Synthesis and thermal transformation of stable monocyclic λ4-thiabenzenes

Article abstract of DOI:10.1039/b102806p

The stable monocyclic λ⁴-thiabenzenes 6a-e, which are stabilized with electron-withdrawing substituents such as benzoyl, cyano and alkoxycarbonyl groups, are synthesized in high yields by proton abstraction from the corresponding thiopyranium salts 5a-e with triethylamine in ethanol. The ylidic properties of the λ⁴-thiabenzenes are established based on spectral and chemical evidence. Thermal decomposition of the λ⁴-thiabenzenes affords alkyl-rearranged products 7,8, and 9, thienofuran derivatives 10 (from benzoyl-substituted λ⁴-thiabenzenes), and thiophene derivatives 11. A plausible mechanism for the formation of those products is also discussed.

Full text of DOI:10.1039/b102806p

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Synthesis and thermal transformation of stable monocyclic
ꢀ4-thiabenzenes
Hiroshi Shimizu,* Noriaki Kudo, Tadashi Kataoka and Mikio Hori
1
Gifu Pharmaceutical University, 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
Received (in Cambridge, UK) 27th March 2001, Accepted 11th July 2001
First published as an Advance Article on the web 23rd August 2001
The stable monocyclic λ4-thiabenzenes 6a–e, which are stabilized with electron-withdrawing substituents such
as benzoyl, cyano and alkoxycarbonyl groups, are synthesized in high yields by proton abstraction from the
corresponding thiopyranium salts 5a–e with triethylamine in ethanol. The ylidic properties of the λ4-thiabenzenes
are established based on spectral and chemical evidence. Thermal decomposition of the λ4-thiabenzenes affords
alkyl-rearranged products 7, 8, and 9, thienofuran derivatives 10 (from benzoyl-substituted λ4-thiabenzenes),
and thiophene derivatives 11. A plausible mechanism for the formation of those products is also discussed.
We have reported a series of cyclic sulfur ylides, so-called
‘thiabenzenes’, in which a sulfur ylide bond participates as part
of a cyclic conjugated ring system having six π-electrons.
However, all of these thiabenzenes are benzo-fused derivatives,
1-1 and 2-thianaphthalenes,2 9-thiaanthracenes,3 and 9-thia-
phenanthrenes.4 It is of more interest to synthesize monocyclic
thiabenzenes in order to investigate in detail the chemistry of
the thiabenzene skeleton itself. Attempts for the preparation
of monocyclic thiabenzenes have been made by Price5 and
Hortmann,6 but their compounds were too unstable to be
isolated. Weber succeeded in stabilization of thiabenzenes as
ligands of metal complexes.7 Thus, there is no report on the
successful isolation of monocyclic thiabenzenes.
We have planned to stabilize the thiabenzenes with an
electron-withdrawing group such as a cyano or carbonyl group
on the basis of our previous knowledge for the isolation
of other benzo-fused thiabenzenes synthesized so far. We
report here in detail the synthesis of stable monocyclic thia-
benzenes together with their thermal reactions affording some
rearranged products including ring contracted ones with an
interesting thienofuran skeleton.8
Scheme 1
Results and discussion
The synthesis of monocyclic thiabenzenes 6 was achieved as
illustrated in Scheme 1. Dihydrothiopyrans 2b–e were prepared
by the hetero-Diels–Alder reaction of various thioaldehydes,
generated in situ from the corresponding Bunte salts and base,
with 2,3-dimethylbuta-1,3-dienes according to the procedure of
Kirby et al.9 The above cycloaddition reaction using buta-1,3-
diene gas as diene from a cylinder for the synthesis of thiopyran
2a with no alkyl substituents on the hetero ring resulted in
a very low yield (14%) of desired product. Therefore, we tried
this synthesis using buta-1,3-diene10 generated in situ from
the thermolysis of sulfolene in xylene–butanol under an
N2 atmosphere to obtain a rather higher yield (63%) of the
thiopyran 2a.
The dihydrothiopyrans 2 were oxidized with m-chloroper-
benzoic acid (MCPBA) in a cooled dichloromethane solution
to afford the corresponding sulfoxides 3 in high yields. All of
these dihydrothiopyran sulfoxides were obtained as a mixture
of cis and trans diastereomers pertaining to the 2-substituent
and sulfoxide oxygen. The structures of cis and trans isomers
were assigned by means of 1H NMR spectroscopy, according to
the ordinarily accepted view that relative configuration of the
substituents at the 1- and 2-position can be established
by assuming that the inductive and deshielding effect of the
sulfoxide function on the proton at the 2-position is larger in the
trans isomer than in the cis isomer and consequently this proton
absorbs at lower field.11,12
On refluxing in toluene in the presence of toluene-p-sulfonic
acid (p-TsOH) catalyst, the dihydrothiopyrans were dehydrated
to give the corresponding 2H-thiopyrans 4 in 68–78% yield.
Alkylation of 6-aroyl(thiopyrans) 4a–c with alkyl iodide in the
presence of silver tetrafluoroborate or with dialkoxycarbenium
tetrafluoroborate in dichloromethane proceeded smoothly to
give the corresponding 1-alkylthiopyranium tetrafluoroborates
5a–c in high yield. Methylation of 6-cyano- 4d and 6-methoxy-
carbonyl(thiopyrans) 4e was accomplished with methyl tri-
fluoromethanesulfonate to give methylthiopyranium salts 5d
and 5e in high yield, respectively, although their alkylation with
the combination of methyl iodide and silver tetrafluoroborate
proceeded in low yields. Deprotonation of thiopyranium salts
5 with triethylamine in ethanol yielded the corresponding
DOI: 10.1039/b102806p
J. Chem. Soc., Perkin Trans. 1, 2001, 2269–2276
This journal is © The Royal Society of Chemistry 2001
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Table 1 Thermal reactions of thiabenzenes 6
Products (% yield)
Entry
Compd.
Solvent
Time (t/h)
7
8
9
10
11
12
1
2
3
4
5
6
7
6b
6b
6b
6bЈ
6bЈ
6d
6d
Benzene
EtOH
MeCN
Benzene
EtOH
Benzene
EtOH
1.7
10
4
1
8
0.8
1
25
15
8
13
13
17
5
20
4
14
15
19
5
11
11
3
12
5
7
24
22
13
7
11
5
10
3
18
4
monocyclic thiabenzenes 6 as orange to yellow compounds in
57–100% yield. These compounds are stable even on exposure
to air at room temperature.
Thermal decomposition of thiabenzenes proceeded faster in
benzene compared with that in acetonitrile and ethanol. This is
probably explained by solvation of the polar ylidic structure
of thiabenzenes by polar solvents. 2-Aroylthiabenzenes 6b
and 6bЈ in the non-polar solvent benzene underwent thermal
rearrangement of 1-alkyl substituents to give three possible
products 7, 8, and 9, and thienofuran derivative 10 (entries
1 and 4). In contrast, they decomposed in the protic solvent
ethanol to afford ring-contracted products 11 as well as two
alkyl-migrated products 8 and 9, and thienofuran 10 (entries 2
and 5). Interestingly, 6b afforded all of the above five products
on refluxing in the polar aprotic solvent acetonitrile for 4 h
(entry 3). 6-Cyano-substituted thiabenzene 6d is less stable than
6-aroyl-substituted ones and was decomposed on refluxing in
solvent within 1 h to give two S-methyl migrated products 7d
and 8d, 11d, and dimerized product 12d in low yield.
The structures of these thiabenzenes were established on the
basis of spectral and chemical evidence. The IR spectra of
compound 6a shows a strong carbonyl absorption at 1535 cmϪ1
,
a lower wavenumber than that of an ordinary aroyl group
(1620–1690 cmϪ1). This indicates the delocalization of the
1
carbanion electron through the carbonyl group. The H NMR
spectrum (CDCl3) of 6a shows a singlet signal at δ 2.17 assign-
able to S-Me, two doublets at δ 5.20 and 6.90 which are
attributed to H-6 and H-3, respectively, and two doublets
of doublets at δ 5.58 and 6.98 attributable to H-4 and H-5,
respectively. The 13C NMR spectrum (CDCl3) of 6a shows
signals at δC 65.7 and 85.0 attributable to C-2 and C-6, respec-
tively. These two 13C signals are assigned to sp3 carbons and
therefore suggest that a resonance form 6B, in which the ylide
carbanion is located on the C-2 position, is an important
contributor to the electronic distribution in 6a, as well as a
resonance form 6A.
