Condensed thiophenes and selenophenes: Thionyl chloride and selenium oxychloride as sulfur and selenium transfer reagents

Article abstract of DOI:10.1021/jo010858m

3,4-Cyanomethyl substituted thiophenes reacted with thionyl chloride in the presence of base to give dicyano substituted thieno(3,4-c)thiophenes. The use of selenium oxychloride furnished the corresponding cyano substituted seleno(3,4-c)thiophene. 1,2-Phenylenediacetonitriles gave the corresponding cyano substituted benzo(c)thiophenes and benzo(c)selenenophenes, respectively, upon reaction with thionyl chloride and selenium oxychloride in the presence of base.

Full text of DOI:10.1021/jo010858m

J . Org. Chem. 2002, 67, 2453-2458
2453
Con d en sed Th iop h en es a n d Selen op h en es: Th ion yl Ch lor id e a n d
Selen iu m Oxych lor id e a s Su lfu r a n d Selen iu m Tr a n sfer Rea gen ts
Ramiya R. Amaresh, M. V. Lakshmikantham, J effrey W. Baldwin, Michael. P. Cava,*
Robert M. Metzger, and Robin D. Rogers
Chemistry Department, University of Alabama, Box 870336, Tuscaloosa, Alabama 35487-0336
mcava@bama.ua.edu
Received August 22, 2001
3,4-Cyanomethyl substituted thiophenes reacted with thionyl chloride in the presence of base to
give dicyano substituted thieno(3,4-c)thiophenes. The use of selenium oxychloride furnished the
corresponding cyano substituted seleno(3,4-c)thiophene. 1,2-Phenylenediacetonitriles gave the
corresponding cyano substituted benzo(c)thiophenes and benzo(c)selenenophenes, respectively, upon
reaction with thionyl chloride and selenium oxychloride in the presence of base.
Sch em e 1
In tr od u ction
Thieno[3,4-c]thiophene (1) is unique among the iso-
meric thienothiophenes (2-4) in that it cannot be rep-
resented by a classical Kekule` structure without invoking
the presence of a tetracovalent sulfur.
Sch em e 2
Whereas compounds 2-4 have been known for long,
only during the last 32 years have a few stable deriva-
tives of 1 been made.1 The first such derivative was the
tetraphenyl derivative 6, which was obtained by an acid-
catalyzed Pummerer dehydration of the corresponding
3,4-dihydrotetraphenylthieno[3,4-c]thiophene sulfoxide 52
(Scheme 1).
Whereas the tetracovalent sulfur structure is written
for convenience, photoelectron spectroscopic studies and
theoretical calculations during the 1970s indicated that
the structure of 1 is best represented as a stable singlet
1,3-diradical.3 Using the sulfoxide dehydration approach
(both acid and base- catalyzed), various analogues were
made or generated.4 The presence of four bulky groups
on the rings appeared to confer stability, and it was
generally assumed that bulky substituents were neces-
sary for isolable derivatives.
Sch em e 3
2,3-bis(methylthio)-1-chlorocyclopropenium salt 7. The
latter was converted to the 2,3-bis(methylthio)cyclopro-
pene-1-thione (8) via several steps. (Scheme 2).5
A
number of 2,3-di-(S)-alkylcyclopropene-1-thiones were
made by this method. These underwent a novel dimer-
ization reaction in the presence of tributyl or triphen-
ylphosphine to give an S-alkyl-substituted thieno[3,4-
c]thiophene.6 Indeed, the mechanism of this reaction has
only recently been elucidated.7
Reaction of methyl (bismethylthio)sulfonium hexachlo-
roantimonate with tetrachlorocyclopropene yielded the
(1) (a) Cava, M. P.; Lakshmikantham, M. V. Acc. Chem. Res. 1975,
8, 139. (b) Cava, M. P.; Lakshmikantham, M. V. In Comprehensive
Heterocyclic Chemistry; Katrizky, A. R., Rees, C. W., Eds.; Pergamon
Press: Oxford, 1984; Vol.4, Chapter 3-18. (c) Krutosikova, A. In
Comprehensive Heterocyclic Chemistry II; Katrizky, A. R., Rees, C. W.,
Scriven E. F. V., Eds.; Elsevier Sci.: Oxford, 1996; Vol. 7, Chapter 7.01.
(2) Cava, M. P.; Husbands, G. E. M. J . Am. Chem. Soc. 1968, 91,
3952.
In 1992, the first example of a purely electronically
stabilized derivative 9 was synthesized by a 1,4-Finkel-
stein elimination (Scheme 3).8b
(3) Mu¨ller, C.; Schweig, A.; Cava, M. P.; Lakshmikantham, M. V.
J . Am. Chem. Soc. 1976, 98, 7187.
