Process for the preparation of the herbicide ethyl α-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate

Abstract

A process is disclosed for the preparation of the herbicide ethyl α-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropionate by the simultaneous diazotization of 4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1-(5-amino-2-fluoro-4-chloro-phenyl)-1H-1,2,4-triazole (the Amine) and arylation of ethyl acrylate with the diazotized Amine. In the process the following reagents are added in sequence and, under specified conditions, to a cooled, stirred solution of the Amine in acetone: cuprous chloride, hydrochloric acid, ethyl acrylate, and sodium nitrite.

We claim:  
     
       1. A process for the preparation of ethyl α2-dichloro-5-[4-(difluoro-methyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropionate (the Product)  formula ( I ) by the simultaneous diazotization of 4-difluoro-methyl-4,5-dihydro-3-methyl-5-oxo-1-(5-amino-2-fluoro-4-chlorophenyl)-1H-1,2,4-triazole (the Amine) and arylation of ethyl acrylate with the diazotized Amine, wherein formula ( I )  is:                     
       which consists of  process comprises the following steps in which the amounts of all components other than the Amine are given in molar equivalents relative to one molar equivalent of the Amine: 
       (a) adding a Meerwein arylation catalyst to a stirred solution of the Amine in 10 to 30 equivalents of acetone 0.05 to 0.5 equivalents of cuprous chloride ;  
       (b) cooling the solution to a temperature in the range of −20° to 30° C. and maintaining the temperature in that range while stirring and adding sufficient hydrochloric acid to convert the Amine to the hydrochloride salt;  
       ( b )  maintaining the temperature in the range of − 20 ° to  30 ° C. and adding a sufficient amount of hydrogen chloride to form a salt of the Amine;   
       (c) maintaining the temperature below about 10° C.  while adding to the resultant slurry, with stirring,  5 to 20 equivalents of ethyl acrylate;  
       (d) bringing the temperature of the stirred reaction mixture to about 0° C.  and adding 1.0 to 2.0 equivalents of sodium nitrite over a period of 1 to 6 hours while maintaining the temperature below about 20° C.  and then continuing stirring for 15 to 90 minutes; and  
       (e) recovering the Product  formula ( I ).  
     
     
       2. The process of  claim 1  in which step (d) is followed by a washing step in which the temperature is maintained in the range of 0° to 20° C., while the reaction mixture is washed successively with dilute aqueous acid, dilute aqueous base, and an aqueous solution of sodium chloride  at least one washing step. 
     
     
       3. The process of  claim 2  in which steps (a) and (b) -( d ) are carried out under an inert atmosphere; 20 to 25 equivalents of acetone are used in step (a); the temperature in step (b) is −10° to 10° C. , and the hydrochloric acid is anhydrous; 10 to 15 equivalents of ethyl acrylate are added in step (c); in step (d) 1.4 to 1.7 equivalents of sodium nitrite are added as an aqueous solution containing 20 to 40 weight percent sodium nitrite over a period of 2 to 3 hours  at a temperature below about 10° C., and the post addition stirring is for 20 to 40 minutes ; and in  the temperature of the at least one washing step the temperature  is maintained at 5° to 10° C., the aqueous acid is 5% hydrochloric acid, and the aqueous base is 5% sodium hydroxide  in the range of  0 ° to  20 ° C. 
     
     
       4. The process of  claim 1 , wherein said Meerwein arylation catalyst is selected from the group consisting of cuprous chloride and cupric chloride. 
     
     
       5. The process of  claim 4 , wherein said Meerwein arylation catalyst is cuprous chloride. 
     
     
       6. A process for the preparation of formula ( I ):                    
         comprising:  ( i )  forming a diazotized salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole by reacting a salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole with sodium nitrite; and  ( ii )  simultaneously reacting said diazotized salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole, as it is produced in step  ( i ) , with ethyl acrylate in the presence of a Meerwein arylation catalyst to obtain said formula  ( I ). 
     
     
       7. The process of  claim 6 , wherein said Meerwein arylation catalyst is selected from the group consisting of cuprous chloride and cupric chloride, and said reactions ( i )  and  ( ii )  proceed in an aqueous medium.   
     
     
       8. A process for the preparation of formula ( I ):                    
         comprising the step of adding aqueous sodium nitrite to a solution comprising a salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole, ethyl acrylate, and a Meerwein arylation catalyst to form formula  ( I ). 
     
     
       9. The process of  claim 8 , wherein said Meerwein arylation catalyst is selected from the group consisting of cuprous chloride and cupric chloride, and said solution is aqueous. 
     
     
       10. The process of  claim 9 , wherein said solution contains acetone. 
     
     
       11. The process of  claim 8 , wherein said ethyl acrylate is added in  5  to  20  equivalents to one equivalent of said salt of  4 - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole.   
     
     
       12. The process of  claim 8 , wherein said aqueous sodium nitrite is added in  1 . 0  to  2 . 0  equivalents of said salt of  4 - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole.   
     
     
       13. The process of  claim 8 , wherein said ethyl acrylate is added in  5  to  20  equivalents to one equivalent of said salt of  4 - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole, and said aqueous sodium nitrite is added in  1 . 0  to  2 . 0  equivalents of said salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole.   
     
     
       14. The process of  claim 10 , wherein said ethyl acrylate is added in  5  to  20  equivalents to one equivalent of said salt of  4 - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole, and said aqueous sodium nitrite is added in  1 . 0  to  2 . 0  equivalents of said salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole.   
     
     
       15. The process of  claim 14 , wherein said ethyl acrylate and aqueous sodium nitrite are added at a temperature below  10 ° C. 
     
     
       16. The process of  claim 6 , wherein the simultaneous reaction in step ( ii )  further occurs in the presence of hydrochloric acid or anhydrous hydrogen chloride.   
     
     
       17. The process of  claim 8 , wherein said solution further contains hydrochloric acid or anhydrous hydrogen chloride. 
     
     
       18. The process of  claim 6 , wherein said salt of  4 - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole is a hydrochloride salt of  4   - difluoro - methyl -   4 , 5   - dihydro -   3   - methyl -   5   - oxo -   1   -(   5   - amino -   2   - fluoro -   4   - chlorophenyl )-   1 H -   1 , 2 , 4   - triazole.