoacetamide (12a–12d)
A mixture of an equimolar amount of (1) (0.01 mmol) and appropriate arylidenecyanoacetamide
(12a–12d) was heated at 150 ◦C in heating mantel in the presence of a catalytic amount of
triethylamine (three to five drops) for 1 h. The resulting product was treated with ethanol. The
solvent was removed and a brown solid was obtained in all cases.

260 M.A. Barsy and E.A. El Rady
3.5. 6-Amino-5-cyano-3-phenyl-thiine-2-thione (17)
Crystallized from ethanol.Yield: 62–58%, m.p.: >300 ◦C. IR: (KBr, ν = cm−1) 3370 (NH2), 2220
1
=
(CN), 1145 (C S); H-NMR: (DMSO, δ = ppm) 4.66 (s, 2H, NH2), 7.10–7.81 (m, 6H, Ar-H,
and thiine γ -proton); 13C-NMR (DMSO-d6, TMS): δ 118.22 122.54, 127.89, 128.11, 128.60,
129.77, 132.66, 134.21, 135.71, 139.34, 141.81, 142.66, 205.32; MS m/z = 244 (M+, 17%), 236
(38%), 219 (20%), 194 (23%), 154 (20%), 127 (27%), 82 (11%), 56 (24%). Calcd. for C12H8N2S2
(244.33): C, 58.99; H, 3.30; N, 11.47; S, 26.24; found: C, 58.96; H, 3.26; N, 11.42; S, 26.20.
3.6. Reaction of 4-phenyl-1,2-dithiol-3-thione (1) with N-arylcyanoacetamide (20a–20c)
3.6.1. General procedure
To a mixture of 4-phenyl-1,2-dithiol-3-thione (1) (2.1 g, 0.01 mmol) and appropriate N-
arylcyanoacetamide (0.01 mmol) in ethanol (30 ml), 0.5 ml of triethylamine was added. The
reaction mixture was refluxed for 5 h. The solvent was removed in vacuo; the solid product
so formed was collected by filtration and crystallized from a proper solvent.
3.7. 5-Cyano-3-phenyl-6-(phenylamino)thiine-2-thione (23a)
Buff powder from (EtOH/H2O). Yield: (265 mg), 83%, m.p.: 199–200 ◦C. IR: (KBr, ν = cm−1
)
1
=
3130 (NH), 2223 (CN), 1130 (C S); H-NMR: (DMSO, δ = ppm) 7.21–7.79 (m, 11H, Ar-H,
and thiine γ -proton), 12.31 (s, 1H, NH); MS m/z = 320 (M+, 40%), 292 (70%), 243 (55), 229
(65%), 197 (31%), 169 (54%), 137 (22%). Calcd. for C18H12N2S2 (320.43): C, 67.47; H, 3.77;
N, 8.74; S, 20.01; found: C, 67.42; H, 3.74; N, 8.70; S, 19.92.
3.8. 5-Cyano-3-phenyl-6-(4-hydroxyphenylamino)thiine-2-thione (23b)
Brown powder from (EtOH/H2O).Yield: (260 mg), 77%, m.p.: 235–236 ◦C. IR: (KBr, ν = cm−1
)
1
3350 (OH), 3137 (NH), 2229 (CN), 1137 (C=S); H-NMR: (DMSO, δ = ppm) 7.10–7.82 (m,
10H, Ar-H, and thiine γ -proton), 8.22 (s, 1H, OH), 13.01 (s, 1H, NH); MS m/z = 336 (M+,
44%), 304 (54%), 276 (67%), 171 (77%), 94 (50%). Calcd. for C18H12N2OS2 (336.43): C, 64.26;
H, 3.60; N, 8.33; S, 19.06; found: C, 64.22; H, 3.55; N, 8.30; S, 19.00.
3.9. 5-Cyano-3-phenyl-6-(4-methylphenylamino)thiine-2-thione (23c)
Orange crystals from (EtOH). Yield: (255 gm), 76%, m.p.: 220–221 ◦C. IR: (KBr, ν = cm−1
)
3130 (NH), 2225 (CN), 1135 (C=S); 1H-NMR: (DMSO, δ = ppm) 2.55 (s, 3H, CH3), 7.01–7.90
(m, 10H, Ar-H, and thiine γ -proton), 13.12 (s, 1H, NH); MS m/z = 334 (M+, 46%), 292 (92%),
246 (69%), 201 (76%), 142 (53%), 89 (100%), 60 (100%). Calcd. for C19H14N2S2 (334.46): C,
68.23; H, 4.22; N, 8.38; S, 19.17; found: C, 68.18; H, 4.10; N, 8.31; S, 19.08.
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