DESC:
A PROCESS FOR PREPARING PYRETHROID COMPOUND
FIELD OF INVENTION
[0001] The present disclosure relates to a process of preparing pyrethroid compounds. The present disclosure provides a facile, simple and industrially applicable process of preparation of Meperfuthrin.

BACKGROUND OF INVENTION
[0002] Pyrethroid compounds, which are similar to natural pyrethrins, constitiute a major portion the commercial household insecticides. Mosquito repellent products used on regular basis in households contain mostly pyrethroid derived compounds. Some of the well known pyrethroid compounds are transfluthrin, metofluthrin, dimefluthrin, and D-trans allethrin.
[0003] Pyrethroid class of compounds are pesticides which are non-systemic and act on contact with insects. These pyrethroid compounds act on the nervous system of the insects or pests and disrupt their neuronic functions. Such pyrethroid compounds are used in a very small quantities yet provide maximum insecticidal effect. In order to achieve high efficiency in maximizing the insecticidal effect, it is necessary to obtain pure form of pyrethroid compounds.
[0004] 8431/DELNP/2011 discloses process of preparing an insecticidal incense of Meperfluthrin i.e. 2,3,5,6-tetrafluro-4-(methoxymethyl)benzyl(1R,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, having (1R,3S) trans single optically active isomer. CN101580471 discloses a reaction of 1R-trans cypermethric acid chloride with 4-methoxymethyl2,3,5,6-tetrafluorobenzyl alcohol in a suitable solvent and in the presence of acid scavenger to yield 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl-(1R-trans)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate. Yet another process reported in CN104628570 involves esterification of 4-methoxymethyl-2,3(5,6-tetrafluorobenzyl alcohol with High trans cypermethric acid or 1R-cypermethric acid (HTCMA) at a temperature of 150-165°C and under pressure of 0.25-0.35MPa in an autoclave.
[0005] However the existing processes involve either use of harsh chemicals orhigh temperatures, hence they are not easily scalable. Moreover attaining high purity of these compounds is still challenging. Hence there is still a lack of an efficient and a simple process in obtaining pure form of the pyrethroid compounds.

SUMMARY OF THE INVENTION
[0006] In an aspect of the present disclosure, there is provided a process for preparing a compound of Formula I, the process comprising: reacting a compound of Formula II with a compound of Formula III in presence of a catalyst and a base to obtain the compound of Formula I,

wherein X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6; Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted with C1-6 alkoxy, halogen, hydroxy, amino, or cyano; the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.
[0007] In another aspect of the present disclosure, there is provided a process for preparing a compound of Formula IA as disclosed herein, the process comprising: reacting a compound of Formula IIA with a compound of Formula IIIA in presence of the catalyst, the base and the solvent to obtain the compound of Formula IA.
[0008] In an embodiment the present invention provides a process for preparing a compound of Formula I, the process comprising: reacting a compound of Formula II with a compound of Formula III at temperature in the range of about 60 to 90?, in presence of a catalyst, a base and suitable solvent(s) to obtain the compound of Formula I,

wherein: X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6; Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted with C1-6 alkoxy, halogen, hydroxy, amino, or cyano; the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.
[0009] In yet another embodiment the present invention provides a process for preparing a compound of Formula IA, the process comprising: reacting a compound of Formula IIA with a compound of Formula IIIA at temperature in the range of about 60 to 90?, in presence of the catalyst, the base and suitable solvent(s) to obtain the compound of Formula IA

wherein: the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.

[00010] In still another embodiment of the process of the present invention, X1 and X2 are independently selected from halogen, hydrogen, or C1-6 alkyl; A is halogen, or hydrogen; n is 3 to 5; Y1 and Y2 are independently selected from hydroxy, halogen, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy; the catalyst is selected from from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methyl pyridine, N,N-dimethylpyridine, triethyl amine or combinations thereof. The catalyst is preferably methanesulfonyl chloride; and the base is potassium carbonate is this process

[00011] In a further embodiment of the process of the present invention the catalyst is methanesulphonyl chloride or toluenesulphonyl chloride.

[00012] In another embodiment of the process of the present invention the catalyst is methanesulfonyl chloride, the base is potassium carbonate, and the solvent is acetonitrile.

