Synthesis Of O-hydroxymandelic Acid

Hydroxymandelic acid is an important intermediate for the synthesis of fragrances,pesticides and pharmaceuticals,and it plays an important role in the synthesis of the precursor benzofuranone of the green pesticide azoxystrobin.Hydroxymandelic acid can be prepared by condensation of glyoxylic acid and phenol,due to the reaction of glyoxylic acid and phenol,it is more likely to occur in the para-position.What's more,the formation of di-substituted or glycolic acid and other substances which makes the synthesis,separating and refining o-hydroxymandelic acid more challenging that under certain conditions.In the thesis,synthesis of o-hydroxymandelic acid by the condensation of glyoxylic acid phenolic under alkaline condition,o-hydroxymandelic acid by o-hydroxyacetophenone and o-hydroxybenzyl alcohol also studied.Then,the dehydration of phenyl boronate by phenol and boric acid and compositing of o-hydroxymandelic acid from the synthesis of glyoxylic acid as the raw material also studied.The research's results are as follows:When mingling glyoxylic acid and phenol under alkaline conditions,it finds that low-temperature alkaline metal ion-free catalytic conditions can easy to generate an alignment product with the combined action of electron cloud density rearrangement and steric hindrance no matter how the reaction conditions changed.When product analyzed by liquid chromatography,there were adjacent small peaks in the target attachment,indicating that the reaction produced a small amount of ortho-products.Based on the theory that the phenolic hydroxyl group in the phenol is the first type of positioner,the ortho-products can be theoretically generated by changing temperature,solution acidity and catalyst during the synthesis of glyoxylic acid and phenol.From the control experiment,found that high-temperature acidity can catalyze by metallic ions,activation of phenolic hydroxyl groups' orthoposition reaches dominant.In addition,the larger the atomic radius of metal ions(such as Ru,Cs,etc.)used in the acid-base adjusting agent(alkali metal hydrate)used in the study is more favorable for synthesizing ortho-products,the smaller the atomic radius of metal ions(such as K,Na,etc.)is more conducive to synthesis para-products.Ortho-advantage reaction conditions after orthogonal test are as follows:phenol 75.3 g,acetic acid aqueous solution 14.8 g,aluminum sulfate 3.3 g,tributylamine 7.6 g,the solution pH is controlled at 4 to 4.5,reaction temperature 80 ?,and reaction time 8 hours,ortho yield is 62%.However,this method has the disadvantages of relatively large amounts of phenol and inorganic difficult to recycle at later reaction period.In addition,o-hydroxymandelic acid is successfully prepared by the o-hydroxy acetophenone hydroxyl group in the alkaline environment,and the keto group can further oxidize to carboxylic acid.Experiments have found that better results can be obtained when aprotic polar solvents and metal oxides are used as catalysts.The optimized reaction conditions are as follows:n(o-hydroxyacetophenone):n(selenium dioxide)=1:0.06,dioxane 40 mL,reaction temperature 100 ?,reaction time 12 h.product yield up to 35%and the purity reaches 85%.There some measures to control the amount of catalyst during preparation.Nevertheless,selenium cannot be complete recovered after the reaction completed which poses a potential threat to the environment.Finally,using phenol and boric acid as the core raw material to dehydrate under high temperature can produce phenylborate,and phenylborate ester can perform the better positional condensation reaction which with aldehydes and esters.Adjacent to hydroxymandelic acid and other similar compounds,the raw materials of the method(phenol&boric acid)are cheap and easy to obtain,then esters can be exchanged with phenylboronate during the reaction to produce target product.What's more,equimolar alcohols removed can continue to react with acids to form esters for subsequent reaction in the next reaction.That is,no alcohol consumed throughout the process.In addition,the entire process of the route has no other material except water which meets the requirements for new synthesis of green pollution-free and high atomic utilization.However,due to time and research restrictions,there is still space for improvement in the yield of this method.