Synthesis and photoreactivity of 4,5-dithienyl[1,3]dithiol-2-ones

Article abstract of DOI:10.1021/jo034301d

Whereas irradiation of 4,5-dithiophen-2-yl[1,3]-dithiol-2-one leads to the expected 2,3,5,6-tetrathiophen-2-yl-l,4-dithiine product, similar reaction of thiophen-3-yl-substituted [1,3]dithioi-2-ones leads to thieno[3,4-c]dithiines via a unique ring cleavage reaction.

Full text of DOI:10.1021/jo034301d

Syn th esis a n d P h otor ea ctivity of
,5-Dith ien yl[1,3]d ith iol-2-on es
SCHEME 1
4
Susan J . Roberts-Bleming, Gemma L. Davies,
Maher Kalaji, and Patrick J . Murphy*
Department of Chemistry, University of Wales,
Bangor Gwynedd LL57 2UW, U.K.
SCHEME 2a
Angela Maria Celli, Donato Donati, and
Fabio Ponticelli*
Department of Chemistry, University of Siena,
5
3100 Siena, Italy
paddy@bangor.ac.uk; ponticelli@unisi.it
Received March 7, 2003
a
Reagents and conditions: (a) 3-benzyl-5-(2-hydroxyethyl)-4-
methyl-1,3-thiazolium chloride (cat.), NEt3, EtOH, ∆, 2.5 h; 53%;
b) PPh3, CCl4/CH2Cl2; (c) KS(CS)OEt, acetone; (d) HBr/AcOH; 50%
(
from 6.
Abstr a ct: Whereas irradiation of 4,5-dithiophen-2-yl[1,3]-
dithiol-2-one leads to the expected 2,3,5,6-tetrathiophen-2-
yl-1,4-dithiine product, similar reaction of thiophen-3-yl-
substituted [1,3]dithiol-2-ones leads to thieno[3,4-c]dithiines
via a unique ring cleavage reaction.
SCHEME 3a
Our research on dithiophenyl[1,3]dithiol-2-ones, for
example, 1 and 2, has shown that these materials are
1
-4
versatile precursors for the synthesis of TTFs
and
a Reagents and conditions: (a) SOCl , ∆, 3 h; (b) thiophene, PhH,
AlCl3; 34%; (c) CuBr2, EtOAc, ∆, 2 h; (d) KS(CS)OEt, acetone; (d)
HBr/AcOH; 36% from 10.
2
metal dithiolenes5 and for the preparation of polymer
6
films for chemical modification. More recently we re-
7
ported the unique photochemical transformation of 4,5-
potassium ethyl xanthate to give 8. Reaction of this with
HBr/AcOH gave 2 in 50% overall yield from 6.
The unsymmetrical 4-thiophen-2-yl-5-thiophen-3-yl-
dithiophen-3-yl[1,3]dithiol-2-one 2 to the thieno[3,4-c]-
dithiin 4 and take this opportunity to report our findings
in this area of research in more detail (Scheme 1).
P r ep a r a tion of Su bstr a tes. We intended to investi-
gate the reaction of the three thiophenyl[1,3]dithiol-2-
ones 1-3 as they represent all the possible substitution
patterns available for the parent class of compounds. The
symmetrical adducts were prepared according to our
previously reported method, and details for 1 have
already been reported.2 The 4,5-dithiophen-3-yl[1,3]-
dithiol-2-one 2 was prepared similarly from thiophene-
[
1,3]dithiol-2-one 3 was prepared first by conversion of
the carboxylic acid 9 to the corresponding acid chloride,
which on Friedel-Crafts reaction with thiophene gave
ketone 10 in 34% yield (Scheme 3). Bromination of this
2
using CuBr in EtOAc gave the bromide 11, which was
then treated with potassium ethyl xanthate to give 12.
Reaction of this with HBr/AcOH gave 3 in 36% overall
yield from 10.
7
P h otoch em istr y. As previously reported, the photo-
3
-carboxaldehyde (5), which was first converted into the
chemical irradiation of 4,5-dithiophen-3-yl[1,3]dithiol-2-
ones 2 led to the formation of the thieno[3,4-c]dithiin 4
in 76% yield. A similar reaction was observed for the
unsymmetrical 4-thiophen-2-yl-5-thiophen-3-yl[1,3]dithiol-
benzoin product 6 in 53% yield (Scheme 2). Reaction of
this with triphenylphosphine and carbon tetrachloride
gave the chloride 7, which was immediately treated with
2
-one 3 in that the 2-thienyl-substituted thieno[3,4-c]-
*
Corresponding author.
dithiin 13 was again formed in 76% yield (Scheme 4).
