Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-tert-butylbenzoic acid with isoniazid and its derivatized forms.

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4-tert-butylbenzoic acid via a one-pot covalent and supramolecular synthesis, namely 4-tert-butylbenzoic acid-isoniazid, C6H7N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(propan-2-ylidene)isonicotinohydrazide, C9H11N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(butan-2-ylidene)isonicotinohydrazide, C10H13N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(diphenylmethylidene)isonicotinohydrazide, C19H15N3O·C11H14O2, and 4-tert-butylbenzoic acid-N'-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C12H17N3O2·C11H14O2. The co-former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan-2-one, butan-2-one, benzophenone and 3-hydroxy-3-methylbutan-2-one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.