An efficient synthetic route to new imidazo[1,2-a]-pyridines by cross-coupling reactions in aqueous medium

Article abstract of DOI:10.3987/COM-05-10548

The Suzuki cross-coupling reaction of 6-bromo-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine and 6-bromo-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine provided an efficient route to the corresponding 6-aryl-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]

Full text of DOI:10.3987/COM-05-10548

HETEROCYCLES, Vol. 65, No. 12, 2005
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HETEROCYCLES, Vol. 65, No. 12, 2005, pp. 2979 - 2989
Received, 31st August, 2005, Accepted, 13th October, 2005, Published online, 14th October, 2005
AN EFFICIENT SYNTHETIC ROUTE TO NEW IMIDAZO[1,2-a]-
PYRIDINES BY CROSS-COUPLING REACTIONS IN AQUEOUS
MEDIUM
*
Caroline Castera, Maxime D. Crozet, and Patrice Vanelle
Laboratory of Pharmaceutical Organic Chemistry (LCOP), UMR CNRS 6517,
University of the Méditerranée, Faculty of Pharmacy, 27 Boulevard Jean Moulin,
13385 Marseille cedex 5, France. Fax: 33 4 91 79 46 77; Email:
patrice.vanelle@pharmacie.univ-mrs.fr
Abstract – The Suzuki cross-coupling reaction of 6-bromo-3-nitro-2-phenyl-
sulfonylmethylimidazo[1,2-a]pyridine
imidazo[1,2-a]pyridine provided an efficient route to the corresponding 6-aryl-
3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridines and 6-aryl-3-nitro-
and
6-bromo-3-nitro-2-tosylmethyl-
2-tosylmethylimidazo[1,2-a]pyridines. The reaction was catalyzed by
palladium(0) in aqueous medium.
INTRODUCTION
Over the last thirty years the use of sulfones in organic chemistry and medicinal chemistry has increased
dramatically. Sulfones have been employed in many synthetic methodologies as intermediates enabling
the preparation of a great number of functionalized products such as natural products and bioactive
substances.1 The Suzuki reaction has proved extremely versatile and has found extensive use in natural
products and heterocyclic synthesis.2 Some examples of Suzuki-type cross-coupling reactions in 3- and
6-haloimidazo[1,2-a]pyridine series were described.3 In continuation of our studies on the reactivity of
nitroheterocyclic sulfones, 4,5 we were then interested in the preparation of new sulfones bearing an aryl
group. We anticipated to prepare original compounds from 6-bromo-3-nitroimidazo[1,2-a]pyridines
bearing an arylsulfonylmethyl group in 2-position by Suzuki reaction with various arylboronic acids
(Scheme 1).

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HETEROCYCLES, Vol. 65, No. 12, 2005
Scheme 1
O2S
R
O2S
R
N
N
ArB(OH)2
N
Suzuki
reaction
N
Br
Ar
NO2
NO2
R = H, CH3
To our knowledge, except the pioneer work on the sodium salt of methyl phenylsulfonyl acetate with
allylic acetates of either geranyl acetate or neryl acetate in the presence of tetrakis (triphenyl-
phosphine)palladium(0) catalyst6 and the intramolecular version of this reaction for the preparation of
medium-ring lactones and macrolides,6 only the palladium-catalyzed monoarylation of a series of
functionalized strongly C-H acidic sulfones by aryl halides has been described.7
As part of an ongoing research program focused on the synthesis of new pyridinones of pharmaceutical
interest for the treatment of central nervous system disorders,8 we wish to report the results of this study
on the functional compatibility in Suzuki reaction of the phenylsulfonylmethyl and tosylmethyl groups in
ortho-like position of the nitro group in the 6-bromo-3-nitroimidazo[1,2-a]pyridine series.
RESULTS AND DISCUSSION
Synthesis of starting materials
The synthesis of 6-bromo-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (2b) was performed with sodium
toluene-4-sulfinate as previously described for the preparation of 6-bromo-3-nitro-2-phenylsulfonyl-
methylimidazo[1,2-a] pyridine (2a) as shown in scheme 2.3
Scheme 2
-
ArSO2 Na+
Cl
O2S
R
N
N
N
N
DMSO / rt / hν
Br
Br
NO2
NO2
1
2
a R = H
b R = CH3
These two compounds (2) served as starting material for the synthesis of several new sulfonyl derivatives
(3a-10b) obtained by cross-coupling reaction with some arylboronic acids in aqueous medium.
