Efficient synthesis of 5-substituted 2,3-diphenyl and 5-substituted 1-aryl-2,3-diphenyl imidazoles using polyethylene glycol

Article abstract of DOI:10.1080/00397910903318633

Treatment of benzoin with an aldehyde and NH4OAc in polyethylene glycol (PEG-400) under reflux afforded a 5-substituted 2,3-diphenyl imidazole while the same reaction along with an additional aniline produced 5-substituted 1-aryl 2,3-diphenyl imidazole. No any catalyst or solvent was required to carry out this conversion, and the imidazoles were formed in excellent yields.

Full text of DOI:10.1080/00397910903318633

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Efficient Synthesis of 5-Substituted 2,3-
Diphenyl and 5-Substituted 1-Aryl-2,3-
diphenyl Imidazoles Using Polyethylene
Glycol
Biswanath Das a , Chithaluri Sudhakar a & Yallamalla Srinivas a
a Organic Chemistry Division I, Indian Institute of Chemical
Technology , Hyderabad, Andhra Pradesh, India
Published online: 09 Aug 2010.
To cite this article: Biswanath Das , Chithaluri Sudhakar & Yallamalla Srinivas (2010) Efficient
Synthesis of 5-Substituted 2,3-Diphenyl and 5-Substituted 1-Aryl-2,3-diphenyl Imidazoles Using
Polyethylene Glycol, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:18, 2667-2675, DOI: 10.1080/00397910903318633
To link to this article: http://dx.doi.org/10.1080/00397910903318633
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Synthetic Communications1, 40: 2667–2675, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903318633
EFFICIENT SYNTHESIS OF 5-SUBSTITUTED
2,3-DIPHENYL AND 5-SUBSTITUTED
1-ARYL-2,3-DIPHENYL IMIDAZOLES USING
POLYETHYLENE GLYCOL
Biswanath Das, Chithaluri Sudhakar, and Yallamalla Srinivas
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, Andhra Pradesh, India
Treatment of benzoin with an aldehyde and NH4OAc in polyethylene glycol (PEG-400)
under reflux afforded a 5-substituted 2,3-diphenyl imidazole while the same reaction along
with an additional aniline produced 5-substituted 1-aryl 2,3-diphenyl imidazole. No any
catalyst or solvent was required to carry out this conversion, and the imidazoles were
formed in excellent yields.
Keywords: Aldehyde; ammonium acetate; benzoin; imidazole; PEG-400
INTRODUCTION
Imidazole derivatives possess various important biological properties including
fungicidal, herbicidal, and plant-growth regulator activities.[1,2] Some of the com-
pounds exhibit antiviral and anticancer properties.[3,4] Substituted imidazoles are
in the core portion in many bioactive molecules such as losartan and olmesartan.[5]
They have also been employed in the preparation of ionic liquids.[6] Thus, the
synthesis of imidazoles is an important task in organic chemistry. Though the
preparation of benzimidazoles has recently been studied[7–13] well, the methods
for the synthesis of other substituted imidazoles starting from benzoin are
limited.[14–17]
RESULTS AND DISCUSSION
In continuation of our work[18–20] on the development of useful synthetic meth-
odologies, we have observed that the treatment of a benzoin with an aldehyde and
NH4OAc in polyethylene glycol (PEG-400) under reflux yielded a 5-substituted
Received May 29, 2009.
Part 185 in the series ‘‘Studies on Novel Synthetic Methodologies.’’
Address correspondence to Biswanath Das, Organic Chemistry Division I, Indian Institute of
Chemical Technology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India. E-mail: biswanathdas@
yahoo.com
2667

