Orthogonal synthesis of densely functionalized pyrroles and thiophenes from the reactions of imidazo[l,5-a]pyridine carbene-derived zwitterions with electron-deficient alkynes

Article abstract of DOI:10.1021/jo100225r

(Figure Presented) 1-Thiocarbamoyl imidazo[l,5-a]pyridinium inner salts, which were obtained readily from the addition of C,N-substituted heterocyclic carbenes imidazo[1,5-a]pyridine-l-ylidenes to isothiocyanates, are powerful ambident nucleophilic zwitterions. They acted as nitrogen nucleophiles toward ethyl propiolate to produce polyfunctionalized pyrrole derivatives in high yields. When treated with dimethyl acetylenedicarboxylate, they behaved exclusively as sulfur nucleophiles to afford fully substituted thiophenes in excellent yields. This work provides highly efficient orthogonal synthesis of polyfunctionalized pyrroles and thiophenes that were not easily obtained by other chemical means.

Full text of DOI:10.1021/jo100225r

pubs.acs.org/joc
Orthogonal Synthesis of Densely Functionalized Pyrroles and Thiophenes
from the Reactions of Imidazo[1,5-a]pyridine Carbene-Derived
Zwitterions with Electron-Deficient Alkynes
Ying Cheng,* Jiang-Hua Peng, and Jia-Qi Li
College of Chemistry, Beijing Normal University, Beijing 100875, China
ycheng2@bnu.edu.cn
Received February 8, 2010
1-Thiocarbamoyl imidazo[1,5-a]pyridinium inner salts, which were obtained readily from the
addition of C,N-substituted heterocyclic carbenes imidazo[1,5-a]pyridine-1-ylidenes to isothiocya-
nates, are powerful ambident nucleophilic zwitterions. They acted as nitrogen nucleophiles toward
ethyl propiolate to produce polyfunctionalized pyrrole derivatives in high yields. When treated with
dimethyl acetylenedicarboxylate, they behaved exclusively as sulfur nucleophiles to afford fully
substituted thiophenes in excellent yields. This work provides highly efficient orthogonal synthesis of
polyfunctionalized pyrroles and thiophenes that were not easily obtained by other chemical means.
Introduction
bisindole pyrroles, lynamicins A-E, show broad-spectrum
activity against both Gram-positive and Gram-negative
organisms,5 while the pyrrole-amidine TAN 868A6 and the
chlorinated pyrrole LL-F422487 are antibiotics. The two
analogous pyrrole-2-carboxylate alkaloids, Agelongine and
Daminin, have antiserotonergic activity and neuroprotective
properties, respectively.8 A number of synthetic pyrrole
derivatives were proven very active against both fungi and
mycobacteria, and other pyrroles are COX-2 (cyclo-
oxygenase) selective inhibitors.2a Similar to the pyrrole
derivatives, many polyfunctional thiophenes have important
The studies of polyfunctionalized pyrroles and thiophenes
continue to be an active field of research, spanning from
natural product synthesis1 through medicinal chemistry2 and
on to material science.3 The pyrrole moiety is ubiquitous in
natural products, and numerous natural and unnatural
pyrrole derivatives possess remarkable biological and phar-
macological activities.4 For example, a series of chlorinated
(1) (a) Agarwal, S.; Caemmerer, S.; Filali, S.; Froehner, W.; Knoell, J.;
Krahl, M. P.; Reddy, K. R.; Knoelker, H.-J. Curr. Org. Chem. 2005, 9, 1601–
1614. (b) Gupton, J. T.; Giglio, B. C.; Eaton, J. E.; Rieck, E. A.; Smith, K. L.;
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62, 7213–7256.
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(4) Gupton, J. T. Top. Heterocycl. Chem. 2006, 2, 53–92.
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D. J.; Grodberg, J.; Lam, K. S.; Potts, B. C. M. J. Nat. Prod. 2008, 71, 1732–
1737.
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J. Antibiot. 1987, 40, 1220–1230.
(7) Carter, G. T.; Nietsche, J. A.; Goodman, J. J.; Torrey, M. J.; Dunne,
T. S.; Borders, D. B.; Testa, R. T. J. Antibiot. 1987, 40, 233–236.
(8) Aiello, A.; D’Esposito, M.; Fattorusso, E.; Menna, M.; Mueller, W. E.
G.; Perovic-Ottstadt, S.; Tsuruta, H.; Gulder, T. A. M.; Bringmann, G.
Tetrahedron 2005, 61, 7266–7270.
2382 J. Org. Chem. 2010, 75, 2382–2388
Published on Web 03/08/2010
DOI: 10.1021/jo100225r
r
2010 American Chemical Society

Cheng et al.
JOCArticle
bioactivities. For instance, some diarylthiophenes are inhi-
bitors of tumor necrosis factor-R,9 and a series of 2-amino-
4-methylthiophenecarboxylate derivatives show good anti-
inflammatory or analgesic activities.10 In addition to the
huge potentials in pharmacological applications, polyfunc-
tional pyrroles and thiophenes are important precursors of
organic functional materials. Polypyrrole- and polythio-
phene-based conducting polymers have various applications
in microelectronics, electrode materials, sensors, and optoe-
lectronics.3,11 Because of the great importance of pyrrole
and thiophene derivatives, the synthetic study remains un-
diminished.12 The traditional Paal-Knorr,13 Knorr,14 and
Hantzsch15 reactions, along with the strategies of 1,3-dipolar
cycloaddition,16 metal-mediated synthesis,17 carbenoidtrans-
fer reactions,18 and ring contractions19 have been well prac-
tised in the construction of pyrroles, and the Hinsberg20
and Gewald21 reactions are two of the most used methods for
the preparation of thiophene derivatives. Although a num-
ber of methods for the construction of pyrroles and
thiophenes have been established, the efficient synthesis of
highly functionalized pyrroles and thiophenes remains chal-
lenging.