(4) (a) Cava, M. P.; Pollack, N. M. J . Am. Chem. Soc. 1967, 89, 3639.
(b) Cava, M. P.; Pollack, N. M.; Dieterle, G. A. J . Am. Chem. Soc. 1973,
95, 2558. (c) Cava, M. P.; Behforouz, M.; Husbands, G. E. M.;
Srinivasan, M. J . Am. Chem. Soc. 1973, 95, 2651. (d) Ishii, A.;
Nakayama, J .; Kazami, J . Ida.; Nakamura, T.; Hoshino, M. J . Org.
Chem. 1991, 56, 78.
(5) Weiss, R.; Schlierf, C.; Schloter. K. J . Am. Chem. Soc. 1976, 98,
4668.
(6) Yoneda, S.; Ozaki, T.; Inoue, T.; Sugimoto, A.; Yangi, K.; Minobe,
M. J . Am. Chem. Soc. 1985, 107, 5801.
(7) Matsumura, N.; Tanaka, H.; Yagyu, Y.; Mizuno, K.; Inoue, H.;
Takada, K.; Yasui, M.; Iwasaki, F. J . Org. Chem. 1998, 63, 163.
10.1021/jo010858m CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/20/2002

2454 J . Org. Chem., Vol. 67, No. 8, 2002
Amaresh et al.
Sch em e 4
Sch em e 5
Å from each other, much larger than van der Waals
intermolecular distances in aromatic crystals. A molec-
ular orbital calculation, using a molecular mechanics
program followed by the PM3 semiempirical all-valence
electron calculation, with geometry optimization (CACHE
programming package), yielded a molecular geometry
close to that shown by the X-ray structure determination,
except that the two carbomethoxy rings have the CdO
bond facing the nitrile carbon atoms for both substitu-
ents. The calculated enthalpy of formation is 4.548 kcal/
mol, the HOMO energy is -9.082 eV, and the LUMO
energy is -3.183 eV. The net atomic charges are also
shown in Figure 1.
In contrast to the minute yields from the tandem
Pummerer-cyanation reaction, the in situ Pummerer-
carbomethoxylation of dicyanodihydrothieno[3,4-c]thio-
phene sulfoxide 11 using NaHMDSA/methyl chlorofor-
mate afforded 10 in 10% yield. The use of ethyl
chloroformate led to the dicarbethoxydicyano derivatives
12 in 15% yield (Scheme 4). The tetraester 14 was made
by this procedure in 10% yield, starting from the corre-
sponding diester sulfoxide 13. (Scheme 4)
In view of the extremely poor yields of 10, it was
decided that the nitrile functionality should be introduced
first, followed by sulfur transfer. The known dibromide8a
15 was converted in good yield to the dinitrile 16 by
reaction with buffered potassium or sodium cyanide at
pH 9-10. Reaction of the 2,5-dicarbomethoxy-3,4-dicya-
nomethylthiophene 16 with sulfur dichloride in the
presence of base gave 10 in varying low yields (2-10%).
In contrast, the use of sulfur monochloride under the
same conditions gave 20-40% yields of 10 reproducibly.
However, when thionyl chloride was used, the yields of
product 10 increased dramatically to 74-84% (Scheme
5). To our knowledge, this is the first example of the
reaction of thionyl chloride with a carbanion acting as a
S-transfer agent.
F igu r e 1. Bond lengths (Å) from X-ray diffraction analysis
and PM3 calculated partial charges (underlined) on atoms in
the molecule.
Resu lts
Recently, we have attempted to synthesize derivatives
of 1 bearing only electron-withdrawing groups, employing
different strategies. One of our target molecules, viz.
dicyanodicarbomethoxythieno[3,4-c]thiophene9 (10), was
first made in miniscule yield via a tandem Pummerer-
cyanation route. The structure of 10 was confirmed by
single-crystal X-ray diffraction analysis, as shown in the
Supporting Information.
The molecule deviates slightly from 2m symmetry,
probably caused by the inequivalent geometries of the
carbomethoxy substituents, presumably dictated by pack-
ing considerations. Figure 1 shows the significant inter-
atomic bond distances (in Å; the estimated standard
deviations are less than (0.003 Å). The thieno[3,4-c]-
thiophene ring is planar: the deviations from the least-
squares plane of its atoms are less than 0.008 Å for five
out of six carbon atoms, but 0.011 Å for C4, 0.008 Å for
S1, and 0.013 Å for S2. This least-squares plane is
inclined by 6.85° from the molecular stacking axis, c. The
C-C bond distances within the thieno[3,4-c] rings are
typical aromatic bond distances; the C-S bond distances
(1.703-1.692 Å) are slightly shorter than in isomeric
thienothiophenes (1.72 and 1.74 Å) or in thiophene itself
(1.714 Å). The carbomethoxy substituents prevent a
dense π-to-π stacking; the least-squares planes of adja-
cent molecules stacked almost along the c axis are 5.25
(8) (a) Wynberg, H.; Zwanenburg, B. J . Org. Chem. 1964, 29, 1919.
