AlCl3-Catalyzed Intermolecular Annulation of Thiol Derivatives and Alkynes by 1,2-Sulfur Migration: Construction of 6-Substituted Benzo[b]thiophenes

Article abstract of DOI:10.1002/ejoc.201700607

A method for the AlCl₃-catalyzed intermolecular oxidative annulation of N-(arylthio)phthalimide derivatives with alkynes has been developed. The annulation reaction occurs at room temperature and involves the oxidative cleavage of the S–N bond and 1,2-sulfur migration, which leads to the construction of diverse arrays of π-conjugated 6-substituted 2,3-diarylbenzo[b]thiophene derivatives.

Full text of DOI:10.1002/ejoc.201700607

A Journal of
Accepted Article
Title: AlCl3-Catalyzed Intermolecular Annulation of Thiol-Derivatives
and Alkynes via 1,2-S-Migration at Room Temperature:
Construction of 6-Substituted Benzo[b]thiophenes
Authors: Akhila Kumar Sahoo, E. Ramesh, and Tirumaleswararao
Guntreddi
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700607
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10.1002/ejoc.201700607
European Journal of Organic Chemistry
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AlCl3-Catalyzed Intermolecular Annulation of Thiol-Derivatives
and Alkynes via 1,2-S-Migration at Room Temperature:
Construction of 6-Substituted Benzo[b]thiophenes
E. Ramesh, Tirumaleswararao Guntreddi and Akhila K. Sahoo*
Dedicated to Prof. S. Chandrasekharan, IISc-Bangalore on the occasion of his 71st Birthday.
Abstract:
A
novel AlCl3-catalyzed intermolecular oxidative
annulation of N-arylthio phthalimide derivatives with alkynes is
showcased at room temperature. The annulation involves oxidative
cleavage of the SN bond and the occurrence of 1,2-S-migration,
which eventually allows the construction of diverse arrays of -
conjugated 6-substituted 2,3-diaryl benzo[b]thiophene derivatives.
Introduction
Development of novel synthetic methods for the efficient
construction of benzo[b]thiophene analogues always draws
significant attention; since the synthetic potential of
benzo[b]thiophene heterocyclic compounds is truly reflected
witnessing its presence in natural products,[1] drug candidates,[2]
and -extended materials.[3] Of course, enormous effort has
gone crafting sustainable synthetic tools for the fabrication of
benzo[b]thiophene core especially from the pre-functionalized
thiol derivatives.[4] By contrast, the intermolecular annulation of
readily accessible non-functionalized thiol-motifs and alkynes
provides a straightforward handle to peripherally decorated
benzo[b]thiophene skeleton, although the method is exceedingly
important but poorly explored.[5] The use of ubiquitous ortho-C-H
bond in thiol-derivatives not only broadens the scope of the
annulation process but also allows the step and atom-efficient
construction of benzo[b]thiophenes. Eventually, this annulation
technique is synthetically viable between thiophenols and the
activated alkynes (Michael acceptor); which involves an
electrophilic/radical mode of cyclization.[6] Whereas the
annulation of thiophenols with unactivated alkynes remains
challenging; perhaps thiols are prone to undergo dimerization,
hydrothiolation to alkynes, and catalyst poisoning. Moreover,
annulation of meta-substituted thiophenols with alkynes
invariably affects the reaction dynamics (on the basis of the
steric and electronic nature of the substituent) forming two
regioisomeric products. As a result, direct synthesis of 6-
substituted benzo[b]thiophenes through oxidative annulation of
thiophenol-derivatives and alkynes draws significant attention.
The direct construction of 2,3-diarylbenzo[b]thiophenes is still
Scheme 1. Direct Strategy towards 2,3-Diarylbenzo[b]thiophenes
challenging; as most of the protocols employ trivial functional
group manipulation of benzo[b]thiophene periphery and
cyclization of highly functionalized ortho--tethered thiols, or
ortho-halo thiol scaffolds in the presence of an activator or
transition-metal catalysis.[4] One such interesting report for the
synthesis of 6-substituted 2,3-diarylbenzo[b]thiophene involves
an intramolecular cyclization of para-substituted arylthiovinyl
sulfonic ester to a vinyl cation formation, a 1,2-sulfur migration
from the thiete/Wheland intermediate (C), and finally
aromatization.[7,8] Nonetheless, a Ni-catalyzed decarbonylative
annulation of thiophthalic anhydride with alkynes directly
provides 2,3-diarylbenzo[b]thiophenes.[9]
The redox-neutral strategy for the TM-catalyzed annulation of an
oxidizable directing group (having ON, NN, NO, and SN
bonds) enabled arenes with alkynes surfaces an efficient
strategy to construct benzannulated heterocyclic compounds.[8,
10]
Interestingly, N-arylthio succinimides and N-arylthio
phthalimides have fruitfully been used for the functionalization of
olefins[11] and alkynes[8] as well as a sulfenylating agent for the
arylthiolation of arenes.[12]
We have recently revealed Ag-catalyzed direct oxidative
cyclization between para-substituted N-arylthio succinimides and
unactivated diaryl bearing alkynes for the selective synthesis of
6-substituted benzo[b]thiophene (Eq 1, Scheme 1).[8a] This
transformation involves oxidative cleavage of SN bond, 1,2-
sulfur migration, and annulation via radical path; equimolar
[a] E. Ramesh, Dr. Tirumaleswararao Guntreddi, Prof. Dr. A. K. Sahoo
School of Chemistry, University of Hyderabad
Gachibowli, Hyderabad, Telangana 500046 (India)
E-mail:akhilchemistry12@gmail.com / akssc@uohyd.ac.in
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700607
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amount of both the reaction partners are smoothly reacted at 80
ºC (Eq 1, Scheme 1).[8a] Later, Glorius and co-workers
the identical transformation of the N-arylthio phthalimide
compounds under the influence of acid catalyst at an ambient
conditions. To begin with, the reaction of N-(thio-p-tolyl)-4-
nitrophthalimide (1a) with 1,2-diphenyl acetylene (2a) was
experimented in the presence of Brønsted and/or Lewis acid
catalyst at room temperature. The reaction optimization details
are shown in Table 1. Pleasingly, the reaction in the presence of
TFA in dichloromethane (DCM) at RT led to 6-methyl-2,3-
diphenyl benzothiophene (3a) in 24% yield with 1,2-migration of
S-moiety (entry 1, Table 1). Motivated with this initial result,
various Brønsted acids camphorsulfonic acid (CSA), TfOH,
MsOH, and AcOH were screened in order to obtain enhanced
amount of 3a. Even a trace of 3a was not detected, when the
reaction was conducted in the presence of CSA and AcOH
(entries 2 & 3); while the use of TfOH or MsOH marginally
promoted the reaction (entries 4 and 5). By contrast, Lewis acid
ZnCl2 mediated reaction of 1a and 2a produced 10% 3a (entry 6).