2668
B. DAS, C. SUDHAKAR, AND Y. SRINIVAS
Scheme 1. Synthesis of 5-substituted 2,3-diphenyl and 5-substituted 1-aryl 2,3-diphenyl imidazoles using
PEG-400.
2,3-diphenyl imidazole and that the same reaction together with an additional aniline
formed 5-substituted 1-aryl 2,3-diphenyl imidazole (Scheme 1).
Various substituted imidazoles were prepared from benzoin, different
aldehydes, and anilines (Table 1). For the preparation of 5-substituted 2,3-diphenyl
imidazole, the molar ratio of benzoin, aldehyde, and NH4OAc was 1:1:2, whereas
for the preparation of 5-substituted 1-aryl 2,3-diphenyl imidazole, an equimolar
ratio of all the substrates (benzoin, aldehydes, aniline, and NH4OAc) was used.
Both the aromatic and aliphatic aldehydes underwent the conversion smoothly.
Aromatic aldehydes containing electron-donating as well as electron-withdrawing
substituents were applied. 5-Substituted 2,3-diphenyl imidazoles were produced
within 20 min, and 5-substituted 1-aryl 2,3-diphenyl imidazoles were produced
within 1.5–2 h. The products were formed in excellent yields and with various
functionalities such as hydroxyl, ether, halogen, and nitro groups remained
unchanged.
When carried out with benzoin, an aldehyde, NH4OAc, and an aniline, no
1-unsubstituted imidazoles were obtained with the present reaction. Moreover, when
heated alone under reflux in PEG, benzoin was converted to benzyl within a few min-
utes. Aerial oxygen acts as the oxidant as the present conversion could not proceed
in the absence of air. Considering all these results, the plausible mechanism of the
reaction is proposed[21] in Scheme 2.
Polyethylene glycol (PEG-400)[22,23] is a biologically acceptable polymer that is
inexpensive and ecofriendly. Its applications in organic synthesis have not yet been
fully explored. In the present conversion, it possibly activates the carbonyl and
hydroxyl groups of the substrates and intermediates through hydrogen bonding.
The experimental procedure is convenient, and no any additional catalyst was
required. The structures of the imidazoles were settled from their spectral [infrared
1
(IR), H NMR, and mass (MS)] and analytical data.
CONCLUSION
In conclusion, we have described how 5-substituted 2,3-diphenyl and
5-substituted 1-aryl 2,3-diphenyl imidazoles can be prepared efficiently in PEG-
400 medium starting from benzoin in short reaction times and in impressive yields.

SYNTHESIS OF IMIDAZOLES USING POLYETHYLENE GLYCOL
2669
Table 1. Synthesis of 5-substituted 2,3-diphenyl imidazolesa
Entry
Aldehyde
Product
Isolated yield (%)
1a
94
1b
1c
1d
1e
96
89
92
92
91
1f
1g
93
(Continued )

2670
Entry
1h
B. DAS, C. SUDHAKAR, AND Y. SRINIVAS
Table 1. Continued
Aldehyde
Product
Isolated yield (%)
92
1i
1j
94
91
1
aThe structures of the products were settled from their spectral (IR, H NMR, and MS) and analytical
data.
EXPERIMENTAL
General Procedure for the Synthesis of 5-Substituted 2,3-Diphenyl
and 5-Substituted 1-Aryl 2,3-Diphenyl Imidazols
A mixture of benzoin (0.5 mmol), an aldehyde (0.5 mmol), and NH4OAc
(1 mmol) was suspended in PEG-400 (5 mL). The mixture was heated under reflux,
and the reaction was monitored by thin-layer chromatography (TLC). After com-
pletion, water (10 mL) was added, and the mixture was extracted with EtOAc
(3 ꢀ 10 mL). The extract was dried over anhydrous Na2SO4 and concentrated. The
residue was purified by column chromatography (silica gel, n-hexane–EtOAc) to
obtain pure 5-substituted 2,3-diphenyl imidazole.
For the preparation of 5-substituted 1-aryl 2,3-diphenyl imidazoles, this experi-
mental procedure was followed using a mixture of benzoin (0.5 mmol), aldehyde
(0.5 mmol), aniline (0.5 mmol), and NH4OAc (0.5 mmol) suspended in PEG-400
(5 mL).
Spectral Data for Selected Compounds
Product 1e (Table 1). Mp 272–274 ꢁC (EtOH); IR (KBr): 3231, 1653, 1586,
1
1484, 1408, 1224 cmꢂ1; H NMR (200 MHz, CDCl3): d 9.02 (1H, brs), 7.62–7.50
(6H, m), 7.31–7.16 (6H, m), 6.75 (2H, d, J ¼ 8.0 Hz); ESIMS: m=z 313 [M þ H]þ.
Anal. calcd. for C21H16N2O: C, 80.77; H, 5.13; N, 8.97%. Found: C, 80.88; H,
5.18; N, 8.91%.