inner salts are unusual ambident 1,3-dipolar reagents.22a On
the basis of the [3 þ 2] cycloaddition reactions of novel 1,3-
dipoles or dipolar intermediates readily available from the
addition of N-heterocyclic carbenes to heterocumulenes such
as isothiocyanates, isoselenocyanates and ketenimines, we
have established and developed a powerful methodology for
the construction of spiro- or fused pyrroles and thiophenes.22
The diverse reaction pathways are regulated by the nature of
both N-heterocyclic carbenes and 1,3-dipolarophiles. Our
continued interest in the chemistry of N-heterocyclic car-
benes led us to study the reactivity of novel dipolar adducts
derived from various N-heterocyclic carbenes and hetero-
cumulenes. Our attention was drawn then by imidazo[1,5-
a]pyridine carbenes, which have been generated easily from
the deprotonation of imidazo[1,5-a]pyridinium salts re-
ported by Lassaletta23 and Glorius24 in 2005. Interestingly,
depending on the position of a substituent on the imidazole
ring, imidazo[1,5-a]pyridinium salts can be deprotonated at
the 1- or 3-position to produce imidazo[1,5-a]pyridine-
1-ylidenes or imidazo[1,5-a]pyridine-3-ylidenes that can be
regarded as C,N-substituted and N,N-substituted carbenes,
respectively. Both imidazo[1,5-a]pyridine-1-ylidenes and
imidazo[1,5-a]pyridine-3-ylidenes have been shown to be
strong C-ligands to Ag, Rh, Ir, and Pd cations and elemental
Se. Surprisingly, their reactions with organic compounds
either as reagents or as organocatalysts have never been
explored. We envisioned that the addition of 3-arylimi-
dazo[1,5-a]pyridine-1-ylidenes, the C,N-substituted carbenes,
to aryl isothiocyanates would form 1-thiocarbamoyl-
imidazo[1,5-a]pyridinium zwitterions. Being different
from the 1,3-dipolar adducts derived from the addition
of N,N- and N,S-substituted heterocyclic carbenes to
heterocumulenes, the 1-thiocarbamoylimidazo[1,5-a]pyri-
dinium zwitterions are not 1,3-dipoles because their cation
and anion centers are separated by more than one atom.
As a new bis-nucleophilic dipolar species, they might
undergo unique reactions with electron-deficient alkynes.
Herein we report highly efficient and orthogonal synthesis
of polyfunctionalized pyrroles and thiophenes from
the reaction of 1-thiocarbamoylimidazo[1,5-a]pyridinium
inner salts with ethyl propiolate and dimethyl acetylene-
dicarboxylate.
In 2006, we discovered that N-heterocyclic carbene-de-
rived 2-thiocarbamoyl benzimidazolium and imidazolinium
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Results and Discussion
In this work, the carbene precursors, 3-arylimidazo[1,5-
a]pyridinium salts 1, were synthesized from pyridine-2-car-
baldehyde and amines via a POCl3-mediated cyclization of
an amide intermediate according to literature methods.23,24
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1217. (b) Cheng, Y.; Liu, M.-F.; Fang, D.-C.; Lei, X.-M. Chem.;Eur. J.
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Fang, D.-C. J. Org. Chem. 2009, 74, 2357–2367. (d) Li, J.-Q.; Liao, R.-Z.;
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J. Org. Chem. Vol. 75, No. 7, 2010 2383

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SCHEME 1. Preparation of 1-Thiocarbamoyl Imidazo[1,5-
a]pyridinium Inner Salts 4
TABLE 2. Reaction of 4a with Ethyl Propiolate under Different Con-
ditions
TABLE 1. Reaction of Imidazo[1,5-a]pyridinium Salts 1 with Aryl
Isothiocyanates in the Presence of t-BuOKa
entry
1
Ar1 or R
3
Ar2
yield of 4 (%)b
reaction conditions
1
2
3
4
5
6
7
8
1a
1b
1b
1c
1c
1d
1d
1d
1d
1f
Ph
3a
3a
3b
3a
3b
3a
3b
3c
3d
3a
3b
Ph
Ph
p-BrC6H4
Ph
p-BrC6H4
Ph
p-BrC6H4
p-ClC6H4
p-MeOC6H4
Ph
4a: 84
4b: 75
4c: 66
4d: 80
4e: 59
4f: 67
4g: 81
4h: 72
4i: 67
4j: 81
4k: 74
entry
solvent
THF
acetone
dichloromethane
acetonitrile
benzene
temp
time
6 h
6 h
6 h
6 h
6 h
6 h
20 min
yield of 6a (%)
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
Et
1
2
3
4
5
6
7
rt
rt
rt
rt
rt
rt
80 °C
77
69
74
65
76
93
68
1,4-dioxane
1,4-dioxane
9
10
11
1g
i-Pr
p-BrC6H4
aReaction conditions: THF, -20 °C, 8 h, 1:3 = 1:1.2. bIsolated yield.
TABLE 3. Reaction of 4 with Ethyl Propiolate under Optimized Con-
ditions
The 3-aryl-1-thiocarbamoylimidazo[1,5-a]pyridinium zwit-
terions 4 were prepared from the reaction of 3-arylimidazo-
[1,5-a]pyridine-1-ylidenes 2 with aryl isothiocyanates. Thus,
the reaction of 3-arylimidazo[1,5-a]pyridinium salts 1 with
aryl isothiocyanates 3 in the presence of t-BuOK took place
at -20 °C for 8 h to afford yellow crystalline 1-thiocarba-
moyl imidazo[1,5-a]pyridinium inner salts 4 in 59-84%
yields (Scheme 1, Table 1).
With 1-thiocarbamoylimidazo[1,5-a]pyridinium zwitter-
ions 4 in hand, we first studied their reaction with ethyl
propiolate. The reaction of 1-(N-phenyl)thiocarbamoyl-2,3-
diphenylimidazo[1,5-a]pyridinium inner salt 4a with ethyl
propiolate in THF proceeded smoothly at ambient tempera-
ture to give a new product. Instead of the formation of spiro
or fused heterocyclic product that was anticipated on the
basis of our previous investigations, the product was surpris-
ingly a polyfunctionalized pyrrole derivative, (Z)-1-phenyl-
5-[phenyl(phenylimino)methylthio]-4-(2-pyridinyl)pyrrole-
3-carboxylate 6a. The reaction conditions were optimized by
varying solvents and reaction temperature in order to obtain
high chemical yield. At room temperature, the reaction was
found to proceed smoothly in both polar and nonpolar
solvents including acetone, acetonitrile, 1,4-dioxane, THF,
dichloromethane, and benzene. The highest yield of product
6a (93%) was obtained when reaction was performed in 1,4-
dioxane at room temperature. The increase of the tempera-
ture led to acceleration of the reaction but with a diminished
chemical yield (Table 2, entries 6 and 7).
