Novel Process For The Green Synthesis Of O-Phenzyl-Hydroxylamine Hydrochloride And Its Derivatives

Benzyloxyamine hydrochloride and its derivatives are a class of o-substituted phenyl hydroxylamine compounds,which can be used as phenyloxyamine reagents in the field of medicines and pesticides.At present,their synthetic process are mainly hydroxylamine hydrochloride procedure,but this procedure exists following problems:long reaction steps,expensive raw materials and much waste.So we use ketoxime to prepare the products by two new green synthetic processes.On the basis of civil and foreign literatures,a new process was studied using butyl ketone oxime as raw materials and benzyl chloride as alkylating reagent.Benzyloxyamine hydrochloride was synthesized by two steps.O-benzyl oxime ethers was prepared and hydrolyzed.Two kinds of processes were also developed for o-benzyl oxime ethers using ionic liquids or organic solvent as reacting solvent.The whole process was optimized and the better process parameters were obtained.The main contents were as follows:1)The new process of o-benzylbutyl oxime ether using ionic liquid as solvent:The product was prepared by butyl ketoxime and benzyl chloride at 25℃for 4 hours,using ionic liquid[Bmim]BF₄ as solvent,NaOH as acid acceptor,their molar ratios were 1:1:2:1.The yield was85.7%.Other oxime ethers were also obtained by above reacting conditions including 2-chlorobenzyloxybutanone oxime ether,2,4-dichlorobenzyl-oxybutanone oxime ether,benzyloxyacetone oxime ether,2-chlorobenzyl-oxyacetone oxime ether,2,4-dichlorobenzyloxyacetone oxime ether,4-fluorobenzyloxybutanone oxime ether,4-trifluoromethylbenzyl oxy-acetone oxime ether,4-fluorobenzyl oxyacetone oxime ether.The yields were 25.1%-93.6%.2)The new process of o-benzylbutyl oxime ether using organic solvent:The product was prepared by butyl ketoxime and benzyl chloride at 10℃for 6 hours,using 30%NaOH solution as acid acceptor and DMSO as solvent,their molar ratios were 1.2:1:1.2.The yield was80.5%.Other oxime ethers were also prepared by above reacting conditions including 2-chlorobenzyloxybutanone oxime ether,2,4-dichlorobenzyl-oxybutanone oxime ether,benzyloxyacetone oxime ether,2-chloro-benzyloxyacetone oxime ether,2,4-dichlorobenzyloxyacetone oxime ether,4-fluorobenzyloxybutanone oxime ether,4-trifluoromethylbenzyl oxyacetone oxime ether,4-fluorobenzyl oxyacetone oxime ether.The yields were 58.3%-89.2%.3)The process of o-benzyl ketone oxime ether by hydrolyzing:The product was prepared by o-benzyl ketone oxime ether,30%hydrochloric acid and ethanol at 70℃for 4 hours.Their molar ratios were 1:1.2:3.The yield was 66.6%.Other phenyloxyamine hydrochlorides were also prepared by above reacting conditions including 2-chlorobenzyloxyamine hydro-chloride,2,4-dichlorobenzyloxyamine hydrochloride,4-fluorine benzyl amine hydrochloride,4-trifluoromethyl benzyl amine hydrochloride.The yields were 58.7%-81.3%.This process uses butyl ketone oxime as raw materials reacting with benzyl chloride.The product is obtained after hydrolysis reaction of substituted oxime ether,and butanone is recycling for synthesis of raw material butyl ketone oxime.So it not only improve the utilization rate of atoms to reduce the production cost,but also reduce the discharge of three wastes.