Ionic liquid phase synthesis (IoLiPS) of 2-aminothiazoles and imidazo[1,2-a]pyridines

Article abstract of DOI:10.1039/c4ra08009b

An efficient and practical ionic liquid phase synthesis (IoLiPS) of aza-heterocycles has been developed through a 'catch-and-release' strategy using an ionic liquid-supported hypervalent iodine reagent. The hypervalent iodine played a dual role as a reagent and as a soluble support. This strategy provided a combinatorial approach for the synthesis of 2-aminothiazoles and imidazo[1,2-a]pyridines directly from substituted acetophenones in good to excellent yields. The use of an ionic liquid supported reagent offered better isolation of the products by simple extraction with organic solvents. This journal is

Full text of DOI:10.1039/c4ra08009b

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Ionic liquid phase synthesis (IoLiPS) of 2-
aminothiazoles and imidazo[1,2-a]pyridines†
Cite this: RSC Adv., 2014, 4, 47368
*
Sunita Choudhary,‡ Manoj Kumar Muthyala‡ and Anil Kumar
An efficient and practical ionic liquid phase synthesis (IoLiPS) of aza-heterocycles has been developed
through a ‘catch-and-release’ strategy using an ionic liquid-supported hypervalent iodine reagent. The
hypervalent iodine played a dual role as a reagent and as a soluble support. This strategy provided a
combinatorial approach for the synthesis of 2-aminothiazoles and imidazo[1,2-a]pyridines directly from
substituted acetophenones in good to excellent yields. The use of an ionic liquid supported reagent
offered better isolation of the products by simple extraction with organic solvents.
Received 2nd August 2014
Accepted 18th September 2014
DOI: 10.1039/c4ra08009b
www.rsc.org/advances
1,2,3-thiadiazoles and 1,2,3-selenadiazoles via catch-and-
release strategy.6
Introduction
Nitrogen-containing heterocyclic compounds 2-amino-
thiazoles and imidazo[1,2-a]pyridines play signicant role in
the pharmaceutical and agrochemical industries.7 Several
synthetic methodologies have been developed for the synthesis
of thiazoles8 and imidazo[1,2-a]pyridines.9 The most widely and
practically used method for the synthesis of these aza-hetero-
cycles is coupling reaction of a-tosyloxycarbonyls/a-hal-
ocarbonyls with thiourea and 2-aminopyridine.10 However, this
method requires isolation and purication of the intermediates
and/or use of lachrymatory a-halocarbonyls and thus novel
method that can address these issues are desired for the
synthesis of these aza-heterocycles. Adding to our continuous
interest and our ongoing research program on functionalized
ionic liquids,6,11 here in we report ionic liquid phase synthesis of
2-aminothiazoles and imidazo[1,2-a]pyridines via catch-and-
release strategy using ionic liquid-supported hypervalent iodine
reagent.
Finding novel and more expedient techniques that will facilitate
the rapid production and purication of desired molecules is an
area of continued creativity for organic chemists. Development
of new linkers for tethering organic compounds to the supports
is an area of active investigation in supported synthesis.1 Choice
of linker is a key consideration in planning a supported
synthesis since the cleavage conditions oen leads to extra or
unwanted functional groups in the molecule and moreover, the
liability of the linker limits the chemistry which may be carried
out on it. In this context, catch-and-release strategies have been
very useful and they have been explored in combinatorial
chemistry for rapid production of library of organic compounds
with adequate purity.2 Although solid-phase catch-and-release
methods enables the efficient generation of many pharmaco-
logical important compounds, difficulties in analyzing the
intermediates, non linear kinetics and heterogeneous reaction
conditions are major concerns in these methods.
