Lewis acid-mediated domino reaction of 3-bromomethylthiophenes with arenes/heteroarenes

Article abstract of DOI:10.1080/00397911.2011.554063

Lewis acid-mediated domino reaction of 3-bromomethylthiophenes with various types of arenes and heteroarenes is reported.

Full text of DOI:10.1080/00397911.2011.554063

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Lewis Acid–Mediated Domino Reaction of
3-Bromomethylthiophenes with Arenes/
Heteroarenes
Vasudevan Dhayalan a & Arasambattu K. Mohanakrishnan a
a Department of Organic Chemistry , University of Madras, Guindy
Campus , Chennai , India
Accepted author version posted online: 19 Dec 2011.Published
online: 26 Mar 2012.
To cite this article: Vasudevan Dhayalan & Arasambattu K. Mohanakrishnan (2012) Lewis
Acid–Mediated Domino Reaction of 3-Bromomethylthiophenes with Arenes/Heteroarenes, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:14, 2149-2160, DOI: 10.1080/00397911.2011.554063
To link to this article: http://dx.doi.org/10.1080/00397911.2011.554063
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Synthetic Communications1, 42: 2149–2160, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.554063
LEWIS ACID–MEDIATED DOMINO REACTION
OF 3-BROMOMETHYLTHIOPHENES WITH
ARENES/HETEROARENES
Vasudevan Dhayalan and Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras, Guindy Campus,
Chennai, India
GRAPHICAL ABSTRACT
Abstract Lewis acid–mediated domino reaction of 3-bromomethylthiophenes with various
types of arenes and heteroarenes is reported.
Keywords Annulation; arylation; benzo[b]thiophene; domino reaction
INTRODUCTION
The electronic properties of p-conjugated oligothiophenes led to many
important applications in molecular electronics.[1] Specifically, benz-annulation at
the 2,3-position of thiophene rings leads to an important class of building blocks
for the construction of optoelectronic materials.[1d,2] Design and synthesis of
p-conjugated heteroacenes are being widely investigated because of their potential
applications in organic thin-film transistors (OTFTs).[3] The densely packed
solid-state structures of the planar p-conjugated heteroacenes are highly beneficial
for efficient charge transport. Recently, a large number of thiophene-based heteroa-
cenes have been explored because the heteroatom influences electronic as well as
solid-state structures, that which them more attractive candidates for organic
devices.[1d,4] Gao and coworkers reported conjugated ladder-type heteroacenes con-
taining thiophene and pyrrole units as high-performance semiconducting materials.[5]
Wex and coworkers described the synthesis of dibenzothiophene analogs[6] via
lithiation followed by formylation and subsequent reductive cyclization. Tedjamulia
et al. established the synthesis of naphtho[b]thiophenes involving Friedel–Crafts
phthaloylation of thiophene followed by successive reductions, oxidation, and
Received November 11, 2010.
Address correspondence to Arasambattu K. Mohanakrishnan, Department of Organic Chemistry,
University of Madras, Guindy Campus, Chennai 600 025, India. E-mail: mohan_67@hotmail.com
2149

2150
V. DHAYALAN AND A. K. MOHANAKRISHNAN
polyphosphoric acid (PPA)–mediated intramolecular cyclization reactions.[7]
Takahashi et al. outlined a facile synthesis of thiophene-fused acenes,[8] via CuCl-
mediated coupling between tetraiodothiophene and a zirconium-based organometal-
lic reagent. The synthesis of dibenzothiophenes[9] involving intermolecular
Diels–Alder reaction of bis-pyrrole with dimethyl acetylenedicarboxylate (DMAD)
followed by an oxidative cleavage of the amine unit has been achieved by Sha and
coworkers. Pouchain et al.[10] reported the synthesis of a thermally stable hybrid
acene-thiophene organic semiconductor via Stille coupling between 2-bromoin-
deno[1,2-b]thiophene and 5,50-bis(tributylstannyl)-2,20-bithiophene.
RESULTS AND DISCUSSION
During our recent study of the synthesis of annulated heterocycles,[11] we
observed that an interaction of malonylidene unit–tethered 3-bromomethylthiophene
1
[12] with veratrole or bithiophene in the presence of 2 eq. ZnBr2 in 1,2-dichloroethane
(DCE) at reflux afforded the annulated heterocycle 2a or 2b in 48%, and 44% yields,
respectively (Scheme 1).
