Unusual thionation via fragmentation

Article abstract of DOI:10.1002/jccs.200500176

Reaction of 4,4-dichloro-2,6-diphenyl-4,4-dihydropyrane (2) with thiols in the presence of triethylamine gives interesting results. The exclusive formation of 2,6-diphenylpyran-4-thione (3) in the reaction with PhSH through cleavage of C_AT-S bo

Full text of DOI:10.1002/jccs.200500176

Journal of the Chinese Chemical Society, 2005, 52, 1223-1225
1223
Unusual Thionation via Fragmentation
Tse-Lok Ho* (
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, R.O.C.
) and Rong-Jie Chein (
)
Reaction of 4,4-dichloro-2,6-diphenyl-4,4-dihydropyrane (2) with thiols in the presence of triethylamine
gives interesting results. The exclusive formation of 2,6-diphenylpyran-4-thione (3) in the reaction with
PhSH through cleavage of CAr-S bond is remarkable.
Keywords: Thionation; Fragmentation; 2,6-Diphenylpyran-4-thione.
INTRODUCTION
+
-
S
SNa
Cl
S
SNa
Cl
For certain research work we required dithioacetals of
-pyrone derivatives. Despite the absence of any report in the
O
O
4
chemical literature on this class of compounds, which sur-
prised us, we thought that somehow they could be prepared.
In the event, to our chagrin we were not able to dithioace-
A
A'
In order to understand the transformation further we in-
vestigated similar reactions with ethanedithiol and benzene-
thiol. It was found that some quantities of the desired com-
pound 4 were generated besides the major product 3. Most as-
tonishingly, the same thione product 3 was obtained exclu-
sively from the reaction with benzenethiol, and there was no
detectable dithioacetal present in the reaction mixture.
1
talize 2,6-diphenyl-4-pyrone (1) in any useful yields by con-
ventional methods or some variants that we could devise. In-
stead, we observed very intriguing results and these form the
subject of the present report.
O
Cl
Cl
O
O
-
+
Cl
S
S
1
2
-
Cl
S
O
O
S
S
+
B
B'
O
O
The generation of 3 from the last reaction is most un-
usual. It implies that a CAr-S bond scission took place and this
notion received some support by our finding diphenyl sulfide
among the reaction products. We ascribed the preferential
nucleophilic attack of the benzenethiolate ion at the phenyl
3
4
RESULTS AND DISCUSSION
S
The failure to dithioacetalize 1 in the presence of a
Cl
S
O
Lewis acid led us to attempt nucleophilic displacement on
2
+ t-AmOCS Na
2
4
,4-dichloro-2,6-diphenyl-4,4-dihydropyrane (2). We iso-
-NaCl
2
-5
lated 2,6-diphenylpyran-4-thione (3) as the major product
from reaction of 2 with 1,3-propanedithiol. Our interpreta-
tion of this result is that intermediate A or the internal salt A¢
suffered fragmentation by loss of either a thietane or thio-
formaldehyde and ethylene units.
O
3
+ COS +
+ HCl
(1)

