Studies On Synthesis Of α-hydroxyarylacetic Acids & Its Intermediates

a -hydroxyarylacetic acids ,which involves in this dissertation are about some Mandelic acid derivatives, in particular about ortho substituted mandelic acid and some other fluorine substituted mandelic acid derivatives. They form a series of important fine chemical intermediates, ortho substituted mandelic acids are the key intermediate in the synthesis of Pharmaceuticals in particular anticoagulants such as clopidogrel. Mandelic acid derivatives also have been widely used in the field of Pharmaceuticals, asymmetric synthesis or optical resolution etc. Nowadays the prices of mandelic acid derivatives are quite expensive. According to a great number of academic references, we are prepared to find a novel method on the synthesis of a -hydroxyarylacetic acids, particularly the synthesis of ortho substituted mandelic acid and some other fluorine substituted mandelic acid derivatives such as 4-fluoromandelic acid and 2,6-difluoromandelic acid, etc.A novel process for the preparation of mandelic acid derivatives has been designed here. During the experiment, we take phenylacetonitrile derivatives as the starting material for synthesizing the mandelic acid derivatives. The process was optimized after experiment and experiment. Through t his method, t he yield o f o -chloromandelic a cid i s 4 2.9% with 99.0% purity of the crude product; the yield of O-fluoromandelic acid has achieved 42.9%. This process has the advantages of being easy to handle, convenient to purify and low-cost, etc, all of which result in great economic potential and promising prospect in practice.Moreover, we have exploded another process of the synthesis on o-chloromandelic acid and some other mandelic acid derivatives, according to the original method for processing the synthesis mandelic acid by acetophenone. There is an insight discussion for the process of intermediate, which has achieved to satisfying consequence.Finally we conducted a optical resolution to mandelic acid, through which the original resolution has been optimized, especially the (-) -2-amino-1 -butanol-D- (-) -mandlate has been purified and the high quality of D- (-) -mandelic acid has been guaranteed Meanwhile, we finished the work for recycling the optical resolution agent, by which we has further saved the cost and gained our research a bright practical prospect.