Full text of DOI:10.1016/S0040-4020(01)83207-5

Tetrahedron. Vol. 29, pp. lg29 to1832. Pergamon Press1973. Printed in Gw.at Britain
DITHIAINDENES
S Y N T H E S I S OF 6 - T H I A - 7 H - B E N Z O [b] T H I O P H E N E
( 1 , 6 - D I T H I A I N D E N E ) A N D 1, 3-DIMETHYL-5-THIA-4H-BENZO [c]
T H I O P E N E (I, 3-DIMETHYL-2, 5-DITHIAINDENE) A N D
A T T E M P T E D S Y N T H E S I S OF 5-THIA-4H-BENZO [b] T H I O P H E N E
(1, 5-DITHIAINDENE)
I. ALAMa and G. THYAGARAJAN*
Regional Research Laboratory, Hyderabad 500009, India
(Receivedin UK 1February 1973; Acceptedfor publication 16February 1973)
AIMtract-Synthesis of the heteroaromatic systems 6-thia-7H-benzo [hi thiophene (3) and 1,3-
dimethyl-5-thia-4H-benzo [c] thiophene (5) have been achieved by reduction and dehydration of
1,6-dithiaindan-4-on¢ (4) and 1,3-dimethyl-2,5-dithiaindan-7-one (8) respectively. A similar attempt
to synthesise 5-thia-4H-benzo [b] thiophene (4) by dehydration of 7-hydroxy-l,5-dithiaindane (16)
resulted in the formation of 7,7'-bis (l,5-dithiaindanyl) ether.
from 2-chloromethylthiophene, easily accessible
Dithiaindenes, of which ten isomers are theoreti-
cally possible, represent a relatively uninvestigated by direct chloromethylation of thiophene. Conden-
class of heterocyclic compounds. The structural sation with thiogiycolic acid afforded 1-(2'-thienyl)-
2-thiabutyric acid (9) which underwent cyclisation
meric studies with the aid of modemphysical tools, in moderate yields, to the desired ketone. The
particularly NMR spectroscopy. Earlier, two ex-
types are of particular value and interest for tauto-
NMR and IR spectral data were in agreement with
amples of this class of compounds 5H-th/eno structure 6.
[3,2-b] tbiinand 6H-thieno [2~-b] thiin (I and 2
1,5-Dithiaindan-7-one (7). Cagniant4 synthesised
respectively) were know~l While this work was in this system applying his original method, using 3-
progress, a reports presenting a description of
some salts containing the isomeric thieno-thia-
thienylmethanethiol as starting material. In the
present investigation, the synthesis of 7 was ac-
pyrilium nuclei 3 and 4 appeared. We now wish to complished by inlramolecular cycfisation of l(Y-
present our results o n t h e synthesis and character-
thienyi)-2-thiabutyric acid (1O), obtained by con-
isatinn of the free heteroaromatic compounds densation of 3-bromomethylthiophene5 and thio-
6-thia-TH-benzo[b]thiophene (3) and 1,3-dimethyl- giycolic acid ina sequence analogous to that out-
5-thia-4H-benzo[c]thiophene (b'), and an attempted lined for 6. Analytical and spectral characterisation
preparation of 5-thin4H-benso[b]thiophene (4).
We considered that the most reasonable mute to
confirmed the structure of7.
1,3-Dimethyl-2,5-dithiaindan-7-one (8). Isolated
these systems lay in the preparation of the ketones instances of 3,4-annelated thiophene are reported.
6, 7 and 8 which could then be reduced to the corre- Stalnkopfe synthesised the first of this kind, 4-oxo-
sponding alcohols and these dehydrated to the di- 1,3-dimethyl-4,5,6,7-tetrahydroisobenzothiophene
thiaindenes.
(11). MacDowelF and Harrisons reported the
prepm-atiunof thienocyclopentanones of the type
12, while Damn and Dammlings described the syn-
thesis of 13.
