Chemoselective reactions of electrophiles with quinazoline amides; 3-alkylquinazoline-2,4-(1H,3H)-diones, and 2-arylquinazoline-4(3H)ones and their thioamide regioisomers

Abd El-Moneim, Mohamed; Megahed, Mohammed Ibrahim; Ali, Ibrahim Ahmed; Fathalla, Walid

doi:10.21608/ajbas.2025.399039.1263

Chemoselective reactions of electrophiles with quinazoline amides; 3-alkylquinazoline-2,4-(1H,3H)-diones, and 2-arylquinazoline-4(3H)ones and their thioamide regioisomers

Document Type : Original Article

Authors

¹ Chemistry Department, Faculty of Science, Port-Said University, Port Said, Egypt.

² Department of Physical Sciences, Faculty of Engineering, Port-Said University, Port-Said, Egypt

³ Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt

⁴ Department of Basic Sciences, Faculty of Engineering, Suez Canal University, Ismailia, Egypt

10.21608/ajbas.2025.399039.1263

Abstract

The study draws a solid theoretical basis governing the reaction of amides and thioamides with electrophiles to give either N, O or S- substitutions. This study was carried out on the model compounds quinazoline amides; 3-alkylquinazoline-2,4-(1H,3H)-diones and 2-arylquinazoline-4(3H)ones and their thioamide regioisomers. The normal behavior of amides represented by 3-alkylquinazoline-2,4-(1H,3H)-diones; amides react with soft electrophiles and gave N-substitution, while expected to give O-subsitution with hard electrophiles. For a special case structure feature represented by 2-arylquinazoline-4(3H)ones, the amide group specially O-atom of the lactim form contributes in a continuous conjugated system, extended by an almost planar aryl group at position 2. Amides react with both soft electrophiles and hard electrophiles to give O-substitution. Similarly, for thioamides the normal behavior represented by 3-alkyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones; thioamides react with soft electrohiles and gave S-substitution while expected to give N-subsitution with hard electrophiles. For a special case structure feature represented by 2-phenylquinazoline-4(3H)thione, the thioamide group specially S-atom of the thiol form contributes in a continuous conjugated system, extended by an almost planar aryl group at position 2. Thioamides react with both soft electrohiles and hard electrophiles to give S-substitution. This behavior was ruled by Hard-Soft Acid-Base Principle (HSAB Principle) and supported computational analysis and reported literature.

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