The Synthesis Of Fumaraic Acid Esters And Study Of Antibacterial Properties

Derivatives of fumaric acid have been extensively applied in the fields of food and medicine.α,β-Unsaturated carbonyl is regarded as an effective group of antimicrobial activity. Fumarate was effect preservatives containing such group. The purpose of this thesis was to synthesize derivatives of fumarate which are of high performance, broad-spectrum, low toxictyand and low hypersusceptibility. So, research on the synthesis and antibacterial activity of the derivatives of fumarate will be of great significance.Two n-monoalkyl fumarates, monoalkyl benzyl fumarates and monoalkyl hydroquinone fumarates were synthesized and their antibacterial properties were studied.Two n-monoalkyl fumarates were prepared in the presence of catalysts( anhydrous aluminum chloride) by isomerization of the corresponding n-monoalkyl maleates, which were prepared by reaction of maleic anhydride with methanol, phemethylol, respectively. The temperature of esterifieation,material ratio, isomerization and isomerization dosage were investigated. Conditions of the mentioned reaction were optimized. As a result, the yield of monoalkyl fumarate(MMF) was about 83.2%, and monobenzyl fumarate was about 74.5%.Synthesis of fumaric acid monoalkyl monochloride from monoalkyl fumarate were further conducted. The reflux time,the reflux temperature, the proportion of reagents were studied as well as the dosing way of reactant and how to add thionyl chloride which had effects on the synthsis of fumaric acid monoalkyl monochioride. The best synthetic condition was obtained. The yield of fumaric acid monomethyl monochloride was 85.6%, and fumaric acid monobenzyl monochloride was 80.5%.Fumaric acid monomethyl monochloride and fumaric acid monobenzyl monochloride were reacted with hydroquinone and methanol to form methyl hydroquinone fumarate(MPHF) and methyl benzyl fumarate(MBHF), respectively. Conditions of the mentioned reaction were optimized. The yield of MPHFwas about 57.6%, and the yield of MBHF was 69.8%.All the products were characterized by melting point, IR, 1H-NMR .Antimicrobial activity of four fumarate esters was systematically studied and the results showed that they could suppress the growth of bacteria. Methyl hydroquinone fumarate antibacterial activitive was good in the mediums of pH from 3to 8. The antibacterial activity decreased in this order MPHF>MBHF>MMF>MBF. The alkyl p-nitrophenyl fumarates are the better bacteriostat. When the concentration of the four fumarate esters was 0.05%, they showed evidently bacteriostatic effect on the growth of the mixed bacteria separated from sour milk.Skin tests showed that four fumarate esters did stimulate skin less than dimethyl fumarate did.