Synthesis of dithiainanones
1,6-Dithiaindan-4-one (6). Cagniants reported
the synthesis of this compound starting from
The 3,4-annelated thiophene system (8) has now
2-thienylmethanethiol
and bromoethylacet_~t_e. been prepared from 2,5-dimethylthiophene.1°
Chloromethyiationusing standard procedures "-Is
gave 3-chloromethyl-2,5-dimethyithiopbene as the
major product. Condensation of this with thiogly-
cofic acid and subsequent cycfisationof the inter-
mediate acid (14) afforded the new system 1,3-
dlmethyl-2,5-dithiaindan-7-one (8).
Hydrolysis of the resultant ethyl l-(2'-thienyl)-2-
thia-4-butanoate gave the thienylthio acid, the acid
chloride of which underwent cycfisation to give 6.
This represented the first report on synthesis of
dithiaindanones.
Employing a different approach, 6 was prepared
Reduction of dithiaindanones. The keto com-
pounds (6, 7 and 8) were smoothly reduced bY LAH
or NaBH4 to the corresponding alcohols, 4-hy-
droxy- 1,6-dithiaindane (lb'), 7-hydroxy- 1,5-dithia-
aPresent address: Department of Chemistry, Uni-
versity ofCalifornia, Berkeley, California 94720 USA.
TET. Voa. 29. lqo. 13--~
1829

1830
I. ALAM and G. THYAGARAJAN
indane (16) and 7-hydroxy-l,3-dimethyl-2,5-dithia-
indane (17). The IR and NMR spectral data of
these products were consistent with their structure
(Experimental). The NaBH4 reduction of 6 and 7
to 15 and 16 respectively has been reported re-
cently,z
Synthesis of dithiaindenes. The hydroxydithia-
indanes were dehydrated using a variety of de-
hydrating agents such as p-toluenesulphonic acid,
p-toluenesulphonyl chloride,14,15 basic alumina16
and phosphorus pentoxide in dry benzene. Thus,
4-hydroxy- 1,6-dithiaindane (15) and 7-hydroxy- 1,3-
dimethyl-2,5-dithiaindane (17) gave the respective
dithiaindenes 3 and 5.
Dehydration of 7-hydroxy-1,5-dithiaindane (16)
under similar conditions gave a white crystalline
product which was different from the expected
dithiaindene (4). Elemental and spectral analysis
showed it to be a symmetrical ether and this com-
pound has been assigned structure 18, 7,7'-bis(1,5-
dithiaindanyl)ether.
O
R
R
R
CH3
11
12
13
OH
CHs
15
OH
CH3 OH
17
16
O
18
1
2
EXPERIMENTAL
All m.ps, taken in capillary tubes are uncorrected. IR
spectra were conducted on a Perkin-Elmer model 221
spectrometer equipped with NaCl optics. NMR spectra
were recorded on a Varian A-60A spectrometer. Chemi-
cal shifts are in 8 values relative to internal TMS. TLC
experiments were done on silica gel G plates.
2-Chloromethylthiophene ~e (b.p. 73-74°/11 nun, 41%
yield), 3-bromomethylthiophene' (b.p. 75-78°/1 ram, 45%
yield) and 2,5-dimethylthiophene~ (b.p. 136°, 87% yield)
were prepared as described in the literature.
H
3
C
~
s
CH3
3
4
5
3-Chloromethyl-2,5-dimethylthiophene. A mixture of
2,5-dimethylthiophene (10 g) and conc. HC1 (50 ml) was
cooled in an ice bath. A rapid stream of HCI was passed
through this mixture with stirring while formalin (14 ml)
was added dropwise during 1 hr. The temp was main-
tained below --5° throughout the addition, after which the
mixture was diluted with water and extracted with ben-
zene. The extract was washed with water, dried over
MgSO4 and concentrated. The residue was distilled under
reduced pressure to give 3-chloromethyl-2,5-dimethyl-
thiophene (5.2g) b.p. 96-115°/13 mm (lit, h.p. 96-115/
13 ram).
