Facile synthesis of trisubstituted imidazoles from 1,2-di(furan-2-yl)-2- oxoethyl carboxylates and their chemiluminescence

Article abstract of DOI:10.1016/j.crci.2012.06.005

A facile synthesis of trisubstituted imidazoles containing furan rings was reported. Imidazoles were produced from 1,2-di(furan-2-yl)-2-oxoethyl carboxylates over solid alumina as solid support impregnated with ammonium acetate under solvent-free microwave-assisted conditions. The method possessed many remarkable advantages, such as the short reaction time (5-10 min), affording moderate to excellent yields and saving resources, conveniently operating process, which provided an attractive and environmentally-friendly approach for the synthesis of the important heterocyclic compounds. Moreover, the chemiluminescence property of some compounds synthesized has been investigated.

Full text of DOI:10.1016/j.crci.2012.06.005

C. R. Chimie 15 (2012) 784–792
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Full paper/Memoire
Facile synthesis of trisubstituted imidazoles from 1,2-di(furan-2-yl)-2-
oxoethyl carboxylates and their chemiluminescence
*
Baozhi Li, Qiang Gu, Yuanhui He, Tianqi Zhao, Shuaijun Wang, Jing Kang, Yumin Zhang
College of Chemistry, Jilin University, Changchun 130012, PR China
A B S T R A C T
A R T I C L E I N F O
Article history:
A facile synthesis of trisubstituted imidazoles containing furan rings was reported.
Imidazoles were produced from 1,2-di(furan-2-yl)-2-oxoethyl carboxylates over solid
alumina as solid support impregnated with ammonium acetate under solvent-free
microwave-assisted conditions. The method possessed many remarkable advantages,
such as the short reaction time (5–10 min), affording moderate to excellent yields and
saving resources, conveniently operating process, which provided an attractive and
environmentally-friendly approach for the synthesis of the important heterocyclic
compounds. Moreover, the chemiluminescence property of some compounds synthesized
has been investigated.
Received 28 April 2012
Accepted after revision 13 June 2012
Available online 4 August 2012
Keywords:
Trisubstituted imidazoles
Microwave-assisted synthesis
1,2-di(furan-2-yl)-2-oxoethyl carboxylates
Solid support
´
ß 2012 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Solvent-free
Chemiluminescence
1. Introduction
methods reported above suffer from one or more
disadvantages such as complex operation process, high
Imidazole and its derivatives as a major kind of
heterocyclic compounds play an important role in
biochemistry [1–5], material chemistry including lumi-
nescent material [6,7] and proton conductivity material
[8,9], medicinal chemistry [10–14] and the determination
of heavy metal ion [15] and albumin in human serum
samples [16] due to their structure nature. Therefore,
effective methods for preparation of imidazole deriva-
tives are of great interest in organic synthesis. The
preparation for imidazole derivatives were usually based
on the condensation of alkyl (aryl)-diones or 2-hydroxy-
solvent consumption and longer reaction time. Moreover,
alkyl- or aryl-diones and aldehydes, benzoin and alde-
hydes were usually used as starting materials in these
methods. Few methods were applied to the synthesis of
furly-substituted imidazoles. Because the furan ring
possess the inherent chemical properties and disadvan-
tages, such as rich electron, lower conjugation energy,
easily ring-opening in Bro¨nsted acid, easily becoming
yellow in oxygen and so on. Therefore, it is very
significant to study and develop new scaleable synthetic
routes able to construct fused imidazole derivatives in
high yields. Especially imidazoles with furan rings which
may extend the application of imidazole derivatives. For
this purpose, microwave heating was introduced into the
synthesis by allowing us to obtain rapid, reproducible,
and scalable processes to synthesize new molecules in
high yield. This methodology can facilitate the cycliza-
tion, and is well-suited for synthesizing the compounds
with heterocyclic rings. In fact, traditional heating
reactions often require high temperature for many hours
or even days in the present of organic solvent, whereas
similar or higher yields and cleaner process can be
1,2-diphenylethanone with aldehydes, or
b-carbonyl-N-
acyl-N-alkylamines in the present of ammonium acetate,
ammonia or primary amines in different solvent by
various chemical methods like refluxing [17–20], solid-
phase synthesis [21], heating in ionic liquid [22], sodium
dihydrogen phosphate acted as catalyst [23], MW/silica-
gel [24], MW/Al2O3 [25], etc. However, many of the
* Corresponding author.
E-mail address: zhang_ym@jlu.edu.cn (Y. Zhang).