1
224 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Ho and Chein
moiety of B instead of C-4 of the pyran derivative in the sec-
ond stage of the reaction to the heavy contribution of reso-
nance stabilization of B¢. Dephenylation becomes more fa-
vorable because an aromatic pyrylium species was retained.
As expected, replacing benzenethiol with pyridine-2-
thiol increased the efficiency of the thionation because the
ratus, were uncorrected.
2,6-Diphenylpyran-4-thione (3)
Method A
A mixture of 1 (50 mg, 0.2 mmol) and thionyl chloride
(1 mL) was refluxed in an oil bath for 2 hr; excess thionyl
chloride was evaporated in vacuo. The yellow solid residue
2
-pyridyl group in the intermediate analogous to B/B¢ is
much more prone to reaction with nucleophiles. A facilitation
was dissolved in CH
O-t-amylxanthate (60 mg, 0.3 mmol) under N
mixture was refluxed for 15 hr, cooled, quenched with water,
and extracted with CH Cl . The combined extracts were
washed with water and brine, dried over Na SO , evaporated
2
Cl
2
(2 mL) and treated with sodium
of the fragmentation pathway to access thione 3 was realized
2
. The resulting
6
also by reacting 2 with sodium O-t-amylxanthate in a pro-
cess represented by eq. 1.
2
2
2
4
and chromatographed over silica gel (eluent: EtOAc/hex 1:9)
O
O
S
to give 3 (50 mg, 93.9%) as a yellow solid. m.p. 168~170 °C.
1
H NMR d 7.50~7.52 (6H, m), 7.63 (2H, s), 7.85~7.88 (4H,
1
3
N
H
5
m); C NMR d 121.91 (d), 126.04 (d), 129.23 (d), 130.62 (s),
31.68 (d), 156.00 (s), 201.00 (s). HRMS 264.0607 (264.0609
N
1
6
7
calcd. for C17H12OS).
Method B
S
S
S
N
A mixture of 1 (1.00 g, 4.0 mmol) and thionyl chloride
(
10 mL) was refluxed in an oil bath for 2 hr, excess thionyl
N
H
chloride was evaporated in vacuo. The resulting yellow solid
residue with either 1,3-propanedithiol, benzenethiol, or 2-
N
8
9
pyridinethiol (8.0 mmol each) were dissolved in CH
mL), placed under N , and treated with triethylamine (1.0 g,
0.0 mmol) slowly via a syringe. The reaction mixture was
stirred at 50 °C overnight, cooled, and poured into water. Ex-
traction with CH Cl was followed by back-wash with 2N
NaOH, water, and brine. The organic solution was dried over
Na SO , evaporated, and chromatographed over silica gel
2 2
Cl (2
2
S
S
1
2
2
1
0
2
4
Starting from 9,10-dihydro-9-acridinone 5 and tropone
, each reaction sequence led to “normal” products 7, 8, 9,
(eluent: EtOAc/hex 1:4) to afford 3 in 75.2% (from 1,3-pro-
pane-dithiol), 79.9% (from benzenethiol) and 88.3% (from
2-pyridinethiol) yield, respectively. Diphenyl sulfide (0.23 g,
30.7%) and di(2-pyridyl) sulfide (0.30 g, 39.6%) was isolated
in the same time.
6
and 10 in high (92.2%) to moderate (40.2%) yield. Thus it ap-
pears that the behavior of 2 is unique.
In conclusion, we report a novel observation on CAr-S
bond scission in the reaction of 2 with thiols. S-Arylation
leading to diarylsulfides is most unusual.
7,9-Diphenyl-8-oxa-1,4-dithiaspiro[4.5]deca-6,9-diene (4)
Successive reaction of 1 (0.50 g, 2.0 mmol) with thionyl
chloride and 1,2-ethanedithiol (0.44 g, 4.0 mmol) were car-
ried out in the same manner as described above (method B);
silica gel chromatography (eluent: EtOAc/hex 1:9) permitted
isolation of 3 (0.20 g, 37.6%) and 4 (0.25 g, 38.3%). m.p.
176~178 °C, IR (neat) n 2963, 2916, 2358, 2330, 1645, 1486,
EXPERIMENTAL SECTION
General Methods
3
NMR spectra were recorded with CDCl as solvent, at
1
13
1
3
00 and 74 MHz, respectively, for H and C absorptions.
1294, 1311, 1099, 1019, 911, 798, 765; H NMR d 3.50 (4H,
1
3
Chemical shifts are reported in ppm relative to 0 for TMS.
Electron impact mass spectra were measured at 70 eV. Silica
gel (70-230 mesh) for chromatography was a Merck product.
Melting points, determined with a Laboratory Devices appa-
s), 5.86 (2H, s), 7.34~7.41 (6H, m), 7.69~7.72 (4H, m); C
NMR d 41.35 (t), 61.84 (s), 102.17 (d), 124.82 (d), 128.39
(d), 128.90 (d), 133.36 (s), 147.37 (s). HRMS calcd for
C H OS : 324.0639, found: 324.0636.
1
9
16
2