6
O
7
8
COOH
I
6
~ - ~ C H ~ C I
Preparation of thienylthioacids (only a typical experiment
is reported here)
Method A. Thioglycollic acid (0.25 mole) was dissolved
in 2N NaOH (150ml) and cooled to 0". A soln of 2-
chloromethylthiophene (0.25mole) in acetone (50 ml) was
added dropwise during 3 hr with stirring. The mixture
was stirred for 24 hr at room temp, then diluted with
water and shaken with CH2C12 (or chloroform) to remove
any unreacted chloromethylthiophene. The acLueous soin
was acidified with 1:1 HCI and extracted with chloro-
form. Evaporation (crystallisation) of the dried chloro-
,CH2SCH2COOH
R
R'
10: R = R'
=
H
> 7
1 4 : R = R ' = C H 3
>8

Dithiaindenes
1831
form extract and distillation gave pure l(2'-thienyl)-2-
thiabutyric acid, b.p. 206°/15 nun, in 80 percent yield.
Method B. To a cooled and stirred soin of thioglycollic
acid (0.25 mole) and triethylamine (0.25 mole) in dry benz-
ene (150ml) was added dropwise during 2hr at 0-5°, a
sohi of 2-chloromethyithiophene (0.25 mole) in dry benz-
ene (50 ml). The mixture was left overnight at room temp.
The Et3NHC1 was filtered and the filtrate was extracted
with NaHCO8 aq. The alkaline sohi was acidified and
extracted with chloroform. Concentration of the dried
chloroform extract and distillation under reducedpressure
afforded the product, l(2'-Thienyl)-2-thiabutyric acid (9)
b.p. 206°/17mm (Lit, b.p. 204/112mm) was obtained in
75-80% yield. (Found: C, 44.69, S, 34.00, H, 4.23.
C~HsO2Se requires C, 44.69, S, 34-04, H, 4.29%); IR
(film): 3065, 3030, 1665, 1300, 1275, 1285 cm-1; NMR
(CCLO: 8 3.05, s, 2H(-S-CH2-COOH), 4-00, s, 2H-
(-CH~-S-), 7.00, m, 3H (aromatic), 11.8, s, 1H-(-COOH)
ppm.
1,3-Dimethyl-2,5-dithiaindan-7-one (g), m.p. 68° (from
benzene-light petroleum), yield 4 0 % (Found: C, 54.50,
S, 32-20, H, 5-03, C9HIoOS2 requires: C, 54-54, S, 32.32,
H, 5.09%); IR (KBr): 1665 cm-I (C==O), N M R (CCID:
8 2-3, s, 3H(C_Hs), 2.66, s, 3H(C_Ha), 3.2, s, 2H(-SC_H2-
CO), 3-59, s, 2H(-CH2-S) ppm.
Reduction of dithiaindanones with lithium aluminium
hydride
A soln of the dithiaindanon¢ (0.2 mole) in THF (100 mi)
was added dropwise to LAH (0.15mole) slurried in THF
(250 ml). The mixture was stirred and gently refluxed for
4 hr. After cooling in ice, the excess reducingagent was
decomposed by the careful addition of 40% KOH aq
(35 mi) and filtered. The ppt was washed with ether. The
combined THF-ether soln was dried and concentrated
leaving the crude product which was purified over a silica
gel column using chloroform-fight petroleum as eluent.
Reduction with sodium borohydride
Similarly prepared employing either method were:
The reduction was carried out in a 2-necked flask equip-
ped with a reflux condenser and N2 gas inlet. The dithia-
indanone (0.2 mole) and NaBH4 (0.08 mole) were mixed
in 50% aq EtOH and refluxed under N2 for 4 hr. The mix-
ture was then poured into 15% NaCI aq (50 mi) and ex-
tracted with methylene chloride. The extract was washed
with dil HCI and water and dried. Evaporation of the
solvent gave the crude product which was purified over a
silica gel column using chloroform.
l(3'-Thienyl)-2-thia-butyric acid (10) from 3-bromo-
methylthiophene and thioglycolic acid, b.p. 201/14ram
(Lit, 200/14 mm), yield 70% (Found: C, 44-64, S, 34.00,
H, 4.25. C:HsO~S2 requires: C, 44-69, S, 34.04, H, 4.29%);
IR (film): 3085, 3030, 1665, 1550, 1400, 1285, 1175 cm-1,
NMR (CC14):
8 3.03, s, 2H(SCH_2 COOH), 3.85, s,
2H(-C_H2S-), 7.18, m, 3H (aromatic), 11.9, s, 1H(COO_H)
ppm.
l(2',5'-Dimethyl-3'-thienyl)-2-thia-butyric
acid (14)
Thus were prepared:
from 3-chloromethyl-2,5-dimethyithiophene and thio-
glycofic acid. The product was isolated by crystallisation,
m.p. 170°, yield 55% (Found: C, 50.10, S, 29.60, H, 5-62.
