A Deep Insight into the Application of Linear Free Energy Relationships (LFER) to Five Membered Heterocyclic Ring Systems: A Chemical Education Review for Graduate Students

Sanjeev Rachuru¹ and V. Jagannadham^2,

¹Department of Chemistry, St. Ann's College for Women, Mehdipatnam Hyderabad-500028, India

²Department of Chemistry, Osmania University, Hyderabad-500007, India

Cite this paper:
Sanjeev Rachuru and V. Jagannadham. A Deep Insight into the Application of Linear Free Energy Relationships (LFER) to Five Membered Heterocyclic Ring Systems: A Chemical Education Review for Graduate Students. World Journal of Chemical Education. 2025; 13(3):65-90. doi: 10.12691/wjce-13-3-5

Abstract

Hammett and Taft equations are applied to the acid dissociation equilibriums of 4 and 5-substituted furan, pyrrole, thiophene, tellurophene, isoxazole, pyrazole carboxylic acids, to solvolysis data of 4 and 5-substituted-2-furylmethylcarbinyl p-nitrobenzoates and to the permanganate ion oxidation of 5-substituted-2-furfurals. Excellent correlations were observed in these studies except in the case of 1-Me-4/5-X-3-pyrazole-COOH. In the case of 5-X-2-furoic, pyrrole, thiophene carboxylic acids only the substituent -COOH deviated from these correlations for which possible explanation is given in terms of intramolecular hydrogen bonding between the -COOH and the ring heteroatom and two types of intramolecular hydrogen bonding between -COOH and ring nitrogen atom and -COOH and H of NH of pyrrole. In the case of 3,5-X-4-isoxazole carboxylic acids the -NH₂ group at 5 position deviated for which the explanation in terms of H-bonding between -NH₂ and -COOH is given. Even the possibility of the formation of zwitterion is not ruled out. 5-X-1,2,3-triazole-4-carboxylic acids did not follow any LFER. The solvolysis rate constants of both 4 and 5-substituted-2-furylmethylcarbinyl p-nitrobenzoates correlated well with para substituent constants. Further the correlation with Brown’s σ⁺ values is still better. It is noteworthy that MnO₄^- oxidation of 5-X-2-furfural correlated well with all the para, meta and ortho substituent constants. An attempt is made for the first time by our laboratory to apply the LFER to 5 membered ring systems with one heteroatom viz. pyrroles, two heteroatoms viz. pyrazoles, imidazoles, isoxazoles, three heteroatoms viz. the triazoles and four heteroatoms viz. tetrazoles. For the first time we have shown that the pK_a values of N(1)H-acidities of 3-X-pyrroles, 3-X-pyrazoles, 4-X-pyrazoles, 4-X-imidazoles, 3-X-1,2,4-triazole, 4-X-1,2,3-triazole and 5-X-1,2,3,4-tetrazoles correlated well with Hammett σ values.

Keywords:
Hammett equation Taft equation 5-membered heterocycles

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