Process Development for the Crop Safener Cloquintocet Acid

A practical one-pot process was developed for (5-chloroquinolin-8-yloxy)acetic acid (CQC acid), known commercially as cloquintocet, a crop safener that is added to various herbicide formulations to reduce crop damage. The process consists of (1) conversion of 5-chloro-8-hydroxyquinoline (5-ChQ) to its corresponding sodium salt 5-ChQ-Na with 50 wt % NaOH in dimethyl sulfoxide (DMSO), (2) alkylation of 5-ChQ-Na with methyl 2-chloroacetate to generate CQC methyl ester (CQC-Me) after removal of water by distillation under reduced pressure, and (3) hydrolysis of CQC-Me with a catalytic amount of 0.1 N HCl (0.5 mol %) or 0.1 N H2SO4 (0.25 mol %) to afford CQC acid in >90% yield with >98% purity. All of the steps were carried out in one pot with only one isolation. Recovery and reuse of DMSO were also demonstrated. Each step/stage of the process was subjected to reactive chemical evaluation by differential scanning calorimetry and/or accelerating rate calorimetry for identification of potential safety hazards.