C9HI~O2S2 requires: C, 50.00, S, 29.62, H, 5.60%); IR
(KBr): 1685 cm-~ (C~---O). NMR (CCI4): 8 3.0, s, 2H-
(-SCI:[2COOH), 3.65, s, 2H(-CH2-S-), 3.33, s, 6H-
(2'-CH3 and 5'-CH3), 6.58, s, 1H (aromatic), 11.6, s,
IH(COO_H) ppm.
4-Hydroxy-l,6-dithiaindane (15), b.p. 123/0.3 mm (Lit.
b.p. 123/0.3 ram), yield 75%. (Found: C, 48.85, S, 37"16,
H, 4.65, C7H8OS2 requires: C, 48.80, S, 37-23, H, 4-68%);
IR (film): 3335, 2900, 1405, 1190, 1030, 775cm-1;
NMR (CDC13): 8 3.66, s, 2H(-C_H2-S-), 2.75, _s, 2H-
(-S-C_H2-), 4.16, t, 1H(> C_H), 3-81, s, 1H(O_H), 6.99, q,
2H (aromatic) ppm.
7-Hydroxy-l,5-dithiaindane (16), b.p. 115-117/0.2 mm
(Lit. b.p. 116/0.2 mm), yield 60% (Found: C, 48.79, S,
37-19, H, 4.69. C7HsOS2 requires: C, 48.80, S, 37.23, H,
4-68%); IR (film): 3375, 2905, 1405, 1185, 1050, 940
cm-l; NMR (CCL0:8 2.85, s, 2H(-S-CH_2-), 3.53, s,
2H(-CH~-S-), 3.65, s, 1H(OH_), 4.75, t, 1H(>C_H-),
6-85, q, 2H (aromatic) ppm.
Cyclodehydration of thineylthioacids
General procedure. The thienylthioacid (1 part) was
dissolved in dry benzene (12-15 parts by weight) and
mixed with P205 (3-5 parts). The mixture was refluxed
for 4-6 hr, cooled, and the benzene layer decanted. The
solid mass was decomposed with ice and extracted sev-
eral times with hot benzene. The combined benzene ex-
tract was washed with NaHCO3 aq, then with water,
dried (Na2SO4) and evaporated. The crude product was
purified by chromatography and crystallisation.
7-Hydroxy- 1,5-dimethyl-2,5-dithiaindane
(17), b.p.
121-5-122/0-5 mm, yield 50%. (Found: C, 54.01, S, 32.20,
H, 6.01. CgHnOS2 requires: C, 53-99, S, 31.96, H, 6-04%);
IR (film): 3380, 2908, 1400, 1216, 1130, 1025, 775 cm-~;
NMR (CC14): 8 2.20, s, 3H(-CH_3), 2.33, s, 3H(-CH3),
2.7, d, 2H(-S-CH2-), 3.36, s, 2H(-CH2-S), 4-58, t,
1H(>CH), 3-13, s, 1H(OH_) ppm.
Alternatively, the thienylthioacid (1 part) was mixed
with 15-17 times its weight of polyphosphoric acid and
heated on a steam bath for 5 hr. The dark mixture was
cooled and poured over crushed ice. Extraction with
chloroform, washing with NaHCO~ aq and water, and
drying gave the crude product which was purified over a dithiaindane (one part) and benzene (50 ml) were refluxed
silica gel column, Thus prepared were:
1,6-Dithiaindan-4-one (6), b.p. 168-69/16 nun (Lit, b.p.
168°/16mm), yield 40%. (Found: C, 49-4, S, 37.60, H,
3.50. C7H6OS2 requires: C, 49.42, S, 37.64, H, 3.56%); silica gel afforded the pure compound.
Dehydration of hydroxy dithiaindanes
Method A. Woelm basic alumina (5 parts), the hydroxy
with stirring for 4 hr. The mixture was then cooled, ill-
tered and evaporated underreduced pressure. Distillation
or column chromatography of the crude product over
IR (film): 1670cm-t (C==O); NMR (CC14): 8 3.38, s,
2H(-S-CH~-CO), 3.96, s, 2H(-CH2-S-), 7-21, q, 2H
(aromatic) ppm.
