Synthesis And Process Optimization Of Florhydral

Designed two synthetic routes of Florhydral by retro synthetic analysis: 3-bromocumene was prepared from 4-isopropylaniline as raw material by the bromination and diazo-deaminate reduction,then Grignard reaction and Michael addition to obtain Florhydral(route 1);3-isopropylaniline by diazotization and Meerwein arylation to obtain Florhydaral(route 2).Explored effect of the temperature,amount of catalysts,molar ratio of material in Michael addition on route 1,the temperature,molar ratio of material,time in Meerwein arylation on route 2,and improved synthesis technology of key intermediate 3-bromocumene on route 1.The structure of main product Flohydral and key intermediate 3-bromocumene was characterized by IR,1H-NMR and MS.Research suggests that: 2-bromo-4-isopropylaniline is prepared from 4-isopropylaniline,the temperature of bromination is 25?,the molar ratio of 4-isopropylaniline and NBS is 1:1.1,the yield is 96%;3-bromocumene is prepared from 2-bromo-4-isopropylaniline,the temperature of diazotization is 0?,the molar ratio of 2-bromo-4-isopropylaniline and sulfuric acid is 1:3.0,the yield is 90%;Florhydral is prepared from 3-bromocumene via 3-isopropylphenylmagnesium bromide,the temperature of Michael addition is-30?,the molar percentage of copper(I)chloride is5%,the molar percentage of manganese(II)chloride is 30%,the molar ratio of manganese(II)chloride and lithium chloride is 1:2,the molar ratio of 3-bromocumene and crotonaldehyde is 1:1.0,the yield is 85%;the total yield of this route is 73%.Florhydral is prepared from 3-isopropylaniline via 3-isopropylphenyldiazonium fluoroborate,the temperature of Meerwein arylation is 30?,the molar ratio of diazonium fluoroborate,crotonaldehyde,titanium(III)chloride is 1:1.4:2.1,the reaction time is 3h,the total yield is 75%.