DESC:FIELD OF THE INVENTION
[001] The present disclosure relates to a process for the preparation of bifenthrin and intermediates thereof.

BACKGROUND OF THE INVENTION
[002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[003] Bifenthrin chemically known as 2-methyl[1,1'-biphenyl]-3-yl)methyl (1R,3R)-rel-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarboxylate is a pyrethroid insecticide. It is a contact insecticide and it affects the central and peripheral nervous system of the pest by interfering with sodium channel gating. Bifenthrin has the following structural formula (I):

[004] The intermediate for preparation of bifenthrin is 3-(chloromethyl)-2-methyl-biphenyl. The intermediate has the following structural formula (III):

[005] Various processes to prepare bifenthrin and the intermediate 3-(chloromethyl)-2-methyl-biphenyl are known in the art. However, such processes known in the art have various serious disadvantages as detailed below.
[006] US4473709 A discloses a process to prepare 3-(chloromethyl)-2-methyl-biphenyl in six steps using 2-biphenylcarboxylic acid as a starting material and also discloses the process to prepare bifenthrin in seven steps as per the below scheme.
3-(chloromethyl)-2-methyl-biphenyl preparation scheme:

Bifenthrin preparation scheme:

[007] The above schemes involve tedious procedures with relatively greater number of steps which leads to excessive production time. Further, the process involves hazardous, moisture sensitive chlorinating reagent SOCl2, toxic and carcinogenic catalyst pyridine, pyrophoric and costly reagents such as lithium aluminium hydride, sodium metal and methyl iodide, ethyl chloroformate and use of multiple and high amount of solvents such as 1,2-dimethoxyethane (DME) and dry toluene that leads to production of high volume of effluent.
[008] CN113387840A and IN201827018975 disclose the process to prepare 3-(chloromethyl)-2-methyl-biphenyl by reacting 2-methyl-3-biphenylmethanol with the chlorinating reagent SOCl2.
.

[009] Thus, even the above two processes to prepare 3-(chloromethyl)-2-methyl-biphenyl use hazardous, moisture sensitive chlorinating reagent SOCl2 and the toxic and carcinogenic catalyst pyridine and highly undesirable water soluble solvents such as acetonitrile and 1,4-dioxane. The thionyl chloride used during the preparation of 3-(chloromethyl)-2-methyl-biphenyl (acid chloride) generate the hazardous gases such as sulphur dioxide and hydrogen chloride which causes significant damage to human health and the increased effluent causes damage to the environment.
[0010] KR100460449B1 discloses the process to prepare bifenthrin by reacting the starting material methyl (1R,3R)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarboxylate (LC acid methyl ester) with the sulphur smelling organophosphate reagent such as dithio diethyl phosphate to get the LC acid thioester and further reacting LC acid thioester with 2-methyl-3-biphenylmethanol to obtain bifenthrin.

[0011] As can be seen, in both the steps, carcinogenic solvent like benzene is used which is not safe for both human kind and environment.
[0012] Two Chinese patent applications CN102827004A and CN103145558A discloses the process to prepare bifenthrin by converting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) to methyl (1R,3R)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarboxylate (LC acid methyl ester) and then combining the LC acid methyl ester with 2-methyl-3-biphenylmethanol to obtain bifenthrin (transesterification reaction).
Scheme of CN102827004A

Scheme of CN103145558A

[0013] Thus, the above schemes use highly expensive catalyst such as isopropyl titanate and the trans esterification reactions are carried out under very high temperature (145 °C to 155 °C as mentioned in scheme of ‘004). Also, during the trans esterification reactions there will be no complete conversion of LC acid methyl ester into bifenthrin due to which the remaining LC acid methyl ester is required to be recovered by an additional step of vacuum distillation.
[0014] A Chinese patent application CN102070454A and a PCT application WO2003053905A1 disclose the process to prepare bifenthrin by converting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) to rel-(1R,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarbonyl chloride (LC acid chloride) and then combining the LC acid chloride with 2-methyl-3-biphenylmethanol to obtain bifenthrin.
Scheme of CN102070454A

