Energy-Efficient Synthesis of Haloquinazolines and Their Suzuki Cross-Coupling Reactions in Propylene Carbonate

Comparative synthesis of some new quinazoline derivatives via tetrakis(triphenylphosphine)palladium(0) catalysed Suzuki-Miyaura cross-coupling reaction in "green" propylene carbonate (PC) and dimethoxyethane. Three haloquinazolines were synthesised for Suzuki-cross-coupling from 5-bromoanthranilic acid. Sufficient and easy method for the elimination of PC is developed, thus the optimization of the synthesis of some quinazoline derivatives was carried out. Reactions with 2-chloro-6-bromo-3-phenylquinazolin-4(3H)-one proceeded faster and with a higher yield in PC than in dimethoxyethane, thus for some reactants PC is a good choice for greener synthesis. Practical considerations for using PC include shorter reaction times, improved yields, and the elimination of unnecessary solvent distillation, leading to significant energy savings. This facilitates the execution of energy-efficient reactions in a notably environmentally friendly solvent. In contrast to DME, the use of PC does not necessitate special pre-treatments. Moreover, less PC is required due to its high boiling point and low volatility. Considering these properties, coupled with the consistent need for chromatographic purification, the use of PC in the Suzuki-Miyaura cross-coupling reaction emerges as a superior and greener alternative compared to DME. Comparing solvents propylene carbonate and dimethoxyethane in Suzuki-Miyaura cross-coupling reaction for the production of new quinazoline derivatives. From 5-bromoanthranilic acid, three haloquinazolines were produced for the synthesis, each bearing bromine in position 6 of the quinazoline ring. Using PC for shorter reaction times, improved yields and significant energy savings. image