Cross-coupling reactions
Reactions in aqueous media are advantageous for largescale industrial processes because of the simplicity
of catalyst-product separation and economy and safety of using water as a solvent.9 Such reactions in
aqueous media are also useful for the biaryl coupling of arylboronic acids.10
Furthermore, owing tothe fact that the nitroheterocyclic sulfones (2) are strongly C-H acidic sulfones, their
expected solubility in the basic medium of the Suzuki experimental conditions offers the opportunity to

HETEROCYCLES, Vol. 65, No. 12, 2005
2981
develop Suzuki reaction in aqueous medium. So, the coupling reactions of the two sulfonyl compounds
with bromine atom in position 6 were tested with arylboronic acids according to Suzuki – Miyaura
reaction in water with Pd(PPh3)4 as catalyst. The method, which was tested to carry out cross-coupling
reaction, used as catalyst 10 mol% of Pd(PPh3)4, as base 5 equivalents of Na2CO3 and 1.3 equivalent of
arylboronic acid. Because of the facile formation of the anion (2a) and (2b), a large amount of base was
employed. The formation of the sulfonyl anion in basic medium could allow a better solubility of the
reagent in water, what would allow the cross-coupling reaction to proceed in aqueous medium.
The mixture of 2-arylsulfonylmethyl-6-bromo-3-nitroimidazo[1,2-a]pyridine, arylboronic acid, Pd(Ph3)4,
Na2CO3 and water was heated under reflux from 1 to 24 h and the disappearance of starting materials was
monitored by TLC. No organic solvent or cosolvent were used or investigated. Although the reaction
mixtures were nonhomogeneous and aggregated, the yields were good overall. Some yields appeared to
suffer due to the difficulties in the workup extractions. The aggregation, coupled with the high surface
tension of water, diminishes the surface contact between hydrophobic species and water molecules.11
These Suzuki couplings in aqueous media were accomplished by the employment of large excess of base
for interaction with sulfonyl anions to give 3-10 in moderate to good yields (Scheme 3, Table 1) and the
structure of the boronic acid has few influence on the yield.
Scheme 3
ArB(OH)2
O2S
R
10% Pd(PPh3)4
O2S
R
N
N
N
N
Na2CO3
Br
Ar
NO2
NO2
∆ / H2O
R = H, CH3
2
3-10
Table 1
Cross-coupling reaction of 2-arylsulfonylmethyl-6-bromo-3-nitroimidazo[1,2-a]pyridines with
arylboronic acidsa
Entry
Arylboronic acid
Product
Compound number
t (h)
Yield
OH
O2S
N
1
3a
20 (3)b
60 (70)b
B
OH
N
N
NO2
OH
O2S
CH3
B
2
3
4
3b
4a
4b
2
2
60
60
72
OH
N
NO2
O2S
OH
N
B
N
N
OH
NO2
CH3
CH3
N
OH
O2S
CH3
B
24
OH
NO2
CH3
CH3

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HETEROCYCLES, Vol. 65, No. 12, 2005
OH
B
O2S
N
OH
5
5a
1.75
60
N
N
CH3O
CH3O
NO2
CH3O
OH
B
O2S
CH3
OH
6
7
8
5b
6a
6b
2
4.5
3
97
77
60
N
NO2
CH3O
OH
O2S
N
B
OH
N
NO2
F
F
F
OH
B
O2S
CH3
N
OH
N
NO2
F
OH
O2S
N
B
OH
9
7a
7b
8a
1.5
1.5
5
76
55
N
NO2
CF3
CF3
NO2
NO2
CF3
OH
B
O2S
CH3
N
OH
10
11
12
13
14
15
N
NO2
CF3
OH
B
O2S
N
OH
50
N
N
NO2
NO2
OH
B
O2S
CH3
OH
8b
9a
2
90
N
NO2
NO2
O2S
OH
B
N
N
1
63
OH
NO2
OH
B
O2S
CH3
N
20 (3)b
20 (90)b
OH
N
9b
10a
NO2
HO
OH
O2S
N
B
N
4.5
63
NO2

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2983
O2S
CH3
N
HO
OH
B
N
16
10b
3
55
NO2
a
Conditions: catalyst Pd(PPh3)4 10% mol, 2-arylsulfonylmethyl-6-bromo-3-nitroimidazo[1,2-a]pyridine
(1 equiv.), arylboronic acid (1.3 equiv.), Na2CO3 (5 equiv.), H2O, 100 °C.
b Time reaction and yields in parenthesis correspond to reactions performed under sonication, 74 °C.