To overcome the problems associated with solid-phase
catch-and-release methods several new alternative approaches
using soluble supports such as uorous,3 PEG and ionic liquid
have been developed.4 For example, Procter group developed an
efficient uorous cyclative-capture strategy for the synthesis of
aza-heterocyles5 and Galan and co-workers introduced ion sup-
ported catch-and-release strategy for the synthesis of b-(1 / 6)
and b-(1 / 2)-linked oligosaccharides.2c Recently, we have
developed a new ionic liquid-supported sulfonyl hydrazine
linker and demonstrated its application in the synthesis of
Results and discussion
Ionic liquid-supported hypervalent iodine reagent (5) has been
synthesized in three steps starting from 1,2-dimethylimidazole
Department of Chemistry, Birla Institute of Technology and Science, Pilani, Pilani
333031, India. E-mail: anilkumar@pilani.bits-pilani.ac.in; Fax: +91 1596 244183;
Tel: +91 1596 515514
† Electronic supplementary information (ESI) available: Experimental procedure,
1H and 13C NMR data of compounds 7a–g, 9a–g and 11a–g, copies of NMR spectra
for compounds 5, 7a–g, 9a–g and 11a–g. See DOI: 10.1039/c4ra08009b
‡ Both authors contributed equally.
Scheme 1 Synthesis of ionic liquid-supported hypervalent iodine
reagent.
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(1) (Scheme 1).11b N-Alkylation of 1 with 1,4-butanesultone (2)
The synthetic procedure for 2-aminothiazoles 9 started by
and acidication with triuoromethanesulfonic acid gave ionic the reaction of 6a with 5 in CH3CN at 80 ꢀC for 12 h in the
liquid-supported sulfonic acid 3 in 98% yield.11e Homogeneous presence of anhydrous Na2SO4 followed by reaction with thio-
solution of 3 was added to the hot solution of iodobenzene urea. Aer complete ‘capture’ of 6a by 5, the reaction mixture
diacetate (4) in CH3CN and the resulting reaction mixture was was ltered to remove Na2SO4 and CH3CN was evaporated
reserved at room temperature for one week to obtain 5.
under reduced pressure and the residue containing 7a was
Reagent 5 was further studied for the capturing of 3-chlor- washed with diethyl ether to remove excess iodobenzene. Next,
oacetopheone (6a). Of the various conditions that were studied, 7a was allowed to react with thiourea under solvent free
it was found that 6a was completely captured by using 2 equiv. conditions at 40 ꢀC for 4 h to ‘release’ 9a. Use of the ionic liquid-
of 5 in CH3CN under reux conditions for 12 h. Aer comple- linked reagent facilitated easy product isolation by simple
tion of the reaction, resulting ionic liquid-supported phase separation. Aer completion of reaction, the product 9a
substituted a-sulfonyloxy-acetophenone 7a was puried by was isolated by extracting with hexane–ethyl acetate (2 : 8 v/v)
passing through
a short silica column using dichlor- mixture. In order to ascertain the scope of the reagent 5 in
omethane : methanol mixture (95 : 5 v/v) as eluent. We want to combinatorial synthesis a library of 2-aminothiazoles 9a–g were
probe whether 7a would have same reactivity that of conven- prepared from acetophenones bearing both electron-donating
tional a-tosyloxy ketones. The reaction of 7a with thiourea and electron-withdrawing substituents. The yield of all the 2-
afforded 4-(3-chlorophenyl)thiazol-2-amine (9a) in good yield. aminothiazoles 9a–g is given in Table 1. It is worthy to mention
Being condent that our ionic liquid-supported a-sulfonyloxy- that the 2-aminothiazoles were of pure enough and no further
acetophenone 7a was emulating its counterpart a-tosyloxy purication was required.
ketones, we then focused our attention to develop a simple and
With our interest in the synthesis of imidazo[1,2-a]pyr-
straight forward, chromatographic free protocol for the idines9a,12 we further extended this catch-and-release method
synthesis of thiazoles from acetophenones.