The generality of the reaction was studied under the
optimized conditions using zwitterions 4 bearing different
substituents. As summarized in Table 3, 1-arylthiocarba-
moyl-2-aryl imidazo[1,5-a]pyridiniums 4 with a p-tolyl,
p-anisyl, or p-halophenyl on the nitrogen atom of the imi-
dazole ring or thiocarbamoyl group reacted efficiently with
ethyl propiolate, furnishing (Z)-1-aryl-5-[aryl(arylimino)-
methylthio]-4-(2-pyridinyl)pyrrole-3-carboxylates 6 in good
to excellent yields. Varying 2-aryl to 2-alkyl, the reactions of
2-ethyl- and 2-isopropyl-substituted imidazo[1,5-a]pyridinium
inner salts 4j and 4k with ethyl propiolate were also exam-
ined. Although these reactions proceeded equally efficiently,
entry
4
Ar1
Ar2
yield of 6 (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
Ph
Ph
Ph
6a: 93
6b: 89
6c: 93
6d: 92
6e: 84
6f: 86
6g: 85
6h: 90
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-BrC6H4
Ph
p-BrC6H4
Ph
p-BrC6H4
p-ClC6H4
4g
4h
p-ClC6H4
p-ClC6H4
they afforded however a mixture of products that were most
probably the Z- and E-isomers determined by 1H NMR and
microanalysis. These isomers could not been separated by
column chromatography or recrystallization, and therefore
pure products from 2-alkylimidazo[1,5-a]pyridinium inner
salts 4 were not obtained.
After the reaction of zwitterions 4 with propiolate, the
interaction of 4 with dimethyl acetylenedicarboxylate
(DMAD), a more electrophilic reagent, was studied. The reac-
tion of 1-N-(p-bromophenyl)thiocarbamoyl-2-(p-methoxy-
phenyl)-3-phenylimidazo[1,5-a]pyridinium inner salt 4e with
DMAD took place more efficiently. In all reaction media
including acetone, acetonitrile, 1,4-dioxane, THF, dichloro-
methane, and benzene, for example, the reaction went to com-
pletion within 2 h at room temperature to yield a single product
in an excellent yield (Table 4). Interestingly, the reaction
afforded a fully substituted thiophene compound, (E)-dimethyl
5-[N-(4-bromophenyl)-N0-(4-methoxyphenyl)benzimidamido]-
4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8e rather than pyr-
role product. Applying the optimized conditions such as using
THF as the solvent, other 2-arylimidazo[1,5-a]pyridiniums 4
2384 J. Org. Chem. Vol. 75, No. 7, 2010

Cheng et al.
JOCArticle
TABLE 4. Reaction of 4e with DMAD under Different Conditions
SCHEME 2. Proposed Mechanism for the Formation of
4-Pyridinylpyrroles 6
reaction conditions
entry
solvent
THF
acetone
dichloromethane
acetonitrile
benzene
temp
time
yield of 6a (%)
1
2
3
4
5
6
rt
rt
rt
rt
rt
rt
2 h
2 h
2 h
2 h
2 h
2 h
94
91
90
90
88
90
1,4-dioxane
TABLE 5. Reaction of 4 with DMAD under Optimized Conditions
single crystal structure of 8f indicated that a E-configured
CdN bond could reduce the steric repulsion between N-aryl
and pyridinyl groups substituted to the imine and thiophene
moiety, respectively. Therefore, the stereoselectivity of the
reaction between 4 and DMAD was probably controlled by
the steric hindrance between N-aryl and pyridinyl groups of
products 8. As aforementioned, the reaction of 2-ethyl- or
2-isopropylimidazo[1,5-a]pyridinium inner salt 4j or 4k with
both propiolate and DMAD had stereoselectivity lower than
that of 2-arylimidazo[1,5-a]pyridinium inner salts 4a-4i,
producing a mixture of isomeric products. Apparently, it is
the steric effect of substituents connected to the imine moiety
that controlled the stereoselectivity, because the steric repul-
sion between an ethyl or an isopropyl and an aryl group is
less than the repulsion between two aryl groups.
Our previous studies have shown that the 1,3-dipolar
adducts derived from N-heterocyclic carbenes and isothio-
cyanates are ambident Cþ-C-S- and Cþ-C-N- 1,3-di-
poles reacting with electron-deficient alkenes, alkynes,
ketenes, and allenes to afford either spiro- or fused-pyrrole
and spiro- or fused-thiophene derivatives.22a-f The respec-
tive formation of 5-aryliminomethylthio-4-pyridinylpyr-
roles 6 and 5-benzimidamido-4-pyridinylthiophenes 8 from
the reactions of zwitterions 4 with propiolate and dimethyl
acetylenedicarboxylate is however intriguing. The pyrrole-
3-carboxylate moiety in 6 and thiophene-2,3-dicarboxylate
moiety in 8 indicated that the overall reactions involved an
annulation of the C-C-N or C-C-S species of zwitterions
4 with the carbon-carbon triple bond of alkynes. To account
for the formations of 4-pyridinylpyrroles 6 and 4-pyridi-
nylthiophenes 8, two different tandem chemo-specific cycli-
zations and the subsequent [2,3]-sigmatropic rearrangements
were proposed. As depicted in Scheme 2, imidazo[1,5-
a]pyridinium inner salts 4 behaved as a nitrogen nucleophile
to undergo a nucleophilic addition and intramolecular cycliza-
tion (or a formal [3 þ 2] cycloaddition) with propiolate to
form spiro-pyrrole intermediate 10. Aromatization of the
dihydropyridine anion of 10 led to the ring opening of imida-
zole forming a 3-iminium ylide substituted pyrrole-2-thione
entry
4
Ar1
Ar2
yield of 8 (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
Ph
Ph
Ph
8a: 94
8b: 83
8c: 90
8d: 84
8e: 86
8f: 94
8g: 94
8i: 93
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-BrC6H4
Ph
p-BrC6H4
Ph
p-BrC6H4
p-MeOC6H4
4g
4i
p-ClC6H4
p-ClC6H4
bearing different substituents underwent reaction with DMAD
very efficiently at ambient temperature to furnish 4-(2-pyridi-
nyl)thiophene-2,3-dicarboxylates 8 in good to excellent yields
(Table 5). Similar to the reaction of 2-alkylimidazo[1,5-a]-
pyridinium zwitterions 4 with propiolate, the interaction of 2-
isopropylimidazo[1,5-a]pyridinium inner salt 4k with DMAD
also gave most probably a mixture of Z- and E-configured
amidino-substituted thiophene isomers, which could not be
separated by column chromatography or recrystallization.