These processes both occur via a photochemical elimina-
tion of carbon monoxide from the substrate, which is
followed by a ring cleavage rearrangement (vide infra),
indicating a common reaction pathway for 3-thienyl-
substituted systems. Structural characterization of these
compounds was achieved by reduction with NaBH to
4
give the corresponding hemithioacetals 14 and 15, the
first of these giving crystals suitable for X-ray analysis.
If, in a single sequence, the reduction step is followed by
treatment of the crude reaction product with methyl
iodide and sodium carbonate at room temperature, the
methylated products 16 and 17 are formed in good yields.
Heating 16 or 17 in the presence of further methyl iodide
(1) Charlton, A.; Underhill, A. E.; Kalaji, M.; Murphy, P. J .; Hibbs,
D. E.; Hursthouse, M. B.; Malik, K. M. A. J . Chem. Soc., Chem.
Commun. 1996, 2423.
(
2) Charlton, A.; Underhill, A. E.; Williams, G.; Kalaji, M.; Murphy,
P. J .; Abdul Malik, K. M.; Hursthouse, M. B. J . Org. Chem. 1997, 62,
098.
3) Charlton, A.; Kalaji, M.; Murphy, P. J .; Salmaso, S.; Underhill,
A. E.; Williams, G.; Hursthouse, M. B.; Malik, K. M. A. Synth. Met.
998, 95, 75.
4) Gelbrich, T.; Roberts-Bleming, S. J .; Kalaji, M.; Hursthouse, M.
3
(
1
(
B.; Murphy, P. J . Acta Crystallogr. 2001, E57, 1143 (http://journal-
s.iucr.org/e/issues/2001/12/00/issconts.html).
7
(
5) Roberts-Bleming, S. J .; Charlton, A.; Kalaji, M.; Murphy, P. J .;
Robertson, N.; Coles, S. J .; Hursthouse, M. B. Unpublished work.
6) Roberts-Bleming, S. J . Ph.D. Thesis, University of Wales, Bangor,
U.K., 2001.
(
(7) Celli, A. M.; Donati, D.; Ponticelli, F.; Roberts-Bleming, S. J .;
Kalaji, M.; Murphy, P. J . Org. Lett. 2001, 3, 3573.
1
0.1021/jo034301d CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/13/2003
J . Org. Chem. 2003, 68, 7115-7118
7115

SCHEME 4a
agent, the dithioketones formed from substrates 2 and 3
cyclize via the diradicals 24 to give the intermediates 25,
which undergoes ring cleavage to 26 and disulfide bond
formation to give the dithiin systems 4 and 13, respec-
tively.
In the case of compound 1, addition of the thioradical
to a 2-thienyl ring would lead to the intermediates 27
and 28, which are unable to undergo this ring cleavage.
It is likely that if these intermediates are formed it will
be in a reversible process, and the eventual fate of the
dithioketone is that it undergoes dimerization with S
2
elimination10 to afford 20.
It is apparent that there are significant differences in
the reactivity of the 2-thienyl (1) and 3-thienyl (2, 3)
substituted substrates, the latter undergoing an unusual
fragmentation process after the common decarbonylation
step. We have illustrated that this reaction has potential
in synthesis as the thieno[3,4-c]dithiins 4 and 13 were
readily converted into the thieno[3,4-b]thiophenes 18 and
19 in high yield. We are currently investigating related
reactions of this type and will report our findings in due
course.
a
Reagents and conditions: (a) hv, 6 h; 4, 76%; 13, 76%; (b)
NaBH4, EtOH; 14, 65%; 15, 78%; (c) (i) NaBH4, EtOH; (ii) MeI,
Na2CO3, rt; 16, 69% from 4; 17, 71% from 13; (d) MeI, ∆; 18, 72%;
9, 66%.