for the synthesis of imidazo[1,2-a]pyridine ring systems. Initial
attempt showed that the capture of 6a with 5, followed by
Table 1 Synthesis of 2-aminothiazoles 9a–g using 5a
Table 2 Synthesis of imidazo[1,2-a]pyridines 11a–g using 5a
S. No.
Ar
Product
Yieldb (%) (purity)c
84 (>98)
S. No.
1
Ar
Product
Yieldb (%) (purity)c
84 (82)
1
2
3
3-ClC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H5
83 [63]d (>99)
80 (99)
2
4-ClC6H4
83 [68]d (>98)
3
4
5
6
4-BrC6H4
4-CH3C6H4
4-OCH3C6H4
C10H7
80 (>99)
71 [57]d (>99)
58 (99)
4
5
6
4-CH3C6H4
71 [58]d (99)
71 (97)
4-OCH3C6H4
C10H7
81 (>89)
63 (99)
7
C4H3S
77 (94)
7
C4H3S
66 (>99)
a
a
Reaction conditions: 6 (0.5 mmol), 5 (1 mmol), Na2SO4 (0.25 mmol),
Reaction conditions: 6 (0.5 mmol), 5 (1 mmol), Na2SO4 (0.25 mmol),
CH3CN (3 mL), 80 ꢀC, 12 h, followed by 8, 40 ꢀC, 4 h (0.5 mmol). CH3CN (3 mL), 80 ꢀC, 12 h, followed by 10 (0.5 mmol), 80 ꢀC, 5 h.
b
c
d
b
c
d
Isolated yields. Purity determined by HPLC. Isolated yields of 9b
Isolated yields. Purity determined by HPLC. Isolated yields of 11b
and 11d when a-tosyloxycarbonyls were used in acetonitrile.
and 9d when a-tosyloxycarbonyls were used in acetonitrile.
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reaction with 2-aminopyridine did not gave desired imidazo-
Synthesis of ionic liquid-supported hypervalent iodine (5)
[1,2-a]pyridines at 40 ꢀC. Heating the reaction mixture at
Ionic liquid supported-sulfonic acid (5 mmol) and IBD (5 mmol)
were taken in different conical asks and were dissolved in
minimum amount of CH3CN under heating conditions. The
homogeneous mixture of ionic liquid-supported sulfonic acid
was added to the clear solution of IBD under hot conditions.
The resulting reaction mixture was kept aside at room temper-
ature for one week. Aer completion of the reaction CH3CN was
evaporated and the reaction mixture was puried by washings
with dry DCM (3 ꢁ 30 mL) to get yellow thick liquid (7.55 g,
96%).
ꢀ
elevated temperature (80 C) was fruitful and the desired imi-
dazo[1,2-a]pyridine 11a was obtained in 84% yield. Under the
optimized reaction conditions, various acetophenones were
found to be suitable substrates to provide the desired imidazo-
[1,2-a]pyridines (Table 2). The results demonstrated that both
electron donating and electron withdrawing groups on the aryl
group of acetophenones were well tolerated to give corre-
sponding imidazo[1,2-a]pyridines in moderate to good yields.
Moreover, heteroaryl substituted imidazo[1,2-a]pyridines (Table
2, 11g) can also be synthesized using this method.
5. 1H NMR (300 MHz, DMSO-d6, CD3OD) d 8.22 (s, 1H), 7.76
(d, J ¼ 1.1 Hz, 1H), 7.73 (d, J ¼ 1.1 Hz, 1H), 7.62 (d, J ¼ 2.1 Hz,
1H), 7.58 (d, J ¼ 2.0 Hz, 1H), 7.44–7.37 (m, 1H), 7.23–7.15 (m,
2H), 4.14 (t, J ¼ 7.3 Hz, 2H), 3.76 (s, 3H), 2.64 (d, J ¼ 7.5 Hz, 2H),
2.59 (s, 3H), 1.91–1.78 (m, 2H), 1.71–1.58 (m, 2H); 13C NMR (75
MHz, DMSO-d6) d 144.6, 137.5, 130.9, 128.0, 123.1, 122.6, 121.2,
121.0 (q, JC–F ¼ 320.25 Hz, OTf), 94.9, 50.7, 34.8, 28.4, 21.9, 9.2;
HRMS (ESI-TOF) calcd for C15H22IN2O4S+ 453.0339 found
453.0356 [M ꢂ CF3SO3]+.
