PROCESS AND INTERMEDIATE FOR THE MANUFACTURE OF DIFLUOROACETYL CHLORIDE

Abstract

The present invention concerns a process and intermediates for the manufacture of difluoro acetyl chloride. The invention further concerns a process for the manufacture of an agrochemically or pharmaceutically active compound, which comprises the process and intermediate for the manufacture of difluoro acetyl chloride for the manufacture of difluoro acetyl chloride or its intermediate.

Claims

1. A process for the manufacture of a compound of formula (I) or at least one compound of formula (III), or a mixture of the compound of formula (I) and at least one compound of formula (III), wherein a compound of formula (II) is reacted with at least one chloride compound selected from the group consisting of SiCl.sub.4, TiCl.sub.4, ZnCl.sub.2 and AlCl.sub.3 ##STR00009## wherein R.sup.1 is selected from the group consisting of C.sub.1-C.sub.12-alkyl groups, C.sub.3-C.sub.10-cycloalkyl groups, aryl and heteroaryl groups, and wherein R.sup.2 is F or Cl.

2. A process for the manufacture of a compound of formula (I), wherein at least one of the compounds of formula (III) is reacted with at least one compound selected from the group consisting of chloride compounds SiCl.sub.4, TiCl.sub.4, ZnCl.sub.2, phosphorus pentachloride, thionyl chloride, SbCl.sub.3, SbCl.sub.5, AlCl.sub.3 and metal oxide, ##STR00010## wherein herein R.sup.1 is selected from the group consisting of C.sub.1-C.sub.12-alkyl, C.sub.3-C.sub.10-cycloalkyl, aryl and heteroaryl, and wherein R.sup.2 is F or Cl.

3. The process according to claim 2, wherein the at least one compound of formula (III) is manufactured by reacting a compound of formula (II) with at least one compound selected from the group consisting of chloride compounds SiCl.sub.4, TiCl.sub.4, ZnCl.sub.2 and AlCl.sub.3, ##STR00011##

4. The process according to claim 1, wherein R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.4 alkyl groups.

5. The process according to claim 4, wherein R.sup.1 is selected from the group consisting of ethyl and methyl.

6. The process according to claim 1, wherein when the at least one compound of formula (III) is manufactured by reaction of a compound of formula (II), the chloride compound is TiCl.sub.4.

7. The process according to claim 1, wherein when the compound of formula (I) is manufactured by reaction of a compound of formula (II), the chloride compound is SiCl.sub.4, AlCl.sub.3 or a mixture of SiCl.sub.4 and AlCl.sub.3.

8. The process according to claim 7, wherein when the compound of formula (I) is manufactured by reaction of a compound of formula (II), the chloride compound is a mixture of SiCl.sub.4 and AlCl.sub.3.

9. The process according to claim 1, wherein the reaction temperature is from 0 C. to 90 C.

10. The process according to claim 1, wherein the reaction is performed in the absence of additional solvents.

11. The process according to claim 1, wherein the reaction is performed in the presence of at least one solvent.

12. A compound of formula (III) ##STR00012## wherein R.sup.1 is selected from the group consisting of C.sub.1-C.sub.12-alkyl, C.sub.3-C.sub.10-cycloalkyl, aryl and heteroaryl, and wherein R.sup.2 is F or Cl.

13. The compound according to claim 12, wherein R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.4 alkyl groups.

14. The compound according to claim 13, wherein R.sup.1 is selected from the group consisting of ethyl and methyl.

15. A process for the manufacture of a pharmaceutically or agrochemically active compound, which comprises the process according to claim 1.

16. The process according to claim 3, wherein when the at least one compound of formula (III) is manufactured by reaction of a compound of formula (II), the chloride compound is TiCl.sub.4.

17. The process according to claim 9, wherein the reaction temperature is from 10 C. to less than 50 C.

18. The process according to claim 2, wherein R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.4 alkyl groups.

19. The process according to claim 18, wherein R.sup.1 is selected from the group consisting of ethyl and methyl.

Description

EXAMPLE 1 DFAC FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE

[0041] 1-ethoxy-1,1,2,2-tetrafluoroethane was mixed with AlCl.sub.3 (0.2 eq) and SiCl.sub.4 (0.4 eq) and stirred at room temperature for one hour. A GC measurement showed complete conversion of the 1,1-dichloro-1-ethoxy-2,2-difluoroethane, wherein more than 99% DFAC was detected by GC-MS and NMR and compared with analytical standard.

EXAMPLE 2.1 1,1-DICHLORO-1-ETHOXY-2,2-DIFLUOROETHANE FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE IN ETHYL ACETATE

[0042] 1-ethoxy-1,1,2,2-tetrafluoroethane was mixed with TiCl.sub.4 (1 eq) in ethyl acetate and heated to 80 C. for 18 hours. The reaction mixture was submitted to GC measurement and was found to contain 91% 1,1-dichloro-1-ethoxy-2,2-difluoroethane.