1
SCHEME 5a
Exp er im en ta l Section
2
-H yd r oxy-1,2-d it h iop h en -3-ylet h a n on e (3,3′-Th eon in ,
6
).3 3-Thiophenecarboxaldehyde (5) (25 g, 223 mmol) was
dissolved in absolute ethanol (67.5 mL), and triethylamine (9.3
mL, 70.3 mmol) and 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-
thiazolium chloride (1.2 g, 4.5 mmol) were added. The reaction
was heated to reflux for 2.5 h, then cooled, diluted with water
a
Reagents and conditions: (a) hv, 5 h; quantitative; (b) AcOH,
H2O2; 75%.
(
750 mL), and extracted with dichloromethane (3 × 100 mL).
The combined organic fractions were washed with sodium
bicarbonate (3 × 100 mL), dried (magnesium sulfate), and
evaporated in vacuo to give a pale brown solid. The solid was
recrystallized from chloroform, producing white crystals of 6
(13.1 g, 53%): mp 108 °C; δH 4.38 (d, 1H, J ) 5.8 Hz, OH), 5.86
(d, 1H, J ) 5.8 Hz, CH), 7.01 (dd, 1H, J ) 1.2, 4.9 Hz, C-H),
and sodium carbonate leads to the formation of the
thieno[3,4-b]thiophenes 18 and 19 in 72% and 66% yield,
8
respectively. Thiophene 18 is a known compound, and
1
9 displayed very similar spectroscopic properties, thus
confirming its structure.
We next investigated the irradiation of 4,5-dithiophen-
7
(
(
.33 (m, 3H, C-H), 7.53 (dd, 1H, J ) 0.9, 4.9 Hz, C-H), 8.06
dd, 1H, J ) 1.2, 2.8 Hz, C-H); δ 192.4 (C), 139.9 (C), 139.9
C), 134.3 (CH), 127.3 (CH), 128.1 (CH), 126.6 (CH), 126.3 (CH),
2.9 (CH); vmax 3428 (O-H), 3097 (C-H), 3018 (C-H), 1667 (Cd
C
2
-yl[1,3]dithiol-2-one 1 and found that a considerably
different process occurred. The crude reaction mixture
was composed largely of a compound with m/z 444, which
was unstable to chromatography and displayed only
signals suggestive of a 2-thienyl-containing moiety. Reac-
tion of this compound with hydrogen peroxide in acetic
7
+
O); MS (EI) m/z (rel intens) 224 (100, [M ]); HRMS (EI) (m/z)
+
C
10
H
8
O
2
S
2
[M ] requires 223.9966, found 223.9974. Anal. Ex-
pected: C, 53.55; H, 3.59. Found: C, 53.85; H, 3.61.
,5-Dith iop h en -3-yl[1,3]d ith iol-2-on e 2. 6 (5.4 g, 24.1
4
9
mmol) was dissolved in dichloromethane (25 mL) and added to
a solution of triphenylphosphine (12.7 g, 48.5 mmol) in tetra-
chloromethane (50 mL). The reaction mixture was stirred in the
dark for 18 h and then diluted with ether (100 mL), which caused
the precipitation of a yellow solid. The solution was decanted
with filtration through a silica pad and the yellow precipitate
redissolved in dichloromethane (20 mL) and precipitated again
by the sequential addition of diethyl ether (100 mL) and
petroleum ether (50 mL). The supernatant layer was decanted
and filtered as before, and the process was repeated twice more.
After evaporation of the combined filtrates, the product was
purified by column chromatography using diethyl ether/petrol
acid gave the known 2,3,4,5-tetrathiophen-2-ylthiophene
(21) in 75% yield (Scheme 5). As a consequence of this
we can assign the 1,4-dithiin structure 20 to be that
formed from the initial photolysis. The transformation
of 1,4-dithiin derivatives into thiophenes by sulfur loss
has been previously described.10
A rationale for the photochemical behavior of the title
compounds is illustrated in Scheme 6. The elimination
of carbon monoxide1
1,12
to give the 1,2-dithioketone 22 is
a common step for each system, which is confirmed by
performing the reactions in the presence of Mo(CO)
f
(30:70, collecting pots containing R 0.2) as eluent to give 7 as a
6
,
white solid (5.3 g, ca. 90%) of sufficient purity to be used
immediately in the next step.
which is able to halt the rearrangement by formation of
blue Mo complexes 23.11 In the absence of this trapping
Chloride 7 (5.3 g) was dissolved in dried acetone (5 mL) and
added to a solution of potassium ethyl xanthate (13.9 g, 86.8
mmol) in acetone (100 mL). The reaction mixture was stirred
for 15 min and then diluted with diethyl ether (200 mL). The
resultant solution was filtered through a silica pad which was
washed with further diethyl ether (2 × 50 mL). These filtrates
on evaporation gave crude 8 (4.5 g, ca. 63%).