(b) Beye, N.; Cava, M. P. J . Org. Chem. 1994, 59, 2223.
(9) A preliminary account of this work was published: Amaresh,
R. R.; Lakshmikantham, M. V.; Geng, R.; Cava, M. P. Tetrahedron
Lett. 2000, 41, 8843.
Mech a n ism of th e Rea ction . A comparison of the
reactions of SCl2, S2Cl2, and SOCl2 as S-transfer agents

Condensed Thiophenes and Selenophenes
J . Org. Chem., Vol. 67, No. 8, 2002 2455
Sch em e 6
Sch em e 10
Sch em e 7
Sch em e 11
Sch em e 8
have not detected the Cl2SdS structure.11,12 On the other
hand, the intermediacy of thiosulfoxides has been in-
voked to explain some reactions.13
The possible extension of the use of thionyl chloride
as a S-transfer agent for the synthesis of benzo[c]-
thiophene derivatives was then investigated. The starting
materials for our studies were 1,2-phenylendiacetonitrile
(20) and 1-chloro-4-bromo-2,3-bis(cyanomethyl)benzene
(25). Diacetonitrile 25 was synthesized from the known
4-bromo-2,3-dimethylacetanlide14 as shown in Scheme 10.
Thus acetanilide 21 was converted to the amino
derivative 22 by acid hydrolysis. Amine 22 was converted
into the chloro derivative 23 by diazotization followed by
the Sandmeyer reaction to give 64% yield of 1-chloro-4-
bromo-2,3-dimethylbenzene. The dimethyl derivative 23
was brominated with NBS to give a 64% yield of dibro-
mide 24. Reaction of dibromide 24 with buffered NaCN
gave dinitrile 25.
Indeed, both 1,2-phenylenediacetonitrile 20 and 4-bro-
mo-1-chloro-2,3-bis(cyanomethyl)benzene 25 yielded the
corresponding 1,3-dicyanobenzo[c]thiophenes 26 and 27
in 37% and 50% yields, respectively (Scheme 11), upon
generation of their respective anions and reaction with
thionyl chloride.
The investigation was then extended to selenium
oxychloride as a selenium transfer reagent. Dinitriles 16,
20, and 25 reacted with SeOCl2 in the presence of base
to give the corresponding selenium analogues 28-30
(Scheme 12). Apparently the reactions follow an analo-
gous pathway via selenoxide intermediates.
Sch em e 9
is in order. It is interesting to note that the product 10
could be isolated in the reaction of the bisnitrile 16 with
SCl2 in the presence of base, since the expected product
would be the dihydro compound 17. (Scheme 6).
Since 17 must be more acidic than 16 and could readily
form an anion/dianion, it is conceivable that oxidation of
16 may have produced 10. However, since we were
unable to improve the yield and most of the starting
material was recovered, we were led to conclude that 10
was really forming from the sulfur monochloride con-
taminant in the SCl2. Indeed, the reaction was carried
out with S2Cl2 in higher yield and the product formation
was rationalized as follows (Scheme 7).
In the case of thionyl chloride as the sulfur transfer
reagent, an intermediate sulfoxide18 must be involved,
which then suffers a spontaneous base-catalyzed Pum-
merer reaction to give 10 in high yield (Scheme 8).
It is intriguing to consider an alternate mechanism for
the S2Cl2 reaction. One can invoke the formation of a
transient thiosulfoxide 19, which could arise by the
reaction of the anion/dianion of 16 with the branched
chain tautomer of S2Cl2, viz Cl2SdS: thiosulfoxide 19
could then undergo an unprecedented base-catalyzed
thio-Pummerer reaction. (Scheme 9) While Cl2SdS is not
known, F2SdS is a well-characterized compound.10 Al-
though some calculations on the two forms of S2Cl2
support its existence, photoelectron spectroscopic studies
Rea ction s of Dica r bom eth oxyd icya n oth ien o[3,4-
c]th iop h en e (10). In contrast to other known derivatives
of thieno[3,4-c]thiophene, 10 does not undergo Diels-
Alder reactions with electron-poor or electron-rich olefins.
(10) (a) Seel, F. Adv. Inorg. Chem. Radiochem. 1974, 86, 297. (b)
Kuczkowski, R. L. J . Am. Chem. Soc. 1963, 85, 3047. For PES studies
see (c) Wagner, G.; Bock, H.; Budenz, R.; Seel, F. Chem. Ber. 1973,
106, 1285.
