World Journal of Organic Chemistry, 2013, Vol. 1, No. 1, 6-10
Available online at http://pubs.sciepub.com/wjoc/1/1/2
© Science and Education Publishing
DOI:10.12691/wjoc-1-1-2
Synthesis of 2,4,5-Triphenyl Imidazole Derivatives Using
Diethyl Ammonium Hydrogen Phosphate as Green, Fast
and Reusable Catalyst
Adel A. Marzouk1,2,*, Vagif. M. Abbasov2, Avtandil H. Talybov2, Shaaban Kamel Mohamed3
1
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al Azhar University, Egypt
Mamedaliev Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
3
Chemistry and Environmental Division, Manchester Metropolitan University, Manchester, England
*Corresponding author: [email protected]
2
Received January 01, 2012; Revised February 4, 2013; Accepted March 17, 2013
Abstract A simple highly versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles is achieved by three
component cyclocondensation of 1,2-dicarbonyl compounds, aldehydes and ammonium acetate as ammonia source
in thermal solvent free condition using Brønsted acidic ionic liquid diethyl ammonium hydrogen phosphate as
catalyst. The key advantages of this process are cost effectiveness of catalyst, reusability of catalyst, easy work-up
and purification of products by non-chromatographic methods, excellent yields and very short time reactions.
Multicomponent reactions enjoy an outstanding status in organic and medicinal chemistry for their high degree of
atom economy and application in the diversity-oriented convergent synthesis of complex organic molecules from
simple and readily available substrates in a single vessel.
Keywords: 2, 4, 5-triarylimidazoles, benzyl and diethyl ammonium hydrogen phosphate
1. Introduction
Imidazoles are a class of heterocyclic compounds that
contain nitrogen and are currently under intensive focus
due to their wide range of applications [1]. Synthetic study
of imidazole units is very important due to their potent
biological activity [2] and synthetic utility [3]. Imidazoles
are an important class of heterocycles being the core
fragment of different natural products and biological
systems. Compounds containing imidazole moiety have
many pharmacological properties and play important roles
in biochemical processes [4]. The potency and wide
applicability of the imidazole pharmacophore can be
attributed to its hydrogen bond donor-acceptor capability
as well as its high affinity for metals (e.g., Zn, Fe, Mg),
which are present in many protein active sites3b [5,6].
Naturally occurring substituted imidazoles, as well as
synthetic derivatives thereof, exhibit wide ranges of
biological activities, making them attractive compounds
for organic chemists. They act as inhibitors of p38 MAP
kinase [7], B-Raf kinase [8], transforming growth factor
b1 (TGF-b1) type 1 activin receptor-like kinase (ALK5)
[9], cyclooxygenase-2 (COX-2) [10] and biosynthesis of
interleukin-1 (IL-1) [11]. Appropriately substituted
imidazoles are extensively used as glucagon receptors [12]
and CB1 cannabinoid receptor antagonists [13],
modulators of P-glycoprotein (P-gp)-mediated multidrug
resistance (MDR) [14], antibacterial and antitumor agents
[15] and also as pesticides [16]. Recent advances in green
chemistry and organometallic catalysis has extended the
application of imidazoles as ionic liquids [17] and Nheterocyclic carbenes [18].
Ionic liquid (IL) technology offers a new and
environmentally benign approach toward modern
synthetic chemistry. Ionic liquids have interesting
advantages such as extremely low vapour pressure,
excellent thermal stability, reusability, and talent to
dissolve many organic and inorganic substrates. Ionic
liquids have been successfully employed as solvents and
catalyst for a variety of reactions which promise
widespread applications in industry and organic syntheses
[19].
