Methods for crystallization of hydroxycarboxylic acids
View Patent ↗The invention aims at producing high-purity crystals of a hydroxycarboxylic acid represented by the following formula (1): in high yield. Provided are a method for crystallization of a compound (1) which comprises acidifying a mixture of a solution of an alkali salt of the compound (1) and an organic solvent, and a method for crystallization of compound (1) by mixing a solution of the compound (1) in a water-miscible good solvent with water, in which a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling is prepared in advance and then a main crystallization is carried out in the presence of said slurry.
1. A method for crystallization of a compound (1) of the following general formula (1):
in which R is CH 3 , CH 2 OH, CH 2 OCOR 1 , CO 2 R 2 , CONR 3 R 4 , OH, CH 2 OR 1 or CH 2 NR 3 R 4 ; R 1 is a C 1-5 alkyl group; R 2 is H or a C 1-5 alkyl group; R 3 and R 4 are independently selected from among H and C 1-5 alkyl groups; a and b each is a double bond, one of a and b is a single bond with the other being a double bond or a and b each is a single bond, which comprises
preparing a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling of the compound (1) in advance, and then
carrying out a main crystallization in the presence of said slurry by mixing a solution of the compound (1) in a water-miscible good solvent with water.
2. The method for crystallization according to claim 1 , wherein the necessary suspension amount is not more than 30 weight % based on the total amount of compound (1) at completion of main crystallization.
3. The method for crystallization according to claim 1 , wherein the slurry is prepared by preliminary crystallization or addition of crystals of compound (1).
4. The method for crystallization according to claim 1 , wherein the mixing of the solution of compound (1) in a water-miscible good solvent with water is carried out by adding water to said solution of compound (1) in the water-miscible good solvent.
5. The method for crystallization according to claim 4 , wherein the addition of water to the solution of compound (1) in a water-miscible good solvent for preliminary crystallization is carried out in such a manner that the weight ratio of said water-miscible good solvent to water will be 0.1 to 20.
6. The method for crystallization according to claim 1 , wherein the mixing of the solution of compound (1) in a water-miscible good solvent with water is carried out by adding said solution of compound (1) in the water-miscible good solvent to water.
7. The method for crystallization according to claim 6 , wherein the addition of said solution of compound (1) in a water-miscible good solvent to water for preliminary crystallization is carried out in such a manner that the weight ratio of the water-miscible good solvent to water will not be greater than 1.
8. The method for crystallization according to claim 4 , wherein the addition of said solution of compound (1) in a water-miscible good solvent or water is carried out either continuously or portion wise.
9. The method for crystallization according to claim 1 , wherein the temperature for preliminary crystallization is not higher than 70° C.
10. The method for crystallization according to claim 1 , wherein the temperature for preliminary crystallization is 0 to 50° C.
11. The method for crystallization according to claim 1 , wherein the temperature for main crystallization is not higher than 70° C.
12. The method for crystallization according to claim 11 , wherein the crystal crop is increased by cooling the main crystallization system to a final temperature of not over 30° C.
13. The method for crystallization according to claim 1 , wherein the weight ratio of the water-miscible good solvent to water at completion of main crystallization is 0.01 to 2.
14. The method for crystallization according to claim 1 , wherein the solution of compound (1) in a water-miscible good solvent is either a solution obtainable by neutralizing the reaction solution resulting from deacylation of a compound (2) of the following general formula (2):
wherein R, a and b are as defined above, and then removing the precipitated salt or other precipitate by filtration, or a solution obtainable by subjecting said reaction solution to concentration or solvent substitution.
15. The method for crystallization according to claim 14 , wherein an impurity or color contaminant by-produced in the deacylation reaction is removed with an adsorbent in advance of crystallization.
16. The method for crystallization according to claim 14 , wherein the deacylation reaction solvent doubles as the water-miscible good solvent for said solution of compound (1) in a water-miscible good solvent.
17. The method for crystallization according to claim 1 , wherein the water-miscible good solvent is a solvent selected from among C 1-6 saturated alcohols represented by C n H 2n+2 O, C 1-8 saturated diols represented by C n H 2n+2 O 2 , C 1-8 saturated triols represented by C n H 2n+2 O 3 , C 3-5 ketones represented by C n H 2n O, ethers, and nitriles.
18. The method for crystallization according to claim 1 , wherein the water-miscible good solvent is a solvent selected from among methanol, ethanol, 1-propanol, 2-propanol, butanol, 2-butanol, 2-methylpropanol, tert-butanol, 2-methylbutanol, 1,2-ethanediol, 1,3-propanediol, 1,5-pentanediol, acetone, methyl ethyl ketone, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, and acetonitrile or a mixture of two or more such solvents.
19. The method for crystallization according to claim 1 , wherein the water-miscible good solvent is a solvent selected from among methanol, ethanol, 1-propanol, 2-propanol, acetone, and acetonitrile or a mixture of two or more such solvents.
20. The method for crystallization according to claim 1 , wherein the water-miscible good solvent is a solvent selected from among methanol, 2-propanol, acetone, and acetonitrile or a mixture of two or more such solvents.