Scheme of WO2003053905A1

[0015] The above processes suffer from the disadvantages that the acid chloride intermediates (LC acid chloride) formed during these reactions are unstable and moisture sensitive, they use hazardous, moisture sensitive chlorinating reagent SOCl2, and highly volatile and highly flammable solvents such as hexane. Also the above processes use an organic weak base such as triethyl amine and inorganic strong base such as aqueous NaOH. However, the addition of inorganic strong bases such as aqueous NaOH additionally requires pH control devices, continuous monitoring and simultaneous addition of LC acid chloride to the aqueous NaOH to control the desired pH throughout the reaction.
[0016] Another three Chinese patent applications CN103319345A, CN104628569A and CN108218696A disclose the process to prepare bifenthrin by reacting the rel-(1R,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarbonyl chloride (LC acid chloride ) with 2-methyl-3-biphenylmethanol to obtain bifenthrin.
Scheme of CN103319345A

Scheme of CN104628569A

Scheme of CN108218696A

[0017] These processes use inorganic strong base such as KOH which additionally demands the use of pH control devices throughout and continuous monitoring to control the desired pH during the entire reaction, also the processes require highly flammable solvents such as hexane and carcinogenic catalysts like triethanolamine.
[0018] Three more Chinese patent applications CN113788754A, CN104628568A and CN109485564A disclose the process to prepare bifenthrin by directly reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) with 2-methyl-3-biphenylmethanol to obtain bifenthrin.
Scheme of CN113788754A

Scheme of CN104628568A

Scheme of CN109485564A

[0019] Apparently, these processes use costly catalysts such as n-butyl titanate and zeolites such as HZSM-5 and costly and moisture sensitive catalysts such as trimethyl silyl magnesium chloride. Also, these reactions are carried out under very high temperature such as 135°C and 150°C and under pressure 0.25 MPa which leads to the formation of impurities. Besides, in these types of reactions there are high possibilities of self coupling of 2-methyl-3-biphenylmethanol which again leads to the impurity formation.
[0020] Thus, the processes known hitherto involves tedious multiple reaction steps, excessive production time, hazardous reagents, extreme reaction conditions, moisture sensitive chlorinating reagents, highly expensive and carcinogenic catalysts, and very volatile and highly flammable solvents which in turn renders the processes more unsafe, costly and less eco-friendly, thus the processes are not suitable for commercial scale up.
[0021] There is thus an unmet need in the art to provide a process for preparation of bifenthrin that can overcome one or more deficiencies of the existing arts as mentioned above to render the process easy to carry out and scalable, environmental friendly and efficient.
[0022] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.

OBJECTS OF THE INVENTION
[0023] It is an object of the present disclosure to provide a process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III).
[0024] It is an object of the present disclosure to provide a process for preparation of bifenthrin of formula (I).

SUMMARY OF THE INVENTION
[0025] In an aspect the present disclosure is directed to provide a process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) comprising reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous acid like aqueous hydrochloric acid (HCl) in presence of a solvent and a catalyst.

[0026] In another aspect, the present disclosure provides a process for preparation of bifenthrin of formula (I) comprising reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of an inorganic weak base and a solvent.

[0027] In yet another aspect, the present disclosure provides a process for preparation of bifenthrin of formula (I), comprising the steps of:
(i) reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous hydrochloric acid (HCl) in presence of a solvent and a catalyst, to produce 3-(chloromethyl)-2-methyl-biphenyl of formula (III)
; and

(ii) reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of a inorganic weak base and a solvent to produce bifenthrin of formula (I)
.

[0028] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

DETAILED DESCRIPTION OF THE INVENTION
[0029] The following is a detailed description of embodiments of the present disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0030] Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
[0031] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0032] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
[0033] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” The term “about” may refer to + 5 of the specific figure preceding the term “about”. Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable.
[0034] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it is individually recited herein.
[0035] All processes described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0036] The headings and abstract of the invention provided herein are for convenience only and not for interpreting the scope or meaning of the embodiments.
[0037] The following discussion provides many exemplary embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[0038] It should also be appreciated that the present invention can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.
[0039] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0040] The compound of formula (I) refers to bifenthrin, chemically known as 2-methyl[1,1'-biphenyl]-3-yl)methyl (1R,3R)-rel-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarboxylate having the structural formula as below:

[0041] The present disclosure provides a process for preparation of bifenthrin of formula (I) and intermediate thereof.
[0042] In one embodiment, the present disclosure provides a process for preparation of an intermediate 3-(chloromethyl)-2-methyl-biphenylof formula (III)
.
[0043] In one embodiment, the present disclosure provides a process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) comprising reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous acid like aqueous hydrochloric acid (HCl) in presence of a solvent and a catalyst
.
[0044] In an embodiment, the aqueous acid used in the process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) is about 30 % - about 35% hydrochloric acid (HCl) in water by weight. Preferably, the aqueous acid used is 30% hydrochloric acid (HCl) in water by weight.
[0045] The aqueous acid like hydrochloric acid acts as a chlorinating reagent.
[0046] The solvent can be selected from the group comprising of but not limiting to toluene, monochlorobenzene and 1,2-dichloroethane. Preferably, the solvent is toluene.
[0047] The catalyst can be selected from the group comprising of but not limiting to tetrabutylammonium bromide, benzyltriethylammonium chloride, and methyltributylammonium chloride. Preferably, the catalyst is tetrabutylammonium bromide.
[0048] The process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) by reacting 2-methyl-3-biphenylmethanol of formula (IV) is carried out at the temperature ranging from about 30 °C to about 70° C. Preferably, the temperature ranging from about 55 °C to about 60° C.
[0049] The processes known in the art use hazardous, moisture sensitive chlorinating reagent SOCl2 and the toxic and carcinogenic catalyst pyridine and highly undesirable water soluble solvents such as acetonitrile and 1,4-dioxane during the process for the preparation of 3-(chloromethyl)-2-methyl-biphenyl. The use of undesirable water soluble solvents such as acetonitrile and 1,4-dioxane during the reaction demand an additional solvents such as ethyl acetate or dichloromethane for the product isolation.
[0050] However, none of the processes known in the art discloses the process to prepare 3-(chloromethyl)-2-methyl-biphenyl of formula (III) by reacting 2-methyl-3-biphenylmethanol of formula (IV) with chlorinating reagent for example aqueous acid like aqueous hydrochloric acid to produce 3-(chloromethyl)-2-methyl-biphenyl of formula (III).
[0051] The use of the chlorinating reagent like aqueous hydrochloric acid, for example 30% aqueous hydrochloric acid in the process of the present invention provides significant advantage over the use of other known chlorinating agents such as thionyl chloride (SOCl2). The 30% aqueous hydrochloric acid is safe, cheap and also easy to handle in comparison to the known chlorinating agent thionyl chloride. Further, the 30% aqueous hydrochloric acid does not generate any hazardous gases such as sulphur dioxide and hydrogen chloride unlike the chlorinating agent thionyl chloride which generates the hazardous gases such as sulphur dioxide and hydrogen chloride which causes significant damage to human health and the increased effluent causes damage to the environment.
[0052] The process of the present invention also uses the safer, economical and water soluble ionic solid catalyst tetrabutylammonium bromide in contrast to the toxic and carcinogenic catalyst pyridine used in the known arts during the preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) and hence makes the process eco-friendly and economical. Also, the present invention uses single, water insoluble and safer solvent such as toluene which even helps during the product isolation thereby avoiding the use of combination of multiple solvents such as DMF, 1,2-dimethoxyethane (DME) and dry toluene unlike the previous approaches for example as used in the scheme disclosed in the known art US4473709A for the preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III).
[0053] In another embodiment, there is provided a process for preparation of an intermediate 3-(chloromethyl)-2-methyl-biphenyl of formula (III) comprising reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous hydrochloric acid (HCl) in presence of a solvent toluene and a catalyst tetrabutylammonium bromide.
[0054] In an embodiment, the reaction of 2-methyl-3-biphenylmethanol of formula (IV) with aqueous hydrochloric acid is carried out at the temperature range of about 55 °C to about 60 °C.
[0055] In an embodiment, there is provided a process for preparation of bifenthrin of formula (I) by reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of an inorganic weak base and a solvent:
.
[0056] The inorganic weak base can be a carbonate selected from the group consisting of potassium carbonate, sodium carbonate, and cesium carbonate or mixture thereof. Preferably, the weak base is potassium carbonate.
[0057] The solvent can be selected from the group comprising of but not limiting to dimethylformamide (DMF), N,N-dimethylacetamide, dimethyl sulfoxide. Preferably, the solvent is DMF.
[0058] The process for preparation of bifenthrin of formula (I) by reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) is carried out at the temperature ranging from about 60 °C to about 70° C. Preferably, the reacton is carried out at a temperature ranging from about 65 °C to about 70° C.
[0059] The process to prepare bifenthrin of formula (I) by reacting rel-(1R,3R)-3-(2-Chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) is carried out at an atmospheric pressure.
[0060] In another embodiment, the present invention discloses a process for preparation of bifenthrin of formula (I) comprising reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of an inorganic weak base potassium carbonate and a solvent DMF.
[0061] The reaction scheme is as follows

