Preparation and uses of N-methylnitrone

• US 5,892,117 A
• Filed: 06/12/1997
• Issued: 04/06/1999
• Est. Priority Date: 06/12/1997
• Status: Expired due to Fees

• Current Assignee: Albemarle Corporation
• Original Assignee: Albemarle Corporation
• Inventors: Theriot, Kevin J.
• Primary Examiner(s): Geist, Gary
• Assistant Examiner(s): Vollano, Jean F
• Application Number:
  US08/873,606
• Time in Patent Office: 663 Days
• Field of Search: 548/240, 514/646, 564/298, 564/299, 564/355, 564/347
• US Class Current: 564/347
• CPC Class Codes: C07C 213/06 from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
• CPC Class Codes: C07C 213/08 by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
• CPC Class Codes: C07C 215/08 with only one hydroxy group and one amino group bound to the carbon skeleton
• CPC Class Codes: C07C 217/20 by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
• CPC Class Codes: C07C 239/10 having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of unsubstituted hydrocarbon radicals or of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 291/02 containing nitrogen-oxide bonds
• CPC Class Codes: C07D 261/02 not condensed with other rings

Abstract

Oxidation of secondary amines with hydrogen peroxide and sodium tungstate is reported to give good yields of nitrones. However, when using dimethylamine in this manner, a considerable amount of N,N-dimethylformamide was produced as a co-product. To more selectively produce N-methylnitrone from dimethylamine, a two-step process is used which comprises (a) mixing together dimethylamine and a peroxidic compound, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed; and (b) mixing together (i) reaction mixture from (a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed. Highest yields of N-methylnitrone are achieved by conducting step (b) at a pH in the range of 7 to about 12, and at a temperature in the range of about -10° to about 100° C.

Claims

1. A process which comprises:

a) adding an aqueous solution of a peroxidic compound to an aqueous solution of dimethylamine and sodium bicarbonate, and maintaining the temperature of the resultant mixture in the range of about 0°

to about 30°

C. to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed; and

b) mixing together (i) reaction mixture from a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed.

2. A process according to claim 1 wherein b) is conducted at pH in the range of 7 to about 12, and at one or more temperatures in the range of about -10°

to about 100°

C.

3. A process according to claim 1 wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof.

4. A process according to claim 1 wherein said peroxidic compound used in forming the mixture in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in forming the mixture in b) is 10% or more aqueous hydrogen peroxide.

5. A process according to claim 4 wherein in a) the amount of said hydrogen peroxide used in forming said mixture of a) is about 1 equivalent relative to the amount of dimethylamine used in forming said mixture of a).

6. A process according to claim 1 wherein said peroxidic compound used in forming the mixture in a) is 10% or more aqueous hydrogen peroxide;

wherein said peroxidic compound used in forming the mixture in b) is 10% or more aqueous hydrogen peroxide;

wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof; and

wherein b) is conducted at pH in the range of 7 to about 12, and at one or more temperatures in the range of about -10°

to about 100°

C.

7. A process according to claim 6 wherein in a) the amount of said hydrogen peroxide used in forming said mixture of a) is about 1 equivalent relative to the amount of dimethylamine used in forming said mixture of a).

8. A process which comprises:

a) feeding aqueous hydrogen peroxide solution to an aqueous solution formed from ingredients comprising water, dimethylamine and sodium bicarbonate while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed; and

b) subjecting a mixture formed from ingredients comprising (i) reaction mixture from a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed.

9. A process according to claim 8 wherein b) is conducted at pH in the range of 7 to about 12 and at one or more temperatures in the range of about -10°

to about 100°

C.

10. A process according to claim 8 wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof.

11. A process according to claim 8 wherein the solution of hydrogen peroxide used in forming the mixture of a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in forming the mixture of b) is 10% or more aqueous hydrogen peroxide.

12. A process according to claim 11 wherein in a) the amount of said hydrogen peroxide used in forming said mixture of a) is about 1 equivalent relative to the amount of dimethylamine used in forming said mixture of a).

13. A process which comprises:

a) adding an aqueous solution of a peroxidic compound to an aqueous solution of dimethylamine and sodium bicarbonate, while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed;

b) mixing together (i) reaction mixture from a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed; and

c) mixing together N-methylnitrone from b) and styrene, and subjecting the resultant mixture to reaction conditions effective to produce a reaction mixture in which 2-methyl-5-phenylisoxazolidine has been formed.

14. A process according to claim 13 wherein b) is conducted at pH in the range of 7 to about 12, and at one or more temperatures in the range of about -10°

to about 100°

C.; and

wherein c) is conducted at one or more temperatures in the range of about -10°

to about 100°

C.

15. A process according to claim 14 wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof.

16. A process according to claim 14 wherein said peroxidic compound used in forming the mixture in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in forming the mixture in b) is 10% or more aqueous hydrogen peroxide.

17. A process which comprises:

a) adding an aqueous solution of a peroxidic compound to an aqueous solution of dimethylamine and sodium bicarbonate, while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed;

b) mixing together (i) reaction mixture from a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed;

c) mixing together N-methylnitrone from b) and styrene, and subjecting the resultant mixture to reaction conditions effective to produce a reaction mixture in which 2-methyl-5-phenylisoxazolidine has been formed; and

d) subjecting 2-methyl-5-phenylisoxazolidine from c) to hydrogenation such that N-methyl-3-phenyl-3-hydroxypropylamine is formed.

