Methods for the production of 2-halo-4-nitroimidazole and intermediates thereof

The process for the production of an antitubercular agent which comprises the steps of:

• (i) nitration of 4-nitroimidazole to obtain 1,4-dinitroimidazole with the aid of nitric acid in a mixture of acetic acid and acetic anhydride;
• (ii) thermally rearranging 1,4-dinitroimidazole into 2,4-dinitroimidazole without isolating and drying operations,
• (iii) reacting 2,4-dinitroimidazole wetted with a solvent with a chlorinating or bromating agent to obtain 2-halo-4-nitroimidazole, wherein the halogen is Cl or Br;
• (iv) reacting 2-halo-4-nitroimidazole with 2-methyloxiran-2-ylmethyl-4-nitrobenzoate;
• (v) reacting the compound obtained in step (iv) with methanesulfonyl chloride;
• (vi) ring closure of the compound obtained in step (v);
• (vii) reacting the compound of step (vi) with a compound of formula RH wherein
• to obtain a compound of formula (VII)
• wherein X—Cl or Br;
• and
• (viii) ring closure of the compound of formula (VIII) to obtain a compound of formula (VIII)

A process for the production of 2-halo-4-nitroimidazole comprising the steps of:

• (i) nitrating 4-nitroimidazole in a nitration reaction to obtain 1,4-dinitroimidazole;
• (ii) subjecting the 1,4-dinitroimidazole dissolved in or wetted with a solvent, without an isolating or drying operation, to a thermal rearrangement reaction to obtain 2,4-dinitroimidazole;
• and
• (iii) subjecting 2,4-dinitroimidazole to a halogenation reaction by halogenating the 2,4-dinitroimidazole wetted with a solvent for the thermal rearrangement reaction using a halogenating agent to obtain 2-halo-4-nitroimidazole.