In order to optimize the reaction yield, we preliminary investigated cross-coupling reaction performed
under sonication at 74 °C on 2a with phenylboronic acid and 2b with naphthalen-2-ylboronic acid. These
conditions, inspired with significative results were obtained by Toma and coworkers.12 They assume that
the beneficial effect of ultrasound on this heterogeneous reaction can be attributed to a better mass
transfer in comparison with magnetically stirred reaction. Sonification seemed to facilitate the treatment
and the purification, accelerate the reaction rate and increase the reaction yield. Our results confirm
acceleration of reaction rate and increase of the yields (Entries 1 and 14). It is noteworthy that under these
experimental conditions, with or without sonication, arylation of the sulfonyl carbanion7 was not
observed or leads to untractable products.
CONCLUSION
In conclusion, a simple general procedure for the preparation of new 6-aryl-3-nitro-2-phenylsulfonyl-
methylimidazo[1,2-a]pyridines and 6-aryl-3-nitro-2-tosylmethylimidazo[1,2-a]pyridines has been
developed on the basis of palladium-mediated coupling of arylboronic acid. Moreover we have shown in
this study the functional compatibility in Suzuki reaction of the phenylsulfonylmethyl and tosylmethyl
groups in ortho-like position of the nitro group in the 6-bromo- 3-nitroimidazo[1,2-a]pyridine series.
EXPERIMENTAL
Melting points were determined with a B-540 Büchi melting point apparatus. 200 MHz 1H NMR and 50
MHz13CNMR spectra were recorded on a Bruker ARX 200 spectrometer in CDCl3 solution at the Faculté
dePharmaciedeMarseille. 1H and 13C NMR chemical shifts (δ) are reported in ppm with respect to CHCl3
7.26 ppm (1H) and 76.9 ppm (13C) and DMSO-d6 2.50 ppm (1H) and 39.70 ppm (13C). Elemental analyses
were carried out at the Centre de Microanalyses de la Faculté des Sciences et Techniques de Saint-Jérôme
and at the Service Central d’Analyse du Centre National de la Recherche Scientifique de Vernaison. The
following adsorbent was used for column chromatography: silica gel 60 (Merck, particle size 0.063-0.200
mm, 70-230 mesh ASTM). TLC were performed on 5 cm × 10 cm aluminium plates coated with silica gel
60F-254 (Merck) in an appropriate solvent. Sonochemical experiments were carried out in the ultrasonic

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cleaning bath Bioblock Scientific (35 kHz). 6-Bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine (1)
and 6-bromo-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (2a) were previously described.3
Preparation of 6-bromo-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (2b)
To a solution of sodium toluene-4-sulfinate (1.78 g, 10 mmol) in DMSO (40 mL) under inert atmosphere
(N2) and irradiation with a tungsten 150W lamp was added 1.45 g (5.0 mmol) of 6-bromo-2-
chloromethylimidazo[1,2-a]pyridine. The mixturewasstirredat rt for 3 h. After disappearance of 6-bromo-
2-chloromethyl-3-nitroimidazo[1,2-a]pyridine (monitored by TLC), the mixture was poured into an
ice-water mixture and a solid precipitated. The solid was collected by filtration and dried in the air to give
after purification by recrystallization from propan-2-ol 1.85 g (90%) of 2b as yellow solid. mp 201 °C. 1H
NMR (CDCl3) δ 2.44 (s, 3H, CH3); 5.09 (s, 2H, CH2); 7.31 (d, J = 7.9 Hz, 2H, CH); 7.72 (s, 2H, CH);
7.73 (d, J = 7.9 Hz, 2H, CH); 9.52 (m, 1H, CH). 13C NMR (CDCl3) δ 21.7 (CH3); 56.7 (CH2); 112.4 (C);
119.1(CH);127.7 (CH); 128.3 (CHx2); 129.9 (CHx2); 134.5 (CH); 136.2 (C); 139.7 (C); 143.3 (C); 145.3
(C). Anal. Calcd for C15H12N3O4BrS: C, 43.92; H, 2.95; N, 10.24. Found: C, 43.97; H, 2.67; N, 10.45.