To further understand the synthetic utility of this domino reaction protocol, the
vinylidene-tethered 3-bromomethylthiophenes 5a–c were prepared, adopting pub-
lished procedure,[12] via condensation of the 3-methylthiophene-2-carboxaldehyde 3
with active methylene compounds such as N,N-dimethylbarbituric acid, Meldrum’s
acid, or malononitrile followed by allylic bromination using N-bromosuccinimide
(NBS). See Scheme 2.
As expected, the interaction of bromo compounds 1=5a–c with arenes as well
as heteroarnes at room temperature followed by subsequent thermolysis at 80 ꢀC
and column chromatographic purification furnished annulated heterocycles 2a–f in
40–67% yields (Scheme 3).
Details such as the nature of arenes=heteroarenes employed, the annulation
products obtained, and their yields are summarized in Table 1. As expected, the
annulation of bromo compound 1/5a with veratrole in the presence of 1 eq. ZnBr2
in 1,2-DCE at room temperature followed by reflux afforded the annulated product
2a in 53% and 62% yields, respectively (entry 1).
The smooth annulation of bromo compounds 1/5a–c could be successfully per-
formed with bithiophene to afford the annulation product 2b in 50%, 67%, 45%, and
43% yields (entry 2). The interaction of bromo compound 1/5a with 1-methylnaph-
thalene in the presence of 1 eq. ZnBr2 at room temperature followed by reflux led
to the synthesis of the naphth-annulated benzo[b]thiophene 2c in 46% and 62% yields
(entry 3). Under identical conditions, the interaction of bromo compound 1/5a/5c
Scheme 1. Domino reaction of bromo compound 1 with veratrole=bithiophene.

DOMINO REACTION OF 3-BROMOMETHYLTHIOPHENES
2151
Scheme 2. Preparation of 3-bromomethylthiophenes 5a–c.
with naphthalene afforded the phenanthro[2,3-b]thiophene 2d in 47–60% yields
(entry 4). A similar annulation of bromo compound 1/5a–c with most of the heteroar-
enes using 1 eq. ZnBr2 was problematic and always led to the formation of a complex
mixture. However, upon interaction of bromo compound 1/5a–c with a heteroarene,
namely benzo[b]furan in the presence of 0.2 eq. of ZnBr2 led to the synthesis of the
mixed heterocycle 2e in 46–63% yields (entry 5). Similarly, the annulation of bromo
compound 1/5a/5c could be successfully performed with 2-methylthiophene to furnish
heterocycle 2f in 40–55% yields (entry 6). Surprisingly, the interaction of bromo
compound 1 or 5a–c with 1-hexylindole in the presence of 0.2 eq. of ZnBr2 failed to
produce the expected heterocycle 2g; instead, only a complex mixture was obtained.
The domino reaction of bromo compound 1 with benzo[b]thiophene in the
presence of 0.2 eq. ZnBr2 in 1,2-DCE at room temperature followed by reflux led
1
to the generation of an inseparable mixture (1:0.4 based on H NMR integration)
of annulated heterocycles 6 and 7 in 54% yield (Scheme 4).
To understand mechanism of the annulation reaction, as a representative case
the domino reaction of the bromo compound 1 in the presence of anhydrous K2CO3
was planned. Accordingly, the reaction of bromo compound 1 with arenes (anisole,
veratrole, and p-xylene) using 2 eq. of ZnBr2 in the presence of anhydrous K2CO3 at
room temperature for 12 h afforded the arylated products 8a–c in 70–80% yields.
However, under identical conditions, the reaction of bromo compound 1 with
heteroarenes (substituted thiophenes and benzo[b]furan) led to the synthesis of the
heterocycles 2b, 2e, and 2f in 54–68% yields (Scheme 5).
Next, thermolysis of the intermediate veratrylmethylthiophene 8b in the pres-
ence of 0.5 eq. of ZnBr2 in 1,2-DCE at reflux furnished the heterocycle 2a in 80%
Scheme 3. Domino reaction bromo compounds 1/5a–c with arenes=heteroarenes.

