ChemicalBook CAS DataBase List Clotrimazole

Clotrimazole synthesis

4synthesis methods

Product Name:Clotrimazole
CAS Number:23593-75-1
Molecular formula:C22H17ClN2
Molecular Weight:344.84

Clotrimazole, 1-(o-chloro-α,α-diphenylbenzyl)imidazole (35.2.21), is synthesized by reacting 2-chlorotriphenylmethylchloride (35.2.20) with imidazole in the presence of triethylamine.

The starting substance 2-chlorotriphenylmethylchloride is made in various ways. In particular, chlorinating 2-chlorotoluene under light makes 2-chlorotrichloromethylbenzene (35.2.22), which is reacted with benzene in the presence of aluminum chloride to give 2-chlorotriphenylmethylchloride (35.2.20).

An alternative way of making 2-chlorotriphenylmethylchloride is a Grignard reaction between 2-chlorobenzolphenone and phenylmagnesium bromide, followed by substitution of the hydroxyl group in the resulting 2-chlorotriphenylmethylcarbinol (35.2.23) with a chlorine using thionyl chloride.

And finally, reacting phosphorous pentachloride with 2-chlorobenzophenone gives 2- chloro-1,1-dichlorodiphenylmethane (35.2.24), which is used for the alkylation of benzene in the presence of aluminum chloride and gives 2-chlorotriphenylmethylchloride (35.2.20).

288-32-4 Synthesis

288-32-4
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102-10-3
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66774-02-5 Synthesis

CLOTRIMAZOLE IMP. A (PHARMEUROPA): (2-CHLOROPHENYL)DIPHENYLMETHANOL

66774-02-5
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108-10-1 Synthesis

108-10-1
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23593-75-1
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Yield:23593-75-1 100%

Reaction Conditions:

with sodium hydroxide

Steps:

6 Preparation of 1-(o-chlorophenyldiphenylmethyl)imidazole

EXAMPLE 6 Preparation of 1-(o-chlorophenyldiphenylmethyl)imidazole A mixture of methyl isobutyl ketone (60 ml), diphenyl phosphite (13.1 g), imidazole (5.44 g) and o-chlorophenyldiphenylmethanol (11.78 g) obtained in Example 1 (B) was heated at 85° C. for 4 hours. To the reaction mixture, a 10% aqueous sodium hydroxide solution (110 g) was added, and the mixture was refluxed for 1 hour. After cooling to room temperature, the organic layer was separated, washed with water and concentrated to dryness under reduced pressure to give 13.8 g of 1-(o-chlorophenyldiphenylmethyl)imidazole. Yield, 100%. M.P., 138°-142° C. Recrystallization from methyl isobutyl ketone gave 12.3 g of the pure compound. Yield, 89%. M.P., 142°-143° C.

References:

US4216333,1980,A

288-32-4 Synthesis

288-32-4
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$5.00/25g

42074-68-0 Synthesis