The structures of all products were fully characterized by
spectroscopic data and microanalysis. The NMR spectra,
mass data, and microanalysis indicated that the constitutions
of all products 6 and 8 were the 1 þ 1 adducts of two starting
materials. Since the spectroscopic data did not allow full
verification of the structures, to identify the products beyond
doubt, the structures of 6g and 8f were determined unam-
biguously by single crystal X-ray diffraction analysis (see
Figure S1 in Supporting Information). Interestingly, the
imine double bonds of products 6 have a Z-configuration,
whereas those of compounds 8 are E-configured. It is most
likely that the reaction of zwitterions 4 with propiolate
preferred to form Z-configured products 6, since the Z-imine
could avoid the steric repulsion between two aryl rings
bearing the CdN bond. However, the predominate forma-
tion of E-configured thiophenes 8 was not expected. The
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Cheng et al.
JOCArticle
SCHEME 3. Proposed Mechanism for the Formation of
4-Pyridinylthiophenes 8
of the double bond of an allyl or propargyl group with the
migration to its vicinal anion center.25,26 In the current
work, however, the reactions most probably proceeded
via two new versions of [2,3]-sigmatropic rearrangements.
One of them involves the conversion of SdC-C-NþdC- to
CdC-S-CdN, while the other is the transformation of
NdC-C-NþdC- to CdC-N-CdN. The driving force
of the unusual [2,3]-sigmatropic rearrangements was probably
attributed to the stabilization energy gained from aro-
matization, the formation of polyconjugated pyrroles and
thiophenes.
Conclusion
In summary, we have shown that 1-thiocarbamoyl
imidazo[1,5-a]pyridinium inner salts, which were derived
readily from addition of imidazo[1,5-a]pyridine-1-ylidenes
with aryl isothiocyanates, were powerful ambident nucleo-
philic zwitterions. Under very mild conditions, they acted
exclusively as nitrogen or sulfur nucleophiles toward ethyl
propiolate or dimethyl acetylenedicarboxylate to produce
4-pyridinylpyrrole or 4-pyridinylthiophene derivatives, re-
spectively, in good to excellent yields. Two different tandem
chemo-specific cyclizations and subsequent novel [2,3]-sig-
matropic rearrangements were proposed for the formations
of products. The reactions provide highly efficient orthogo-
nal synthesis of polyfunctionalized pyrroles and thiophenes
that were not easily obtained by other chemical means.
intermediate 11. Most likely, an [2,3]-sigmatropic rearrange-
ment of SdC-C-NþdC- to NdC-S-CdC furnished
5-aryliminomethylthio-4-pyridinylpyrroles 6 (Scheme 2).
When treated with DMAD, the ambident zwitterions 4 acted
as a sulfur nucleophile to cyclize with the triple bond of DMAD
to form spiro-thiophene intermediate 13. Aromatization of the
dihydropyridine anion of 13 produced an 3-iminium ylide
substituted 2-aryliminothiophene intermediate 14. The [2,3]-
sigmatropic rearrangement from NdC-C-NþdC- to
NdC-N-CdC moiety of 14 afforded the final 5-benzimida-
mido-4-pyridinylthiophenes 8 (Scheme 3). It should be noted
that the chemoselectivity of the reactions of 1-thiocarbamoyl
imidazo[1,5-a]pyridinium zwitterions 4 with propiolate and
with DMAD was in good agreement with our previous ob-
servations on the reactions of 1,3-dipoles derived from N,N-
and N,S-substituted heterocyclic carbenes. On the basis of our
theoretical study, it is the electronic and steric effects of
dipolarophile that controlled the chemoselectivity of the dipoles
derived from N-heterocyclic carbenes and isothiocyanates.22b-d
It is also worth addressing that all documented [2,3]-sigmatropic
rearrangements generally involve either the transformation
of CdC-C-Xþ-Y- to X-Y-C-CdC or the conversion
of CtC-C-Xþ-Y- to X-Y-CdCdC, the transposition
Experimental Section
General Procedure for the Reaction of 1-Thiocarbamoyl
Imidazo[1,5-a]pyridinium Inner Salts 4 with Ethyl Propiolate.
At ambient temperature (summer time, around 25 °C), the ethyl
propiolate (1.1 mmol) was added dropwise to the 1-thiocarba-
moyl imidazo[1,5-a]pyridinium salts 4 (0.6 mmol) in 1,4-dioxane
(30 mL). The reaction mixture was stirred at room temperature
for about 6 h. After removal of solvent under vacuum, the pro-
ducts, (Z)-1-aryl-5-[aryl(arylimino)methylthio]-4-(2-pyridinyl)-
pyrrole-3-carboxylates 6, were isolated in 84-93% yields by
chromatography on a silica gel column eluting with a mixture of
ethyl acetate and petroleum ether (30-60 °C) (1:2).
(Z)-Ethyl 1-Phenyl-5-[phenyl(phenylimino)methylthio]-4-(2-
pyridinyl)pyrrole-3-carboxylate 6a. Yield 93%, mp 146-147 °C;
IR v (cm-1) 1714, 1612, 1591, 1509; 1H NMR (400 MHz,
DMSO-d6, 70 °C) δ (ppm) 8.67 (d, J = 4.3 Hz, 1H), 7.85 (dt,
J = 7.7, 1.6 Hz, 1H), 7.65 (br, 1H), 7.54-7.58 (m, 3H), 7.34-
7.41 (m, 4H), 7.22-7.26 (m, 5H), 7.00-7.04 (m, 3H), 6.43 (d,
J = 7.4 Hz, 2H), 4.03 (q, J = 7.1 Hz, 2H), 1.05 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, DMSO-d6) δ (ppm) 162.6, 161.5,
152.6, 149.3, 148.6, 137.2, 136.1, 135.4, 133.2, 130.6, 130.1,
129.1, 128.8, 128.4, 127.5, 126.4, 126.0, 124.1, 122.0, 120.2,
118.9, 118.6, 115.1, 59.3, 13.8; MS (ESI) 504 (M þ 1), 526
(M þ Naþ). Anal. Calcd for C31H25N3O2S: C 73.93, H 5.00, N
8.34. Found: C 73.64, H 5.38, N 8.31.
(25) Some reviews for the [2,3]-sigmatropic rearrangements, see: (a)
Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885–902. (b) Somfai, P.;
Panknin, O. Synlett 2007, 1190–1202. (c) Braverman, S.; Cherkinsky, M.
