Process Research Of Indoxacarb

As the population explosion and people’s awareness of sustainable development increasing, the demand for the coordination between grain and environment is arresting. Herbicide and pesticide create an ecologic dominant environment for crops, and contribute much to the high production of grain. The bioactivity, selectivity, security and moreover the resistance due to overuse restrict the progress of insecticide. The security and the resistance of insecticide result in obsoleteing of old varieties and developing of new classes with novel formation or mechanism. Biorational insecticide is emerging in the pesticide market as people focus much of their attention on the security. We classify the insecticide as seven groups according to its development history:the organophosphorus insecticides, the carbamate insecticides, the synthetic pyrethroid insecticides, the heterocyclic insecticides, the insect growth regulators, the ryanodine receptor insecticides and the biopesticides. In the part of review, we enumerate the typical products of each category and illustrate their mechanism.Indoxacarb, an carbamate insecticides with a composition of oxadiazine, was developed by DuPont in1992, registered and listed in2001. There is a chiral center in the structure of indoxacarb and only the S-isomer shows activity. The current commercial code of indoxacarb is DPX-MP062, which is comprised of S-isomer and R-isomer at the rate of3:1. Indoxacarb is the first commercial insecticide that acts as a sodium channel blocker. The N-decarbmethoxylated metabolite (DCJW) of indoxacarb is the active form in vivo according to previous study. DCJW is a substance that can restrain the voltage-dependent sodium channel and block the conduction of the nervous impulse irreversibly.Indoxacarb occupied the insecticide market rapidly for advantages of novel mechanism, dramatic activity, ecological security and low residue. And the global sales achieved200million in2008. However, the synthetic procedures of indoxacarb reported at present have drawbacks of high cost, moderate yield, and inevitable contamination. We analyzed the route reported and selected the most feasible one. We optimized the procedure selected in order to find out a series of processes with low cost, high yield and low pollution. At present, most reported synthetic route of indoxacarb took methyl5-chloro-l-oxo-2,3-dihydro-lH-indene-2-carboxylate (compound3) or methyl5-chloro-2-hydroxy-l-oxo-2,3-dihydro-lH-indene-2-carboxylate (compound4) and methyl4-(trifluoromethoxy)phenylcarbamate (Compound6) as key intermediate. We summarize the synthetic procedure of the key intermediates and the final product in the part of review.After comparation and analysis, we finally selected the chlorobenzene and the4-trifluoromethoxyaniline as starting materials. A series of Friedel-Crafts acylation, cyclization, Claisen condensation, oxidation and hydrazinolysis starting from chlorobenzene gave methyl5-chloro-1-hydrazono-2-hydroxy-2,3-dihydro-1H-indene-2-carboxylate (compound5) as an intermediate. After two condensation of4-trifluoromethoxyaniline with methyl chloroformate and triphosgene in proper sequence, N-chlorocarbonyl-N-methyl4-(trifluoromethoxy)phenylcarbamate (Compound7) was obtained as another intermediate. A condensation between the two intermediates took place and subsequently a cyclization gave the final product-indoxacarb (compound9-a). Eventually, we found out a convenient process to the synthesis of compound3with low cost, low contamination and high yield. Besides, we discover two inexpensive reagents to synthetize compound6. These findings will be very valuable for developing practical applications in the manufacture of indoxacarb and other chemicals, lowering production costs and reducing environmental pollution. Thus, we reported them respectively. With regards to other intermediates and the final product, we found there were not much potential or value to do further optimization, therefore, we just took appropriate explorations.