To our delight, enhanced yield of 3a (78%) was achieved, when
the reaction was performed in presence of AlCl3 at RT (entry 7);
interestingly, complete consumption of 1a was observed with the
isolation of 92% protecting group (4-nitrophthalimide; PG1) (entry
7). However, the same reaction in 0.5 mmol scale provided 67%
of 3a (entry 7). Other Lewis acid catalysts FeCl3 and BF3·OEt2
were found moderate (entries 8 and 9). Among the screening of
various solvents, CH2Cl2 (DCM) was found facile, while 1,4-
dioxane was ineffective (entries 1012). The use of acid-catalyst
is therefore indispensible, as no product was detected in the
absence of Lewis acid catalyst (entry 13). The reaction in
presence of radical quencher TEMPO (1.0 equiv) / BHT (1.0
equiv) did not affect the reaction outcome (entries 14 & 15),
precluding the possible involvement of radical intermediate in
this reaction.
demonstrated
the
synthesis
of
6-substituted
2,3-
diarylbenzo[b]thiophene from Sc(OTf)3-mediated annulation of
para-substituted N-arylthio succinimides (2.0 equiv) and alkynes
(1.0 equiv) at 130 C; the reaction involves vinyl-cation
intermediate followed by cyclization, 1,2-S-migration, and
aromatization (Eq 1, Scheme 1).[8b] Very recently, Chatani group
showed Pd-catalyzed annulation between ortho-bromo-thiols
(1.0 equiv) and alkynes (3.0 equiv) to furnish 2,3-disubstituted
benzo[b]thiophenes at 130 ºC (Eq 2, Scheme 1).[13] The
requirement of more equivalents of reaction partners and
elevated temperature are essential to accomplish the
intermolecular annulation of thiophenol derivatives with
unactivated alkynes yielding the desired benzo[b]thiophenes,
which eventually limits the synthetic potential of the strategy.
These shortcomings inspired us to unravel an effective modified
synthetic technique for AlCl3-catalyzed annulation of para-
substituted N-arylthio phthalimides (1.0 equiv) with diaryl
alkynes (1.0 equiv) for the selective synthesis of 6-substituted
2,3-diarylbenzo[b]thiophene (Eq 3, Scheme 1). Interestingly, the
reaction smoothly ensued at room temperature (RT) isolating the
desired benzo[b]thiophene product along with the recovery of
the phthalimide, which can be further reused.
Results and Discussion
The synthesis of 6-substituted 2,3-diarylbenzo[b]thiophene from
N-arylthio succinimide and alkyne in the presence of Ag-
catalysis at an elevated temperature inspired us to investigate
Table 1. Optimization of Reaction Conditions[a]
entry
LA/BA
(20 mol %)
Solvent
(0.5 mL)
Temperature
(oC)
yield
(%)[b]
1
2
3
4
5
6
7
8
9
TFA
CSA
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
24
NR
NR
18
AcOH
TfOH
MsOH
ZnCl2
AlCl3
FeCl3
BF3.OEt2
AlCl3
15
10
78 (67[c]
52
)
40
61
NR
54
10
11
12
ClCH2CH2Cl
Dioxane
CH3CN
AlCl3
AlCl3
13
14
15
16
17
18
19
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
RT
RT
RT
RT
RT
50
NR
71[d]
52[e]
65[f,c]
52[g,c]
68[c]
29[c]

AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
Scheme
2
.
Synthesis of 6-Methyl-2,3-diphenylbenzo[b]thiophenes.[a,b]
[a]Reaction conditions:
1
(0.5 mmol), 2a (0.5 mmol), AlCl3 (20 mol %),
CH2Cl2 (2.0 mL) at RT,
1
h. [b]Isolated yields.
10
[a]Reaction conditions: 1a (0.1 mmol), 2a (0.1 mmol). [b]Conversion based on
crude 1H NMR of starting material. [c]1a (0.5 mmol), CH2Cl2 (2.0 mL), isolated
yields. [d]TEMPO (0.1 mmol). [e]BHT (0.1 mmol), [f]AlCl3 (25 mol%), [g]AlCl3 (10
mol%). NR = no reaction.
The reaction outcome was not largely affected, when AlCl3
(25/10 mol%) was employed (entries16 and 17). Conducting the
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Table 2. Synthesis of 2,3-Diphenylbenzo[b]thiophenes: Substrate Scope I.[a,b]
bearing 4-methyl thiophenol derivatives with 2a (Scheme 2).
The SN protected 4-methyl-thiophenol compounds having
electron-deficient phthalimide moiety (4-NO2; 1a and 4,5-di-
Cl; 1c) underwent annulation with 2a more effectively than
the electron-neutral 1b and electron-rich phthalimide (4-Me;
1d) derivatives. The succinimide bearing thiol 1e is equally
effective, providing 54% of 3a. As the electron-deficient
Entry
1
Substrate
Product
phthalimide moiety enhances polarizability of SN bond,
which in turn is responsible for deliberating the better reaction
outcome. Thus, formation of 3a is effectively sensed from the
4-nitrophthalimide SN protecting group containing 1a.
The optimized condition [1a (0.5 mmol, 1.0 equiv), 2a (0.5
mmol, 1.0 equiv), AlCl3 (20 mol %), CH2Cl2 (2.0 mL), RT, 1 h]
was next examined to probe the scope and limitations for the
synthesis of benzothiophene derivatives through direct
annulation of N-(arylthio)-phthalimide/-succinimide derivatives
2
3
4
5
6
7
8
1
with 2a. The results were summarized in Table 2. The 4-
NO2-phthalimide bearing electron-rich thiophenol derivatives
successfully underwent annulation with 2a to afford the
desired benzothiophene products 3a
3c in good yields
(entries 1 3). The corresponding 4-NO2-phthalimide bearing

4-OMe thiol compound was found unstable; pleasingly,
annulation of phthalimide containing 4-OMe thiophenol 1h
with 2a led to 3d (57%) (entry 4). Repeated attempts to
isolate the phthalimide enabled halo (F, Cl) containing thiol
derivatives were failed. By contrast, the stable N-(halo-
arylthio)-succinimides 1i and 1j were reacted with 2a to
construct 3e (61%) and 3f (22%), respectively (entries 5 and
6). The chloro group is amenable to further synthetic
manipulations. As such, the annulations proceed through 1,2-
S-migration
to
provide
the
desired
6-substituted
benzo[b]thiophene derivatives. Structure of 3a and 3f was
further elucidated by the X-ray crystallographic analysis
(Table 2). Likewise, 2,3-diphenyl benzo[b]thiophene (3g) was
accessed from N-(phenylthio)-succinimide 1k (entry 7).
Disappointingly, the p-NO2-substituted thiol derivative 1l did
not provide the desired product 3h; a consequence of strong
electron withdrawing (NO2) group of arenes, which eventually
affects the effective generation of sulfonium species and the
electrophilic ipso-attack of arene motifs to the in-situ
generated vinylic-cation.
