DESC:PROCESS FOR THE PREPARATION OF ESTER OF HALO ACRYLIC ACID
Field of the invention
The present invention provides a process for the preparation of methyl 2-fluoroacrylate of Formula VI.
Background of the invention
The methyl 2-fluoroacrylate (MFA) of Formula VI is a key intermediate for agrochemicals and pharmaceuticals. Crossed Claisen condensation of alkyl monofluoroacetates with esters of formic acid or oxalic acid in the presence of strong bases, followed by a reaction with paraformaldehyde represents one of the most widely used methods for the synthesis of a-fluoroacrylates.
Formula VI
The PCT Publication No. WO 2014/034906 relates to a method for producing a-fluoroacrylic acid ester having the formula H2CCFCO2R, wherein, R represents the alkyl group that may be substituted by one or more fluorine atoms. The a-fluoroacrylic acid ester is obtained by reacting a compound having the formula H2CCFX, wherein X is Br or Cl, with an alcohol and carbon monoxide in the presence of a transition metal catalyst and a base.
The PCT Publication No. WO 2014/001365 provides a process for the manufacture of an alkylfluoroacrylate, by reacting an alkylfluoroacetate with an ester of formic acid or oxalic acid in the presence of a base in a crossed Claisen condensation resulting in a Claisen salt. The Claisen salt is reacted with paraformaldehyde to isolate alkylfluoroacrylate, using an alkane as solvent. The process disclosed suffers from the disadvantages that the isolated MFA contains residual methyl fluoroacetate and solvents. Purification of MFA from starting material, residual solvents and side-products is difficult because of very close boiling points and careful column vacuum distillation is required. Also, the starting material methyl monofluoro acetate is highly toxic and hence there is difficulty in handling at the industrial level.
It is therefore, an object of the present invention to provide an improved process for the preparation of methyl 2-fluoroacrylate with high purity and high yield. The present invention provides a process of preparation of methyl 2-fluoroacrylate using elemental fluorine, which is simple, economically viable and industrially doable, due to easy isolation of methyl 2-fluoroacrylate in comparison to prior arts.
Summary of the invention
The present invention provides a process for the preparation of a compound of Formula VI, comprising;
a) reacting a compound of Formula I with chlorine in the presence of dimethyl formamide to produce a compound of Formula II;
b) reacting the compound of Formula II with an organic base to produce a compound of Formula III;
c) reacting the compound of Formula III with bromine to produce a compound of Formula IV;
d) reacting the compound of Formula IV with bromine and free fluorine in a solvent to produce a compound of Formula V;
e) reacting the compound of Formula V with zinc to produce a compound of Formula VI; and
f) isolating the compound of Formula VI from Formula IV Formula V Formula VI
Detailed description of the invention
The present invention provides a process for the preparation of a compound of Formula VI, comprising;
a) reacting a compound of Formula I with chlorine in the presence of dimethyl formamide to produce a compound of Formula II;
b) reacting the compound of Formula II with an organic base to produce a compound of Formula III;
c) reacting the compound of Formula III with bromine to produce a compound of Formula IV;
d) reacting the compound of Formula IV with bromine and free fluorine in a solvent to produce a compound of Formula V;
e) reacting the compound of Formula V with zinc to produce a compound of Formula VI; and
f) isolating the compound of Formula VI from The compound of Formula I may be obtained commercially or may be prepared by any of the methods known in the art, for example, as in the U.S. Patent no. 3,925,463.
The step a) may be carried out at a temperature in the range of 10oC to 50oC. The step b) may be carried out at a temperature in the range of 20oC to 60oC. The step c) may be carried out at a temperature in the range of 10oC to 58oC. The step d) may be carried out at a temperature in the range of 15oC to 40oC. The step e) may be carried out at a temperature in the range of 55oC to 100oC.

The step b) may be carried out in the presence of polymerization inhibitors such as 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT), methyl hydroquinone, hydroquinone, phenothiazine or other polymerization inhibitors known in the art.

The organic base may be selected from triethyl amine, diethyl amine, trimethyl amine and other organic base as known in the art.
The bromine may be in gaseous form or liquid form. The bromine utilized in present invention is greater than 90% pure.
The free fluorine used may be generated electrochemically or by other methods known in the art.
The solvent may be selected from bromine, perfluorinated solvents or a mixture thereof. The perfluorinated solvent may be selected from perfluoro 2-methyl pentane, perfluorohexane, perfluoromethyl cyclohexane.

