Synthetic Technology Study Of Indoxacarb

Indoxacarb is a chiral enrichment oxadiazines sodium channel blockerswhich was listed in2001by the United States Du Pont. It has the characteristicsof ultra high performance, high selectivity, low residues. After comparing varioussynthetic routes in the literature comprehensively, we design a synthetic routewhich has the advantages of more reasonable, lower cost, higher yield and moresuitable for industrialized production in this paper. This course mainly includessynthesis of three intermediates and final product Indoxacarb, and theintermediates and target compounds are characterized through FT-IR, NMR andMS.We use nine-step reactions to synthesize (S)-methyl-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (A), benzyl carbazate (B) and [4-(tri-fluoro-methoxy)phenyl]-n-(chlorocarbonyl)carbamic acid methyl-ester (C) in thispaper, then Indoxacarb is obtained by3steps.Specific content is as follows:1. Synthesis of A: In this paper, with3-chlorobenzaldehyde as the startingmaterial, we consider Knoevenagel condensation, Catalytic hydrogenation,Friedel-Crafts acylation reaction, Methoxycarbonylation reaction andAsymmetric hydroformylation reaction as the five-steps to synthesize A. In thecondensation reaction, we use piperazine instead of piperidine that is controlleddrugs firstly, and the yield is94.8%; the high-pressure reaction of catalytichydrogenation was improved to the reaction under atmospheric pressure. Thereaction conditions were more moderate. The average of enantiomeric excessvalue of asymmetric hydroxylation products was56.7%. It has a great marketprospects, is applicable for industrial production. Due to carbonylation productsshould be kept cut off the air, this paper tries to adopt "one-pot" to cut the twosteps into one.2. Synthesis of B: In this paper, with benzyl alcohol and dimethyl carbonate as starting materials, the benzyl carbazate was synthesized by transesterificationand hydrazine gasification reaction under microwave. The superiority ofmicrowave-assisted synthesis is in terms of high selectivity, less time-consuming,and low energy consumption. Total yield was88.9%(traditional synthetic yieldwas only68.5%) and the reaction time was shortened from8h to20min.3. Synthesis of C: We synthesize C by two steps reaction with4-trifluorome-thoxyaniline as raw materials. We use pyridine instead of highly toxic deacidreagent N,N-Dimethylaniline, and try to use green reagent dimethyl carbonate inthis reaction.4. Synthesis of Indoxacarb: With three intermediates as raw materials, wesynthesize Indoxacarb by three steps reaction including condensation reaction,cyclization, hydrogenation deprotection and acylation.This paper has studied on synthetic method of Indoxacarb and threeintermediates by using simple raw material. These reactions have the advantagesof easily available raw materials, mild reaction conditions, convenient operation,and high yield, low cost, suitable for industrialized production.