One-pot synthesis of N-(imidazo[1,2-a]pyridin-3-yl)-and N-(imidazo[2,1-b][1,3]thiazol-5-yl)sulfonamides

Article abstract of DOI:10.1002/ejoc.201201006

The reaction of 2-aminopyridines or 2-aminothiazole with N-(2,2-dichloro-2-phenylethylidene)arensulfonamides affords the corresponding products of nucleophilic addition to the azomethine group, N-[2,2-dichloro-2- phenyl-1-(heterylamino)ethyl]sulfonamides, in good yields. The latter are easily cyclized to (imidazo[1,2-a]pyridin-3-yl)sulfonamides and (imidazo[2,1-b] thiazol-5-yl)sulfonamides in the presence of alkali, whereas the expected isomeric (imidazo[1,2-a]pyridin-2-yl)sulfonamides and (imidazo[2,1-b]thiazol-6- yl)sulfonamides are not formed. A one-pot two-stage method for the synthesis of target heterocyclic compounds without the isolation of intermediates has been developed. A tentative mechanism of the formation of annulated heterocyclic derivatives has been proposed.

Full text of DOI:10.1002/ejoc.201201006

FULL PAPER
DOI: 10.1002/ejoc.201201006
One-Pot Synthesis of N-(Imidazo[1,2-a]pyridin-3-yl)- and
N-(Imidazo[2,1-b][1,3]thiazol-5-yl)sulfonamides
Igor B. Rozentsveig,*[a] Valery Y. Serykh,[a] Gulnur N. Chernysheva,[a]
Kirill A. Chernyshev,[a] Evgeniy V. Kondrashov,[a] Evgeny V. Tretyakov,[b] and
Galina V. Romanenko[b]
Keywords: Synthetic methods / Domino reactions / Nucleophilic addition / Nitrogen heterocycles / Sulfonamides
The reaction of 2-aminopyridines or 2-aminothiazole with N-
(2,2-dichloro-2-phenylethylidene)arensulfonamides affords
the corresponding products of nucleophilic addition to the
azomethine group, N-[2,2-dichloro-2-phenyl-1-(heteryl-
amino)ethyl]sulfonamides, in good yields. The latter are eas-
ily cyclized to (imidazo[1,2-a]pyridin-3-yl)sulfonamides and
(imidazo[2,1-b]thiazol-5-yl)sulfonamides in the presence of
alkali, whereas the expected isomeric (imidazo[1,2-a]pyr-
idin-2-yl)sulfonamides and (imidazo[2,1-b]thiazol-6-yl)sulf-
onamides are not formed. A one-pot two-stage method for
the synthesis of target heterocyclic compounds without the
isolation of intermediates has been developed. A tentative
mechanism of the formation of annulated heterocyclic deriv-
atives has been proposed.
photoluminescent reagents,[11] ionic liquids,[12] ligands,[6]
and key reagents in modern heterocyclic chemistry for the
synthesis of diverse annulated structures.[10f,13]
Introduction
Heterocyclic compounds containing an imidazo[1,2-a]-
pyridine moiety are widely applied in medicine[1] as somni-
facient, sedative, and anxiolytic agents[1a–1c] (alpidem, zolpi-
dem, saripidem), drugs and promising agents for treatment
of gastroesophageal reflux and peptic ulcer diseases[2] (zoli-
midine and analogues), acute heart failure (olprinone), os-
teoporosis (minodronic acid derivatives),[3] diabetes,[4] her-
pes viruses,[5] and cancer.[6] Imidazo[1,2-a]pyridines act as
receptor agonists or antagonists,[7] ferment inhibitors and
modulators,[8] stimulators of neuroactive steroid synthesis
in plasma and in the brain.[9] These properties are associ-
ated with a range of pharmacological activities, including
anticonvulsant, anxiolytic, immunomodulating, and cardio-
vascular ones. Prospective radioligands for positron emis-
sion tomography for β-amyloid in Alzheimer’s disease
based on imidazo[1,2-a]pyridine derivatives have been
widely reported.[10] Accordingly, the development of new
methods for the preparation of imidazo[1,2-a]pyridines is
urgent, because heterocycles of this type are pharmaceuti-
cally attractive. Furthermore, imidazopyridines serve as
The most generally applied methods for the synthesis of
pharmaceutical imidazo[1,2-a]pyridines are based on the re-
actions of 2-aminopyridines with bromoaldehydes or
bromoketones.[5,9a,9c,13a,14] New methods leading to func-
tionalized imidazo[1,2-a]pyridines through N-(pyridin-2-
yl)amidines have been recently reported.[15a,15b] Multi-com-
ponent reactions[16] of 2-aminopyridine with aldehydes and
isocyanides, nitrile, thiocyanates, imidazoline-2,4,5-trione
or acetylene, cascade synthesis,[17] and palladium catalyzed
C–C bond cross-coupling reactions[18] are very promising
for the preparation of imidazo[1,2-a]pyridine derivatives.
Synthetic approaches based on benzotriazoles,[19] pyridi-
nium fluorides,[20] diazoketones,[21] oxothioamide,[22] and
vicinal diols[23] are also known. A simple method is cou-
pling of 2-aminopyridine with acetophenones in the
presence of acids.[24]
The protocols described open up approaches to obtain a
broad range of various imidazo[1,2-a]pyridines. However,
described methods for the synthesis of imidazo[1,2-a]pyr-
idines have disadvantages; high costs of reagents, labor in-
tensive syntheses, low selectivity and difficulties optimizing
reaction conditions for multigram quantities of products. In
this regard, improving the range of methods available to
chemists and technologists for the synthesis of imidazo[1,2-
a]pyridines or related heterocyclic systems remains a chal-
lenge.
[a] A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch
of the Russian Academy of Sciences,
Favorsky Str. 1, Irkutsk 664033, Russian Federation
Fax: +7-3952-419346
E-mail: i_roz@irioch.irk.ru
Homepage: http://www.irkinstchem.ru
[b] International Tomography Center, Siberian Branch of the
Russian Academy of Sciences,
To develop a synthetic route for unknown N-(2,2,2-tri-
chloroethyl)- and N-(2,2-dichloro-2-phenylethyl)sulfon-
amides as well as new derivatives of imidazo[1,2-a]pyridine
Institutskaya Str. 3a, Novosibirsk 630090, Russia
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201006.
