An efficient route towards R-2-phenoxypropionic acid synthesis for biotransformative production of R-2-(4-hydroxyphenoxy)propionic acid

R-2-(4-hydroxyphenoxy)propionic acid (R-HPPA) is a key intermediate for the synthesis of classic herbi-cides with high selectivity against grassy weed. The main route for R-HPPA biosynthesis is to hydroxylate the substrate R-2-phenoxypropionic acid (R-PPA) at C-4 position with microbes. In order to provide suf-ficient R-PPA for the industrial production of R-HPPA, an effective R-PPA synthesis method was estab-lished and optimized in this work. The synthesis process mainly consisted of two steps: (1) synthesis of S-2-chloropropionic acid from L-alanine via diazotization and chlorination reactions;and (2) synthesis of R-PPA from S-2-chloropropionic acid and phenol via etherification reaction. The optimal reaction con-ditions were as follows:HCl:NaNO2:KI:L-Ala=2.0:1.2:0.7:1.0 (in molar), 125 ℃ reflux for 1.5 h, with KI as catalyst, and KI: S-2-chloropropionic acid: phenol=0.075: 1.2: 1.0 (in molar). Under these condi-tions, an improved molar conversion rate (74.9％, calculated in phenol) was achieved. After extraction using anionic exchange resin Amberlite IRA-400 (CI), R-PPA product with a purity of 95.08％was obtained. The purified R-PPA was identified and evaluated in the application of the biotransformative production of R-HPPA. The results indicated that the synthesized R-PPA supported the R-HPPA biosynthesis with a com-parable yield as that of the standard R-PPA. The R-PPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials, less toxicity of reagents, simple manipu-lations, and low equipment/instrument requirements.