微波条件下NH_4CI催化合成3，4-二氢嘧啶-2-酮的研究
作者：戴冲之
院校:南京工业大学
关键字:微波辐射;有机合成;Biginelli反应;3,4-二氢嘧啶-2-酮氯化钱
学位：硕士
专业:应用化学
摘要:
近年来，微波辐射作为一种有效的热源正广泛应用于化学各个领域，尤其在有机化学领域。本课题综述了微波辐射对有机反应的作用机理和特点及微波技术在有机合成中研究和应用的进展情况。通常在常规加热情况下需要较长回流时间才能完成的反应可在微波反应器中方便、快速地完成。与常规加热相比，微波辐射往往具有反应时间短、产率高、产品纯度较高、操作简便等优点，因而，微波用于活化有机反应前景广阔。迄今研究过并取得明显效果的有机合成反应有：酯化和皂化、氧化、水解、加成、取代、缩合、烃基化、重排、Diels-Alder反应、Reformatsky反应、Knovenagel反应、Perkin反应、Deckman反应、保护及脱保护、协同反应、环化与开环、成醚等反应。 从1986年至今，微波促进有机反应的研究已发展成为一门引入注目的全新领域—MORE化学(Microwave-Induced Organic Reaction Enhancement Chemistry)。 1893年Biginelli首次报道了乙酰乙酸乙酯、芳香醛和脲在浓盐酸催化下于乙醇中加热回流18h得到了3，4-二氢嘧啶-2-酮衍生物，这一合成法称为Biginelli反应。近十年来，研究发现3，4-二氢嘧啶-2-酮化合物具有与1，4-二氢吡啶衍生物相似的药理活性，如钙拮抗剂、降压剂、α_(13)-拮抗物等。因此，Biginelli反应的研究引起了人们的极大重视，3，4-二氢嘧啶-2-酮衍生物的合成法及反应研究正逐渐成为生物活性有机杂环化合物研究的热点之一。 以往进行的Biginelli反应都不同程度地存在一些缺点，如较长的反应时间、较高的反应温度、强酸性的反应环境和较大的催化剂用量，以及有些催化剂的不易得到等，使Biginelli反应的应用受到了一定的限制。 在以往的文献报道中，并未有人在微波辐射下的Biginelli反应中使用NH_4Cl作为催化剂。我们发现，NH_4Cl作为一种温和且易于获得的催化剂，可以高效地催化Biginelli反应，同时对环境友好。本文将微波方法用于传统的Biginelli反应，使用氯化铵作为催化剂，在微波作用下合成3，4-二氢嘧啶-2-酮衍生物衍生物。反应在适当的功率下平稳、快速地完成。结果表明：反应时间极大缩短，反应产率均有提高。该法可拓展用于合成一系列具有生理活性的3，4-二氢嘧啶-2-酮类化合物。 戴冲之:微波条件下NH4CI催化合成3，4一二氢啥咤·2一酮的研究 2004年5月 以氯化按作催化剂，乙醇作溶剂，将乙酞乙酸乙(甲)酉旨、芳香醛和尿素 (硫脉)用微波辐射，在4min左右发生缩合反应，重结晶后得到30种3，4一二 氢心咙一2一酮化合物，收率在64一93%。其中十一种产品未见文献报道，经熔点测 定、IR、‘I叫INMR分析验证了其结构的正确性。当前研究为该种有机反应提供了 一种简便、节能、有效的方法，显示了微波技术在有机合成中潜在的价值。
Abstract:
During the last few years, microwave irradiation as an efficient thermal energy source is becoming a standard technique in various fields of chemistry, especially in the application in organic chemistry .The catalytic mechanism and characteristic of the microwave irradiation to organic reactions and the recent progress in the research and application of the microwave technique in organic synthesis are reviewed. Synthesis of chemical compounds which normally require long reflux time can be achieved conveniently and very rapidly in microwave oven. Compared with the classical heating methods as reported in literature, the benefit of microwave irradiation includes short reaction time, high yields, pure products and easy workup. The use of microwave energy to activate organic reactions has been taking a new dimension very recently. It has been used for a great variety of organic reaction as esterification and saponification, sulfonation, oxidation, hydrolysis, olefm addition, replacement, condensation, alkylation , rearrangement, Diels-Alder reaction, Reformatsky reaction, Knovenagel reaction, Perkin reaction, Deckmann reaction, Witting reaction, Bischler-Napieraski reaction, Protection and deprotection, concerted reaction, cyclization and ring-opening, etherification, etc. The Biginelli reaction, which was first reported by Biginelli more than a centry ago, involves the synthesis of 3,4-dihydropyrimidin-2-(lH)-ones by a very simple one pot condensation reaction of ethyl acetoacetate, benzaldehyde and urea in ethanol. In the past decade, dihydropyrimidinone derivatives have exhibited important pharmacological properties, e.g. as the integral backbones of several calcium channel blockers, antihypertensive agents, alpha-la-antagonists, and neuropeptide Y (NPY) antagonists. Now Dihydropyrimidinones are an important class of compounds which are becoming increasingly interesting due to their therapteutic and pharmacological activities. Recently, many synthetic methods for preparing these compounds have been reported by using Lewis acids as well as protic acid promoters such as: zirconium(IV) chloride, indium(III) bromide, ytterbium(III)-resin, eerie ammonium nitrate (CAN), Mn(OAc)3-2H2O, lanmanide triflate, indium(III) chloride, lanthanum chloride, HiSCM, HOAc, montmorillonite KSF, polyphosphate ester (PPE),13 BF3-OEt2/CuCl/HOAc, and cone. HC1. However, in spite of their potential utility, many of these methods involve expensive reagents, strongly acidic conditions, long reaction times, high temperatures and stoichiometric amounts of catalysts, and give unsatisfactory yields. Application of microwave irradiation in organic synthesis is becoming an increasingly popular technology because of its rapid reaction rates, cleaner reaction conditions and ease of manipulation. A study of the preparation 3,4-dihydropyrimidin-2-(lH)-ones with NtUCl as a very inexpensive and easily available catalyst under microwave irradiation has never been reported. As shown in the paper, this is a novel method that not only preserved the simplicity of Biginelli's one-pot reaction but also consistently produced 64-93% yields of the dihydropyrimidine-2-ones. In our attempt towards a non-traditional approach to the experimental set up of organic reactions, the concept of """"Microwave-Induced Organic Reaction Enhancement"""" (MORE) Chemistry has been utilized for rapid and efficient synthesis of 3,4-dihydropyrimidin-2-(lH)-ones. The reaction can be carried out by the condensation of ethyl acetoacetate, aromatic aldehyde and urea or thiourea in present of ammonium chloride as catalyst and ethanol as solvent under microwave irradiation. The results obtained demonstrate the versatility of the process as considerable reaction rate enhancement has been observed bringing down the reaction time form hours to minutes. The products obtained have improved yields with respect to conventional methods. The authenticity of the end products was established by their melting points and spectral data (IR, !HNMR). The present investigation thus provides a very simple,