1631-0748/$ – see front matter ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2012.06.005

B. Li et al. / C. R. Chimie 15 (2012) 784–792
785
Scheme 1. The pathway of trisubstituted imidazoles containing furan rings.
obtained by microwave heating for a few minutes [13,24–
2.1. Experimental procedures for compounds (2a–2k)
28]. Our work focused on the synthesis of 2-substituted-
4,5-di(2-furyl)imidazoles from 1,2-di(furan-2-yl)-2-
oxoethyl carboxylates. It is known that the use of alumina
or silica-gel in a solvent-free fashion greatly eases work-
up procedures. To the best of our knowledge, the
microwave-assisted and starting from 1,2-di(furan-2-
yl)-2-oxoethyl carboxylates version of this reaction has
not been reported, although several papers describing
other microwave-assisted syntheses of imidazoles with
benzene rings [24,25] and other synthesis of few furly-
substituted imidazoles by heating in ionic liquid [22]
have been published.
1,2-di(furan-2-yl)-2-oxoethyl carboxylates were syn-
thesized according to the literature [30]. Furoin (5 mmol,
0.96 g) and acyl chlorides (5.5 mmol) were mixed in the
three-neck flask. The mixture was heated to 30À40 8C in
water bath with stirring for 15 min. Pyridine (3 mL) was
slowly dropped into the mixture and stirred at the above
temperature until the reaction was over by TLC analysis.
Then the mixture was cooled, filtered and the residue was
washed with iced ethanol (3 Â 5 mL), water (3 Â 10 mL),
and recrystallized from 95% ethanol to give the pure
product.
Herein, we wish to report a facile and environmentally-
friendly method for the synthesis of trisubstituted imida-
zoles containing furan rings from 1,2-di(furan-2-yl)-2-
2.2. Experimental procedures for the synthesized compounds
(3a–3k) under solventÀfree condition
oxoethyl carboxylates and using alumina as
a safe,
inexpensive solid support under solvent-free and micro-
wave-assisted conditions (Scheme 1). In addition, when the
method was used to synthesize trisubstituted imidazoles
containing benzene rings, the desired products were also
obtained. However, the yields were appreciably lower than
that of trisubstituted imidazoles containing furan rings.
Typical procedure for the synthesis of trisubstituted
imidazoles as follows:
a mixture of alumina (0.8 g,
7.84 mmol) or silica-gel (0.5 g, 8.32 mol) ammonium
acetate (0.23 g, 3 mmol) and 1,2-di(furan-2-yl)-2-oxoethyl
carboxylates (1 mmol) was fully ground in a mortar, and
then transferred to
a 50 mL dried two-neck round-
bottomed flask containing a thermometer and condenser,
and heated with microwave irradiation for 5 min (the
reaction temperature was 130 8C when the reaction was
over.) or conventional heating at 130 8C for 40–90 min. The
procedure was repeated twice. The reaction progress was
monitored by TLC on Silufol-254 plates. When the
microwave-assisted reaction was over, the residue was
cooled to room temperature and was directly purified by
column chromatography on Chemapol (200–300 mesh)
silica gel (eluent, petroleum ether/ethyl acetate = 3/1) to
give the desired products.
2. Experimental
Furoin (1,2-di(furan-2-yl)-2-hydroxyethanone) was
generatedfromfurfuralaccording to the reportedprocedure
[29]. All reagents were of analytical-reagent grade and used
without further purification. All reported yields were
isolated yields. All melting points were determined on a
XT À 4 melting point apparatus and were uncorrected. 1H
and 13C NMR spectra were measured using a Varian
Mercury-300 NMR spectrometer or a Bruker AVANCE-500
NMR spectrometer and with TMS as an internal standard.
MS and HRMS were collected with an Agilent HP1100/6890
LC/MS spectrometer and an Agilent1290-micrOTOF Q II
spectrometer, respectively. Elemental analyses were deter-
mined with a FlashEA1112 elemental analyzer. FT-IR
spectra were obtained as KBr pellets using an IRAffinity-1
instrument in the range of 500–3500 cmÀ1. A MCL-3-type
microwave reactor with a thermometer was used in all
experiments (Microwave chemical lab, College of Electron-
ics and information Engineering, Sichuan University Sich-
uan, China). The CL emission was detected by an ultra-weak
luminescence analyzer (type BPCL manufactured at the
Institute of Biophysics, Chinese Academy of Sciences,
Beijing, China). The acquisition and treatment of data were
performed with BPCL software running under Windows XP.
