Preparation of trisubstituted benzoic acid precursors

• US 5,055,605 A
• Filed: 10/15/1990
• Issued: 10/08/1991
• Est. Priority Date: 10/15/1990
• Status: Expired due to Fees

• Current Assignee: Zeneca Incorporated (Astrazeneca PLC)
• Original Assignee: Imperial Chemical Industries PLC (IMPERIAL CHEMICAL INDUSTRIES)
• Inventors: Ludvik, Charles N.
• Primary Examiner(s): Dees, Jose G.
• Assistant Examiner(s): CLARKE, VERA
• Application Number:
  US07/599,203
• Time in Patent Office: 358 Days
• Field of Search: 560/11, 560/12, 562/429, 562/430, 568/28, 568/30, 568/31, 568/33
• US Class Current: 560/11
• CPC Class Codes: C07C 315/02 by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
• CPC Class Codes: C07C 317/44 having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton

Abstract

The process of the present invention relates to the preparation of precursor trisubstituted benzoic acid intermediates having the structural formula ##STR1## wherein R is --COOR^a wherein R^a is C₁ -C₆ alkyl; C₁ -C₄ alkyl; formyl or C(O)R^b wherein R^b is C₁ -C₄ alkyl;

R¹ is hydrogen, halogen, nitro, C₁ -C₂ alkyl, C₁ -C₂ alkoxy or trifluoromethyl;

R² is hydrogen, halogen, C₁ -C₄ alkoxy, C₁ -C₄ alkyl --OCH₂ CH₂ OCH₃, --OCH₂ CH₂ OC₂ H₅ or a substituted methyl group and

R³ is C₁ -C₄ alkyl or C₁ -C₄ haloalkyl.

Claims

1. An improved process for the preparation of a compound having the structural formula ##STR7## wherein R is --COOR^a wherein R^a is C₁ -C₆ alkyl;

C₁ -C₄ alkyl;

formyl or C(O)R^b wherein R^b is C₁ -C₄ alkyl;

R¹ is hydrogen, halogen, nitro, C₁ -C₂ alkyl, C₁ -C₂ alkoxy or trifluoromethyl;

R² is hydrogen, halogen, C₁ -C₄ alkoxy, C₁ -C₄ alkyl, --OCH₂ CH₂ OCH₃, --OCH₂ CH₂ OC₂ H₅ or a substituted methyl group and

R³ is C₁ -C₄ alkyl or C₁ -C₄ haloalkyl

comprising a step of reacting a compound having the structural formula ##STR8## wherein R, R¹, R² and R³ are as defined with hydrogen peroxide and water wherein the improvement comprises a) running the reacting step in a solvent that is immisicible with water and has an azeotroping temperature with the water of less than 100°

C., and b) maintaining during the reacting step the concentration of the hydrogen peroxide at above 70 percent by weight based upon the combined weight of the hydrogen peroxide and water in the reaction mixture.

2. The process of claim 1 wherein R is --COOR^a wherein R^a is C₁ -C₆ alkyl, R¹ is chlorine, bromine, nitro, trifluoromethyl, or methyl;

R² is hydrogen, chlorine, C₁ -C₂ alkoxy, --OCH₂ CH₂ OCH₃, --OCH₂ CH₂ OC₂ H₅, or --CH₂ OCH₃ ;

R³ is C₁ -C₂ alkyl and the solvent is toluene.

3. The process of claim 2 wherein R^a is n-propyl, R¹ is chlorine, R² is hydrogen and R³ is methyl.

4. The process of claim 2 wherein R^a is n-propyl, R¹ is nitro, R² is hydrogen, R³ is methyl.

5. The process of claim 2 wherein R^a is n-propyl, R¹ is chlorine, R² is ethoxy and R³ is ethyl.

6. The process of claim 1 wherein the solvent is toluene, xylene or ethylene dichloride.

7. The process of claim 1 wherein the solvent is toluene and concentration of the hydrogen peroxide is maintained at above 90 percent by weight based upon the combined weight of the hydrogen peroxide and water in the reaction mixture.

8. The process of claim 2 wherein the solvent is toluene and concentration of the hydrogen peroxide is maintained at above 90 percent by weight based upon the combined weight of the hydrogen peroxide and water in the reaction mixture.

9. An improved process for the preparation of a compound having the structural formula ##STR9## wherein R is --COOR^a wherein R^a is C₁ -C₆ alkyl;

C₁ -C₄ alkyl;

formyl or C(O)R^b wherein R^b is C₁ -C₄ alkyl;

R¹ is hydrogen, halogen, nitro, C₁ -C₂ alkyl C₁ -C₂ alkoxy or trifluoromethyl;

R² is hydrogen, halogen, C₁ -C₄ alkoxy, C₁ -C₄ alkyl --OCH₂ CH₂ OCH₃, --OCH₂ CH₂ OC₂ H₅ or a substituted methyl group and

R³ is C₂ -C₄ alkyl or C₁ -C₄ haloalkyl

comprising a step of reacting a compound having the structural formula ##STR10## wherein R, R¹, R² and R³ are as defined with hydrogen peroxide and water wherein the improvement comprises a) running the reacting step in a solvent that is immisicible with water and has an azeotroping temperature with the water of less than 100°

C., and b) maintaining during the reacting step the concentration of the hydrogen peroxide at above 70 percent by weight based upon the combined weight of the hydrogen peroxide and water in the reaction mixture by the azeotropic distillation of water and solvent.

10. The process of claim 9 wherein the solvent is toluene, xylene or ethylene dichloride and the azeotropic distillation is carried out at a temperature below about 100°

C.