(
(
8) Yang, S.-M.; Fang, J .-M. J . Org. Chem. 1999, 64, 394.
9) Nakayama, J .; Yomoda, R.; Hoshino, M. Heterocycles 1987, 26,
2
215.
(10) Shimizu, T.; Murakami, H.; Kamigata, N. J . Org. Chem. 1999,
6
4, 8489.
(11) Kusters; de Mayo, P. J . Am. Chem. Soc. 1974, 96, 3502.
12) Hartke, K.; Kissel, T.; Quante, J .; Matusch, R. Chem. Ber. 1980,
(
Xanthate ester 8 (4.5 g) was dissolved in glacial acetic acid
(15 mL), and 45% hydrobromic acid solution in acetic acid (15
1
13, 1898.
7
116 J . Org. Chem., Vol. 68, No. 18, 2003

SCHEME 6
mL) was added. The mixture was stirred vigorously for 15 min,
whereupon dichloromethane (50 mL) and water (200 mL) were
added. The organic phase was separated and the aqueous phase
extracted with dichloromethane (3 × 25 mL), and the combined
organic fractions were washed with saturated sodium bicarbon-
ate (3 × 25 mL), dried (magnesium sulfate), and evaporated.
The crude product was purified by column chromatography using
diethyl ether/petrol (3:97, 10:90, 30:70) collecting fractions
layer was decanted and filtered through a Celite pad. This
process was repeated three times and the combined filtrate
evaporated to give crude bromide 11 (4.3 g, ca. 85%).
Bromide 11 (4.3 g) was dissolved in dried acetone (30 mL)
and added to a solution of potassium ethyl xanthate (5.6 g, 35
mmol) dissolved in dried acetone (100 mL). The reaction mixture
was stirred for 15 min and then diluted with diethyl ether (200
mL). The resultant solution was filtered through a silica pad
and washed with further diethyl ether (2 × 50 mL). Evaporation
gave crude 12 (3.0 g ca. 58%).
Xanthate ester 12 (3.0 g) was dissolved in glacial acetic acid
(20 mL), and 45% hydrobromic acid solution in acetic acid (20
mL) was added. The mixture was stirred vigorously for 1 h,
whereupon dichloromethane (50 mL) and water (200 mL) were
added. The reaction was then separated and the aqueous phase
extracted with dichloromethane (3 × 25 mL). The combined
organic fractions were washed with saturated sodium bicarbon-
ate (3 × 25 mL), dried (magnesium sulfate), and evaporated.
The crude product was purified by column chromatography using
diethyl ether/petrol (5:95, 10:90, 30:70, collecting fractions
containing spots at R ) 0.25 (diethyl ether/petrol, 10:90).
f
Recrystallization from ether/hexane gave 2 (3.4 g, 50% from 6)
as needles: mp 102 °C.
δ
H
6.86 (dd, 2H, J ) 4.0, 1.2 Hz, 2 CH), 7.24 (dd, 2H, J ) 3,
1
1
3
2
2
.2 Hz, 2 CH), 7.28 (dd, 2H, J ) 4.0, 3.0 Hz, 2 H); δ
C
189.9 (C),
31.8 (C), 127.6 (CH), 126.5 (CH), 125.8 (CH), 123.5 (C); vmax
111 (C-H), 1659 (CdO), 1629 (CdC); MS (EI) m/z (rel intens)
82 (100, [M ]); HRMS (EI) (m/z) C11
+
+
6 4
H OS [M ] requires
81.9302, found 281.9302.
2
-Th ioph en -3-yl-1-th ioph en -2-yleth an on e (10).3-Thiophene-
acetic acid (9) (5 g, 35.2 mmol) was dissolved in thionyl chloride
13.7 mL, 70.4 mmol) and heated under reflux for 3 h. After
(
removal of the excess thionyl chloride by evaporation on a
vacuum pump, thiophene (3.6 g, 42.3 mmol) and dry benzene
containing R
f
0.25). Recrystallization from ether/hexane gave 3
(1.76 g, 36% from 10): mp 95 °C;
(
50 mL) were added and the solution was cooled (5 °C).