2.3. Physical and spectroscopic data
4,5-di(furan-2-yl)-2-phenyl-1H-imidazole (3a) Mp:
197–198 8C (lit. [21] 218 8C). Yield: 74.5%. IR (KBr):
(cmÀ1) 3118, 3054, 1599, 1551, 1481, 1404, 1233, 1090,
886, 732, 590. 1H NMR (300 MHz, CDCl3):
(ppm): 7.92
n
d
(dd, J = 8.2, 1.5 Hz, 2H), 7.57–7.33 (m, 5H), 6.99 (d,
J = 3.3 Hz, 2H), 6.53 (dd, J = 3.4, 1.8 Hz, 2H). 13C NMR
(125 MHz, CDCl3): d (ppm) 146.74, 129.64, 129.52, 129.23,
125.96, 112.13, 108.00. MS, m/z: (M + H)+ 277.9, (M)+ 276.9
(Calcd 276.29). Anal. calcd for C17H12N2O2: C, 73.90; H,
4.38; N, 10.14. Found: C, 73.62; H, 4.34; N, 9.95.
4,5-di(furan-2-yl)-2-(4-methylphenyl)-1H-imidazole
(3b) Mp: 217–219 8C. Yield: 75.5%. IR (KBr): n
(cmÀ1) 3125,

786
B. Li et al. / C. R. Chimie 15 (2012) 784–792
3017, 2917, 2853, 1599, 1530, 1493, 1433, 1374, 1262,
1200, 1021, 912, 823, 732, 590. 1H NMR (300 MHz, CDCl3):
for C17H11N3O4: C, 63.55; H, 3.45; N, 13.08. Found: C,
63.25; H, 3.52; N, 12.98.
d
(ppm) 7.79 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 1.2 Hz, 2H),
7.19(s, 2H), 6.97 (d, J = 3.2 Hz, 2H), 6.64–6.35 (m, 2H),
2.34(s, 3H). 13C NMR (125 MHz, CDCl3):
(ppm) 146.74,
3-(4,5-di(furan-2-yl)-1H-imidazol-2-yl)pyridine (3h)
Mp: 244–246 8C. Yield: 82.5%. IR (KBr):
3150, 3106, 3045, 1600, 1545, 1523, 1474, 1450, 1373,
1264, 1210, 1091, 1010, 962, 909, 884, 731, 594. 1H NMR
n
(cmÀ1) 3440,
d
139.70, 129.98, 126.84, 125.80, 112.16, 107.89, 21.77. MS,
m/z: (M + H)+ 291.2 (Calcd 291.31). Anal. calcd for
(300 MHz, DMSO):
d (ppm) 9.27 (s, 1H), 8.61 (d, J = 3.5 Hz,
C
18H14N2O2: C, 74.47; H, 4.86; N, 9.65. Found: C, 74.52;
1H), 8.47–8.42 (m, 1H), 7.80 (d, J = 1.1 Hz, 2H), 7.55 (dd,
J = 8.1, 4.9 Hz, 1H), 6.89 (d, J = 3.0 Hz, 2H), 6.64 (dd, J = 3.3,
H, 4.76; N, 9.95.
4,5-di(furan-2-yl)-2-(4-chlorophenyl)-1H-imidazole
1.8 Hz, 2H). 13C NMR (125 MHz, DMSO):
d (ppm): 149.82,
(3c) Mp: 216–218 8C. Yield: 81.6%. IR (KBr):
3052, 1598, 1525, 1483, 1432, 1374, 1260, 1201, 1011, 835,
736, 590. 1H NMR (300 MHz, CDCl3):
(ppm): 7.87 (d,
J = 8.6 Hz, 2H), 7.51 (d, J = 1.7 Hz, 2H), 7.42 (d, J = 8.6 Hz,
2H), 7.01 (d, J = 3.2 Hz, 2H), 6.54 (dd, J = 3.4, 1.8 Hz, 2H). 13
NMR (125 MHz, DMSO): (ppm) 145.44, 141.99, 135.56,
n
(cmÀ1) 3115,
147.17, 144.41, 143.32, 134.14, 126.65, 124.83, 112.57,
108.86. MS, m/z: (M + H)+ 278.8 (Calcd 278.29). Anal. calcd
for C16H11N3O2: C, 69.31; H, 4.00; N, 15.15. Found: C,
69.05; H, 4.12; N, 15.30.
