Study And Application Of Green Methodologies For Halogenation By DCDMH/DBDMh

In the second half of the20th century, green chemistry, that aims to improve the reasonable usage of chemicals and reduce hazardous substances and environmental pollution, rised rapidly and became the focus and cutting edge of chemical research. Based on this background, it is necessary for people to re-think and re-examine the organic halogenation from a new point of view, which is one of the oldest basic reactions in the research history of organic chemistry. On one hand, organic halides are a class of useful compounds that are extensively used to play important roles in many fields. On the other hand, halogenation is viewed as one of the reactions that can not meet the requirements of green chemistry by many organic chemists, governmental safety management, chemical companies and the general public. Some reagents that are usually used in the halogenation and some places where halogenation reactions are carried out for research or manufacturing are the key monitoring targets of the governmental safety department. So it has academic and practical significance to research various kinds of green halogenations.From the point of view of green chemistry, a-brominations and chlorinations of carbonyl compounds are systematically studied in this dissertation.1,3-Dibromo-5,5-dimethylhydantoin (DBDMH) and1,3-dichloro-5,5-dimethylhydantoin (DCDMH) that are cheap general merchandises with low toxicity are used as halogenating reagents and acetophenones are selected as the main tested substrates in this study. On the basis of the brominations and chlorinations mentioned above, green methods to prepare a-fluoroacetophenones are also studied to find a new way of conversion of acetophenones or a-bromoacetophenones to a-fluoroacetophenones. This dissertation may provide some theoretical and practical references for academic research and application of green halogenations.This dissertation is divided into four chapters and the details are as follows:Chapter One:firstly, the basic elements of green chemistry are outlined and the research progresses in four fields that are green reagents, high selective reactions, high efficient reactions and green media are described. Secondly, the current situation and research progresses of brominations, chlorinations and fluorinations are partly introduced according to the different types of halogenating reagents. On this basis, the main idea of this dissertation is clarified.Chapter Two:the brominations of carbonyl compounds using DBDMH in various green media are systematically studied. Firstly, aliphatic ketones and β-ketoesters are tested to extend the application scope of the p-TsOH-CH3OH brominating system. Secondly, a reusable brominating system that makes use of water, methanol and acid is developed and some carbonyl compounds and aromatic compounds are tested. This system can reduce the emissions of strong acids. Thirdly, a bromination reaction that is carried out in a new deep eutectic solvent (DES) that prepared from tetrabutyl ammonium bromide (TBAB) is developed and the yields of a-bromoacetophenones are75-80%. Fourthly, a no-solvent bromination reaction catalyzed by an ion exchange resin is developed. Fifthly, a rapid non-acid brominating reaction is realized, in which silica gel and methanol are used and the brominated products are obtained with the yields of90～96%. Finally, on the basis of analysis of these green brominations, the bromination in DES is used in the synthesis of an important antimicrobial, difenoconazole. The intermediate,1-(4-(4-chlorophenoxy)-2-chlorophenyl)-2-bromoethanone is obtained in high yield of97%by the new method that replaces the usage of elemental bromine. On the basis of this new method, difenoconazole is finally prepared by a five-step routine.Chapter Three:Some chlorination reactions with high selectivity that are close to the requirements of green chemistry are developed by DCDMH. Firstly, a-monochlorination of acetophenones in a new DES that is prepared from choline chloride and p-TsOH is studied and a-chloroacetophenones are obtained in the yields of75～82%. Secondly, on the basis of the a-monochlorination in DES, rapid α,α-dichlorination with high efficiency is developed and after only45min, a,a-di chloroacetophenones are obtained in high yields of86～96%with high selectivity. Thirdly, a rapid a-monochlorination of carbonyl compounds with high efficiency is developed, in which silica gel is used as catalyst and methanol is used as solvent, and a-chloroacetophenones are obtained in high yields of92～98%with high selectivity. The intermediate with O-Cl structure may involve in the mechanism of this a-mono chlorination. The a,a-dichlorination catalyzed by DES and a-mono chlorination catalyzed by silica gel are complementary and they forms a set of solutions for the selectivity of chlorination. Finally, on the basis of bromination in water, three chlorinations of aromatic compounds that are carried out in water or catalyzed by common salt are developed and the yields of chlorinated compounds are not bad. These three chlorinations are also complementary and they are also an effective, cheap and green set of solutions for aromatic chlorination.Chapter Four:on the basis of nucleophilic fluorination, a group of fluorinations that include a one-pot method are developed using fluoride salt. Firstly, a fluorination is realized using PEG-400as co-solvent, KF as nucleophilic source and acetonitrile as solvent and a-fluoroacetophenones are obtained. Secondly, a new nucleophilic fluorinating method that use TBAF-3H2O/ZnF2/KF as mixed fluorinating source is realized and a-fluoroacetophenones are obtained in the yields of60～90%. Thirdly, on the basis of the two nucleophilic fluorinations mentioned above, a new method in DES that formed between choline chloride and p-TsOH is realized and a-fluoro acetophenones are obtained directly from acetophenones by nucleophilic strategy. The chlorination and fluorination are carried out in just one flask, which is commonly realized by electrophilic reagents. Fourthly,1-(2-bromo-1,1-dimethoxyethyl) benzenes are tested in the nucleophilic fluorination and a-fluoroacetophenones are obtained directly. Further, an aromatic fluorination in a new DES is also developed. Finally, N,N’-bis(1-phenylethylidene)ethane-1,2-diamines and N-(2-fluoro-l-phenyl ethylidene)-1-phenylethanamine are prepared by DES that formed between choline chloride and p-TsOH. These two compounds are important in the R&D of medicine and pesticide.