2152
V. DHAYALAN AND A. K. MOHANAKRISHNAN
Table 1. Domino reaction of bromo compounds 1=5a–c with arenes=heteroarenes
Entry
Substrate
Arene=heteroarene
Product
Yield (%)a
1
2
1=5a
53=62
1=5a–c
1=5a
50=67=45=43
3
4
46=62
1=5a=5c
48=60=47
5
6
1=5a–c
50=63=52=46
40=55=42
1=5a=5c
7
1=5a–c
0
aIsolated yield after column chromatography.
yield. However, under identical conditions, the thermolysis of either anisylmethythio-
phene 8a or p-xylenylmethylthiophene 8c failed to produce the expected annulated
heterocycle 9 or 10; instead only the starting material was recovered unchanged
(Scheme 6).
Now, it is clear that the nucleophilic character of the aryl=heteroaryl unit plays a
crucial role in the formation of annulated heterocycles. Obviously, in the case of 8a or
8c, the moderately electron-rich nature of the aryl unit does not favor the subsequent
Friedel–Crafts-type intramolecular cyclization reaction. Hence, the mechanism of
the domino reaction involves the initial arylation followed by ZnBr2-mediated
intramolecular cyclization of 11 to produce intermediate 13. Aromatization of the

DOMINO REACTION OF 3-BROMOMETHYLTHIOPHENES
2153
Scheme 4. Domino reaction of bromo compound 1 with benzo[b]thiophene.
intermediate 13 via elimination of diethyl malonate led to the formation of annulated
heterocycles 2a–f (Scheme 7).
In conclusion, a facile ZnBr2-mediated domino reaction of 3-bromomethylthio-
phenes containing the vinylidene unit has been successfully performed with arenes
as well as heteroarenes to afford the respective aryl=heteroaryl annulated benzo[b]
Scheme 5. The reaction of bromo compound 1 with arenes=heteroarenes.
Scheme 6. Thermolysis of arylmethylthiophenes 8a–c.

2154
V. DHAYALAN AND A. K. MOHANAKRISHNAN
Scheme 7. Mechanism of domino reaction.
thiophene analogs. A suitable mechanism for the formation of annulated heterocycles
via arylation followed by intramolecular cyclization and subsequent aromatization
reactions has been proposed.
EXPERIMENTAL
All melting points were uncorrected. Reagents were purchased from commer-
cial sources and used as received without purification. Solvents were dried by stan-
dard procedures. Column chromatography was carried out on silica gel (grade 60,
mesh size 230–400, Merck). Infrared (IR) spectra were recorded on a Shimadzu Four-
1
ier transform (FT)–IR 8300 instrument. H and 13CNMR spectra were recorded in
CDCl3 using tetramethylsilane (TMS) as an internal standard on a Bruker-300 spec-
trometer. Chemical shift values were quoted in parts per million (ppm), and coupling
constants were quoted in hertz (Hz). Chemical shift multiplicities were reported as s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Mass spectra were recorded on a
Jeol DX 303 HF spectrometer. Elemental analyses were carried out on Perkin-Elmer
series II 2400 (IIT Madras) equipment.
Diethyl-2-((3-(bromomethyl)thiophen-2-yl)methylene)malonate (1)[12]
Allylic bromination of diethyl-2-((3-(methyl)thiophen-2-yl)methylene)malonate
(2.68 g, 10 mmol) using NBS (2.12 g, 12 mmol) and azobisisobutyronitrile (AIBN,
0.05 g) in dry carbon tetrachloride (50 mL) using the published procedure[13] afforded
bromo compound 1 as a yellow solid. Yield: 2.96 g (85%). Mp: 59 ꢀC (lit.[13] 58–59 ꢀC).
n
max (KBr): 1725, 1710, 1610 cmꢁ1. dH (CDCl3, 300 MHz): 7.94 (s, 1H, Ar-H), 7.46 (d,
J ¼ 5.1 Hz, 1H, Ar-H), 7.11 (d, J ¼ 5.1 Hz, 1H, Ar-H), 4.59 (s, 2H, -CH2), 4.39 (q,
J ¼ 7.2 Hz, 2H, -OCH2), 4.31 (q, J ¼ 7.2 Hz, 2H, -OCH2), 1.39–1.31 (m, 6H, -CH3).
dC (CDCl3, 75 MHz): 166.1, 164.1, 142.6, 132.7, 130.6, 130.4, 129.7, 123.7, 62.0,
61.8, 25.1, 14.1, 13.9.