δ
H
7.35-7.25 (m, 3H, 3 CH), 7.02-6.92 (m, 3H, 3 CH); δ
C
Aluminum chloride (5.5 g, 42.3 mmol) was then added in small
portions and the reaction stirred to room temperature overnight.
The reaction mixture was then poured carefully onto a mixture
of crushed ice (200 mL) and concentrated HCl (100 mL), the
organic phase separated, and the aqueous layer extracted with
further dichloromethane (3 × 50 mL). The combined extracts
186.7 (C), 129.8 (C), 128.1 (C), 126.2 (CH), 125.0 (CH), 124.9
(CH), 122.4 (CH), 123.9 (CH), 123.8 (CH), 121.2 (C), 119.2 (C);
v
max 3105 (C-H), 1663 (CdO), 1637 (CdC); MS (CI) m/z (rel
+
+
intens) 300 (100, [M + NH
4
]), 282 (15, [M ]); HRMS (CI) (m/z)
+
C
11
H
10NOS
4
[M + NH
4
] requires 299.9645, found 299.9641.
7-Th iop h en -3-ylth ien o[3,4-c]-1,2-d ith iin (4). A solution of
were dried (MgSO
4
) and evaporated, following which column
1,3-dithiol-2-one 2 (0.25 g, 0.89 mmol) in benzene (15 mL) was
irradiated in an air-cooled Pyrex tube for 6 h with a Rayonet
apparatus at 350 nm. After removal of solvent, column chro-
matography gave 140 mg (92%, based on recovered 1) of crude
dithiin 4 (yellow oil) and starting material (80 mg). Compound
4 was further purified (yield 76%) by preparative TLC followed
by sublimation at 40 °C and 0.03 mmHg:
chromatography of the crude product (diethyl ether/petrol, 20:
8
0) gave the ketone 10 (2.52 g, 34%) as an oil:
7.77 (dd, 1H, J ) 4.0, 1.0 Hz, CH), 7.66 (1H, dd, J ) 4.9,
.9 Hz, CH), 7.31 (1H, dd, J ) 4.9, 3.1 Hz, CH), 7.19 (1H, m,
δ
H
0
CH), 7.15 (1H, dd, J ) 4.0, 4.9 Hz, CH), 7.06, (1H, dd, J ) 4.9,
0
1
(
2
.9, CH), 4.24, (2H, s, CH
33.9 (C), 132.6 (CH), 128.5 (CH), 125.9 (CH), 122.94 (CH), 40.9
2 C
); δ 189.9 (C), 131.9 (C), 134.1 (CH),
δ 6.50 (1H, dd, J ) 9.5, 0.4 Hz, H-3), 6.92 (1H, dd, J ) 9.5,
H
CH
2
); vmax 3099 (C-H), 1656 (CdO) MS (CI) m/z (rel intens)
0.5 Hz, H-4), 7.09 (1H, dd, J ) 0.5, 0.4 Hz, H-5), 7.39 (1H, d, J
) 1.8 Hz, H-2′), 7.41 (1H, d, J ) 2.5 Hz, H-4′), 7.51 (1H, dd, J )
+
+
26 (100, [M + NH
4
]), 209 (33, [M + H ]); HRMS (CI) (m/z)
+
C
10
H
8
OS
2
([M + NH
4
]) requires 226.0360, found 226.0356.
C
2.5, 1.8 Hz, H-5′); δ 121.6 (C-3), 121.8 (C-5), 122.6 (C-7a), 123.5
4
-Th iop h en -2-yl-5-th iop h en -3-yl[1,3]d ith iol-2-on e 3. Ke-
tone 10 (3.64 g, 17.5 mmol) was dissolved in dry ethyl acetate
80 mL), copper(II) bromide (8.6 g, 38.5 mmol) was added, and
the mixture was then stirred while being heated at 60 °C. After
h the reaction was cooled and filtered through a Celite pad
(C-5′), 126.2, 127.4 (C-2′, C-4′), 127.25 (C-4), 133.0 (C-3′), 133.5
(C-7), 136.1 (C-4a); vmax (KBr) 1652. MS (EI) m/z 254 (rel intens)
(M , 100), 221 (32), 209 (11), 190 (14), 177 (13), 127 (16), 69 (18).