368
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 368–375

One-Pot Synthesis of Imidazopyridine Derivatives
and imidazo[2,1-b]thiazole containing pharmacophoric amides 3 and 4. The reaction proceeds under mild condi-
sulfonylamino groups we studied the reaction of 2-amino- tions (room temperature, no catalyst) owing to the high
pyridines and 2-aminothiazole with N-(2,2-dichloro-2- electrophilicity of imines 1 and 2 resulting from the strong
phenylethylidene)- and N-(2,2,2-trichloroethylidene)arenes- electron-withdrawing substituents. The best yields are
ulfonamides 1 and 2.
achieved when the reaction is carried out in polar aprotic
Imines 1 and 2 represent electron-deficient halogen-con- solvents [N,N-dimethylformamide (DMF), dioxane] in
taining azomethines.[25] At present, these highly electro- which the reagents are easy soluble. At the same time, for
philic reagents are available through synthetic methods adducts 4 the experiment is less laborious when trichloro-
based on free-radical reactions of N,N-dichlorosulfon- ethylene is used. Imines 2 can be used without isolation
amides with trichloroethylene or phenylacetylene[25,26] from the resulting reaction mixture (Table 1, Entry 11).
(Scheme 1). The ability of polyhalogenated N-sulfonylald- However, in this case the reaction time is 20 h.
imines to react with various nucleophiles is used to design
diverse acyclic and heterocyclic sulfonamide deriva-
tives.[25,26b,27]
Scheme 1. Synthesis of imines 1 and 2 from N,N-dichlorosulfon-
amides.
It was found that the reaction of imines 1 and 2 with
primary and secondary amines depends on the nature of
the amine. Anilines and primary amines gave products aris-
ing from N-nucleophilic addition to the activated C=N
group,[25] whereas more basic secondary amines led to the
Scheme 2. Formation of adducts 3a–f and 4a–c by the reaction of
imines 1a, 1b and 2 with 2-aminopyridine, 2-amino-5-chloropyr-
formation of amidine derivatives, which are the products of
idine or 2-aminothiazole.
haloform cleavage.[25,26]
Adducts 3 and 4 are efficient precursors of imidazopyrid-
ine or imidazothiazole derivatives owing to the presence of
Results and Discussion
exo- and endocyclic nitrogen atoms and a polychloromethyl
We have found that reactions of imines 1 and 2 with 2- group in the structure. So, we have studied their heterocy-
aminopyridine, 2-amino-5-chloropyridine or 2-aminothi- clization under different conditions with 3a (Scheme 3).
azole are efficient in all the solvents studied (Scheme 2,
It has been found that the heterocyclization of com-
Table 1). The resulting corresponding products of nucleo- pound 3a occurs in the presence of NaOH or KOH in 1,4-
philic addition of the aromatic amines to the activated C=N dioxane (Table 2, Entry 14) or in toluene (Table 2, Entry 16)
group were N-[2-polychloro-1-(2-pyridinylamino)ethyl]- or and unexpectedly delivers 3-sulfonamido-2-phenylimid-
N-[2-polychloro-1-(1,3-thiazol-2-ylamino)ethyl]arenesulfon- azo[1,2-a]pyridine (5a), instead of the anticipated 2-sulfon-
Table 1. Screening of solvents for the synthesis of adducts 3 and 4.[a]
Entry
Imine 1, 2
X
Ar
Adduct 3, 4
R
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1a
1b
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cl
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
4a
4a
4b
4c
H
H
H
H
H
Cl
H
Cl
–
CCl4
ethyl acetate
CH3CN
31
47
76
92
93
98
85
90
DMF
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
trichloroethylene[c]
1,4-dioxane
1,4-dioxane
1,4-dioxane
9
94
92
10
11
12
13
14
–
H
H
Cl
–
51 (90)[d]
93
2
Cl
Cl
Cl
2
2
90
88
[a] Conditions: Stirred imine 1 or 2 (3 mmol), aminopyridine or aminothiazole (3.4 mmol), in solvent (10 mL) for 4 h at room temp.
[b] Isolated yield. [c] Without isolation of imine 2 from the reaction mixture. [d] Reaction time was 20 h.
Eur. J. Org. Chem. 2013, 368–375
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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369

I. B. Rozentsveig et al.
FULL PAPER
of 4-chlorobenzenesulfonamide in 15–70% yields. The high-
est yields of 4-chlorobenzenesulfonamide were obtained in
the polar solvents DMF or dimethyl sulfoxide (DMSO).
A tentative route for the formation of imidazopyridines
can be rationalized as follow. The reaction is triggered by
heterocyclization affording aziridine A, which is then trans-
formed into anion B, followed by formation of intermediate
C and diimine D as a result of the aziridine cycle opening
and chlorine anion elimination. The heterocyclization in-
volving the pyridine nitrogen atom and carbon atom of the
Scheme 3. Synthesis of imidazo[1,2-a]pyridine 5a from adduct 3a.
azomethine group furnishes annulated structure
E
(Scheme 4). Subsequent aromatization owing to elimination
of a proton from the 3-position leads to anion F, which is
quenched by hydrolysis with water produced in the reaction
mixture.
The reactivity research of adducts 3b–f has shown that
these products (similar to compound 3a) give hitherto un-
known 3-sulfonamido-2-phenylimidazo[1,2-a]pyridines 5b–
d or the corresponding derivatives of imidazo[2,1-b]thi-
azoles 6a and 6b.
amido-3-phenylimidazo[1,2-a]pyridine (5aЈ). Attempts to
use other solvents or solvent-free conditions were unsuc-
cessful or gave 5a in lower yield. In the presence of potas-
sium or sodium carbonate or triethylamine as base, the re-
action does not take place (Table 2, Entries 2–7). Upon
heating (Table 2, Entries 1, 3, 7, 10, 13) resinification in-
creased, and was accompanied by cleavage and formation
Under the conditions employed, we failed to synthesize
the corresponding imidazopyridine derivatives from ad-
ducts 4a–c prepared from chloral-imine 2, and compounds
4a–c were recovered unchanged. Under harsher conditions
(application of base and above 100 °C), resinification of the
reaction mixture took place.
To optimize the protocol for the preparation of com-
pounds 5a–d, 6a and 6b, we selected conditions for a two-
stage one-pot synthesis, which would exclude isolation of
intermediate adducts 3a–f (Scheme 5, Table 3). The first
stage comprises the reaction of the starting azomethines 1a
and 1b with aminopyridines or aminothiazole, further
NaOH is added to the reaction mixture to accomplish the
synthesis of target heterocycles 5a–d, 6a and 6b.
To prove the relative positions of the sulfonamide frag-
ment and benzene ring in the structure of compounds 5a–
d, 6a and 6b, we have accomplished the methylation reac-
tion of these annulated heterocycles (Scheme 6, Table 4), be-
cause the presence of the methyl groups allows 2D NMR
spectroscopic techniques for determination of relative posi-
tions of the substituents (see Supporting Information). Be-
sides, methylated derivatives 7a, 7b and 8 readily form crys-
Table 2. Effect of solvent, temperature and base on the yield of
imidazo[1,2-a]pyridine 5a.[a]
Entry Solvent
Base
Temp.