[00013] In yet another embodiment of the process of the present invention the catalyst the temperature in about 60 to 85?.

[00014] In still another embodiment of the process of the present invention the mole ratio of the compound of Formula III to the catalyst to the base is in range of 1:1:1 to 1:2:3.
[00015] In a further embodiment of the process of the present invention, X1 and X2 are independently selected from halogen; A is halogen; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1-6 alkyl substituted with C1-6 alkoxy.

[00016] In another preferred embodiment of the process of the present invention,, X1 and X2 are independently Cl; A is F; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1 alkyl substituted with C1 alkoxy.

[00017] In another embodiment of the process of the present invention, the suitable solvent(s) are selected from acetonitrile, ethylenedichloride, cyclohexane, hexane, toluene, xylene, mesitylene, halosubstituted benzene, dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulphoxide, or combinations thereof.

[00018] In a further embodiment of the process of the present invention, the suitable solvent(s) are preferably acetonitrile, ethylenedichloride, cyclohexane, hexane, or combinations thereof.

[00019] In yet another embodiment of the process of the present invention, the suitable solvent(s) are preferably acetonitrile, ethylenedichloride, dimethyl formamide or combinations thereof.

[00020] In another embodiment of the present invention, the yield of compound of formula I or IA obtained by the process is 90 to 99%, preferably 96 to 98% and the purity is in the range of 96 to 98%, preferably 97 to 98%.

[00021] In a further embodiment of the present invention, the compound of formula I or IA obtained by the process is an insecticide or an agrochemical such as Meperfluthrin.

[00022] In a further embodiment the present invention provides a Compound of formula I or IA prepared by the process decsbied herein.

[00023] These and other features, aspects, and advantages of the present subject matter will be better understood with reference to the following description. This summary is not intended to identify key features or essential features of the disclosed subject matter, nor is it intended to be used to limit the scope of the disclosed subject matter.
DESCRIPTION OF THE INVENTION
[00024] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features.
Definitions
[00025] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are delineated here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.
[00026] The articles “a”, “an” and “the” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.
[00027] The terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included. It is not intended to be construed as “consists of only”.
[00028] Throughout this specification, unless the context requires otherwise the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.
[00029] The term “including” is used to mean “including but not limited to”. “Including” and “including but not limited to” are used interchangeably.
[00030] The term “alkyl” refers refers to straight or branched aliphatic hydrocarbon groups having the specified number of carbon atoms, which are attached to the rest of the molecule by a single atom, which may be optionally substituted by one or more substituents. C1-6alkyl groups includes methyl, ethyl, n-propyl, butyl, isobutyl, t-butyl, and the like.
[00031] The term “halogen” refers to fluorine, chlorine, bromine, or iodine represented as F, Cl, Br or I.
[00032] The term “amino” refers to the amine -NH2 group which may be optionally substituted.
[00033] The term “hydroxy” refers to -OH group.
[00034] The term “cyano” refers to -CN group.
[00035] The term “alkoxy” refers to an alkyl group attached via an oxygen linkage to the rest of the molecule, which may be optionally substituted by one or more substituents. Alkoxy groups refers to compounds with 1 to 6 carbon atoms and preferred alkoxy groups include, without limitation, –OCH3, –OC2H5 and the like.
[00036] Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a temperature range of 5 to 40? should be interpreted to include not only the explicitly recited limits of 5 to 40? but also to include sub-ranges, such as 5 to 39?, 7 to 38?, 11 to 40?, and so forth, as well as individual amounts, including fractional amounts, within the specified ranges, such as 5?, 10?, 22.2?, 33.5?, 35?, 37? and so on.
[00037] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned herein are incorporated herein by reference.
[00038] As discussed in the background, the existing processes do not address the challenges in preparing pyrethroid compounds in their highest purity. The conventional process are complicated, involving multiple reaction sequences and harsh chemicals. The processes also additionally include exclusive purification process to obtain highly pure pyrethroid compounds. The present disclosure provides a simple, facile and an industrially scalable process for preparing pyrethroid compounds of Formula I. Accordingly the process of present disclosure, comprises reacting a compound of Formula II with a compound of Formula III in presence of a catalyst, a base and a solvent. The catalyst is methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof preferably the catalyst is methanesulphonyl chloride or toluenesulphonyl chloride. The process of the present disclosure is carried out at a temperature in a range of 60 to 90?. The process of the present disclosure results in a higher yield and a higher purity of compounds of Formula I. The present disclosure in specific provides a process for preparing Meperfluthrin.
[00039] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. Functionally-equivalent products, compositions, and methods are clearly within the scope of the disclosure, as described herein.
In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I, the process comprising: reacting a compound of Formula II with a compound of Formula III at a sutable temeparture, in presence of a catalyst, solvent(s) and a base to obtain the compound of Formula I, wherein X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6; Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy, halogen, hydroxy, amino, or cyano; the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.
[00040]