General procedure for cross-coupling reaction of heteroaryl bromides with arylboronic acids
A solution of 2-arylsulfonylmethyl-6-bromo-3-nitroimidazo[1,2-a]pyridine (1.26 mmol), arylboronic acid
(1.64 mmol), Na2CO3 (6.31 mmol), Pd(PPh3)4 (0.13 mmol) in water was heated under reflux for a time t.
After disappearance of 2-arylsulfonylmethyl-6-bromo-3-nitroimidazo[1,2-a]pyridine (monitored by TLC),
the mixture was cooled and the solid was collected by filtration and dried in the air. The crude product
was purified by column chromatography on silica gel with appropriate solvent to give 6-aryl-2-
arylsulfonylmethyl-3-nitroimidazo[1,2-a] pyridine.
3-Nitro-6-phenyl-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (3a)
Cross-coupling reaction of phenylboronic acid (200 mg, 1.64 mmol) with 2a (500 mg, 1.26 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CHCl3-ethyl acetate 9:1) and recrystallization from ethyl acetate 300 mg (60%) of 3a. Reaction
1
performed under sonication gave 350 mg (70%) of 3a as yellow solid. mp 238 °C. H NMR (CDCl3)
δ 5.17 (s, 2Η, CH2); 7.47-7.90 (m, 12H, CH); 9.55 (m, 1H, CH). 13C NMR (CDCl3): δ 56.9 (CH2); 118.4
(CH); 125.0 (CH); 127.4 (CHx2); 128.4 (CHx2); 129.1 (CH); 129.3 (CHx2); 129.5 (CHx2); 131.6 (CH);
132.0 (C); 134.2 (CH); 135.7 (C); 139.3 (C); 139.8 (C); 144.2 (C). Anal. Calcd for C20H15N3O4S: C,
61.06; H, 3.84; N, 10.68. Found: C, 61.30; H, 3.74; N, 10.38.
3-Nitro-6-phenyl-2-tosylmethylimidazo[1,2-a]pyridine (3b)
Cross-coupling reaction of phenylboronic acid (190 mg, 1.6 mmol) with 2b (500 mg, 1.22 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CHCl3-ethyl acetate 1:1) and recrystallization from propan-2-ol 300 mg (60%) of 5a as yellow solid. mp
205 °C. 1H NMR (CDCl3) δ 2.44 (s, 3H); 5.14 (s, 2H, CH2); 7.32 (d, J = 8.1 Hz, 2H, CH); 7.50-7.64 (m,
13
5H, CH); 7.76 (d, J = 8.1 Hz, 2H, CH); 7.90 (s, 2H, CH); 9.55 (m, 1H, CH). C NMR (CDCl3) δ 21.6

HETEROCYCLES, Vol. 65, No. 12, 2005
2985
(CH3); 56.9 (CH2); 118.4 (CH); 124.9 (CH); 127.3 (CHx2); 128.3 (CHx2); 129.3 (CH); 129.4 (CHx2);
129.8 (CHx2); 131.5 (CH); 131.8 (C); 135.6 (C); 136.3 (C); 139.9 (C); 144.1 (C); 145.2 (C). Anal. Calcd
for C21H17N3O4S: C, 61.90; H, 4.21; N, 10.31. Found: C, 61.68; H, 4.24; N, 10.18.
