Org. Synth. 1939, 19, 12
DOI: 10.15227/orgsyn.019.0012
BENZIMIDAZOLE
Submitted by E. C. Wagner and W. H. Millett.
Checked by W. W. Hartman and G. W. Sawdey.
1. Procedure
In a 500-cc. round-bottomed flask 54 g. (0.5 mole) of o-phenylenediamine (Note 1) is treated with 32 cc. (34.6 g.) of 90 per cent formic acid (0.75 mole) (Note 2). The mixture is heated in a water bath at 100° for two hours. After cooling, 10 per cent sodium hydroxide solution is added slowly, with thorough mixing by rotation of the flask, until the mixture is just alkaline to litmus. The crude benzimidazole is collected with suction in a 75-mm. Büchner funnel; ice-cold water is used to rinse all solid out of the reaction flask. The crude product is pressed thoroughly on the filter, washed with about 50 cc. of cold water, and then purified without previous drying (Note 3).
The benzimidazole is dissolved in 750 cc. of boiling water in a 1.5-l. beaker. The solution is digested for fifteen minutes with about 2 g. of Norite and filtered rapidly through a well-heated filter (Note 4). The filtrate is cooled to 10–15°, and the benzimidazole is filtered and washed with 50 cc. of cold water. The white (Note 5) product is dried at 100°. The melting point is 170–172°, and the yield is 49–50.5 g. (83–85 per cent of the theoretical amount) (Note 6) and (Note 7).
2. Notes
1.
The
o-phenylenediamine used was a good grade of commercial material, m.p.
99–101°. The
hydrochloride can be used with or without addition of
sodium formate. Directions for preparing
o-phenylenediamine are given on
p. 501.
2.
The yield is not greatly affected if the amount of
formic acid is decreased almost to the theoretical, but a safe excess is recommended to ensure utilization of the
o-phenylenediamine.
Formic acid of considerably less than 90 per cent concentration will form
benzimidazole; good yields were obtained with
40 per cent acid.
3.
The crude
benzimidazole, if dried at 100°, weighs
57.5–59 g. (
97–99 per cent of the theoretical amount), melts at
167–168°, and is yellow tinged. This discoloration is difficult to remove and persists after two crystallizations
(Note 5).
4.
The solution is almost saturated when boiling, and crystallization begins at once on cooling. The filter must be thoroughly heated and filtration must be rapid, or crystallization will occur in the filter.
5.
If the crystallized
benzimidazole is discolored, the following treatment will yield a good product. The
benzimidazole is dissolved in boiling water (13 cc. per gram), and a strong solution of
potassium permanganate is added until the liquid becomes opaque owing to the precipitated brown
oxide of manganese. To the hot mixture solid
sodium bisulfite is added until clarification results.
Decolorizing carbon is introduced, and the mixture is digested for fifteen minutes and filtered hot. The recovery is
90–92 per cent.
6.
A small additional amount (
2–2.5 g.) can be obtained by evaporation of the mother liquor to about 30 cc.
7.
This is a general method of preparing benzimidazoles. Using an equivalent of
acetic acid (45 g.) in place of
formic acid,
2-methyl-benzimidazole, m.p.
172–174°, can be prepared in
68 per cent yield.
3. Discussion
Benzimidazole has been prepared from
o-phenylenediamine by the action of
chloroform and alcoholic
potassium hydroxide1 and of
formic acid,
2 and by the reduction of
o-nitroformanilide.
3 Less serviceable methods include the interaction of
o-phenylenediamine and
dichloromethylformamidine,
4 or
diphenylformamidine,
5 or
formoacetic anhydride,
6 and the thermal decarboxylation of
benzimidazole-2-carboxylic acid.
7 The procedure described was developed
8 from that of Wundt.
2
The conversion of aliphatic acids to
2-alkylbenzimidazoles, by heating with
o-phenylenediamine, has been proposed as a general method for preparing solid derivatives for identification.
9This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
oxide of manganese
formoacetic anhydride
acetic acid (64-19-7)
sodium hydroxide (1310-73-2)
chloroform (67-66-3)
potassium permanganate (7722-64-7)
formic acid (64-18-6)
sodium bisulfite (7631-90-5)
decolorizing carbon,
Norite (7782-42-5)
potassium hydroxide (1310-58-3)
sodium formate
Benzimidazole (51-17-2)
dichloromethylformamidine
diphenylformamidine
benzimidazole-2-carboxylic acid
o-Phenylenediamine (95-54-5)
2-methyl-benzimidazole (615-15-6)
o-nitroformanilide
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