(11) Harpp, D. N. In Perspectives in the Organic Chemistry of Sulfur;
Zwanenburg, B., Klunder, A. J . H., Eds.; Elsevier: Amsterdam, 1987;
pp 1-22.
(12) Solouki, R.; Bock, H. Inorg. Chem. 1977, 16, 665.
(13) Ho¨fle, G.; Baldwin, J . E. J . Am. Chem. Soc. 1971, 93, 6307.
(14) Kleinschmidt, E. G.; Braeuiger, H. Pharmazie 1969, 24(2), 87.

2456 J . Org. Chem., Vol. 67, No. 8, 2002
Amaresh et al.
benzene (65 mL) was added a solution of sodium periodate
(3.84 g, 17.9 mmol) in a water (14 mL). After refluxing for 3
h, the solution was concentrated and extracted with methylene
chloride to give 11 in 82% yield. This crude product was used
for the next step without further purification: mp 185 °C (dec);
1H NMR (CDCl3, 360 MHz) δ 4.26 (d, 2H, J ) 16.92 Hz), 4.07
(d, 2H, J ) 16.92 Hz).
Sch em e 12
1,3-Dica r b om e t h oxy-4,6-d icya n ot h ie n o[3,4-c]t h io-
p h en e (10). Meth od I. To a stirred, ice-cold solution of
dicyanide 16 (0.15 g, 0.53 mmol) in dichloromethane (3 mL)
was added slowly a solution of sulfur monochloride (0.14 g,
1.07 mmol) in dichloromethane (3 mL). After a few minutes,
triethylamine (0.16 g, 1.61 mmol) was added to the above
solution. The mixture was stirred overnight. Evaporation of
the solvent and column chromatography (50:50, hexane:
dichloromethane) gave 10 as a red solid in 44% yield.
Meth od II. To a stirred, ice cold solution of dicyanide 16
(0.15 g, 0.53 mmol) in THF (3 mL) was added slowly a solution
of sulfur dichloride (0.11 g, 1.07 mmol) in THF (3 mL).
Triethylamine (0.16 g, 1.61 mmol) was added to the above
solution. The mixture was stirred overnight. Evaporation of
the solvent and column chromatography of the residue gave
10 as a red solid in 10% yield (best yield).
Sch em e 13
Meth od III. To a stirred, ice-cold solution of dicyanide 16
(1.0 g, 3.59 mmol) in dichloromethane (25 mL) was added
slowly a solution of thionyl chloride (0.85 g, 7.19 mmol) in
dichloromethane (15 mL). After a few minutes, triethylamine
(1.08 g, 10.7 mmol) was added to the above solution. Standard
workup gave 10 as a red solid in 74-84% yield.
While the lack of reaction with electron-poor double bonds
was not unexpected, absence of reaction with electron-
rich olefins such as norbornene was a surprise. Indeed,
a highly fluorescent solution of 10 is not quickly decol-
orized under ambient laboratory conditions. The decom-
position was extremely slow, as indicated by changes in
the UV-visible spectrum over a period of weeks.
The diester can be hydrolyzed readily at room temper-
ature by aqueous alkali in THF. The resulting aqueous
solution of the dianion of the diacid is highly fluorescent.
Acidification produced the diacid dinitrile 31 as a stable
deep red insoluble solid (Scheme 13).
Con clu sion . The utility of thionyl chloride as a
superior S-transfer agent for the synthesis of nonclassical
thienothiophenes and benzo[c]thiophenes has been dem-
onstrated. The use of selenium oxychloride produces the
analogous annelated selenophene derivatives, albeit in
lesser yield than in the case of thionyl chloride giving
thiophenes. The tandem Pummerer-alkoxycarbonylation
is superior to the tandem Pummerer-cyanation reaction
for the synthesis of 10 and its analogues.
Meth od IV. To a stirred solution of sulfoxide 11 (0.33 g,
1.5 mmol) in THF (25 mL) at -78 °C was added slowly sodium
bis(trimethylsilylamide) (2.4 mL, 6.0 mmol). After 1 h the
mixture was warmed to room temperature for 30 min. The
reaction mixture was recooled to -78 °C, and TMEDA (0.87
g, 7.5 mmol) and n-butyllithium (2.4 mL, 6.0 mmol) were
added. After 45 min, a solution of methyl chloroformate (0.56
g, 6.0 mmol) in THF (5 mL) was added. After 4 h, the mixture
was quenched with saturated ammonium chloride solution,
extracted with dichloromethane, washed with water and
sodium chloride solution, and dried. Chromatotron separation
1
of the residue gave 10 in 10% yield: mp 226.4-226.6 °C; H
NMR (CDCl3, 360 MHz) δ 4.06 (s, 6H); 13C NMR (CDCl3, 90
MHz) δ 160.37, 144.88, 122.29, 118.82, 100.40, 52.82; MS m/z
(relative intensity, %) 306 (M+, 97), 275 (100), 248 (39), 217
(21), 205 (119), 190 (21), 118 (31); IR (KBr) ν 2213, 1715 cm-1
;
UV-vis (CH2Cl2) λmax nm (log ꢀ) 476 (3.86), 317 (3.70), 250
(3.81), 222 (3.88); fluorescence λexcitation 476 nm, λemision 525 nm.
