METHOD FOR PRODUCING 2-HALOGEN-ACRYLIC ACID ESTERS

Abstract

The present invention relates to a process for preparing 2-haloacrylic esters from 2-hydroxymethyl- or 2-halomethyl- or 2-chlorosulfinyloxymethyl-2-halomalonic diesters. The invention further provides novel 2-halomethyl-2-halomalonic diesters or 2-chlorosulfinyloxymethyl-2-halomalonic diesters which can be used for preparation of the 2-haloacrylic esters.

Claims

1. A process for preparing 2-haloacrylic esters of the formula (IV) ##STR00013## in which R.sub.1 is C.sub.1-C.sub.15-alkyl, preferably C.sub.1-C.sub.6-alkyl, or C.sub.3-C.sub.6-cycloalkyl or C.sub.6-C.sub.24-aryl and X.sub.1 is fluorine, chlorine, chlorosulfinyloxy or bromine, preferably fluorine, comprising the step of: a) reacting compounds of the formula (II) ##STR00014## and/or compounds of the formula (III) ##STR00015## in each of which R.sub.1 and X.sub.1 have the definition given for formula (IV) and the two R.sub.1 radicals are identical or different, preferably identical, and where X.sub.2 in formula (III) is fluorine, chlorine or bromine, preferably chlorine or bromine, in the presence of base to give compounds of the formula (IV).

2. A process for preparing 2-haloacrylic esters of the formula (IV) ##STR00016## in which R.sub.1 is C.sub.1-C.sub.15-alkyl, preferably C.sub.1-C.sub.6-alkyl, or C.sub.3-C.sub.6-cycloalkyl or C.sub.6-C.sub.24-aryl and X.sub.1 is fluorine, chlorine or bromine, preferably fluorine, comprising the step of: a) reacting compounds of the formula (II) ##STR00017## and/or compounds of the formula (III) ##STR00018## in each of which R.sub.1 and X.sub.1 have the definition given for formula (IV) and the two R.sub.1 radicals are identical or different, preferably identical, and where X.sub.2 in formula (III) is fluorine, chlorine or bromine, preferably chlorine or bromine, in the presence of base to give compounds of the formula (IV).

3. The process as claimed in claim 1 or 2, characterized in that R.sub.1 in the formulae (I) to (IV) specified is C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.6-C.sub.24-aryl, preferably methyl, ethyl, n-propyl, i-propyl, n-, i-, s- or t-butyl, n-pentyl or n-hexyl, more preferably methyl or ethyl. X.sub.1 in the formulae (I) to (IV) specified is fluorine, chlorine or bromine. More preferably, X.sub.1 is fluorine.

4. The process as claimed in claim 1 or as claimed in claim 2 or 3, characterized in that X.sub.2 in the formulae (I) to (IV) specified is chlorine or bromine, preferably chlorine.

5. The process as claimed in claim 1, characterized in that X.sub.2 in the formula (III) specified is chlorosulfinyloxy.

6. The process as claimed in claim 1 or as claimed in any of claims 2 to 5, characterized in that the compounds of the formula (II) are prepared by hydroxymethylation of dialkyl 2-halomalonates of the formula (I) with formaldehyde ##STR00019## in which R.sub.1 and X.sub.1 have the definitions given in claims 1 to 5.

7. The process as claimed in claim 1 or as claimed in any of claims 2 to 6, characterized in that the compounds of the formula (II) are prepared by reaction of compounds of the formula (II) with a halogenating agent.

8. The process as claimed in claim 7, characterized in that halogenating agents used are those selected from the group of thionyl chloride, thionyl bromide, phosphorus trichloride, phosphorus tribromide, sulfuryl chloride, sulfuryl bromide and hydrogen halides such as hydrogen chloride and bromide.

9. The process as claimed in claim 1 or as claimed in any of claims 2 to 8, characterized in that methyl 2-fluoroacrylate or ethyl 2-fluoroacrylate is prepared in step a) proceeding from dimethyl 2-fluoro-2-hydroxymethylmalonate or diethyl 2-fluoro-2-hydroxymethylmalonate or proceeding from dimethyl 2-fluoro-2-chloromethylmalonate or diethyl 2-fluoro-2-chloromethylmalonate, preference being given to the preparation proceeding from dimethyl 2-fluoro-2-chloromethylmalonate or diethyl 2-fluoro-2-chloromethylmalonate.

10. The process as claimed in claim 1, characterized in that methyl 2-fluoroacrylate or ethyl 2-fluoroacrylate is prepared in step a) proceeding from dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate or diethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate, preference being given to the preparation proceeding from dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate or diethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate.

11. The process as claimed in claim 1 or as claimed in any of claims 2 to 10, characterized in that bases used are organic or inorganic bases.