DOMINO REACTION OF 3-BROMOMETHYLTHIOPHENES
2155
1,3-Dimethyl-5-((3-methylthiophen-2-yl)methylene)pyrimidine-2,4,6-
(1H, 3H, 5H)-trione (4a)
N,N-Dimethylbarbituric acid (4.08 g, 26.13 mmol), piperidine (0.3 mL), and
acetic acid (0.2 mL) were added to a solution of 3-methyl-2-thiophenecarboxaldehyde
3 (3.0 g, 23.77 mmol) in dry benzene (80 mL), and refluxed in a 250 mL RB flask fitted
with a Dean–Stark apparatus for 12 h. Removal of solvent followed by crystallization
from methanol afforded the compound 4a as a yellow solid. Yield: 5.0 g (80%). Mp:
142–144 ꢀC. nmax (KBr): 1722, 1656, 1552 cmꢁ1. dH (CDCl3, 300 MHz): 8.79 (s, 1H,
Ar-H), 7.83 (d, J ¼ 4.8 Hz, 1H, Ar-H), 7.04 (d, J ¼ 5.1 Hz, 1H, Ar-H), 3.32 (s, 6H,
-NCH3), 2.52 (s, 3H, -CH3). dC (CDCl3, 75 MHz): 163.0, 161.9, 154.5, 151.4, 145.9,
140.4, 131.6, 131.2, 109.1, 28.9, 28.1, 15.8.
1,3-Dimethyl-5-((3-bromomethylthiophen-2-yl)methylene)
pyrimidine-2,4,6(1H, 3H, 5H)-trione (5a)
AIBN (0.05 g) and finely powdered NBS (0.70 g, 3.93 mmol) were added to a
solution of compound 4a (1.0 g, 3.78 mmol) in dry carbon tetrachloride (20 mL),
refluxed for 2 h, and cooled to room temperature. The floated succinimide was filtered
off and washed with carbon tetrachloride (10 mL). The combined filtrate was concen-
trated in vacuo to afford the bromo compound 5a as a yellow solid. Yield: 1.1 g (85%).
Mp: 204–206 ꢀC. nmax (KBr): 1721, 1654, 1557 cmꢁ1. dH (CDCl3, 300 MHz): 8.84 (s,
1H, Ar-H), 7.85 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.25 (d, J ¼ 5.1 Hz, 1H, Ar-H), 4.70 (s, 2H,
-CH2), 3.36 (s, 3H, -NCH3) 3.35 (s, 3H, -NCH3). dC (CDCl3, 75 MHz): 162.6, 161.7,
151.2, 150.8, 143.9, 139.7, 132.8, 130.5, 111.0, 29.0, 28.2, 23.4.
2,2-Dimethyl-5-((3-methylthiophen-2-yl)methylene)-1,3-dioxane-4,
6-dione (4b)
Condensation of 3-methylthiophene-2-carboxaldehyde 3 (3.0 g, 23.77 mmol)
with Meldrum’s acid (3.76 g, 26.08 mmol) in the presence of piperidine (0.3 mL), and
acetic acid (0.2 mL) following the procedure described for 4a, furnished compound
4b as a yellow solid. Yield: 5 g (84%). Mp: 134–136 ꢀC. nmax (KBr): 1707, 1551 cmꢁ1
.
dH (CDCl3, 300 MHz): 8.70 (s, 1H, Ar-H), 7.85 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.03 (d,
J ¼ 4.2 Hz, 1H, Ar-H), 2.51 (s, 3H, -CH3), 1.70 (s, 6H, -CH3). dC (CDCl3, 75 MHz):
164.0, 161.3, 154.5, 146.2, 140.4, 131.2, 131.0, 105.4, 104.4, 27.5, 15.7.
