Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-<i>tert</i>-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, C 6 H 7 N 3 O·C 11 H 14 O 2 , 4- tert -butylbenzoic acid– N ′-(propan-2-ylidene)isonicotinohydrazide, C 9 H 11 N 3 O·C 11 H 14 O 2 , 4- tert -butylbenzoic acid– N ′-(butan-2-ylidene)isonicotinohydrazide, C 10 H 13 N 3 O·C 11 H 14 O 2 , 4- tert -butylbenzoic acid– N ′-(diphenylmethylidene)isonicotinohydrazide, C 19 H 15 N 3 O·C 11 H 14 O 2 , and 4- tert -butylbenzoic acid– N ′-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C 12 H 17 N 3 O 2 ·C 11 H 14 O 2 . 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.