Top. Curr. Chem. 2007, 275, 67–101. (d) Reggelin, M. Top. Curr. Chem. 2007,
275, 1–65.
(26) For some examples for the [2,3]-sigmatropic rearrangements, see: (a)
Hodgson, D. M.; Angrish, D.; Erickson, S. P.; Kloesges, J.; Lee, C. H. Org.
Lett. 2008, 10, 5553–5556. (b) Armstrong, A.; Emmerson, D. P. G. Org. Lett.
2009, 11, 1547–1550. (c) Armstrong, A.; Challinor, L.; Cooke, R. S.; Moir,
J. H.; Treweeke, N. R. J. Org. Chem. 2006, 71, 4028–4030. (d) Blid, J.;
Panknin, O.; Somfai, P. J. Am. Chem. Soc. 2005, 127, 9352–9353. (e) Roberts,
E.; Sancon, J. P.; Sweeney, J. B. Org. Lett. 2005, 7, 2075–2078. (f) Workman,
J. A.; Garrido, N. P.; Sancon, J.; Roberts, E.; Wessel, H. P.; Sweeney, J. B.
J. Am. Chem. Soc. 2005, 127, 1066–1067. (g) Crich, D.; Zou, Y.; Brebion, F.
J. Org. Chem. 2006, 71, 9172–9177. (h) Ma, M.; Peng, L.-L.; Li, C.-K.;
Zhang, X.; Wang, J.-B. J. Am. Chem. Soc. 2005, 127, 15016–15017. (i) Cere,
V.; Paolucci, C.; Pollicino, S.; Sandri, E.; Fava, A. J. Org. Chem. 1979, 44,
4128–4135. (j) Blid, J.; Panknin, O.; Tuzina, P.; Somfai, P. J. Org. Chem.
2007, 72, 1294–1300. (k) Crich, D.; Krishnamurthy, V.; Hutton, T. K. J. Am.
Chem. Soc. 2006, 128, 2544–2545. (l) Reich, H. J.; Yelm, K. E. J. Org. Chem.
1991, 56, 5672–5679.
(Z)-Ethyl 1-Phenyl-5-[phenyl(p-tolylimino)methylthio]-4-(2-
pyridinyl)pyrrole-3-carboxylate 6b. Yield 89%, mp 120-121 °C;
IR v (cm-1) 1713, 1611, 1589, 1506; 1H NMR (400 MHz,
DMSO-d6, 70 °C) δ (ppm) 8.64 (d, J = 4.1 Hz, 1H), 7.83 (dt,
J = 7.7, 1.8 Hz, 1H), 7.61 (br, 1H), 7.52-7.54 (m, 3H),
7.31-7.37 (m, 3H), 7.23 (d, J = 7.7 Hz, 4H), 7.03 (d, J = 6.8
Hz, 2H), 6.97 (d, J = 6.4 Hz, 2H), 6.31 (d, J = 8.2 Hz, 2H), 4.01
(q, J = 7.1 Hz, 2H), 2.23 (s, 3H), 1.03 (t, J = 7.1 Hz, 3H); 13
C
NMR (125 MHz, CDCl3) δ (ppm) 163.5, 162.0, 153.2, 149.0,
147.0, 137.9, 136.8, 135.3, 134.0, 133.6, 130.5, 130.0, 129.2,
129.1, 128.8, 128.3, 127.6, 126.6, 126.3, 122.0, 120.8, 119.7,
115.7, 59.8, 21.0, 14.1; MS (ESI) 518 (M þ 1), 540 (M þ Naþ).
2386 J. Org. Chem. Vol. 75, No. 7, 2010

Cheng et al.
JOCArticle
Anal. Calcd for C32H27N3O2S: C 74.25, H 5.26, N 8.12. Found:
C 73.96, H 5.62, N 8.09.
Calcd for C31H23BrClN3O2S: C 60.35, H 3.76, N 6.81. Found: C
60.15, H 4.07, N 6.79.
(Z)-Ethyl 1-(p-Bromophenyl)-5-[phenyl(p-tolylimino)methylthio]-
4-(2-pyridinyl)pyrrole-3-carboxylate 6c. Yield 93%, mp 130-
(Z)-Ethyl 1-(p-Chlorophenyl)-5-[phenyl(p-chlorophenylimino)-
methylthio]-4-(2-pyridinyl)pyrrole-3-carboxylate 6h. Yield 90%,
1
1
131 °C; IR v (cm-1) 1704, 1607, 1590, 1504, 1493; H NMR
mp 133-134 °C; IR v (cm-1) 1704, 1602, 1590, 1511, 1496; H
NMR (400 MHz, DMSO-d6, 70 °C) δ (ppm) 8.64 (d, J = 4.0 Hz,
1H), 7.84 (dt, J = 7.7 1.8 Hz, 1H), 7.68 (brs, 1H), 7.59 (d, J =
8.7 Hz, 2H), 7.34-7.38 (m, 3H), 7.24-7.27 (m, 6H), 7.00 (d, J =
7.5 Hz, 2H), 6.45 (d, J = 8.6 Hz, 2H), 4.02 (q, J = 7.1 Hz, 2H),
1.04 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm)
163.3, 162.6, 152.9, 149.0, 147.8, 136.4, 135.3, 134.4, 134.1, 130.4,
129.9, 129.2, 129.0, 128.8, 127.8, 126.2, 122.1, 121.5, 121.3,
119.4, 116.1, 59.9, 14.0; MS (ESI) 572 (M þ 1). Anal. Calcd for
C31H23Cl2N3O2S: C 65.04, H 4.05, N 7.34. Found: C 64.92, H
4.32, N 7.16.
