Study On Preparation Of Substituted Benzaldehyde By Substituted Toluene Oxidation

In drug synthesis,the oxidation of substituted toluene into substituted benzaldehyde is widely used.Usually,the preparation of substituted benzaldehyde is as follows:The direct oxidation method of substituted benzyl alcohol is obtained by hydrolysis of substituted benzyl chloride in solution and distillation,and then substituted benzaldehyde is obtained by oxidation.However,this method has no industrial significance because of its high cost.Benzyl chloride hydrolysis（also known as chlorination hydrolysis）is one of the most common methods for the preparation of substituted benzaldehyde in industry.Instead of side chain chlorination toluene under appropriate conditions,get the main product of benzyl chloride,then through acidic or alkaline hydrolysis and distillation to replace benzaldehyde,benzoic acid is replaced,the by-product of the hydrolysis yield can reach more than 80%,but the hydrolysis can produce a large amount of acidic waste liquid treatment is difficult to solve,do not conform to the principles of green chemistry.Therefore,this article through the experiment with different synthetic methods and carries on the contrast,developed a new green synthesis of substituted benzene formaldehyde method,the methoxy toluene as the main research object,acetylacetone oxygen vanadium（VO（acac）₂）as the catalyst of hydrogen peroxide solution as oxidant,made of methoxy benzene oxidation formaldehyde,and through gas chromatography,The structure of p-methoxy-benzaldehyde was characterized by ~1H-NMR and ¹³C-NMR.In this paper,the preparation of p-methoxy-benzaldehyde with p-methoxy-toluene is the main research object,and the reaction mechanism and influencing factors are studied.Paramethoxybenzaldehyde,also known as paranisaldehyde,has a strong and persistent hawthorn flower odor.It is a very important synthetic flavor,widely used in daily chemical industry and edible flavor deployment.Compared with other aromatic aldehydes,p-methoxy-benzaldehyde has a softer smell and better diffusion and chemical stability.As an important organic intermediate,it is also the raw material of synthetic drugs.For example,amoxicillin,obtained from an antihistamine intermediate based on p-methoxbenzaldehyde,has good antibacterial and anti-inflammatory effects and is widely used in the pharmaceutical industry to manufacture antimicrobial drugs such as hydroxybenzylpenicillin.Sulazodone hydrochloride prepared from p-methoxybenzaldehyde can effectively relieve angina pectoris and cardiomyopathy.The trisulfide synthesized from p-methoxy benzaldehyde has the function of protecting gallbladder and liver.In addition,p-methoxy benzaldehyde is also widely used in cosmetics,polymer materials,edible flavors,pharmaceutical intermediates and other fields.Therefore,the green and efficient synthesis of p-methoxy benzaldehyde is of great significance in industry.In the synthesis of substituted benzaldehyde,the effects of molar ratio of catalyst and reaction substrate[n（VO（acac）₂）:n（Ar CH₃）],concentration of hydrogen peroxide solution and reaction temperature on the yield of substituted benzaldehyde were investigated by single factor experiment.In the reaction of p-methoxy benzaldehyde as reaction raw material,the optimum reaction conditions were obtained:Vanadium oxyacetyl acetonate as catalyst,and n（VO（acac）₂）:n（Ar CH₃）=1:10.The reaction temperature was 85℃.Under this condition,the yield of p-methoxylbenzaldehyde reached 86.3%.In addition,the effect of different substituents on the yield of substituted toluene was explored through different substrates（p-methoxyltoluene,toluene,p-chlorotoluene,o-chlorotoluene,p-bromotoluene,p-nitrotoluene,o-nitrotoluene）.To sum up,this process uses vanadium acetyl acetonate oxygen as catalyst,hydrogen peroxide solution as oxidant,and develops a green and environmentally friendly synthetic process route to replace benzaldehyde,which has a certain application prospect.