SYNTHESIS OF IMIDAZOLES USING POLYETHYLENE GLYCOL
2671
Scheme 2. Mechanism of 5-substituted 2,3-diphenyl and 5-substituted 1-aryl 2,3-diphenyl imidazoles using
PEG-400.
Product 1f (Table 1). Mp 247–249 ꢁC (EtOH); IR (KBr): 3420, 1651, 1601,
1
1482, 1432, 1203 cmꢂ1; H NMR (200 MHz, CDCl3): d 8.02 (2H, d, J ¼ 8.0 Hz),
7.77 (1H, brs), 7.60–7.52 (6H, m), 7.38–7.21 (6H, m); ESIMS: m=z 375, 377
[M þ H]þ. Anal. calcd. for C21H15BrN2: C, 67.20; H, 4.00; N, 7.47%. Found: C,
67.31; H, 4.09; N, 7.42%.
Product 2e (Table 2). Mp 184–186 ꢁC (EtOH); IR (KBr): 1670, 1600, 1495,
1450, 1235 cmꢂ1
;
1H NMR (200 MHz, CDCl3): d 7.54 (2H, d, J ¼ 8.0 Hz),
7.32–7.01 (17H, m), 2.85 (1H, m), 1.22 (6H, d, J ¼ 7.0 Hz); ESIMS: m=z 415
[M þ H]þ. Anal. calcd. for C30H26N2: C, 86.96; H, 6.28; N, 6.76%. Found: C,
86.82; H, 6.33; N, 6.68%.
Product 2h (Table 2). Mp 197–199 ꢁC (EtOH); IR (KBr): 1674, 1599, 1498,
1456, 1279 cmꢂ1
;
1H NMR (200 MHz, CDCl3): d 7.49 (2H, d, J ¼ 8.0 Hz),

2672
Entry
2a
B. DAS, C. SUDHAKAR, AND Y. SRINIVAS
Table 2. Synthesis of 5-substituted 1-aryl 2,3-diphenyl imidazolesa
Time
(h)
Isolated
yield (%)
Aldehyde
Amine
Product
1.5
94
2b
2c
2d
2
91
96
89
1.5
2.0
2e
1.5
94
2f
1.5
1.5
92
2g
92
(Continued )

SYNTHESIS OF IMIDAZOLES USING POLYETHYLENE GLYCOL
2673
Table 2. Continued
Time
(h)
Isolated
yield (%)
Entry
2h
Aldehyde
Amine
Product
1.5
94
2i
1.5
94
2j
2
92
1
aThe structures of the products were settled from their spectral (IR, H NMR, and MS) and analytical
data.
7.38–7.02 (13H, m), 2.84 (1H, m), 1.31 (6H, d, J ¼ 7.0 Hz); ESIMS: m=z 339
[M þ H]þ. Anal. calcd. for C24H22N2: C, 85.21; H, 6.51; N, 8.28%. Found: C,
85.13; H, 6.62; N, 8.34%.
Product 2i (Table 2). Mp 171–173 ꢁC (EtOH); IR (KBr): 1649, 1602, 1508,
1444, 1247 cmꢂ1
;
1H NMR (200 MHz, CDCl3): d 7.54 (2H, d, J ¼ 8.0 Hz),
7.48–7.39 (2H, m), 7.30–7.04 (11H, m), 6.99 (2H, d, J ¼ 8.0 Hz), 6.72 (2H, d,
J ¼ 8.0 Hz), 3.80 (3H, s); ESIMS: m=z 403 [M þ H]þ. Anal. calcd. for C28H22N2O:
C, 83.58; H, 5.47; N, 6.97%. Found: C, 83.67; H, 5.42, N, 6.89%.
ACKNOWLEDGMENTS
The authors thank the Council of Scientific and Industrial Research and the
University Grants Commission, New Delhi, for financial assistance.

2674
B. DAS, C. SUDHAKAR, AND Y. SRINIVAS
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