[0062] The reaction of rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) to obtain bifenthrin can be carried out at the temperature range of about 65°C to about 70 °C and at an atmospheric pressure.
[0063] The step of reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) to obtain bifenthrin in accordance with the present invention is carried out at the temperature range of about 65°C to about 70 °C and at an atmospheric pressure, in contrast to the processes known in the art carried out at the high temperature such as 135°C and 150°C and under pressure of 0.25MPa to obtain the crude bifenthrin.
[0064] Further, the obtained crude bifenthrin can be treated with methanol for purification. After the purification, the pure bifenthrin of formula (I) with over 90% yield and 99% purity (HPLC) is obtained.
[0065] The present invention provides a process for preparation of bifenthrin by converting 2-methyl-3-biphenylmethanol of formula (IV) to 3-(chloromethyl)-2-methyl-biphenyl of formula (III) and then reacting the LC acid (rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid) of formula (II) with the obtained intermediate 3-(chloromethyl)-2-methyl-biphenyl of formula (III) to obtain bifenthrin with high yield and purity.
[0066] It has been surprisingly found that in the process of the present invention, the intermediate 3-(chloromethyl)-2-methyl-biphenyl of formula (III) formed during the process for the preparation of bifenthrin is more stable than the LC acid chloride intermediate rel-(1R,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarbonyl chloride formed during the process for preparation of bifenthrin by processes known in the art.
[0067] The process for preparation of bifenthrin by reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) can be carried out in presence of a inorganic weak base and a solvent was surprisingly discovered by the inventors of the present invention for the first time.
[0068] It has been surprisingly found that, the use of the inorganic weak base like potassium carbonate in the process of the present invention has significant advantage over the use of other known inorganic strong bases such as sodium hydroxide and potassium hydroxide and organic weak base such as triethyl amine used in the known processes for the preparation of bifenthrin. The addition of inorganic strong bases such as sodium hydroxide and potassium hydroxide in the processes known in the art additionally throughout require pH control devices and continuous monitoring to control the desired pH of the range of 7 to 12 during the entire reaction. Whereas, by adding the weak bases such as potassium carbonate and sodium carbonate as per the process of the present invention, it was surprisingly found that the pH is automatically maintained at the pH range of 7 to 12 during the entire reaction without any need for the use of any additional pH control devices and continuous monitoring to control the pH in the range of 7 to 12. Such unexpected advantage renders process easy and avoids the variation of pH which leads to the formation of impurities that result into the lower yield of the product. Further, as per one of the processes known in the art as disclosed in CN102070454, the addition of inorganic strong base such as sodium hydroxide demand the controlled addition of rel-(1R,3S)-3-[(1Z)-2-Chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethylcyclopropanecarbonyl chloride (LC acid chloride) along with aqueous NaOH to maintain the desired pH during the preparation of bifenthrin, unlike such stringent requirement, the process of the present invention obviates requirement of such controlled addition of any reagent thereby making the process simple, easy to carry out and scalable.
[0069] The hitherto known processes require the use of combination of different solvents such as DMF, 1,2-dimethoxyethane (DME) and dry toluene during the preparation of bifenthrin leading to the production of high volume of effluent. Besides, the solvents used in known processes are highly volatile and flammable such as hexane and carcinogenic solvents like benzene.
[0070] The process of the present invention has surprisingly been found to be carried out with the use of single and safer solvent such as DMF, which has been found to be sufficient for the preparation of bifenthrin thereby avoiding the use of multiple solvents or highly volatile, highly flammable, and carcinogenic solvents and thereby minimizing the formation of high amounts of effluent. The inventors of the present invention have thus unexpectedly been able to arrive at a process, which is cost effective as well as ecofriendly.
[0071] The process of the present invention avoids tedious multiple reaction steps of processes known in the art, excessive production time, unstable single step processes, unsuitable inorganic strong bases or organic weak bases, hazardous reagents, extreme reaction conditions, moisture sensitive chlorinating reagents, highly expensive and carcinogenic catalysts, and highly volatile and highly flammable solvents. Contrary to the known processes, the process of the present invention can be carried out using safer solvents and reagents in mild and easy to operate conditions, which is conducive to reducing production cost, rendering process eco-friendly, providing high yield and purity making the process not only efficient and suitable for small-scale preparation in the laboratory, but also can be directly scaled up for production, and expanding the actual industrial production.
[0072] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
[0073] The present invention is further explained in the form of following examples. However, it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