1,5-Dithiaindan-7-one (7), m.p. 66° (from benzene-
light petroleum), yield 48% (Lit. m.p. 67°). (Found: C,
49.40, S, 37.61, H, 3.50. CTHeOS~ requires: C, 49.42, S,
37-64, H, 3.56%); IR (KBr): 1650cm-1 (C~-------O); NMR
(CDCI~): 8 3-45, s, 2H(-SC_H2-S-), 7.25, q, 2H (arom-
atic) ppm.
Method B. The hydroxydithialndane was heated with a
small amount of p-toluenesulfonic acid or tosyl chloride
in dry benzene for 1-3 hr. After cooling, the organic
layer was decanted and washed with NaHCO3 aq and
water to remove acidic impurities. The dried benzene
layer was evaporated leaving the product which was puri-
fied by distillation and column chromatography.
1,6-Dithiaindene (3), b.p. 125-26/0.2mm, yield 65%
(Found: C, 54.40, S, 41.50, H, 3-92. C~HoS2 requires:

I. ALAM and G. THYGARAJAN
1832
8p. Casniant and D. Casniant, Bull. Soc. Chim. Fr, 7,
1534 (1964).
C, 54.44, S, 41-53, H, 3.96~); IR (film): 2915, 2880, 1660,
1420, 1175, 775 and 745 cm-x, NMR (CC14): 8 3.96, s,
2H(-CH2-S), 6.92, q, 2H (vinyfic), 6.48, q, 2H (aromatic)
ppm.
7,7'-Bis(1,5-dithiaindanyl)ether (18), m.p. 152 (from
benzene), yield 65%. (Found: C, 51.52, S, 39.12, H, 4.35.
CI+Ha4OS4 requires: C, 51.54, S, 39.24, H, 4.33%); IR
(KBr): 2900, 1420, 1310, 1050, 840 and 715 cm-l; NMR
(CDCIs): 8 3-13, m, 4H(-CHv-S-)2, 3.6, m, 4H(-S-CI-I~,
-S.CH~-), 5.08, m, 2H(>CI-I-, >CH-), 7.02, q, 4H
(aromatic) ppm.
1,3-Dimethyl-2,5-dithiaindene (5), b.p. 132/0.5mm,
yield 85%. (Found: C, 59.32, S, 35.15, H, 5.52. C~-ImS2
requires: C, 59-33, S, 35.13, H, 5.53%); IR (film): 3030,
2908, 1672, 1585, 1545, 1440, 1218, 795 and 730cm-~;
NMR (CC14): 8 2-23, s, 3H(CH3), 2-25, s, 3H(C_Hs),
3.65, s, 2H(CH~S-), 6.25, q, 2H(vinylic) ppm.
4p. Casniant and D. Casniant, Ibid. 7, 2591 (1967).
SE. Campaigne and B. F. Tullar, Org. Synthesis 33, 96
(1953).
eN. Steinkopf and I. Poulsson, Liebigs Ann. 536, 128
(1938).
7D. MacDowell and T. Patrick, J. Org. Chem. 32, 1266
(1967).
8L. Harrison and T. Cantrell, Tetrahedron Letters 45,
4477 (1967).
90. Dann and W. Dal~mling, Chem. Ber. 87, 373 (!954).
1°(3. Jean and F. Nord, J. Org. Chem. 20, 1363 (1955).
UR. Gaerther and G. Tonkyn, J. Am. Chem. Soc. 73,
5878 (1951).
riM. P. Casniant and D. Cagniant, Bull. Soc. Chim. Fr,
713 (1953).
mYa. L. Goldfarb and M. S. Kondakova, Bull. Acad.
Sci. USSR, (Engl), 486 (1956).
~+N. Gunnel, Acta. Chem. Scand. 16, 1329 (1962)+
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17K. B. Wiberg and H. F. Meshane, Org. Synthesis 3, 197.
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