The structures of the above products were easily elucidated
on the basis of their spectral evidence. For example, structure
determination of three methyl-migrated products was made on
1
the basis of H NMR spectra which showed allylic coupling
The thiabenzene 6a was treated with tetrafluoroboric acid in
ether to give 5a as the sole product in 84% yield. This indicates
that 6a reacted with acid in the resonance form 6A rather
than in the resonance form 6B. The spectral and chemical
observations described above show that the thiabenzene 6a has
ylidic character. Similar spectral and chemical behaviour was
observed for the other thiabenzenes 6b, 6bЈ, 6c, 6d, and 6e
(Experimental section).
Thiabenzenes are very soluble in several solvents such as
benzene, ethanol and acetonitrile and can be stored without
decomposition at room temperature for several days. We next
investigated a thermal reaction of thiabenzenes 6b, 6bЈ, and 6d
in refluxing solvents. The results are summarized in Scheme 2
and Table 1.
(J 1.7 Hz) between each methyl group and olefinic proton for
the compound 7b, and a singlet signal of two methyl groups at
the 4-position at δ 1.22 and allyl coupling between the 5-methyl
and 6-olefinic proton at δ 1.87 for the compound 8b, and a
doublet (J 6.8 Hz) of the 6-methyl group at δ 1.28 for com-
pound 9b.
The structure of 10b was also elucidated on the basis of
spectral data: the 1H NMR spectrum showing a doublet (δ 1.83,
J 1.7 Hz) of the 6-methyl group coupled with the olefinic
proton (δ 5.80, J 1.7 Hz), and a doublet (δ 1.86, J 1.3 Hz)
of the 6a-methyl group with a long-range coupling with 3a-
methine proton (δ 4.64, J 1.3 Hz), as well as a lack of both
IR absorption and 13C NMR signal due to a carbonyl group
in the molecule.
High-resolution mass spectral data indicated a molecular
formula of C15H15BrOS for compound 11b. The IR spectrum
of compound 11b showed a characteristic absorption band at
1
1690 cmϪ1 for the benzoyl group. The H NMR spectrum of
compound 11b showed a characteristic singlet at δ 6.76 for the
thiophene ring proton, and in the phenacyl substituent a methyl
doublet (J 6.8 Hz) at δ 1.53 coupled with a methine proton
appearing at δ 4.83.
The complete structure determination of compound 11b was
made by comparison with an authentic sample prepared by
the route depicted in Scheme 3. The Friedel–Crafts reaction of
3,4-dimethylthiophene 13 in the presence of anhydrous ZnCl2
with α-chloro-4-bromophenacyl methyl sulfide 14 prepared by
chlorination of 4-bromophenacyl methyl sulfide13 with NCS
afforded 2-substituted 3,4-dimethylthiophene 15 in 39% yield.
Treatment of 15 with Zn in acetic acid led to the reduction
product 16 in 27% yield, according to the method of Tamura
et al.14 Deprotonation of 16 with LDA in THF, followed by
addition of methyl iodide, gave the expected compound 11b in
48% yield.
Finally, we discuss the mechanism for the formation of
compounds 10, 11, and 12. The thienofuran 10b was found to
Scheme 2
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isomerize to the thiophene derivative 11b on storage at room
temperature for about one week. The rearranged product 7b
was also isomerized partly to the thiophene 11b on storage at
room temperature for more than one month. In addition, the
isolated product 7b was subjected to further thermolysis under
conditions of refluxing in ethanol for 2.5 h to give 10b in 11%
yield.
Taking account of the above results, the products 10 and 11
are considered to be formed by decomposition of the
rearranged products 7. In considering the mechanism for
the formation of products 10 and 11, we propose the formation
of the common intermediate C as a key intermediate from the
thiopyran 7 as shown in Scheme 4.
The attack of the lone-pair electrons of sulfur of 7 at the
olefinic carbon at the 3-position generates episulfonium
ylide intermediate A (path a). The three-membered ring of
the intermediate A is opened to give intermediate C. Enolate
ion of the intermediate C attacks at the 3-position to afford the
corresponding compound 10. The enolate ion abstracts the
acidic proton at the 2-position activated by the adjacent
sulfonium ion, followed by tautomerization to furnish the
corresponding compound 11. The intermediate C might be
generated by an alternative mechanism involving the thermally
provoked electrocyclic ring-opening of the thiopyran 7 to
the thiocarbonyl intermediate B (path b), followed by Michael
addition of the sulfur atom at an electron-deficient olefinic
carbon.
In order to get information pertaining to the formation of the
thiocarbonyl intermediate B, we attempted to trap such a highly
reactive thioaldehyde intermediate by the hetero-Diels–Alder
reaction with 2,3-dimethylbuta-1,3-diene. However, we could
not detect any cycloaddition product. This result suggests the
low possibility of path b. In addition, higher yields of products
10 and 11 were obtained in polar solvents such as ethanol and
acetonitrile than in non-polar solvents as described above,
suggesting the preferred formation of polar ylidic intermediate
A in path a.
Porter and co-workers also discussed the two plausible
intermediates, an episulfonium ylide intermediate and a thio-
carbonyl one for the similar thermal ring contraction of 1,2-
bis(alkoxycarbonyl)-2H-thiopyran derivatives to thiophenes,
and they ruled out the thiocarbonyl intermediate based on the
failure of trapping such an intermediate.15 We also discussed
the similar episulfonium ylide intermediate in the mechanism
for the ring contraction of 2-benzothiopyran derivatives to
benzothiophenes in our previous report.16
Thermal equilibration between the intermediate C and
compound 10 explains the transformation of 10 to the
compound 11.
Similar thermal decomposition of 2-cyano-substituted
derivative 7d forms the corresponding intermediate CЈ, which
isomerizes only to compound 11d, with no cyclization to the
bicyclic product corresponding to compound 10, probably
because of the linear structure of the heterocummulene moiety
of the estimated intermediate CЈ.
The formation of product 12 might be explained by a
mechanism involving self-coupling of the thiopyranyl radical
intermediate formed by homolytic demethylation of the
thiabenzene 6d. Such a homolytic dealkylation has been often
observed in the thermal decomposition of sulfonium salts.17
Experimental
Mps were determined on a Yanagimoto micro melting-point
apparatus, and are uncorrected. IR spectra were measured on a
JASCO IRA-100 spectrophotometer. NMR spectra were
recorded on a JEOL JNM GX-270 spectrometer at 270 MHz
(1H) and 67.5 MHz (13C) or a JEOL JNM GX-400 spectrometer
at 400 MHz (1H) and 100 MHz (13C). Chemical shifts were
measured in ppm on the δ-scale downfield from tetra-
methylsilane as internal standard; J-values are recorded in Hz.
Scheme 3
Scheme 4
J. Chem. Soc., Perkin Trans. 1, 2001, 2269–2276
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13C Data are quoted with 1H multiplicity (off-resonance results
in parentheses), although this multiplicity was usually inferred
from a DEPT experiment. Mass spectra were obtained by
electron impact at 70 eV on a JEOL JMS-D300 spectrometer.
Elemental analyses were performed at the Microanalytical
Laboratory of Gifu Pharmaceutical University. Analytical
and preparative TLC (PLC) were carried out on E. M. Merck
silica gel 60PF-254 plates. Spots were visualized with a UV
hand lamp.