3-Nitro-2-phenylsulfonylmethyl-6-o-tolylimidazo[1,2-a]pyridine (4a)
Cross-coupling reaction of o-tolylboronic acid (220 mg, 1.64 mmol) with 2a (500 mg, 1.26 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
1
CH2Cl2) and recrystallization from toluene 300 mg (60%) of 4a as black solid. mp 191 °C. H NMR
13
(CDCl3) δ 2.30 (s, 3H, CH3); 5.17 (s, 2H, CH2); 7.25-7.94 (m, 11H, CH); 9.33 (m, 1H, CH). C NMR
(CDCl3)δ20.3(CH3); 56.8 (CH2); 117.7 (CH); 126.4 (CH); 126.5 (CH); 128.3 (CHx2); 129.1 (CH); 129.2
(CHx2); 129.9 (CH); 131.0 (CH); 132.1 (C); 133.5 (CH); 134.1 (CH); 135.8 (C); 139.3 (C); 139.6 (C);
144.0 (C). Anal. Calcd for C21H17N3O4S: C, 61.90; H, 4.21; N, 10.31. Found: C, 62.13; H, 4.24; N, 10.42.
3-Nitro-6-o-tolyl-2-tosylmethylimidazo[1,2-a]pyridine (4b)
Cross-coupling reaction of o-tolylboronic acid (210 mg, 1.6 mmol) with 2b (500 mg, 1.22 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CHCl3-ethyl acetate 9:1) and recrystallization from toluene 370 mg (72%) of 4b as beige solid. mp
249 °C. 1H NMR (CDCl3) δ 2.32 (s, 3H, CH3); 2.46 (s, 3H, CH3); 5.16 (s, 2H, CH2); 7.26-7.91 (m, 10H,
13
CH); 9.35 (m, 1H, CH). C NMR (CDCl3) δ 20.4 (CH3); 21.7 (CH3); 56.9 (CH2); 117.7 (CH); 126.4
(CH); 126.6 (CH); 128.4 (CHx2); 129.1 (CH); 129.9 (CHx2); 130.0 (CH); 130.9 (CH); 132.1 (C); 133.4
(CH); 135.8 (Cx2); 136.5 (C); 139.9 (C); 144.0 (C); 145.2 (C). Anal. Calcd for C22H19N3O4S: C, 62.69; H,
4.54; N, 9.97. Found: C, 62.64; H, 4.54; N, 9.97.
6-(4-Methoxyphenyl)-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (5a)
Cross-coupling reaction of 4-methoxyphenylboronic acid (250 mg, 1.64 mmol) with 2a (500 mg, 1.26
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: CH2Cl2-ethyl acetate 4:1) and recrystallization from toluene 320 mg (60%) of 5a as green solid.
1
mp 249 °C. H NMR (CDCl3) δ 3.89 (s, 3H, CH3); 5.17 (s, 2H, CH2); 7.06 (d, J = 8.6 Hz, 2H, CH);
13
7.46-8.00 (m, 9H, CH); 9.52 (m, 1H, CH). C NMR (CDCl3): δ 55.5 (CH3); 56.9 (CH2); 115.0 (CHx2);
118.3 (CH); 124.3 (CH); 128.0 (C); 128.4 (CHx2); 128.5 (CHx2); 129.2 (CHx2); 131.4 (CH); 131.7 (C);
134.1 (CH); 139.3 (C); 139.7 (C); 144.0 (C); 160.5 (C). Anal. Calcd for C21H17N3O5S: C, 59.57; H, 4.05;
N, 9.92. Found: C, 59.72; H, 4.05; N, 9.83.
6-(4-Methoxyphenyl)-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (5b)
Cross-coupling reaction of 4-methoxyphenylboronic acid (240 mg, 1.6 mmol) with 2b (500 mg, 1.22
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: Petroleum ether-ethyl acetate 3:7) and recrystallization from toluene gave 520 mg (97%) of 5b as

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green solid. mp 221 °C. 1H NMR (CDCl3) δ 2.44 (s, 3H, CH3); 3.88 (s, 3H, CH3); 5.14 (s, 2H, CH2); 7.04
(d, J = 8.8 Hz, 2H, CH); 7.31 (d, J = 8.3 Hz, 2H, CH); 7.55 (d, J = 8.8 Hz, 2H, CH); 7.75 (d, J = 8.3 Hz,
2H, CH); 7.86 (s, 2H, CH); 9.50 (m, 1H, CH); 13C NMR (CDCl3) δ 21.7 (CH3); 55.4 (CH3); 56.9 (CH2);
114.9 (CHx2); 118.3 (CH); 124.3 (CH); 128.4 (CHx2); 128.5 (CHx2); 129.8 (CHx2); 131.3 (CH); 131.6
(C); 134.5 (C); 136.3 (C); 139.8 (C); 143.9 (C); 145.2 (C); 160.5 (C). Anal. Calcd for C22H19N3O5S: C,
60.40; H, 4.38; N, 9.61. Found: C, 60.79; H, 4.39; N, 9.28.