We next explored scrutinizing the annulation of various
unactivated diaryl alkynes
2 with 1a/1g (Table 3). The
reaction of electron donating p-t-Bu containing thiol derivative
1g with p-t-Bu (2b) or p-Me (2c) substituted diaryl alkynes
under the standard conditions delivered the corresponding 6-
t-Bu containing 2,3-diarylbenzothiophenes 4a (64%) and 4b
(76%). Pleasingly, electron-rich alkyne having p-OMe aryl
moiety 2d reacted with p-Me substituted thiol derivative 1a to
afford 52% of 4c; this reaction was previously not successful
under the Ag-catalyzed conditions.[8a] Likewise, annulation of
[a]Reaction conditions:
CH2Cl2 (2.0 mL) at RT for
1
(0.5 mmol), 2a (0.
1
5
mmol), AlCl3 (20 mol %),
.
h. [b]Isolated yields
1g with m,p-di-methyl substituted 1,2-diaryl acetylene (2e
furnished 4d in moderate yield. The products 4e and 4f were
constructed through the annulation of p-Cl (2f) and p-F (2g
)
o
experiment at 50 C did not improve the product yield (entry
18); moreover, the reaction at 10 oC was inefficient (entry 19).
The synthesis of benzothiophene 3a from 1a with 4-
)
substituted 1,2-diaryl acetylenes with 1g and 1a, respectively
(Table 3). The annulation of 1a/1g with the unsymmetrical
alkynes was next examined. In general, the reaction with
unsymmetrical alkynes produces mixture of two regioisomeric
nitrophthalimide SN protecting group and 2a under the AlCl3
at RT (shown in entry 7, Table 1) provoked us probing the
identical annulations of various phthalimide/succinimide
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Table 3. Synthesis of 2,3-Diarylbenzo[b]thiophenes: Substrate Scope II. [a,b]
Table 4. Reaction of ortho and meta-Substituted N-Arylthio Succinimides with
2a. [a,b]
Entry
Substrate (1)
3; yield (%)
1
(3i+3i′) = (4:1; 46%)
2
(3a+3i+3j) = (5:3:2; 41%)
[a]Reaction conditions:
1 (0.5 mmol), 3a (0.5 mmol), AlCl3 (20 mol %),
CH2Cl2 (2.0 mL) at RT for 1 h. [b]mixture of products.
We next explored examining the annulation of ortho/meta
substituted thiol of N-arylthio succinimide derivatives and the
results were summarized in Table 4.
Interestingly, the
annulation of N-(thio-o-tolyl)-succinamide (1m) with 2a provided
inseparable mixture of two different products [with 1,2-S-
migration 3i' and S-retention 3i in 1:4 ratio] (entry 1, Table 4).[8a]
Not surprisingly, cyclization of N-(thio-m-tolyl)-succinimide (1n)
with 2a also furnished inseparable
mixture of three
benzothiophene products with the S-retention (3a), 1,2-S-
migration (3i) and 1,2′-S-migration (3j) in overall 48% yield (entry
2, Table 4).
We next studied the annulation of the challenging alkyl-bearing
alkynes (Table 5). To our surprise, the reaction of 1a with 1,2-
dialkyl/aryl-alkyl acetylenes under the optimized conditions
results chloro-thiolation of alkyne providing -chloroalkenyl
[14]
sulfides 5a (52%) and 5b (38%) (Table 5);
probably
quenching of the less stable alkyl-substituted vinyl cation,
obtained in situ via the attack of alkyne to the activated
sulfonium species, with the chloride ion is favored over the
electrophilic ipso substitution by the arene motif. Disappointingly,
repeated attempts for the annulation of terminal alkyne (i.e.
phenyl acetylene) with 1a failed under the oxidative conditions.
Table 5. Reaction of 1a with alkyl substituted alkynes.[a,b]
[a]Reaction conditions: 1a/1g (0.5 mmol),
CH2Cl2 (2.0 mL) at RT for
h. [b]Isolated yields.
2 (0.5 mmol), AlCl3 (20 mol %),
2
products. Surprisingly, product 4g (single regioisomer) was
formed from the unsymmetrical diaryl alkyne 2h with 1g
under the optimized conditions (Table 3). Probably, the
electronic perturbation of arene motifs affects the delivery of
single product 4g. Likewise, annulation of 1a with halo group
substituted unsymmetrical diaryl alkynes 2i or 2j produced
inseparable mixture of two regioisomers 4h or 4i (1:1) in good
yields (Table 3). Gratifyingly, annulation of EWG-p-NO2/EDG-
p-OMe bearing unsymmetrical alkyne 2k with 1h/1a
exclusively furnished the corresponding benzo[b]thiophene 4j
and 4k, respectively, as single regioisomer (Table 3); a
consequence from the electronic perturbation of arene motifs.
[a]Reaction conditions: 1a (0.5 mmol),
CH2Cl2 (2.0 mL) at RT for
h. [b]Isolated yields.
2 (0.5 mmol), AlCl3 (20 mol %),
2
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The robustness of the catalytic conditions is successfully tested
performing the annulation of 1f (0.9 g) with 2a (0.47 g) at RT to
provide 3b (630 mg) in 73% yield, offering opportunity for
reaction scalability. The isolation of 4-nitrophthalimide (451 mg,
89%) truly demonstrates the atom-efficient protocol of the
current transformation (Eq 1, Scheme 3). As expected,
independent oxidation of 3b with m-CPBA and aq. H2O2
delivered the corresponding sulfone (6, 93%) and sulfoxide (7,
89%), respectively (Eq 2, Scheme 3).
In conclusion, we have successfully demonstrated a modified
direct annulation method of N-arylthio phthalimide derivatives
with unactivated alkynes to access the challenging conjugated
6-substituted 2,3-diaryl benzo[b]thiophenes. The reaction is
successfully performed at room temperature in the presence of
inexpensive AlCl3 and is efficient. The reaction is scalable with
the isolation of phthalimide moiety, which makes the current
process practicable. The identical reaction with dialkyl alkynes
provides -chloroalkenyl sulfides. The synthetic utility of the
current method for the construction of extended and V-shaped
benzothiophene analogues are being actively pursued in our
laboratory.
Experimental Section
General Experimental: All the reactions were performed in an oven-
dried Schlenk flask/pressure tubes under an argon atmosphere.
Commercial grade solvents were distilled prior to use. Column
chromatography was performed using either 100-200 Mesh or 230-400
Mesh silica gel eluting with hexane and ethyl acetate mixture. Thin layer
chromatography (TLC) was performed on silica gel GF254 plates.
Visualization of spots on TLC plate was accomplished with UV light (254
nm) and staining over I2 chamber.
Scheme 3. Synthetic Elaboration of Benzothiophene
.
