CLIAMS:1. An improved process for the preparation of fenpyroximate having formula [I], said process comprises reacting 4-chloromethylbenzoic acid tertiary butyl ester having formula [II] and 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime having formula [III] in an organic solvent, in presence of a base, water and a tetraalkylammonium halide at a temperature between 25°C and 100°C.

2. The process as claimed in claim 1, wherein said solvent is selected from benzene, toluene, xylene, dichloromethane, chloroform. 1,2-dichloroethane or 1,2-dichlorobenzene.
3. The process as claimed in claim 2, wherein said solvent is toluene.
4. The process as claimed in claim 1, wherein the ratio of said 4-chloromethylbenzoic acid tertiary butyl ester to said solvent is between 1:5 and 1:10.
5. The process as claimed in claim 4, wherein the ratio of said 4-chloromethylbenzoic acid tertiary butyl ester to said solvent is 1:6 to 1:7.
6. The process as claimed in claim 1, wherein said base is selected from alkali or alkaline earth metal hydroxide such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide or barium hydroxide.
7. The process as claimed in claim 6, wherein said base is potassium hydroxide.
8. The process as claimed in claim 6, wherein said molar ratio of potassium hydroxide is between 1.0 and 2.0 mole equivalents.
9. The process as claimed in claim 8, wherein said molar ratio of potassium hydroxide is preferably 1.1 moles equivalent.
10. The process as claimed in claim 1, wherein said tetraalkylammonium halide is selected from benzyltriethylammonium chloride , tetrabutylammonium bromide, tetrabutylammonium bisulphate, or tricaprylmethyl chloride.
11. The process as claimed in claim 10, wherein said tetraalkylammonium halide is tetrabutyl ammonium bromide.
12. The process as claimed in claim 1, wherein said mole ratio of tetraalkylammonium halide ranges from 1 mole percent to 10 mole percent, of 4-chloromethylbenzoic acid tertiary butyl ester.
13. The process as claimed in claim 12, wherein said mole ratio of tetraalkylammonium halide is 1.5 mole percent of 4-chloromethylbenzoic acid tertiary butyl ester.
14. The process as claimed in claim 1, wherein proportion of said water is between 10 and 20 percent, weight for weight, of 4-chloromethylbenzoic acid tertiary butyl ester.
15. The process as claimed in claim 1, wherein proportion of said water is 15 percent, weight for weight, of 4-chloromethylbenzoic acid tertiary butyl ester.
16. The process as claimed in claim 1, wherein said temperature ranges between 25°C and 100°C.
17. The process as claimed in claim 15, wherein said temperature ranges between 30°C and 35°C.
18. Fenpyroximate of formula [I] as obtained by process as claimed in claim 1 having yield between 90% and 100%.
19. Fenpyroximate of formula [I] as obtained by process as claimed in claim 1 having purity between 92% and 99%.
,TagSPECI:Field of invention
The present invention relates to a process for preparation of fenpyroximate, a phenoxypyrazole acaricide commonly used against mites.
Background and prior art of the invention
Phenylpyrazoles with an herbicidal activity have been known in the art since the 1990s. The first uses of such compounds were reported in European patent applications EP 234,045, EP 361,114, EP 447,055, EP 839,808 and Japanese patent applications JP 3,151,367, JP 3,163,063. Fenpyroximate as known as t-Butyl (E)-alpha-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneaminooxy)-p-toluate represented below as Formula I, is a phenoxypyrazole acaricide that is commonly used against mites.