[00041] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein X1 and X2 are independently selected from halogen, hydrogen, or C1-6 alkyl; A is halogen, or hydrogen; n is 3 to 5; Y1 and Y2 are independently selected from hydroxy, halogen, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy; the catalyst is selected from from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methyl pyridine, N,N-dimethylpyridine, triethyl amine or combinations thereof.
[00042] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein X1 and X2 are independently selected from halogen, hydrogen, or C1-6 alkyl; A is halogen, or hydrogen; n is 3 to 5; Y1 and Y2 are independently selected from hydroxy, halogen, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy; the catalyst is methanesulfonyl chloride; and the base is potassium carbonate.
[00043] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein X1 and X2 are independently selected from halogen; A is halogen; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1-6 alkyl substituted with C1-6 alkoxy.
[00044] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein X1 and X2 are independently Cl; A is F; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1 alkyl substituted with C1 alkoxy.
[00045] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein reacting a compound of Formula II with a compound of Formula III is carried out in presence of a solvent selected from acetonitrile, ethylenedichloride, cyclohexane, hexane, toluene, xylene, mesitylene, halosubstituted benzene, dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulphoxide, or combinations thereof. In another embodiment of the present disclosure, wherein the solvent is acetonitrile, ethylenedichloride, cyclohexane, hexane, or combinations thereof. In yet another embodiment of the present disclosure, the solvent is acetonitrile, ethylenedichloride, dimethyl formamide or combinations thereof.
[00046] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein the compound of Formula III to the catalyst to the base is in mole ratio range of 1:1:1 to 1:2:3.
[00047] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein reacting a compound of Formula II with a compound of Formula III is carried out at a temperature in a range of 60 to 90?. In another embodiment of the present disclosure, wherein reacting a compound of Formula II with a compound of Formula III is carried out at a temperature in a range of 65 to 85?.
[00048] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, the compound of Formula I is yield in a range of 90 to 99%; and purity in a range of 96 to 98%. In another embodiment of the present disclosure, wherein the compound of Formula I is yield in a range of 96 to 98%; and purity in a range of 97 to 98%.
[00049] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I, the process comprising: reacting a compound of Formula II with a compound of Formula III in presence of a catalyst selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methyl pyridine, N,N-dimethylpyridine, triethylamine or combinations thereof and the solvents selected from acetonitrile, ethylenedichloride, cyclohexane, hexane, toluene, xylene, mesitylene, halosubstituted benzene, dimethyl formamide, N-methyl-2-pyrrolidone, dimethyl sulphoxide, or combinations thereof, at a temperature in a range of 60 to 90? to obtain the compound of Formula I, wherein X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6; Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy, halogen, hydroxy, amino, or cyano; the compound of Formula III to the catalyst to the base is in mole ratio range of 1:1:1 to 1:2:3; and the compound of Formula I is yield in a range of of 90 to 99%; and purity in a range of 96 to 98%.
[00050] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, reacting a compound of Formula IIA with a compound of Formula IIIA in presence of the catalyst, the base and the solvent to obtain the compound of Formula IA, wherein the catalyst is methanesulfonyl chloride; the base is potassium carbonate, and the solvent is acetonitrile.

[00051] In an embodiment of the present disclosure, there is provided a process for preparing a compound of Formula I as disclosed herein, wherein the compound of Formula I is an insecticide or an agrochemical.
[00052] Although the subject matter has been described in considerable detail with reference to certain examples and implementations thereof, other implementations are possible.