EXAMPLES

EXAMPLES AS PER THE PRESENT INVENTION:

Example 1
Synthesis of bifenthrin of Formula (I)
Step 1: Preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) from 2-methyl-3-biphenylmethanol of formula (IV)
[0074] 3-(chloromethyl)-2-methyl-biphenyl of formula (III) was prepared from 2-methyl-3-biphenylmethanol of formula (IV) as per the following reaction scheme:

[0075] Solvent toluene (500 g, (3.06 w/w)), starting material 2-methyl-3-biphenylmethanol (163.5 g (1.0 equivalent)), 30% aqueous HCl (752.2g (7.5 equivalent)) and catalyst tetrabutylammonium bromide (2.12 g (0.008 equivalent)) were charged into a 2 L round bottomed flask to obtain a mixture. The mixture was heated to 55-60°C. The mixture was stirred continuously for about 7 to 8 hours while maintaining the temperature at 55-60°C till the completion of the reaction. After completion of the reaction, the mixture was cooled to 45-50°C to obtain a heterogeneous solution containing two layers, an aqueous layer and an organic layer. The aqueous layer was discarded and the organic layer containing the product was distilled under vacuum to recover the solvent toluene and to obtain an oily liquid containing 3-(chloromethyl)-2-methyl-biphenyl compound of formula (III). Yield: ~100%. HPLC purity: >96%.

Step 2: Preparation of Bifenthrin of formula (I) from rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) and 3-(chloromethyl)-2-methyl-biphenyl of formula (III)
Bifenthrin of formula (I) was prepared from rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) and 3-(chloromethyl)-2-methyl-biphenyl of formula (III) as per the following scheme:

[0076] Solvent N, N-Dimethyl formamide (400 g, (2 w/w)), rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid (200 g (1.0 equivalent)), inorganic weak base potassium carbonate (125.36 g (1.1 equivalent)), 3-(chloromethyl)-2-methyl-biphenyl compound of formula (III) obtained from step 1 (178.8 g (1.0 equivalent) were charged into a 2 L round bottomed flask to obtain a mixture. The mixture was heated to 65-70 °C. The mixture was stirred continuously for about 5 to 6 hours while maintaining the temperature at 65-70°C till the completion of the reaction. After completion of the reaction the solvent DMF was distilled out under vacuum 20-50 mbar at 65-85°C to obtain the slurry. Toluene (600 g) and water (500 g) were added into the slurry and the slurry was stirred for about 15-30 minutes to obtain an heterogeneous solution containing two layers an aqueous layer and an organic layer. The aqueous layer was discarded and the organic layer containing the product was distilled under vacuum 300-50 mbar at 55-80°C to recover toluene and to obtain an oily liquid containing the crude bifenthrin. After completion of the distillation, methanol (800 g)was charged into the oily liquid containing the crude bifenthrin and was stirred for about 15-30 minutes at 45-50°C and then cooled to 0 to 5°C for about 1-2 hours to obtain the thick suspension. The suspension was filtered to obtain the wet cake. The wet cake was washed with MeOH (50 g) and the was dried at 25-30°C under vacuum ~300-200 mbar for about 8-10 h to obtain white solid containing the pure bifenthrin of formula (I) with yield: 92% and HPLC purity: >99%.

