Claims:1. A process for the preparation of Picoxystrobin of Formula (I) which comprises;
(a) reacting methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate (MMCP) with 2-hydroxy-6-trifluoromethylpyridine (HTFMP) in presence of phase transfer catalyst and a base in a solvent, and

(b) isolating picoxystrobin.
2. The process as claimed in claim 1, wherein the phase transfer catalyst is selected from tetrabutylammonium bromide (TBAB), tetrabutylammonium iodide (TBAI), sodium iodide (NaI), potassium iodide (KI), and 1,4-diazabicyclo [2.2.2] octane (DABCO).
3. The process as claimed in claim 1, wherein the solvent is selected from dimethylformamide, dimethylacetamide, dimethyl sulfoxide, acetonitrile, propionitrile, butyronitrile, acetone, methyl ethyl ketone, tetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane and mono chlorobenzene.
4. The process as claimed in claim 1, wherein the base is selected from lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate and magnesium carbonate.
5. The process as claimed in claim 1, wherein the product is isolated by filtration.
, Description:FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of Picoxystrobin of Formula (I) using a phase transfer catalyst.

Formula (I)

BACKGROUND OF THE INVENTION
Strobilurins are a group of natural products and their synthetic analogs. Several strobilurins are used in agriculture as fungicides. They are part of the larger group of QoI inhibitors, which act to inhibit the respiratory chain at the level of Complex III.

Picoxystrobin belongs to the strobilurin group of chemicals, which are used as fungicide, in particular to control a range of fungal diseases including brown rust, tan spot, powdery mildew and net blotch in cereals, pulses and oilseeds. Picoxystrobin is a preventive and curative fungicide with systemic and translaminar movement, acting by the inhibition of mitochondrial respiration by blocking electron transfer at the Qo centre of cytochrome Bc1.

Picoxystrobin, having the chemical name methyl (E) -3-methoxy-2- [2- (6-trifluoromethyl-2-pyridyloxymethyl) phenyl] acrylate, has the following structural formula (I).

Formula (I)

The commercially available picoxystrobin product is usually manufactured by processes as described in EP0278595, CN102115458A, CN103030598A and CN 103626691A.

The purpose of the present invention is to provide a simple, economical, and commercially feasible process for the synthesis of Picoxystrobin using a phase transfer catalyst with a high yield.

SUMMARY OF THE INVENTION
The main aspect of the present invention is to provide a process for the preparation of Picoxystrobin of Formula (I) using a phase transfer catalyst.

Formula (I)
The further aspect of the present invention is to provide a process for the preparation of Picoxystrobin, which comprises;
(a) reacting methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate (MMCP) with 2-hydroxy-6-trifluoromethylpyridine (HTFMP) in presence of a phase transfer catalyst and a base in a solvent, and

(b) isolating picoxystrobin.

In another aspect of the present invention is to provide a simple, economical, and commercially feasible process for the synthesis of picoxystrobin using a phase transfer catalyst with a high yield without any purification.

DETAILED DESCRIPTION OF THE INVENTION
It is to be understood that the description of the present invention has been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known.

For the purpose of clarity and as an aid in the understanding of the invention, as disclosed and claimed herein, the following terms and abbreviations are defined below:

MMCP Methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate
HTFMP 2-hydroxy-6-trifluoromethylpyridine
DMF N, N-dimethylformamide
ACN Acetonitrile
PTC Phase transfer catalyst.
TBAB Tetrabutylammonium bromide
TBAI Tetrabutylammonium iodide
NaI Sodium iodide
KI Potassium iodide
DABCO 1,4-diazabicyclo [2.2.2] octane

The main embodiment of the present invention is to provide a process for the preparation of Picoxystrobin of Formula (I) which comprises;
(a) reacting methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate with 2-hydroxy-6-trifluoromethylpyridine in presence of a phase transfer catalyst and a base in a solvent, and

(b) isolating picoxystrobin.