To rationalize the observed results, a tentative mechanism of the
current annulation is proposed in Scheme 4. Corroborated with
the insightful theoretical supporting data resulted from Glorius
and co-workers for benzothiophene synthesis,[8b] we formally
believe that the reaction begins with the coordination of AlCl3 to
the phthalimide moiety of 1, which eventually triggers the
polarization of SN bond and generates the electrophilic
thiophenol intermediate I.[8b] Next, the nucleophilic attack of the
alkyne to I then produce the vinyl cation species II with the
release of Al-enabled phthalimide derivative III.[8b] Then
intramolecular electrophilic 4-endo-trig spirocyclization of the
proximal ipso-carbon with the vinyl cation II rapidly forms the
unstable spirocyclohexadienyl arenium-intermediate IV.[8] The
Proton and carbon nuclear magnetic resonance spectra (1H NMR and
13C NMR) were recorded based on the resonating frequencies as follows:
(1H NMR, 400 MHz; 13C NMR, 101 MHz) and (1H NMR, 500 MHz; 13C
NMR, 126 MHz) having the solvent resonance as internal standard (1H
NMR, CDCl3 at 7.26 ppm; 13C NMR, CDCl3 at 77.0 ppm). Few cases
tetramethylsilane (TMS) at 0.00 ppm was used as reference standard.
Data for 1H NMR are reported as follows: chemical shift (ppm),
multiplicity (s = singlet; bs = broad singlet; d = doublet; bd = broad
doublet, t = triplet; bt = broad triplet; q = quartet; m = multiplet), coupling
constants, J, in (Hz), and integration. Data for 13C NMR, 19F NMR were
reported in terms of chemical shift (ppm). IR spectra were reported in
cm1. High resolution mass spectra were obtained in ESI mode. LC-MS
spectra were obtained with ionization voltage of 70ev; data was reported
in the form of m/z (intensity relative to base peak = 100). Elemental (C, H,
N) analysis were carried out using FLASH EA 1112 analyzer. Melting
points were determined by electro-thermal heating and are uncorrected.
Materials: Unless otherwise noted, all the reagents and intermediates
were obtained commercially and used without purification. Following the
standerd procedures, the solvents were dried and stored over molecular
sieves under inert gas (nitrogen, argon) atmosphere. Diphenyl acetylene
(2a), 4-octyne(2l), 1-Phenylpropyne(2m), TFA, CSA, TfOH, MsOH,
AcOH, AlCl3, FeCl3, and BF3.OEt2 were purchased, and used as received.
Analytical and spectral data of all the known compounds are exactly
matching with the reported values.
General Procedure for the Perparation of Symmetrical Diaryl
Alkynes (2bg):[15] To a mixture of PdCl2(PPh3)2 (6.0 mol %), CuI (10
mol %) and aryl iodide (1.0 mmol) in benzene (5.0 mL) was added DBU
(6.0 mmol) followed by trimetyhylsilyl acetylene (0.5 mmol) and de-
ionized water (40 mol %) under an argon atmosphere at RT. The
resulting mixture was heated at 80 oC for 18 h in the absence of light.
Upon completion, the reaction mixture was cooled to RT and diluted with
diethyl ether. The organic layer was washed with water, 10% HCl (2  5.0
mL), and brine and dried over Na2SO4. Solvent was filtered and
evaporated under the reduced pressure. The crude residue was purified
using column chromatography on silica gel using hexane/ethyl acetate.
Analytical and spectral data of these compounds are exactly matching
with the reported values.
Scheme 4. Plausible Mechanism
ring expansion of species IV through 1,2-S-migration produces
the intermediate V.[10] Finally, deprotonation-aromatization of V
affords final product 3. The protonation of III generates
phthalimide-derivative, liberating AlCl3 for the next cycle.
Conclusions
General Procedure for the Perparation of Unsymmetrical Diaryl
Alkynes (2hk):[16] To a mixture of PdCl2(PPh3)2 (2.0 mol %), CuI (4.0
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10.1002/ejoc.201700607
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mol %) and aryl iodide (1.0 mmol) in THF (5.0 mL) was added Et3N (3.0
mmol) followed by aryl/alkyl bearing acetylenes (1.0 mmol) under an
argon atmosphere at RT. The resulting mixture was heated at 60 oC for
16 h in the absence of light. Upon completion, the reaction mixture was
cooled to RT and diluted with diethyl ether. The organic layer was
washed with water, 10% HCl (2  5.0 mL), and brine and dried over
Na2SO4. Solvent was filtered and evaporated under reduced pressure.
The crude residue was purified using column chromatography on silica
gel using hexane/ethyl acetate. Analytical and spectral data of these
compounds are exactly matching with the reported values.
CDCl3) 165.9, 165.6, 154.2, 151.9, 136.3, 133.5, 133.4, 130.3, 129.6,
126.6, 125.2, 119.3, 34.8, 31.0; IR (KBr) max 2962, 2868, 1737, 1540,
1277, 1062, 716 cm1; MS (EI) m/z (%) 355 (M+1, 100); Anal. Calcd. for
C18H16N2O4S: C, 60.66; H, 4.53; N, 7.86; Found: C, 60.72; H, 4.49; N,
7.81.
General Procedure for Preparation of N-Arylthio Succinimide (1):[10a]
To a solution of N-chlorosuccinimide (NCS) (1.0 equiv) in CH2Cl2 (5.0 mL
for 2.0 mmol) was added thiophenols (1′, 1.0 equiv) and Et3N (1.0 equiv)
drop wise under an argon atmosphere at 0 oC. The resulting mixture was
stirred for 12 h at RT. After completion, the reaction mixture was
quenched with saturated aqueous NH4Cl solution. The organic layer was
separated; the aqueous layer was extracted with CH2Cl2 (2  10 mL, for
1.0 mmol). The combined extracts were washed with brine. The organic
layer was dried over Na2SO4. Solvent was filtered and evaporated under
reduced pressure. The crude residue was purified using column
chromatography on silica gel using hexane/ethyl acetate (4:1). Following
this procedure, the Nthioaryl succinamides 1e and 1in were prepared.
Analytical and spectral data of these compounds are exactly matching
with the reported values.
General Procedure for the Preparation of N-Arylthio Phthalimide (1):
[17]
To a solution of thiophenols (1′, 1.0 equiv) and Et3N (0.1 equiv) in
CH2Cl2 (5.0 mL for 2.0 mmol) was added SO2Cl2 (1.0 equiv) drop wise
o
under an argon atmosphere at 0 C. After stirring for 15 min, the mixture
was warmed to RT and stirred for 30 min and then cooled to 0 oC. The
resulting solution was transferred via cannula to a solution of phthalimide
(1.0 equiv) and Et3N (0.1 equiv) in CH2Cl2 (5.0 mL for 2.0 mmol) at 0 oC,
and the mixture was warmed to RT over 1 h. The resulting mixture
diluted with water and extracted with CH2Cl2 (2  10 mL, for 1.0 mmol).
The combined extracts were washed with brine. The organic layer was
dried over Na2SO4. Solvent was filtered and evaporated under reduced
pressure. The crude residue was purified using column chromatography
on silica gel using hexane/ethyl acetate (5:1). Analytical and spectral
data of compounds 1b, 1h are exactly matching with the reported values.
General
Procedure
for
Annulation,
Synthesis
of
Benzo[b]thiophenes:
The N-arylthio succinimide/phthalimide (1, 0.5
mmol) and 1,2-diarylalkyne (2, 0.5 mmol) were taken in a Schlenk tube.
