Method for producing specific crystalline modifications of polmorphous substances
View Patent ↗The present invention pertains to a process for the production of a specific crystal modification of a polymorphic, organic substance by precipitation of the specific crystal modification from the aqueous solution of the salt of the polymorphic substances using ordinary water-soluble organic solvents as additives as well as an acid or base.
1. A process for the production of a specific crystal modification of 2-(2-chloro-4-mesyl-benzoyl)-cyclohexane-1,3-dione comprising precipitating the specific crystal modification from an aqueous solution of a salt of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione with an acid or base in the presence of a water-soluble organic solvent selected from the group consisting of ketones and alcohols and mixtures thereof.
2. A process according to claim 1 additionally comprising adding seed crystals of the specific crystal modification when the solution is supersaturated.
3. A process according to claim 1 comprising adding the acid or base to an existing mixture of the aqueous solution of the salt of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione, the additive, and optional seed crystals.
4. A process according to claim 1 comprising adding the aqueous solution of the salt of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione to an existing mixture of acid or base, the additive, and optional seed crystals.
5. A process according to claim 1 comprising steadily adding the aqueous solution of the salt of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione and the acid or base at the same time with stirring to an existing mixture of the aqueous solution of an additive, optionally in the presence of seed crystals.
6. A process according to claim 1 in which the pH value is kept at about pH 2.7.
7. A process according to claim 1 in which the organic solvent is an alcohol with 1 to 10 carbon atoms, a ketone with 3 to 10 carbon atoms, or a mixture thereof.
8. A process according to claim 1 in which the acid or base is used in an amount equinormal to the salt of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione.
9. A process according to claim 1 in which the amount (w/w) of the organic solvent is less than 10% of the amount of the crystal modification of 2-(2-chloro-4-mesyl-benzoyl)cyclohexane-1,3-dione to be precipitated.
10. A process according to claim 1 carried out at a temperature at which the desired crystal modification is the stable form.
11. A process according to claim 1 in which the arrangement of the dosing locations for the reagents and/or the power input from the stirrer ensures mixing that avoids local supersaturation peaks.
12. A process according to claim 1 in which the organic solvent is acetone, 2-butanone, methanol, ethanol, 2-propanol, or a mixture thereof.