Economical, efficient, and environmentally friendly synthesis strategy of O-Alkylation strategy based on phenolphthalein reactions with electrophiles: Characterization, DFT study, and molecular docking

A new series of phenolphthalein derivatives were obtained by an esterification of diols function of phenolphthalein product. The synthesis of a series of (3, 3-bis (4-hydroxyphenyl)-2-benzofuran-1-one) derivatives ( R1 ) was carried out using O-alkylation reactions of phenolphthalein ( R1 ) with different electrophiles (4-toluenesulfonyl chloride ( 2a ), benzoyl chloride ( 2b ), and acetic anhydride ( 2c )) in basic medium without the use of catalysts. The synthesized compounds were characterized by 1H and 13C NMR spectroscopic techniques. The infrared (IR) and absorbance spectra show that the phenolphthalein derivatives remain stable in a basic medium with a weak adsorption band. Theoretical calculation results (DFT) are in good agreement with the experimental synthesis mechanisms. The theoretical in-silico toxicity study of the synthetic molecules shows that the products ( P1, P2 , and P3 ) are classified as environmentally friendly compounds. In addition, a molecular docking study was analyzed for compounds P1, P2 , and P3 with KSHV thymidylate synthase binding proteins (PDB: 5H38) using the Auto-Dock Vina program. Compound P2 showed-10.9 kcal/mol while compounds P1 and P3 showed a binding score of-10.0 kcal/mol.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of phenolphthalein derivatives were synthesized successfully through an esterification reaction of phenolphthalein. These derivatives remained stable in a basic medium and exhibited environmentally friendly properties. Theoretical and experimental results showed consistent synthesis mechanisms with computational calculations.