Subsequently, AlCl3 (14 mg, 20 mol %) was introduced into the flask in a
Glove box. Solvent 1,1-dichloromethane (2.0 mL) was added to the
mixture and the resulting mixture was stirred at RT for 12 h. Upon
completion, the mixture was diluted with CH2Cl2 (10 mL) and filtered over
a small pad of Celite. Solvent was evaporated under the reduced
pressure and the crude residue was purified through silica gel column
chromatography using n-hexane eluent to give the desired product 3/4.
5-Nitro-2-(p-tolylthio)isoindoline-1,3-dione (1a): 1a (1.3 g, 51%),
yellow solid. mp 164165C; Rf = 0.50 (8:2 hexane/EtOAc); 1H NMR
(400 MHz, CDCl3)8.68 (d, J 1.6 Hz, 1H), 8.61 (dd, J  8.2 & 1.8 Hz,
1H), 8.09 (d, J 8.0 Hz, 1H), 7.62 (d, J 8.4 Hz, 2H), 7.14 (d, J 8.0 Hz,
2H), 2.31 (s, 3H); 13C NMR (101 MHz, CDCl3) 165.8, 165.5, 151.9,
141.2, 136.3, 133.7, 133.3, 130.3, 130.2, 129.6, 125.2, 119.2, 21.3; IR
(KBr) max 2915, 1735, 1539, 1278, 1064, 717 cm1; HRMS (ESI) for
C15H14N3O4S (M+NH4)+: calcd. 332.0700, found 332.0705.
6-Methyl-2,3-diphenylbenzo[b]thiophene (3a):[8a] 3a (101 mg, 67%),
colorless solid. 1H NMR (400 MHz, CDCl3) 7.71 (s, 1H), 7.53 (d, J  8.4
Hz, 1H), 7.467.34 (m, 8H), 7.297.26 (m, 2H), 7.19 (d, J  8.0 Hz, 1H),
2.53 (s, 3H); 13C NMR (101 MHz, CDCl3) 139.1, 138.7, 138.3, 135.7,
134.5, 134.4, 133.0, 130.4, 129.5, 128.6, 128.3, 127.5, 127.3, 126.1,
123.0, 121.9, 21.5.
5,6-Dichloro-2-(p-tolylthio)isoindoline-1,3-dione (1c): 1c (0.92 g,
59%), colorless solid. mp  162163 C; Rf = 0.77 (8:2 hexane/EtOAc);
1H NMR (400 MHz, CDCl3) 7.96 (s, 2H), 7.59 (d, J 8.4 Hz, 2H), 7.14
(d, J 8.0 Hz, 2H), 2.32 (s, 3H); 13C NMR (101 MHz, CDCl3) 166.0,
140.9, 139.7, 133.3, 131.0, 130.7, 130.1, 125.9, 21.3; IR (KBr) max 1733,
1315, 1069, 734 cm1; HRMS (ESI) for C15H13Cl2N2O2S (M+NH4)+: calcd.
355.0069, found 355.0073.
6-iso-Propyl-2,3-diphenylbenzo[b]thiophene (3b):[8a] 3b (107 mg,
65%), colorless solid. 1H NMR (400 MHz, CDCl3)  7.72 (s, 1H), 7.51 (d,
J 8.4 Hz, 1H), 7.417.29 (m, 8H), 7.247.19 (m, 3H), 3.082.97 (m, 1H),
1.32 (d, J 6.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) 145.7, 139.1,
138.6, 135.7, 134.4, 133.0, 131.6, 130.4, 129.5, 128.6, 128.3, 127.5,
127.3, 123.8, 123.1, 119.2, 34.2, 24.2.
5-Methyl-2-(p-tolylthio)isoindoline-1,3-dione (1d): 1d (1.08 g, 61%),
pale yellow solid. mp 175176 C; Rf = 0.54 (8:2 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) 7.797.73 (m, 1H), 7.727.63 (m, 1H),
6-tert-Butyl-2,3-diphenylbenzo[b]thiophene (3c):[8a] 3c (124 mg, 72%),
colorless solid. 1H NMR (400 MHz, CDCl3) 7.95 (s, 1H), 7.60 (d, J 8.8
Hz, 1H), 7.497.37 (m, 8H), 7.317.27 (m, 3H), 1.47 (s, 9H); 13C NMR
(101 MHz, CDCl3)148.0, 139.0, 138.8, 138.6, 135.7, 134.4, 132.9,
130.4, 129.6, 128.6, 128.3, 127.5, 127.3, 122.8, 122.7, 118.2, 34.9, 31.5.
7.597.49 (m, 3H), 7.11 (d, J 7.6 Hz, 2H), 2.49 (s, 3H) 2.29 (s, 3H); 13
C
NMR (101 MHz, CDCl3)168.0, 167.8, 146.0,140.0, 135.1, 134.8, 132.3,
131.5, 129.9, 129.4, 124.3, 123.8, 22.0, 21.2 ; IR (KBr) max 3488, 1729,
1275, 1049, 734 cm1; HRMS (ESI) for C16H13NNaO2S (M+Na)+: calcd.
306.0559, found 306.0567.
6-Methoxy-2,3-diphenylbenzo[b]thiophene (3d):[8a] 3d (90 mg, 57%),
2-((4-iso-Propylphenyl)thio)isoindoline-1,3-dione (1f): 1f (1.14 g,
62%), yellow solid. mp  138139 C; Rf = 0.61 (8:2 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3)  8.71 (d, J 2.0 Hz, 1H), 8.62 (dd, J  8.0 & 2.0
Hz, 1H), 8.10 (d, J8.0 Hz, 1H), 7.69 (d, J 8.0 Hz, 2H), 7.21 (d, J 8.4
Hz, 2H), 2.922.81 (m, 1H), 1.20 (d, J 6.8 Hz, 6H); 13C NMR (101 MHz,
CDCl3) 165.8, 165.6, 151.95, 151.88, 136.3, 133.9, 133.3, 130.6, 129.6,
127.6, 125.2, 119.2, 33.9, 23.6; IR (KBr) max 2930, 2359, 1735, 1541,
1276, 716 cm1; HRMS (ESI) for C17H15N2O4S (M+H)+: calcd. 343.0747,
found 343.0748.
1
pale yellow solid. H NMR (400 MHz, CDCl3)  7.46 (d, J = 8.8 Hz, 1H),
7.417.27 (m, 8H), 7.247.20 (m, 3H), 6.95 (dd, J  9.0 & 2.2 Hz, 1H),
3.88 (s, 3H); 13C NMR (101 MHz, CDCl3) 157.6, 140.1, 136.8, 135.7,
135.0, 134.4, 132.8, 130.3, 129.4, 128.6, 128.3, 127.4, 127.3, 124.0,
114.4, 104.5, 55.6.
[8a]
6-Fluoro-2,3-diphenylbenzo[b]thiophene (3e):
3e (93 mg, 61%),
colorless solid. 1H NMR (400 MHz, CDCl3) 7.567.48 (m, 2H),
7.417.34 (m, 3H), 7.327.27 (m, 4H), 7.257.20 (m, 3H), 7.06 (td, J =
8.8 & 2.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) 160.6 (d, J = 246 Hz),
139.6 (d, J = 10 Hz), 139.0 (d, J = 3 Hz ), 137.4, 135.2, 133.9, 132.7,
130.3, 129.5, 128.7, 128.4, 127.8, 127.5, 124.4 (d, J = 9 Hz), 113.3 (d, J
= 24 Hz), 108.1 (d, J = 25 Hz).