5-((3-Bromomethylthiophen-2-yl)methylene)-2,2-dimethyl-1,3-
dioxane-4,6-dione (5b)
Allylic bromination of compound 4b (2.0 g, 7.93 mmol) using NBS (1.55 g,
8.70 mmol) in the presence of AIBN (0.05 g) in dry CCl4 (30 mL), following the pro-
cedure described for 5a, furnished the bromo compound 5b as a yellow solid. Yield:
2.30 g (88%). Mp: 174–176 ꢀC. nmax (KBr): 1706, 1566 cmꢁ1. dH (CDCl3, 300 MHz):
8.70 (s, 1H, Ar-H), 7.87 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.24 (d, J ¼ 5.1 Hz, 1H, Ar-H),
4.66 (s, 2H, -CH2), 1.71 (s, 6H, -CH3). dC (CDCl3, 75 MHz): 163.3, 161.0, 150.9,
144.0, 139.8, 132.3, 130.4, 107.7, 104.8, 27.6, 23.1.

2156
V. DHAYALAN AND A. K. MOHANAKRISHNAN
2-((3-Methylthiophen-2-yl)methylene)malononitrile (4c)
Condensation of 3-methylthiophene-2-carboxaldehyde 3 (3.0 g, 23.77 mmol)
with malononitrile (1.64 g, 24.88 mmol) in the presence of piperidine (0.3 mL) and
acetic acid (0.2 mL) following the procedure described for 4a, furnished compound
4c as a yellow solid. Yield: 3.56 g (86%). Mp: 196 ꢀC. nmax (KBr): 2215, 1569 cmꢁ1
.
dH (CDCl3, 300 MHz): 7.93 (s, 1H, Ar-H), 7.78 (d, J ¼ 4.8 Hz, 1H, Ar-H), 7.07 (d,
J ¼ 5.1 Hz, 1H, Ar-H), 2.46 (s, 3H, -CH3). dC (CDCl3, 75 MHz): 150.3, 149.1,
135.8, 131.2, 130.7, 114.5, 113.2, 14.8.
2-((3-Bromomethylthiophen-2-yl)methylene)malononitrile (5c)
Allylic bromination of compound 4c (1.0 g, 5.74 mmol) using NBS (1.12 g,
6.29 mmol) in the presence of AIBN (0.05 g) in dry CCl4 (15 mL), following the pro-
cedure described for 5a, furnished the bromo compound 5c as a yellow solid. Yield:
1.30 g (90%). Mp: 104–106 ꢀC. nmax (KBr): 2215, 1568 cmꢁ1. dH (CDCl3, 300 MHz):
8.06 (s, 1H, Ar-H), 7.82 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.27 (d, J ¼ 4.8 Hz, 1H, Ar-H),
4.58 (s, 2H, -CH2). dC (CDCl3, 75 MHz): 149.2, 147.7, 135.8, 132.1, 131.2, 130.5,
114.4, 113.2, 29.6.
ZnBr2-Mediated Domino Reaction of Bromo Compounds 1/5a–c
with Arenes/Heteroarenes
Anhydrous ZnBr2 (3 mmol), and arene=heteroarene (3.6 mmol) were added to a
solution of bromo compound 1/5a–c (3 mmol) in dry dichloroethane (DCE, 15 mL).
The mixiture was then stirred at room temperature for 8 h and then refluxed for 1 h
under N2 atmosphere. The solvent was removed, and the residue was quenched with
icewater (50 mL) containing 1 mL of concentrated HCl, extracted with chloroform
(3 ꢂ 10 mL), and dried (Na2SO4). Removal of solvent followed by flash column chro-
matographic purification (n-hexane=ethyl acetate) led to the isolation of annulated
product.
6,7-Dimethoxynaphtho[2,3-b]thiophene (2a). Mp: 210–212 ꢀC (lit.[11]
210 ꢀC). dH (CDCl3, 300 MHz): 8.18 (s, 1H, Ar-H), 8.14 (s, 1H, Ar-H), 7.41 (d,
J ¼ 5.4 Hz, 1H, Ar-H), 7.35 (d, J ¼ 5.4 Hz, 1H, Ar-H), 7.19 (s, 1H, Ar-H), 7.14 (s,
1H, Ar-H), 4.03 (s, 6H, -OCH3). dC (CDCl3, 75 MHz): 149.6, 149.3, 137.6, 136.7,
127.4, 127.1, 126.6, 123.3, 120.1, 118.8, 105.8, 105.0, 55.9, 55.8. MS (m=z) %: 244
(Mþ, 63%). Anal. calcd. for C14H12O2S: C, 68.83; H, 4.95; S, 13.12%. Found: C,
68.99; H, 4.73; S, 13.39%.