[°C]
Conversion Yield of
of 3a [%]
5a [%][b]
1
2
3
4
5
6
7
8
–
–
150
25
50
25
25
25
50
25
25
50
25
25
50
25
25
25
25
100[c]
8
78
5
0
0
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Et2O
CH3CN
CH3CN
1,4-dioxane NaOH
1,4-dioxane KOH
DMSO
toluene
K2CO3
K2CO3
Na2CO3
NaHCO3
Et3N
0[d]
0
2
0
0
17
91
52
45
93
83
15
76
100
100
91
100
Et3N
KOH
0[d]
38
41
0[d]
48
0
9
NaOH
NaOH
NaOH
NaOH
NaOH
10
11
12
13
14
15
15
16
5[d]
91
87
15
85
NaOH
NaOH
[a] Adduct 3a (3 mmol) and base (12 mmol) were stirred in solvent
(5 mL) for 3 h. [b] Isolated yield. [c] Strong resinification. [d] The
process was accompanied with formation of 4-chlorobenzenesulf-
onamide.
Scheme 4. A tentative route for the formation of imidazo[1,2-a]pyridines 5.
370
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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One-Pot Synthesis of Imidazopyridine Derivatives
Scheme 5. One-pot synthesis of imidazo[1,2-a]pyridines 5a–d and
imidazo[2,1-b]thiazoles 6a and 6b. (i) Imine 1 (3 mmol) and hetero-
cyclic amine (3.4 mmol) were stirred in 1,4-dioxane (10 mL) at
room temp. for 4 h; (ii) NaOH (12 mmol) was added and the reac-
tion mixture was stirred for 4 h at room temp.
Figure 1. X-ray structure of compound 7b.
Table 3. Yields of imidazo[1,2-a]pyridines 5a–d and imidazo[2,1-b]-
thiazoles 6a and 6b obtained through a two-stage one-pot protocol
without isolation of intermediate adducts 3a–f.
Entry
Imine 1 Ar
Product 5, 6
R
Yield [%][a,b]
to deliver a mixture of mono- and dimethylated derivatives
7a and 7b with the participation of both sulfonamide and
one of endocyclic nitrogen atoms.
1
2
3
4
5
6
1a
1a
1b
1b
1a
1b
4-ClC6H4
5a
5b
5c
5d
6a
6b
H
Cl
H
Cl
–
84
97
72
60
92
67
4-ClC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
4-MeC6H4
–
Conclusions
[a] Calculated from starting imine 1. [b] Isolated yield.
The reaction of N-sulfonylpolychloroacetaldimines with
2-aminopyridine, 2-amino-5-chloropyridine and 2-amino-
thiazole has been studied for the first time. It has been
found that heterocyclic amines adds to electron-deficient
imines at room temperature without catalysts to afford the
corresponding adducts N-[2-polychloro-1-(2-aminopyr-
idyl)ethyl]- and N-[2-polychloro-1-(1,3-thiazol-2-ylamino)-
ethyl]arenesulfonamides. Heterocyclization of the adducts
obtained to give imidazopyridine and imidazothiazole de-
rivatives was investigated. It has been shown that the reac-
tion unexpectedly leads to hitherto unknown (imidazo[1,2-
a]pyridin-3-yl)sulfonamides and (imidazo[2,1-b]thiazol-5-
yl)sulfonamides, whereas the expected isomeric (imid-
azo[1,2-a]pyridin-2-yl)sulfonamides and (imidazo[2,1-b]thi-
tals suitable for X-ray analysis (Figure 1) that makes it pos-
sible to establish unambiguously the structure of the hetero-
cyclic compounds synthesized.
Table 4. Yields of methylation products 7a, 7b, 8 and 9.
Entry
Ar
R
Product of
methylation
Yield [%][a]
1
2
3
4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
H
H
Cl
–
7a
7b
8
30
68
87
83
9
[a] Isolated yield.
It has been found that under the studied conditions, in azol-6-yl)sulfonamides are not formed. A tentative reaction
the case of compounds 5b and 6a, sulfonamide nitrogen mechanism has been proposed. The one-pot method for the
atom undergoes methylation even in the presence of excess preparation of substituted 3-aminoimidazo[1,2-a]pyridines
MeI to afford monomethyl derivatives 8 and 9. In the case and 5-aminoimidazo[2,1-b]thiazoles bearing the protected
of imidazopyridine 5a, the reaction proceeds non-selectively amino group has been developed.
Scheme 6. Methylation of compounds 5a, 5b and 6a.
Eur. J. Org. Chem. 2013, 368–375
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371

I. B. Rozentsveig et al.
FULL PAPER
140 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 2.17 (s, 1 H,
CH3), 6.27 (m, 1 H, 3-H), 6.43 (m, 1 H, 5-H), 6.50 (d, 3J = 9.7 Hz,
1 H, NH), 6.61 (dd, J = 9.4, 9.7 Hz, 1 H, CH), 6.94 (AAЈBBЈ, 2
H, 3,5-H 4-CH3C6H4), 7.17 (m, 1 H, 4-H), 7.34 (m, 3 H, 3,4,5-H
C6H5), 7.45 (AAЈBBЈ, 2 H, 2,6-H 4-CH3C6H4), 7.73 (m, 2 H, 2,6-
H C6 H5 ), 7.77 (m, 1 H, 6-H), 8.23 (d, 3J = 9.4 Hz, 1 H,
NHSO2) ppm. 13C NMR (100.61 MHz, [D6]DMSO): δ = 20.8
(CH3), 68.5 (CH), 96.0 (CCl2), 108.7 (C-3), 113.2 (C-5), 126.5 (C-
3,5, 4-CH3C6H4), 127.1 (C-2,6, C6H5), 127.8 (C-3,5, C6H5), 128.4
(C-2,6, 4-CH3C6H4), 129.1 (C-4, C6H5), 136.3 (C-4), 138.3 (C-1, 4-
CH3C6H4), 139.4 (C-1, C6H5), 141.9 (C-4, 4-CH3C6H4), 146.4 (C-
Experimental Section
3
General Remarks: Imines 1a, 1b, and 2 were obtained by known
methods.[22] All other reagents were reagent grade. The solvents
were dried by standard procedures and distilled prior to use. NMR
spectra were recorded with a Bruker DPX 400 spectrometer (1H,
400.13 MHz; 13C, 100.61 MHz) at 25 °C with hexamethyldisiloxane
as an internal standard. IR spectra were recorded with a Bruker
IFS-25 spectrophotometer in KBr. All melting points were
measured with a Kofler micro hot stage apparatus. Elemental
analyses were obtained by using a Thermo Finnigan Flash
series1112 EA analyzer. Single-crystal diffraction data for the com-
pounds were collected with a SMART APEX II CCD (Bruker
AXS) automatic diffractometer (Mo-Kα, λ = 0.71073 Å, T =
240 K); an absorption correction was applied by using the Bruker
SADABS program, version 2.10. The structures were solved by di-
rect methods and refined by the full-matrix least-squares method
in an anisotropic approximation for non-hydrogen atoms. The H
atoms were calculated geometrically and used in riding model re-
finement. All structure solution and refinement calculations were
carried out with SHELX-97 and Bruker SHELXTL Version 6.14
program packages.