2-((4-(tert-Butyl)phenyl)thio)-5-nitroisoindoline-1,3-dione (1g): 1g
(1.16 g, 54%), yellow solid. mp
 166167 C; Rf = 0.59 (8:2
hexane/EtOAc); 1H NMR (400 MHz, CDCl3)  8.70 (d, J 1.6 Hz, 1H),
8.62 (dd, J  8.0 & 2.0 Hz, 1H), 8.10 (d, J 8.0 Hz, 1H), 7.68 (d, J  8.8
Hz, 2H), 7.37 (d, J  8.4 Hz, 2H), 1.27 (s, 9H); 13C NMR (101 MHz,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700607
European Journal of Organic Chemistry
FULL PAPER
6-Chloro-2,3-diphenylbenzo[b]thiophene (3f):[8a] 3f (36 mg, 22%),
colorless crystalline solid. 1H NMR (400 MHz, CDCl3)  7.83 (d, J  1.6
Hz, 1H), 7.48 (d, J  8.4 Hz, 1H), 7.417.37 (m, 3H), 7.317.27 (m, 5H),
7.257.23 (m, 3H); 13C NMR (101 MHz, CDCl3) 140.0, 139.7, 139.4,
135.0, 133.8, 132.8, 130.5, 130.3, 129.5, 128.7, 128.4, 127.9, 127.6,
125.2, 124.2, 121.6.
2,3-bis(4-Methoxyphenyl)-6-methylbenzo[b]thiophene (4c) and 2,3-
bis(4-Methoxyphenyl)-5-methylbenzo[b]thiophene (4c′): The reaction
between 1a and 2d under the optimization conditions provided
inseparable mixture of 4c and 4c′ (97:3) (94 mg, 52%), pale yellow solid.
mp 137138C; Rf = 0.32 (19:1 hexane/EtOAc); 1H NMR (500 MHz,
CDCl3)  7.63 (s, 1H), 7.44 (d, J 8.5 Hz, 1H), 7.24 (d, J  8.5 Hz, 4H),
7.13 (dd, J  8.0 & 1.0 Hz, 1H), 6.93 (d, J  8.5 Hz, 2H), 6.78 (d, J  9.0
Hz, 2H), 3.85 (s, 3H), 3.78 (s, 3H) 2.47 (s, 3H); 13C NMR (126 MHz,
CDCl3) 159.0, 158.8, 139.1, 138.7, 137.8, 134.2, 131.8, 131.5, 130.6,
128.1, 127.0, 126.0, 122.8, 121.8, 114.1, 113.8, 55.21, 55.19, 21.5; IR
(KBr) max 2955, 2835, 1607, 1540, 1248, 811 cm1; HRMS (ESI) for
C23H20NaO2S (M+Na)+: calcd. 383.1076, found 383.1077.
2,3-Diphenylbenzo[b]thiophene (3g):[8a] 3g (36 mg, 25%), colorless
crystalline solid. 1H NMR (400 MHz, CDCl3)  7.907.85 (m, 1H),
7.627.57 (m, 1H), 7.407.28 (m, 9H), 7.267.21 (m, 3H); 13C NMR (101
MHz, CDCl3) 140.9, 139.5, 138.8, 135.5, 134.2, 133.2, 130.4, 129.6,
128.6, 128.3, 127.7, 127.4, 124.5, 124.4, 123.3, 122.0.
7-Methyl-2,3-diphenylbenzo[b]thiophene (3i) and 4-Methyl-2,3-
diphenylbenzo[b]thiophene (3i'):[8a] Inseparable mixture of 3i/3i′ (4:1)
(69 mg, 46%), colorless crystalline solid. 1H NMR (400 MHz, CDCl3)
7.74 (d, J  7.6 Hz, 1H), 7.477.17 (m, 19H), 7.06 (d, J  7.2 Hz, 1H),
2.62 (s, 1H), 1.98 (s, 3H); 13C NMR (101 MHz, CDCl3)  140.7, 139.6,
139.2, 138.9, 138.5, 138.2, 135.8, 134.52, 134.47, 134.45, 134.37, 133.9,
131.6, 131.1, 130.4, 129.6, 128.6, 128.3, 128.1, 127.9, 127.6, 127.4,
127.35, 127.30, 127.1, 124.9, 124.8, 124.1, 121.0, 120.0, 21.5, 20.2.
Ratio of the both regioisomers 3i:3i' was determined based on the
characteristic Me-1H proton integretion. 1H NMR (400 MHz, CDCl3) 1H for
3i/3i': = 1.98 (s, 3H, 78%, major)/2.62 (s, 3H, 22%, minor).
6-(tert-Butyl)-2,3-bis(3,4-dimethylphenyl)benzo[b]thiophene (4d) and
5-(tert-Butyl)-2,3-bis(3,4-dimethylphenyl)benzo[b]thiophene
(4d′):
The reaction between 1g and 2e under the optimization conditions
provided inseparable mixture of 4d and 4d′ (87:13) (122 mg, 61%),
colorless crystalline solid. mp  C; Rf = 0.30 (hexane); 1H NMR
(400 MHz, CDCl3)  7.87 (d, J 1.6 Hz, 1H), 7.52 (d, J  7.6 Hz 1H),
7.40 (dd, J  8.6 & 1.8 Hz, 1H), 7.227.13 (m, 3H), 7.076.96 (m, 3H),
2.33 (s, 3H), 2.28 (s, 3H), 2.24 (s, 3H), 2.21 (s, 3H), 1.42 (s, 9H); 13C
NMR (101 MHz, CDCl3)147.6, 139.1, 138.7, 138.6, 136.6, 136.4,
136.0, 135.4, 133.3, 132.5, 132.1, 131.3, 130.6, 129.8, 129.5, 127.8,
126.8, 122.8, 122.4, 118.1, 34.9, 31.5, 19.8, 19.7, 19.6, 19.5; IR (KBr)
max 2963, 2866, 1449, 1263, 821 cm1; HRMS (ESI) for C28H30NaS
(M+Na)+: calcd. 421.1960, found 421.1960.