Conclusions
In summary, a new approach have been developed for the
synthesis of 2-aminothiazoles and imidazo[1,2-a]pyridines by
the combination of ionic liquid phase synthesis and ‘catch-and-
release’ strategy. The method developed for the synthesis of aza-
heterocycles using ionic liquid-supported hypervalent iodine
reagent provided good to excellent yield of aza-heterocycles and
allows easy monitoring of the reaction progress. This combi- Procedure for the synthesis of ionic liquid-supported
natorial approach could be a good alternative for the synthesis sulfonate (7a)
of 2-aminothiazoles and imidazo[1,2-a]pyridines and can also
be extended to other heterocyclic compounds.
Acetophenone (6a, 0.5 mmol) and dry Na2SO4 (0.25 mmol) were
added to the solution of 5 (1 mmol) in CH3CN (5 mL) and the
resulting reaction mixture was heated at reux until 6a was
completely captured in the form of ionic liquid-supported
sulfonates (as indicated by thin layer chromatography). The
Experimental section
reaction mixture was ltered to remove Na2SO4 and CH3CN was
evaporated under reduced pressure. The resulting crude
compound was puried by silica-gel column chromatography
(dichloromethane–methanol 3 : 1 as eluent) to give the desired
compound 7a.
General information
The NMR spectra were recorded on 300 MHz, 400 MHz and 500
MHz spectrometers using CDCl3, DMSO-d6 and CD3OD as
solvents. The chemical shis were expressed in ppm. Reactions
were monitored by thin-layer chromatography (TLC) carried out
on silica-coated aluminium plates (60F-254) using UV light as
visualizing agent. High resolution mass spectra (HRMS) were
recorded on a mass spectrometer using electrospray ionization-
time of ight (ESI-TOF). All the chemicals and reagents were
purchased at the highest commercial quality and used without
further purication, unless otherwise stated.
7a. Yield 50%; yellow liquid; 1H NMR (300 MHz, DMSO-d6) d
8.01–7.97 (m, 1H), 7.92 (d, J ¼ 7.9 Hz, 1H), 7.80 (dd, J ¼ 8.0, 1.1
Hz, 1H), 7.67–7.62 (m, 3H), 5.74 (s, 2H), 4.19 (t, J ¼ 6.9 Hz, 2H),
3.76 (s, 3H), 3.59–3.52 (m, 2H), 2.60 (s, 3H), 1.94–1.76 (m, 4H);
13C NMR (75 MHz, DMSO-d6) d 189.2, 142.8, 142.6133.7, 132.2,
129.3, 126.0, 124.9, 120.7, 119.2, 119.0 (q, JC–F ¼ 320.25 Hz, OTf),
69.6, 47.2, 45.1, 33.0, 25.8, 18.3, 7.5; HRMS (ESI-TOF) calcd for
C
17H22ClN2O4S+ 385.0983 found 385.1015 [M ꢂ CF3SO3]+.
Synthesis of ionic liquid-supported sulfonic acid (3)
General procedure for synthesis of 2-aminothiazoles (9a–g)
1,4-Butanesultone (6.0 g, 44.0 mmol) was added drop-wise to
1,2-dimethylimidazole (4.24 g, 44.0 mmol) at 30 ꢀC and the Substituted acetophenone derivative (6) (0.5 mmol), Na2SO4
resulting solution was then heated at 60 ꢀC for 2 h and then (0.25 mmol) and 5 (1 mmol) were added to the round bottom
cooled to room temperature to give a white solid. The solid was ask containing CH3CN (5 mL) and the resulting reaction
washed with toluene (3 ꢁ 15 mL) followed by diethyl ether (2 ꢁ mixture was heated at 40 ꢀC until the acetophenone is
10 mL) to remove unreacted starting materials. Tri- completely consumed (TLC). Aer completion of the reaction,
uoromethanesulfonic acid (47.0 mmol) was added drop-wise the reaction mixture was cooled and Na2SO4 was separated by
to the zwitter ion at 0 ꢀC. The reaction mixture was warmed ltration and the CH3CN was evaporated under reduced pres-
slowly and stirred at 60 ꢀC for 1 h and a thick liquid was sure. The residue was washed with ether (3 ꢁ 10 mL) and ionic
obtained. The thick liquid was washed with toluene (3 ꢁ 15 mL) liquid-supported sulfonates (7) obtained was treated with
to remove excess of triic acid. The residue was dried under thiourea (0.5 mmol) under vigorous stirring at room tempera-
reduced pressure to give a pale yellow thick liquid of ionic ture under solvent free conditions. Progress of the reaction was
liquid-supported sulfonic acid (3) in 98% yield.