+
(
Anal. Calcd for C10
2.02.
6 4
H S : C, 47.21; H, 2.38. Found: C, 47.46; H,
2
and the filtrate evaporated. Diethyl ether (25 mL) was then
added to the crude product, followed by petroleum ether (50 mL)
to precipitate any inorganic material, following which the organic
7-Th iop h en -2-ylth ien o[3,4-c]-1,2-d ith iin (13). A solution
of 1,3-dithiol-2-one 3 (0.050 g, 0.177 mmol) in benzene (20 mL)
was irradiated in a Pyrex tube for 5 h with a Rayonet apparatus
J . Org. Chem, Vol. 68, No. 18, 2003 7117

at 350 nm. After removal of solvent, the residue was purified
resultant solution dried and evaporated to give 17 (0.023 g, 71%)
by preparative TLC to give dithiin 13 (26 mg, 76%, based on
recovered 3) (yellow oil, R 0.46, cyclohexane) and starting
f
material (12 mg):
as a yellow oil (R 0.21 in cyclohexane):
f
δ
H-3
H
2.26 (3 H, s, SMe), 3.10 (1 H, ABX, J ) 15.9, 5.4, 1.0 Hz,
), 3.39 (1 H, ABX, J ) 15.9, 7.3, 1.0 Hz, H-3 ), 5.33 (1 H,
A
B
δ 6.52 (1H, dd, J ) 9.5, 0.5 Hz, H-3), 6.92 (1H, dd, J ) 9.5,
H
dd, J ) 7.3, 5.4 Hz, H-2), 6.79 (1H, t, J ) 1.0 Hz, H-4), 7.04 (1H,
dd, J ) 4.7, 3.6 Hz, H-4′), 7.13 (1H, dd, J ) 3.6, 1.0 Hz, H-3′),
0
4
.5 Hz, H-4), 7.08 (1H, t, J ) 0.5 Hz, H-5), 7.10 (1H, dd, J ) 5.3,
.5 Hz, H-4′), 7.28 (1H, dd, J ) 4.5, 1.3 Hz, H-3′), 7.38 (1H, dd,
7
C
.24 (1H, dd, J ) 4.7, 1.0 Hz, H-5′); δ 14.25 (SMe), 37.1 (C-3),
J ) 5.3, 1.3 Hz, H-5′); δ
C
121.8 (CH), 122.0 (CH), 123.1 (C), 126.6
6
3.3 (C-2), 114.2 (CH), 123.55 (CH), 124.3 (CH), 125.9 (C), 127.7
(
1
CH), 126.7 (CH), 127.2 (CH), 127.5 (CH), 132.0 (C), 134.3 (C),
+
(CH), 135.1 (C), 136.6 (C), 144.2 (C); MS (EI) m/z (rel intens)
36.3 (C); MS (EI) m/z (rel intens) 254 (M , 100), 221 (38), 209
+
(
C
16), 190 (25), 177 (18), 127 (41), 69 (43); HRMS (EI) (m/z)
270 (M , 57), 223 (100), 190 (45), 177 (12); HRMS (m/z) C11
H
10
S
4
+
+
10
H
6
S
4
[M ] requires 253.9352, found 253.9349.
[M ] requires 269.9665, found 269.9668.
6
-Th iop h en -3-yl-2,3-d ih yd r ot h ien o[3,4-b]t h iop h en e-2-
6
-Th iop h en -3-ylth ien o[3,4-b]th iop h en e (18). Methyl io-
th iol (14). Sodium borohydride (0.015 g, 0.4 mmol) was added
to a stirred solution of 1,2-dithiin 4 (0.03 g, 0.12 mmol) in ethanol
2 mL) under nitrogen. After 30 min the solvent was removed
and the residue treated with hydrochloric acid (0.1 N). This
solution was extracted with ether (3 × 5 mL), and the combined
extracts were dried (sodium sulfate) and evaporated to give 14
dide (0.2 mL) and sodium carbonate (0.1 g) were added to a
stirred solution of the thioether 16 (0.050 g, 0.19 mmol) in
ethanol (5 mL). The reaction mixture was heated to reflux, and
further aliquots (0.1 mL) of methyl iodide were added until the
starting material was consumed (TLC). The solvent was removed
in vacuo and the residue purified by chromatography (silica gel
eluting with cyclohexane) to give compound 18 (0.030 mg, 72%)
(
(
0.02 g, 65%) as a white solid: mp 193-195 °C;
δ 2.59 (1H, exch. d, J ) 8.5 Hz, SH), 3.06 (1H, ddd, J ) 15.6,
H
1
13
8
5
5
.9, 1.3 Hz, H-3), 3.50 (1H, ddd, J ) 15.6, 6.7, 1.3 Hz, H-3′),
.32 (1H, ddd, J ) 8.5, 6.7, 5.9 Hz, H-2), 6.86 (1H, t, J ) 1.3 Hz,
identical ( H and C NMR) with an authentic sample.