12. The process as claimed in claim 1 or as claimed in any of claims 2 to 11, characterized in that bases used are alkaline earth metal or alkali metal hydroxides, amides, alkoxides, carbonates, hydrogenphosphates, phosphates, for example sodium amide, lithium diethylamide, sodium methoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, trisodium phosphate, tripotassium phosphate, disodium hydrogenphosphate, dipotassium hydrogenphosphate, sodium dihydrogenphosphate, potassium dihydrogenphosphate.

13. The process as claimed in claim 1 or as claimed in any of claims 2 to 12, characterized in that it is conducted in the presence of solvent.

14. The process as claimed in claim 1 or as claimed in any of claims 2 to 13, characterized in that it is conducted at a temperature in the range from 120 to 170 C., preferably at 140 to 160 C.

15. A process for producing plastics and polymeric additives in medicaments, characterized in that it comprises a process as claimed in claim 1 or any of claims 2 to 14.

16. A dialkyl 2-halomethyl-2-halomalonate of the formula (III) ##STR00020## in which R.sub.1 is C.sub.1-C.sub.15-alkyl, preferably C.sub.1-C.sub.6-alkyl, or C.sub.3-C.sub.6-cycloalkyl or C.sub.6-C.sub.24-aryl and X.sub.1 is fluorine, chlorine or bromine, preferably fluorine, and X.sub.2 is fluorine, chlorine or bromine, preferably chlorine or bromine.

17. A dialkyl 2-chlorosulfinyloxymethyl-2-halomalonate of the formula (III) ##STR00021## in which R.sub.1 is C.sub.1-C.sub.15-alkyl, preferably C.sub.1-C.sub.6-alkyl, or C.sub.3-C.sub.6-cycloalkyl or C.sub.6-C.sub.24-aryl and X.sub.1 is fluorine, chlorine or bromine, preferably fluorine, and X.sub.2 is chlorosulfinyloxy.

18. Dimethyl 2-fluoro-2-chloromethylmalonate and diethyl 2-fluoro-2-chloromethylmalonate.

19. Dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate and diethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate.

20. A process for preparing dialkyl 2-halomethyl-2-halomalonates of the formula (III) ##STR00022## by reacting dialkyl 2-hydroxymethyl-2-halomalonates of the formula (II) ##STR00023## with a halogenating agent, where, in the formulae (II) and (III), R.sub.1, X.sub.1 and X.sub.2 have the definition given in claim 16 or 18.

21. A process for preparing dialkyl 2-chlorosulfinyloxymethyl-2-halomalonates of the formula (III) ##STR00024## by reacting dialkyl 2-hydroxymethyl-2-halomalonates of the formula (II) ##STR00025## with thionyl chloride, where, in the formulae (II) and (III), R.sub.1, X.sub.1 and X.sub.2 have the definition given in claim 17 or 19.

Description

EXAMPLES

Example 1: Preparation of dimethyl 2-fluoro-2-hydroxymethylmalonate

(Analogously to the Manner Described in EP-A-0203462 or EP-A-0249867).

[0075] Into a solution, prepared at room temperature, of 8 g of potassium hydrogencarbonate in 80 g of a 30% aqueous formaldehyde solution were metered, at an internal temperature of 20 to 25 C., 100 g of dimethyl 2-fluoromalonate within 1 hour. After stirring at room temperature for a further 1 hour, 112 g of product were obtained in a purity of about 88% by extraction with ethyl acetate and concentration of the extract in the form of a colorless oil which solidified rapidly at room temperature to give a colorless solid. For further purification, the product was recrystallized from toluene.

Example 2: Preparation of diethyl 2-fluoro-2-hydroxymethylmalonate

(Analogously to the Manner Described in EP-A-0203462 or EP-A-0249867).

[0076] Into a solution, prepared at room temperature, of 7 g of potassium hydrogencarbonate in 70 g of a 30% aqueous formaldehyde solution were metered, after addition of 7.0 g of ethanol, 100 g of diethyl 2-fluoromalonate at an internal temperature of 20 to 25 C. within 1 hour. After stirring at room temperature for a further 3 hours, 122 g of product were obtained in a purity of about 84% by extraction with ethyl acetate and concentration of the extract in the form of a pale beige oil. For further purification, the product was recrystallized from toluene.

