Synthesis of benzimidazole by mortar–pestle grinding method

Figures & data

Figure 1. Biologically active benzimidazole derivatives.

Scheme 1. Strategies for the synthesis of benzimidazoles.

Table 1. Optimization of the reaction condition for benzomidazole.^a

Entry	Acid	Amount of acid (mL)	t (min)	Yield (%)^b
1	None	0	10	20
2	H2SO4^c	0.5	10	10
3	TsOH	0.5	10	Trace
4	HNO3^c	0.5	10	25
5	HCl^c	0.5	10	30
6	CF3COOH	0.5	10	36
7	HCOOH	0.5	10	41
8	C6H5COOH	0.5	10	30
9	CH3CH2COOH	0.5	10	76
10	ClCH2COOH	0.5	10	74
11	HOAc	0.5	10	80
12	HOAc	0.2	10	44
13	HOAc	1	10	59
14	HOAc	1.5	10	62
15	HOAc	2	10	60
16	HOAc	0.5	15	96
17	HOAc	0.5	20	95

^a Reaction conditions: the reactions were carried out using 1,2-diaminobenzene (1 mmol), benzaldehyde (1 mmol), and acid, grinding the reaction mixture.

^b Determined by GC with 1,4-dichlrobenzene as internal standard.

^c 98% H₂SO₄, 65–68% HNO₃, 37% HCl were used.

Table 2. Synthesis of benzimidazoles.^a

^a Reaction conditions: o-phenylenediamine, o-mercaptonoaniline or o-hydroxyaniline (1 mmol), aldehyde (1 mmol), acetic acid (0.5 mL) grinding 15 min at rt.

^b Isolated yield.

^c 20 min at rt.

Scheme 2. Explore the reaction pathway.

Figure 2. Optimized geometry of transition state B.

Scheme 3. Proposed reaction mechanism.

Scheme 4. Reaction conditions: 1,2-diaminobenzene (5 mmol), benzaldehyde (5 mmol), acetic acid (2.5 mL), grinding 15 min.

Scheme 5. Synthesis of fenbendazole.