6-H), 4.49 (1H, dd, J 5.6 and 4.1, 2-H), 7.41–7.57 (3H, m, ArH)
and 7.97–8.01 (2H, m, ArH); δC (CDCl3) 19.5 (q), 20.0 (q), 29.9
(t), 32.7 (t), 41.9 (d), 122.6 (s), 126.3 (s), 128.5 (d), 128.6 (d),
133.0 (d), 135.2 (s) and 195.7 (s); m/z 232 (Mϩ) (Found: Mϩ,
232.0931. C14H16OS requires M, 232.0922).
2-Cyano-3,6-dihydro-4,5-dimethyl-2H-thiopyran 2d. Yield
68.3%, a pale yellow oil from sodium cyanomethyl thiosulfate 1d
after refluxing for 5 h; νmax (neat)/cmϪ1 2240 (CN); δH (CDCl3)
1.71 and 1.77 (each 3H, s, Me), 2.42 and 2.60 (each 1H, dd,
J 17.1 and 4.4, 3-H), 2.96 and 3.51 (each 1H, d, J 17.1, 6-H) and
3.79 (1H, t, J 4.4, 2-H); δC (CDCl3) 19.3 (q), 19.7 (q), 25.5 (d),
28.7 (t), 34.6 (t), 118.7 (s), 123.2 (s) and 123.5 (s); m/z 153 (Mϩ,
base) (Found: Mϩ, 153.0612. C8H11NS requires M, 153.0612).
2-(4-Bromobenzoyl)-3,6-dihydro-2H-thiopyran 2a
A solution of triethylamine (7.3 g, 72.1 mmmol) in xylene (a
mixture of o-, m- and p-isomers) (40 cm3) was added dropwise
under nitrogen atmosphere to a stirred mixture of sodium
S-4-bromophenacyl thiosulfate 1a (5.01 g, 15.04 mmol), 2,5-
dihydrothiophene S,S-dioxide (sulfolene) (15.1 g, 0.13 mol) and
CaCl2ؒ2H2O (2.9 g, 19.5 mmol) in a mixture of butan-1-ol (40
cm3) and xylene (a mixture of o-, m- and p-isomers) (80 cm3)
with reflux over a period of 50 min. The mixture was then
refluxed for an additional 2.5 h. After cooling, the reaction
mixture was acidified with 10% aq. HCl and extracted with
chloroform. The chloroform layer was washed successively with
10% aq. HCl, 10% aq. NaOH, and water, and dried (MgSO4).
Evaporation of the mixture gave an oil, which was chromato-
graphed on silica gel with hexane–ethyl acetate (40 : 1) to afford
the thiopyran 2a (2.68 g, 62.9%) as colourless columns, mp
99–102 ЊC (from dichloromethane–hexane); νmax (KBr)/cmϪ1
1670 (CO); δH (CDCl3) 2.47–2.66 (2H, m, 3-H), 2.99–3.15 (2H,
m, 6-H), 4.44 (1H, t, J 5.1, 2-H), 5.85–5.97 (2H, m, 4-, 5-H)
and 7.59 and 7.87 (each 2H, d, J 8.8, ArH); δC (CDCl3) 24.2 (t),
25.7 (t), 40.3 (d), 122.6 (d), 126.9 (d), 128.1 (s), 130.2 (d), 131.8
(d), 133.7 (s) and 194.1 (s); m/z 282 (Mϩ) (Found: C, 50.78; H,
3.95. C12H11BrOS requires C, 50.90; H, 3.92%).
3,6-Dihydro-2-methoxycarbonyl-4,5-dimethyl-2H-thiopyran
2e. Yield 72.5%, a pale yellow oil from sodium methoxy-
carbonylmethyl thiosulfate 1e after refluxing for 10 h in
methanol; νmax (neat)/cmϪ1 1735 (ester); δH (CDCl3) 1.70 and
1.73 (each 3H, s, Me), 2.46 (2H, br d, J 6.3, 3-H2), 3.05 and 3.12
(each 1H, d, J 16.4, 6-H), 3.64 (1H, t, J 6.3, 2-H) and 3.73 (3H,
s, OMe); δC (CDCl3) 19.5 (q), 20.1 (q), 30.7 (t), 34.2 (t), 41.0 (d),
52.4 (q), 123.2 (s), 125.8 (s) and 172.3 (s); m/z 186 (Mϩ) (Found:
Mϩ, 186.0720. C9H14O2S requires M, 186.0716).
General procedure for the preparation of thiopyran 1-oxides 3a–e
2-(4-Bromobenzoyl)-3,6-dihydro-2H-thiopyran 1-oxide 3a.
MCPBA (85% purity; 1.95 g, 9.62 mmol) was added to an ice-
cooled solution of 2a (2.67 g, 9.4 mmol) in dichloromethane
(100 cm3) and the mixture was stirred for 3.5 h. Aq. NaHCO3
was added to the reaction mixture, and the dichloromethane
layer was separated, washed with water, and dried (MgSO4).
The solvent was evaporated off under reduced pressure to give
a residue, which was triturated with diethyl ether to give
an inseparable mixture of cis and trans diastereomers of the
thiopyran oxide 3a (2.73 g, 97.0%) as crystals in the ratio 1 : 3.4
judging from the integration of the 2-H signal in the 1H NMR
spectrum. Data for the diastereomeric mixture of 3a: colourless
needles, mp 148–165 ЊC (from chloroform–diethyl ether);
m/z 298 (Mϩ) (Found: C, 47.95; H, 3.72. C12H11BrO2S requires
C, 48.18; H, 3.71%); cis-3a: δH (CDCl3) 2.50 (1H, br d, J 19.0,
3-H), 3.05–3.13 (1H, m, 3-H), 3.46–3.52 (2H, m, 6-H2), 4.51
(1H, dd, J 10.0 and 4.6, 2-H), 5.63–5.70 (1H, m, 5-H), 6.06–
6.10 (1H, m, 4-H) and 7.65 and 7.81 (each 2H, d, J 8.8, ArH);
δC (CDCl3) 20.4 (t), 46.9 (t), 58.2 (d), 115.7 (d), 128.0 (d), 129.2
(s), 130.3 (d), 132.0 (d), 134.2 (s) and 193.5 (s); trans-3a:
δH (CDCl3) 2.77 (2H, br s, 3-H2), 3.46–3.52 (1H, m, 6-H), 3.78
(1H, ddd, J 16.6, 5.4 and 1.5, 6-H), 4.87 (1H, t, J 7.1, 2-H),
5.63–5.70 (1H, m, 5-H), 5.91–5.95 (1H, m, 4-H), 7.66 and 7.90
(each 2H, d, J 8.8, ArH); δC (CDCl3) 26.4 (t), 48.6 (t), 63.9 (d),
117.4 (d), 127.7 (d), 129.6 (s), 130.4 (d), 132.1 (d), 134.7 (s) and
194.5 (s).
General procedure for the preparation of 3,6-dihydro-4,5-
dimethyl-2H-thiopyrans 2b–e
2-(4-Bromobenzoyl)-3,6-dihydro-4,5-dimethyl-2H-thiopyran
2b. A solution of triethylamine (4.87 g, 48.2 mmol) in benzene
(60 cm3) was added dropwise to a stirred mixture of the
4-bromophenacyl thiosulfate 1a (16.04 g, 48.2 mmol), 2,3-
dimethylbuta-1,3-diene (4.75 g, 57.8 mmol) and CaCl2ؒ2H2O
(7.08 g, 48.1 mmol) in a mixture of ethanol (60 cm3) and
benzene (120 cm3) with reflux over a period of 30 min. The
mixture was then refluxed with stirring for an additional
4.5 h. After having cooled to room temperature, the reaction
mixture was acidified by 10% aq. HCl, and extracted with
chloroform. The extract was washed successively with 10% aq.
HCl, 10% aq. NaOH, and water, and dried (MgSO4). The
solvent was evaporated off to leave a crude oil, which was sub-
jected to column chromatography on silica gel with hexane–
ethyl acetate (40 : 1) to afford the thiopyran 2b (10.7 g, 71.6%) as
colourless prisms, mp 38 ЊC (from dichloromethane–hexane);
νmax (KBr)/cmϪ1 1675 (CO); δH (CDCl3) 1.73 and 1.74 (each 3H,
s, Me), 2.42 (1H, dd, J 16.8 and 3.9, 3-H), 2.52 (1H, dd, J 16.8
and 3.8, 3-H), 2.96 (2H, br s, 6-H), 4.41 (1H, dd, J 3.9 and 3.8,
2-H) and 7.58 and 7.85 (each 2H, d, J 8.6, ArH); δC (CDCl3)
19.5 (q), 20.0 (q), 29.7 (t), 32.4 (t), 41.7 (d), 122.5 (s), 126.1 (s),
128.0 (s), 130.1 (d), 131.7 (d), 133.9 (s) and 194.4 (s); m/z 310
(Mϩ) (Found: C, 54.27; H, 4.87. C14H15BrOS requires C, 54.03;
H, 4.86%).