According to the present embodiment, process for preparing Picoxystrobin involves, reaction of methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate (MMCP) with 2-hydroxy-6-trifluoromethylpyridine (HTFMP) in a solvent, in the presence of phase transfer catalyst and a base at a temperature of 70oC to 80oC for 10 to 12 hrs to get the reaction mixture. The resulting reaction mixture is dissolved in a mixture of water and methanol at 60 to 65oC for 1-2 hrs. Cooled the reaction mixture to 0oC to 5oC, the obtained solid is filtered and dried to get Picoxystrobin.

According to the present embodiment, the solvent used in the reaction is selected from polar-aprotic solvents such as N, N-dimethylformamide (DMF), dimethylacetamide (DMAc) and dimethyl sulfoxide (DMSO); nitrile solvents such as acetonitrile, propionitrile and butyronitrile; ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone; ether solvents such as tetrahydrofuran and 1,4-dioxane; hydrocarbon solvents such as toluene and mono chlorobenzene; chlorinated solvents such as 1,2- dichloroethane.

According to the present embodiment, the base used in the reaction is selected from alkali metal carbonates, such as potassium carbonate, sodium carbonate, calcium carbonate, magnesium carbonate and lithium carbonate.

According to the present embodiment, the phase transfer catalyst (PTC) used in the reaction is selected from tetrabutylammonium bromide (TBAB), tetrabutylammonium iodide (TBAI), sodium iodide (NaI), potassium iodide (KI), and 1,4-diazabicyclo [2.2.2] octane (DABCO).

According to the present embodiment, the product is isolated by filtration, agitated thin film drier (ATFD) or lyophilization.

According to the present embodiment methyl (E)-2-(2-(chloromethyl) phenyl)-3-methoxyacrylate (MMCP) is prepared from 3-isochromanone as per the procedure described in US5663370.

According to the present embodiment 2-hydroxy-6-trifluoromethylpyridine (HTFMP) is prepared from 2-picoline as per the procedure described in Jingxi Huagong Zhongjianti (2009), 39(3), 21-24, WO2015151116A2 and US6143899.

According to the present embodiment, process for the preparation of Picoxystrobin using phase transfer catalyst provides commercially feasible with high yield without further purification.

The further embodiment of the present invention is illustrated by the following examples, which are provided merely to be exemplary of the inventions and is not intended to limit the scope of the invention. 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.

EXAMPLES

Preparation of Picoxystrobin with Phase transfer catalyst:
Example 1
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and TBAB (6.7 g, 0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-30 oC) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol, stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 2
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and TBAI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 3
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and NaI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and Dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 4
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and KI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-30 oC) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 5
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 6
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and TBAB (6.7 g, 0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and Dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 7
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and TBAI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 8
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5eq) and NaI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 9
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and KI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 10
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 11
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and TBAB (6.7 g, 0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filter the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 12
Acetone (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and TBAI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 13
1,4-Dioxane (600 mL, 6 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and NaI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filter the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 14
Toluene (800 mL, 8 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and KI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 15
1,2-dichloroethane (400 mL, 4 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-92% yield.

Example 16
Mono chlorobenzene (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-92% yield.

Example 17
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and TBAB (6.7 g, 0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 18
Acetone (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and TBAI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80°C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 19
1,4-dioxane (600 mL, 6 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5eq) and NaI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 20
Toluene (800 mL, 8 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and KI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80°C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-95% yield.

Example 21
1,2-dichloroethane (400 mL, 4 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-92% yield.

Example 22
Monochloro benzene (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), sodium carbonate (1.5 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-92% yield.

Example 23
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and TBAI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 24
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and NaI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 25
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and KI (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. Filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 95-97% yield.

Example 26
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq), potassium carbonate (69g, 1.2 eq) and DABCO (0.05 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 10-12 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 90-92% yield.

Preparation of Picoxystrobin without Phase transfer catalyst:
Example 27
Acetonitrile (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 22 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 85-87% yield.

Example 28
Acetone (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 24 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 85-87% yield.

Example 29
1,4-Dioxane (600 mL, 6 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 26-28 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 82-84% yield.

Example 30
Toluene (800 mL, 8 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 24-26 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 82-84% yield.

Example 31
1,2-dichloroethane (400 mL, 4 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 24 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 82-84% yield.

