Synthesis of 2, 4, 5-Triphenyl Imidazole Derivatives Using Diethyl

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]

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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.

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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,

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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.


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

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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.

References [1]

Saikat Das Sharma, Parasa Hazarika, Dilip Konwar An efficient and one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-

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[2] [3] [4] [5]

[6] [7]

[8]

[9]

[10]

[11]

[12] [13] [14] [15] [16]

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