Process for preparing clomazone, novel form and use of the same
View Patent ↗A process for preparing clomazone is provided, the process comprising reacting 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride in an aqueous medium in the presence of a base, in particular an alkali metal hydroxide. A method for preparing clomazone is also disclosed, the method comprising (a) crystallizing clomazone from solution in an organic solvent; and (b) isolating the resulting crystals. N-benzene is a particularly suitable solvent. Further, there is provided Form I crystalline 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (clomazone), wherein the polymorph Form I is characterized by at least one of the following properties: (i) an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ(+/−0.20° θ) at one or more of the following positions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and 28.80; and (ii) an infrared (IR) spectrum having a characteristic peak: at about 2967 and 2870 cm −1 .
1. A process for preparing clomazone, the process comprising: mixing 4,4-dimethyl-3-isoxazolidinone, 2-chlorobenzyl chloride, water, and a first base to form a basic reaction mixture, and adjusting the basic reaction mixture to a pH in the range of from 7.5 to 9.5 to react 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride at the pH of from 7.5 to 9.5.
2. The process according to claim 1 , wherein the first base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
3. The process according to claim 1 , wherein the first base is a metal base.
4. The process according to claim 3 , wherein the metal is an alkali or alkaline earth metal.
5. The process according to claim 4 , wherein the metal is sodium or potassium.
6. The process according to claim 1 , wherein the pH is in the range of from 8.5 to 9.5.
7. The process according to claim 1 , wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at an elevated temperature.
8. The process according to claim 7 , wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at a temperature in the range of 50 to 95° C.
9. The process according to claim 8 , wherein the reaction of 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is conducted at a temperature in the range of from 60 to 90° C.
10. The process according to claim 1 , wherein 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is prepared by cyclizing 3-chloro-N-hydroxy-2,2-dimethylpropanamide with a second base.
11. The process according to claim 10 , wherein the cyclizing reaction is conducted in the presence of a solvent.
12. The process according to claim 11 , wherein the solvent is water.
13. The process according to claim 10 , wherein the second base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
14. The process according to claim 10 , wherein the second base is a metal base.
15. The process according to claim 14 , wherein the metal is an alkali or alkaline earth metal.
16. The process according to claim 15 , wherein the metal is sodium or potassium.
17. The process according to claim 10 , wherein the pH of the cyclization reaction mixture is in the range of from 7.5 to 9.5.
18. The process according to claim 10 , wherein the cyclizing reaction is conducted at an elevated temperature.
19. The process according to claim 18 , wherein the cyclizing reaction is conducted at a temperature in the range of from 20 to 60° C.
20. The process according to claim 19 , wherein the cyclizing reaction is conducted at a temperature in the range of from 30 to 50° C.
21. The process according to claim 10 , wherein 3-chloro-N-hydroxy-2,2-dimethylpropanamide is prepared by the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride in the presence of a third base.
22. The process according to claim 21 , wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted in the presence of a solvent.
23. The process according to claim 22 , wherein the solvent is water.
24. The process according to claim 21 , wherein the third base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.
25. The process according to claim 21 , wherein the third base is a metal base.
26. The process according to claim 25 , wherein the metal is an alkali or alkaline earth metal.
27. The process according to claim 26 , wherein the metal is sodium or potassium.
28. The process according to claim 21 , wherein the pH of the reaction mixture of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is in the range of from 7.0 to 9.5.
29. The process according to claim 21 , wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at an elevated temperature.
30. The process according to claim 29 , wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at a temperature in the range of from 50 to 95° C.
31. The process according to claim 30 , wherein the reaction of 3-chloro-2,2-dimethylpropanoyl chloride with hydroxylamine hydrochloride is conducted at a temperature in the range of from 60 to 90° C.