Example 32
Mono chlorobenzene (500 mL, 5 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 22-24 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 85-87% yield.

Example 33
Dimethylformamide (300 mL, 3 vol), MMCP (100 g, 1 eq), HTMP (75 g, 1.0 eq) and potassium carbonate (69g, 1.2 eq) were taken into a 4 neck RBF equipped with mechanical stirrer. The reaction mass was stirred to 75- 80 °C and maintained for 22-24 hrs. The reaction was monitored by HPLC till the MMPC content is less than 0.5 % (Area normalization). After the completion of reaction, the reaction mass was cooled to room temperature (25-300C) and filtered under vacuum. The filtrate was collected and dimethylformamide was under vacuum at temp-80-900C, the obtained crude material was treated with solution of 10% water in methanol and stirred and heated to 64-650C and maintained for 1 hr. After completion of heating, the reaction mass was cooled to 0-50C and maintained for 1 hr. filtered the obtained precipitated solid under vacuum to afford 98% pure picoxystrobin technical with 85-87% yield.

Table 1: Comparison of reaction time and yield with PTC and without PTC:
Entry Base Catalyst Solvent Reaction time (hrs) Yield
(%)
Ex-1 K2CO3 TBAB Dimethylformamide 10-12 95-97
Ex-2 K2CO3 TBAI Dimethylformamide 10-12 95-97
Ex-3 K2CO3 NaI Dimethylformamide 10-12 95-97
Ex-4 K2CO3 KI Dimethylformamide 10-12 95-97
Ex-5 K2CO3 DABCO Dimethylformamide 10-12 90-95
Ex-6 Na2CO3 TBAB Dimethylformamide 10-12 90-95
Ex-7 Na2CO3 TBAI Dimethylformamide 10-12 90-95
Ex-8 Na2CO3 NaI Dimethylformamide 10-12 90-95
Ex-9 Na2CO3 KI Dimethylformamide 10-12 90-95
Ex-10 Na2CO3 DABCO Dimethylformamide 10-12 90-95
Ex-11 K2CO3 TBAB Acetonitrile 10-12 95-97
Ex-12 K2CO3 TBAI Acetone 10-12 95-97
Ex-13 K2CO3 NaI 1,4-Dioxane 10-12 95-97
Ex-14 K2CO3 KI Toluene 10-12 95-97
Ex-15 K2CO3 DABCO 1,2-dichloroethane 10-12 90-92
Ex-16 K2CO3 DABCO Monochloro benzene 10-12 90-92
Ex-17 Na2CO3 TBAB Acetonitrile 10-12 90-95
Ex-18 Na2CO3 TBAI Acetone 10-12 90-95
Ex-19 Na2CO3 NaI 1,4-dioxane 10-12 90-95
Ex-20 Na2CO3 KI Toluene 10-12 90-95
Ex-21 Na2CO3 DABCO 1,2-Dichloroethane 10-12 90-92
Ex-22 Na2CO3 DABCO Monochloro benzene 10-12 90-92
Ex-23 K2CO3 TBAI Acetonitrile 10-12 95-97
Ex-24 K2CO3 NaI Acetonitrile 10-12 95-97
Ex-25 K2CO3 KI Acetonitrile 10-12 95-97
Ex-26 K2CO3 DABCO Acetonitrile 10-12 90-92
Ex-27 K2CO3 Without PTC Acetonitrile 22 85-87
Ex-28 K2CO3 Without PTC Acetone 24 85-87
Ex-29 K2CO3 Without PTC 1,4-Dioxane 26-28 82-84
Ex-30 K2CO3 Without PTC Toluene 24-26 82-84
Ex-31 K2CO3 Without PTC 1,2-Dichloroethane 24 82-84
Ex-32 K2CO3 Without PTC Monochloro benzene 22-24 85-87
Ex-33 K2CO3 Without PTC Dimethylformamide 22-24 85-87

Advantages of the present invention with phase transfer catalyst:
1. Reaction time reduces from 22-28 hrs to 10-12 hrs.
2. Yield improves from 82-84% to 95-97%.
3. Involves simple crystallization and filtration method.
4. Further purification is not required.
5. Industrially and economically robust process with safe operations.