Studies On Halogenation, Amidation, And Cyclization Reactions Under Mechanical Milling Conditions

Today,the development of organic synthetic chemistry has been growing into people's lives in all aspects,in which the synthesis and application of drugs is the most representative one.For some traditional synthesis,or synthesis of new compounds,chemists have always been making them more and more convenient for the synthesis of the target path.With a better understanding of life science and environmental science,the public's awareness of environmental protection has been generally improved.In this context, the "green chemistry" concept came into being.How to reduce the use of toxic reagents and reduce the emission of hazardous waste has become a major research goal for green synthetic chemistry.Among a good many green synthesis methods, mechanical milling has developed in recent years as a novel and promising method. This thesis is a research of green synthetic chemistry of small organic molecules under mechanical milling conditions.The main contents include the following four aspects.1.Bromination of 1,3-Diearbonyl Compounds,Substituted Phenols,Chaleones, and Azachalcones using Oxone/NaBr under Mechanical Milling Conditions.A series of 1,3-dicarbonyl compounds,substituted phenols,chalcones,and azachalcones,were brominated successfully using NaBr as bromine source and Oxone as the oxidant under mechanical milling conditions.Most substrates were converted into corresponding monobromides or dibromides quantitatively.Compared with traditional bromination methods,the reaction did not require any toxic organic solvents,base,Lewis acid,or other catalyst.The oxidant Oxone was non-toxic, harmless,cheap and easy to get.Also,short reaction time,high yields and selectivity and wide generality all make this method fully embodied the concept of green chemistry.2.CeCl₃·7H₂O/ZnX₂:A novel Reagent System for the Synthesis of Halohydrins from EpoxidesRing-opening reaction ofα,β-epoxy aryl ketones to halohydrins was achieved in good to excellent yields using zinc halides,including ZnCl₂,ZnBr₂,and ZnI₂,as halogen sources for the first time and mediated by CeCl₃·7H₂O under mechanical milling conditions.For the synthesis of chlorohydrins and iodohydrins,the reactions afforded anti-and syn-halohydrins exclusively in high yields,respectively,while the reaction of epoxides with ZnBr₂ afforded a mixture of syn/anti isomers.The advantages of mild reaction conditions,non-toxiticity and low cost of reagents,and simple isolation of the products make these ring-opening reactions more appealing and useful in organic synthesis.3.Direct Oxidative Amidation of Aldehydes with Anilines under Mechanical Milling Conditions.A simple and novel one-pot protocol to oxidize aryl aldehydes and anilines directly to amides was proposed in synthetic useful yields under mechanical milling conditions for the first time.Compared with the traditional liquid-phase reaction,this novel solvent-and metal catalyst-free procedure makes the synthesis of amides more efficient,low cost and eco-friendly.To the best of our knowledge,this is unprecedented.4.Selective Formation of Spiro Dihydrofurans and Cyclopropanes through Unexpected Reaction of Aldehydes with 1,3-Dicarbonyl CompoundsThe reactions of aldehydes with dimedone were performed mediated by DMAP/I₂ under mechanical milling conditions afforded unexpected products of dihydrofurans. When another 1,3-dicarbonyl compound,i.e.,1,3-indandione,was explored,a cyclopropane ring structure instead of dihydrofuran was formed under similar conditions.We also discussed this unusual reaction process and proposed a reasonable "one method,two paths" mechanism.These novel iodine-mediated oxidative cycloadditions provide a rapid and efficient route to the preparation of a variety of spiro dihydrofuran and cyclopropane derivatives.The non-use of expensive catalyst and toxic organic solvent,short reaction time and high yields,and surpring results make this protocol more charming.