6), 155.9 (C-2) ppm. IR (KBr): ν = 1163, 1338 (SO ), 1601 (C=N),
˜
2
3240, 3364 (NH) cm–1. C20H19Cl2N3O2S (436.36): calcd. C 55.05,
H 4.39, Cl 16.25, N 9.63, S 7.35; found C 55.15, H 4.42, Cl 16.31,
N 9.57, S 7.39.
N-{2,2-Dichloro-1-[(5-chloro-2-pyridinyl)amino]-2-phenylethyl}-4-
methylbenzenesulfonamide (3d): Colorless needles, yield 1.20 g,
90%; m.p. 153–156 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ =
3
3
2.20 (s, 3 H, CH3), 6.34 (d, J = 8.7 Hz, 1 H, 3-H), 6.46 (dd, J =
9.4, 9.5 Hz, 1 H, CH), 6.85 (d, 3J = 9.4 Hz, 1 H, NH), 6.97
(AAЈBBЈ, 2 H, 3,5-H 4-CH3C6H4), 7.23 (d, 3J = 8.7 Hz, 1 H, 4-
H), 7.31–7.39 (m, 3 H, 4,5,6-H C6H5), 7.47 (AAЈBBЈ, 2 H, 2,6-H
4-CH3C6H4), 7.71 (m, 3 H, 6-H, 2,6-H C6H5), 8.39 (d, 3J = 9.5 Hz,
1 H, NHSO2) ppm. 13C NMR (100.61 MHz, [D6]DMSO): δ = 20.8
(CH3), 68.7 (CH), 95.6 (CCl2), 110.1 (C-3), 119.1 (C-5), 126.6 (C-
3,5, 4-CH3C6H4), 127.1 (C-2,6, C6H5), 127.8 (C-3,5, C6H5), 128.4
(C-2,6, 4-CH3C6H4), 129.13 (C-4, C6H5), 136.0 (C-4), 138.2 (C-1,
4-CH3C6H4), 139.3 (C-1, C6H5), 142.1 (C-4, 4-CH3C6H4), 144.4
General Procedure for Synthesis of Adducts 3 and 4: 2-Aminopyr-
idine, 2-amino-5-chloropyridine or 2-aminothiazole (3.4 mmol) was
added to a solution of imine 1 or 2 (2.8 mmol) in 1,4-dioxane
(10 mL) and stirred with a magnetic stirrer for 4 h at room temp.
After this time, the reaction mixture was diluted with water
(100 mL), the precipitate was filtered, dried and washed with di-
ethyl ether (50 mL).
(C-6), 154.7 (C-2) ppm. IR (KBr): ν = 1161, 1335 (SO ), 1597
˜
2
(C=N), 3268, 3367 (NH) cm–1. C20H18Cl3N3O2S (470.80): calcd. C
51.02, H 3.85, Cl 22.59, N 8.93, S 6.81; found C 50.27, H 3.91, Cl
22.49, N 8.88, S 6.87.
N-[2,2-Dichloro-2-phenyl-1-(2-pyridinylamino)ethyl]-4-chlorobenz-
enesulfonamide (3a): Colorless needles, yield 1.22 g, 95%; m.p. 144–
1
147 °C. H NMR (400.13 MHz, [D6]DMSO): δ = 6.29 (m, 1 H, 3-
N-[2,2-Dichloro-2-phenyl-1-(2-thiazolamino)ethyl]-4-chlorobenzene-
sulfonamide (3e): Colorless needles, yield 1.22 g, 94%; m.p. 141–
143 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 6.37 (dd, 3J =
H), 6.44 (m, 1 H, 5-H), 6.58–6.65 (m, 2 H, CH, NH), 7.17 (m, 1
H, 4-H), 7.20 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.30–7.39 (m, 3 H,
3,4,5-H C6H5), 7.58 (AAЈBBЈ, 2 H, 3,5-H 4-ClC6H4), 7.72–7.78 (m,
3 H, 2,6-H C6H5, 6-H), 8.54 (m, 1 H, NHSO2) ppm. 13C NMR
(100.61 MHz, [D6]DMSO): δ = 68.5 (CH), 95.6 (CCl2), 108.7 (C-
3), 113.3 (C-5), 127.0 (C-2,6, C6H5), 127.8 (C-3,5, C6H5), 128.0 (C-
2,6, 4-ClC6H4), 128.3 (C-3,5, 4-ClC6H4), 129.1 (C-4, C6H5), 136.4
(C-4), 136.7 (C-1, 4-ClC6H4), 139.4 (C-1, C6H5), 139.9 (C-4, 4-
3
3
9.4, 9.6 Hz, 1 H, CH), 6.51 (d, J = 3.3 Hz, 1 H, 4-H), 6.84 (d, J
= 3.3 Hz, 1 H, 5-H), 7.32 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.38
(m, 3 H, 3,4,5-H C6H5), 7.61 (AAЈBBЈ, 2 H, 3,5-H 4-ClC6H4), 7.71
3
3
(m, 2 H, 2,6-H C6H5), 8.09 (d, J = 9.6 Hz, 1 H, NH), 8.77 (d, J
= 9.4 Hz, 1 H, NHSO2) ppm. 13C NMR (100.61 MHz, [D6]-
DMSO): δ = 72.0 (CH), 94.9 (CCl2), 107.9 (C-4), 127.0 (C-2,6,
C6H5), 128.0 (C-3,5, C6H5), 128.26 (C-2,6, 4-ClC6H4), 128.37 (C-
3,5, 4-ClC6H4), 129.3 (C-4, C6H5), 136.9 (C-1, C6H5), 137.4 (C-5),
139.2 (C-1, 4-ClC6H4), 140.0 (C-4, 4-ClC6H4), 166.4 (C-2) ppm. IR
ClC H ), 146.4 (C-6), 155.8 (C-2) ppm. IR (KBr): ν = 1163, 1344
˜
6
4
(SO2), 1602 (C=N), 3209, 3250, 3399 (NH) cm–1. C19H16Cl3N3O2S
(456.77): calcd. C 49.96, H 3.53, Cl 23.28, N 9.20, S 7.02; found C
50.06, H 3.51, Cl 23.32, N 9.15, S 7.09.
(KBr): ν = 1163, 1338 (SO ), 1520 (C=N), 3228, 3358 (NH) cm–1.