In recent years, ionic liquids (ILs) have become a
rapidly expanding topic of chemical research on account
of their unique properties that include a negligible vapor
pressure, nonflammability, excellent thermal stability,
reusability and ability to dissolve organic and inorganic
compounds, and even polymeric materials [20,21]. These
unusual properties mean that ionic liquids are superior
media for a broad range of potential uses, for example, as
environmentally friendly solvents for chemical synthesis
[22], biocatalysis [23], separation technologies [24], and
as solvents or “all-in-one” solvent/templates for
nanomaterial preparation [25]. More recently, ILs with
nitrogen, sulfur, or phosphorus as the central atom of
cations have been extensively investigated. These include
imidazolium,
pyrrolidinium,
tetraalkylammonium,
pyridinium, piperidinium, sulfonium and phosphonium
based ILs. Moreover, ILs consisting of large organic,
asymmetrical ions, such as 1-ethyl-3-methylimidazolium,
1,3-dialkyl imidazolium, 1-alkyl-2,3-dimethylimidazolium,
1-alkylpyridinium, 1-alkyl pyrazolium, tetra alkyl
World Journal of Organic Chemistry
ammonium, or tetra alkyl phosphonium cations and BF 4−,
PF6 − , CF3 SO3, or N(SO2CF3)2 − anions have been
developed. The easy modification of the cations and
anions in RTILs allows the development of task specific
RTILs for catalysis organic synthesis, nanoparticles,
extraction and dissolution. However, structural
modifications affect RTIL physio-chemical properties. As
a consequence, it is of great importance to understand the
relationship between structural changes and the properties
of ILs. This paper reports the synthesis of
diethylammonium hydrogen phosphate that contain alkyl
moiety with nitrogen and phosphorus atom [26,27].
We report here a simple, mild and efficient method for
the preparation of the 2,4,5-triarylimidazoles using diethyl
ammonium hydrogen phosphate as Brønsted acidic ionic
liquid catalyst that is considered as efficient and reusable
catalyst. The procedure reported herein is not cumbersome;
consequently, the methodology represents a good addition
to the list of methods available for the synthesis of highly
substituted imidazoles.
2. Experimental
2.1. Chemicals and Instruments
All reagents were purchased from Aldrich and Merck
and used without further purification. Products were
characterized by spectroscopy data (FTIR, 1H NMR and
13
C NMR spectra and Mass) and melting points.
SHIMADZU FT-IR-8400s spectrometer was used to
record IR spectra using KBr pellets. NMR spectra were
recorded on a Bruker (300-MHz) Ultrasheild NMR and
DMSO-d6 was used as a solvent. The purity of the
substances and the progress of the reactions were checked
on TLC and melting points that determined by open
capillary method using a Galen Kamp melting point
apparatus and are uncorrected.
7
2.2. General Methods for Synthesis of Ionic
Liquid
Diethylamine (20mmol) was added into a 150ml three
necked flask with a magnetic stirrer. Then equimolar
concentrated phosphoric acid was added dropwise slowly
into the flask at 0°C then stirring at 80°C for 12h. The
mixture was washed with diethyl ether three times to
remove non-ionic residues and dried in vacuum by a
rotary evaporator to obtain the viscous clear diethyl
ammonium hydrogen phosphate [19].
2.3. General Methods for Synthesis of 2,4,5Trisubstituted Imidazoles
In rounded bottom flask Benzil (10mmol), aldehyde
(10mmol), and ammonium acetate (40mmol) were added
to diethyl ammonium hydrogen phosphate (0.513g,
3mmol) in an oil bath at room temperature as in Scheme 1.
Then the reaction mixture was heated to 100°C for the
stipulated period of time reported in Table 1. After
completion of the reaction which was monitored by TLC,
the mixture washed with water, the solid product purified
by recrystallization from ethanol. All of the desired
product(s) were characterized by comparison of their
physical data with those of known compounds. Some
characterization data for selected known products are
given below.
Scheme 1. Diethylammonium hydrogen phosphate as Brønsted acidic
ionic liquid for synthesis of 2,4,5-trisubstituted imidazoles.
Table 1.
No
Aldehydes
Yield%
R.T(min)
M.p.
M.Wt.
M. Formula
1a
C6H598
20
271-272
296.37
C21 H16 N2
b
2-OHC6H495
15
204-205
312.36
C21 H16 N2O
c
4-OHC6H496
15
267-269
312.36
C21 H16 N2O
d
4-CH3OC6H596
20
230-232
326.39
C22 H18 N2O
e
4-(CH3)2NC6H494
30
256-258
339.43
C23 H21 N3
f
3,5-CH3OC6H596
30
222-224
356.42
C23 H20 N2O2
g
4-NO2C6H594
20
241-242
341.36
C21H15 N3O2
h
2-NO2C6H595
20
230-231
341.36
C21H15 N3O2
i
4-CHOC6H592
30
221-223
324.38
C22H16N2O
j
2,4-CH3OC6H596
35
217-219
356.42
C23 H20 N2O2
k
2,6-ClC6H594
20
228-231
365.26
C21 H14 Cl2N2
l
4-HOOCC6H595
20
320-323
340.37
C22H16N2O2
m
4-ClC6H596
15
262-264
330.81
C22 H15Cl N2
n
2,5-CH3OC6H5
93
27
181-183
356.42
C23 H20 N2O2
o
3-CH3OC6H5
94
35
266-268
326.39
C22 H18 N2O
p
4-BrC6H586
23
249-252
375.26
C22 H15 Br N2
Synthesis of 2, 4, 5-trisubstituted imidazoles via a one-pot three component reaction in the presence of diethyl ammonium hydrogen phosphate as
Brønsted acidic ionic liquid under thermal solvent-free condition at 100°C.