6
-Th iop h en -2-ylth ien o[3,4-b]th iop h en e (19). Methyl io-
H-4), 7.31 (2H, m, H-2′, H-4′), 7.37 (1H, dd, J ) 4.7, 3.1 Hz, H-5′);
dide (0.2 mL) and sodium carbonate (0.1 g) were added to a
stirred solution of the thioether 17 (0.050 g, 0.19 mmol) in
ethanol (5 mL). The reaction mixture was refluxed with further
addition of methyl iodide until the starting material was
consumed (TLC). Solvent was removed in vacuo and the residue
purified by chromatography (silica gel eluting with cyclohexane)
δ
(
1
2
4
4
C
42.26 (C-3), 54.76 (C-2), 114.48 (C-4), 120.00 (C-4′), 124.74
C-6), 125.89, 126.35 (C-2′, C-5′), 134.26 (C-3a), 134.36 (C-3′),
43.36 (C-6a); vmax 1650; MS (EI) m/z (rel intens) 256 (M , 71),
23 (100), 190 (57), 177 (10), 127 (11), 111 (8), 95 (10), 69 (15),
5 (17). Anal. Calcd for C10
6.56; H, 3.39.
+
8 4
H S : C, 46.84; H, 3.14. Found: C,
f
to give compound 19 (28 mg, 66%) as an orange oil (R 0.53 in
cyclohexane):
6
-Th iop h en -2-ylth ien o[3,4-b]th iop h en e-2-th iol (15). So-
dium borohydride (0.015 g, 0.4 mmol) was added to a stirred
solution of 1,2-dithiin 13 (0.03 g, 0.12 mmol) in ethanol (2 mL)
under nitrogen. After 30 min the solvent was removed and the
residue treated with hydrochloric acid (0.1 N). This solution was
extracted with ether (3 × 5 mL), and the combined extracts were
dried (sodium sulfate) and evaporated to gave 15 (0.024 g, 78%)
contaminated with a small amount of the corresponding disulfide
derivative:
δ
H
(CD
1H, dd, J ) 5.0, 3.6 Hz, H-4′), 7.29 (1H, dd, J ) 3.6, 0.9 Hz,
H-3′), 7.42 (1H, s, H-4), 7.43 (1H, dd, J ) 5.0, 0.9 Hz, H-5′), 7.52
1H, d, J ) 5.5 Hz, H-2); δ 111.6 (CH), 118.5 (CH), 124.3 (CH),
25.4 (C-H), 129.0 (CH), 133.8 (CH), 136.4 (C), 137.2 (C),149.6
3
OD, 600 MHz) δ 6.98 (1H, d, J ) 5.5, Hz, H-3), 7,13
(
(
1
(
1
2
C
+
C); MS (EI) m/z (rel intens) 222 (M , 100), 190 (20), 177 (20),
45 (7); HRMS (m/z) C10
21.9630.