Anal. Calcd for C12H6N2O4S2: C, 47.05; H, 1.97; N, 9.15; S,
20.94. Found: C, 46.64; H, 2.13; N, 9.03; S, 20.82.
Exp er im en ta l Section
1,3-Dica r b et h oxy-4,5-d icya n ot h ien o[3,4-c]t h iop h en e
(12). The dicarbethoxy analogue 12 was prepared in 15% yield
in an analogous fashion using sulfoxide 11 and ethyl chloro-
Gen er a l Com m en ts. Melting points are uncorrected. THF
was freshly distilled from sodium-benzophenone.
1
2,5-Dica r bom eth oxy-3,4-d icya n om eth ylth iop h en e 16.
formate: mp 161.8-162.2 °C; H NMR (CDCl3, 360 MHz) δ
8a
To a stirred solution of dibromide 15 (6.0 g, 15.4 mmol) in
4.55 (q, 4H), 1.47 (t, 6H); 13C NMR (CDCl3, 90 MHz) δ 160.06,
144.94, 122.54, 111.98, 100.29, 62.83, 14.33; MS m/z (relative
intensity, %) 334 (M+, 50), 306 (16), 234 (100), 190 (36), 145
(11); IR (KBr) ν 2210, 1719 cm-1; UV-vis (CH2Cl2) λmax nm
(log ꢀ) 281 (3.97), 481 (3.53); fluorescence λexcitation481 nm,
acetonitrile (135 mL) was added a solution of buffered sodium
cyanide (9.09 g, 185.5 mmol) in water (30 mL) (the pH of this
was adjusted to 9-10 by the slow addition of glacial acetic
acid). After adding more acetonitrile (150 mL), the heteroge-
neous solution was refluxed for about 15-20 min. The solvent
was evaporated and ice water was added. The resulting brown
solid was filtered and washed with water to give the crude
dicyanide in 84% yield. Crystallization from methylene chlo-
ride gave the pure product: mp 167.8-168.2 °C; 1H NMR
(CDCl3, 360 MHz) δ 4.36 (s, 4H), 3.96 (s, 6H); 13C NMR (CDCl3,
90 MHz) δ 161.17, 135.58, 133.90, 115.40, 53.07, 15.38; MS
m/z (relative intensity, %) 278 (M+, 37), 263 (35), 246 (99), 236
λ
541 nm. Anal. Calcd for C14H10N2O4S2. C, 50.29; H,
emission
3.01; N, 8.38; S, 19.18. Found: C, 50.13; H, 3.14; N, 8.14; S,
18.97.
1,3,4,6-Tetr a ca r bom eth oxyth ien o[3,4-c]th iop h en e (14).
To a stirred solution of sulfoxide 134b (0.41 g, 1.5 mmol) in
THF (20 mL) at -78 °C was added slowly sodium bis-
(trimethylsilylamide) (2.4 mL, 6.0 mmol). After 1 h the mixture
was warmed to room temperature for 30 min. The reaction
mixture was recooled to -78 °C, and TMEDA (0.87 g, 7.5
mmol) and n-butyllithium (2.4 mL, 6.0 mmol) were added.
After 45 min, a solution of methyl chloroformate (0.56 g, 6.0
mmol) in THF (5 mL) was added. After 4 h, the mixture was
quenched with saturated ammonium chloride solution, ex-
tracted with dichlormethane, washed with water and sodium
chloride solution, and dried. Chromatotron separation gave 14
in 10% yield: mp 171.1-172.6 °C; 1H NMR (CDCl3, 360 MHz)
δ 3.96 (s, 6H), 3.86 (s, 3H), 3.76 (s, 3H); 13C NMR (CDCl3, 90
(31), 220 (26), 181 (39), 136 (100); IR (KBr) ν 2260, 1715 cm-1
.