The following thiopyran 1-oxides were prepared from the
corresponding thiopyrans 2 in a similar manner to that
described above. 2-Benzoyl-3,6-dihydro-4,5-dimethyl-2H-thio-
pyran 3c was also synthesized by this method. However, since
compound 3c is a known compound prepared by Zwanenburg
and co-workers,12 we give no description for it here.
2-(4-Bromobenzoyl)-3,6-dihydro-4,5-dimethyl-2H-thiopyran
1-oxide 3b. A mixture of cis and trans forms (93.5%) in the ratio
1 : 3 was subjected to fractional recrystallization from dichloro-
methane–hexane to afford pure cis and trans isomers. cis-3b:
colourless needles, mp 148–165 ЊC (decomp.); νmax (KBr)/cmϪ1
1675 (CO) and 1035 (SO); δH (CDCl3) 1.77 and 1.79 (each 3H,
s, Me), 2.27 and 2.33 (each 1H, br s, 3-H), 3.33 and 3.51 (each
1H, d, J 17.1, 6-H), 4.46 (1H, dd, J 9.6 and 4.7, 2-H), 7.61 and
7.80 (each 2H, d, J 8.1, ArH); δC (CDCl3) 19.5 (q), 19.7 (q), 26.0
(t), 52.1 (t), 59.0 (d), 115.3 (s), 127.3 (s), 129.0 (s), 130.2 (d),
The following 3,6-dihydro-2H-thiopyrans were prepared
from the proper thiosulfates 1 in a similar manner to that
described above.
2-Benzoyl-3,6-dihydro-4,5-dimethyl-2H-thiopyran 2c. Yield
63.5%, a pale yellow oil from sodium phenacyl thiosulfate 1c
after refluxing for 4 h; νmax (neat)/cmϪ1 1670 (CO); δH (CDCl3)
1.74 (6H, s, 2 × Me), 2.43 (1H, dd, J 16.7 and 4.1, 3-H), 2.53
(1H, dd, J 16.7 and 5.6, 3-H), 2.98 and 3.00 (each 1H, d, J 17.5,
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131.9 (d), 134.2 (s) and 193.5 (s); m/z 326 (Mϩ) (Found: C,
51.16; H, 4.60. C14H15BrO2S requires C, 51.39; H, 4.62%). trans-
3b: pale yellow columns, mp 154–169 ЊC (decomp.); νmax (KBr)/
cmϪ1 1680 (CO) and 1035 (SO); δH (CDCl3) 1.71 and 1.75 (each
3H, s, Me), 2.65 (2H, br s, 3-H2), 3.48 and 3.58 (each 1H, d,
J 15.8, 6-H), 4.74 (1H, dd, J 6.4 and 5.0, 2-H) and 7.62 and 7.87
(each 2H, d, J 7.3, ArH); δC (CDCl3) 19.1 (q), 19.8 (q), 32.3 (t),
54.0 (t), 65.5 (d), 117.7 (s), 127.7 (s), 129.4 (d), 130.3 (d), 132.0
(d), 134.7 (s) and 194.6 (s); m/z 326 (Mϩ) (Found: C, 51.53; H,
4.62. C14H15BrO2S requires C, 51.39; H, 4.62%).
m/z 151 (Mϩ) (Found: Mϩ, 151.0460. C8H9NS requires M,
151.0456).
6-Methoxycarbonyl-3,4-dimethyl-2H-thiopyran 4e. Yield
73.7%, a pale yellow oil after refluxing for 9 h; νmax (neat)/cmϪ1
1710 (ester); δH (CDCl3) 1.84 and 1.98 (each 3H, s, Me), 3.22
(2H, s, 2-H2), 3.80 (3H, s, OMe) and 7.09 (1H, s, 5-H);
δC (CDCl3) 17.4 (q), 19.5 (q), 31.2 (t), 51.8 (q), 123.4 (s), 125.7
(s), 127.2 (s), 135.3 (d) and 164.9 (s); m/z 184 (Mϩ) (Found:
Mϩ, 184.0569. C9H12O2S requires M, 184.0598).
2-Cyano-3,6-dihydro-4,5-dimethyl-2H-thiopyran 1-oxide 3d.
An inseparable mixture of cis and trans forms (96%) in the ratio
1 : 1, data for a diastereomeric mixture of 3d: νmax (neat)/cmϪ1
2250 (CN) and 1065 (SO); δH (CDCl3) 3.97 (t, J 4.9, 2-H for the
cis form) and 4.09 (t, J 5.6, 2-H for the trans form); m/z 169
(Mϩ) (Found: Mϩ, 169.0547. C8H11NOS requires M, 169.0561).
General procedure for the preparation of thiopyranium salts 5
6-(4-Bromobenzoyl)-1-methyl-2H-thiopyranium tetrafluoro-
borate 5a. Silver tetrafluoroborate (1.05 g, 4.85 mmol) was added
portionwise with ice-cooling to a stirred solution of 4a (840 mg,
2.97 mmol) and methyl iodide (4.34 g, 30.59 mmol) in dichloro-
methane (50 cm3) and the mixture was stirred for 5 h at room
temperature. The precipitated silver iodide was filtered off and
the filtrate was diluted with diethyl ether. The white precipitate
was collected and recrystallized from acetone–diethyl ether to
give the thiopyranium salt 5a (1.16 g, quant.) as white needles,
mp 117–118 ЊC (decomp.); νmax (KBr)/cmϪ1 1635 (CO) and
1090–1025 (BF4Ϫ); δH (CD3CN ϩ CDCl3) 2.84 (3H, s, SMe),
4.27 (2H, dd, J 4.5 and 1.5, 2-H2), 6.62 (1H, dt, J 9.8 and 4.5,
3-H), 6.76 (1H, ddt, J 9.8, 6.8 and 1.5, 4-H), 7.64 (1H, d,
J 6.8, 5-H) and 7.70 and 7.76 (each 2H, d, J 8.8, ArH);
δC (CD3CN ϩ CDCl3) 21.1 (q), 32.2 (t), 121.0 (s), 124.3 (d),
126.8 (d), 128.4 (s), 130.9 (d), 132.0 (d), 132.4 (s), 143.3 (d) and
188.9 (s) (Found: C, 40.77; H, 3.21. C13H12BBrF4OS requires C,
40.77; H, 3.16%).
3,6-Dihydro-2-methoxycarbonyl-4,5-dimethyl-2H-thiopyran
1-oxide 3e. An inseparable mixture of cis and trans forms (99%)
in the ratio 1 : 5, data for the diastereomeric mixture of 3e: νmax
(neat)/cmϪ1 1740 (ester) and 1060 (SO); δH (CDCl3) 1.79 (6H, br
s, 2 × Me of the cis form) and 1.74 (6H, br s, 2 × Me of the
trans form); m/z 202 (Mϩ) (Found: Mϩ, 202.0659. C9H14O3S
requires M, 202.0663).
General procedure for the preparation of 2H-thiopyrans 4a–e
6-(4-Bromobenzoyl)-2H-thiopyran 4a.
A mixture of 3a
(3.93 g, 13.14 mmol) and p-TsOH monohydrate (100 mg)
in toluene (170 cm3) was refluxed with stirring for 3 h.
Evaporation of the mixture left a crude oil, which was subjected
to column chromatography on silica gel using hexane–ethyl
acetate (10 : 1) to afford the thiopyran 4a (2.51 g, 67.8%) as pale
brown needles after recrystallization from dichloromethane–
hexane, mp 95–96 ЊC; νmax (KBr)/cmϪ1 1630 (CO); δH (CDCl3)
3.37 (2H, dd, J 5.4 and 1.5, 2-H2), 5.96 (1H, dt, J 9.3 and 5.4,
3-H), 6.20 (1H, ddt, J 9.3, 6.4 and 1.5, 4-H), 6.80 (1H, d, J 6.4,
5-H) and 7.59 (4H, s, ArH); δC (CDCl3) 24.6 (t), 122.3 (s), 126.4
(s), 127.0 (s), 130.5 (d), 131.5 (d), 132.9 (d), 135.4 (s), 136.9 (s)
and 192.5 (s); m/z 280 (Mϩ) (Found: C, 51.05; H, 3.24.
