What is the synthesis of the insecticide Flometoquin?

Synthesis of Flometoquin

Flometoquin (XXVII) is efficiently prepared in a seven-step synthesis starting from p-toluoyl chloride (218). Regioselective chlorination in the meta-position of 218 is followed by the conversion of the acid chloride into an isopropyl ester, to yield compound 220. Nitration of 220 occurs at the less sterically demanding ortho-position of this molecule to yield the tetrasubstituted benzene derivative 221. This is coupled by an SNAr reaction with 4-(trifluoromethoxy)phenol (222) to the yield 223 in almost quantitative yield. After the catalytic reduction of the nitro group, the resulting anthranilic ester 224 undergoes ring closure with diethyl ketone to yield quinolinone 225. The pyridine ring of the latter intermediate is then aromatized in the final step by Oacylation with methyl chloroformate to deliver flometoquin (XXVII).

Introduction of Flometoquin

Flometoquin has been presented by Nippon Kayaku as a new insecticide, which is active on thrips, white flies and some lepidoptora spp. Flometoquin, 2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy)phenoxy]quinolin-4-yl methyl carbonate, is a novel insecticide with a structurally unique phenoxy-quinoline. It was discovered in 2004 by the collaborative research of Nippon Kayaku and Meiji Seika Kaisha, Ltd. (currently, Mitsui Chemicals Crop & Life Solutions, Inc.). The compound demonstrates strong and quick insecticidal action against a variety of thrips species at the nymphal and adult stages through contact and feeding activity, which could minimize crop damage and economic loss by insect pest species. In addition, flometoquin is safe for tested non-target arthropods, which makes it suitable for controlling the insect pests mentioned above under Integrated Pest Management (IPM) programs.

References:

[1] KOBAYASHI T, HOTTA H, MIYAKE T, et al. Discovery of flometoquin, a novel quinoline insecticide[J]. Journal of Pesticide Science, 2023, 39 1: 0. DOI:10.1584/jpestics.d23-035.