EXAMPLES
[00053] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may apply.
[00054] The present disclosure provides a process for preparing compound of Formula I particularly Meperfluthrin. The process of the present disclosure is simple and facile, and involves use of a catalyst and a base. The process of the present disclosure is carried out at an optimum temperature. The process of preparing the compound of Formula I is carried out by reacting a compound of Formula II and Formula III in the presence of a solvent. The process of the present disclosure provides a higher yield and greater purity of the compounds of Formula I.
Materials and Methods:
[00055] For the purpose of the present disclosure, the following materials were used.
a. Acetonitrile- laboratory reagent (LR)/98%(purity)/Avra (make)
b. Ethylene dichloride (EDC)- laboratory reagent (LR)/98%/Avra
c. Methanesulphonyl chloride -LR/98%/Avra
d. Potassium carbonate - LR/98%/Avra
e. 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol - LR/98%/Avra
f. 1R-trans cypermethric acid - LR/98%/Avra
[00056] The purity of the obtained compound of Formula I was determined using HPLC analyser of make Agilent GC 7890B GC DB-1, 30 meter length, 0.25mm id, 0.25 micron film thickness and Waters Alliance HPLC Zorbax Eclipse plus C8, 4.6 X 250 mm, 5 micron.
General Scheme of preparation of compound of Formula I
[00057] The compounds of Formula I are prepared by the scheme illustrated below.

wherein X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6; Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl; Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy, halogen, hydroxy, amino, or cyano.
[00058] The catalyst is selected from from methane sulfonyl chloride, toluene sulphonyl chloride, trifluoromethane sulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methyl pyridine, N,N-dimethyl pyridine, triethyl amine or combinations thereof.. The reaction is carried out at a temperature in a range of 60 to 90?, in the presence of a solvent selected from acetonitrile, ethylenedichloride, cyclohexane, hexane, toluene, xylene, mesitylene, halosubstituted benzene, dimethyl formamide, N-methyl pyridine, dimethyl sulphoxide, or combinations thereof.
Example 1
Preparation of (1R,3S)-2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate

Formula II Formula III Formula I
(1R-trans cypermethric acid)
[00059] 300 ml of acetonitrile (solvent) was charged to a 2 litre capacity 4-necked RB flask fitted with a mechanical stirrer, thermometer pocket with thermometer, a reflux condenser circulated with cold water. 224 grams (1.0 mole) of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (Formula III), 158 grams (2.0 mole) of pyridine (base) and 115 grams (1.0 mole) of methanesulfonyl chloride (catalyst) were charged in to reaction mass heated to 70 ? and maintained for 3 hrs. 215.3 grams (1.03 moles) of 1R-trans cypermethric acid (Formula II) in 100ml of acetonitrile was added into reaction mass for the period of 1hr and maintained the temperature for 6 hrs. After completion of the reaction, acetonitrile was distilled out and the crude mass quenched with water and EDC. The organic layer was separated and concentrated to obtain 415 gof crude Meperfluthrin (Formula I). This crude meperfluthrin was recrystallized with 200 ml of IPA to obtain white solid 405g of pure meperfluthrin with the yield of 97.5%.
Example 2
[00060] 300 ml of acetonitrile (solvent) was charged to a 2 litre capacity 4-necked RB flask fitted with a mechanical stirrer, thermometer pocket with thermometer, a reflux condenser circulated with cold water. 224 grams (1.0 mole) of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (Formula III), 276.4 grams (2.0 mole) of potassium carbonate (base) were added and stirred well. 115 grams (1.0 mole) of methanesulfonyl chloride (catalyst) were charged in to reaction mass heated to 70 ? and maintained for 3 hrs. 215.3 grams (1.03 moles) of 1R-trans cypermethric acid in (Formula II) 100ml of acetonitrile was added into reaction mass for the period of 1hr and maintained the temperature for 6 hrs. After completion of the reaction, acetonitrile was distilled out and the crude mass quenched with water and EDC. The organic layer was separated and concentrated to obtain 412 g of crude Meperfluthrin (Formula I). This crude meperfluthrin was recrystallized with 200 ml of IPA to obtain white solid 407g of pure meperfluthrin with the yield of 97.5%.
Example 3
[00061] 300 ml of acetonitrile (solvent) was charged to a 2 litre capacity 4-necked RB flask fitted with a mechanical stirrer, thermometer pocket with thermometer, a reflux condenser circulated with cold water. 224 grams (1.0 mole) of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (Formula III), 202 grams (2.0 mole) of triethylamine (base) and 115 grams (1.0 mole) of methanesulfonyl chloride (catalyst) were charged in to reaction mass heated to 70 ? and maintained for 3 hrs. 215.3 grams (1.03 moles) of 1R-trans cypermethric acid (Formula II) in 100ml of acetonitrile was added into reaction mass for the period of 1hr and maintained the temperature for 6 hrs. After completion of the reaction, acetonitrile was distilled out and the crude mass quenched with water and EDC. The organic layer was separated and concentrated to obtain 405 gof crude Meperfluthrin (Formula I). This crude meperfluthrin was recrystallized with 200 ml of IPA to obtain white solid 390g of pure meperfluthrin with the yield of 94.0%.
Example 4
[00062] 300 ml of dimethylformamide (DMF) (solvent) was charged to a 2 litre capacity 4-necked RB flask fitted with a mechanical stirrer, thermometer pocket with thermometer, a reflux condenser circulated with cold water. 224 grams (1.0 mole) of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (Formula III), 276.4 grams (2.0 mole) of potassium carbonate (base) were added and stirred well. 115 grams (1.0 mole) of methanesulfonyl chloride (catalyst) were charged in to reaction mass heated to 70 ? and maintained for 3 hrs. 215.3 grams (1.03 moles) of 1R-trans cypermethric acid in (Formula II) 100ml of DMF was added into reaction mass for the period of 1hr and maintained the temperature for 6 hrs. After completion of the reaction, DMF was distilled out and the crude mass quenched with water and EDC. The organic layer was separated and concentrated to obtain 404 g of crude Meperfluthrin (Formula I). This crude meperfluthrin was recrystallized with 200 ml of IPA to obtain white solid 385 g of pure meperfluthrin with the yield of 92.0%.
Example 5
[00063] 300 ml of acetonitrile (solvent) was charged to a 2 litre capacity 4-necked RB flask fitted with a mechanical stirrer, thermometer pocket with thermometer, a reflux condenser circulated with cold water. 215.3 grams (1.03 moles) of 1R-trans cypermethric acid and 276.4 grams (2.0 mole) of potassium carbonate (base) added slowly for the period of 2hr and stirred well, reaction mass heated to 70 ? and maintained for 3 hrs. 224 grams (1.0 mole) of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (Formula III) in 100 ml of acetonitrile was addition into reaction mass for the period of 1hr and maintained the temperature for 4 hrs. After completion of the reaction, acetonitrile was distilled out and the crude mass quenched with water and EDC. The organic layer was separated and concentrated to obtain 400 g of crude Meperfluthrin (Formula I). This crude meperfluthrin was recrystallized with 200 ml of IPA to obtain white solid 380g of pure meperfluthrin with the yield of 91.0%.

ADVANTAGES OF THE PRESENT DISCLOSURE
[00064] The above-mentioned implementation examples as described on this subject matter and its equivalent thereof have many advantages, including those which are described.
[00065] The present diosclosure provides a process for preparing the compounds of Formula I particularly Meperfluthrin using a catalyst and a base. The process of the present disclosure is carried out at an optimum temperature in a range of 60 to 80?. The process of the present disclosure results in a higher yield of Meperfluthrin and a greater purity in a range of 96 to 98%. The process of the present disclosure is simple and is an industrially scalable process. The process is carried out at optimum temperature and hence incurs less energy and less cost compared to conventional process. The compound of Formula I obtained by the process of the present disclosure is of higher purity and hence avoids any additional steps associated with purification of the compounds. Therefore the process of the present disclosure is economically viable and environmentally benign process.
[00066] Although the subject matter has been described in considerable detail with reference to certain embodiments thereof, other embodiments are possible. As such, the spirit and scope of the disclosure should not be limited to the description of the embodiments contained herein.


