Synthesis Technique Development Of 4-Aminophenylboronic Acid And Its Derivatives

The substituented phenylboronic acid are important pesticide intermediates, pharmaceutical intermediates and chemical raw materials, widely used in the synthesis of new LCD materials and sugars sensor. Using n-butyllithium by traditional methods under temperature at -78 ? circumstance in laboratory is too complex to suit Industrialization. With the requirement Increasing of the substituented phenylboronic acid, developing a new synthetic route of inexpensive, simple is important.In this paper,4-bromoaniline is the starting material of 4-aminophenylboronic acid.Because the starting material containing amino, in order to prevent active hydrogen interference in the course of the reaction, we use three different measures:1? DMF as solvent, by BOC anhydride in T= 30 ? to protect amino.2?Toluene as solvent, by succinic anhydride in T= 120 ? reflux to protect amino.3?Toluene as the solvent, by o-phthalic anhydride in T= 120 ? reflux to protect amino.After the formation of amino protected intermediate, and then reacting with n-butyllithium magnesium form aryl magnesium-lithium complex. The nucleophilic substitution reaction that aryl magnesium lithium complex intermediate reacting with trimethyl borate get aryl borate. Finally, aryl boronic ester intermediate deaminate protection to form the target product.Three synthetic routes, the route one has the highest yield. We optimize reaction conditions of the route one. When n (Mg):n (BuLi):n (C6H6NBr):n (B (OR) 3)= 0.57:0.80:1.0:2.5, trimethylborate as borohydride reagents, nucleophilic substitution temperature T=-15 ?,and after the end of nucleophilic substitution, can be rapid heating. Under these conditions the yield of p-aminophenyl boronic acid is 51%.In this paper, N,N-dimethylaniline is the starting material of 4-(dimethylamino) phenylboronic acid. Starting material first reacting with NBS obtains the active spot of arylate, and endure react with magnesium to aryl Grignard reagent. After nucleophilic substitution reaction that Grignard reagent react with trimethylborate, under acidic conditions arylborate intermediates hydrolysis to get the product. The yield of the product is 72.3%.We optimize reaction conditions of synthetic route of 4-(dimethylamino) phenyl boronic acid. When n (Grignard reagent):n (trimethyl borate)= 1.0:1.2, After Grignard reagent addition is completed and then incubated 30min, nucleophilic substitution temperature T=-15 ?, dropping Grignard reagent to trimethyl borate and other factors. Considering the cost and yield of the reaction, these conditions are more conducive to industrial mass production.In the process of which 4-bromoaniline is the starting material of 4-(N-isopropyl) benzene boronic acid pinacol ester, under catalytic PdCl2 the yield of product can get to 63%.