COMPARITIVE EXAMPLES
Comparative Example 1A
Synthesis of bifenthrin as per known process using chlorinating reagent SOCl2

[0077] Solvent toluene (150 g), starting material Rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) (100 g), catalyst DMF (0.9 g) were charged into 2 L round bottomed flask and SOCl2 (51.49 g) was added drop wise into the flask to obtain a solution 1. The solution 1 was heated to 45°C and was stirred continuously for about 2 hours.
[0078] In another 2 L round bottomed flask, 2-methyl-3-biphenylmethanol (80.1 g), and solvent toluene (150 g) were charged to obtain a mixture. The mixture was heated to 50°C -55°C to obtain a solution 2.
[0079] Solution 1 was added drop wise to solution 2 at 50°C to 55°C to obtain a reaction mass. The reaction mass was stirred for 5-6 h and then it was cooled to room temperature which was further subjected to aqueous workup followed by distillation to obtain crude bifenthrin. The crude bifenthrin was crystallized in methanol to obtain a white solid containing pure bifenthrin (151.5 g). Yield: 86.9 % and HPLC purity: 94.97 %.

Comparative Example 2A
Synthesis of bifenthrin as per known process using chlorinating reagent SOCl2 and base TEA

[0080] Solvent toluene (400 g), starting material Rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) (200 g), catalyst DMF (1.81 g) were charged into 2 L round bottomed flask and SOCl2 (103 g) was added drop wise into the flask to obtain a solution 1. The solution 1 was heated to 45°C and was stirred continuously for about 2 hours.
[0081] In another 2 L round bottomed flask, 2-methyl-3-biphenylmethanol (163.4 g), organic base triethylamine (TEA) (104.3 g), catalyst DMAP (1.61 g), and solvent toluene (300 g) were charged to obtain a mixture. The mixture was cooled to 15°C -20°C to obtain a solution 2.
[0082] Solution 1 was added drop wise to solution 2 at 15°C -20°C to obtain a reaction mass. The reaction mass was stirred for 6-8 h and then it was brought to room temperature which was further subjected to aqueous workup followed by distillation to obtain crude bifenthrin. The crude bifenthrin was crystallized in methanol to obtain a white solid containing pure bifenthrin (265 g). Yield: 76 % and HPLC purity: 96.5%.

Comparative Example 3A
Synthesis of bifenthrin as per known process using chlorinating reagent SOCl2 and base NaOH

[0083] Solvent toluene (100 g), starting material Rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) (50 g), and catalyst DMF (0.45 g) were charged into 1 L round bottomed flask and SOCl2 (25.74 g) was added drop wise into the flask to obtain a solution 1. The solution 1 was heated to 45°C and was stirred continuously for about 2 hours.
[0084] In another 1 L round bottomed flask, 2-methyl-3-biphenylmethanol (40.9 g), strong inorganic base 48% aqueous NaOH (18.9 g), catalyst DMAP (0.4 g), and solvent toluene (75 g) were charged to obtain a mixture. The mixture was cooled to 5°C -10°C to obtain a solution 2.
[0085] Solution 1 was added drop wise to solution 2 at 5°C -15°C to obtain a reaction mass. The reaction mass was stirred for 30 mins and then it was brought to room temperature which was further subjected to aqueous workup followed by distillation to obtain crude bifenthrin. The crude bifenthrin was crystallized in methanol to obtain a white solid containing pure bifenthrin (70.5 g). Yield: 80.9% and HPLC purity: 95.6%

Comparative Example 4A
Synthesis of bifenthrin as per known process using catalyst KHSO4 and carried out at higher temperatures

[0086] Starting material Rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) (50 g) and 2-methyl-3-biphenylmethanol (40.86 g), catalyst potassium bisulphate (3 g), solvent toluene (125 g) were added into 1L autoclave at room temperature and applied 5.5-6 Kg/cm2 of nitrogen pressure to obtain a reaction mixture.
[0087] The reaction mixture was heated upto high temperature 160-165 oC and stirred continuously for about 8 to 9 hours and then cooled to room temperature which was further subjected to aqueous workup followed by distillation to obtain crude bifenthrin with HPLC purity: 21.5%. The same could not be isolated.

Comparison of the process of preparation of bifenthrin of the present invention as per Example 1, with known processes as per comparative Examples 1A to 4A:
The following Table summarizes the yield and purity of bifenthrin prepared as per Example 1 of the process of the present invention with that of the known processes of Examples 1A to 4A.

