Pyridine → HCID 178419409, compound

Participants

Reaction Steps

An arylhydrazine, e.g., 3-chloro-5-trifluoromethyl-2-pyridylhydrazine, 2,6-dichloro-4-trifluoromethylphenylhydrazine, or 2,4,6-trichlorophenylhydrazine, was reacted with either ethyl 2-ethoxymethyleneacetoacetate or ethyl 2-dimethylaminomethyleneacetoacetate to produce the corresponding 1-aryl-4-ethoxycarbonyl-1H-5-methylpyrazole. Hydrolysis of the ester group to the acid was followed by reaction of the acid group with thionyl chloride and sulfamide in sulfolane, producing the corresponding 4-cyanopyrazole. Monobromination of the 5-methyl group with N-bromosuccinimide was followed by reaction of the bromomethylpyrazole with pyridine to produce the corresponding N-pyrazolylmethylpyridinium bromide. The pyridinium bromide was then reacted with N,N-dimethyl-4-nitrosoaniline to form the corresponding 5-(4-dimethylaminophenyl-N-oxyiminomethyl)pyrazole. Hydrolysis of this latter intermediate with 6N hydrochloric acid yielded the corresponding 1-aryl-4-cyano-1H-5-formylpyrazole (1), an intermediate also used in the alternative synthesis described below. Reaction of this final intermediate with 2-aminooxypropionic acid yielded the 2-[(1-aryl-4-cyano-1H-5-pyrazolyl)methyliminooxy]propionic acid. Examples 1, 3, and 6 detail this synthetic route for different aryl groups. Ester derivatives were made by reacting the propionic acid compound with methanol, for example, in the presence of p-toluenesulfonic acid (Example 2 and Example 6, Step I) or with 3-chlorophenylmethyl bromide in the presence of potassium carbonate in toluene (Example 4).

Provenance & Evidence