monitored by TLC. Aer completion of the reaction, the product
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was extracted with hexane–ethyl acetate mixture (3 ꢁ 10 mL, layers were dried with anhydrous sodium sulfate, and evapo-
2 : 8 v/v). The combined organic layers were washed with water, rated under reduced pressure to give the desired products in
dried with anhydrous sodium sulfate, and evaporated under pure form without chromatographic purication.
reduced pressure to give the pure 2-aminothiazoles (9) without
chromatographic purication.
4-(3-Chlorophenyl)H-imidazo[1,2-a]pyridine (11a). Yield
84%; yellow solid; mp 105–107 ꢀC; 1H NMR (300 MHz, CDCl3) d
4-(3-Chlorophenyl)-1,3-thiazol-2-amine (9a). Yield 84%; off 8.11 (d, J ¼ 4.7 Hz, 1H), 7.96 (s, 1H), 7.84 (s, 2H), 7.63 (d, J ¼ 6.4
white solid; mp 132–133 ꢀC; 1H NMR (300 MHz, CDCl3) d 7.77 (s, Hz, 1H), 7.42–7.23 (m, 2H), 7.19 (d, J ¼ 5.6 Hz, 1H), 6.79 (s, 1H);
1H), 7.64 (d, J ¼ 7.2 Hz, 2H), 7.36–7.19 (m, 2H), 6.74 (s, 1H), 5.18 13C NMR (75 MHz, CDCl3) d 145.7, 144.4, 135.6, 134.7, 130.0,
(s, 2H); 13C NMR (75 MHz, CDCl3) d 167.4, 149.9, 136.4, 134.9, 127.9, 126.1, 125.7, 125.0, 124.1, 117.6, 112.7, 108.5.
129.83, 127.7, 126.2, 124.0, 103.9.
4-(4-Chlorophenyl)H-imidazo[1,2-a]pyridine (11b). Yield
1
4-(4-Chlorophenyl)-1,3-thiazol-2-amine (9b). Yield 83%; 83%; yellow solid; mp 199–201 C (lit.14 201–202 C); H NMR
colorless solid; mp 163–165 ꢀC (lit.10a 163–164 ꢀC); 1H NMR (300 (300 MHz, CDCl3) d 8.00 (d, J ¼ 6.8 Hz, 1H), 7.79 (d, J ¼ 8.5 Hz,
MHz, CDCl3) d 7.71 (s, 2H), 7.36 (d, J ¼ 6.8 Hz, 2H), 6.73 (s, 1H), 2H), 7.72 (s, 1H), 7.53 (d, J ¼ 9.1 Hz, 1H), 7.31 (d, J ¼ 8.5 Hz, 2H),
5.10 (s, 2H); 13C NMR (101 MHz, CDCl3) d 167.33, 135.42, 7.09 (dd, J ¼ 11.4, 4.4 Hz, 1H), 6.69 (t, J ¼ 6.7 Hz, 1H); 13C NMR
ꢀ
ꢀ
133.52, 133.19, 128.80, 127.34, 103.29.
(75 MHz, CDCl3) d 144.7, 143.6, 132.6, 131.3, 127.9, 126.2, 124.6,
4-(4-Bromophenyl)-1,3-thiazol-2-amine (9c). Yield 80%; 123.9, 116.50, 111.6, 107.2.
