The Synthesis Of Novel 3,4-Dihydro-pyrimidin-(1H)-(thio)ones Derivatives Including Pyrazole Ring

3,4-Dihydropyrimidin-2(1H)-(thio)one and its'derivatives have an extensive application in the realm of antimicrobes, antiviral, antitumor, anti-inflammatory, antibacterial and antimould due to their important therapeutic and pharmacological properties. They are usually used for synthesis of many peroral medicines, such as calcium channel blockers,α1a-antagonists and neuropeptide Y (NPY) antagonists, antihypertensive agents. Biginelli reaction is a significant path for synthesis of 3,4-Dihydropyrimidin-2(1H)-(thio)ones which have important pharmacological activities. More than 100 years has past since the Biginelli reaction was first reported by the Italian chemist Pietro Biginelli in 1893, which involves the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by a very simple one-pot condensation reaction of an aldehyde, acetoacetic ester and urea in the presence of a strongly hydrochloric acid as a catalyst. Biginelli reaction has become an important branch in area of the organic synthesis after more than one hundred years development. Consequently, several improved procedures of Biginelli reaction have been reported, various Lewis acid catalysts, solid phase synthesis, ionic liquid and ultrasonic, microwave accelerate means, and so on. Besides, participants of Biginelli reaction also have many changes, different types of aliphatic aldehyde, aromatic aldehyde, substituted urea and thiourea and new style 1,3-dicarbonyl compounds used in Biginelli reaction have been reported recently.Pyrazole derivatives represent important physiological and pharmacologic activities, such as antisepsis, antiphlogistic, adjusting plant growth and anti-platelet aggregation, so they're a significant class of compounds in the realm of medical and agricultural chemicals, which have very strong exploitation prospect. In order to obviously improve or intensify the biological activities of products, we designed and have synthesized a series of novel 3,4-dihydropyrimidin-2(1H)-(thio)one derivatives which containing pyrazole ring systems through Biginelli reaction. These kinds of compounds have wided applicative prospect of 3,4-dihydropyrimidin-2(1H)-(thio)one derivatives. They have extended the research fields of such compounds and provided abundant leading compounds for later selecting work of effective drugs.This thesis consists of two major parts:The first part is about literature review. The progress in application and synthesis of 3,4-dihydropyrimidin-2(1H)-(thio)ones, Biginelli reaction, pyrazole derivatives and the application and development of ultrasonic radiation, microwave accelerate in the Biginelli reaction were systematic exposition. The second part is about experimental content. Major work aork as follows:1 Synthesis of novel 4-substituted pyrazolyl-3,4-dihydropyrimidin-2(1H)-(thio)ones using 5-chloro/phenoxyl-4-formyl-3-methyl-1-phenylpyrazole as substrates and employing Mg(ClO4)2 as the catalyst by the Biginelli reaction. Comparison of the conventional refluxing method and ultrasonic radiation accelerate means, discussed for the results.2 Synthesis of novel 4-substituted pyrazolyl-6-substituted phenyl-3,4-dihydropyrimidin- 2(1H)- (thio)ones using 5-chloro-4-formyl-3-methyl-1-phenyl pyrazole as substrates, reacted with urea, thiourea, sis substituted thiourea and four substituted acetophenone, employing Mg(ClO4)2 as the catalyst by the Biginelli reaction.The innovations of the thesis are based on the follows:1 4-substituted pyrazolyl-3,4-dihydropyrimidin-2(1H)-(thio)ones, 4-substituted pyrazolyl-6- substituted phenyl-3,4-dihydropyrimidin-2(1H)-(thio)ones were synthesized unreported in the literatures;2 Eight novel 4-(5-chloro-3-methyl-1-phenylpyrazole-4-yl)-3,4-dihydropyrimidin-2(1H)-(thio) one derivatives have been synthesized from the reaction of 5-chloro-4-formyl-3-methyl- 1-phenylpyrazole with urea, thiourea and four substituted 1,3-dicarbonyl compounds; Eight novel 4-(5-methoxyl-3-methyl-1-phenylpyrazole-4-yl)-3,4-dihydro-pyrimidin-2(1H)-(thio) one derivatives have been synthesized from the reaction of 5-methoxyl-3-methyl-1- phenyl-4-formylpyrazole with urea, thiourea and four substituted 1,3-dicarbonyl compounds;3 Thirty two novel 4-(5-chloro-3-methyl-1-phenylpyrazole-4-yl)-6-substituted phenyl-3,4- dihydropyrimidin-2(1H)-(thio)one derivatives have been synthesized from the reaction of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with four substituted acetophenone and urea, thiourea, six substituted thiourea.