The Study On The Synthesis Of Substituted Phenylboronic Acid

Arylboronic acids are boronic compounds which have single phenyl or multiphenyls. Various substituted arylboronic acids are important intermediates of organic synthesis. They play an important role in the synthesis and modification of asymmetry pesticides and medicines. Besides that, they also play an important role in the synthesis of biologic reagents and materials. Therefore, it is very important to study the preparation of substituted phenylboronic acids and the improvement of the preparation process. In this thesis, the synthesises of 2,6-dimethylphenylboronic acid and 4-isopropylphenyl boronic acid and their process improvement were studied in detail. Meanwhile, the synthesis of 1,4-benzenediboronic acid was also investigated preliminarily.2,6-Dimethylphenyl boronic acid was prepared according to classic Grignard reagent method. An optimized process was obtained by investigating the influence of the temperature, reactant proportion, temperature rising rate and mixed solvent on the yield. The molar ratio of reactants is n(Mg):n(C8H9Br): n(B(OC4H9)3)=1.2:1.0:2.0, Grignard reagent was prepared from 2,6-dimethylphenyl bromide and magnesium, then it was reacted with tributyl borate at–10℃, and the reaction mixture was hydrolyzed in acid medium after the temperature was increased to 20℃in a short time. The total yield is 72.2%.Based on the analysis of the experiment results,"one-pot"method was proposed and checked to synthesize the 2,6-dimethylphenylboronic acid. An optimized process was obtained by investigating the influence of the boronation reagent, reactant proportion and solvent on the yield. The solution of 2,6-dimethylphenyl bromide, tributyl borate and THF(Tetrahydrofuran) was added to the magnesium chip dropwise, the reactant proportion was n(Mg):n(C8H9Br):n(B(OC4H9)3)= 1.2:1:1.5. The reactant solution was kept in a water bath at 30℃for 2 hours, then hydrolyzed in a acid medium. The isolated yield is 80.1%. The product was characterized by IR, UV, MS and 1H NMR.4-Isopropylphenylboronic acid was also prepared from Grignard reagent. An optimized process was obtained by investigating the influence of the temperature, reactant proportion, temperature rising rate on the yield. The molar ratio of reactants is n(Mg):n(C₈H₉Br): n(B(OC₄H₉)3)=1.2:1.0:1.5, the nucleophilic substitution temperature is -10℃, and the reaction mixture was increased to 20℃in a short time and hydrolyzed in acid medium after the THF was recycled by vacuum distillation. The isolated total yield is 56.6%. The 4-isopropyl- -phenylboronic acid was characterized by IR, MS and 1H NMR. The method of grey correlation analysis was applied to analyze the experiment results. It was showed that the sequence of component factors to influence the yield is: reactants ratio>additional time>temperature. According to this information, experiments were carried out and an optimized process was obtained.1,4-Benzenediboronic acid was prepared from dimagnesium Grignard reagent. The dimagnesium Grignard reagent of p-dibromobenzene was prepared from p-dibromobenzene and magnesium. The dimagnesium Grignard reagent was cooled to -40℃and poured to tributyl borate which had also been cooled to -40℃under stirring vigorously. The reaction mixture was hydrolyzed in acid medium after the temperature was increased to 20℃. The isolated total yield is 48.5%. The 1,4-benzene- -diboronic acid was characterized by IR.