4,5-di (furan-2-yl)-2-undecyl-1H-imidazole (3i) Mp:
80–82 8C. Yield: 56.0%. IR (KBr): n
(cmÀ1) 3423, 3120, 3024,
d
C
d
129.53, 127.97, 127.15, 112.22, 108.25. MS, m/z:
(M + 2 + H)+ 313.8, (M + 2)+ 312.8, (M + H)+ 311.8, (M)+
310.8 (Calcd 310.7). Anal. calcd for C17H11ClN2O2: C, 65.71;
H, 3.57; N, 9.02. Found: C, 65.46; H, 3.65; N, 8.83.
4,5-di(furan-2-yl)-2-(2-furylvinyl)-1H-imidazole
2920, 2850, 1600, 1550, 1512, 1470, 1415, 1380, 1270,
1210, 1194, 1160, 1080, 1020, 912, 883, 806, 733, 660, 593.
1H NMR (300 MHz, DMSO):
d
(ppm) 12.30 (s, 1H), 7.72 (s,
2H), 6.74 (s, 2H), 6.58 (s, 2H), 2.63 (s, 2H), 1.67 (s, 2H), 1.24
(s, 16H), 0.85 (s, 3H). 13C NMR (125 MHz, DMSO):
(ppm)
d
(3d) Mp: 213–215 8C. Yield: 89.7%. IR (KBr):
3027, 1625, 1482, 1425, 1370, 1255, 1201, 1021, 885, 733,
589. 1H NMR (300 MHz, CDCl3):
(ppm) 7.46 (d, J = 1.7 Hz,
n
(cmÀ1) 3121,
150.11, 142.52, 132.58, 129.53, 112.39, 107.33, 32.16,
30.88, 29.87, 29.79, 29.57, 29.47, 28.81, 28.46, 19.52, 14.81.
MS, m/z: (M + H)+ 355.1. (Calcd 354.49). Anal. calcd for
d
2H), 7.37–7.29 (m, 2H), 7.00 (d, J = 3.4 Hz, 2H), 6.83 (d,
J = 16.2 Hz, 1H), 6.49 (dd, J = 3.4, 1.8 Hz, 2H), 6.40–6.34 (m,
C22H30N2O2: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.26; H,
8.48; N, 7.70.
2H).13C NMR (125 MHz, CDCl3):
d
(ppm) 152.38, 147.03,
2,4,5-tri (furan-2-yl)-1H-imidazole (3j) Mp: 196–
145.58, 143.54, 142.00, 120.98, 113.11, 112.34, 112.19,
111.49, 108.31. MS, m/z: (M)+ 292.9, (M + H)+ 293.9 (Calcd
293.30). Anal. calcd for C17H12N2O3: C, 69.86; H, 4.14; N,
9.58. Found: C, 69.68; H, 4.29; N, 9.30.
197 8C. Yield: 73.3%. IR (KBr):
1400, 1200, 1420, 1540, 885, 733, 590. 1H NMR
(500 MHz, CDCl3): (ppm) 10.48 (s, 1H),7.42 (s, 2H),
n
(cmÀ1) 3110, 3420,
d
7.36 (s, 1H, furan-5H), 6.92 (d, J = 3.3 Hz, 3H), 6.46 (dd,
J = 3.0, 1.7 Hz, 2H), 6.41 (dd, J = 3.1, 1.6 Hz, 1H). 13C NMR
4,5-di(furan-2-yl)-2-(1-chloro-2,2-dimethylethyl)-
1H-imidazole (3e) Mp: 186–187 8C. Yield: 48.9%. IR (KBr):
(125.5 MHz, CDCl3)
d (ppm) 147.2, 145.2, 143.1, 141.9,
n
(cmÀ1) 3444, 3130, 3026, 2983, 2940, 2815, 1602, 1544,
139.5, 112.4, 112.1, 108.9, 108.1. MS, m/z: (M + H)+
267.3, (M)+ 266.9, (Calcd 266.25). Anal. calcd for
1517, 1473, 1410, 1367, 1215, 1190, 1074, 1011, 976, 885,
812, 738, 593. 1H NMR (300 MHz, CDCl3):
(ppm) 7.48 (s,
2H), 6.88 (s, 2H), 6.50 (dd, J = 3.4, 1.8 Hz, 2H), 3.81 (s, 2H),
1.56 (s, 6H). 13C NMR (125 MHz, DMSO):
(ppm) 152.23,
d
C15H10N2O3: C, 67.67; H, 3.79; N, 10.52. Found: C, 67.57;
H, 3.73; N, 10.46.
