α-Chymotrypsin-catalyzed synthesis of 2-substituted benzimidazole through retro-Claisen reaction

Figures & data

Table 1. Catalytic activities of different enzymes.^a

Entry	Catalyst	Yield (%)^b
1	No enzyme	0
2	α-Chymotrypsin	93
3	Pepsin from porcine gastric mucosa	45
4	Lipase from porcine pancreas	48
5	Protease from A. saitoi	23
6	Amano Lipase from P. fluorescens	11
7	Amano Lipase M from M. javanicus	14
8	Protease from B. licheniformis	10
9	Albumin from bovine serum	0
10	Papain from papaya latex	<1
11	Amano Lipase A from A. niger	<1
12	Amano Lipase PS from Burkholderiacepacia	<1
13	Amano Acylase	<1
14	Lipase B from C. antarctica	<1
15	Denatured α-Chymotrypsin^c	0

^aReaction conditions: o-phenylenediamine (0.25 mmol), β-ketoester (0.25 mmol), enzyme (10 mg), ethanol (2 mL), 50°C, 18 h; ^bYield of isolated compound; ^cPretreated with urea at 100°C for 8 h.

Figure 1. Influence of temperature on the model reaction^a. Notes: ^aConditions: o-phenylenediamine (0.25 mmol), β-ketoester (0.25 mmol), α-Chymotrypsin (10 mg), ethanol (2 mL). ^bYield was determined by HPLC.

Table 2. α-Chymotrypsin catalyzed synthesis of 2-substituted benzimidazole.^a

^aReaction conditions: o-phenylenediamine (0.25 mmol), β-ketoester (0.25 mmol), α-chymotrypsin (10 mg), ethanol (2 mL), 50°C, 18 h.

^bYield was determined by column chromatography.

Scheme 1. Probable mechanism of α-chymotrypsin-catalyzed retro-Claisen reaction.