Formula I
Various methods and processes are known for the preparation of fenpyroximate. They usually involve a reaction between 4-halomethylbenzoic acid tertiary butyl ester (Formula II) and 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime (Formula III)

Formula II Formula III
Such reactions are usually carried out using high boiling polar solvents such as dimethylformamide or dimethyl sulphoxide in the presence of a base. Conventionally, as disclosed in EP0234045, fenpyroximate was prepared in 67% yield by reacting of tert-butyl 4-(bromomethyl)benzoate with 1,3-dimethy 1-5-phenoxypyrazole-4--carboxaldehyde oxime in the presence of potassium hydroxide in dimethyl sulphoxide. Park Hvun-Ja et al reported in Bulletin of Korean Chemical Society 26, 668-670 (2005) that the reaction of 4-chloromethylbenzoic acid tertiary butyl ester with 1,3-dimethyl-5-phenoxypyrazole-4-carboxaldehyde oxime when carried out in dimethyl sulphoxide in presence of potassium hydroxide provided fenpyroximate having an yield of 79%. In CN 101273720 the above reaction has been carried out in presence of sodium methoxide in dimethylformamide. Park Hyun-Ja et al reported in Bioorganic & Medicinal Chemistry Letters 15, 3307 (2005) that fenpyroximate can also prepared from the same two intermediates using sodium hydride in tetrahydrofuran. Ma Hongtig et al, carried out the same reaction in presence of potassium carbonate in ethyl methyl ketone and reported the results in Jingxi Huangong Zhongjiianti 37, 22-24 (2007), which had an overall fenpyroximate yield of 55% in five steps.
However all these processes utilize solvents miscible with water and thus suffer from recovery problems. The fact that the solvents used are miscible with water makes the recovery and recycling less than optimal besides increasing the level of organics in the effluent streams.
In 96/MUM/2012, the applicant acknowledged these problems and sought to overcome it by carrying out the reaction under the conditions liquid-liquid phase transfer catalysis (LLPTC). It reacted 4--chloromethylbenzoic acid tertiary butyl ester with 1,3-dimethyl-5-.phenoxy-pyrazole-4-carboxaldehyde oxime in presence of about 25% w/w aqueous sodium hydroxide and benzyltriethylammonium chloride without using any solvent. The process gave a yield of around 79%, possibly due to side reaction of 4- chloromethylbenzoic acid tertiary butyl ester to the corresponding bisether. It is similar to results reported by Wang T-T et al in J. Molecular Catalysis 57, 271-289 (1990) wherein benzyl chloride led to the formation of dibenzyl ether under similar experimental conditions of LLPTC.
Therefore, there remains a need for a process for preparation of fenpyroximate which does not utilize high boiling organic solvents, has simpler recovery steps and provides significantly better yield and purity.
Accordingly, the present invention provides a novel and improved process for preparation of fenpyroximate in higher yield and better purity.
OBJECTS OF THE INVENTION
It is an object of the present invention to overcome the disadvantages of prior art methods.
It is another object of the present invention to provide a novel and improved process for preparation of fenpyroximate in higher yield and better purity.
It is another object of the present invention to provide a method which involves simple recovery steps and is easy to carry out.
It is yet another object of the present invention to provide a method which avoids the use of high boiling organic solvents and other expensive solvents/reagents.
SUMMARY OF THE INVENTION
In one aspect, the invention provides a novel and improved process for preparation of fenpyroximate by reacting of 4-chloromethylbenzoic acid tertiary butyl ester with 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime in an organic solvent, in presence of a base, water and a phase transfer catalyst at a mildly elevated temperature.
In another aspect the invention provides a process results in fenpyroximate having better purity and higher yield.
In yet another aspect, the invention provides an efficient process utilizing aromatic solvents that are easy to recover and recycle.
In a further aspect, the invention employs the conditions of solid liquid phase transfer catalysis to obtain fenpyroximate under mild conditions and reduced batch time cycles for improved purity and increased productivity.
DETAILED DESCRIPTION
According to the invention, there is provided a process for the preparation of fenpyroximate by the reaction of 4-chloromethylbenzoic acid tertiary butyl ester with 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime. The reaction is carried out by stirring 4-chloromethylbenzoic acid tertiary butyl ester with 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime in an organic solvent in presence of a base and a phase transfer catalyst at a mildly elevated temperature for a period such that the starting material, 4-chloromethylbenzoic acid tertiary butyl ester is less than 1 % in the reaction mixture by high performance liquid chromatography.