3. Spectral and Analytical Data
1. 2,4,5-Triphenyl-1H-imidazole (1a). Mp. 271–
272°C. FTIR (KBr, cm−1): 3434 (NH), 2993, 2470, 1638
(C=C), 1510 (C=N); 1H NMR (300 MHz, DMSO-d6):
12.7 (s, 1H, NH), 8.1 (d, J¼7.8 Hz, 2H), 7.1–7.9 (m, 13H,
Ar-H); 13C NMR (300 MHz, DMSO-d6): d 146, 136,
135.4, 130.8, 130, 129, 128.75, 128.3, 127.5, 127, 125.6.
2. 2-2-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol (1b):
Mp. 204–205°C. FTIR (KBr, cm−1): 3596 (OH),
3432(NH), 2998, 2465, 1636 (C=C), 1216; 1H NMR (300
MHz, DMSO-d6): 12.74 (br. s. 1Н, NH), 7.17-7.23 (m,
10Н, Ar-H), 6.96-7.01 (d, J = 8.05Hz, 1Н), 6.8 - 6.95 (d,
j=7.4 Hz, 2H); 13C NMR (300 MHz, DMSO-d6): 146.0,
8
World Journal of Organic Chemistry
136.0, 130.08, 130.0, 129.0, 128.9, 128.4, 128.2, 127.6,
126.7, 125.6.
3. 4-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol
(1c):
Mp 267–269°C. FTIR (KBr, cm−1): 3590 (OH), 3454
(NH), 3284, 3064, 1701(C=C), 1283; 1HNMR (300 MHz,
DMSO-d6): 12.20 (s, 1H, NH), 9.40 (s, 1H, OH), 7.90 (d,
J¼8.4 Hz, 2H), 7.52–7.29 (m, 10H, Ar-H), 6.80 (d, J¼8.4
Hz, 2H); 13C NMR (300 MHz, DMSO-d6): 157.6, 146.65,
127.12, 125.7, 124.3, 121.9, 114.75, 112.85, 98.55,
95.46ppm.
4. 2-(4-Methoxyphenyl)-4,5-diphenylimidazole (1d):
Mp. 230–232°C. IR (KBr, cm−1): 3400, 3060, 1611, 1490,
1179, 1028, 830, 761; 1HNMR (DMSO-d6, 300MHz):
12.52 (s, 1H, NH), 8.03 (d, J=8.80 Hz, 2.0 Hz, 2H), 7.707.10(m, 10H, Ar-H), 7.03 (dt, J=8.8 Hz, 2.0 Hz, 2H), 3.81
(s, 3H, CH3); 13C NMR (300 MHz, DMSO-d6): 158.32,
145.09, 136.01, 134.62, 131.38, 12130, 127.4, 126.01,
123,07, 113.89, 54.62ppm.
5. 4-[4-(4,5-Diphenyl-1H-imidazole-2-yl)-phenyl]dimethylamine (1e): Mp 256–259°C. FTIR (KBr, cm−1):
3447, 3061, 1614, 1501; 1H NMR (300 MHz, DMSO-d6):
12.31 (s, 1H, NH), 7.92 (d, J¼8.4 Hz, 2H), 7.7–7.11 (m,
10H, Ar-H), 6.80 (d, J¼8.4 Hz, 2H), 2.97 (s, 6H (CH 3)2N);
13
CNMR (300 MHz, DMSO-d6): 150.46, 145.64, 137.4,
135.08, 131.85, 127.4, 126.38, 125.55, 117.4, 111.85,
30.00ppm.
