Enamine Rearrangement of Pyridinium Salts to Indole Ring: A Combined Experimental and Molecular Modeling Study

N-Alkyl pyridinium (II) and N-alkyl isoquinolinium salts V undergo cyclization reaction when heated with sodium bicarbonate to give the corresponding indolizine derivatives III and VIa, VIb, VIc, VId, VIe, respectively, which undergo ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding indole derivatives IV and IXa, IXb, IXc, IXd, IXe, respectively. Molecular modeling tools including Molecular Mechanics using Augmented MM3 parameters followed by geometry optimization calculations in MO-G using PM3 parameters were performed to gain better understanding and more insights on the thermodynamic properties of the recyclization reactions of compounds IIa, IIb, IIc, IId, IIe, IIf, IIg to the corresponding IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg and IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg to the corresponding IVa, IVb, IVc, IVd, IVe, IVf, IVg. The results were in excellent agreement with the experimental data and hence were proven to be a good tool in explaining different yields % because of the steric and electronic effects of electron-withdrawing groups on the reactivity of the pyridine ring for nucleophilic attack.