Study On The “One-Pot” Preparation Of Trifluoromethylated Homoallylic N-Acylhydrazines Or α-Methylene-β-Trifluoromethyl γ-Lactams Promoted By Tin Powder

Fluorine-containing organic compounds have been extensively applied in pharmaceuticals, agrochemicals and materials science in recent years and received more and more attentions, The main reason is that hydrogen atoms of organic molecules are replaced by fluorine atoms can greatly change chemical properties, physical properties and biological activity of these parent compounds. Trifluoromethylated organic compounds represented a large part of the various fluorine-containing organic compounds. Trifluoromethyl group has been found in listing of many pharmaceutical and pesticide molecules, especially quite a few of them are chiral trifluoromethyl group. Hence, how to intruduce trifluoromethyl group into organic molecules has received extensively attentions and research in recent years. On the other hand, N-acylhydrazines are also one of the most important compounds in organic synthesis, and have been widely used in pesticide, medicine, materials science and so on. In particular, trifluoromethylated N-acylhydrazines were proved to be anticancer agents. So exploring synthesis of trifluoromethyl compounds show important theoretical and practical significances. The thesis consists of four parts: Chapter one: Research Progress in trifluoroacetaldehyde and derivatives as a trifluoromethyl building block.Traditioanl methods on how to make fluorine-containing organic compounds were summarized in this chapter based on the intruduction of application of trifluoromethylated organic compounds in pharmaceuticals, agrochemicals, materials science and other fields, then the applications of trifluoroacetaldehyde and its derivatives as a trifluoromethyl building block in organic synthesis were mainly reviewed. Chapter two: One-pot preparation of trifluoromethylated homoallylic N-acylhydrazines from acylhydrazines, trifluoroacetaldehyde methyl hemiacetal, allyl bromide and tin.In this chapter, we mainly studied one-pot reaction of acylhydrazines, trifluoroacetaldehyde methyl hemiacetal, allyl bromide and tin, and 17 trifluoromethylated homoallylic N-acylhydrazines were obtained. In this method cheap and commercially available aqueous trifluoroacetaldehyde methyl hemiacetal was used as trifluoromethyl bulding block, tin powder and allyl bromide formed organotin reagents in situ to directly react with acylhydrazones, which avoids the use of toxic organotin reagents. Our reaction has following advantages: high atom utilization, environment friendly, simple operation and high yield, which provides a new method for the synthesis of trifluoromethylated homoallylic N-acylhydrazines. Chapter three: One-pot preparation of α-methylene-β-trifluoromethyl-γ-la-cta-ms from acylhydrazines, trifluoroacetaldehyde methyl hemiacetal, ethyl 2-(b-romomethyl)acrylate and tin.α-methylene-γ-lactams show lots of bioactivities,such as cytotoxicity, antitum or and anti-inflammatory and exploring the synthesis of these compounds is of important theoretical and practical significance. This chapter mainly studied on e-pot reaction of acylhydrazines, trifluoroacetaldehyde methyl hemiacetal, ethyl 2-(bromomethyl)acrylate and tin, and 10 α-methylene-β-trifluoromethyl-γ-la-ctams were obtained. Our method has following advantages: raw material easily obtained, low cost, catalysis free, environmentally benign, simple operation and high yield, which provides a new method to prepare for α-methylene-β-trifluorometh yl-γ-lactams. Chapter four: Study on the Morita-Baylis-Hillman reaction of trifluorometh-ylated acyl hydrazonesMorita-Baylis-Hillman reaction is a atom economic reaction in the construction of C-C bond in organic synthesis. In this chapter, trifluoromethylated acyl hydrazones were used as a trifluoromethyl building block, and Morita-Baylis-Hillman reaction of methyl acrylate with trifluoromethylated acyl hydrazones was preliminarily explored.