6. 2-(3,4-Dimethoxyphenyl)-4,5-diphenylimidazole
(1f): Mp 222-224°C. FTIR (KBr, cm-1): 3381(NH),
3062(C-H), 3002, 2960, 1593 (C=N), 1512, 1265, 1023,
765. 1HNMR (DMSO-d6, 300MHz): 4.2(s., 6H, 2CH3O),
7.02-7.60 (m., 13H, Ar-H), 10.4 (br. S., 1Н, NH); 13C
NMR (300 MHz, DMSO-d6): 149.769 148.931, 147.904,
136.733, 134.943, 131.467, 131.357, 129.900, 129.355,
129.107, 128.298, 126.696, 126.430, 123.772, 122.146,
113.294, 111.752, 55.747, 55.678ppm.
7. 2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (1g):
Mp 241–242°C. (KBr, cm-1): 3421(NH), 2928,
1596(C=N), 1515, 856; 1HNMR (DMSO-d6, 300MHz):
11.7 (s. br., NH), 7.00-8.52 (m., 14H, Ar-H); 13C NMR
(300 MHz, DMSO-d6): 148.069, 147.460 145.633,
137.891, 134.737, 131.435, 131.103, 130.341, 129.631,
128.568, 126.862, 126.659, 124.165ppm.
8. 2-(2-Nitrophenyl)-4,5-diphenyl-1H-imidazole (1h):
Mp 230-231°C. FTIR (KBr, cm-1): 3421 (NH), 2928, 1596
(C=N), 1515, 1345, 856. 1H NMR (300 MHz, DMSO-d6):
12.10 (br. S., 1Н, NH), 7.9 - 8.2 (m, 14Н, Ar-H). 13C
NMR (300 MHz, DMSO-d6): 147.0, 141.0, 136.1, 130.6,
129.70, 128.4, 127.0, 126.9, 126.1, 125.4, 124.0, 122.0,
118.5ppm.
9. 4-(4,5-diphenyl-1H-imidazol-2-yl)benzaldehyde
(1i): Mp 221-223°C. FTIR (KBr, cm-1): 3300 (NH),
3052(C-H), 2980, 1593 (C=N), 1696 (C=O), 1504, 1345,
876. 1H NMR (300 MHz, DMSO-d6): 12.76 (br. S., 1Н,
NH) 10.03 (br. S., 1Н, CHO), 7.22 - 8.19 (m, 14Н, Ar-H).
13
C NMR (300 MHz, DMSO-d6): 194.78, 135.50, 130.06,
129.56, 129.47, 128.72, 128.64, 128.57, 127.0, 128.51,
128.39, 128.22, 128.16, 128.08, 127.08ppm.
10. 2-(2,4-Dimethoxyphenyl)-4,5-diphenylimidazole
(1j): Mp 217-219°C. FTIR (KBr, cm-1): 3390 (NH),
3055(C-H), 3005, 2860, 1590 (C=N), 1515, 1274, 1028,
770. 1HNMR (DMSO-d6, 300MHz): 11.71 (br. S., 1Н,
NH), 7.79-7.94 (m., 13H), 3.91(s., 3H, CH3O), 3.83(s., 3H,
CH3O); 13C NMR (300 MHz, DMSO-d6): 160.837157.204,
151.245, 143.350, 135.389, 134.512, 131.366, 129.792,
129.592, 129.506, 128.524, 128.315, 128.086, 127.437,
127.027, 126.865, 126.751, 126.265, 111.953, 105.584,
98.357, 55.890, 55.623ppm.
11. 2-(2,6-Dichlorophenyl)-4,5-diphenyl-1Himidazole (1k): Mp 228-231°C. FTIR (KBr, cm-1):
3390(NH), 3055(C-H), 2962, 2830, 1679 (C=N), 1559,
1194, 1096, 765, 695. 1HNMR (DMSO-d6, 300MHz):
11.82 (br. S., 1Н, NH), 7.79-7.94 (m., 13H); 13C NMR
(300 MHz, DMSO-d6): 160.737, 157.104, 151.345,
143.150, 135.289, 134.312, 131.166, 129.592, 129.392,
129.306, 128.224, 128.186, 128.115, 127.234, 127.122,
126.661, 126.453, 126.262, 111.751, 105.380, 98.151ppm.
