STRUCTURE-PROPERTY RELATIONSHIP IN SUBSTITUTED BENZENES: MULTIFIDELITY METHODS TO QUANTIFY AND UNDERSTAND INTERACTIONS AMONG SUBSTITUENTS ON THE BENZENE RING

Vecchio Ciprioti S.⁽¹⁾, Silva Ferraz J.M.⁽¹⁾, Samarov A.A.⁽²⁾, Verevkin S.P.⁽³⁾

⁽¹⁾ Sapienza University of Rome

00161, Rome, Italy, Via del Castro Laurenziano, 7

⁽²⁾ Saint Petersburg State University

198504, Saint Petersburg, Russia, University Embankment, 7

⁽³⁾ University of Rostock

18059, Rostock, Germany, Dr.-Lorenz-Weg, 1

Derivatives of benzene bearing electron-withdrawing or electron attracting substituents occupy a prominent position in synthetic organic chemistry, food chemistry, pharmaceutical science, energetic materials research, and, ultimately, in chemical thermodynamics [1]. A classical challenge in physical organic chemistry is the quantitative assessment of steric versus electronic interactions between neighboring groups in aromatic systems or the effect of the introduction of one or more groups into the aromatic ring as both can significantly alter its properties [2]. Whereas electron-donating groups make the benzene ring more reactive towards electrophilic aromatic substitution, while electron-withdrawing groups make it less reactive [3], being the extent of reactivity be assessed by determining their thermodynamic parameters.

A comprehensive study of the thermodynamic properties of methyl-, mono- and dinitro-substituted benzoic acids was carried out using various methods: thermogravimetry (under both isothermal and non-isothermal conditions), differential scanning calorimetry, combustion calorimetry, and transpiration method. In addition, complementary quantum chemical (high-fidelity) and empirical (low-fidelity) methods were employed to cross-validate the results obtained. This multifidelity approach is essential for the benchmarking of thermodynamic properties.

1. Johnson C.D., The Hammet Equation // Cambridge University Press. London. 1973.

2. Verevkin S.P., Zaitsau D.H., Emel’yanenko V.N., Stepurko E.N., Zherikova, K.V. Benzoic acid derivatives: Evaluation of thermochemical properties with complementary experimental and computational methods. Thermochim. Acta. 2015. Vol. 622, P. 18–30. https://doi.org/10.1016/j.tca.2015.03.026

3. Silva Ferraz J.M., Emel’yanenko V.N., Zaitsau D.H., Samarov A.A., Brunetti, B., Ciccioli A., Vecchio Ciprioti S., Verevkin S.P. Thermodynamic Insights on the Structure-Property Relationships in Substituted Benzenes: Are the Pairwise Interactions in Tri-Substituted Methyl-Nitro-Benzoic Acids Still Valid? Chem. Plus. Chem. 2025. Vol. 90, P. e202400703. https://doi.org/10.1002/cplu.202400703

Project funded under the National Recovery and Resilience Plan (NRRP) - NextGenerationEU, Mission 4, Component 1, Investment 3.4, 4.1, CUP B53C23001630006.