(400 MHz, DMSO-d6, 70 °C) δ (ppm) 8.66 (ddd, J = 4.8, 1.8, 0.9
Hz, 1H), 7.85 (dt, J = 7.7, 1.8 Hz, 1H), 7.72 (d, J = 8.6 Hz, 2H),
7.67 (brs, 1H), 7.32-7.37 (m, 3H), 7.24 (t, J = 7.8 Hz, 2H), 7.23
(br, 2H), 7.05 (d, J = 7.1 Hz, 2H), 7.01 (d, J = 7.3 Hz, 2H), 6.35
(d, J = 8.2 Hz, 2H), 4.02 (q, J = 7.1 Hz, 2H), 2.25 (s, 3H), 1.04 (t,
J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 163.4,
161.2, 152.9, 149.0, 146.7, 136.8, 135.4, 134.3, 133.8, 132.2,
130.1, 129.3, 128.8, 128.1, 127.7, 126.3, 122.1, 120.7, 119.9,
116.0, 59.9, 21.0, 14.1; MS (ESI) 596 (M þ 1), 618 (M þ Naþ).
Anal. Calcd for C32H26BrN3O2S: C 64.43, H 4.39, N 7.04.
Found: C 64.21, H 4.72, N 7.02.
General Procedure for the Reaction of 1-Thiocarbamoyl
Imidazo[1,5-a]pyridinium Inner Salts 4 with Dimethyl Acetylene-
dicarboxylate. At ambient temperature (winter time, around
15 °C), DMAD (1.0 mmol) was added dropwise to the 1-
thiocarbamoyl imidazo[1,5-a]pyridinium salts 4 (0.6 mmol) in
THF (30 mL). The reaction mixture was stirred at room
temperature for about 2 h. After removal of solvent under
vacuum, the residue was chromatographied on a silica gel
column (ethyl acetate/petroleum ether (30-60 °C) = 1:2) to
afford (E)-dimethyl 5-(N-aryl-N0-arylbenzimidamido)-4-(2-
pyridinyl)thiophene-2,3-dicarboxylates 8 in 83-94% yields.
(E)-Dimethyl 5-(N,N0-Diphenylbenzimidamido)-4-(2-pyridinyl)-
thiophene-2,3-dicarboxylate 8a. Yield 93%, mp 182-181 °C; IR v
(cm-1) 1725, 1717, 1635, 1590, 1491; 1H NMR (400 MHz,
CD3COCD3) δ (ppm) 8.66 (ddd, J = 4.8, 1.7, 0.9 Hz, 1H), 7.89
(dt, J = 7.8, 1.8 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.34-7.38
(m, 3H), 7.24 (dt, J = 8.2, 2.1 Hz, 2H), 7.02-7.13 (m, 6H), 6.94
(dt, J = 8.4, 1.6 Hz, 2H), 6.75 (dt, J = 7.2, 1.2 Hz, 1H), 6.19
(dt, J = 8.4, 1.1 Hz, 2H), 3.82 (s, 3H), 3.73 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 165.8, 161.4, 157.6, 151.7, 151.5,
149.4, 149.2, 144.4, 139.1, 136.3, 131.6, 130.1, 129.1, 128.9, 128.3,
128.1, 127.7, 126.6, 125.9, 125.1, 123.9, 122.6, 122.1, 121.6, 52.7,
52.5; MS (ESI) 548 (M þ 1), 570 (M þ Naþ). Anal. Calcd for
C32H25N3O4S: C 70.18, H 4.60, N 7.67. Found: C 70.10, H 4.83,
N 7.63.
(Z)-Ethyl 1-Phenyl-5-[phenyl(p-methoxyphenylimino)methylthio]-
4-(2-pyridinyl)pyrrole-3-carboxylate 6d. Yield 92%, mp 104-
105 °C; IR v (cm-1) 1717, 1614, 1590, 1501; 1H NMR (400 MHz,
DMSO-d6, 70 °C) δ (ppm) 8.66 (d, J = 4.1 Hz, 1H), 7.84 (dt, J =
7.7, 1.8 Hz, 1H), 7.63 (br, 1H), 7.53-7.54 (m, 3H), 7.34-7.37
(m, 4H), 7.24 (t, J = 7.4 Hz, 3H), 7.00 (brs, 2H), 6.82 (d, J = 6.7
Hz, 2H), 6.41 (d, J = 8.6 Hz, 2H), 4.02 (q, J = 7.1 Hz, 2H), 3.73
(s, 3H), 1.05 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, DMSO-
d6) δ (ppm) 162.6, 160.8, 156.2, 152.6, 148.6, 142.3, 137.2, 136.3,
135.4, 133.0, 130.4, 130.0, 129.1, 128.4, 127.5, 126.4, 125.9,
122.0, 121.6, 120.5, 119.0, 115.1, 114.0, 59.3, 55.1, 13.8; MS (ESI)
534 (M þ 1), 556 (M þ Naþ). Anal. Calcd for C32H27N3O3S:
C 72.02, H 5.10, N 7.87. Found: C 71.75, H 5.46, N 7.84.
(Z)-Ethyl 1-(p-Bromophenyl)-5-[phenyl(p-methoxyphenylimino)-
methylthio]-4-(2-pyridinyl)pyrrole-3-carboxylate 6e. Yield 84%,
1
mp 138-139 °C; IR v (cm-1) 1712, 1621, 1590, 1501; H NMR
(400 MHz, DMSO-d6, 70 °C) δ (ppm) 8.64 (d, J = 4.0 Hz, 1H),
7.83 (dt, J = 7.7, 1.7 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.63 (br,
1H), 7.31-7.37 (m, 3H), 7.23 (t, J= 7.4 Hz, 3H), 7.20 (br, 1H), 6.99
(d, J = 6.4 Hz, 2H), 6.82 (d, J = 6.0 Hz, 2H), 6.41 (d, J = 8.6 Hz,
2H), 4.01 (q, J = 7.1 Hz, 2H), 3.72 (s, 3H), 1.03 (t, J = 7.1 Hz, 3H);
13C NMR (400 MHz, DMSO-d6) δ (ppm) 162.6, 160.4, 156.4,
152.4, 148.7, 142.0, 136.3, 135.4, 133.2, 132.0, 130.3, 130.0, 128.4,
128.3, 127.6, 125.9, 122.0, 121.4, 120.6, 119.1, 115.3, 113.9, 59.4,
55.1, 13.8; MS (ESI) 612 (M þ 1), 623 (M þ Naþ). Anal. Calcd for
C32H26BrN3O3S: C 62.75, H 4.28, N 6.86. Found: C 62.64, H 4.32,
N 6.86.