Unusual Thionation via Fragmentation
J. Chin. Chem. Soc., Vol. 52, No. 6, 2005 1225
9
-(Phenylsulfanyl)acridine (7)
130.42 (d), 136.79 (d), 137.37 (s), 148.43 (s), 149.52 (d),
Dihydroacridinone (1.0 g, 5.1 mmol) was reacted with
12 2
159.30 (s). Anal. Calcd for C18H N S: N, 9.72; C, 74.97; H,
thionyl chloride (10 mL) for 6 hr. The product was heated
with benzenethiol (1.13 g, 10.3 mmol) and triethylamine
4.19. Found: N, 9.69; C, 74.94; H, 4.62.
4
(
1.55 g, 15.3 mmol) in CH
2
Cl
2
(20 mL) at 50 °C overnight.
1-(1l -Thiopyran-1-yl)-2,4,6-cycloheptatrienyl phenyl sul-
Workup and chromatography over silica gel (eluent:
fide (10)
EtOAc/hex 1:9), gave 7 (1.34 g, 91.1%) as a yellow solid.
After reaction of 6 (0.3 g, 4.7 mmol) with thionyl chlo-
m.p. 138~139 °C, IR (neat) n 3069, 3049, 2989, 2351, 1723,
2 2
ride and then benzenethiol (0.62 g, 5.6 mmol) in CH Cl (5
1
1
7
8
1
1
669, 1433, 1396, 1273; H NMR d 6.95~7.07 (5H, m),
.46~7.51 (2H, m), 7.70~7.76 (2H, m), 8.26 (2H, d, J = 9 Hz),
mL) in the presence of triethylamine (0.86 g, 8.5 mmol), sil-
ica gel chromatography (eluent: EtOAc/hex 1:9) gave 10
(0.35 g, 40.2%). IR (neat) n 3072, 3057, 3006, 2890, 2828,
1948, 1880, 1801, 1580, 1475, 1438, 1423, 1320, 1230, 1083,
1
3
.64 (2H, d, J = 8.7 Hz); C NMR d 125.74 (d), 126.54 (d),
26.95 (d), 127.26 (d), 128.77 (s), 129.01 (d), 129.93 (d),
30.18 (d), 136.78 (s), 139.08 (s), 148.77 (s). Anal. Calcd for
1
1069, 1024, 906, 841, 738; H NMR d 6.23 (2H, dd, J = 4.2,
C
19
H
13NS: N, 4.88; C, 79.41; H, 4.56. Found: N, 4.82; C,
2.7 Hz), 6.36 (2H, dd, J = 4.2, 2.7 Hz), 7.10~7.33 (12H, m);
1
3
7
9.26; H, 4.84.
C NMR d 124.17 (d), 125.00 (s), 127.62 (d), 127.78 (d),
1
28.90 (d), 129.00 (d), 132.28 (d), 133.31 (s). HRMS calcd.
9
,9-(Ethylendithio)acridan (8)
16 2
for C19H S : 308.0690, found: 308.0692.
After reaction of 5 (0.5 g, 2.6 mmol) with thionyl chlo-
ride and then 1,2-ethanedithiol (0.26 g, 2.8 mmol) in CH
10 mL) in the presence of triethylamine (0.8 g, 7.9 mmol),
silica gel chromatography (eluent: EtOAc/hex 1:9) gave 8
0.44 g, 63.3%). m.p. 238~240 °C, IR (neat) n 3394, 3260,
2 2
Cl
(
ACKNOWLEDGMENT
(
We thank the National Science Council, R. O. C. for fi-
nancial support of this work.
3
1
064, 2966, 2922, 2864, 2381, 2340, 1806, 1580, 1510, 1476,
1
332, 1261, 1154, 747; H NMR d 3.63 (4H, s), 6.66 (2H, dd,
J = 8.1, 1.2 Hz), 6.71 (1H, s), 6.96~7.02 (2H, m), 7.12~7.17
1
3
(
(
2H, m), 8.06 (2H, d, J = 8.1 Hz); C NMR d 42.00 (t), 60.52
Received June 22, 2005.
s), 113.52 (d), 120.50 (d), 123.87 (s), 128.05 (d), 129.05 (d),
1
2
37.28 (s). HRMS calcd. for C15
71.0494.
2
H13NS : 271.0487, found:
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9
-(2-Pyridylsulfanyl)acridine (9)
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2
3
4
5
2
2
1
the presence of triethylamine (0.8 g, 7.9 mmol), silica gel
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4
9
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568, 1446, 1415, 1308, 1150, 1121, 1089, 1042, 841, 747;
1
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Hz), 7.13~7.18 (1H, m), 7.46 (2H, dd, J = 8.4, 7.2 Hz), 7.71
1
837-1840.
(
2H, dd, J = 8.5, 7.2 Hz), 8.23 (2H, d, J = 9 Hz), 8.26 (1H, d, J
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1
3
=
1
4.8 Hz), 8.55 (2H, d, J = 8.7 Hz); C NMR d 120.08 (d),
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