4,5-di(furan-2-yl)-2-styryl-1H-imidazole (3k) Mp:
209–211 8C. Yield: 90.3%. IR (KBr): n
(cmÀ1) 3420, 3110,
2970, 2920, 1626, 1540, 1501, 1430, 1372, 1260, 1200,
1160, 1070, 1020, 987, 962, 912, 883, 806, 733, 685, 590. 1H
d
141.73, 112.29, 111.77, 107.60, 54.85, 38.51, 25.45. MS, m/
z: (M + H)+ 291.8 (M)+ 290.8 (Calcd 290.74); Anal. calcd for
C15H15ClN2O2: C, 61.97; H, 5.20; N, 9.64. Found: C, 61.77;
H, 5.18; N, 9.66.
NMR (500 MHz, DMSO): d (ppm) 12.75 (s, 1H), 7.78 (d,
4,5-di(furan-2-yl)-2-methyl-1H-imidazole (3f) Mp:
164–166 8C. Yield: 60.4%. IR (KBr):
3000, 2902, 2786, 1610, 1560, 1430, 1272, 1216, 1159,
1091, 1022, 927, 886, 912, 813, 724, 594. 1H NMR
J = 48.9 Hz, 2H), 7.59 (d, J = 7.5 Hz, 2H), 7.52 (d, J = 16.5 Hz,
1H), 7.41 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.06 (d,
J = 16.5 Hz, 1H), 6.97 (s, 1H), 6.66 (dd, J = 44.5, 31.3 Hz, 3H).
n
(cmÀ1) 3415, 3131,
13C NMR (125 MHz, DMSO):
d (ppm): 146.66, 137.09,
(300 MHz, CDCl3):
(d, J = 3.3 Hz, 2H), 6.50 (dd, J = 3.3, 1.8 Hz, 2H), 2.47 (s, 3H).
13C NMR (125 MHz, DMSO):
(ppm) 147.73, 145.36,
141.55, 123.55, 111.99, 107.20, 14.19. MS, m/z: (M)+ 214.8
(Calcd 214.22). Anal. calcd for C12H10N2O2: C, 67.28; H,
4.71; N, 13.08. Found: C, 67.43; H, 4.65; N,13.10.
d
(ppm) 7.45 (d, J = 1.1 Hz, 2H), 6.90
129.78, 127.45, 117.37, 112.86, 112.32, 108.86, 107.61. MS,
m/z: (M + H)+ 303.0 (Calcd 303.34). Anal. calcd for
C19H14N2O2: C, 75.58; H, 4.67; N, 9.27. Found: C, 75.82;
d
H, 4.81; N, 9.45.
4,5-di(phenyl)-2-(2-furylvinyl)-1H-imidazole
(3l)
Mp: 194–196 8C. Yield: 83.3%. IR (KBr)
1600, 1580, 1480, 1450, 1320, 1260, 1200, 1070, 1010, 968,
883, 764, 696, 592 cmÀ1. 1H NMR (CDCl3, 500 MHz)
: 7.51
n: 3060, 2960,
4,5-di(furan-2-yl)-2-(4-nitrophenyl)-1H-imidazole
(3g) Mp: 208–210 8C (lit. [21] 208 8C). Yield: 86.2%. IR
d
(KBr):
1201, 1110, 1080, 991, 906, 886, 850, 798, 731, 629. 1H
NMR (300 MHz, CDCl3): (ppm) 8.29 (d, J = 8.9 Hz, 2H),
8.09 (d, J = 8.9 Hz, 2H), 7.53 (d, J = 1.3 Hz, 2H), 7.04 (s, 2H),
6.56 (dd, J = 3.5, 1.8 Hz, 2H). 13C NMR (125 MHz, DMSO):
n
(cmÀ1) 3428, 3095, 3032, 1600, 1510, 1340, 1250,
(d, J = 7.2 Hz, 4H), 7.39 (d, J = 1.1 Hz, 1H), 7.32 (t, J = 7.3 Hz,
4H), 7.28 (d, J = 7.2 Hz, 2H), 7.22 (d, J = 16.1 Hz, 1H), 6.85 (d,
J = 16.1 Hz, 1H), 6.41 (dd, J = 3.2, 1.8 Hz, 1H), 6.38 (d,
d
J = 3.3 Hz, 1H); 13 C NMR (DMSO, 126 MHz)
d: 152.29,
d
145.16, 142.80, 132.50, 129.15, 128.56, 127.84, 127.47,
119.36, 113.69, 111.87, 110.39; HRMS, m/z: (M + H)+
313.1334 (Calcd 313.1335).