˜
2
N-{2,2-Dichloro-1-[(5-chloro-2-pyridinyl)amino]-2-phenylethyl}-4-
chlorobenzenesulfonamide (3b): Colorless needles, yield 1.25 g, 98%;
m.p. 160–163 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 6.35 (d,
3J = 10.2 Hz, 1 H, 3-H), 6.47 (dd, 3J = 9.2, 9.8 Hz, 1 H, CH), 6.97
(d, 3J = 9.8 Hz, 1 H, NH), 7.24 (m, 3 H, 2,6-H 4-ClC6H4, 4-H),
7.28–7.38 (m, 3 H, 3,4,5-H C6H5), 7.60 (AAЈBBЈ, 2 H, 3,5-H 4-
ClC6H4), 7.70–7.73 (m, 3 H, 6-H, 2,6-H C6H5), 8.66 (d, 3J =
9.2 Hz, 1 H, NHSO2) ppm. 13C NMR (100.61 MHz, [D6]DMSO):
δ = 68.7 (CH), 95.3 (CCl2), 110.1 (C-3), 119.4 (C-5), 127.1 (C-2,6,
C6H5), 127.9 (C-3,5, C6H5), 128.2 (C-2,6, 4-ClC6H4), 128.5 (C-3,5,
4-ClC6H4), 129.2 (C-4, C6H5), 136.2 (C-4), 137.0 (C-1, 4-ClC6H4),
139.2 (C-1, C6H5), 139.9 (C-4, 4-ClC6H4), 144.40 (C-6), 154.6 (C-
C17H14Cl3N3O2S2 (462.80): calcd. C 44.12, H 3.05, Cl 22.98, N
9.08, S 13.85; found C 44.19, H 3.08, Cl 23.05, N 9.03, S 13.91.
N-[2,2-Dichloro-2-phenyl-1-(2-thiazolamino)ethyl]-4-methylbenz-
enesulfonamide (3f): Colorless needles, yield 1.20 g, 92%; m.p. 155–
158 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 2.25 (s, 3 H,
3
3
CH3), 6.40 (dd, J = 9.7, 9.8 Hz, 1 H, CH), 6.51 (d, J = 3.6 Hz, 1
3
H, 4-H), 6.87 (d, J = 3.6 Hz, 1 H, 5-H), 7.06 (AAЈBBЈ, 2 H, 3,5-
H 4-CH3C6H4), 7.34–7.39 (m, 3 H, 3,4,5-H C6H5), 7.49 (AAЈBBЈ,
3
2 H, 2,6-H 4-CH3C6H4), 7.71 (m, 2 H, 2,6-H C6H5), 8.02 (d, J =
9.7 Hz, 1 H, NH), 8.49 (d, 3J = 9.8 Hz, 1 H, NHSO2) ppm. 13C
NMR (100.61 MHz, [D6]DMSO): δ = 20.9 (CH3), 72.0 (CH), 95.2
(CCl2), 107.7 (C-4), 126.5 (C-3,5, 4-CH3C6H4), 127.0 (C-2,6,
C6H5), 127.9 (C-3,5, C6H5), 128.6 (C-2,6, 4-CH3C6H4), 129.2 (C-
4, C6H5), 137.4 (C-5), 138.4 (C-1, 4-CH3C6H4), 139.2 (C-1, C6H5),
2) ppm. IR (KBr): ν = 1164, 1343 (SO ), 1598 (C=N), 3274, 3233,
˜
2
3377 (NH) cm–1. C19H15Cl4N3O2S (491.22): calcd. C 46.46, H 3.08,
Cl 28.87, N 8.55, S 6.53; found C 46.58, H 3.12, Cl 28.81, N 8.49,
S 6.57.
142.1 (C-4, 4-CH C H ), 166.5 (C-2) ppm. IR (KBr): ν = 1161,
˜
3
6
4
1335 (SO2), 1597 (C=N), 3268, 3367 (NH) cm–1. C18H17Cl2N3O2S2
(442.38): calcd. C 48.87, H 3.87, Cl 16.03, N 9.50, S 14.49; found
C 48.81, H 3.83, Cl 16.08, N 9.53, S 14.42.
N-[2,2-Dichloro-2-phenyl-1-(2-pyridinylamino)ethyl]-4-methylbenz-
enesulfonamide (3c): Colorless needles, yield 1.04 g, 85%; m.p. 137–
372
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 368–375

One-Pot Synthesis of Imidazopyridine Derivatives
N-[2,2,2-Trichloro-1-(2-pyridinylamino)ethyl]-4-chlorobenzenesulf- H 3.68, Cl 9.24, N 10.95, S 8.35; found C 59.55, H 3.64, Cl 9.30,
onamide (4a): Colorless needles, yield 1.08 g, 93 %; m.p. 161– N 10.89, S 8.41.
1
163 °C. H NMR (400.13 MHz, [D6]DMSO): δ = 6.43 (m, 1 H, 5-
N-(6-Chloro-2-phenylimidazo[1,2-a]pyridine-3-yl)-4-chlorobenzene-
3
H), 6.50–6.60 (m, 2 H, C H, 3-H), 6.96 (d, J = 9.6 Hz, 1 H, NH),
sulfonamide (5b): Colorless needles, yield 1.13 g, 97%; m.p. 232–
7.27 (m, 3 H, 4-H, 2,6-H 4-ClC6H4), 7.65 (AAЈBBЈ, 2 H, 3,5-H 4-
1
235 °C. H NMR (400.13 MHz, [D6]DMSO): δ = 7.22–7.32 (m, 5
ClC6H4), 7.88 (m, 1 H, 6-H), 8.95 (br. s, 1 H, NHSO2) ppm. 13C
H, 3,4,5-H C6H5, 2,6-H 4-ClC6H4), 7.47 (AAЈBBЈ, 2 H, 3,5-H 4-
NMR (100.61 MHz, [D6]DMSO): δ = 70.7 (CH), 102.0 (CCl3),
ClC6H4), 7.67 (m, 2 H, 2,6-H C6H5), 7.69 (dd, 3J = 9.5, 4J = 1.5 Hz,
109.0 (C-3), 114.0 (C-5), 128.3 (C-2,6, 4-ClC6H4), 128.5 (C-3,5, 4-
3
4
1 H, 7-H), 7.82 (d, J = 9.5 Hz, 1 H, 8-H), 8.51 (d, J = 1.5 Hz, 1
H, 5-H) ppm. 13C NMR (100.61 MHz, [D6]DMSO): δ = 114.5 (C-
3), 116.1 (C-8), 121.5 (C-6), 122.5 (C-5), 127.2 (C-2,6, C6H5), 128.2
(C-3,5, C6H5), 128.5 (C-3,5, 4-ClC6H4), 128.6 (C-4, C6H5), 129.0
(C-1, C6H5), 129.1 (C-2,6, 4-ClC6H4), 130.1 (C-7), 137.5 (C-1, 4-
ClC6H4), 137.8 (C-2), 138.5 (C-4, 4-ClC6H4), 139.2 (C-8a) ppm. IR
ClC6H4), 136.8 (C-4), 137.1 (C-1, 4-ClC6H4), 139.5 (C-4, 4-
ClC H ), 146.5 (C-6), 155.7 (C-2) ppm. IR (KBr): ν = 1163, 1341
˜
6
4
(SO2), 1603 (C=N), 3247, 3382 (NH) cm–1. C13H11Cl4N3O2S
(415.12): calcd. C 37.61, H 2.67, Cl 34.16, N 10.12, S 7.72; found
C 37.58, H 2.70, Cl 34.20, N 10.17, S 7.77.