5-(2’-Thienyl)thieno[3,2-d]benzothiophene (2b). Mp: 252–254 ꢀC (lit.[11]
252 ꢀC). dH (CDCl3, 300 MHz): 8.45 (s, 2H, Ar-H), 7.80 (d, J ¼ 5.4 Hz, 1H, Ar-H),
7.68 (s, 1H, Ar-H), 7.65 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.48 (d, J ¼ 4.8 Hz, 2H, Ar-H),
7.17 (t, J ¼ 4.5 Hz, 1H, Ar-H). dC (CDCl3, 75 MHz): 137.8, 137.5, 137.1, 136.6,
136.4, 135.5, 128.5, 128.2, 126.9, 125.7, 123.2, 118.9, 116.9, 116.7. MS (m=z) %:
272 (Mþ, 73%). Anal. calcd. for C14H8S3: C, 61.73; H, 2.96; S, 35.31%. Found: C,
61.53; H, 2.80; S, 35.53%.

DOMINO REACTION OF 3-BROMOMETHYLTHIOPHENES
2157
5-Methyl phenanthro[2,3-b]thiophene (2c). Mp: 146 ꢀC. dH (CDCl3,
300 MHz): 9.02 (s, 1H, Ar-H), 8.72 (d, J ¼ 7.8 Hz, 1H, Ar-H), 8.19 (s, 1H, Ar-H),
7.96 (d, J ¼ 7.5 Hz, 1H, Ar-H), 7.58–7.44 (m, 5H, Ar-H), 2.65 (s, 3H,-CH3). dC
(CDCl3, 75 MHz): 138.6, 138.5, 132.2, 132.0, 130.7, 129.7, 127.3, 126.5, 126.4,
126.3, 124.7, 124.1, 122.8, 120.6, 117.1, 20.1. MS (m=z) %: 248 (Mþ, 43%). Anal.
Calcd. for C17H12S: C, 82.22; H, 4.87; S, 12.91%. Found: C, 82.02; H, 4.99; S, 12.73%.
Phenanthro[2,3-b]thiophene (2d). Mp: 148 ꢀC. dH (CDCl3, 300 MHz): 9.13
(s, 1H, Ar-H), 8.76 (d, J ¼ 8.1 Hz, 1H, Ar-H), 8.36 (s, 1H, Ar-H), 7.87 (d, J ¼ 7.5 Hz,
1H, Ar-H), 7.77–7.54 (m, 6H, Ar-H). dC (CDCl3, 75 MHz): 139.1, 138.6, 131.8,
130.6, 129.6, 128.6, 127.9, 127.8, 126.8, 126.7, 126.6, 126.5, 124.1, 122,6, 121.5,
117.2. MS (m=z) %: 234 (Mþ, 73%). Anal. calcd. for C16H10S: C, 82.01; H, 4.30;
S, 13.68%. Found: C, 82.20; H, 4.13; S, 13.89%.
Thieno[3,2-b]dibenzofuran (2e). Mp 166 ꢀC. dH (CDCl3, 300 MHz): 8.32 (s,
1H, Ar-H), 7.92 (t, J ¼ 4.8 Hz, 1H, Ar-H), 7.86 (s, 1H, Ar-H), 7.50–7.34 (m, 4H,
Ar-H), 7.28 (t, J ¼ 7.5 Hz, 1H, Ar-H). dC (CDCl3, 75 MHz): 157.1, 154.6, 139.3,
134.4, 127.7, 127.5, 123.8, 123.1, 122.7, 120.7, 113.8, 111.6, 105.1, 104.5. MS (m=z)
%: 224 (Mþ, 43%). Anal. calcd. for C14H8OS: C, 74.97; H, 3.60; S, 14.30%. Found:
C, 74.80; H, 3.85; S, 14.45%.