C12H9BrOS requires C, 51.26; H, 3.23%).
6-(4-Bromobenzoyl)-1,3,4-trimethyl-2H-thiopyranium tetra-
fluoroborate 5b. By a similar method to that described for 5a,
the thiopyranium salt 5b was obtained in 96.2% yield as colour-
less needles after recrystallization from acetone–diethyl ether,
mp 135–136 ЊC (decomp.); νmax (KBr)/cmϪ1 1640 (CO) and
1120–1040 (BF4Ϫ); δH (CD3CN ϩ CDCl3) 2.01 and 2.16 (each
3H, s, Me), 2.78 (3H, s, SMe), 4.00 and 4.26 (each 1H, d, J 18.1,
2-H), 7.50 (1H, s, 5-H) and 7.69 and 7.75 (each 2H, d, J 8.8,
ArH); δC (CD3CN ϩ CDCl3) 17.2 (q), 20.0 (q), 20.5 (q), 36.4 (t),
117.8 (s), 127.4 (s), 127.9 (s), 130.8 (d), 131.8 (d), 132.6 (s),
133.0 (s), 148.7 (d) and 188.9 (s) (Found: C, 43.61; H, 3.79.
C15H16BBrF4OS requires C, 43.83; H, 3.92%).
The following thiopyrans were prepared from the corre-
sponding thiopyran 1-oxides 3 in a similar manner to that
described above.
6-(4-Bromobenzoyl)-1-ethyl-3,4-dimethyl-2H-thiopyranium
tetrafluoroborate 5bЈ. By the same method as that described
for 5a except using ethyl iodide as alkylating agent instead of
methyl iodide, the thiopyranium salt 5bЈ was obtained in 58.1%
yield as colourless needles after recrystallization from acetone–
diethyl ether, mp 120–121 ЊC (decomp.); νmax (KBr)/cmϪ1 1630
(CO) and 1080–1010 (BF4Ϫ); δH (CD3CN ϩ CDCl3) 1.39 (3H,
t, J 7.6, SCH2CH3), 2.00 and 2.16 (each 3H, s, Me), 3.28–
3.41 (2H, m, SCH2Me), 4.04 and 4.31 (each 1H, d, J 18.3, 2-H),
7.53 (1H, s, 5-H), 7.68 and 7.74 (each 2H, d, J 8.8, ArH);
δC (CD3CN ϩ CDCl3) 8.4 (q), 16.9 (q), 19.7 (q), 33.5 (t),
34.7 (t), 127.3 (s), 127.5 (s), 130.4 (d), 131.5 (d), 132.5 (s),
133.4 (s), 149.2 (d) and 188.9 (s) (Found: C, 44.98; H, 4.38.
C16H18BBrF4OS requires C, 45.21; H, 4.27%).
6-(4-Bromobenzoyl)-3,4-dimethyl-2H-thiopyran 4b. Yield
67.5%, colourless needles, mp 71–73 ЊC (from dichloromethane–
hexane); νmax (KBr)/cmϪ1 1630 (CO); δH (CDCl3) 1.81 and 1.98
(each 3H, br s, Me), 3.29 (2H, br s, 2-H2), 6.69 (1H, s, 5-H) and
7.57 and 7.59 (each 2H, d, J 9, ArH); δC (CDCl3) 17.9 (q),
20.1 (q), 31.4 (t), 126.7 (s), 127.7 (s), 128.4 (s), 130.5 (d), 131.6
(d), 133.7 (s), 135.9 (s), 139.0 (s) and 192.7 (s); m/z 308 (Mϩ)
(Found: C, 54.29; H, 4.27. C14H13BrOS requires C, 54.38; H,
4.24%).
6-Benzoyl-3,4-dimethyl-2H-thiopyran 4c. Yield 78.3%,
a
yellow oil; νmax (neat)/cmϪ1 1630 (CO); δH (CDCl3) 1.79 and
1.96 (each 3H, q, J 1.3, Me), 3.28 (2H, br s, 2-H2), 6.73 (1H, s,
5-H), 7.41–7.57 (3H, m, ArH) and 7.67–7.71 (2H, m, ArH);
δC (CDCl3) 17.8 (q), 20.0 (q), 31.3 (t), 127.6 (s), 128.0 (s), 128.2
(d), 128.8 (d), 131.8 (d), 133.9 (s), 137.1 (s), 138.9 (d) and 193.7
(s); m/z 230 (Mϩ) (Found: Mϩ, 230.0757. C14H14OS requires M,
230.0765).
6-Benzoyl-1,3,4-trimethyl-2H-thiopyranium tetrafluoroborate
5c. By a similar method to that described for 5a, the thiopyr-
anium salt 5c was obtained in 88% yield as colourless needles
after recrystallization from acetone–diethyl ether, mp 138–
139 ЊC (decomp.); νmax (KBr)/cmϪ1 1630 (CO) and 1120–1040
(BF4Ϫ); δH (CD3CN ϩ CDCl3) 2.00 and 2.15 (each 3H, s, Me),
2.79 (3H, s, SMe), 4.02 and 4.26 (each 1H, d, J 18.1, 2-H), 7.50
(1H, s, 5-H) and 7.57–7.81 (5H, m, ArH); δC (CD3CN ϩ
CDCl3) 16.7 (q), 19.5 (q), 20.1 (q), 35.9 (t), 117.7 (s), 126.9 (s),
128.1 (d), 128.6 (d), 132.2 (s), 133.0 (d), 133.1 (s), 148.0 (d) and
6-Cyano-3,4-dimethyl-2H-thiopyran 4d. Yield 73.7%,
a
yellow oil after refluxing for 8 h; νmax (neat)/cmϪ1 2225 (CN);
δH (CDCl3) 1.82 and 1.94 (each 3H, br s, Me), 3.28 (2H,
br s, 2-H2), 6.71 (1H, s, 5-H); δC (CDCl3) 17.1 (q), 19.6 (q),
30.9 (t), 101.7 (s), 116.2 (s), 126.4 (s), 126.8 (s) and 140.0 (d);
J. Chem. Soc., Perkin Trans. 1, 2001, 2269–2276
2273

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189.2 (s) (Found: C, 54.08; H, 5.16. C15H17BF4OS requires
C, 54.24; H, 5.16%).
(s), 149.6 (s) and 183.7 (s); m/z 336 (Mϩ) (Found: Mϩ, 336.0199.
C16H17BrOS requires M, 336.0184).
6-Cyano-1,3,4-trimethyl-2H-thiopyranium triflate 5d.
A
2-Benzoyl-1,4,5-trimethyl-1-thiabenzen-1-ium-2-ide 6c. Yield
98%, a red oil; νmax (neat)/cmϪ1 1535 (CO); δH (CDCl3) 1.89 and
2.07 (each 3H, br s, Me), 2.04 (3H, s, SMe), 5.03 (1H, s, 6-H),
6.59 (1H, br s, 3-H) and 7.36–7.58 (5H, m, ArH); δC (CDCl3)
19.3 (q), 21.4 (q), 29.2 (q), 53.3 (s), 83.5 (d), 113.7 (s), 127.8 (d),
128.9 (d), 129.6 (d), 130.4 (d), 139.7 (d), 148.9 (d) and 184.7 (s);
m/z 244 (Mϩ) (Found: Mϩ, 244.0899. C15H16OS requires M,
244.0921).
mixture of 4d (1 g, 6.61 mmol) and methyl trifluoromethane-
sulfonate (0.94 cm3, 8.27 mmol) was stirred at room tem-
perature for 1 h, during which time solid materials appeared
gradually and finally the whole of the mixture solidified.
