Kinetics and Mechanism of the Base-Catalysed Cyclisation of 2-(Substituted benzoylamino)benzamides Giving Quinazolin-4-one and Quinazolin-4-thione Derivatives

• Published in: European journal of organic chemistry Vol. 2002; no. 11; pp. 1855 - 1863
• Main Authors: Hanusek, Jiří, Sedlák, Miloš, Šimůnek, Petr, Štěrba, Vojeslav
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.06.2002; WILEY‐VCH Verlag GmbH; Wiley
• Subjects: Chemistry; Chemistry, Organic; Cyclisations; Kinetics; Nitrogen heterocycles; Physical Sciences; Science & Technology; Sulfur; SUBSTITUTION; cyclisations; nitrogen heterocycles; HYDROLYSIS; REACTIVITY; sulfur; IONS; ACYL; kinetics; ALKALI-METAL ETHOXIDES; METHANOLYSIS; ACIDITY
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/1099-0690(200206)2002:11<1855::AID-EJOC1855>3.0.CO;2-A

Acylation of 2‐aminobenzamide and 2‐(methylamino)benzamide with substituted benzoyl chlorides in acetone has been used to prepare the respective 2‐(substituted benzoylamino)benzamides 1a−i, which were then subjected to sodium methoxide catalysed ring closure to give the respective 2‐(substituted phenyl)quinazolin‐4‐ones 2a−i. The kinetics of the cyclisation reactions were monitored by UV/Vis spectroscopy at 25 °C in methanolic solutions of sodium methoxide. In the case of 2‐(substituted benzoylamino)benzamides 1a−i and 2‐(substituted benzoylamino)thiobenzamides 3a−j, non‐linear dependences of observed rate constants kobs on the sodium methoxide concentrations were obtained, the shape of them being typical of a reaction with rapid pre‐equilibrium. All the cyclisation reactions satisfactorily obeyed the Hammett correlation. In the case of 2‐[(benzoyl)(methyl)amino]benzamides 1e−i, increasing sodium methoxide concentration resulted in a progressive increase in kobs values which is probably due to formation of dianion. In the case of 2‐(substituted benzoylamino)thiobenzamides 3b and 3h, which differ in the presence of a methyl group on the nitrogen atom the values of the activation Gibbs energy ΔG‡25 °C, activation enthalpy ΔH‡25 °C, and activation entropy ΔS‡25 °C for their respective cyclisations to 2‐(substituted phenyl)quinazoline‐4‐thiones 4b and 4h were determined. Whereas the ΔG‡25 °C values were very close for the two substances, the ΔH‡25 °C and ΔS‡25 °C distinctly differed. This was interpreted by the enthalpy and entropy factors operating against each other in the cyclisation. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)