12. 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoic
acid
(1l): Mp 320-223°C. FTIR (KBr, cm-1): 3400(NH),
3057(C-H), 2980, 2875, 1696(C=O), 1613(C=N), 1585,
1180, 1072, 721, 697. 1HNMR (DMSO-d6, 300MHz):
12.71 (br. S., 1Н, NH), 11.40 (br. S., 1Н, OH), 8.0498.087 (d, J=8.8 Hz, 2.0 Hz, 2H), 8.191-8.229(d, J=8.8 Hz,
2.0 Hz, 2H), 7.32-7.74 (m, 10H, Ar-H); 13C NMR (300
MHz, DMSO-d6): 167.359, 159.474, 154.258, 144.657,
136.104, 133.759, 131.919, 131.003, 130.879, 129.802,
129.230, 129.096, 128.772, 128.477, 128.181, 127.809,
127.704,
127.333,
126.570,
126.484,
126.141,
124.968ppm.
13. 2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole
(1m): Mp 262-264°C. FTIR (KBr, cm-1): 3148 (NH),
3082(C-H), 2959, 2912, 1601(C=N), 1502, 1128, 1072,
730, 694, 634. 1HNMR (DMSO-d6, 300MHz): 10.544 (br.
S., 1Н, NH), 8.11 (d, J¼8.4 Hz, 2H, Ar-H), 7.294-7.562
(m, 12H, Ar-H); 13C NMR (300 MHz, DMSO-d6):
144.428, 137.296, 135.008, 132.748, 130.927, 129.201,
128.772, 128.667, 128.562, 128.429, 128.200, 127.857,
127.075, 126.837, 126.598ppm.
14. 2-(2,5-Dimethoxyphenyl)-4,5-diphenyl-1Himidazole (1n): Mp 181-183°C. FTIR (KBr, cm-1):
3333(NH), 3059(C-H), 2962, 2834, 1648(C=N), 1524,
1221, 1175, 1047, 742, 696. 1HNMR (DMSO-d6,
300MHz): 11.90 (br. S., 1Н, NH), 7.43-8.132 (m, 13H,
Ar-H), 3.91(s., 3H, CH3O), 3.82(s., 3H, CH3O); 13C NMR
(300 MHz, DMSO-d6): 159.435, 153.066, 150.235,
145.219, 142.950, 136.467, 136.076, 135.199, 131.156,
130.832, 128.725, 128.610, 128.543, 128.133, 127.666,
126.132, 126.446, 119.371, 115.014, 113.383, 112.764,
55.919, 55.470ppm.
15. 2-(3-Methoxyphenyl)-4,5-diphenyl-1H-imidazole
(1o): Mp 266-268°C. IR (KBr, cm−1): 3390 (NH), 3054
(C-H), 2960, 2832, 1634(C=N), 1589, 1180, 1050, 889,
765, 697; 1HNMR (DMSO-d6, 300MHz): 10.97 (s, 1H,
NH), 6.90-7.67 (m, 14H, Ar-H), 3.68 (s, 3H, CH3); 13C
NMR (300 MHz, DMSO-d6): 166.424, 159.550, 158.940,
145.755, 142.010, 136.200, 134.300, 134.175, 131.623,
129.812, 128.667, 128.486, 128.191, 127.056, 119.667,
117.607, 114.213, 113.059, 112.335, 110.161, 55.203ppm.
16. 2-(4-Bromophenyl)-4,5-diphenyl-1H-imidazole
(1p): Mp 249-252°C. FTIR (KBr, cm-1): 3420(NH),
3027(C-H), 2924, 2835, 16034(C=N), 1501, 1126, 1069,
826, 728, 715, 696. 1HNMR (DMSO-d6, 300MHz): )
11.54 (br. S., 1Н, NH), 8.057 (d, J¼ 8.2 Hz, 1.1 Hz, 2H),
7.702 (d, J¼ 8.2 Hz, 1.1Hz, 2H), 7.20-7.698 (m, 10H, ArH),; 13C NMR (300 MHz, DMSO-d6): 144.457, 137.315,
134.970, 131.680, 131.356, 129.621, 129.516, 128.658,
128.410, 128.219, 127.876, 127.209, 127.094, 126.617,
121.392ppm.
World Journal of Organic Chemistry
4. Results and Discussion
As a result of the versatile biological activities of
substituted imidazoles numerous classical methods for the
synthesis of these compounds have been reported [28,29].
In a typical procedure, benzil or benzoin, aldehydes and
ammonium acetate are condensed in the presence of
strong protic acid such as H3PO4 [29], H2SO4 [30], HOAc
[31] as well as organo catalyst in HOAc [32] under reflux
conditions. These homogeneous catalysts present
limitations due to the use of corrosive reagents and the
necessity of neutralization of the strong acid media. In
addition, the synthesis of these heterocycles in polar
organic solvents such as ethanol, methanol, acetic acid,
DMF and DMSO lead to complex isolation and recovery
procedures.