2-Methylthieno[3,2-b]benzothiophene (2f). Mp: 168–170 ꢀC. dH (CDCl3,
300 MHz): 8.09 (s, 1H, Ar-H), 8.05 (s, 1H, Ar-H), 7.33 (d, J ¼ 5.7 Hz, 1H, Ar-H),
7.24 (d, J ¼ 5.7 Hz, 1H, Ar-H), 6.91 (s, 1H, Ar-H), 2.53 (s, 3H, -CH3). dC (CDCl3,
75 MHz): 141.6, 138.4, 137.2, 136.9, 136.7, 126.2, 123.0, 120.6, 116.4, 115.6, 16.5.
MS (EI) m=z (%): 204 (Mþ, 33%). Anal. calcd. for C11H8S2: C, 64.66; H, 3.95; S,
31.39. Found: C, 64.50; H, 3.79; S, 31.58.
Annulation of Bromo Compound 1 with Benzo[b]thiophene
Domino reaction of bromo compound 1 (1 g, 2.88 mmol) with benzo[b]thio-
phene (0.46 g, 3.42 mmol) in dry DCE (15 mL) in the presence of anhydrous ZnBr2
(0.13 g, 0.57 mmol) was performed at room temperature for 8 h followed by refluxing
for 0.5 h. The usual workup, followed by flash column chromatographic purification
(n-hexane=ethyl acetate 99:1), led to the isolation of an inseparable mixture of
isomeric thieno[3,2-b]dibenzothiophene 6 and thieno[2,3-b]dibenzothiophene 7 as a
colorless solid. Yield: 372 mg (54%). Mp: 142–144 ꢀC. dH (CDCl3, 300 MHz): 8.64
(s, Ar-H), 8.58 (s, Ar-H), 8.31 (s, Ar-H), 8.26 (s, Ar-H), 8.23–8.19 (m, Ar-H),
7.87–7.84 (m, Ar-H), 7.55–7.39 (m, Ar-H). dC (CDCl3, 75 MHz): 139.9, 139.5,
139.2, 137.4, 137.0, 136.6, 136.5, 135.3, 134.9, 133.5, 133.4, 127.7, 127.0, 126.9,
126.2, 124.4, 123.8, 123.1, 122.9, 121.5, 121.4, 117.0, 115.9, 115.8, 115.1.
ZnBr2-Mediated Arylation of Bromo Compound 1 with Arenes
Anhydrous ZnBr2 (6.0 mmol), K2CO3 (6.0 mmol) and arene (6.0 mmol) were
added To a solution of bromo compound 1 (3.0 mmol), in dry DCE (15 mL). The
reaction mixture was stirred at room temperature for 12 h under N2 atmosphere.
The solvent was removed, and the residue was quenched with icewater (50 mL),

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V. DHAYALAN AND A. K. MOHANAKRISHNAN
extracted with chloroform (3 ꢂ 10 mL), and dried (Na2SO4). Removal of solvent
followed by flash column chromatographic purification (n-hexane=ethyl acetate)
led to the isolation of arylated product 8a–c.
Diethyl-2-((3-(4-methoxybenzyl)thiophen-2-yl)methylene)malonate (8a).
Yield: 0.82 g (76%). Mp: 82–84 ꢀC. nmax (KBr): 1722, 1610 cmꢁ1. dH (CDCl3,
300 MHz): 8.19 (s, 1H, Ar-H), 7.36 (d, J ¼ 5.1 Hz, 1H, Ar-H), 7.18 (d, J ¼ 7.8 Hz,
1H, Ar-H), 7.06 (d, J ¼ 7.8 Hz, 1H, Ar-H), 6.89–6.83 (m, 3H, Ar-H), 4.40 (q,
J ¼ 6.9 Hz, 2H, -OCH2), 4.29 (q, J ¼ 6.9 Hz, 2H, -OCH2), 4.06 (s, 2H, -CH2), 3.82
(s, 3H, -OCH3), 1.40–1.29 (m, 6H, CH3). dC (CDCl3, 75 MHz): 166.7, 164.6,
157.1, 147.6, 133.0, 130.2, 129.9, 129.8, 127.9, 120.6, 119.1, 110.4, 61.8, 61.4, 55.2,
25.2, 14.2, 13.9. MS (EI) m/z (%): 374 (Mþ, 77%). Anal. calcd. for C20H22O5S: C,
64.15; H, 5.92; S, 8.56. Found: C, 64.37; H, 5.78; S, 8.79.