6-Methyl-2,3-diphenylbenzo[b]thiophene
diphenylbenzo[b]thiophene (3j)
(3a),
and
5-Methyl-2,3-
7-Methyl-2,3-
diphenylbenzo[b]thiophene (3i):[8a] The reaction between 1-(m-
tolylthio)pyrrolidine-2,5-dione 1m and 2a under the optimization
conditions provided inseparable mixture of 3a, 3i, and 3j (5:3:2) (61 mg,
41%), colorless crystalline solid. 1H NMR (400 MHz, CDCl3) 7.75 (dd, J
 10.0, 5.0 Hz, 2H), 7.67 (bs, 1H), 7.47 (d, J  8.4 Hz, 2H), 7.427.29 (m,
19H), 7.277.14 (m, 12H), 7.06 (d, J  7.2 Hz, 1H), [2.49 (s, 3H), 2.41 (s,
1H), 1.98 (s, 2H)]; 13C NMR (101 MHz, CDCl3)  141.1, 139.7, 139.6,
139.2, 139.1, 138.7, 138.5, 138.3, 138.2, 136.0, 135.7, 134.51, 134.47,
134.45, 134.37, 134.2, 133.0, 132.9, 131.1, 130.44, 130.38, 129.6,
129.55, 129.52, 128.62, 128.59, 128.3, 128.1, 127.9, 127.6, 127.5, 127.4,
127.35, 127.27, 127.1, 126.2, 126.1, 124.1, 123.2, 123.0, 121.9, 121.7,
121.1, 120.0, 21.54 (3i), 21.50 (3a).
6-tert-Butyl-2,3-bis(4-chlorophenyl)benzo[b]thiophene (4e):[8a] 4e
(162 mg, 79%), colorless crystalline solid. 1H NMR (400 MHz, CDCl3)
7.87 (bs, 1H), 7.49 (d, J  8.4 Hz, 1H), 7.447.36 (m, 3H), 7.267.21 (m,
6H), 1.40 (s, 9H); 13C NMR (101 MHz, CDCl3) 148.5, 139.0, 138.1,
137.8, 133.8, 133.5, 132.6, 132.0, 131.6, 130.7, 129.0, 128.7, 123.0,
122.6, 118.3, 35.0, 31.5.
2,3-bis(4-Fluorophenyl)-6-methylbenzo[b]thiophene (4f):[8a] 4f (123
mg, 73%), colorless crystalline solid; 1H NMR (400 MHz, CDCl3) 7.67
(bs, 1H), 7.43 (d, J  6.4 Hz, 1H), 7.297.23 (m, 4H), 7.17 (dd, J  6.4 &
0.8 Hz, 1H), 7.117.08 (m, 2H), 6.986.92 (m, 2H), 2.49 (s, 3H); 13C
NMR (101 MHz, CDCl3) 162.25 (d, J  250 Hz), 162.16 (d, J  248 Hz),
138.9, 138.5, 137.4, 134.8, 132.0 (d, J  3 Hz), 131.3 (d, J  4 Hz), 131.2
(d, J  8 Hz), 130.3 (d, J  3 Hz), 126.3, 122.8, 121.9, 115.7 (d, J  21
Hz), 115.4 (d, J  21 Hz), 21.5.
Ratio of the three regioisomers 3a:3i:3j was determined based on the
characteristic Me-1H proton integration. 1H NMR (400 MHz, CDCl3) 1H for
3a/3i/3j: = 2.49 (s, 3H, 48%, major)/ 1.98 (s, 3H, 30%, minor)/ 2.41 (s,
3H, 22%, minor). The Me peak appeared at 2.49 and 1.98 is matching
with the previously observed compound 3a and 3i, respectively.
6-(tert-Butyl)-2-phenyl-3-(p-tolyl)benzo[b]thiophene (4g): 4g (142 mg,
80%), colorless crystalline solid. mp  169170C; Rf = 0.27 (hexane);
1H NMR (400 MHz, CDCl3) 7.86 (s, 1H), 7.53 (d, J  8.4 Hz, 1H), 7.38
(dd, J  8.4 & 1.6 Hz, 1H), 7.357.29 (m, 2H), 7.257.15 (m, 7H), 2.38 (s,
3H), 1.39 (s, 9H); 13C NMR (101 MHz, CDCl3)147.9, 139.0, 138.7,
138.5, 136.9, 134.6, 132.9, 132.6, 130.2, 129.5, 129.3, 128.3, 127.4,
122.9, 122.6, 118.1, 34.9, 31.5, 21.3; IR (KBr)max 2960, 2866, 1597,
1263, 866, 820 cm1; HRMS (ESI) for C25H25S (M+H)+: calcd. 357.1671,
found 357.1670.
6-(tert-Butyl)-2,3-bis(4-(tert-butyl)phenyl)benzo[b]thiophene (4a) and
5-(tert-Butyl)-2,3-bis(4-(tert-butyl)phenyl)benzo[b]thiophene
(4a'):
The reaction between 1g and 2b under the optimization conditions
provided inseparable mixture of 4a and 4a′ (97:3) (146 mg, 64%),
colorless crystalline solid. mp  116117 C; Rf = 0.35 (hexane); 1H NMR
(500 MHz, CDCl3)  7.87 (bd, J 1.5 Hz, 1H), 7.53 (d, J  8.5 Hz, 1H),
7.43 (d, J  8.5 Hz, 2H), 7.40 (dd, J  8.5 & 2.0 Hz, 1H), 7.317.27 (m,
6H), 1.42 (s, 9H), 1.40 (s, 9H) 1.32 (s, 9H); 13C NMR (126 MHz, CDCl3)
150.4, 150.1, 147.7, 139.2, 138.7, 138.6, 132.8, 132.5, 131.6, 129.9,
128.9, 125.4, 125.2, 122.9, 122.5, 118.1, 34.9, 34.6, 34.5, 31.5, 31.4,
31.2; IR (KBr) max 2961, 2867, 1462, 1363, 1265, 836 cm1; HRMS (ESI)
for C32H39S (M+H)+: calcd. 455.2767, found 455.2765.
3-(4-Fluorophenyl)-6-methyl-2-phenylbenzo[b]thiophene (4h) and 2-
(4-Fluorophenyl)-6-methyl-3-phenylbenzo[b]thiophene
(4h′):[8a]
Inseparable mixture of 4h and 4h′ (1:1, 110 mg, 69%), colorless
crystalline solid.1H NMR (400 MHz, CDCl3) 7.65 (bs, 1H), 7.487.34 (m,
2H), 7.317.22 (m, 6H), 7.15 (dd, J  8.6 & 1.0 Hz, 1H), 7.07 (t, J  8.8
Hz, 1H), 6.91 (t, J  8.8 Hz, 1H), 2.47 (s, 3H); 13C NMR (101 MHz,
CDCl3)  162.2 (d, J  248 Hz), 162.1 (d, J  247 Hz), 139.1, 139.0,
138.6, 137.1, 135.4, 134.7, 134.2, 132.0 (d, J  8 Hz), 131.8, 131.6,
131.2 (d, J  8 Hz),130.3, 129.5, 128.7, 128.4, 127.6, 127.4, 126.2, 123.0,
122.7, 122.0, 121.96, 121.87, 115.6 (d, J  22 Hz), 115.3 (d, J  22 Hz),
21.5.
6-tert-Butyl-2,3-di-p-tolylbenzo[b]thiophene (4b):[8a] 4b (141 mg,
76%), colorless crystalline solid. 1H NMR (400 MHz, CDCl3)  7.85 (s,
1H), 7.51 (d, J  8.4 Hz, 1H), 7.38 (dd, J  8.8 & 1.6 Hz, 1H), 7.247.17
(m, 6H), 7.04 (d, J  8.0 Hz, 2H), 2.39 (s, 3H), 2.30 (s, 3H) 1.39 (s, 9H);
13C NMR (101 MHz, CDCl3) 147.7, 138.9, 138.8, 138.7, 137.3, 136.8,
132.8, 132.5, 131.7, 130.2, 129.4, 129.3, 129.0, 122.9, 122.5, 118.1,
34.9, 31.5, 21.3, 21.2.