Anal. Calcd for C12H10N2O4S: C, 51.79; H, 3.62; N, 10.07; S,
11.52. Found: C, 51.95; H, 3.54; N, 9.93; S, 11.40.
CAUTION: sodium cyanide is extremely toxic and reaction
mixtures should be properly disposed according to safety
guidelines
4,6-Dicya n o-1H,3H-th ien o[3,4-c]th iop h en e Su lfoxid e
(11). To a stirred solution of 1,3-dihydro-4,6-dicyanothieno-
[3,4-c]thiophene8b (2.3 g, 11.7 mmol) in methanol (65 mL) and

Condensed Thiophenes and Selenophenes
J . Org. Chem., Vol. 67, No. 8, 2002 2457
MHz) δ 172.40, 166.14, 149.95, 144.06, 128.53, 120.60, 48.19,
52.68, 52.80, 53.01; MS m/z (relative intensity, %) 372 (M+,
100), 341 (97), 314 (69), 283 (72), 256 (32), 225 (25), 184 (28),
154 (32), 126 (21); IR (KBr) 1729, 1715 ν cm-1; UV-vis (CH2-
Cl2) λmax nm (log ꢀ) 482 (3.98), 319 (4.07); fluorescence λexcitation
481 nm, λ emission 541 nm; HRMS for C14H12O8S2 371.9973, found
371.9965.
4-Br om o-2,3-d im eth yla n ilin e (22). A mixture of acet-
anilide 2114 (29.6 g, 122 mmol) in ethanol (125 mL) containing
51 mL of concentrated HCl was refluxed till the disappearance
of starting material. The reaction mixture was poured into ice
water and was neutralized with a 2 M solution of sodium
hydroxide. The light brown solid that separated was filtered
and washed with water to give 22 in 90% yield: mp 214 °C
(dec); 1H NMR (CDCl3, 360 MHz) δ 7.16 (d, 1H, J ) 8.64 Hz),
6.39 (d, 1H, J ) 8.64 Hz), 3.47 (brs, 2H), 2.08 (s, 3H); 13C NMR
(CDCl3, 90 MHz) δ 143.70, 136.02, 129.89, 122.60, 114.33,
114.22, 20.0, 14.11; MS m/z (relative intensity, %) 334 (M+,
50), 306 (16), 234 (100), 190 (36), 145 (11).
1-Ch lor o-4-br om o-2,3-d im eth ylben zen e (23). A solution
of aniline 22 (19.0 g, 95 mmol) dissolved in concentrated HCl
(21.8 mL), concentrated H2SO4 (11 mL), and glacial HOAc (33
mL) was cooled to -5 °C. A solution of sodium nitrite (6.55 g,
95 mmol) in water (28.5 mL) was added slowly, so that the
temperature of the reaction mixture did not exceed -3 °C.
After 15 min of stirring and filtration, and the filtrate was
added to a mixture of CuCN (8.50 g, 95 mmol) in concentrated
HCl (19 mL) and refluxed for 1 h. The reaction mixture was
poured into ice water containing ammonia, extracted with
methylene chloride, and washed with 10% HCl solution, water,
and brine. The extract was dried over sodium sulfate, and
column chromatography of the residue with hexane as eluent
gave 23 in 65% yield: 1H NMR (CDCl3, 360 MHz) δ 7.30 (d,
1H, J ) 8.64 Hz), 7.05 (d, 1H, J ) 8.64 Hz), 2.38 (s, 3H), 2.35
(s, 3H); 13C NMR (CDCl3, 90 MHz) δ 137.85, 136.19, 133.69,
130.50, 127.65, 123.34, 20.66, 17.77; MS m/z (relative intensity,
%) 219 (M+, 75), 221 (M+ + 2, 99.0), 223 (M+ + 4, 26.1), 183
(39.5), 139 (100), 102 (71.1).
1-Ch lor o-4-br om o-2,3-bis(br om om eth yl)ben zen e (24).
The dibromide 24 was obtained by the treatment of dimethyl
derivative 23 with NBS in a standard procedure and used
directly in the next step: mp 101.9-102.3 °C;1H NMR (CDCl3,
360 MHz) δ 7.58 (d, 1H, J ) 8.28 Hz), 7.51 (d, 1H, J ) 8.28
Hz), 4.78 (s, 2H),4.76 (s, 2H); 13C NMR (CDCl3, 90 MHz)
141.88, 140.60, 136.39, 133.53, 130.86, 115.85, 25.48, 24.50;
MS m/z (relative intensity, %) 377 (M+, 24.1), 379 (M + 2, 19.4),
381 (M + 4, 18.1), 297 (71.8), 218 (100), 183 (12.0), 137 (41.0),
109 (15.4).
p h en e (26). LDA solution was prepared at -78 °C by slow
addition of n-butyllithium (1.75 mL, 4.5 mmol) to a stirred
solution of diisopropylamine (0.45 g, 4.5 mmol) in THF (5 mL).