(ppm) 147.71, 144.93, 136.31, 127.12, 125.05, 112.63. MS,
m/z: (M + H)+ 322.9, (M)+ 321.8 (Calcd 321.29). Anal. calcd

B. Li et al. / C. R. Chimie 15 (2012) 784–792
787
Table 1
Synthesis of 1,2-di(furan-2-yl)-2-oxoethyl carboxylates from furoin with acyl chlorides catalysed by pyridine.a
Entry
R-COCl
Product
Yieldb (%)
94.1
Mp.(8C)
1
2a
78-79
2
3
2b
2c
91.5
94.3
115-117
96-98
4
5
2d
2e
92.3
85.4
108-110
95-97
6
7
2f
90.9
94.7
72-73
2g
117-118
8
2h
90.5
92-94
9
2i
2j
88.2
90.4
54-55
10
129-130
11
2k
92.6
105-107
a
Reaction condition: 5 mmol Furoin, 5.5 mmol acyl chlorides, 3 mL pyridine at 35 8C.
Isolated yield.
b

788
B. Li et al. / C. R. Chimie 15 (2012) 784–792
Table 2
Optimization of the reaction conditions for the mode of heating and solid support.
Products
Conventional syntheses (%)
Microwave heated syntheses
No solid support (%)
Alumina (%)
Silica-gel (%)
3a
3d
3j
64.8
80.3
63.5
81.1
67.7
82.2
72.4
82.7
74.5
89.7
73.3
90.3
75.2
89.0
73.8
89.4
3k
4,5-di-phenyl-2-styryl-1H-imidazole (3m) Mp: 227–
229 8C. Yield: 77.6%. IR (KBr) : 3030, 2960, 1600, 1500,
1450, 1200, 1070, 1030, 958, 764, 696, 602 cmÀ1. 1H NMR
(DMSO, 500 MHz) : 12.60 (s, 1H), 7.60 (d, J = 7.4 Hz, 2H),
7.48 (d, J = 22.8 Hz, 5H), 7.44–7.18 (m, 9H), 7.10 (d,
J = 16.5 Hz, 1H); 13 C NMR (DMSO, 126 MHz) : 145.71,
or silica-gel with the identical diameter (200–300 mesh)
was more suitable for the synthesis of 3a, 3d, 3j and 3k
from 2a, 2d, 2j and 2k (Table 2). Because the loading of
solid supports is relative to their specific surface area, the
optimum amounts for alumina and silica-gel are around
0.8 g (7.84 mmol) and 0.5 g (8.32 mmol), respectively.
Alternatively, all the other compounds were synthesized
under microwave heating on solid support alumina.
In addition, the effect of microwave irradiation times on
the yields of product was investigated by employing 1,2-
di(furan-2-yl)-2-oxoethyl-4-nitrobenzoate and ammoni-
um acetate on solid support alumina under microwave
radiation in the absence of any organic solvent. It was
observed that the yield of 4,5-di(furan-2-yl)-2-(4-nitro-
phenyl)-1H-imidazole (3h) was substantially increased
under microwave irradiation for 5 min compared with that
at shorter irradiation time (Fig. 1). However, the yield was
not obviously enhanced when reaction time was further
increased to 10 min and 15 min. Consequently, trisubsti-
tuted imidazoles containing furan rings were synthesized
in moderate to excellent yield from 1,2-di(furan-2-yl)-2-
oxoethyl carboxylates and ammonium acetate by the same
method and heated for 5 min in microwave. No reaction
was observed without heating. Furthermore, the yield of
product was reduced when the reaction mixture was
deficiently mixed with solid support.
n
d
d
136.91, 130.45, 129.37, 128.92, 128.48, 128.03, 126.93,
117.68; HRMS, m/z: (M + H)+ 323.1543 (Calcd 323.1543).
3. Results and discussion
3.1. Synthesis of compounds
In our previous work, many subsequent products
correlated with furfural had been synthesized in our
laboratory [29–32]. In the present work, eleven 1,2-
di(furan-2-yl)-2-oxoethyl carboxylates were readily syn-
thesized by the esterification of furoin with 1.1 equivalent
of acyl chlorides and using pyridine as catalyst in excellent
yields (85.4–94.7%) under mild reaction conditions refer-
ring to our reported method [30] (Table 1).