6-(4-Fluorophenyl)-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (6a)
Cross-coupling reaction of 4-fluorophenylboronic acid (230 mg, 1.64 mmol) with 2a (500 mg, 1.26
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: CH2Cl2) and recrystallization from propan-2-ol 400 mg (77%) of 6a as yellow solid. mp 229 °C.
13
1H NMR (CDCl3) δ 5.17 (s, 2H, CH2); 7.19-7.94 (m, 11H, CH); 9.53 (m, 1H, CH). C NMR (CDCl3) δ
56.9 (CH2); 116.4 (CH); 116.8 (CH); 118.6 (CH); 124.9 (CH); 128.4 (CHx2); 129.1 (CH); 129.3 (CHx3);
131.0 (CH); 131.3 (CH); 131.8 (C); 134.2 (C); 139.3 (C); 139.8 (C); 144.1 (C); 163.5 (C). Anal. Calcd for
C20H14N3O4FS: C, 58.39; H, 3.43; N, 10.21. Found: C, 58.52; H, 3.57; N, 10.19.
6-(4-Fluorophenyl)-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (6b)
Cross-coupling reaction of 4-fluorophenylboronic acid (220 mg, 1.6 mmol) with 2b (500 mg, 1.22 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CH2Cl2) and recrystallization from propan-2-ol 306 mg (60%) of 6b as yellow solid. mp 241 °C. 1H NMR
13
(CDCl3) δ 2.45 (s, 3H, CH3); 5.15 (s, 2H, CH2); 7.20-7.94 (m, 10H, CH); 9.54 (m, 1H, CH). C NMR
(CDCl3) δ 21.8 (CH3); 56.9 (CH2); 116.4 (CH); 116.8 (CH); 118.6 (CH); 124.9 (CH); 128.4 (CHx2);
129.1 (CH); 129.3 (CH); 129.9 (CHx2); 131.0 (C); 131.3 (CH); 131.9 (C); 136.4 (C); 140.0 (C); 144.1
(C); 145.3 (C); 161.9 (C). Anal. Calcd for C21H16N3O4FS: C, 59.29; H, 3.79; N, 9.88. Found: C, 59.42; H,
3.92; N, 9.87.
3-Nitro-2-phenylsulfonylmethyl-6-(3-trifluoromethylphenyl)imidazo[1,2-a]pyridine (7a)
Cross-coupling reaction of 3-trifluoromethylphenylboronic acid (310 mg, 1.64 mmol) with 2a (500 mg,
1.26 mmol) according to the general procedure gave after purification by column chromatography (silica
gel, eluent: CHCl3-ethyl acetate 7:3) and recrystallization from propan-2-ol 440 mg (76%) of 7a as
1
yellow solid. mp 221 °C. H NMR (CDCl3) δ 5.18 (s, 2H, CH2); 7.51-7.99 (m, 11H, CH); 9.59 (m, 1H,
CH). 13C NMR (CDCl3) δ 56.8 (CH2); 118.9 (CH); 123.8 (C); 124.2 (CH); 125.3 (CH); 125.8 (CH);
128.4 (CHx2); 129.3 (CHx2); 130.1 (CH); 130.5 (C); 130.7 (CH); 131.1 (CH); 132.1 (C); 134.2 (CH);
136.6 (C); 139.2 (C); 140.0 (C); 144.2 (C). Anal. Calcd for C21H14N3O4F3S: C, 54.66; H, 3.06; N, 9.11.
Found: C, 54.63; H, 3.06; N, 9.11.