The compound of Formula VI, obtained by the process of the present invention has a purity greater than 90% by gas chromatography, preferably greater than 93%.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
The following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.
Examples
Example 1: Preparation of Methyl 2,3-dichloropropanoate
Methyl acrylate (2366 g, 27.5 mol) and dimethylformamide (DMF) (40 g, 0.55 mol) was placed in a 3-liter three necked flask fitted with a stirrer, thermometer, inlet tube and gas trap. Chlorine (950 g, 0.48 mol) was passed into the methyl acrylate rapidly over a period of ten hours while the temperature was kept below 40°C. Reaction progress was monitored by gas chromatography (GC). When it seemed that 50 percent of chlorine was consumed, the reaction was stopped. The reaction mass was taken for distillation to separate methylacrylate and Methyl 2,3-dichloropropanoate. The contents were subjected to vacuum distillation. Methyl 2,3-dichloropropanoate was collected distilling at 70°C.
Yield (%):77.2
Purity (%) = 98

Example 2: Preparation of methyl 2-chloropropenoate
Methyl 2,3-dichloropropanoate (200 g, 1.27mol), water (174g) and BHT (1.12 g, 0.005 mol) were taken into a reaction vessel fitted with a mechanical stirrer. Triethylamine (128.3 g, 1.27mol) was added drop wise to methyl 2,3-dichloropropanoate for 0.50 hours and the progress of the reaction was monitored by gas chromatography. After the completion of reaction, the organic layer was separated from the aqueous layer and the organic layer contained the crude methyl 2-chloropropenoate.
Yield (%): 93.12
Purity (%): 97.5 Example 3: Preparation of methyl 2,3-dibromo-2-chloropropanoate
Methyl 2-chloropropenoate (496 g, 4.13 mol) and BHT (3.65 g, 0.016 mol) were taken into the reaction vessel with mechanical stirrer. Bromine (670 g, 4.18 mol) was added drop-wise to the vessel while keeping the temperature below 40°C to obtain methyl 2,3-dibromo-2-chloropropanoate. Progress of the reaction was monitored by gas chromatography.
Yield (%): 92
Purity (%): 98
Example 4: Preparation of methyl 3-bromo-2-chloro-2-fluoropropanoate
Methyl-2, 3-dibromo-2-chloro propionate 150g (0.539 mole) and Bromine 614g (3.83 mole), were charged into a 450 mL hast alloy reactor and 15.37g (0.40 mole) of fluorine was passed into the reactor at 100mL per hour. The temperature was maintained at 15 to 35°C. After completion of addition the reaction mass was stirred for 1 hour. Reaction was monitored using Gas chromatography. After completion of reaction, the reaction mass was unloaded.
The reaction mixture was fed to boil off, The Bromine was boiled out and the crude reaction mixture treated with sodium metabisulphite solution then organic layer was separated. The organic layer was distilled under vacuum, the compound collected at 10 mmHg at 62°C.
Yield - 85%.
Example 5: Preparation of methyl 2-fluoroacrylate
Zinc (6g, 0.092 mol), water (20g, 1.11 mol), conc. H2SO4 (0.2g, 0.002 mol) and phenothiazine (0.5g, 0.0025 mol) were added sequentially in a reaction vessel. The reaction mixture was heated to 82°C to 86°C and methyl 3-bromo-2-chloro-2- fluoropropanoate (15 g, 0.068 mol) was added to the reaction mass slowly over a period of 20 minutes. An azeotropic mixture was distilled off at 55°C and 550 mbar simultaneously. Then, 10 ml saturated calcium chloride solution was added to the azeotropic mixture and the organic layer was separated and dried to give methyl 2-fluoroacrylate as a clear colourless liquid.
Yield (%): 85
Purity (%): 94

CLAIMS:1. A process for the preparation of a compound of Formula VI, comprising:
a) reacting a compound of Formula I with chlorine in the presence of dimethyl formamide to produce a compound of Formula II;
b) reacting the compound of Formula II with an organic base to produce a compound of Formula III;
c) reacting the compound of Formula III with bromine to produce a compound of Formula IV;
d) reacting the compound of Formula IV with bromine and free fluorine in a solvent to produce a compound of Formula V;
e) reacting the compound of Formula V with zinc to produce a compound of Formula VI; and
f) isolating the compound of Formula VI from step e)

Formula I Formula II Formula III

Formula IV Formula V Formula VI

2. The process as claimed in claim 1, wherein the process is carried out at a temperature in the range of 10oC to 100oC;
3. The process as claimed in claim 1, wherein the step b) is carried out in the presence of polymerization inhibitors selected from the group consisting of 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT), methyl hydroquinone, hydroquinone and phenothiazine.
4. The process as claimed in claim 1, wherein the organic base used in step b) is selected from the group consisting of triethyl amine, diethyl amine and trimethyl amine.
5. The process as claimed in claim 1, wherein the bromine used in step c) and step d) is in gaseous form or liquid form.
6. The process as claimed in claim 1 or claim 5, wherein the bromine used in step c) and step d) has purity greater than 90%.
7. The process as claimed in claim 1, wherein the solvent used in step d) is selected from the group consisting of bromine and perfluorinated solvents or a mixture thereof.
8. The process as claimed in claim 7, wherein the perfluorinated solvent is selected from the group consisting of perfluoro 2-methyl pentane, perfluorohexane, perfluoromethyl and cyclohexane.
9. The compound of Formula VI, obtained by the process as claimed in claim 1 has purity greater than 90%, preferably greater than 93% by gas chromatography.