Gonzalez et al. recently reported new modifications of INH cocrystals synthesised from isoniazid (INH) with various polyphenolic coformers such as catechol (CAT), orcinol (ORC), 2-methylresorcinol (MER), pyrogallol (PYR), and phloroglucinol (PLG). Our study focuses on the phenol-pyridine heterosynthons embedded within these cocrystals, where synthonI is derived from an isoniazid-orcinol cocrystal crystallizes in a monoclinic P21/n space with one molecule of INH and one molecule of ORC in the asymmetric unit. The orcinol molecule is hydrogen bonded to two INH molecules by identical O2-H32-O33 bonds (see While many experimental and theoretical work on the reaction between hydrazides and aromatic aldehydes have been conducted previously, no literature provides a comprehensive outline of the mechanism. Therefore, we employed computational DFT calculations to further understand the mechanism shown in Fig. . All transition states were verified based on their negative imaginary frequencies. The intial transition state commences by a proton-catalyzed attack of the α-effect nucleophile on the carbonyl carbon atom of electrophile, resulting in the deprotonation of either of atoms H6/H7 from the NH2 group of [pyridine-4-carbaldehyde]phenylhydrazide to O10 of benzaldehyde's functional -CHO group. Upon proton transfer, a C-N bond between the nitrogen atom of the [pyridine-4-carbaldehyde]phenylhydrazide and the carbonyl carbon of benzaldehyde is formed to generate the hemiaminal/tetrahedral intermediate. The partial negative charge on O10 is then stabilized by resonance with the adjacent benzene ring.