Table 1: Comparison of the Present invention with conventional processes to prepare bifenthrin.
Process Example number Bifenthrin Yield Purity
Present Invention Example 1 92% >99%
Comparative Examples Example 1A 86.9% 94.97%
Example 2A 76% 96.5%
Example 3A 80.9% 95.6%
Example 4A Not isolated 21.05%

[0088] Accordingly, from the test results shown above, it is evident that the process of the present invention provides an unexpected and surprising advantages including high yield (92%) and purity (>99%) of the bifenthrin prepared by the process of the present invention, greater than the yield and purity of the bifenthrin prepared by the conventional processes providing much lower yield (below 86.9%) as well as purity (below 96.5%) as shown in the comparative Examples 1Ato 4A. Further, the process of the present invention is advantageous over the known processes, which use moisture sensitive chlorinating agents such as thionyl chloride (SOCl2) that generates the hazardous gases such as sulphur dioxide and hydrogen chloride which causes significant damage to human health as well as the known processes produced increased effluent that causes damage to the environment. In contrast, the present invention uses 30% aqueous hydrochloric acid which is safe, cheap and also easy to handle in comparison to the known chlorinating agent thionyl chloride. Further, the 30% aqueous hydrochloric acid as employed in the process of the present invention does not generate any hazardous gases such as sulphur dioxide and hydrogen chloride. Also, the comparative Examples use an organic weak base such as triethyl amine and inorganic strong base such as aqueous NaOH. However, the addition of inorganic strong bases such as aqueous NaOH additionally requires pH control devices, continuous monitoring and simultaneous addition of LC acid chloride to the aqueous NaOH to control the desired pH throughout the reaction. In contrast, in the process of the present invention by adding the weak bases such as potassium carbonate and sodium carbonate, it was surprisingly found that the pH is automatically maintained at the pH range of 7 to 12 throughout the reaction without any need for the use of any additional pH control devices and continuous monitoring to control the pH in the range of 7 to 12. Thus, the process of the present invention possesses advantages over known processes in terms of the process being simple, easy to carry out and scalable, environmental friendly and efficient by providing higher yield and purity at the same time.
[0089] A skilled artisan will appreciate that the quantity and type of each ingredient can be used in different combinations or singly. All such variations and combinations would be falling within the scope of present disclosure.
[0090] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.
,CLAIMS:

1. A process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) by reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous hydrochloric acid in presence of a solvent and a catalyst
.

2. The process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) as claimed in claim 1, wherein the aqueous hydrochloric acid is 30% to 35% hydrochloric acid.

3. The process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) as claimed in claim 1, wherein the solvent is selected from the group consisting of toluene, monochlorobenzene and 1,2-dichloroethane.

4. The process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) as claimed in claim 1, wherein the catalyst is selected from the group consisting of tetrabutylammonium bromide, benzyltriethylammonium chloride and methyltributylammonium chloride.

5. The process for preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) as claimed in claim 4, wherein the catalyst is tetrabutylammonium bromide.

6. A process for preparation of bifenthrin of formula (I) by reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of a inorganic weak base and a solvent
.

7. The process for preparation of bifenthrin of formula (I) as claimed in claim 6, wherein the inorganic weak base is a carbonate selected from the group consisting of potassium carbonate, sodium carbonate, and cesium carbonate.

8. The process for preparation of bifenthrin of formula (I) as claimed in claim 6, wherein the solvent is selected from the group consisting of dimethylformamide (DMF), N,N-dimethylacetamide and dimethyl sulfoxide.

9. A process for preparation of bifenthrin of formula (I), comprising the steps of:
(i) reacting 2-methyl-3-biphenylmethanol of formula (IV) with aqueous hydrochloric acid (HCl) in presence of a solvent and a catalyst, to produce 3-(chloromethyl)-2-methyl-biphenyl of formula (III)

; and
(ii) reacting rel-(1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (LC acid) of formula (II) with 3-(chloromethyl)-2-methyl-biphenyl of formula (III) in presence of a inorganic weak base and a solvent to produce bifenthrin of formula (I)
.

10. The process for preparation of bifenthrin as claimed in claim 9, wherein the preparation of 3-(chloromethyl)-2-methyl-biphenyl of formula (III) is carried out in the presence of 30% aqueous HCl.

11. The process for preparation of bifenthrin as claimed in claim 9, wherein the catalyst is tetrabutylammonium bromide.

12. The process for preparation of bifenthrin as claimed in claim 9, wherein the inorganic weak base is potassium carbonate.

13. The process for preparation of bifenthrin as claimed in claim 9, wherein the solvent is DMF.