Synthesis Of L-glufosinate

Glufosinate is one of non-selective herbicide with a phosphorus-containing amino acid structure,and it has D/L two configurations but just L-glufosinate has herbicidal activity.People mainly use the racemic glufosinate now.The usage amount of single L-glufosinate is just half amount of the racemic glufosinat so that L-glufosinate has high cost efficiency and broader development prospects.In this paper,We studied the synthesis approach of the racemic glufosinate and explored a new method to synthsise L-glufosinate.Four resulting work have been summarized as following:?1?Synthesis of 2-oxo-4-?hydroxymethylphosphoryl?butyric acid:Diethyl phosphinate reactes with acrylic acid to produce the ethyl 3-?ethoxymethylphosphoryl?propionate intermediate,then the it reactes with dimethyl oxalate by condensation and hydrolyzing to synthesis of 2-oxo-4-?hydroxymethylphosphoryl?butyric acid.The affect factors of the reaction are discussed.The optimized route process is as following:the mole ratio of acrylic acid to diethyl phosphinate is 1.01:1;the reaction temperature is 5°C,the reaction time is 5h,the yield can reach 98.2%,and the purity is 95.1%determined by gas chromatography.In the Claisen condensation reaction.Another optimized procedure is following:the molar ratio of 2-oxo-4-?hydroxymethylphosphoryl?butyric acid dimethyl oxalate to sodium methoxide is 1:1.2:1.4,sodium methoxide or sodium ethoxide is used as a base,and ethyl 3-?ethoxymethylphosphoryl?propionate is added dropwise to mixture of sodium methoxide and dimethyl oxalate at a low temperature,the yield is best.The total yield in two steps can reach 84.4%.?2?Synthesis of D/L glufosinate:The D/L glufosinate is prepared by direct reductive amination of 2-oxo-4-?hydroxymethylphosphono?butyric acid with ammonia and hydrogen under the catalysis of Pd/C.The optimized route process is following:the solution of 2-oxo-4-?hydroxymethylphosphono?butanoic acid is pre-neutralized with sodium hydroxide,the amount of the palladium carbon catalyst is 5%of the mass of the reduced substrate,the reaction temperature is 50°C,the hydrogen pressure is 0.5 MPa,and the reaction time is 12 h,at this time the reaction yield is up to 90.2%.?3?Synthesis of 2-acetamido-[hydroxy?methyl?phosphonyl]but-2-enoic acid:?a?Intermediate 2-Acetylamino-4-[hydroxy?methyl?phosphonyl]but-2-enoic acid can be synthesized by hydrolyzing of acetylaminomalonate and condensing with2-[ethoxy?methyl?phosphonyl]acetaldehyde under weak basic conditions.In the hydrolysis reaction,when the molar ratio of sodium hydroxide and diethyl acetylaminomalonate is 1.02:1,the temperature is 25-30?,the reaction time is 16hours,the yield of acetamidomalonic acid monoethyl ester can reach 85.3%;In the condensation reaction,the optimized molar ratio of acetaminomalonate monoethyl ester:phosphonaldehyde:pyridine:acetic anhydride=1.1:1:10:3-4,and the final product yield can reach 74%.?b?In another route,2-oxo-4-?hydroxymethylphosphoryl?butyric acid react with acetamide to produce 2-acetylamino-4-Hydroxy?methyl?phosphono]but-2-enoic acid under the catalysed by p-toluenesulfonic acid:The ratio of acetamide to2-oxo-4-?hydroxymethylphosphoryl?butyric acid is 2:1,the molar amount of p-toluenesulfonic acid is 3%of 2-oxo-4-?hydroxymethylphosphoryl?,and the toluene was refluxed to take off water,the yield can reach 68.4%.?4?Synthesis of L-glufosinate by asymmetric hydrogenation:we take[Rh?nbd?₂]Sb F₆as a metal precursor and Duanphos as a ligand.When the molar amount of the catalyst to the chiral hydrogenation substrate is 1/1000,the reaction temperature is50°C,the reaction pressure is 5-6 MPa and the reaction time is 12 h,the conversion rate is over 99%.The specific optical rotation is+2.27°?c=1.00,H₂O?and the e.e.value is about26.7%.Duanphos has a high reactivity in the catalytic reaction,and the L-glufosinate is a dominant configuration,but the enantioselectivity is poor.The main intermediates and target products are characterized by nuclear magnetic resonance spectroscopy.