Applications of microwave technology to rapid synthesis of substituted imidazoles on silica-supported SbCl₃ as an efficient heterogeneous catalyst

Peer review under responsibility of Taibah University

Figures & data

Scheme 1 Synthesis of substituted imidazoles by SbCl₃/SiO₂ catalyst under solvent-free conditions.

Scheme 2 Reaction of SbCl₃ with silica gel to form a highly active catalyst.

Table 1 Optimization of catalyst amount in synthesis of 1,2,4,5-tetrasubstituted imidazole derivatives under microwave irradiation.

Entry	Catalyst (g)	Time (min)	Yield (%)
1	0.02 (SbCl3/SiO2)	15	40
2	0.04 (SbCl3/SiO2)	15	52
3	0.06 (SbCl3/SiO2)	15	70
4	0.08 (SbCl3/SiO2)	15	83
5	0.09 (SbCl3/SiO2)	15	90
6	0.1 (SbCl3/SiO2)^a	15	95
7	0.1 (SbCl3/SiO2)^b	20	90
8	0.11 (SbCl3/SiO2)	15	95
9	0.1 (SiO2)	15	80
10	0.1 (1.99 g SbCl3 and 1.54 g SiO2)	15	85
11	–	25	30

a The best yield of product.

b Under heating condition at 120 °C.

Table 2 Synthesis of 1,2,4,5-tetrasubstituted imidazole derivatives catalyzed by SbCl₃/SiO₂.

R	Amine	Product	Time (min) (MW)/(120 °C)	Yield (%) (MW)/(120 °C)	Melting-point (°C) [References]
H	Ph-NH2	5a	15/45	95/87	216–218 [47]
4-Me	Ph-NH2	5b	17/60	90/80	186–188 [47]
4-Cl	Ph-NH2	5c	12/35	97/92	160–163 [48]
2-OH	Ph-NH2	5d	18/70	76/73	252–254 [48]
2-F	Ph-NH2	5e	10/30	96/92	165–168 [49]
3,4-(OMe)2	Ph-NH2	5f	23/75	85/75	178–180 [50]
4-Br	Ph-NH2	5g	13/35	96/90	207–211 [48]
4-OMe	Ph-NH2	5h	20/65	87/78	177–180 [47]
H	n-Pr-NH2	5i	10/40	96/90	87–89 [50]
4-Cl	n-Pr-NH2	5j	6/35	96/93	85–87 [50]
4-Me	n-Pr-NH2	5k	15/50	91/82	78–83 [50]
4-OMe	n-Pr-NH2	5l	15/65	90/78	76–80 [50]

Table 3 Synthesis of 2,4,5-trisubstituted imidazole derivatives catalyzed by SbCl₃/SiO₂.

R	Product	Yield (%) (MW)/(120 °C)	Time (min) (MW)/(120 °C)	Melting-point (°C)^a
H	6a	10/35	95/87	272–273
4-Me	6b	10/40	90/80	226–227
4-OMe	6c	10/43	88/78	227–228
4-Cl	6d	10/25	97/94	272–273
3-Cl	6e	10/15	97/92	226–227
2-OMe	6f	10/45	86/73	227–228
3-NO2	6g	10/20	93/95	259–261
2-OH	3h	2/45	85/70	282–284
3-Cl	6i	10/20	92/93	207–209
3,5-(OMe)2	6j	12/45	90/80	269–271
4-Br	6k	10/25	98/92	203–205
4-N(Me)2	6l	10/40	88/77	260–261

a From Ref. [49].

Scheme 3 Proposed mechanism for the formation of substituted imidazoles in the presence of SbCl₃/SiO₂.

Table 4 Comparison of SbCl₃/SiO₂ with other catalysts reported in the literature for the synthesis of imidazoles.

Catalyst	Time	Yield^a (%)	References
Ionic liquid [EMIM]OAc	1.5 h	95	[39]
Zr(acac)4	45 min	88	[27]
Zinc (II) [tetra(4-methylphenyl)] porphyrin	70 min	94	[36]
BO3H3	30 min	98	[40]
SbCl3/SiO2	10 min	95	This work

Benzil (1 mmol), aldehyde (1 mmol), NH₄OAc (5 mmol).

a Isolated yields.