Mechanistic Evaluation by Mass Spectrometry and Computational Modeling of the Reaction Between 2ABP and Thiourea for Formation of 4-phenilquinazoline

Author(s)

Eric Lobato Graef

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2022-08-12

Examining board members

Thiago Carita Correra; Célio Fernando Figueiredo Angolini; Daví Alexsandro Cardoso Ferreira

• Advisor: Thiago Carita Correra

Abstract

This work consists of a study of the reactional system developed by Wang et. al. (formation of 4-phenilquinazoline from the reaction between 2-aminobenzophenone and thiourea in dimethyl sulfoxide) with focus on the reaction mechanism and in the structural identification of the species involved. The original reaction and a few variations were reproduced and a combination of techniques was employed for the analysis of aliquots from the reaction medium and for the structural identification of some of the species present. These techniques include: ESI-MS (electrospray ionization mass spectrometry); CID (collision induced dissociation); HRMS (high resolution mass spectrometry); IRMPD spectroscopy (infrared multiple photon dissociation). The main species identified by Wang et. al. (m/z: 198; 207; 222; 223; respectively: 2- aminobenzophenone, 4-phenilquinazoline, an intermediary and a subproduct) were observed in mass spectra and their fragmentation patterns were obtained by CID and analyzed. Besides these species, it was also possible to study subproducts not previously reported. A computational modeling (with static electronic structure calculations) of the mechanism proposed by Wang et. al. for the original reaction was done as well. It included the construction of Gibbs free energy curves, as well as evaluations of the transition states involved and of the effects of Bronsted acid catalysis (for some of the steps) and of implicit solvation on the system. The calculations were performed using DFT (density functional theory). At last, attempts were made to accelerate this reaction by increasing the distance travelled by the ESI (electrospray ionization) droplets between the ESI source and the interior of the spectrometer, as previously observed for other reactions. The acceleration wasnt observed, however, it was possible to record good intensity spectra even with the droplets having to travel one meter under atmospheric pressure. Therefore, it was possible to assemble an experimental system capable of, in principle, promoting this kind of phenomena. (AU)

• FAPESP's process: 19/22047-5 - Mechanistic evaluation of carbodiimides by mass spectrometry
• Grantee: Eric Lobato Graef
• Support Opportunities: Scholarships in Brazil - Master