,CLAIMS:We claim:

1. A process for preparing a compound of Formula I, the process comprising: reacting a compound of Formula II with a compound of Formula III at temperature in the range of about 60 to 90?, in presence of a catalyst, a base and suitable solvent(s) to obtain the compound of Formula I,

wherein:
X1 and X2 are independently selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl;
A is selected from halogen, hydrogen, hydroxy, amino, cyano, or C1-6 alkyl; n is 2 to 6;
Y1 and Y2 are independently selected from hydroxy, halogen, hydrogen, amino, cyano, or C1-6 alkyl;
Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted with C1-6 alkoxy, halogen, hydroxy, amino, or cyano;
the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and
the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.
2. A process for preparing a compound of Formula IA, the process comprising: reacting a compound of Formula IIA with a compound of Formula IIIA at temperature in the range of about 60 to 90?, in presence of the catalyst, the base and suitable solvent(s) to obtain the compound of Formula IA

wherein:
the catalyst is selected from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and
the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methylpyridine, N,N-dimethylpyridine, triethylamine or combinations thereof.

3. The process as claimed in claim 1 or 2, wherein:
X1 and X2 are independently selected from halogen, hydrogen, or C1-6 alkyl;
A is halogen, or hydrogen; n is 3 to 5;
Y1 and Y2 are independently selected from hydroxy, halogen, or C1-6 alkyl;
Z is selected from C1-6 alkyl; and wherein C1-6 alkyl is optionally substituted C1-6 alkoxy;
the catalyst is selected from from methanesulfonyl chloride, toluenesulphonyl chloride, trifluoromethanesulphonyl chloride, CF3SOCl, cyanuric acid chloride or combinations thereof; and
the base is selected from inorganic base sodium carbonate, potassium carbonate and organic base pyridine, methyl pyridine, N,N-dimethylpyridine, triethyl amine or combinations thereof.
4. The process as claimed in claims 1 or 2, wherein the catalyst is methanesulphonyl chloride or toluenesulphonyl chloride.

5. The process as claimed in claim 3, wherein the catalyst is methanesulfonyl chloride; and the base is potassium carbonate.

6. The process as claimed in claim 2, wherein, the catalyst is methanesulfonyl chloride, the base is potassium carbonate, and the solvent is acetonitrile.

7. The process as claimed in any preceding claim, wherein the temperature in about 60 to 85?.

8. The process as claimed in any preceding claim, wherein the mole ratio of the compound of Formula III to the catalyst to the base is in range of 1:1:1 to 1:2:3.

9. The process as claimed in any preceding claim, wherein, X1 and X2 are independently selected from halogen; A is halogen; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1-6 alkyl substituted with C1-6 alkoxy.

10. The process as claimed in claim 9, wherein, X1 and X2 are independently Cl; A is F; n is 4; Y1 and Y2 are independently hydroxy; and Z is selected from C1 alkyl substituted with C1 alkoxy.

11. The process as claimed in any preceding claim, wherein said suitable solvent(s) are selected from acetonitrile, ethylenedichloride, cyclohexane, hexane, toluene, xylene, mesitylene, halosubstituted benzene, dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulphoxide, or combinations thereof.

12. The process as claimed in claim 11, wherein said suitable solvent(s) are preferably acetonitrile, ethylenedichloride, cyclohexane, hexane, or combinations thereof.

13. The process as claimed in claim 11, wherein said suitable solvent(s) are preferably acetonitrile, ethylenedichloride, dimethyl formamide or combinations thereof.

14. The process as claimed in any preceding claim, wherein the yield of compound of formula I or IA is 90 to 99%, preferably 96 to 98% and the purity is in the range of 96 to 98%, preferably 97 to 98%.

15. The process claimed in any preceding claim, wherein said compound of formula I or IA is an insecticide or an agrochemical such as Meperfluthrin.

16. Compound of formula I or IA prepared by the process as claimed in any preceding claim.

Dated this 26th day of February 2024.

Gayatri Bhasin
(IN/PA-1246)
Of SUBRAMANIAM & ASSOCIATES
Attorneys for the Applicants