The present inventors surprisingly found that upon using an organic solvent under the solid-liquid phase transfer catalysis reaction conditions leads to significantly higher yield and better purity of fenpyroximate. The solvents used are aromatic hydrocarbons like benzene, toluene, xylene or chlorinated solvents such as dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dichlorobenzene. The preferred solvent is toluene.
The base used can be an alkali or alkaline earth metal hydroxide such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide or barium hydroxide. The preferred base used is potassium hydroxide.
The phase transfer catalyst can be a tetra-alkylammonium halide like benzyltriethylammonium chloride, tetrabutylammonium bromide and tetrabutylammonium bisulphate or tricaprylmethyl chloride. The preferred phase transfer catalyst is tetrabutyl ammonium bromide.
The reaction can be carried out at 25°C to reflux temperature of the solvent used. The preferred temperature is between 30°C and 35°C. There was no adverse effect on yield or purity of the product when the reaction was carried out at elevated temperatures up to 1000C.
The present process also avoids use of any corrosive chemicals thereby rendering it more efficient and less hazardous.
The conversions in the reaction are close to 100% leading to high yields and purities.
Therefore the present invention is simple, easy, convenient and time effective. For these reasons, the process is easily scalable, economical and commercially viable.
The invention is now illustrated by way of non-limiting examples
EXAMPLE-1: Preparation of fenpyroximate under LLPTC
A mixture of 4-chloromethylbenzoic acid tertiary butyl ester (22.67g: 0.1 mol) and 1,3�dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime ( 25.0g: 0.105 mol) was stirred in 100ml of water containing 0.5g of tetrabutylammonium bromide at 30° and a solution of potassium hydroxide (7.42g; 0.11 mol) was added at rate that the temperature did not rise above 35°. The contents were stirred at 30-35° for 12 hours. Tine organic layer was extracted with toluene (150 ml) and the toluene extract was washed free of alkali. Toluene was distilled off under reduced pressure and the residue was suspended in ethanol (50 ml). The solid precipitate was filtered and dried at 55-60° under vacuum to provide 30.0 grams of a solid containing 67 % of fenpyroximate (by HPLC)
EXAMPLE-II: Preparation of fenpyroximate without using phase transfer catalyst
To a solution of 4-chloromethylbertzoic acid tertiary butyl ester (22.67g; 0.1 mol) and 1,3-dimethyl-5-phenoxy-pyrazole-4-,carboxaldehyde oxime (25.0g; 0.105 mol) in 150 ml. of toluene were added 3.4 ml of water and potassium hydroxide (7.42g: 0.11 mol). The reaction mixture was stirred at 30-35° for 12 hours. The organic layer was washed free of alkali with water (100ml x 3). After removal of toluene under reduced pressure, the residue was suspended in 50 ml. of ethanol. The solid so obtained was filtered and dried at 55-60° under vacuum to give 18.0 g of a solid which contained 71.19 % of fenpyroximate (by HPLC)
EXAMPLE-III: Preparation of fenpyroximate under SLPTC
To a solution of 4-chloromethylbenzoic acid tertiary butyl ester (22.67g; 0.1 mol) and 1,3-dimethyl-5-phenoxy-pyrazole-4-carboxaldehyde oxime ( 25.0 g: 0.105 mol) in 150 ml. of toluene were added 3.4 ml of water , potassium hydroxide (7.42g; 0.11 mol) and 0.5g of tetrabutylammonium bromide at room temperature. The reaction mixture was stirred at 30-35° for 12 hours. The organic layer was washed free of alkali with water (100 ml x 3). After removal of toluene under reduced pressure, the residue was suspended in 50 ml of ethanol. The solid so obtained was filtered and dried at 55-60°C under vacuum to give 40.0 g of a solid which contained 98.42 % of fenpyroximate (by HPLC); yield, 93.42%