Diethyl ether was added to the solids, which were then pulver-
ized to afford thiopyranium salt 5d (1.98 g, 95%). Recrystalliz-
ation from acetone–diethyl ether gave pale grey needles, mp
119–120 ЊC (decomp.); νmax (KBr)/cmϪ1 2230 (CN) and 1250
and 1030 (SO2); δH (CD3CN ϩ CDCl3) 2.03 and 2.12 (each 3H,
s, Me), 2.97 (3H, s, SMe), 4.13 and 4.47 (each 1H, d, J 18.3,
2-H) and 7.67 (1H, s, 5-H); δC (CD3CN ϩ CDCl3) 16.2 (q), 19.3
(q), 20.3 (q), 37.1 (t), 87.8 (s), 111.9 (s), 127.0 (s), 132.1 (s) and
152.7 (d) (Found: C, 38.08; H, 3.75; N, 4.43. C10H12F3NO3S2
requires C, 38.09; H, 3.84; N, 4.44%).
2-Cyano-1,4,5-trimethyl-1-thiabenzen-1-ium-2-ide 6d. Yield
76.3%, orange prisms, mp 68–69 ЊC (decomp., from diethyl
ether); νmax (KBr)/cmϪ1 2170 (CN); δH (CDCl3) 1.89 and 1.98
(each 3H, s, Me), 2.04 (3H, s, SMe), 4.68 (1H, br s, 6-H), 6.54
(1H, br s, 3-H); δC (CDCl3) 18.6 (q), 20.5 (q), 28.9 (q), 31.9 (s),
74.0 (d), 115.2 (s), 121.4 (s), 130.2 (d) and 145.8 (s); m/z 165
(Mϩ) (Found: C, 65.16; H, 6.78; N, 8.51. C9H11NS requires
C, 65.41; H, 6.71; N, 8.48%).
6-Methoxycarbonyl-1,3,4-trimethyl-2H-thiopyranium triflate
5e. By a similar method to that for 5d, the thiopyranium salt 5e
was obtained in 93% yield as colourless leaflets after recrystal-
lization from dichloromethane–diethyl ether, mp 99–102 ЊC;
νmax (KBr)/cmϪ1 1705 (ester), 1260 and 1030 (SO2); δH (CDCl3)
2.09 and 2.17 (each 3H, s, Me), 2.88 (3H, s, SMe), 3.93 (3H, s,
OMe), 4.38 (2H, br s, 2-H2) and 7.73 (1H, s, 5-H); δC (CDCl3)
18.2 (q), 20.7 (q), 21.2 (q), 37.3 (t), 53.7 (q), 110.0 (s), 126.9 (s),
132.2 (s), 147.1 (d) and 161.5 (s) (Found: C, 37.90; H, 4.33.
C11H15F3O5S2 requires C, 37.93; H, 4.34%).
2-Methoxycarbonyl-1,4,5-trimethyl-1-thiabenzen-1-ium-2-ide
6e. Yield 92.3%, a red oil; νmax (neat)/cmϪ1 1655 (ester);
δH (CDCl3) 1.89 and 1.97 (each 3H, br s, Me), 2.01 (3H, br s,
SMe), 3.07 (3H, s, OMe), 4.75 (1H, s, 6-H) and 6.98 (1H, br s,
3-H); δC (CDCl3) 18.8 (q), 20.7 (q), 28.9 (q), 45.5 (s), 50.4 (q),
77.9 (d), 113.2 (s), 129.8 (d), 147.3 (d) and 165.5 (s); m/z 198
(Mϩ) (Found: Mϩ, 198.0699. C10H14O2S requires M, 198.0714).
General procedure for thermolysis of thiabenzenes 6
General procedure for the preparation of 1-alkyl-ꢀ4-thiabenzenes
A solution of 6 (1.5 mmol) in an appropriate solvent (35 cm3)
was refluxed with stirring and the reaction was followed by TLC
until completion. After evaporation of the mixture, the residue
was subjected to PLC on silica gel using an appropriate solvent.
The results, including reaction conditions and yields, are
summarized in Table 1.
From the thiabenzene 6b, the following products were
obtained after PLC with hexane–ethyl acetate (10 : 1) as
solvent.
6
2-(4-Bromobenzoyl)-1-methyl-1-thiabenzen-1-ium-2-ide
6a.
Triethylamine (2.3 g, 22.7 mmol) was added to a stirred suspen-
sion of 5a (2.12 g, 5.5 mmol) in ethanol (90 cm3) with ice-
cooling and the mixture was stirred for 4 h, poured into water,
and extracted with dichloromethane. The extract was washed
with water and dried (MgSO4). Evaporation of the mixture
in vacuo gave a crude residue, which was recrystallized from
diethyl ether to afford the λ4-thiabenzene 6a (0.75 g, 45.7%) as
light brown crystals, mp 90–92 ЊC; νmax (KBr)/cmϪ1 1535 (CO);
δH (CDCl3) 2.17 (3H, s, SMe), 5.20 (1H, d, J 7.8, 6-H), 5.58 (1H,
dd, J 7.6 and 8.3, 4-H), 6.90 (1H, d, J 8.3, 3-H), 6.98 (1H, dd,
J 7.6 and 7.8, 5-H) and 7.52 and 7.58 (each 2H, d, J 8.5, ArH);
δC (CDCl3) 28.5 (q), 65.7 (s), 85.1 (d), 105.0 (s), 124.5 (s), 130.6
(d), 131.1 (d), 132.6 (d), 137.0 (s), 138.1 (s) and 184.8 (s);
m/z 294 (Mϩ) (Found: C, 52.82; H, 3.86. C13H11BrOS requires
C, 52.90; H, 3.76%).
2-(4-Bromobenzoyl)-2,4,5-trimethyl-2H-thiopyran 7b.
A
yellow oil; νmax (neat)/cmϪ1 1680 (CO); δH (CDCl3) 1.65 (3H, s,
Me), 1.88 and 1.89 (each 3H, d, J 1.7, Me), 5.45 and 5.92 (each
1H, br s, olefinic H) and 7.54 and 8.01 (each 2H, d, J 8.6, ArH);
δC (CDCl3) 20.3 (q), 20.6 (q), 25.2 (q), 52.3 (s), 113.5 (d), 120.2
(d), 127.2 (s), 130.3 (s), 131.1 (d), 131.8 (d), 133.8 (s), 134.5 (s)
and 197.9 (s); m/z 322 (Mϩ) (Found: Mϩ, 322.0001. C15H15BrOS
requires M, 322.0027).
The following 1-alkyl-λ4-thiabenzenes were synthesized by
the same general method.
2-(4-Bromobenzoyl)-4,4,5-trimethyl-4H-thiopyran 8b. Colour-
less plates, mp 84–85 ЊC (from ethanol); νmax (KBr)/cmϪ1 1650
(CO); δH (CDCl3) 1.22 (6H, s, 2 × Me), 1.87 (3H, s, J 1.3,
Me), 5.91 (1H, q, J 1.3, 6-H), 6.15 (1H, s, 3-H) and 7.58 and
7.60 (each 2H, d, J 9.0, ArH); δC (CDCl3) 19.8 (q), 26.8 (q),
37.0 (s), 111.6 (d), 127.2 (s), 130.9 (d), 131.6 (d), 133.0 (s),
134.0 (s), 135.6 (s), 143.4 (d) and 192.0 (s); m/z 322 (Mϩ)
(Found: C, 55.71; H, 4.72. C15H15BrOS requires C, 55.74; H,
4.68%).
2-(4-Bromobenzoyl)-1,4,5-trimethyl-1-thiabenzen-1-ium-2-ide
6b. Yield 89%, dark red needles, mp 123–125 ЊC (decomp., from
diethyl ether); νmax (KBr)/cmϪ1 1545 (CO); δH (CDCl3) 1.90 and
2.08 (each 3H, br s, Me), 2.05 (3H, s, SMe), 5.06 (1H, s, 6-H),
6.53 (1H, br s, 3-H) and 7.45 and 7.52 (each 2H, d, J 9.0, ArH);
δC (CDCl3) 19.3 (q), 21.4 (q), 29.1 (q), 76.6 (s), 84.1 (d), 114.1
(s), 124.0 (s), 129.7 (d), 130.6 (d), 130.9 (d), 138.5 (s), 149.0 (s)
and 183.1 (s); m/z 322 (Mϩ) (Found: C, 55.50; H, 4.69.
C15H15BrOS requires C, 55.74; H, 4.68%).