Subsequently, the synthesis of trisubstituted imida-
zoles containing furan ring was explored starting from 1,2-
di(furan-2-yl)-2-oxoethyl carboxylates. Herein, the nucleo-
philic addition and self-cycloaddition reaction of 1,2-
di(furan-2-yl)-2-oxoethyl carboxylates with 3.0 equiva-
lent of ammonium acetate was readily carried out. Under
otherwise similar experimental conditions, the effect of
different heating conditions and solid support on the yield
of the products is shown in Table 2. We successfully used
alumina or silica-gel as solid support to synthesize the
desired product in almost equal yields, and the yield is
higher than that of the product obtained under conven-
tional heating (over 9.0%) and under microwave heating
(6.8–7.6% except product 3j) in the absence of solid
support, respectively. This is because alumina and silica-
gel possess the predominant ability to disperse reactant
and microwave, together with possible catalysis which
sufficiently promoted the reaction. The effect is consonant
with that of solid support in literature [26]. Comparison of
different heating conditions and solid supports
showed that microwave heating on solid support alumina
Fig. 1. The effect of microwave irradiation time on yield.

B. Li et al. / C. R. Chimie 15 (2012) 784–792
789
Table 3
Synthesis of trisubstituted imidazoles containing furan ring from the reaction of 1,2-di(furan-2-yl)-2-oxoethyl carboxylates with ammonia dispersed by
Al2O3 under solvent-free and microwave heating conditions.a
Entry
1
R
Time (min)
5
Product
Yieldb (%)
74.5
3a
2
5
75.5
3b
3
5
81.6
3c
3d
3e
3f
4
5
6
7
8
5
5
89.7
48.9
60.4
86.2
82.5
5
5
3g
10
3h

790
B. Li et al. / C. R. Chimie 15 (2012) 784–792
Table 3 (Continued )
Entry
9
R
Time (min)
5
Product
Yieldb (%)
56.0
3i
3j
10
5
73.3
11
5
90.3
3k
12c
5
83.3
3l
13c
5
77.6
3m
a
Reaction condition: 1,2-di(furan-2-yl)-2-oxoethyl carboxylates (1 mmol), ammonium acetate (3 mmol).
The yield purified by column chromatography.
b
c
Reaction condition: 1,2-di-phenyl-2-oxoethyl carboxylates (1 mmol), ammonium acetate (3 mmol)
In the previous literature [33], there were two products
1,3-oxazole and 1,3-imidazole which were obtained in
approximately equal yield (about 40%) by traditional
Table 3. In all examples, excellent yields were obtained
after 5 min. The nucleophilic addition and self-cycloaddi-
tion reaction of 1,2-di(furan-2-yl)-2-oxoethyl carboxylates
with 3.0 equivalent of ammonium acetate was readily
carried out. The structures of imidazole derivatives were
confirmed by elemental analysis, IR, 1H and 13C NMR and
MS analysis. The –NH–RC N– protons of compounds
exhibit resonances at 9.27–12.75 ppm (DMSO as solvent)
or not exhibit resonances (CD3Cl as solvent), while the
resonances for the corresponding –NH–RC N– carbon
atoms are observed at 136–145 ppm.
As shown in Table 3, it is clear that this approach could be
applied to a broad range of 2-oxoethyl carboxylates. The
results indicated that good yields were obtained when 2-
oxoethyl carboxylates containing aromatic rings, hetero-
cyclic rings and the longer conjugated substituted groups
were used as starting materials (entries 1–4, 7, 8, 10 and 11),
heating based on
a-acyloxy ketones as raw materials
and ammonium acetate in boiling glacial acetic acid.
Besides, the substituted oxazoles were prepared in
moderate yield by improving the above-mentioned
synthesis procedures in the literature [34]. In our work,
eleven trisubstituted imidazoles with furan rings were
synthesized by using 1,2-di(furan-2-yl)-2-oxoethyl car-
boxylates under microwave radiation and solvent-free
conditions (Table 3). Herein, only a few trisubstituted
oxazoles reported in the literature [33–35] were found in
the synthesizing process of trisubstituted imidazoles. The
results of microwave-assisted nucleophilic addition from a
range of 1,2-di(furan-2-yl)-2-oxoethyl carboxylates 2a–k
with ammonia to obtain the products 3a–k are listed in

B. Li et al. / C. R. Chimie 15 (2012) 784–792
791
and increasingtheconjugated chain, the yield of the products
was enhanced (entries 4 and 11). However, when 2-oxoethyl
aliphatic ester was used, the yield was lower (entries 5, 6 and
9). This is due to that the conjugated effect of the substituted
aromatic rings and the longer conjugated substituted groups
enhanced the stability of the hypothetic intermediates N-(2-
amino-1,2-di-furan-2-vinyl)-amides(m), N-(1,2-di-furan-2-
yl-2-oxo-ethyl)-amides(n) and the products. Besides, the
electron-withdrawing effect of aromatic rings with electron-
withdrawing group and pyridyl (entries 3, 7 and 8) made the
electrophilicity of the carbon of carboxyl much stronger, and
the self-cycloaddition easily perform. Therefore, the yield of
products was high, whereas, when there is phenyl, 2-furyl
and electron-donating group on the aromatic rings, better
yields were obtained (entries 1–3 and 10), due to the fact that
the electron-donating effect led to the self-cycloaddition
becoming a little difficult. Simultaneously, the effect of
substituted groups on the yield was also explained by the
proposed possible mechanism (Scheme 2).