1
ꢀ
yellow solid; mp 178–180 C; H NMR (300 MHz, DMSO-d6) d
4-(4-Bromophenyl)H-imidazo[1,2-a]pyridine (11c). Yield
1
7.75 (d, J ¼ 8.0 Hz, 2H), 7.55 (d, J ¼ 8.2 Hz, 2H), 7.10 (s, 2H), 7.08 80%; yellow solid; mp 196–198 C (lit.9a 201–203 C); H NMR
ꢀ
ꢀ
(s, 1H); 13C NMR (75 MHz, DMSO-d6) d 168.8, 149.1, 134.5, (300 MHz, CDCl3) d 8.10 (s, 1H), 7.83 (s, 3H), 7.59 (d, J ¼ 16.6 Hz,
131.8, 128.0, 120.5, 102.8.
3H), 7.19 (s, 1H), 6.79 (s, 1H); 13C NMR (75 MHz, CDCl3) d 145.7,
4-(4-Methylphenyl)-1,3-thiazol-2-amine (9d). Yield 71%; off 144.6, 132.7, 131.8, 127.6, 125.6, 125.1, 121.9, 117.5, 112.7,
1
white solid; mp 130–131 ꢀC (lit.10a 125–126 ꢀC); H NMR (300 108.3.
MHz, CDCl3) d 7.65 (d, J ¼ 6.4 Hz, 2H), 7.18 (d, J ¼ 6.1 Hz, 2H),
6.65 (s, 1H), 5.26 (s, 2H), 2.35 (s, 3H); 13C NMR (75 MHz, CDCl3) 71%; off white solid; mp 142–144 ꢀC (lit.15 144–145 ꢀC); 1H NMR
d 167.4, 151.4, 137.5, 132.0, 129.3, 125.9, 102.0, 21.2.
4-(4-Methylphenyl)H-imidazo[1,2-a]pyridine (11d). Yield
(300 MHz, CDCl3) d 8.06 (d, J ¼ 6.0 Hz, 1H), 7.84 (d, J ¼ 7.5 Hz,
4-(4-Methoxyphenyl)-1,3-thiazol-2-amine (9e). Yield 71%; off 2H), 7.79 (s, 1H), 7.61 (d, J ¼ 8.7 Hz, 1H), 7.24 (d, J ¼ 7.5 Hz, 2H),
white solid; mp 200–203 ꢀC (lit.13 204–207 ꢀC); 1H NMR (300 7.18–7.06 (m, 1H), 6.79–6.67 (m, 1H), 2.38 (s, 3H); 13C NMR (75
MHz, CDCl3) d 7.70 (d, J ¼ 7.5 Hz, 2H), 6.91 (d, J ¼ 7.5 Hz, 2H), MHz, CDCl3) d 145.9, 145.6, 137.8, 130.9, 129.4, 126, 125.5,
6.58 (s, 1H), 3.83 (s, 3H); 13C NMR (75 MHz, CDCl3) d 168.4, 124.5, 117.4, 112.3, 107.7, 21.3.
159.3, 150.4, 127.4, 127.2, 113.9, 100.5, 55.2.
4-(4-Methoxyphenyl)H-imidazo[1,2-a]pyridine (11e). Yield
4-(Naphthalen-6-yl)thiazol-2-amine (9f). Yield 81%; solid; 58%; colorless solid; mp 142–144 ꢀC (lit.15 137–138 ꢀC); 1H NMR
mp 152–154 ꢀC (lit.13 152–153 ꢀC); 1H NMR (500 MHz, DMSO-d6) (500 MHz, CDCl3) d 8.08 (d, J ¼ 6.7 Hz, 1H), 7.89 (d, J ¼ 8.8 Hz,
d 8.30 (s, 1H), 7.89 (dd, J ¼ 37.4, 4.3 Hz, 4H), 7.47 (s, 2H), 7.15 (s, 2H), 7.76 (s, 1H), 7.60 (d, J ¼ 9.1 Hz, 1H), 7.14 (ddd, J ¼ 9.0, 6.8,
1H), 7.09 (s, 2H); 13C NMR (126 MHz, DMSO-d6) d 168.7, 150.2, 1.1 Hz, 1H), 6.97 (d, J ¼ 8.8 Hz, 2H), 6.74 (t, J ¼ 6.7 Hz, 1H), 3.85
133.6, 132.8, 132.7, 128.5, 128.3, 128.0, 126.8, 126.2, 124.5, (s, 3H); 13C NMR (126 MHz, CDCl3) d 159.6, 145.7, 145.6, 127.3,
124.4, 102.8.