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10.1002/ejoc.201700607
European Journal of Organic Chemistry
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Both the regioisomeric products 4h and 4h′ are indistinguishable by 1H
NMR, however, the 13C NMR studies clearly reveals the formation of both
regioisomers 4h and 4h′.
CDCl3)151.9, 138.1, 136.7, 136.5, 131.6, 131.0, 130.8, 129.42, 129.36,
129.2, 129.1, 129.0, 128.6, 127.2, 124.1, 119.5, 34.2, 23.7; IR (Neat)max
2963, 1479, 1297, 741, 698 cm1; HRMS (ESI) for C23H20NaO2S
(M+Na)+: calcd. 383.1076, found 383.1077.
3-(4-Chlorophenyl)-6-methyl-2-phenylbenzo[b]thiophene (4i) and 2-
(4-Chlorophenyl)-6-methyl-3-phenylbenzo[b]thiophene
(4i′):[8a]
Synthesis of 6-iso-Propyl-2,3-diphenylbenzo[b]thiophene 1-oxide
(7):[18] To a solution of 3b (1.0 mmol) in CH2Cl2 (5.0 mL) was added
aq.H2O2 (5.0 mmol). The resulting mixture was stirred at RT overnight.
Upon completion, the reaction mixture saturated with aqueous Na2S2O3
and extracted with CH2Cl2. The organic layer was dried over Na2SO4.
Solvent was evaporated and the crude material was purified by column
chromatography eluting with hexane/EtOAc 90:10 to give 7 (306 mg,
89%), colorless crystalline solid. mp 126127 C; Rf = 0.55 (85:15
hexane/EtOAc); H NMR (400 MHz, CDCl3) 7.81 (s, 1H), 7.61 (d, J 
8.4, Hz, 1H), 7.487.39 (m, 7H), 7.337.28 (m, 4H), 3.17-3.08 (m, 1H),
1.41 (d, J  6.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) 145.7, 139.1,
138.6, 135.7, 134.4, 133.0, 131.6, 130.4, 129.5, 128.6, 128.3, 127.5,
127.3, 123.8, 123.1, 119.2, 34.2, 24.2; IR (Neat)max 2957, 2923, 1595,
1439, 1029, 694 cm1; HRMS (ESI) for C23H20NaOS (M+Na)+: calcd.
367.1127, found 367.1127.
Inseparable mixture of 4i and 4i′ (1:1, 104 mg, 62%), colorless crystalline
solid. 1H NMR (400 MHz, CDCl3) 7.65, (bs, 1H), 7.46 (d, J  8.4 Hz,
1H), 7.437.34 (m, 3H), 7.317.23 (m, 4H), 7.20 (bd, J  3.4 Hz, 2H),
7.187.13 (m, 1H), 2.48 (s, 3H); 13C NMR (101 MHz, CDCl3) 139.1,
139.0, 138.8, 138.6, 138.3, 136.8, 135.4, 134.8, 134.7, 134.13, 134.06,
133.51, 133.48, 133.2, 132.9, 131.7, 130.7, 130.3, 129.6, 128.9, 128.7,
128.5, 128.4, 127.7, 127.5, 126.3, 123.1, 122.7, 122.0, 121.9, 21.5.
Both the regioisomeric products 4i and 4i′ are indistinguishable by 1H
NMR, however, the 13C NMR studies clearly reveals the formation of both
regioisomers 4i and 4i′.
6-Methoxy-3-(4-methoxyphenyl)-2-(4-nitrophenyl)benzo[b]thiophene
(4j): 4j (113 mg, 58%), pale yellow solid. mp  152153C; Rf = 0.25
(49:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) 8.8 (d, J  8.8 Hz,
2H), 7.48 (d, J  8.8 Hz, 1H), 7.41 (d, J  8.8 Hz, 2H), 7.34 (d, J  2.0 Hz,
1H), 7.22 (d, J  8.4 Hz, 2H), 7.207.92 (m, 3H), 3.90 (s, 3H), 3.87 (s,
3H); 13C NMR (101 MHz, CDCl3) 159.3, 158.3, 146.3, 141.4, 140.6,
135.3, 134.9, 133.2, 131.2, 129.6, 126.9, 124.7, 123.6, 115.0, 114.5,
104.4, 55.6, 55.2; IR (Neat)max 2863, 1642, 1237, 728, 628 cm1; HRMS
(ESI) for C22H17NNaO4S (M+Na)+: calcd. 414.0770, found 414.0773.
Acknowledgements
We thank SERB, CSIR, UPE-II, and PURSE for the financial
support. E.R thank CSIR, India for a fellowship. The N-PDF
fellowship from SERB to T.G is acknowleged. Dr. Nagrjuna and
Balaraju UoH are thanked for the X-ray crystallograpic analysis.
3-(4-Methoxyphenyl)-6-methyl-2-(4-nitrophenyl)benzo[b]thiophene
(4k): 4k (105 mg, 56%), yellow solid. mp  164165C; Rf = 0.31 (49:1
hexane/EtOAc); 1H NMR (400 MHz, CDCl3) 8.10 (d, J 8.8 Hz, 2H),
7.69 (s, 1H), 7.50 (d, J  8.4 Hz, 1H), 7.45 (d, J  8.8 Hz, 2H), 7.237.17
(m, 3H), 6.97 (d, J  8.8 Hz, 2H), 3.87 (s, 3H), 2.50 (s, 3H); 13C NMR
(101 MHz, CDCl3) 159.3, 146.5, 141.5, 139.4, 138.7, 135.7, 135.4,
134.8, 131.3, 129.9, 126.9, 126.6, 123.6, 122.0, 114.5, 55.3, 21.6; IR
(Neat)max 2923, 1579, 1237, 749, 632 cm1; HRMS (ESI) for
C22H18NO3S (M+H)+: calcd. 376.1002, found 376.1005.
Keywords: Benzo[b]thiophene • Annulation • Lewis acid •
unactivated alkynes • 1,2-S-Migration
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AlCl3 Catalysis
E. Ramesh, T. Guntreddi and A. K.
Sahoo*
AlCl3-Catalyzed Intermolecular
Annulation of Thiol-Derivatives
and Alkynes via 1,2-S-Migration
A novel AlCl3-catalyzed intermolecular oxidative annulation
of N-arylthio phthalimide derivatives with alkynes is
showcased at room temperature. The annulation involves
oxidative cleavage of the SN bond and the occurrence of
1,2-S-migration, which eventually allows the construction of
diverse arrays of -conjugated 6-substituted 2,3-diaryl
benzo[b]thiophene derivatives.
at
Room
Temperature:
Construction of 6-Substituted
Benzo[b]thiophenes
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