Improved Synthesis of 3-Nitrophenylacetic Acid

In the development of certain work in our laboratory, we needed large quantities of 3-nitrophenylacetic acid. This material is very expensive commercially. It therefore became necessary to find a convenient and efficient process since none of the reported procedures is suitable for a large scale preparation of 3-nitrophenylacetic acid. In the first synthesis reported by Frederick et al.¹, 3-nitrobenzyl chloride was converted to 3-nitrophenylaceto-nitrile which was hydrolyzed to 3-nitrophenylacetic acid in 38% yield. The utility of this method for making large quantities of 3-nitrophenylacetic acid is restricted by the high cost of 3-nitrobenzyl halides. The second 2 method published by Jennings² is a multistep process starting with 3-nitrobenzaldehyde and the reported overall yield is 31%. This method also is not suitable for a large scale preparation due to the hazardous nature of the acid azide which is formed as one of the intermediates in this five step sequence. The third method describes the conversion of 3-nitroacetophenone to 3-nitrophenyl-acetic acid by willgerodt reaction.³ Although the starting material 3-nitroacetophenone is inexpensive but the reported yield of 3-nitrophenylacetic acid is only 7%. The high temperature required in the willgerodt reaction causes the reduction of nitro group by sulfur resulting in a bad mixture thus lowering the yield of nitrothio-morpholide (3) and making its isolation difficult.