6-(4-Bromobenzoyl)-2,3,4-trimethyl-2H-thiopyran 9b. Colour-
less prisms, mp 102–103 ЊC (from dichloromethane–hexane);
νmax (KBr)/cmϪ1 1620 (CO); δH (CDCl3) 1.28 (3H, d, J 6.8, Me),
1.84 and 1.98 (each 3H, br s, Me), 3.29 (1H, q, J 6.8, 2-H), 6.70
(1H, s, 5-H) and 7.56 and 7.59 (each 2H, d, J 9.0, ArH); δC
(CDCl3) 18.4 (q), 19.1 (q), 19.2 (q), 38.9 (d), 125.6 (s), 126.7 (s),
130.0 (s), 130.6 (d), 131.6 (d), 134.7 (s), 136.3 (s), 137.1 (d) and
193.2 (s); m/z 322 (Mϩ) (Found: C, 55.66; H, 4.70. C15H15BrOS
requires C, 55.74; H, 4.68%).
2-(4-Bromobenzoyl)-1-ethyl-4,5-dimethyl-1-thiabenzen-1-ium-
2-ide 6bЈ. Yield 57.5%, a dark red oil after column chrom-
atography on silica gel with ethyl acetate; νmax (KBr)/cmϪ1 1530
(CO); δH (CDCl3) 1.12 (3H, t, J 7.3, CH2CH3), 1.87 (3H, br s,
Me), 2.05 (3H, s, Me), 2.34–2.62 (2H, m, CH2Me), 5.04 (1H, s,
6-H), 6.55 (1H, br s, 3-H) and 7.44 and 7.52 (each 2H, d, J 8.5,
ArH); δC (CDCl3) 6.7 (q), 19.4 (q), 21.5 (q), 39.3 (t), 76.0 (s),
82.5 (d), 114.3 (s), 123.8 (s), 130.5 (d), 131.0 (d), 131.1 (d), 138.9
2274
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2-(4-Bromophenyl)-3a,6a-dihydro-3,6,6a-trimethylthieno[3,2-
b]furan 10b. An orange oil; δH (CDCl3) 1.57 (3H, s, Me), 1.83
(3H, d, J 1.7, Me), 1.86 (3H, d, J 1.3, Me), 4.64 (1H, q, J 1.3,
3a-H), 5.80 (1H, q, J 1.7, olefinic H) and 7.39 and 7.47 (each
2H, d, J 8.6, ArH); δC (CDCl3) 11.9 (q), 13.0 (q), 22.8 (q), 66.6
(d), 97.6 (s), 107.0 (s), 119.1 (d), 122.0 (s), 128.9 (d), 130.5 (s),
131.2 (d), 133.8 (s) and 146.6 (s); m/z 322 (Mϩ).
2-Cyano-2,4,5-trimethyl-2H-thiopyran 7d and 2-(1-cyano-
ethyl)-3,4-dimethylthiophene 11d. An inseparable mixture, as a
yellow oil; νmax (neat)/cmϪ1 2220 (CN); m/z 165 (Mϩ) (Found:
Mϩ, 165.0619. C9H11NS requires M, 165.0612); δH (CDCl3)
assigned to 7d: 1.78 (3H, s, Me), 1.88 and 1.98 (each 3H, d,
J 1.5, Me) and 5.23 and 6.08 (each 1H, br s, olefinic H);
δH (CDCl3) assigned to 11d: 1.25 (3H, d, J 6.8, Me), 1.84 and
1.93 (each 3H, s, Me), 3.17 (1H, q, J 6.8, CHCN) and 6.71 (1H,
s, 5-H).
2-[1-(4-Bromobenzoyl)ethyl]-3,4-dimethylthiophene 11b.
A
colourless oil; νmax (neat)/cmϪ1 1690 (CO); δH (CDCl3) 1.53 (3H,
d, J 6.8, Me), 2.10 and 2.11 (each 3H, s, Me), 4.83 (1H, q, J 6.8,
CH), 6.76 (1H, s, thiophene ring-H) and 7.54 and 7.78 (each
2H, d, J 8.6, ArH); δC (CDCl3) 12.3 (q), 15.3 (q), 19.0 (q), 41.9
(d), 119.0 (d), 128.0 (s), 130.0 (d), 131.8 (d), 132.9 (s), 135.0 (s),
136.7 (s), 138.0 (s) and 198.5 (s); m/z 322 (Mϩ) (Found: Mϩ,
322.0011. C15H15BrOS requires M, 322.0027).
2-Cyano-4,4,5-trimethyl-4H-thiopyran 8d. A pale orange oil;
νmax (neat)/cmϪ1 2230 (CN); δH (CDCl3) 1.20 (6H, s, 2 × Me),
1.85 (3H, d, J 1.5, Me), 5.80 (1H, q, J 1.5, 6-H), 6.21 (1H, s,
3-H); m/z 165 (Mϩ) (Found: Mϩ, 165.0611. C9H11NS requires
M, 165.0612).
From the thiabenzene 6bЈ, the following products were
obtained after PLC on silica gel with hexane–dichloromethane
(3 : 2).
Bis(6-cyano-3,4-dimethyl-2H-thiopyran-2-yl) 12d. Yellow
prisms, mp 189–190 ЊC (from ethanol); νmax (KBr)/cmϪ1 2220
(CN); δH (CDCl3) 1.82 and 1.87 (each 6H, s, 2 × Me), 3.27 (2H,
s, 2-H), 6.83 (2H, s, olefinic H); δC (CDCl3) 18.2 (q), 21.8 (q),
44.8 (d), 100.7 (s), 116.4 (s), 128.1 (s), 129.1 (s) and 138.0 (d);
m/z 150 (base, Mϩ/2) (Found: C, 63.97; H, 5.37; N, 9.32.
C16H16N2S2 requires C, 63.88; H, 5.39; N, 9.26%).
2-(4-Bromobenzoyl)-2-ethyl-4,5-dimethyl-2H-thiopyran 7bЈ.
A yellow oil; νmax (neat)/cmϪ1 1680 (CO); δH (CDCl3) 0.91 (3H, t,
J 7.3, CH2CH3), 1.85 and 1.88 (each 3H, s, Me), 2.00–2.16 (2H,
m, CH2CH3), 5.46 and 5.92 (each 1H, br s, olefinic H) and 7.53
and 7.91 (each 2H, d, J 8.5, ArH); δC (CDCl3) 8.8 (q), 20.1 (q),
20.7 (q), 31.2 (t), 57.4 (s), 113.9 (d), 118.4 (d), 126.8 (s), 130.3
(s), 131.12 (d), 131.14 (d), 134.6 (s), 135.2 (s) and 197.7 (s);
m/z 336 (Mϩ) (Found: Mϩ, 336.0173. C16H17BrOS requires M,
336.0183).
2-[4-Bromobenzoyl(methylsulfanyl)methyl]-3,4-dimethylthio-
phene 15
NCS (452 mg, 3.38 mmol) was added to an ice-cooled solution
of 4-bromophenacyl methyl sulfide13 (798 mg, 3.26 mmol) in
tetrachloromethane (15 cm3) with stirring. The mixture was
stirred for 2 h and the precipitate was filtered off. The filtrate
was concentrated under reduced pressure and dichloromethane
(8 cm3) and 3,4-dimethylthiophene18 13 (1.83 g, 16.3 mmol)
were added to the residue. This mixture was ice-cooled and zinc
chloride (311 mg, 2.28 mmol) was added with stirring. After the
reaction mixture had been stirred for 40 min, water was added
and the organic layer was separated, washed with water, and
dried (MgSO4). Evaporation of the mixture gave a crude oil,
which was chromatographed on silica gel with hexane–ethyl
acetate (100 : 1) to afford 15 (448 mg, 38.7%) as a pale yellow
oil; νmax (neat)/cmϪ1 1675 (CO); δH (CDCl3) 2.05, 2.12 and 2.15
(each 3H, s, Me) and 5.67 (1H, s, CH), 6.89 (1H, br s, 5-H)
and 7.58 and 7.87 (each 2H, d, J 8.5, ArH); δC (CDCl3) 12.9 (q),
13.6 (q), 15.1 (q), 47.7 (d), 121.3 (d), 128.4 (s), 130.2 (d),
130.7 (s), 131.9 (d), 134.2 (s), 135.2 (s), 137.5 (s) and 191.4 (s);
m/z 354 (Mϩ) (Found: Mϩ, 353.9728. C15H15BrOS2 requires M,
353.9747).