(KBr): ν = 1172, 1341 (SO ), 1653 (C=N) cm–1. C H Cl N O S
˜
2
19 13
2
3
2
N-{2,2,2-Trichloro-1-[(5-chloro-2-pyridinyl)amino]ethyl}-4-chloro-
benzenesulfonamide (4b): Colorless needles, yield 1.13 g, 90%; m.p.
(418.30): calcd. C 54.56, H 3.13, Cl 16.95, N 10.05, S 7.66; found
C 54.36, H 3.16, Cl 16.88, N 10.12, S 7.59.
1
3
158–160 °C. H NMR (400.13 MHz, [D6]DMSO): δ = 6.37 (dd, J
3
= 9.0, 9.7 Hz, 1 H, CH), 6.50 (d, J = 9.4 Hz, 1 H, 3-H), 7.27 (d,
N-(2-Phenylimidazo[1,2-a]pyridine-3-yl)-4-methylbenzenesulfon-
amide (5c): Colorless needles, yield 0.73 g, 72%; m.p. 169–172 °C.
1H NMR (400.13 MHz, [D6]DMSO): δ = 2.20 (s, 3 H, CH3), 6.99
(AAЈBBЈ, 2 H, 2,6-H 4-CH3C6H4), 7.23 (m, 2 H, 3,5-H C6H5), 7.31
(m, 1 H, 4-H C6H5), 7.35–7.40 (m, 3 H, 3,5-H 4-CH3C6H4, 6-H),
7.64 (m, 2 H, 2,6-H C6H5), 7.80 (m, 1 H, 7-H), 7.87 (m, 1 H, 8-
H), 8.55 (m, 1 H, 5-H) ppm. 13C NMR (100.61 MHz, [D6]DMSO):
δ = 20.9 (CH3), 113.7 (C-8), 114.7 (C-3), 115.7 (C-5), 125.1 (C-6),
126.6 (C-3,5, 4-CH3C6H4), 127.4 (C-2,6, C6H5), 127.5 (C-1, C6H5),
128.3 (C-3,5, C6H5), 128.9 (C-4, C6H5), 129.5 (C-2,6, 4-CH3C6H4),
131.6 (C-7), 134.2 (C-2), 136.2 (C-1, 4-CH3C6H4), 139.4 (C-8a),
3J = 9.0 Hz, 1 H, NH), 7.30 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.37
(dd, 3J = 9.4, J = 2.5 Hz, 1 H, 4-H), 7.67 (AAЈBBЈ, 2 H, 3,5-H 4-
4
4
3
ClC6H4), 7.87 (d, J = 2.5 Hz, 1 H, 6-H), 9.06 (d, J = 9.7 Hz, 1
H, NHSO2) ppm. 13C NMR (100.61 MHz, [D6]DMSO): δ = 70.9
(CH), 101.5 (CCl3), 110.3 (C-3), 120.0 (C-5), 128.3 (C-2,6, 4-
ClC6H4), 128.5 (C-3,5, 4-ClC6H4), 136.6 (C-4), 137.3 (C-1, 4-
ClC6H4), 139.5 (C-4, 4-ClC6H4), 144.5 (C-6), 154.4 (C-2) ppm. IR
(KBr): ν = 1168, 1330 (SO ), 1601 (C=N), 3238, 3391 (NH) cm–1.
˜
2
C13H10Cl5N3O2S (449.57): calcd. C 34.73, H 2.24, Cl 39.43, N 9.35,
S 7.13; found C 34.68, H 2.26, Cl 39.48, N 9.37, S 7.19.
143.7 (C-4, 4-CH C H ) ppm. IR (KBr): ν = 1162, 1340 (SO ),
˜
3
6
4
2
N-[2,2,2-Trichloro-1-(2-thiazolamino)ethyl]-4-chlorobenzenesulfon-
amide (4c): Colorless needles, yield 1.04 g, 88%; m.p. 162–165 °C.
1H NMR (400.13 MHz, [D6]DMSO): δ = 6.26 (dd, 3J = 9.2, 9.5 Hz,
1650 (C=N) cm–1. C20H17N3O2S (363.43): calcd. C 66.10, H 4.71,
N 11.56, S 8.82; found C 65.97, H 4.77, N 11.49, S 8.78.
N-(6-Chloro-2-phenylimidazo[1,2-a]pyridine-3-yl)-4-methylbenzene-
sulfonamide (5d): Colorless needles, yield 0.67 g, 60%; m.p. 204–
207 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 2.21 (s, 3 H,
CH3), 7.03 (AAЈBBЈ, 2 H, 2,6-H 4-CH3C6H4), 7.28–7.38 (m, 3 H,
3,4,5-H C6H5), 7.41 (AAЈBBЈ, 2 H, 3,5-H 4-CH3C6H4), 7.75 (m, 2
3
3
1 H, CH), 6.65 (d, J = 3.5 Hz, 1 H, 4-H), 6.96 (d, J = 3.5 Hz, 1
H, 5-H), 7.38 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.70 (AAЈBBЈ, 2
3
3
H, 3,5-H 4-ClC6H4), 8.38 (d, J = 9.2 Hz, 1 H, NH), 9.22 (d, J =
9.5 Hz, 1 H, NHSO2) ppm. 13C NMR (100.61 MHz, [D6]DMSO):
δ = 74.0 (CH), 100.9 (CCl3), 108.7 (C-4), 128.44 (C-2,6, 4-ClC6H4),
128.48 (C-3,5, 4-ClC6H4), 137.3 (C-1, 4-ClC6H4), 137.5 (C-5), 139.7
3
4
3
H, 2,6-H C6H5), 7.90 (dd, J = 9.5, J = 1.8 Hz, 7-H), 7.95 (d, J
= 9.5 Hz, 1 H, 8-H), 8.46 (d, 4J = 1.8 Hz, 1 H, 5-H) ppm. 13C NMR
(100.61 MHz, [D6]DMSO): δ = 20.9 (CH3), 114.5 (C-8), 115.5 (C-
3), 123.1 (C-6), 123.2 (C-5), 126.5 (C-1, C6H5), 126.7 (C-3,5, 4-
CH3C6H4), 127.5 (C-2,6, C6H5), 128.5 (C-3,5, C6H5), 129.5 (C-4,
C6H5), 129.7 (C-2,6, 4-CH3C6H4), 132.9 (C-7), 134.4 (C-2), 136.1
(C-1, 4-CH3C6H4), 137.6 (C-8a), 144.2 (C-4, 4-CH3C6H4) ppm. IR
(C-4, 4-ClC H ), 166.4 (C-2) ppm. IR (KBr): ν = 1160, 1340 (SO ),
˜
6
4
2
1551 (C=N), 3292 (NH) cm–1. C11H9Cl4N3O2S2 (421.14): calcd. C
31.37, H 2.15, Cl 33.67, N 9.98, S 15.23; found C 31.43, H 2.17,
Cl 33.71, N 10.04, S 15.29.