3-Nitro-2-tosylmethyl-6-(3-trifluoromethylphenyl)imidazo[1,2-a]pyridine (7b)
Cross-coupling reaction of 3-trifluoromethylphenylboronic acid (300 mg, 1.6 mmol) with 2b (500 mg,

HETEROCYCLES, Vol. 65, No. 12, 2005
2987
1.22 mmol) according to the general procedure gave after purification by column chromatography (silica
gel, eluent: CH2Cl2) and recrystallization from propan-2-ol 310 mg (55%) of 7b as yellow solid. mp
221 °C. 1H NMR (CDCl3) δ 2.46 (s, 3H, CH3); 5.16 (s, 2H, CH2); 7.32-7.99 (m, 10H, CH); 9.60 (m, 1H,
CH). 13C NMR (CDCl3) δ 21.7 (CH3); 56.9 (CH2); 118.8 (CH); 123.7 (C); 124.2 (CH); 125.3 (CH); 125.8
(CH); 128.3 (CHx2); 129.9 (CHx2); 130.1 (CH); 130.4 (C); 130.7 (C); 131.1 (CH); 132.0 (C); 136.3 (C);
136.7 (C); 140.2 (C); 144.2 (C); 145.3 (C). Anal. Calcd for C22H16N3O4F3S: C, 55.58; H, 3.39; N, 8.84.
Found: C, 55.54; H, 3.43; N, 8.79.
3-Nitro-6-(3-nitrophenyl)-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (8a)
Cross-coupling reaction of 3-nitrophenylboronic acid (270 mg, 1.64 mmol) with 2a (500 mg, 1.26 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CH2Cl2-ethyl acetate 9:1) and recrystallization from toluene 280 mg (50%) of 8a as green solid. mp
252 °C. 1H NMR (DMSO-d6) δ 5.28 (s, 2H, CH2); 7.58-8.59 (m, 11H, CH); 9.57 (m, 1H, CH). 13C NMR
(DMSO-d6) δ 56.3 (CH2); 118.2 (CH); 122.3 (CH); 123.6 (CH); 126.3 (CH); 128.1 (CHx2); 128.3 (CH);
129.5 (CHx2); 131.4 (CH); 131.9 (CH); 134.1 (CH); 134.4 (CH); 137.5 (C); 139.1 (C); 140.1 (C); 143.9
(C); 148.3 (C). Anal. Calcd for C20H14N4O6S: C, 54.79; H, 3.22; N, 12.78. Found: C, 54.78; H, 3.25; N,
12.65.
3-Nitro-6-(3-nitrophenyl)-2-tosylmethylimidazo[1,2-a]pyridine (8b)
Cross-coupling reaction of 3-nitrophenylboronic acid (270 mg, 1.6 mmol) with 2b (500 mg, 1.22 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
CHCl3-ethyl acetate 9:1) and recrystallization from toluene 500 mg (90%) of 8b as yellow solid. mp
249 °C. 1H NMR (CDCl3) δ 2.45 (s, 3H, CH3); 5.15 (s, 2H, CH2); 7.35-8.49 (m, 10H, CH); 9.64 (m, 1H,
13
CH). C NMR (CDCl3) δ 21.7 (CH3); 56.9 (CH2); 119.1 (CH); 122.3 (CH); 123.8 (CH); 125.5 (CH);
128.4 (CHx2); 129.5 (C); 129.9 (CHx2); 130.6 (CH); 130.7 (CH); 133.2 (CH); 136.3 (C); 137.5 (C);
140.3 (C); 144.2 (C); 145.3 (C); 149.0 (C). Anal. Calcd for C21H16N4O6S: C, 55.75; H, 3.56; N, 12.38.
Found: C, 56.06; H, 3.63; N, 12.49.
6-Naphthalen-2-yl-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (9a)
Cross-coupling reaction of naphthalen-2-ylboronic acid (230 mg, 1.31mmol) with 2a (400 mg, 1.01
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: CHCl3-ethyl acetate 9:1) and recrystallization from toluene 280 mg (63%) of 9a as yellow solid.
mp 220 °C. 1H NMR (CDCl3) δ 5.18 (s, 2Η, CH2); 7.17-8.07 (m, 15H, CH); 9.65 (m, 1H, CH). 13C NMR
(CDCl3) δ 56.9 (CH2); 118.5 (CH); 124.5 (CH); 125.2 (CH); 126.7 (CH); 127.1 (CH); 127.8 (CH); 128.2
(CH); 128.3 (CH); 128.4 (CHx2); 129.2 (CHx2); 129.4 (CH); 131.6 (CH); 131.8 (C); 132.8 (C); 133.2
(C); 133.5 (CH); 134.1 (CH); 139.2 (C); 139.8 (C); 144.1 (C). Anal. Calcd for C24H17N3O4S: C, 65.00; H,
3.86; N, 9.48. Found: C, 65.39; H, 3.75; N, 9.22.