18. A process according to claim 17 wherein b) is conducted at pH in the range of 7 to about 12, and at one or more temperatures in the range of about -10°

to about 100°

C.; and

wherein the hydrogenation of d) is effected catalytically by use of hydrogen and a catalytically effective amount of a hydrogenation catalyst.

19. A process according to claim 18 wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof;

and wherein c) is conducted at one or more temperatures in the range of about -10°

to about 100°

C.

20. A process according to claim 18 wherein said peroxidic compound used in forming the mixture in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in forming the mixture in b) is 10% or more aqueous hydrogen peroxide.

21. A process which comprises:

a) adding an aqueous solution of a peroxidic compound to an aqueous solution of dimethylamine and sodium bicarbonate, while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form a reaction mixture in which N,N-dimethylhydroxylamine has been formed;

b) mixing together (i) reaction mixture from a), (ii) a peroxidic compound, and (iii) a transition metal-containing oxidation catalyst, and subjecting the resultant mixture to reaction conditions effective to form a reaction mixture in which N-methylnitrone has been formed;

c) mixing together N-methylnitrone from b) and styrene, and subjecting the resultant mixture to reaction conditions effective to produce a reaction mixture in which 2-methyl-5-phenylisoxazolidine has been formed;

d) subjecting 2-methyl-5-phenylisoxazolidine from c) to hydrogenation such that N-methyl-3-phenyl-3-hydroxypropylamine is formed; and

e) mixing together N-methyl-3-phenyl-3-hydroxypropylamine from d) and 4-halobenzotrifluoride, and subjecting the resultant mixture to reaction conditions effective to produce a reaction mixture in which N-methyl-3-phenyl-3- (4-trifluoromethyl)phenoxy!propylamine is formed.

22. A process according to claim 21 wherein b) is conducted at pH in the range of 7 to about 12, and at one or more temperatures in the range of about -10°

to about 100°

C;

wherein the hydrogenation of d) is effected catalytically by use of hydrogen and a catalytically effective amount of a hydrogenation catalyst; and

wherein in e) the 4-halobenzotrifluoride is 4-chlorobenzotrifluoride.

23. A process according to claim 22 wherein said transition metal-containing oxidation catalyst used in forming the mixture of b) is sodium tungstate or one or more hydrates thereof;

and wherein c) is conducted at one or more temperatures in the range of about -10°

to about 100°

C.

24. A process according to claim 22 wherein said peroxidic compound used in forming the mixture in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in forming the mixture in b) is 10% or more aqueous hydrogen peroxide.

25. A process which comprises:

a) adding an aqueous solution of hydrogen peroxide to an aqueous solution of dimethylamine and sodium bicarbonate, while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form N,N-dimethylhydroxylamine;

b) reacting N,N-dimethylhydroxylamine from a) with a peroxidic compound in the presence of an added transition metal-containing oxidation catalyst to form N-methylnitrone;

c) reacting N-methylnitrone from b) and styrene to form 2-methyl-5-phenylisoxazolidine;

d) hydrogenating 2-methyl-5-phenylisoxazolidine from c) to form N-methyl-3-phenyl-3-hydroxypropylamine; and

e) reacting N-methyl-3-phenyl-3-hydroxypropylamine from d) and 4-halobenzotrifluoride to form N-methyl-3-phenyl-3- (4-trifluoromethyl)phenoxy!propylamine.

26. A process which comprises:

a) adding an aqueous solution of hydrogen peroxide to an aqueous solution of dimethylamine and sodium bicarbonate, while maintaining the reaction temperature in the range of about 0°

to about 30°

C. to form an N,N-dimethylhydroxylamine-containing reaction mixture; and

b) reacting reaction mixture from a) and a peroxidic compound, in the presence of an added transition metal-containing oxidation catalyst, to form a reaction mixture in which N-methylnitrone has been formed.

27. A process according to claim 26 wherein the solution of hydrogen peroxide used in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxide-compound used in b) is 10% or more aqueous hydrogen peroxide.

28. A process according to claim 27 wherein said added transition metal-containing oxidation catalyst is sodium tungstate or one or more hydrates thereof.

29. A process according to claim 26 which further comprises:

c) reacting N-methylnitrone from b) and styrene to form a 2-methyl-5-phenylisoxazolidine-containing reaction mixture.

30. A process according to claim 29 which further comprises:

d) hydrogenating 2-methyl-5-phenylisoxazolidine from c) to form N-methyl-3-phenyl-3-hydroxypropylamine.

31. A process according to claim 30 which further comprises:

e) reacting N-methyl-3-phenyl-3-hydroxypropylamine from d) and 4-halobenzotrifluoride to form N-methyl-3-phenyl-3- 4-trifluoromethyl)phenoxy!propylamine.

32. A process according to claim 31 wherein the solution of hydrogen peroxide used in a) is 10% or more aqueous hydrogen peroxide, and wherein said peroxidic compound used in b) is 10% or more aqueous hydrogen peroxide.

33. A process according to claim 32 wherein said added transition metal-containing oxidation catalyst of b) is sodium tungstate or one or more hydrates thereof.