The organic synthesis of versatile hydrazones has proven to be an attractive alternative in the development of new pharmaceutics yet has received limited practical applications due to the their hydrolytic instability. Herein, we map the 2 transition state mechanism between hydrazides and aromatic aldehydes using a DFT approach which was then applied to reactions between INH and two [pyridine 3carbaldehydehydrazine] derivatives which are bonded to phenol at O2 of the acyl R'-C(=O)-group (syn-thonI) and H3 of the -NH-NH2 functional group (synthonII)respectively with benzaldehyde. However, since the use of DFT methods to model these reactions still entails large errors, even for hybrid density functional theory calculations, future studies should explore additional reaction pathways and integrate experimental data to enhance the study's accuracy. Hence, the mechanism should be tested on a wider range of cocrystals of INH with polyphenols.