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6-Naphthalen-2-yl-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (9b)
Cross-coupling reaction of naphthalen-2-ylboronic acid (140 mg, 0.8 mmol) with 2b (250 mg, 0.61
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: CH2Cl2-ethyl acetate 9:1) and recrystallization from ethyl acetate 55 mg (20%) of 9b. Reaction
1
performed under sonication gave 250 mg (90%) of 9b as yellow solid. mp 277 °C. H NMR (CDCl3)
δ 2.45 (s, 3H, CH3); 5.17 (s, 2H, CH2); 7.31-8.09 (m, 13H, CH); 9.69 (m, 1H, CH). 13C NMR (CDCl3) δ
21.7 (CH3); 57.0 (CH2); 118.5 (CH); 124.6 (CH); 125.2 (CH); 126.7 (CH); 127.1 (CH); 127.8 (CH);
128.2 (CH); 128.3 (CHx2); 128.4 (CH); 129.5 (CH); 129.9 (CHx2); 131.6 (CH); 131.8 (C); 132.9 (C);
133.2 (C); 133.5 (C); 136.4 (C); 140.0 (C); 144.2 (C); 145.2 (C). Anal. Calcd for C25H19N3O4S: C, 65.63;
H, 4.10; N, 9.18. Found: C, 65.67; H, 4.21; N, 9.12.
6-Naphthalen-1-yl-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine (10a)
Cross-coupling reaction of naphthalen-1-ylboronic acid (280 g, 1.64 mmol) with 2a (500 mg, 1.26 mmol)
according to the general procedure gave after purification by column chromatography (silica gel, eluent:
1
CH2Cl2) and recrystallization from ethyl acetate 350 mg (63%) of 10a as yellow solid. mp 249 °C. H
NMR (CDCl3) δ 5.21 (s, 2H, CH2); 7.49-7.97 (m, 14H, CH); 9.50 (m, 1H, CH). 13C NMR (CDCl3) δ 56.9
(CH2); 117.7 (CH); 124.6 (CH); 125.4 (CH); 126.5 (CH); 127.1 (CH); 127.2 (CH); 127.9 (CH); 128.4
(CHx2); 128.8 (CH); 129.3 (CHx2); 129.6 (CH); 131.2 (C); 131.4 (C); 133.8 (C); 133.9 (C); 134.2
(CHx2); 139.4 (C); 139.7 (C); 144.2 (C). Anal. Calcd for C24H17N3O4S: C, 65.00; H, 3.86; N, 9.48.
Found: C, 65.24; H, 3.88; N, 9.29.
6-Naphthalen-1-yl-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine (10b)
Cross-coupling reaction of naphthalen-1-ylboronic acid (270 mg, 1.6 mmol) with 2b (500 mg, 1.22
mmol) according to the general procedure gave after purification by column chromatography (silica gel,
eluent: CHCl3-ethyl acetate 9:1) and recrystallization from toluene 300 mg (55%) of 10b as yellow solid.
1
mp 266 °C. H NMR (CDCl3) δ 2.45 (s, 3H, CH3); 5.18 (s, 2H, CH2); 7.37-8.01 (m, 13H, CH); 9.49 (m,
1H CH). 13C NMR (CDCl3) δ 21.7 (CH3); 56.9 (CH2); 117.7 (CH); 124.7 (CH); 125.4 (CH); 126.5 (CH);
127.1 (CH); 127.2 (CH); 127.9 (CH); 128.4 (CHx2); 128.8 (CH); 129.6 (CH); 129.9 (CHx2); 131.1 (C);
131.3 (C); 133.8 (C); 133.9 (C); 134.1 (C); 136.5 (C); 139.9 (C); 144.2 (C); 145.2 (C). Anal. Calcd for
C25H19N3O4S: C, 65.63; H, 4.19; N, 9.18. Found: C, 65.92; H, 4.23; N, 9.11.
ACKNOWLEDGMENTS
This paper is dedicated to Dr Michel P. Crozet for his retirement. This work was supported by the CNRS
and the Universities of Aix-Marseille. C. Castera thanks the AP-HM for hospital appointment.
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