Synthesis Of Vitamin A Intermediate 4-acetoxy-2-methyl-2-butene-1-aldehyde

Vitamin A is a fat-soluble alcohols that can not only promote bone growth and development and maintain vision,but also promote cell metabolism normalization,make the aging skin surface thin and the wrinkle effect is obvious.The deficiency of vitamin A will cause anorexia,dry skin,night blindness and other adverse symptoms.Therefore,vitamin A and its derivatives are a kind of important drugs.Due to the instability of vitamin A,its derivatives become the main production in industry in the world,such as vitamin A acetate,vitamin A palmitate and so on,which are widely used in medicine,food additives and feed additives.4-acetoxy-2-methyl-2-buten-l-al(abbreviated as five-carbon aldehyde)is a key intermediate for the synthesis of vitamin A acetate by the C1s+Cs route characterized by the Wittig-Homer reaction.The existing industrial synthetic route is:the raw material,isoprene,first reacts to hypochlorous acid to obtain a mixture of 1-chloro-2-methyl-3-buten-2-ol and 4-chloro-3-methyl-2-buten-l-ol,and the mixture is desolvated and then esterifies with acetic anhydride and rearranges with propylene to give 1-acetoxy-4-chloro-3-methyl-2-butene,finally,it reacts with urotropine by salt formation and sulfuric acid hydrolysis to obtain five-carbon aldehyde.In the synthesis process,the route is long,the product yield is low(only about 23%),and a large amount of raw materials including isoprene,trichloroisocyanuric acid,acetic anhydride,urotropine,sulfuric acid,acetone,hexane and toluene are used,which lead to a low atomic utilization rate and high production cost.In addition,the amount of three wastes generated is large and the treatment method is difficult,including cyanuric acid which is a by-product of the reaction of trichloroisocyanuric acid with water,ammonia compound produced by urotropine after salt formation,high extraction of high COD wastewater from washing operationuro.Therefore,it is necessary to develop a green and efficient five-carbon aldehyde synthesis route.In this paper,a green and efficient five-carbon aldehyde synthesis route was developed:1,4-butenediol reacts with acetic anhydride to obtain 1,4-butenediol diacetate,then 1,4-butenediol diacetate rings with ozone.The oxidation reaction is followed by hydrogenation ring opening to obtain acetoxyacetaldehyde,and acetoxyacetaldehyde reacts with propionaldehyde in a mixed catalytic system of dimethylamine and acetic acid to obtain five-carbon aldehyde.By optimizing various process parameters,this paper obtains the following key processes and conditions:1,4-butenediol diacetate synthesis process:the molar ratio of 1,4-butenediol to acetic anhydride is 1:1.5,the reaction temperature is controlled below 140 ?,the reaction time is 5-8 h.After the completion of the reaction,the mixture was distilled under reduced pressure.The pressure of the system was less than 200 Pa,and the temperature of the kettle was controlled to be below 130 ?.The product 1,4-butenediol diacetate was collected in a yield of 96%.Acetoxyacetaldehyde synthesis process:the mass ratio of 1,4-butenediol diacetate to dichloromethane is 1:3,ozone is passed at-30?-20 ?.and the reaction time is 3?5 h.Then,the temperature was raised to room temperature,and hydrogen gas was passed through at 25 to 45 ? and 0.2 to 0.4 MPa to carry out a reduction ring-opening reaction,that catalyzed by Pd/C.After the completion of the reaction,the solvent and the product acetoxyacetaldehyde were obtained under reduced pressure,and the product yield was 82.4%.Five-carbon aldehyde synthesis process:In the mixed catalyst system of dimethylamine and acetic acid,the pH of the reaction solution is adjusted to 6?8,and the condensation reaction of acetoxyacetaldehyde and propionaldehyde carries out in a molar ratio of 1:2 in the tubular reactor,the reaction temperature is 30?50 ? and residence time is 60?100 s,the reaction liquid was extracted with dichloromethane,the organic phase was distilled under reduced pressure to obtain the product in a yield of 62.6%.The indexes of the five carbon aldehydes are:boiling point:66?72?/2mmHg,yield:50.0%,purity:96.4%,and the related products are verified by 1H-NMR and GC-MS,the structure is correct.The synthetic route has been verified by pilot test and proved to be of guiding significance for industrial production.