2-(4-Bromobenzoyl)-4-ethyl-4,5-dimethyl-4H-thiopyran 8bЈ.
A colourless oil; νmax (neat)/cmϪ1 1655 (CO); δH (CDCl3) 0.91
(3H, t, J 7.3, CH2CH3), 1.22 (3H, s, Me), 1.72–1.78 (2H, m,
CH2CH3), 1.81 (3H, d, J 1.5, Me), 5.93 (1H, q, J 1.5, 6-H), 5.99
(1H, s, 3-H), 7.57 and 7.60 (each 2H, d, J 8.8, ArH); δC (CDCl3)
10.0 (q), 19.8 (q), 27.1 (q), 33.3 (t), 41.6 (s), 112.5 (d), 127.1 (s),
130.8 (d), 131.2 (s), 131.6 (d), 133.4 (s), 135.6 (s), 142.5 (d) and
192.0 (s); m/z 336 (Mϩ) (Found: Mϩ, 336.0194. C16H17BrOS
requires M, 336.0184).
6-(4-Bromobenzoyl)-2-ethyl-3,4-dimethyl-2H-thiopyran 9bЈ.
A colourless oil; νmax (neat)/cmϪ1 1640 (CO); δH (CDCl3) 0.97
(3H, t, J 7.3, CH2CH3), 1.60 (2H, quint, J 7.3, CH2CH3), 1.83
and 1.99 (each 3H, br s, Me), 3.04 (1H, t, J 7.3, 2-H), 6.70 (1H,
s, 5-H), 7.55 and 7.59 (each 2H, d, J 8.8, ArH); δC (CDCl3) 11.0
(q), 18.4 (q), 20.2 (q), 25.3 (t), 46.6 (d), 126.0 (s), 130.3 (s), 130.5
(d), 131.5 (d), 133.6 (s), 136.2 (s), 137.5 (d) and 193.0 (s);
m/z 336 (Mϩ) (Found: Mϩ, 336.0158. C16H17BrOS requires M,
336.0184).
2-(4-Bromophenacyl)-3,4-dimethylthiophene 16
Zinc dust (1.4 g, 21 mmol) was added to a solution of 15
(350 mg, 0.99 mmol) in acetic acid (5 cm3) and the mixture
was stirred at 100 ЊC for 1 h. The cooled reaction mixture was
poured into water and extracted with dichloromethane. The
extract was washed with water, dried (MgSO4), and evaporated.
The oily residue was purified by PLC on silica gel with hexane–
ethyl acetate (40 : 1) to afford 16 (81 mg, 27%) as a pale orange
oil; νmax (neat)/cmϪ1 1690 (CO); δH (CDCl3) 2.04 (3H, s, Me),
2.06 (3H, br s, Me), 4.32 (2H, s, CH2), 6.79 (1H, s, 5-H) and 7.60
and 7.86 (each 2H, d, J 8.5, ArH); δC (CDCl3) 12.5 (q), 15.3 (q),
38.3 (t), 118.9 (d), 128.3 (s), 128.4 (s), 130.0 (d), 131.9 (d), 135.0
(s), 135.2 (s), 137.9 (s) and 195.0 (s); m/z 308 (Mϩ) (Found:
Mϩ, 307.9845. C14H13BrOS requires M, 307.9870).
2-(4-Bromophenyl)-3-ethyl-3a,6a-dihydro-6,6a-dimethyl-
thieno[3,2-b]furan 10bЈ. A colourless oil; δH (CDCl3) 1.10 (3H, t,
J 7.6, CH2CH3), 1.56 (3H, s, Me), 1.83 (3H, d, J 1.5, Me), 2.17–
2.46 (2H, m, CH2CH3), 4.76 (1H, br s, 3a-H), 5.82 (1H, q, J 1.5,
5-H) and 7.36 and 7.47 (each 2H, d, J 8.6, ArH); δC (CDCl3)
12.7 (q), 13.0 (q), 19.1 (t), 22.8 (q), 64.0 (d), 97.8 (s), 112.8 (s),
119.5 (d), 122.2 (s), 128.9 (d), 130.6 (s), 131.3 (d), 133.5 (s) and
146.6 (s); m/z 336 (Mϩ).
2-[1-(4-Bromobenzoyl)propyl]-3,4-dimethylthiophene
11bЈ.
A yellow oil; νmax (neat)/cmϪ1 1680 (CO); δH (CDCl3) 0.93 (3H,
t, J 7.6, CH2CH3), 1.75–1.95 and 2.12–2.22 (each 1H, m,
CH2CH3), 2.10 (3H, d, J 1.0, Me), 2.13 (3H, s, Me), 4.64 (1H, t,
J 7.3, CHCO), 6.76 (1H, s, 5-H) and 7.54 and 7.79 (each 2H, d,
J 8.5, ArH); δC (CDCl3) 12.1 (q), 12.7 (q), 15.3 (q), 27.4 (t), 49.0
(d), 119.3 (d), 128.0 (s), 129.9 (d), 131.9 (d), 133.6 (s), 135.2 (s),
135.6 (s), 137.8 (s) and 198.4 (s); m/z 336 (Mϩ) (Found:
Mϩ, 336.0195. C16H17BrOS requires M, 336.0184).
2-[1-(4-Bromobenzoyl)ethyl]-3,4-dimethylthiophene 11b
Butyllithium (1.62 mol dmϪ3 solution in hexane; 0.25 cm3,
0.41 mmol) was added with stirring to a solution of diiso-
propylamine (0.1 cm3, 0.41 mmol) in dry THF (5 cm3) at Ϫ30 ЊC
under nitrogen. After 30 min, a solution of 16 (58 mg, 0.19
mmol) in dry THF (2 cm3) was added in a stream of nitrogen to
From the thiabenzene 6d, the following compounds were
obtained after PLC on silica gel with hexane–ether (2 : 1).
J. Chem. Soc., Perkin Trans. 1, 2001, 2269–2276
2275

View Article Online
7 L. Weber, Angew. Chem., 1981, 93, 304.
the above solution at Ϫ70 ЊC. After the mixture had been
stirred for 50 min at the same temperature, methyl iodide
(0.1 cm3, 1.6 mmol) was added and the mixture was allowed to
warm to room temperature. Saturated aq. NH4Cl was added
and the mixture was extracted with dichloromethane. The
extract was washed with water, dried (MgSO4), and evaporated
to dryness. The residual oil was subjected to PLC on silica
gel with hexane–ethyl acetate (13 : 1) to afford 11b (29 mg,
48%) as a colourless oil. This compound showed the same
spectral properties as those of compound 11b obtained from
thermolysis of 6b.
8 Part of this work has appeared in preliminary form: H. Shimizu,
N. Kudo, T. Kataoka and M. Hori, Tetrahedron Lett., 1990, 31, 115.
9 G. W. Kirby, A. W. Lochead and G. N. Sheldrake, J. Chem. Soc.,
Chem. Commun., 1984, 922.
10 T. E. Sample, Jr. and L. F. Hatch, J. Chem. Educ., 1968, 45, 55;
T. E. Sample, Jr. and L. F. Hatch, Org. Synth., 1970, 50, 43; L. R.
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68, 2521.
11 M. Hori, T. Kataoka, H. Shimizu and Y. Imai, Chem. Pharm. Bull.,
1979, 27, 1982; H. Shimizu, N. Ueda, T. Kataoka and M. Hori,
Chem. Pharm. Bull., 1984, 32, 2571.
12 B. G. Lenz, H. Regeling, H. L. M. van Rozendaal and
B. Zwanenburg, J. Org. Chem., 1985, 50, 2930.
13 S. Kano, T. Yokomatu, T. Ono, S. Hibino and S. Shibuya, Synthesis,
1978, 305.
14 Y. Tamura, H. Shindo, J. Uenishi and H. Ishibashi, Tetrahedron
Lett., 1980, 21, 2547.
15 T. Bowles, R. J. Gillespie, A. E. A. Porter, J. A. Rechka and
H. S. Rzepa, J. Chem. Soc., Perkin Trans. 1, 1988, 803.
16 M. Hori, T. Kataoka, H. Shimizu and J. Hongo, J. Chem. Soc.,
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