Study On The C(2)/N(3) Cyclization Reaction Of3,4-Dihydropyrimidine-2(1H)-thiones/Octahydroquinazoline-2-thiones

In1893, Italian chemist Pietro Biginelli reported the synthesis of functionalized3,4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensationreaction of an aromatic aldehyde, urea, and ethyl acetoacetate. Since the Biginellireaction was reported, lots of catalysis are applied in Biginelli condensation reaction.With the development of organic chemistry, aldehyde, β-ketoestre, urea are greatlyextended and a series of new compands are afford. The octahydroquinazolines can beprepared by replacing β-ketoestre for5,5-dimethyl-1,3-cyclohexanedione. At thesame time, these nonplanar heterocyclic compounds have received considerableattention from the pharmaceutical industry because of their interesting multifacetedpharmacological profiles and biological actives.In this thesis, the recent developments in the synthesis of DHPMs,tetrazolo[1,5-a]pyrimidines and thiazolo[2,3-b]quinazolines are reviewed and twonew methods for the synthesis of tetrazolo[1,5-a]pyrimidines andthiazolo[2,3-b]quinazolines are described by the cyclization reactions through directfunctionalization of the pyrimidinethione core. The research results are summarizedbelow:1. An novel, versatile and cost-effective approach for tetrazolo[1,5-a]pyrimidinesand tetrazolo[1,5-a]quinazolines from cyclization reaction ofdihydropyrimidinethiones with sodium azide in the presence of mercuric acetate isdescribed. To compare this procedure with the conventional method, we carried outthe cyclization reactions through direct functionalization of the pyrimidinethione core,which obtained from Biginelli3,4-dihydropyrimidine-2-thiones or4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones.2. The novel thiazolo[2,3-b]quinazolines were prepared through directcyclization reactions from octahydroquinazoline-2-thiones with α-bromo-ketones,which provides a readily accessible multifunctionalized quinazoline template fordiversity oriented synthesis. This method has some advantages: short reaction time, simple procedures and base-free.