Fig. 2. CL kinetic curves of different systems: a: H2O2: b: 3a-H2O2; c: 3j-
H2O2; d: Cu2+-3a-H2O2; e: Cu2+-3j-H2O2 system. Concentration: 3a,
0.1 mmol/L; 3j, 0.1 mmol/L; NaOH, 0.1 mol/L; H2O2, 1 mol/L; Cu2+
,
0.01 mmol/L.
Table 4
The possible mechanism to generate trisubstituted
imidazoles including furan rings from 1,2-di(furan-2-yl)-
2-oxoethyl carboxylic esters is proposed, as shown in
Scheme 2. The ammonium acetate decomposed to produce
the catalyst acetic acid, which further forms hydrogen
Optimal conditions of 3j/3a-H2O2-Cu2+ systems.
System
3j
3a
NaOH
H2O2
(mmol/L)
(mmol/L)
(mol/L)
(mol/L)
3j-H2O2-Cu2+
3a-H2O2-Cu2+
0.1
–
–
0.25
0.25
0.01
0.1
0.005
bond with the carboxyl group on 1,2-di (furan-2-yl)-2-
oxoethyl carboxylates. As a result, the electrophilicity of
the carbon of carboxyl was substantially enhanced, which
accelerated the following nucleophilic addition and self-
cycloaddition with ammonia to form the 1,2-di(furan-2-
yl)-2-oxoethyl carboxylates–ammonia adduct and the
final product. Based on the results described above, we
can conclude that microwave-assisted one-pot procedure
on the surface of alumina provides a simple and efficient
method for the synthesis of trisubstituted imidazoles
under solvent-free conditions. In addition, the method was
applied to the synthesis of trisubstituted imidazoles with
benzene rings, 4,5-dipenyl-2-styryl-1H-imidazole and 2-
(furan-2-yl) vinyl-4,5-dipenyl-1H-imidazole were suc-
cessfully synthesized in 83.3% and 77.6% (entries 12 and
13 in Table 3), respectively.
3.2. The determination of Cu2+ by CL reaction of the
synthesized compounds
The compounds synthesized (3a and 3j) were applied to
the determination of Cu2+ by the CL reaction with H2O2.
The H2O2 could directly oxidize 3j/3a to produce CL
emission in basic solution. The dynamic CL intensity-time
profiles of the 3j/3a-H2O2 systems are shown in Fig. 2
(curves b and c). It has been found experimentally that the
addition of Cu2+ into the system could induce significant
enhancement of CL signal. The results are shown in Fig. 1
(curve d and e). So, Cu2+ was chosen to enhance the CL
intensity of the 3j/3a-H2O2 system in the experiment. The
effects of experimental conditions were investigated. The
results are shown in Table 4. Under the optimal conditions,
the relationship between enhanced CL intensity and the
concentration of Cu2+ was obtained. The linear ranges of
Scheme 2. The possible mechanism to generate trisubstituted
imidazoles.

792
B. Li et al. / C. R. Chimie 15 (2012) 784–792
the calibration curves are 5.0 Â 10À10–1.0 Â 10À5 mol/L for
3j-H2O2-Cu2+ system, 1.0 Â 10À10–5.0 Â 10À6 mol/L for 3a-
H2O2-Cu2+ system, and the corresponding detection limits
are 2.7 Â 10À10 and 6.5 Â 10À11 mol/L, respectively. The
proposed method has been used to determine trace
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In conclusion, we have developed a novel and efficient
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chemistry procedure, could be applied to the synthesis
of heterocyclic compounds including nitrogen atom. The
method afforded the guidance to synthesize substituted
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j.crci.2012.06.005.
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