After 15 min, a solution of dicyanide 20 (0.23 g, 1.5 mmol) in
THF (5 mL) was added slowly, with continued stirring for 15
min. To this mixture, a solution of thionyl chloride (0.35 g,
3.0 mmol) in THF (3 mL) was added. The reaction mixture
was warmed to room temperature and stirred for 7-8 h. After
quenching with 10% HCl solution, standard workup and
column chromatography (80:20, hexane: dichloromethane)
gave 26 as a yellow solid in 37% yield. The analytical sample
was obtained by recrystallization from benzene: mp 183.1-
183.4 °C; 1H NMR (CDCl3, 360 MHz) δ 7.88 (2H, dd, J ) 2.88
Hz), 7.53 (2H, dd, J ) 3.24 Hz); 13C NMR (CDCl3, 90 MHz) δ
142.21, 129.04, 120.89, 112.25, 106.31; MS m/z (relative
intensity, %) 184 (M+, 100), 157 (16), 140 (10); IR (KBr) ν 2211
cm-1. Anal. Calcd for C10H4N2S2: C, 65.20; H, 2.19; N, 15.20;
S, 17.40. Found: C, 64.92; H, 2.20; N, 14.98; S, 17.35.
1,3-Dicya n oben zo[c]selen op h en e (29). The foregoing
general procedure was followed, using 20 (0.23 g, 1.5 mmol)
and selenium oxychloride (0.49 g, 3.0 mmol). Column chro-
matography (80:20, hexane:dichlormethane) gave 29 as a
yellow solid in 10% yield: mp 231.0-232.1 °C; 1H NMR
(CDCl3, 360 MHz) δ 7.78 (2H, dd, J ) 2.88 Hz), 7.53 (2H, dd,
J ) 3.24 Hz); 13C NMR (CDCl3, 90 MHz) δ 145.30, 128.69,
121.73, 114.36, 112.62; MS m/z (relative intensity, %) 232 (M+,
100), 152 (43); IR (KBr) ν 2203 cm-1. Anal. Calcd for C10H4N2-
SSe: C, 51.96; H, 1.74; N, 12.12. Found: C, 52.63; H, 1.83; N,
11.85.
4-Br om o-7-ch lor o-1,3-d icya n oben zo[c]th iop h en e (27).
The general procedure was followed, using dicyanide 25 (0.25
g, 1.0 mmol) and thionyl chloride (0.49 g, 3.0 mmol). After 5
h, workup and column chromatography (65:35, hexane:dichlor-
methane) gave 27 as a yellow solid in 50% yield. An analytical
sample was obtained by recrystallization from benzene: mp
1
270.5-271.0 °C; H NMR (CDCl3, 360 MHz) δ 7.60 (1H, d, J
) 7.92 Hz), 7.31 (1H, d, J ) 7.92 Hz); 13C NMR (CDCl3, 90
MHz) δ 139.46, 133.11, 129.22, 127.14, 114.11, 111.99, 111.89;
MS m/z (relative intensity, %) 297 (M+, 100), 217 (69), 182 (76),
149 (15); IR (KBr) ν 2211 cm-1. Anal. Calcd for C10H2-
BrClN2S: C, 40.36; H, 0.68; N, 9.41; S, 10.78. Found: C, 40.23;
H, 0.75; N, 9.24; S, 10.62.
4-Br om o-7-ch lor o-1,3-dicyan oben zo[c]selen oph en e (30).
The general procedure was followed, using dicyanide 25 (0.25
g, 1.0 mmol) and selenium oxychloride (0.33 g, 2.0 mmol). After
10 h, workup and column chromatography (50:50, hexane:
dichloromethane) yielded 30 as a reddish brown solid in 30%
yield. An analytical sample was obtained by recrystallization
from benzene: mp 324.0-325.0 °C; 1H NMR (C6D6, 360 MHz)
δ 6.48 (1H, d, J ) 7.92 Hz), 6.51 (1H, d, J ) 7.92 Hz); MS m/z
(relative intensity, %) 345 (M+, 16), 344 (100), 298 (64), 282
(25), 265 (38), 230 (40), 182 (25), 149 (32), 113 (56); IR (KBr)
ν 2208 cm-1. Anal. Calcd for C10H2BrClN2Se: C, 34.87; H, 0.59;
N, 8.13. Found: C, 34.70; H, 0.70; N, 8.04.
Diels-Ald er Rea ction of 1,3-Dica r bom eth oxy-4,6-d i-
cya n oth ien o[3,4-c]th iop h en e. The starting material (10)
was recovered from all attempted Diels-Alder reactions with
N-phenylmaleimide or norbornene, even after refluxing ben-
zene solutions for 3-4 days.
1-Ch lor o-4-br om o-2,3-b is(cya n om et h yl)b en zen e (25).