126.5, 125.4, 124.4, 117.3, 114.3, 112.2, 107.2, 55.3.
4-Thiophen-2-yl-thiazol-2-ylamine (9g). Yield 77%; off white
2-(Naphthalen-1-yl)imidazo[1,2-a]pyridine (11f). Yield 63%;
1
solid; mp 135–136 ꢀC; 1H NMR (300 MHz, DMSO-d6) d 7.42–7.36 colorless liquid; H NMR (300 MHz, CDCl3) d 8.52 (s, 1H), 8.11
(m, 2H), 7.14 (s, 2H), 7.04 (dd, J ¼ 5.0, 3.7 Hz, 1H), 6.84 (s, 1H); (d, J ¼ 6.0 Hz, 1H), 8.06–7.78 (m, 5H), 7.67 (d, J ¼ 8.6 Hz, 1H),
13C NMR (75 MHz, DMSO-d6) d 168.7, 144.9, 139.7, 128.2, 125.1, 7.47 (s, 2H), 7.20 (dd, J ¼ 19.1, 12.1 Hz, 1H), 6.77 (s, 1H); 13C
123.2, 100.2.
NMR (75 MHz, CDCl3) d 145.8, 145.8, 133.8, 133.2, 131.1, 128.4,
128.3, 127.7, 126.3, 126.0, 125.6, 124.8, 124.8, 124.2, 117.6,
112.5, 108.6.
General procedure for synthesis of imidazo[1,2-a]pyridine
(11a–g)
2-(Thiophen-2-yl)H-imidazo[1,2-a]pyridine (11g). Yield 66%;
1
ꢀ
ꢀ
off white solid; mp 134–137 C (lit. 137–139 C); H NMR (500
To a stirred solution of substituted acetophenone derivative (6, MHz, CDCl3) d 8.03 (d, J ¼ 6.7 Hz, 1H), 7.73 (s, 1H), 7.59 (d, J ¼
0.5 mmol) and Na2SO4 (0.25 mmol) in CH3CN (3 mL), 5 (1 9.1 Hz, 1H), 7.49–7.42 (m, 1H), 7.29 (dd, J ¼ 4.9, 0.9 Hz, 1H),
mmol) was added and the resulting reaction mixture was heated 7.16–7.10 (m, 1H), 7.08 (dd, J ¼ 4.9, 3.6 Hz, 1H), 6.74 (dd, J ¼ 9.7,
at 80 ꢀC until the acetophenone is completely consumed. Aer 3.7 Hz, 1H); 13C NMR (126 MHz, CDCl3) d 145.4, 140.8, 137.5,
completion of the reaction (as indicated by TLC), reaction 127.7, 125.4, 125.0, 124.8, 123.7, 117.3, 112.5, 107.4.
mixture was ltered and the CH3CN was evaporated under
reduced pressure. The resulting residue was washed with ether
Acknowledgements
(3 ꢁ 10 mL) and subsequently treated with 2-aminopyridine (0.5
mmol) and stirred vigorously at 80 ꢀC temperature under We thank the Council of Scientic and Industrial Research
solvent free conditions. Aer completion of the reaction, the (CSIR), New Delhi for research funding grant no. 02(0115)/13/
product was extracted with hexane–ethyl acetate mixture (3 ꢁ EMR-II. SC and MMK thank CSIR for providing research
10 mL, 2 : 8 v/v) and washed with water. The combined organic fellowship.
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47372 | RSC Adv., 2014, 4, 47368–47372
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