Study On The Synthesis Of Glufosinate

Glufosinate is a non-selective herbicide with a phosphorus-containing amino acid structure.It has D/L two configurations and only the L-glufosinate has herbicidal activity.At present,the Strecker route is the most used for industrial production of glufosinate and gives the racemic product.In this route,the highly toxic cyanide is needed as material and it isn't a good route to L-glusoinate,So,we need further reseach for other routes.Among all the glufosinate synthetic routes,we chose the keto-acid route for deeper research.It has prospect for industrial application because the materials needed in the keto-acid route are fairly cheap and it has mild reaction conditions.The key intermediate of this route,2-oxo-4-[hydroxy(methyl)phosphinyl]butyric acid,reactes with ammonia and hydrogen through reductive amination gives the D/L-glufosinate.When chemical or enzymatic asymmetric synthesis methods are used,L-glufosinate could be obtained.This thesis contained three parts:Synthesis of the keto-acid intermediate,2-oxo-4-[hydroxy-(methyl)phosphinyl]butyric acid,from O,O-Diethyl methyl-phosphonite.Synthesis of D/L-glufosinate through the reductive amination of the keto-acid intermediate with ammonia and hydrogen.Synthesis of L-glufosinate starting from keto-acid intermediate using chiral auxiliary method and asymmetric catalytic method.The main contents are as follows:1)Optimization of the keto-acid intermediate synthesis process:The addition and self-rearrangement of O,O-Diethyl methyl-phosphonite to acrylic acid alkyl ester yielded 3-[ethoxy(methyl)phosphinyl]propionic acid methyl ester which was then converted by Claisen condensation with oxalic acid ethyl ester.The reactants was directly hydrolyzed and decarboxylated without further purification,giving the product of keto acid intermediate 2-oxo-4-[hydroxy(methyl)phosphinyl]butyric acid.The structure of the products were affirmed through 1H-NMR and 13C-NMR.The overall analytic yield was 78.9%and the separation yield was 46.9%through mixed solvent crystallization.2)Synthesis of racemic glufosinate:The keto-acid intermediate reacted with ammonia and hydrogen under the catalysis of Raney Ni through direct reductive amination reaction could produce D/L-glufosinate.Structure of the products were affirmed through 1H-NMR and 13C-NMR.The side reaction was inhibited after the reaction conditions was optimized and the reaction yield could achieve 92.5%.Under the optimal conditions,the catalyst could be reused more than 5 batches.3)Synthesis of L-glufosinate using chiral auxiliary method:using(S)-methylbenzylamine as the chiral auxiliary to induce the formation of new chiral center during the reductive amination of keto-acid intermediate,glufosinate was prepared after removal of the chiral auxiliary.The dorminant configuration of the product was L-form and the highest enantiomeric excess could reach 69.3%.4)Synthesis of L-glufosinate cataylzed by chiral catalysts:we tried to proceed the asymmetric reductive amination of the keto-acid with benzylamine intermediate using chiral catalysts.The catalysts we chose showed no enantioselectivity.