Diethyl-2-((3-(3,4-dimethoxybenzyl)thiophen-2-yl)methylene)malonate
(8b). Thick liquid; yield: 0.93 g (80%). nmax (KBr): 1706, 1609 cmꢁ1. dH (CDCl3,
300 MHz): 8.03 (s, 1H, Ar-H), 7.42 (d, J ¼ 5.1 Hz, 1H, Ar-H), 6.85–6.77 (m, 2H,
Ar-H), 6.68 (d, J ¼ 6.3 Hz, 2H, Ar-H), 4.41 (q, J ¼ 7.2 Hz, 2H, -OCH2), 4.29 (q,
J ¼ 7.2 Hz, 2H, -OCH2), 4.05 (s, 2H, -CH2), 3.85 (s, 3H, -OCH3), 3.83 (s, 3H,
-OCH3), 1.40-1.29 (m, 6H, CH3). dC (CDCl3, 75 MHz): 166.6, 164.5, 149.1, 147.8,
147.6, 132.4, 132.0, 130.4, 130.2, 130.1, 122.1, 120.6, 111.8, 111.3, 61.9, 61.6, 55.9,
55.8, 34.3, 14.2, 13.9. MS (EI) m=z (%): 404 (Mþ, 89%). Anal. calcd. for
C21H24O6S: C, 62.36; H, 5.98; S, 7.93. Found: C, 62.21; H, 5.80; S, 7.73.
Diethyl-2-((3-(2,5-dimethylbenzyl)thiophen-2-yl)methylene)malonate
(8c). Thick liquid; yield: 0.75 g (70%). nmax (KBr): 1719, 1603 cmꢁ1. dH (CDCl3,
300 MHz): 8.01 (s, 1H, Ar-H), 7.37 (d, J ¼ 4.8 Hz, 1H, Ar-H), 7.06–6.81 (m, 3H,
Ar-H), 6.67 (d, J ¼ 5.1 Hz, 1H, Ar-H), 4.41 (q, J ¼ 6.9 Hz, 2H, -OCH2), 4.30 (q,
J ¼ 6.9 Hz, 2H, -OCH2), 4.01 (s, 2H, -CH2), 2.26 (s, 3H, -CH3), 2.21 (s, 3H,
-CH3), 1.40–1.29 (m, 6H, CH3). dC (CDCl3, 75 MHz): 166.6, 164.5, 147.3, 137.4,
135.7, 133.1, 132.3, 130.3, 130.2, 130.1, 130.0 (2C), 127.5, 122.0, 62.0, 61.5, 32.5,
21.0, 19.2, 14.2, 13.9. MS (EI) m=z (%): 372 (Mþ, 90%). Anal. calcd. for
C21H24O4S: C, 67.72; H, 6.49; S, 8.61. Found: C, 67.56; H, 6.67; S, 8.48.
ZnBr2-Mediated Domino Reaction of Bromo Compound 1 with
Heteroarenes in the Presence of K2CO3
Anhydrous ZnBr2 (6.0 mmol), K2CO3 (6.0 mmol), and heteroarene (6.0 mmol)
were added to a solution of bromo compound 1 (3.0 mmol) in dry DCE (15 mL). The
reaction mixture was stirred at room temperature for 8 h under N2 atmosphere. The
solvent was removed, and the residue was quenched with icewater (50 mL), extracted
with chloroform (3 ꢂ 10 mL), and dried (Na2SO4). Removal of solvent followed
by flash column chromatographic purification (n-hexane=ethyl acetate) led to the
isolation of annulated product 2b, 2e, and 2f.
ACKNOWLEDGMENTS
We thank the University Grants Commission, New Delhi (32-194=2006=SR),
for financial support. V. D. thanks the Council for Scientific and Industrial

DOMINO REACTION OF 3-BROMOMETHYLTHIOPHENES
2159
Research, New Delhi, for a senior research fellowship. We thank the Department of
Science and Technology (DST-FIST) for a 300-MHz NMR facility.
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