Synthesis and crystal structure of 4-amino-3-fluorophenylboronic acid

Abstract

Amino-3-fluorophenyl boronic acid has been synthesized from 4-bromo-2-fluoroaniline by protecting the amine group and then carrying out a lithium-bromine exchange, followed by addition of trimethyl borate and then acidic hydrolysis. We obtained a 47% yield. We also measured the X-ray crystal structure. This derivative has a relatively low boronic acid pKa value of 7.8 when acetylated or attached to acrylamide hydrogels. It also contains a pendant amine which facilitates attachment to polymers, for example. We are using this compound to construct glucose sensing materials that operates at the physiological pH of bodily fluids. © 2003 Published by Elsevier Ltd. There is a continuing interest in the synthesis of new boronic acid derivatives. This interest stems from the importance of boronic acids in the synthesis of biologi- cally active compounds, and the use of boronic acids themselves as pharmaceutical agents. In the area of synthetic chemistry, boronic acids have been widely used in Suzuki cross-coupling reactions, 1 Petasis reac- tion, 2 asymmetric synthesis of amino acids, 3 Diels- Alder reactions, 4 protection of diols, 5 selective reduction of aldehydes, 6 carboxylic acid activation, 7,8 and as reagents and starting materials in organic synthesis. 9