General Procedure for the Synthesis of Imidazopyridines 5 and Imid-
azothiazoles 6: 2-Aminopyridine, 5-chloro-2-aminopyridine or 2-
aminothiazole (3.4 mmol) was added to a solution of imine 1
(2.8 mmol) in 1,4-dioxane (10 mL) and stirred with a magnetic stir-
rer for 4 h at room temp. Then sodium hydroxide (11.2 mmol) was
added to the reaction mixture and stirred for an additional 5 h
at room temp. The reaction mixture was then diluted with water
(100 mL), acidified with hydrochloric acid (pH 3), the precipitate
was filtered, dried and washed with diethyl ether (50 mL).
(KBr): ν = 1168, 1333 (SO ), 1653 (C=N) cm–1. C H ClN O S
˜
2
20 16
3
2
(397.88): calcd. C 60.38, H 4.05, Cl 8.91, N 10.56, S 8.06; found C
60.51, H 4.01, Cl 8.97, N 10.61, S 8.11.
N-(6-Phenylimidazo[2,1-b]thiazol-5-yl)-4-chlorobenzenesulfonamide
(6a): Colorless needles, yield 0.95 g, 92 %; m.p. 229–231 °C. 1H
NMR (400.13 MHz, [D6]DMSO): δ = 7.13–7.20 (m, 3 H, 3,4,5-H
3
C6H5), 7.29 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.37 (d, J = 4.4 Hz,
1 H, 3-H), 7.48 (AAЈBBЈ, 2 H, 3,5-H 4-ClC6H4), 7.50 (m, 2 H, 2,6-
H C6H5), 7.67 (d, 3J = 4.4 Hz, 1 H, 2-H) ppm. 13C NMR
(100.61 MHz, [D6]DMSO): δ = 114.7 (C-3), 114.9 (C-3), 118.6 (C-
2), 126.2 (C-2,6, C6H5), 127.3 (C-4, C6H5), 127.9 (C-3,5, C6H5),
128.5 (C-3,5, 4-ClC6H4), 129.1 (C-2,6, 4-ClC6H4), 131.4 (C-1,
C6H5), 137.9 (C-1, 4-ClC6H4), 138.1 (C-4, 4-ClC6H4), 139.7 (C-6),
N-(2-Phenylimidazo[1,2-a]pyridine-3-yl)-4-chlorobenzenesulfon-
amide (5a): Colorless needles, yield 0.90 g, 84%; m.p. 218–221 °C.
1H NMR (400.13 MHz, [D6]DMSO): δ = 7.02 (m, 1 H, 6-H), 7.15
(m, 3 H, 3,4,5-H C6H5), 7.23 (AAЈBBЈ, 2 H, 2,6-H 4-ClC6H4), 7.36
(m, 1 H, 7-H), 7.41 (AAЈBBЈ, 2 H, 3,5-H 4-ClC6H4), 7.55–7.62
(m, 3 H, 2,6-H C6H5, 8-H), 8.31 (m, 1 H, 5-H) ppm. 13C NMR
(100.61 MHz, [D6]DMSO): δ = 112.7 (C-6), 113.4 (C-3), 116.8 (C-
8), 124.0 (C-5), 126.3 (C-7), 126.9 (C-2,6, C6H5), 127.4 (C-4, C6H5),
146.7 (C-7a) ppm. IR (KBr): ν = 1165, 1345 (SO ) cm–1
.
˜
2
C17H12ClN3O2S2 (389.87): calcd. C 52.37, H 3.10, Cl 9.09, N 10.78,
S 16.45; found C 52.41, H 3.14, Cl 9.15, N 10.71, S 16.52.
127.9 (C-3,5, C6H5), 128.4 (C-3,5, 4-ClC6H4), 129.1 (C-2,6, 4- N-(6-Phenylimidazo[2,1-b]thiazol-5-yl)-4-methylbenzenesulfonamide
ClC6H4), 132.4 (C-1, C6H5), 138.1 (C-1, 4-ClC6H4), 138.4 (C-4, 4- (6b): Colorless needles, yield 0.70 g, 67 %; m.p. 199–202 °C. 1H
ClC H ), 139.7 (C-2), 142.5 (C-8a) ppm. IR (KBr): ν = 1167, 1351 NMR (400.13 MHz, [D6]DMSO): δ = 2.24 (s, 3 H, CH3), 7.10–7.53
˜
6
4
(SO2), 1650 (C=N) cm–1. C19H14ClN3O2S (383.85): calcd. C 59.45, (m, 11 H, 2-H, 3-H, Ar), 10.60 (br. s, 1 H, NHSO2) ppm. 13C NMR
Eur. J. Org. Chem. 2013, 368–375
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
373

I. B. Rozentsveig et al.
FULL PAPER
(100.61 MHz, [D6]DMSO): δ = 20.9 (CH3), 114.4 (C-3), 115.4 (C-
H 3.50, Cl 16.40, N 9.72, S 7.42; found C 55.33, H 3.46, Cl 16.47,
5), 118.5 (C-2), 126.2 (C-2,6, C6H5), 126.6 (C-3,5, 4-CH3C6H4), N 9.66, S 7.48.
127.2 (C-4, C6H5), 127.9 (C-3,5, C6H5), 129.5 (C-2,6, 4-CH3C6H4),
4-Chloro-N-methyl-N-(6-phenylimidazo[2,1-b]thiazol-5-yl)benzene-
131.6 (C-1, C6H5), 136.4 (C-1, 4-CH3C6H4), 139.5 (C-6), 143.52
sulfonamide (9): Yellow cube crystals, yield 0.80 g, 83%; m.p. 167–
(C-4, 4-CH C H ), 146.6 (C-7a) ppm. IR (KBr): ν = 1164, 1343
˜
3
6
4
169 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 3.42 (s, 3 H,
(SO2) cm–1. C18H15N3O2S2 (369.46): calcd. C 58.52, H 4.09, N
3
NCH3), 7.20–7.23 (m, 3 H, 3,4,5-H, C6H5), 7.30 (d, J = 4.5 Hz, 1
11.37, S 17.36; found C 58.66, H 4.03, N 11.41, S 17.29.
H, 3-H), 7.44–7.48 (m, 5 H, 2-H, 2,6-H 4-ClC6H4, 2,6-H C6H5),
7.61 (AAЈBBЈ,
2
H, 3,5-H 4-ClC6H4) ppm. 13C NMR
General Procedure for the Methylation of Imidazopyridines 5a and
5b, and Imidazothiazole 6a: Methyl iodide (4.8 mmol) was added to
a stirred mixture of imidazopyridine 5a and 5b, or imidazothiazole
6a (2.4 mmol), potassium carbonate (7.2 mmol), triethylbenzylam-
monium chloride (0.24 mmol) and acetonitrile (10 mL). The reac-
tion mixture was stirred with a magnetic stirrer for 6 h at room
temp. Then the solvent was removed under reduced pressure, the
residue was washed with water (100 mL), dried and washed with
diethyl ether (50 mL). To isolate compounds 7a and 7b the mixture
of 7a and 7b was washed with acetone (50 mL). The insoluble resi-
due was filtered off (compound 7a); evaporation of the filtrate gave
compound 7b.
