Improvement On The Synthetic Process Of The Resveratrol

Resveratrol bears a variety of pharmacological activities,such as anti-tumor property,anti-oxidation,antibacterial and anti-inflammatory effect,anti-senile dementia and so on.It has been widely used in health care products.However,the output of resveratrol extracted from plants is low,and the extraction cost remains high.Therefore,the efficient synthetic method for resveratrol has become the focus of most researchers.There’re many problems in the traditional industrial production of resveratrol,for instance,expensive raw materials,harsh reaction conditions,large amounts of wastewater production and relatively low yield.Therefore,it is always desirable for people to explore a process route with the following advantages:lower cost,mild reaction conditions and less waste.This thesis proposed some modifications on the traditional process route.Instead of using the expensive and rare raw material 3,5-dihydroxybenzoic acid,the inexpensive and readily available p-toluidine was employed as the starting material,and the detailed process was as follows:First,p-toluidine was brominated to produce 2,6-dibromo-4-methylaniline in 90%yield,which was refluxed in sulfuric acid and ethanol with sodium nitrite yielding 3,5-dibromotoluene in 91.6%yield;3,5-dibromotoluene reacted with CH3ONa in DMF under the catalyst of cuprous bromide to deliver 3,5-dimethoxytoluene in 86.7%yield;demethylation of 3,5-dimethoxytoluene reacted under catalysis of AlC13 gave 3,5-dihydroxytoluene in 83.6%yield,which was acetylated by acetic anhydride under reflux producing 3,5-diacetoxytoluene in the yield of 82%;bromination of 3,5-diacetoxytoluene with NBS initiated by BPO in tetrachloromethane at reflux affording 3,5-diacetoxybenzyl bromide in 92%yield.The total yield from p-toluidine was 45.1%3,5-Diacetoxybenzyl bromide was treated with triphenylphosphine in chlorobenzene at refluxed providing 3,5-diacetoxybenzyl triphenyl bromide in the yield of 97.1%;Wittig reaction of 3.5-diacetoxybenzyltriphenyl bromide and p-acetoxybenzaldehyde gave(E)-3,4’,5-triacetoxystilbene in 87.5%yield;deprotection produced the target product resveratrol in the yield of 90.6%.Using p-toluidine as the starting material,the total yield of resveratrol obtained via Wittig method was 34.2%.In order to reduce the cost of the Wittig reaction process,this thesis also tried reduction of triphenoxyphosphine to triphenylphosphine for recycling.3,5-Diacetoxybenzyl bromide obtained as above was reacted with urotropine to obtain 3,5-diacetoxybenzaldehyde in a yield of 25.3%;meanwhile,catalyzed by a self-made solid acid catalyst,anisole was submitted to the F-C acylation reaction giving 4-methoxybenzophenone in a yield of 91%;4-methoxybenzophenone underwent Willgerodt-Kindler redox amidation rearrangement reaction with sulfur and morpholine affording 4-methoxy-benzeneacetic acid,yield 88.5%;then 4-methoxy-benzeneacetic acid was demethylated under AlC13 catalysis to obtain 4-hydroxybenzeneacetic acid in 91.8%yield,which reacted with acetic anhydride to produce 4-acetyloxy-benzeneacetic acid in the yield of 93.7%.Based on the successful synthesis of the above compounds,Perkin reaction of 3,5-diacetoxybenzaldehyde with p-acetoxyphenylacetic acid yielded 2-(4’-acetoxyphenyl)-3-(3’,5’-Diacetoxyphenyl)-acrylic acid in 78.3%yield;then decarboxylation reaction produced(E)-3,4’,5-triacetoxystilbene in the yield of 85.4%;deprotection then delivered thetarget product resveratrol in a yield of 90.6%.The total yield of resveratrol obtained by the Perkin method was 7.2%.This thesis optimized the conditions of relevant reactions and established the corresponding analysis methods.Thi’s synthesis method of resveratrol has the advantages of low reaction cost,mild conditions,and simple work up;it provides feasible process for its industrial production The product of each step was characterized by 1H NMR,IR and MS,and the spectrum was consistent with the structural characteristics of each.