Method for preparing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid
The present invention provides a method for preparing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, comprising the following steps: a) mixing acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide, performing a substitution reaction, and performing distillation under reduced pressure to obtain an acryloyl cyanide intermediate; b) mixing the acryloyl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, performing a hydrolysis reaction, and then performing purification treatment to obtain crude 2-carbonyl-3-butenoic acid; c) mixing the crude 2-carbonyl-3-butenoic acid obtained in step b) with a second solvent and methyldichlorophosphine, and performing an addition reaction to obtain a solution containing diacyl chloride; d) mixing the solution containing diacyl chloride obtained in step c) with water, performing a hydrolysis reaction, and performing purification to obtain 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid. The preparation method provided by the present invention has simple process, mild conditions, good controllability, low cost and high yield.
1 . A method for preparing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, comprising the following steps:
a) mixing acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide, performing a substitution reaction, and performing distillation under reduced pressure to obtain an acryloyl cyanide intermediate;
b) mixing the acryloyl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, performing a hydrolysis reaction, and then performing purification treatment to obtain crude 2-carbonyl-3-butenoic acid;
c) mixing the crude 2-carbonyl-3-butenoic acid obtained in step b) with a second solvent and methyldichlorophosphine, and performing an addition reaction to obtain a solution containing diacyl chloride;
d) mixing the solution containing diacyl chloride obtained in step c) with water, performing hydrolysis a reaction, and performing purification to obtain 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid.
2 . The method according to claim 1 , wherein in step a), the first solvent is selected from the group consisting of acetonitrile, ethyl acetate, tetrahydrofuran, phenylacetonitrile and a combination thereof.
3 . The method according to claim 1 , wherein in step a), the polymerization inhibitor is selected from the group consisting of 4-methoxyphenol, butylated hydroxytoluene, mono tert-butyl hydroquinone, methyl hydroquinone and a combination thereof; wherein the polymerization inhibitor and acryloyl chloride are in a mass ratio of (0.001-0.05):1.
4 . The method according to claim 1 , wherein in step a), the catalyst is cuprous cyanide; the catalyst, potassium ferrocyanide and acryloyl chloride are in a molar ratio of (0.01-0.1):(0.3-3):1.
5 . The method according to claim 1 , wherein in step a), the substitution reaction is conducted at a temperature of 0° C.-100° C. for 0.5 h-48 h.
6 . The method according to claim 1 , wherein in step a), the distillation under reduced pressure is conducted at a temperature of 10° C.-60° C.
7 . The method according to claim 1 , wherein in step b), the hydrolysis reaction is conducted at a temperature of 50° C.-130° C. for 1 h-24 h.
8 . The method according to claim 1 , wherein in step c), the second solvent is selected from the group consisting of dichloromethane, dichloroethane, chloroform, hexane, heptane, benzene, toluene, xylene and a combination thereof.
9 . The method according to claim 1 , wherein in step c), the addition reaction is conducted at a temperature of 0° C.-100° C. for 1 h-24 h.
10 . The method according to claim 1 , wherein in step d), the hydrolysis reaction is conducted at a temperature of 0° C.-100° C. for 0.1 h-24 h.