Preparation of lactams from aliphatic alpha , omega -dinitriles

摘要

A process for the preparation of five-membered or six-membered ring lactams from aliphatic alpha , omega -dinitriles has been developed. In the process an aliphatic alpha , omega -dinitrile is first converted to an ammonium salt of an omega -nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the omega -nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate omega -nitrilecarboxylic acid or omega -aminocarboxylic acid. When the aliphatic alpha , omega -dinitrile is also unsymmetrically substituted at the alpha -carbon atom, the nitrilase produces the omega -nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the omega -nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.