Study On The Reduction Process Of Hydroxymandelic Acids To Hydroxyphenylacetic Acids

Hydroxyphenylacetic acids have a wide range of applications,but their traditional synthesis methods have the disadvantages of highly toxic materials,highly contaminated intermediate products,harsh conditions and expensive or complicatedly-prepared catalysts,which have restricted their development to some extent.So there is a great importance to study the new preparation process of hydroxyphenylacetic acids.Based on above reasons,this paper explored a synthesis method which has the advantages of easy availability of raw material,environmental protection,simple process and easy industrialization,that is,one-step reduction of hydroxymandelic acids,which can be clean and efficient prepared,to synthesize hydroxyphenylacetic acids.The main research contents of this paper are as follows:1.A series of 4-hydroxymandelic acids were prepared by the condensation reaction of glyoxylic acid with phenol and other substituted phenols(2-chlorophenol,2-methylphenol,2-methoxyphenol)under alkaline condition.Then,the condensation products were characterized by melting point instrument and infrared spectrometer,which shows that both the product yield and quality meet the need for further reduction.The qualitative and quantitative analysis methods for the reduction process of 4-hydroxymandelic acids were established by HPLC,which lays a foundation for the next experiments.2.The catalytic hydrogenation reduction of 4-hydroxymandelic acid was studied by using Raney nickel and palladium carbon as catalysts.The results show that Raney nickel and palladium carbon have similar effects,and the cheaper Raney nickel is preferred for further optimization.The single-factor experiment and orthogonal experiment were used to explore the influence rule of reaction temperature,reaction pressure,catalyst dosage and reaction time as well as the optimal process conditions.The results show that the effects of different factors can be ranked from large to small as catalyst dosage,reaction time,reaction pressure and reaction temperature,of which the catalyst dosage has a distinctive effect;the optimal process conditions are raw material and catalyst(mass ratio)2:1,reaction temperature 90℃,reaction pressure 0.5 MPa and reaction time 12 h,under which the conversion rate is 98.32%and the yield is 91.14%.After researching the recycling use of catalyst,it was found that the catalyst still have a good performance after three times of recycle.The chemical reduction of 4-hydroxymandelic acid was studied by using sodium borohydride and sodium bisulfite as catalysts.The results show that the alone use of sodium borohydride or sodium bisulfite can’t achieve the reduction of 4-hydroxymandelic acid;the mixed use of sodium bisulfite with reducing acid phosphorous acid or formic acid have certain effects,and the mixed use with formic acid has better result and can be used for further optimization.The single-factor experiment and orthogonal experiment were used to explore the influence rule of reaction temperature,sodium bisulfite dosage,formic acid dosage and reaction time as well as the optimum process conditions.The results show that the effect of different factors can be ranked from large to small as sodium bisulfite dosage,formic acid dosage,reaction time and reaction temperature,of which all factors have certain effects but not distinctive;the optimal process conditions are raw material and catalyst(mass ratio)40:3,formic acid and raw material equimolar ratio,reaction temperature 100℃ and reaction time10 h,under which the conversion rate is 98.56%and the yield is 93.17%.For the reduction of 4-hydroxymandelic acid,the yields of Raney nickel catalytic hydrogenation system and sodium bisulfite-formic acid system are both more than 90%,and the latter is higher.The former has a larger usage of catalyst but the catalyst can be recycled.The latter’s catalyst is non-recyclable but its usage is smaller and its price is cheaper.Both methods have their advantages and disadvantages,and they all have the necessity to be popularized for the reduction of other hydroxymandelic acids.3.With 4-hydroxymandelic acid as the research object,the separation and purification process of reduction product were studied to obtain the optimal purification conditions:recrystallization solvent toluene,recrystallization temperature 5℃,and recrystallization time 10 h,under which the purity of the product is 94.7%and the yield is 91.6%.After three times of mother liquor recycle,the product purity remains above 93.6%,and the yield remains above 92.1%.4.After popularizing the reduction conditions of 4-hydroxymandelic acid to 4-hydroxy-3-chloromandelic acid,4-hydroxy-3-methylmandelic acid and 4-hydroxy-3-methoxymandelic acid,we discussed the reduction mechanism,and explored the effects of different substituents as well as their respectively suitable reduction method.The relative conclusions are as follows:the introduction of substituents will increase the steric hindrance effect and inhibit the reduction process,and the inhibitory effect on sodium bisulfite-formic acid system is more obvious.The electron donating property of substituent is favorable to the reduction process,while the electron withdrawing property is unfavorable to the reduction process,and the substitution of the drawing electron group chlorine during the Raney nickel catalytic hydrogenation even causes a side reaction to generate HCl to acidify the system,which in turn deactivates Raney nickel.From the above,we can come to the conclusion that 4-hydroxy-3-methylmandelic acid and 4-hydroxy-3-methoxy mandelic acid are more suitable for the Raney nickel catalytic hydrogenation system,and 4-hydroxy-3-chloromandelic acid is more suitable for the sodium bisulfite-formic acid reduction system.