The above dibromide 24 was converted into dicyanide 25 in
95% yield as described for 16: mp 191.6 °C (recrystallized from
ethanol);1H NMR (CDCl3, 360 MHz) δ 7.63 (d, 1H, J ) 8.64
Hz), 7.38 (d, 1H, J ) 8.64 Hz), 4.08 (s, 2H), 4.05 (s, 2H); 13C
NMR (CDCl3, 90 MHz) δ 134.99, 134.49, 131.41, 131.16,
129.55, 124.29, 115.02, 114.96; MS m/z (relative intensity, %)
269 (M+, 46.3), 271 (M + 2, 14.07), 273 (M + 4, 3.3), 243 (100),
216 (8.0), 206 (8.7), 189 (14.0), 162 (28.8), 127 (29.5). Anal.
Calcd for C10H6BrClN2: C, 44.58; H, 2.24; N, 10.39. Found:
C, 44.45; H, 2.23; N, 10.39.
1,3-Dica r b om et h oxy-4,6-d icya n ot h ien o[3,4-c]selen o-
p h en e (28). To a stirred, ice-cold solution of dicyanide 16 (0.15
g, 0.53 mmol) in dichloromethane (3 mL) was added slowly a
solution of selenium oxychloride (0.17 g, 1.07 mmol) in dichlo-
romethane (3 mL). Triethylamine (0.16 g, 1.61 mmol) was
added to the above solution. The mixture was stirred over-
night. Evaporation of the solvent and column chromatography
(12:88, ethyl acetate:hexane) gave 28 as a rose-red solid in 10%
yield: mp 181.1-182.8 °C; 1H NMR (CDCl3, 360 MHz) δ 4.05
(s, 6H); 13C NMR (CDCl3, 90 MHz) δ 160.53, 148.01, 114.0,
107.52, 52.79; MS m/z (relative intensity, %) 353 (M+, 20), 352
(76), 334 (25), 333 (100), 303 (51), 282 (33), 268 (49), 251 (48),
236 (51), 171 (35), 118 (36); IR (KBr) ν 2212, 1716 cm-1; HRMS
for C12H6N2O4Se 353.921, found 353.921.
1,3-Dica r boxy-4,6-d icya n oth ien o[3,4-c]th iop h en e (31).
To a stirred solution of thieno[3,4-c]thiophene 10 (0.1 g, 0.32
mmol) in THF (14 mL) was added potassium hydroxide (0.065
g, 1.1 mmol) in water (5 mL) After 4 h, the red potassium salt
of the carboxylic acid was filtered. The mother liquor was
evaporated. The total crude salt was dissolved in 10 mL of
water and neutralized to pH 3-4 with 10% HCl solution, to
give the diacid as a red solid in quantitative yield.
Potassium salt of carboxylic acid 31: 13C NMR (D2O, 360
MHz) δ 170.33, 147.59, 130.21, 116.47, 101.32; IR (KBr) ν 3268,
2214, 1690 cm-1. Acid 31: mp 226.4-226.0 °C (dec); MS m/z
(relative intensity, %) 234 (M+ - CO2, 13), 217 (10), 190 (100),
146 (9), 118 (10); IR (KBr) ν 3447, 2212, 1687 cm-1
.
Gen er a l P r oced u r e for th e Syn th esis of Dicya n oben -
zo[c]th iop h en e Der iva tives. 1,3-Dicya n oben zo[c]th io-
X-r a y Cr ysta l Str u ctu r e of 10. The crystal structure was
determined by mounting an orange-red single crystal of 10

2458 J . Org. Chem., Vol. 67, No. 8, 2002
Amaresh et al.
under a stream of cold nitrogen gas (173 K) on a Siemens
SMART diffractometer equipped with a CCD area detector and
Mo KR X-radiation (λ ) 0.71073 Å). The compound crystallizes
in the monoclinic space group P21/c with latttice constants a
) 8.2844(5) Å, b ) 11.4189(7) Å, c ) 13.2859(8) Å, â )
101.300(2)°, V ) 1232.46 (13) Å3, Dcalc ) 1.651 g cm-3 for Z )
-4. A total of 2842 reflections were collected, corrected for
Lorentz and polarization effects, and empirically corrected for
absorption using simulated Ψ-scans from area detector data.
The crystal structure solution (by direct methods) and refine-
ment were carried out using the SHELXTL package of
computer programs. The final refinement, using data for which
F2 > 2σ(F2), had R (based on Fobs) ) 4.04%.
Ack n ow led gm en t. This work was supported by a
grant from the National Science Foundation (CHE
9910177). We thank Mr. Grant A. Broker for help with
the X-ray data.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
10-12, 14, 16, and 22-30; 13C NMR spectra of 10, 12, 14, 16,
22-29, and 31; ORTEP drawings of 10; and tables of crystal
structure and refinement data for 10, including observed and
calculated structure factors. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O010858M