These processes also generate waste containing catalyst
and solvent, which have to be recovered, treated and
disposed of. The toxicity and volatile nature of many
organic solvents, particularly chlorinated hydrocarbons
that are widely used in huge amounts for organic reactions
have posed a serious threat to the environment. Thus,
design of solvent-free catalytic reaction has received
9
tremendous attention in recent times in the area of green
synthesis [33].
2,4,5-Trisubstituted imidazole was prepared in
quantitative yield by condensing benzyl (10mmol),
ammonium acetate with benzaldehyde derivatives
(10mmol), in the presence of brønsted ionic liquid
diethylammonium hydrogen phosphate (0.513g, 3mmol),
as a catalyst in solvent free condition at 100°C.
The stoichiometric amount of ammonium acetate in the
preparation of 2,4,5-trisubstituted imidazoles is two. We
can prepare 2,4,5-trisubstituted imidazoles using two
equivalents of ammonium acetate but we observed in our
experiment and other published papers, if we use
inexpensive and available ammonium acetate having more
than two equivalents, the reaction will show better results.
Thus, a slight excess of the ammonium acetate was found
to be advantageous and hence the molar ratio of benzil to
ammonium acetate was kept at 1:4. The efficiency and
versatility of the ionic liquid as a catalyst for the
preparation of 2,4,5-trisubstituted imidazoles were
demonstrated by the wide range of substituted and
structurally diverse aldehydes to synthesize the
corresponding products in high to excellent yields (Table
2).
Table 2.Comparison between our catalyst diethylammonium hydrogen phosphate and the other used catalyst
No
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
1
2
InCl3·
3H2O
MeOH/R.T
492
76
[34]
KH2PO4
Reflux in EtOH
60
89
[35]
3
Yb(OPf)3
C10F18/80°C
360
80
[29]
4
Zr(acac)4
Reflux in EtOH
120
95
[36]
5
L-proline
Methanol/60°C
540
87
[37]
6
[H bim]BF4
100°C
60
94
[29]
7
NiCl2·
6H2O/Al2O3
Reflux in EtOH
90
89
[38]
8
N-methyl-2-pyrrolidonium hydrogen sulfate
100°C
60
98
[29]
9
Diethyl ammonium hydrogen phosphate
100°C
15-40
98
Present work
The presence of electron withdrawing groups afforded
the corresponding 2,4,5-trisubstituted imidazoles in
shorter reaction time with higher yields, however the
presence of electron donating groups (Scheme 2) on the
aromatic aldehyde resulted in the corresponding products
in low yields and the reaction was sluggish.
OH
O P O
O H
N
H
H
R
NH 3 +
CH 3 COONH 4
O
R
- H2 O
NH
H
H
N
H
Ph
Ph
H
OH
O P O
O H
R
O
NH3
O
-H2 O Ph
NH4 OAC
H O
O P O
OH
Ph
H
H
+H +
NH
HO H
N
Ph
Ph
H
C
R
NH
H
N
N
R
Ph
Ph
HN
O
N
H
-H+
Ph
N
C
Ph
N
H
H
R
-H2 O
HO
NH
Ph
H
C R
N
Ph
H
Scheme 2. Mechanism of Condensation Reaction between Benzil,
Benzaldehyde, and Ammonium Acetate in the Presence of
Diethylammonium Hydrogen Phosphate as Brønsted Acidic Ionic Liquid
5. Conclusion
Multicomponent reactions enjoy an outstanding status
in organic and medicinal chemistry for their high degree
of atom economy and application in the diversity-oriented
convergent synthesis of complex organic molecules from
simple and readily available substrates in a single vessel.
A simple highly versatile and efficient synthesis of
2,4,5-trisubstituted imidazoles is achieved by three
component
cyclocondensation
of
1,2-dicarbonyl
compounds, aldehydes and ammonium acetate as
ammonia source in thermal solvent free condition using
Brønsted acidic ionic liquid diethyl ammonium hydrogen
phosphate as catalyst. The key advantages of this process
are cost effectiveness of catalyst, reusability of catalyst,
easy work-up and purification of products by nonchromatographic methods, excellent yields and very short
time reactions.
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