(Z)-Ethyl 1-Phenyl-5-[phenyl(p-chlorophenylimino)methylthio]-
4-(2-pyridinyl)pyrrole-3-carboxylate 6f. Yield 86%, mp 156-
157 °C; IR v (cm-1) 1716, 1610, 1589, 1507; 1H NMR (400 MHz,
DMSO-d6, 70 °C) δ (ppm) 8.64 (ddd, J = 4.8, 1.7, 1.0 Hz, 1H), 7.84
(dt, J = 7.7, 1.8 Hz, 1H), 7.64 (brs, 1H), 7.52-7.58 (m, 3H),
7.33-7.38 (m, 3H), 7.23-7.26 (m, 6H), 6.98 (d, J = 7.3 Hz, 2H),
6.41 (d, J = 8.6 Hz, 2H), 4.02 (q, J = 7.1 Hz, 2H), 1.04 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm): 163.4, 153.2,
149.0, 148.0, 137.9, 136.6, 135.2, 133.9, 130.6, 130.2, 129.6, 129.0,
128.7, 128.4, 127.7, 126.6, 126.3, 122.0, 121.1, 119.3, 115.8, 59.8,
14.0; MS (ESI) 538 (M þ 1), 560 (M þ Naþ). Anal. Calcd for
C31H24ClN3O2S: C 69.20, H 4.50, N 7.81. Found: C 68.94, H 4.85,
N 7.78.
(Z)-Ethyl 1-(p-Bromophenyl)-5-[phenyl(p-chlorophenylimino)-
methylthio]-4-(2-pyridinyl)pyrrole-3-carboxylate 6g. Yield 85%, mp
119-120 °C; IR v (cm-1) 1712, 1609, 1589, 1536, 1508, 1493; 1H
NMR (400 MHz, DMSO-d6, 70 °C) δ (ppm) 8.67 (ddd, J = 4.8,
1.6, 0.9 Hz, 1H), 7.85 (dt, J = 7.7, 1.8 Hz, 1H), 7.74 (d, J = 8.6 Hz,
2H), 7.70 (br, 1H), 7.34-7.40 (m, 3H), 7.24-7.28 (m, 6H), 7.03 (d,
J = 7.4 Hz, 2H), 6.46 (d, J = 8.6 Hz, 2H), 4.03 (q, J = 7.1 Hz, 2H),
1.05 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm)
163.3, 162.6, 152.8, 149.0, 147.6, 136.8, 136.5, 135.3, 134.0, 132.3,
130.4, 130.3, 130.0, 128.8, 127.8, 126.3, 122.4, 122.2, 121.3, 119.5,
116.1, 60.0, 14.1; MS (ESI) 617 (M þ 2), 638 (M þ Naþ). Anal.
(E)-Dimethyl 5-[N-Phenyl-N0-(p-tolyl)benzimidamido]-4-(2-
pyridinyl)thiophene-2,3-dicarboxylate 8b. Yield 83%, mp 148-
1
149 °C; IR v (cm-1) 1732, 1715, 1626, 1591, 1490; H NMR
(400 MHz, CDCl3) δ (ppm) 8.58 (d, J = 4.5 Hz, 1H), 7.61 (dt,
J = 7.8, 1.8 Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.08-7.17 (m,
5H), 6.93-7.03 (m, 5H), 6.89 (d, J = 7.3 Hz, 2H), 6.73 (d, J =
8.1 Hz, 2H), 6.09 (d, J = 8.2 Hz, 2H), 3.78 (s, 3H), 3.74 (s, 3H),
2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 165.8, 161.2,
157.5, 151.8, 151.6, 149.4, 146.5, 144.4, 139.1, 136.2, 134.9,
131.7, 131.4, 130.1, 129.0, 128.9, 128.8, 127.7, 126.5, 125.8,
125.0, 124.0, 122.6, 121.5, 52.6, 52.1, 20.7; MS (ESI) 562 (M þ
1), 584 (M þ Naþ). Anal. Calcd for C33H27N3O4S: C 70.57, H
4.85, N 7.48. Found: C 70.52, H 5.17, N 7.48.
(E)-Dimethyl 5-[N-(p-Bromophenyl)-N0-(p-tolyl)benzimidamido]-
4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8c. Yield 90%, mp
168-169 °C; IR v (cm-1) 1724, 1634, 1586, 1486; 1H NMR (400
MHz, CD3COCD3) δ (ppm) 8.52 (d, J = 4.2 Hz, 1H), 7.72 (dt, J =
7.8, 1.7 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.25 (d, J = 8.8 Hz, 2H),
7.20-7.23 (m, 1H), 7.14 (d, J=8.8Hz, 2H), 6.3-7.00(m, 5H), 6.63
(d, J = 8.1 Hz, 2H), 5.98 (d, J = 8.2 Hz, 2H), 3.69 (s, 3H), 3.59 (s,
3H), 1.97 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm)
165.7, 161.4, 158.1, 152.3, 151.7, 150.4, 147.7, 144.9, 140.3, 137.5,
136.4, 132.8, 132.6, 132.0, 131.1, 130.1, 129.6, 129.5, 128.6, 125.9,
124.5, 123.9, 122.0, 119.6, 52.9, 52.7, 20.7; MS (ESI) 640 (M þ 1),
664 (M þ Naþ). Anal. Calcd for C33H26BrN3O4S: C 61.88, H 4.09,
N 6.56. Found: C 61.51, H 3.80, N 6.45.
(E)-Dimethyl 5-[N0-(p-Methoxyphenyl)-N-phenylbenzimidamido]-
4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8d. Yield 84%, mp
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Cheng et al.
JOCArticle
178-179 °C; IR v (cm-1) 1737, 1721, 1615, 1592, 1456; 1H NMR
(400 MHz, CD3COCD3) δ (ppm) 8.63-8.65 (ddd, J = 4.8, 1.7, 1.0
Hz, 1H), 7.86 (dt, J= 7.8, 1.8 Hz, 1H), 7.69 (dt, J= 7.9, 1.0 Hz, 1H),
7.30-7.36 (m, 3H), 7.22 (dt, J = 8.3, 1.8 Hz, 2H), 7.05-7.10 (m,
6H), 6.53 (dd, J = 6.7, 2.0 Hz, 2H), 6.13 (dd, J = 6.7, 2.0 Hz, 2H),
3.83(s, 3H),3.73(s, 3H),3.62(s, 3H);13CNMR(125MHz,DMSO-
d6) δ (ppm) 165.2, 160.7, 157.7, 155.0, 151.8, 151.2, 149.9, 144.5,
142.6, 139.5, 137.4, 134.7, 131.9, 130.3, 129.6, 128.2, 127.2, 126.8,
124.1, 123.7, 123.6, 122.3, 121.7, 114.0, 55.4, 53.2, 52.9; MS (ESI) 578
(M þ 1), 600 (M þ Naþ). Anal. Calcd for C33H27N3O5S: C 68.61, H
4.71, N 7.27. Found: C 68.32, H 4.75, N 6.91.