EXAMPLE 2.2 1,1-DICHLORO-1-ETHOXY-2,2-DIFLUOROETHANE AND DFAC FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE IN ACETONITRILE

[0043] ##STR00006##

[0044] A mixture of 1-ethoxy-1,1,2,2-tetrafluorethane (0.5 g, 3.42 mmol, 1.00 eq) and acetonitrile (5.0 mL) was treated with titanium tetrachloride (0.65 g, 3.42 mmol, 1.00 eq) in a sealed vial at 80 C. for five hours. Complete conversion to DFDCE (80%) and DFAC (20%) was observed using .sup.1H-NMR analysis

EXAMPLE 3 1,1-DICHLORO-1-ETHOXY-2,2-DIFLUOROETHANE FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE

[0045] 1-ethoxy-1,1,2,2-tetrafluoroethane is mixed with TiCl.sub.4 (1 eq) in ethyl acetate and stirred at 23 C. for 18 hours. The reaction mixture is submitted to GC measurement and essentially complete conversion into 1,1-dichloro-1-ethoxy-2,2-difluoroethane is found.

EXAMPLE 4 DFAC FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE IN THE PRESENCE OF SICL.SUB.4 .AND ALCL.SUB.3

[0046] Aluminium chloride (5.5 g, 41.2 mmol, 0.40 eq) was filled into a steel reactor with Teflon inlet. Then silicon tetrachloride (8.7 g, 51.2 mmol, 0.50 eq) and TFEE (1-ethoxy-1,1,2,2-tetrafluorethane) (15.0 g, 102.7 mmol, 1.00 eq) were added, the reactor was rapidly sealed and the reaction mixture was stirred one hour at room temperature. The pressure was released through a flask cooled to 40 C. Then the reactor was heated to 50 C. and the distillate was collected. After complete transfer 18.2 g of a colourless liquid, containing 71% of DFAC (difluoroacetyl chloride) and 29% of EtCl (ethyl chloride), was obtained.

EXAMPLE 5 DFAC FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE WITH ALCL.SUB.3 .IN TETRACHLOROETHYLENE

[0047] Aluminium chloride (0.45 g, 3.38 mmol, 1.00 eq) was filled in a vial under inert atmosphere and then suspended in tetrachloroethylene (1.5 mL). Then 1-ethoxy-1,1,2,2-tetrafluorethane (0.5 g, 3.42 mmol, 1.00 eq) was added, vial sealed and reaction mixture was stirred one hour at 50 C. 1H-NMR showed complete conversion to DFAC.

EXAMPLE 6 DFAC FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE VIA DFDCE WITH TICL.SUB.4 .IN TETRACHLOROETHYLENE

[0048] ##STR00007##

[0049] Sulfolane (157 g) was preheated to 50 C. in a flask equipped with a condenser cooled to 20 C., before titanium tetrachloride (32.5 g, 171 mmol, 0.50 eq) was added and the mixture was stirred one hour at 50 C. Then 1-ethoxy-1,1,2,2-tetrafluorethane (50.0 g, 342 mmol, 1.00 eq) was added and the mixture was stirred 4 h at 60 C. Titanium tetrachloride (13.0 g, 68 mmol, 0.20 eq) was added and the temperature was reduced to 50 C. for additional 3.5 h; NMR analysis showed 98.9% conversion. The reaction mixture was cooled down with ice and then stored overnight in the fridge. The next day a Raschig-fitted column equipped with a distillation head and a condenser cooled at 20 C. was installed. The thermal cracking was started at 100 C., until reflux was observed in the column. After four hours of cracking the temperature was increased to 140 C. for 2 h and the distillate was transferred into cooled flasks (78 C.) in several fractions to give a colorless liquids giving an overall calculated DFAC yield (combined fractions) of 81%.

EXAMPLE 7 1,1-DICHLORO-1-ETHOXY-2,2-DIFLUOROETHANE FROM 1-ETHOXY-1,1,2,2-TETRAFLUOROETHANE WITH AL.SUB.2.O.SUB.3 .AND SICL.SUB.4

[0050] ##STR00008##

[0051] Alumina (36.3 g, 356 mmol, 0.52 eq) was dried in a three-necked-flask. Then the flask was equipped with a condenser cooled to 20 C. and a temperature probe. Silicon tetrachloride (60.5 g, 356 mmol, 0.52 eq) was introduced in one portion and stirring was started. Then 1-ethoxy-1,1,2,2-tetrafluorethane (100.0 g, 685 mmol, 1.00 eq) was added slowly under ice-cooling maintaining the temperature at 10-15 C. The formed gas (silicon tetrafluoride) was allowed to evaporate and was scrubbed with potassium hydroxide. After two hours of stirring at 10 C., the reaction mixture was allowed to warm up to room temperature for 2.5 hours; .sup.1H-NMR analysis showed complete conversion. The fine suspension was filtered and the filtrate was distilled at 60 mbar and 46 C. to give 78.7 g of 1-ethoxy-1,1-dichloro-2,2-difluoroethane (purity: 99.9% (GC); yield: 64%).