Asymmetric Synthesis Of Nifenalol And The New Method And Its Application Of Dehalosenation Of α-haloketones

A wide variety of highly selective asymmetric reactions catalyzed by chiral(salen)metal complexes have been disclosed over the past decade. Salen ligands areamong the most synthetically accessible frameworks for asymmetric catalysts, andtheir structures are readily tuned both sterically and electronically. However, oneclasic chiral salen ligand has been demonstrated to be highly effective for a widevariety of useful asymmetric transformations catalyzed by different metals. Thesimplicity of this ligand, the high enantioselectivities and broad substrate generalityoften observed, and the synthetic utility of the catalytic transformations have inspiredsubstantial effort directed toward the commercial development of asymmetric salenchemistry.In this thesis, we completed the asymmetric synthesis of adrenergic drugsNifenalol; in the process of studying of Nifenalol, we discovered a new reaction:dehalogenation of α-haloketones;then we applied this reaction to the synthesis of4-methylcatechol.First, we synthesized the chiral (R,R)-Salen-CoIIIcatalyst according to theliterature; then using4-nitroacetophenone as a raw marerial, we obtained racemic4-nitrostyrene oxide through the brominating of copper (II) bromide and thereduction and ring-closing reaction with KBH4. Highly optical purity(R)-4-nitrostyrene oxide and (S)-1-(4-nitrophenyl)-1,2-ethanediol were prepared fromthe racemic4-nitrostyrene oxide of hydrolytic kinetic resolution(HKR), which wascontroled by the reaction time, the quilty of water and the reaction time using thechiral (R,R)-Salen-CoIIIcatalyst.(R)-Nifenalol was synthesized by nucleophilicring-opening reaction of (R)-4-nitrostyrene oxide with isopropylamine;(S)-1-(4-nitrophenyl)-1,2-ethanediol firstly treated with thionyl chloride to form4-(p-nitrophenyl)-1,2,3-dioxathiolane-2-oxide, and then via nucleophilic ring-openingof isopropylamine to obtained (S)-Nifenalol.We discovered that the desired product1-(4-nitrophenyl)-2-bromo-alcohol wasnot obtained,but high yield product4-nitroacetophenone was formed with zinc-ammonium formate-ethanol system in the precess of synthesizing Nifenalol.Whether the sistem have an effect on most substitutedα-haloketones or not? Theuse of sistem for reduction of a range of different α-halo-substituted phenyl ketone togive a high yield of corresponding ketone after dehalogenation. We tried to applythis reaction conditions to the reduction of α,α-dibromoacetophenone and benzylhalide that the high yield desired products were obtained.Finally,4-methylcatechol was synthesized by using1,2-dimethoxybenzene,which subjected to chloromethyl, reduction and demethylation.We also optimizd thereaction procedures.The structures of the above compounds and some intermediates were verified bymeans of IR,1HNMR.