The preparation of 4- and 6-chloro-2-chloromethylpyridine

6-Chloro-2-chloromethylpyridine is prepared from 6-chloro-2-methylpyridine by a route in which the 2-Me substituent was successively converted to 2-acetoxymethyl, 2-hydroxymethyl and finally to the required 2-chloromethyl substituent. Attempts to simultaneously monochlorinate the Me group and reduce the N-oxide function of 6-chloro-2-methylpyridine-N-oxide with methanesulphonyl chloride and p-toluenesulphonyl chloride gave only very small yields of 6-chloro-2-chloromethyl-pyridine. 4-Chloro-2-chloromethylpyridine is prepared from 2-methylpyridine-N-oxide by nitration, followed by substitution of the 4-nitro group by chloro using conc HCl; side chain chlorination of the 2-Me group using p-toluenesulphonyl chloride yields 4-chloro-2-chloromethylpyridine. Phosphoryl chloride reacts with 2-chloromethylpyridine-N-oxide hydrochloride to yield only 14.4% of 4-chloro-2- chloromethylpyridine, together with 2-chloromethylpyridine (2.2%), 2-dichloromethylpyridine (41.6%) and 6-chloro-2- chloromethylpyridine (41.8%). Attempts to N-oxidise 2-chloromethylpyridine with peracids led to either 2-hydroxymethylpyridine (peracetic, m-chloroperbenzoic and performic acid) or no reaction (pertrifluoroacetic acid); none of the peracids led to any detectable N-oxidation.