Synthesis and commercialization of selective herbicide quizalofop-ethyl

Phenoxy- and pyridyloxypropinates have been known as selective herbicides. In the course of extensive investigation on this series with various condensed heterocyclic moieties, we have found among the guinoxalines some promising compounds to replace phenyl or pyridyl, which show excellent hervicidal activities against grass weeds. Among them, ispecially quizalofop-ehyl (Code No. NC-302) showed a potent herbicidal activity, so that it has been commercialized as a novel post-emergence herbicide. The quinoxaline moiety of quizalofop-ethyl, whose economical synthesis was one of the most important problems on the commercialization of this compound and has been intensively researched, is now able to be synthesized from low-priced raw materials economically. Quizalofop-ethyl has an asymmetric carbon atom, so it exists as a mixture of two antipodes. Active ingredient of this compound depends upon (R)-(+) isomer, which is twice as active as the racemate. (R)-(+) isomer can be stereoselectively synthesized from a chiral compound on retaining its chirality. Furthermore, there are two crystal fomrs of (R)-(+) isomer, while the rasemate shows only one crystal form. The discovery of this effective fractional crystallization of (R)-(+) isomer has enabled its commercialization. In this paper, the economical syntheses of chiral quizalofopethyl and its important intermediate chiral ethyl 2-(4-hydorxyphenoxy)propionate are described in detail.