Example 3: Preparation of dimethyl 2-fluoro-2-chloromethylmalonate (Inventive)

[0077] To 60 g of the product from example 1 were added, at 0 to 5 C., 300 g of thionyl chloride, and the suspension that occurred as the primary product became a clear, pale beige solution after a short time. After stirring at 0 to 5 C. for a further 1 hour, 1.8 g of triethylamine were added at this temperature, and the reaction mixture was heated to reflux and heated under reflux for 48 hours. The residue that remained after concentration to dryness was taken up in 200 g of dichloromethane and the resulting solution was washed to neutrality at room temperature with 200 g of a 5% by weight aqueous sodium hydrogencarbonate solution. The organic phase was reconcentrated to dryness and the remaining residue was fractionally distilled at about 10 mbar. Nearly 50 g of a yellowish oil having a purity of >98% were obtained (about 75% of theory).

Example 4: Preparation of diethyl 2-fluoro-2-chloromethylmalonate (Inventive)

[0078] To 100 g of the product from example 2 were added, at 0 to 5 C., 400 g of thionyl chloride, and a clear brown solution formed after a short time. After stirring at 0 to 5 C. for a further 1 hour, 5.0 g of triethylamine were added at this temperature, and the reaction mixture was heated to reflux and heated under reflux for 48 hours. The residue that remained after concentration to dryness was taken up in 300 g of dichloromethane and the resulting solution was washed to neutrality at room temperature with 300 g of a 5% by weight aqueous sodium hydrogencarbonate solution. Concentrating the organic phase to dryness gave nearly 107 g of a beige oil having a purity of about 91% (about 88% of theory). For further purification, the product was fractionally distilled at 20 mbar in a distillation yield of about 80% of theory.

Example 5: Preparation of dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate (Inventive)

[0079] 60 g of the product from example 1 were melted and metered in molten form into an initial charge of 80 g of thionyl chloride at room temperature. After stirring at room temperature for a further 5 hours, the reaction mixture was concentrated to dryness under reduced pressure. The liquid phase that remained was 86 g of a beige oil having a purity of 90% (about 90% of theory).

Example 6: Preparation of dimethyl 2-fluoro-2-chloromethylmalonate from dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate (Inventive)

[0080] 68 g of the product for example 5 were fractionally distilled at 20 mbar. The distillate obtained was 27.7 g of a colorless oil having a purity of nearly 97% (about 60% of theory).

Example 7: Preparation of methyl 2-fluoroacrylate from dimethyl 2-fluoro-2-chloromethylmalonate (Inventive)

[0081] Into a mixture of 100 g of N-methylpyrrolidone, 70 g of sodium carbonate and 5 g of 2,6-di-tert-butyl-4-methylphenol were metered, at 300 mbar and 150 C., 50 g of the product from example 3 within about 4 hours. 27 g of a colorless liquid having a purity of 88% were obtained (about 93% of theory). For further purification, the product was fractionally distilled under reduced pressure with addition of 2,6-di-tert-butyl-4-methylphenol in a distillation yield of about 92% of theory.

Example 8: Preparation of methyl 2-fluoroacrylate from dimethyl 2-fluoro-2-hydroxymethylmalonate (Inventive)

[0082] A mixture, prepared at room temperature, of 50 g of N-methylpyrrolidone, 30 g of sodium carbonate, 2.5 g of 2,6-di-tert-butyl-4-methylphenol and 50 g of the product from example 1 was heated gradually to 150 C. at a reduced pressure of 300 mbar. The distillate obtained was washed at 0 C. with a 20% by weight aqueous sodium chloride solution to free it of methanol. 24 g of a colorless liquid having a purity of 96% were obtained (about 82% of theory).

[0083] For further purification, the product was fractionally distilled under reduced pressure with addition of 2,6-di-tert-butyl-4-methylphenol in a distillation yield of about 92% of theory.

Example 9: Preparation of methyl 2-fluoroacrylate from dimethyl 2-fluoro-2-chlorosulfinyloxymethylmalonate (Inventive)

[0084] Into a mixture of 40 g of N-methylpyrrolidone, 32 g of sodium carbonate and 1.4 g of 2,6-di-tert-butyl-4-methylphenol were metered, at 300 mbar and 130 C., 48.6 g of the product from example 5 within about 4 hours. The distillate obtained was washed with water at 0 C. 14.8 g of a colorless liquid having a purity of nearly 88% were obtained (about 82% of theory).

Example 10: Preparation of ethyl 2-fluoroacrylate from diethyl 2-fluoro-2-chloromethylmalonate (Inventive)

[0085] Into a mixture of 100 g of N-methylpyrrolidone, 24 g of sodium carbonate and 2.5 g of 2,6-di-tert-butyl-4-methylphenol were metered, at 300 mbar and 140 C., 50.7 g of the distilled product from example 4 within about 3 hours. The distillate obtained was 16.2 g of a colorless liquid having a purity of 80% (about 47% of theory). The crude product was freed of methanol by washing with a 20% by weight aqueous sodium chloride solution at 0 C.