(100.61 MHz, [D6]DMSO): δ = 37.9 (NCH3), 114.0 (C-3), 118.6
(C-2), 118.9 (C-5), 126.0 (C-2,6, C6H5), 127.3 (C-4, C6H5), 128.1
(C-3,5, C6H5), 128.9 (C-3,5, 4-ClC6H4), 129.5 (C-2,6, 4-ClC6H4),
132.6 (C-1, C6H5), 136.7 (C-1, 4-ClC6H4), 138.7 (C-4, 4-ClC6H4),
141.3 (C-6), 147.6 (C-7a) ppm. IR (KBr):
ν
=
1160,
˜
(SO2) 1350 cm–1. C18H14ClN3O2S2 (403.90): calcd. C 53.53, H 3.49,
Cl 8.78, N 10.40, S 15.88; found C 53.42, H 3.44, Cl 8.83, N 10.45,
S 15.83. H 3.49 C 53.53 N 10.40 O 7.92 S 15.88 Cl 8.78.
CCDC-878862, -878863 and -878864 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
4-Chloro-N-methyl-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzene-
sulfonamide (7a): Yellow cube crystals, yield 0.30 g, 30%; m.p. 151–
Supporting Information (see footnote on the first page of this arti-
1
154 °C. H NMR (400.13 MHz, [D6]DMSO): δ = 3.51 (s, 3 H, N-
1
cle): H and 13C NMR spectra of all compounds, crystal data and
CH3), 7.02 (m, 1 H, 6-H), 7.18–7.26 (m, 3 H, 3,4,5-H C6H5), 7.39
(m, 3 H, 7-H, 2,6-H 4-ClC6H4), 7.51 (m, 2 H, 2,6-H C6H5), 7.57
(AAЈBBЈ, 2 H, 3,5-H 4-ClC6H4), 7.63 (m, 1 H, 8-H), 8.14 (m, 1 H,
5-H) ppm. 13C NMR (100.61 MHz, [D6]DMSO): δ = 37.9 (NCH3),
112.9 (C-6), 117.1 (C-8), 117.2 (C-3), 123.9 (C-5), 126.4 (C-7), 126.7
(C-2,6, C6H5), 127.7 (C-4, C6H5), 128.1 (C-3,5, 4-ClC6H4), 128.8
(C-3,5, C6H5), 129.4 (C-2,6, 4-ClC6H4), 132.4 (C-1, C6H5), 137.2
(C-1, 4-ClC6H4), 138.6 (C-4, 4-ClC6H4), 140.2 (C-2), 142.5 (C-
details of X-ray experiments for compounds 7a, 7b and 8.
Acknowledgments
This research was supported by the Russian Foundation for Basic
Research (grant number 12-03-31762).
8a) ppm. IR (KBr): ν = 1160, 1350 (SO ) cm–1. C H ClN O S
˜
2
20 16
3
2
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(397.88): calcd. C 60.38, H 4.05, Cl 8.91, N 10.56, S 8.06; found C
60.45, H 4.11, Cl 8.95, N 10.47, S 8.11.
3-{[(4-Chlorophenyl)sulfonyl]methylamino}-1-methyl-2-phenylimid-
azo[1,2-a]pyridin-1-ium Iodide (7b): Yellow cube crystals, yield
0.88 g, 68 %; m.p. 157–159 °C. 1H NMR (400.13 MHz, [D6]-
DMSO): δ = 3.49 (s, 3 H, SO2NCH3), 3.76 (s, 3 H, NCH3), 7.32–
7.42 (m, 6 H, 2,3,5,6-H C6H5, 2,6-H 4-ClC6H4), 7.54 (m, 3 H, 3,5-
H 4-ClC6H4, 4-H C6H5), 7.74 (m, 1 H, 6-H), 8.23 (m, 1 H, 7-H),
8.40 (m, 1 H, 8-H), 8.86 (m, 1 H, 5-H) ppm. 1 3 C NMR
(100.61 MHz, [D6]DMSO): δ = 32.4 (NCH3), 39.45 (SO2NCH3),
111.8 (C-8), 118.0 (C-6), 120.2 (C-3), 123.2 (C-1, C6H5), 126.2 (C-
5), 128.7 (C-3,5, C6H5), 128.9 (C-3,5, 4-ClC6H4), 129.5 (C-2,6, 4-
ClC6H4), 130.0 (C-2,6, C6H5), 130.6 (C-4, C6H5), 135.0 (C-2, C-7),
135.5 (C-1, 4-ClC6H4), 137.8 (C-8a), 139.0 (C-4, 4-ClC6H4) ppm.
IR (KBr): ν = 1158, 1350 (SO ) cm–1. C H ClIN O S (539.82):
˜
2
21 19
3
2
calcd. C 46.73, H 3.55, Cl 6.57, N 7.78, S 5.94; found C 46.79, H
3.59, Cl 6.51, N 7.81, S 5.97.
N-(6-Chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)-N-methyl-4-chloro-
benzenesulfonamide (8): Yellow cube crystals, yield 0.93 g, 87 %;
m.p. 200–203 °C. 1H NMR (400.13 MHz, [D6]DMSO): δ = 3.54 (s,
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7.52–7.59 (m, 4 H, 2,6-H C6H5, 3,5-H 4-ClC6H4), 7.68 (d, 3J =
S. Kelly, A. P. Owens, W. P. Blackaby, R. T. Lewis, J. Stanley,
A. J. Smith, P. Ferris, B. Sohal, S. M. Cook, A. Pike, N. Brown,
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4
9.4 Hz, 1 H, 8-H), 8.12 (d, J = 1.6 Hz, 1 H, 5-H) ppm. 13C NMR
(100.61 MHz, [D6]DMSO): δ = 38.1 (CH3), 117.9 (C-3), 118.1 (C-
8), 119.9 (C-6), 121.9 (C-5), 126.7 (C-2,6, C6H5), 127.3 (C-7), 128.0
(C-4, C6H5), 128.2 (C-3,5, C6H5), 128.8 (C-3,5, 4-ClC6H4), 129.5
(C-2,6, 4-ClC6H4), 132.0 (C-1, C6H5), 137.1 (C-1, 4-ClC6H4), 138.8
(C-4, 4-ClC H ), 140.9 (C-2), 141.3 (C-8a) ppm. IR (KBr): ν =
˜
6
4
1162, 1360 (SO2) cm–1. C20H15Cl2N3O2S (432.32): calcd. C 55.56,
374
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 368–375

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Received: July 27, 2012
Published Online: November 12, 2012
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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