(E)-Dimethyl 5-[N-(p-Bromophenyl)-N0-(p-methoxyphenyl)-
benzimidamido]-4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8e.
Yield 86%, mp 158-159 °C; IR v (cm-1) 1737, 1725, 1618, 1487;
1H NMR (400 MHz, CD3COCD3) δ (ppm) 8.52 (d, J = 4.2 Hz,
1H), 7.72 (dt, J = 7.8, 1.8 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.26
(dd, J = 6.8, 1.9 Hz, 2H), 7.20-7.23 (m, 1H), 7.14 (d,
J = 6.8, 1.9 Hz, 2H), 6.98-7.02 (m, 1H), 6.94-7.06 (m, 4H),
6.41 (d, J = 8.8 Hz, 2H), 6.03 (d, J = 8.8 Hz, 2H), 3.70 (s, 3H),
3.60 (s, 3H), 3.49 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ
(ppm) 165.7, 161.4, 158.2, 156.2, 152.4, 151.8, 150.4, 144.9,
143.4, 140.3, 137.5, 136.3, 132.8, 132.6, 131.2, 130.1, 129.4,
128.7, 125.8, 124.5, 123.8, 123.1, 119.5, 114.4, 55.4, 52.9, 52.7;
MS (ESI) 656 (M þ 1), 678 (M þ Naþ). Anal. Calcd for
C33H26BrN3O5S: C 60.37, H 3.99, N 6.40. Found: C 60.34, H
3.86, N 6.28.
(E)-Dimethyl 5-[N0-(p-Chlorophenyl)-N-phenylbenzimidamido]-
4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8f. Yield 94%, mp
181-182 °C; IR v (cm-1) 1736, 1709, 1625, 1587, 1488; 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.65 (d, J = 4.3 Hz, 1H), 7.65 (dt, J =
7.8, 1.7 Hz, 1H), 7.50 (d, J= 7.9 Hz, 1H), 7.21-7.23 (m, 3H), 7.16 (t,
J = 8.4 Hz, 2H), 7.05-7.10 (m, 2H), 7.01 (t, J = 7.2 Hz, 2H), 6.94
(d, J = 7.2 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.07 (d, J = 8.7 Hz,
2H), 3.83 (s, 3H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 165.7, 161.1, 158.1, 151.8, 151.4, 149.4, 147.7, 144.1, 139.0,
136.5, 131.2, 130.1, 129.3, 129.0, 128.3, 128.2, 127.9, 127.3, 126.8,
126.2, 125.1, 123.9, 123.0, 122.7, 52.7, 52.5; MS (ESI) 582 (M þ 1),
604 (M þ Naþ). Anal. Calcd for C32H24ClN3O4S: C 66.03, H 4.16,
N 7.22. Found: C 66.09, H 4.36, N 7.17.
(E)-Dimethyl 5-[N-(p-Bromophenyl)-N0-(p-chlorophenyl)-
benzimidamido]-4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8g.
Yield 94%, mp 175-176 °C; IR v (cm-1) 1725, 1631, 1484; 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.67 (d, J = 4.4 Hz, 1H), 7.67
(t, J = 7.7 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.24-7.29 (m, 3H),
7.10-7.13 (m, 3H), 7.04 (t, J = 7.2 Hz, 2H), 6.94-6.95 (m, 2H),
6.90 (d, J = 8.8 Hz, 2H), 6.06 (d, J = 8.6 Hz, 2H), 3.84 (s, 3H),
3.78 (s, 3H); 13C NMR (400 MHz, CDCl3) δ (ppm) 165.6, 161.0,
157.7, 151.6, 150.6, 149.5, 147.6, 143.3, 138.9, 136.5, 135.2,
132.1, 130.9, 130.0, 129.6, 128.2, 128.1, 127.5, 125.6, 123.8,
122.8, 122.0, 119.5, 52.8, 52.6; MS (ESI) 662 (M þ 1), 684
(M þ Naþ). Anal. Calcd for C32H23BrClN3O4S: C 58.15, H
3.51, N 6.36. Found: C 58.05, H 3781, N 6.25.
(E)-Dimethyl 5-[N0-(p-Chlorophenyl)-N-(p-methoxyphenyl)-
benzimidamido]-4-(2-pyridinyl)thiophene-2,3-dicarboxylate 8i.
Yield 93%, mp 171-172 °C; IR v (cm-1) 1723, 1625, 1587, 1509;
1H NMR (400 MHz, CD3COCD3) δ (ppm) 8.54 (d, J = 4.6 Hz,
1H), 7.73 (dt, J = 7.8, 1.4 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.22
(dd, J = 7.3, 5.1 Hz, 1H), 7.16 (d, J = 8.8 Hz, 2H), 6.91-6.97
(m, 5H), 6.77 (d, J = 8.6 Hz, 2H), 6.66 (d, J = 8.9 Hz, 2H), 5.95
(d, J = 8.6 Hz, 2H), 3.68 (s, 3H), 3.59 (s, 3H), 3.58 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ (ppm) 165.8, 161.2, 158.0, 157.9,
152.1, 152.0, 149.4, 147.8, 139.0, 137.2, 136.4, 134.0, 131.4,
130.0, 129.1, 128.3, 128.1, 127.8, 127.1, 124.6, 123.8, 123.0,
122.6, 114.3, 55.3, 52.7, 52.4; HRMS (ESI) 612.1368 (M þ 1).
Anal. Calcd for C33H27ClN3O5S: 612.1360 (M þ 1).
Acknowledgment. This work was supported by the Na-
tional Natural Science Foundation of China (No. 20832006),
the Ministry of Science and Technology of China (2009ZX-
09501-006), and Beijing Municipal Commission of Education.
Supporting Information Available: General procedure for
the preparation of 1-thiocarbamoyl imidazo[1,5-a]pyridinium
inner salts 4 and full characterization for 4, copies of 1H NMR
and 13C NMR spectra of products 4, 6 and 8, as well as single
crystal data of 6g and 8f in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
2388 J. Org. Chem. Vol. 75, No. 7, 2010