+
H
6
S
3
[M ] requires 221.9632, found
δ
H
2.59 (1 H, exch. d, J ) 8.6, SH), 3.05 (1 H, ABX, J ) 15.8,
.0, 1.2 Hz, H-3 ), 3.50 (1 H, ABX, J ) 15.8, 6.8, 1.2 Hz, H-3 ),
.32 (1 H, ddd, J ) 8.6, 6.8, 6.0 Hz, H-2) 6.83 (1H, t, J ) 1.2 Hz,
6
5
A
B
2
,3,5,6-Tetr a th iop h en -2-yl-1,4-d ith iin (20). A solution of
H-4), 7.02-7.29 (3 H, m, H-3′,4′,5′); MS (EI) m/z (rel intens) 256
1
,3-dithiol-2-one 1 (0.050 g, 0.177 mmol) in benzene (20 mL) was
+
(
(
4
M , 46), 255 (21), 223 (100), 222 (96), 209 (12), 190 (62), 177
26). Some data for the disulfide derivative: δ 3.34 (2H, d, J )
irradiated in a Pyrex tube for 5 h with a Rayonet apparatus at
50 nm. Removal of the solvent gave crude 1,4-dithiin 20 as a
yellow oil in quantitative yield:
6.96 (1H, dd, J ) 5.1, 3.7 Hz, H-4), 7.24 (1H, dd, J ) 3.7,
H
3
.4 Hz, 3-H), 5.43 (1 H, t, J ) 4.4 Hz, 2-H); MS (EI) m/z (rel
+
intens) 510 (M , 2), 442 (0.5). Attempted purification of 15 led
to further disulfide formation.
δ
H
2
-Meth ylsu lfa n yl-6-th iop h en -3-yl-2,3-d ih yd r oth ien o[3,4-
1.2 Hz, H-3), 7.32 (1H, dd, J ) 5.1, 1.2 Hz, H-5); δ
C
26.9 (CH),
+
b]th iop h en e (16). Sodium borohydride (0.015 g, 0.4 mmol) and
a solution of sodium carbonate (0.012 g, dissolved in the
minimum amount of water required) were added under nitrogen
to a stirred solution of 4 (0.03 g, 0.12 mmol) in ethanol (5 mL).
After 30 min methyl iodide (0.1 mL) was added and the reaction
stirred for 3 h at rt. After evaporation of the reaction solvent,
the residue obtained was dissolved in chloroform and the
resultant solution dried and evaporated to give 16 (0.022 g, 69%)
127.9 (CH), 129.35 (CH); MS (EI) m/z (rel intens) 444 (M , 15),
412 (100), 378 (8), 367 (6), 333 (7). Attempted purification by
preparative layer or column chromatography resulted in com-
plete decomposition.
2
,3,4,5-Tetr a th iop h en -2-ylth iop h en e (21). The crude dithi-
in 20 (0.030 g, 0.067 mmol) was dissolved in acetic acid (4 mL),
and 30% hydrogen peroxide (2 mL) was added. After 12 h the
product 21 (21 mg, 75%) was removed by filtration and was
as a yellow oil (R
δ
f
0.21 in cyclohexane):
1
2.23 (3 H, s, SMe), 3.07 (1 H, ABX, J ) 15.9, 5.4, 1.0 Hz,
found to be identical (mp and H NMR) with an authentic
H
sample.9
H-3), 3.36 (1 H, ABX, J ) 15.9, 7.3, 1.0 Hz, H-3′), 5.30 (1 H,
ABX, J ) 7.3, 5.4 Hz, H-2) 6.76 (1H, t, J ) 1.0 Hz, H-4), 7.21-
7
1
(
2
2
C
.48 (3H, m, H-2′,4′,5′); δ 14.25 (SMe), 37.0 (C-3), 63.0 (C-2),
Ack n ow led gm en t. We thank the University of
Wales for funding (S.R.B.), the EPSRC Mass Spectrom-
etry Centre at Swansea, and the “Centro di Analisi e
Determinazioni Strutturali” of the University of Siena.
14.0 (CH), 119.9 (CH), 124.45 (C), 125.9 (CH), 126.2 (CH), 133.2
+
C), 134.55 (C), 144.2 (C); MS (EI) m/z (rel intens) 270 (M , 46),
23 (100), 190 (53); HRMS (EI) (m/z) C11H S [M ] requires
10 4
69.9665, found 269.9670.
2
+
-Meth ylsu lfa n yl-6-th iop h en -2-yl-2,3-d ih yd r oth ien o[3,4-
b]th iop h en e (17). Sodium borohydride (0.015 g, 0.4 mmol) and
a solution of sodium carbonate (0.012 g, dissolved in the
minimum amount of water required) were added under nitrogen
to a stirred solution of 13 (0.03 g, 0.12 mmol) in ethanol (5 mL).
After 30 min methyl iodide (0.1 mL) was added and the reaction
stirred for 3 h at rt. After evaporation of the reaction solvent,
the residue obtained was dissolved in chloroform and the
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and spectral data for the synthetic intermediates. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O034301D
7
118 J . Org. Chem., Vol. 68, No. 18, 2003