Description:FIELDOF THE INVENTION
The present disclosure relates to the field of chemical synthesis, specifically the preparation of pyrethroid insecticides. More particularly, the disclosure provides an improved and efficient process for the preparation of Bifenthrin using the LC Acid Chloride route. The present disclosure focuses on optimizing reaction conditions, enhancing yield, reducing impurities, and making the process suitable for industrial-scale production of Bifenthrin.
BACKGROUND OF THE DISCLOSURE
Bifenthrin, a highly effective pyrethroid insecticide, is widely used for its potent neurotoxic effects on pests by disrupting their sodium channels, leading to paralysis and death. Due to its efficacy and relatively low toxicity to mammals, Bifenthrin has gained widespread use in agriculture, commercial pest control, and residential settings. However, the industrial production of Bifenthrin has historically faced several challenges related to the complexity of the chemical synthesis, safety concerns, and environmental impact.
The conventional methods for synthesizing Bifenthrin typically involve multiple reaction steps, high mount of hazardous reagents, and volatile solvents. These methods pose serious safety risks, require stringent reaction conditions, and generate significant amounts of waste, making the process inefficient and environmentally unsustainable.
Bifenthrin exhibits strong insecticidal activity, particularly against economically significant pests such as lepidopteran larvae, whiteflies, aphids, and phytophagous mites. It is known for its high efficacy in pest control, coupled with low toxicity to non-target organisms and minimal residue formation, making it a desirable choice in agriculture and pest management. However, there is an unmet need for the development of an industrial-scale production method that can consistently deliver bifenthrin with high purity and optimal yield, ensuring its widespread and efficient use in the agricultural sector.
One of the key intermediates in the production of Bifenthrin is LC Acid Chloride. Traditionally, this intermediate is synthesized by reacting LC Acid with thionyl chloride (SOCl2) under controlled conditions. While this method effectively produces LC Acid Chloride, it involves the generation of by-products such as sulfur dioxide (SO2) and hydrogen chloride (HCl), which require careful management to minimize their impact. Additionally, common methods for Bifenthrin synthesis utilize solvents like hexane, which play a crucial role in extraction and purification processes. As with any solvent, hexane requires proper handling and containment measures during large-scale operations to ensure safe and efficient industrial application while managing emissions responsibly.
Several methods have been developed for the preparation of Bifenthrin, focusing on improving efficiency and reducing waste. Two notable Chinese patents, CN102827004A and CN103145558A, describe processes that aim to reduce waste by eliminating certain steps. However, these methods do not fully address the challenges associated with hazardous reagent use or the complexity of reaction controls.
CN102827004A: This method utilizes isopropyl titanate as a reagent for transesterification. While effective, isopropyl titanate is a costly reagent, which increases production costs.

CN103145558A: In this method, catalytic sodium methoxide is employed for transesterification, but it does not result in the complete conversion of LC Acid methyl ester to Bifenthrin, leading to inefficiencies in the process.

In addition to these methods, processes such as those described in KR100460449B1 and WO2003053905A1 use specific catalysts and solvents but still rely on substantial quantities of reagents like thionyl chloride (SOCl2) and hexane. Furthermore, the use of organophosphorus compounds and catalysts such as triethylamine, triethanolamine, and hexamethyltetramine presents environmental challenges due to the difficulties in managing waste effluents, making these approaches less favorable for large-scale commercial applications.
In addition to these issues, the conventional processes require careful monitoring of reaction conditions, particularly with respect to temperature and pH. For instance, in methods like those described in CN102070454A, inorganic strong bases, such as sodium hydroxide (NaOH), are used to maintain the pH during the reaction. However, the use of strong bases necessitates the implementation of pH control devices and continuous monitoring throughout the reaction to ensure that the pH remains within the desired range. Failure to maintain the correct pH can result in incomplete reactions, the formation of by-products, and lower yields of Bifenthrin.
The preparation of LC Acid Chloride is well-established in prior art, as referenced in patents WO2004074237, CN113896712, CN103435474, WO2003053905, and US4332815. LC Acid is converted to LC Acid Chloride using chlorinating agents such as thionyl chloride, phosgene, oxalyl chloride, POCl3, PCl5, or chlorine gas, often in the presence of catalytic amounts of polar aprotic solvents like N,N-dimethylformamide (DMF) or dimethylacetamide (DMA).
Furthermore, many traditional methods for synthesizing Bifenthrin involve multiple extraction and purification steps, which not only prolong the process but also increase the complexity and cost of production. The need for multiple solvent extractions, combined with the use of hazardous reagents, makes the process cumbersome, costly, and difficult to scale efficiently for industrial production.
The Advancements of the present invention include: Conversion of LC Acid to LC Acid Chloride in the Same Medium: The present invention advances the conversion of LC Acid to LC Acid Chloride within the same reaction medium, streamlining the overall process. This innovative approach facilitates a more efficient reaction pathway, allowing for easier handling and reduced processing times. By conducting the conversion in a single medium, the invention minimizes the need for multiple transfers between vessels, which can enhance operational efficiency. Moreover, while the method necessitates precise control over reaction conditions, such as temperature and reagent concentrations, this requirement fosters the production of a high-quality final product with improved consistency.
Subsequent Reaction with Bifenthrin Alcohol: Following the conversion of LC Acid to LC Acid Chloride, this intermediate is further reacted with Bifenthrin alcohol to synthesize the desired Bifenthrin compound. This step represents a significant advancement as it allows for a targeted synthesis while maintaining the integrity of the intermediate. The careful control implemented in this reaction phase ensures a high yield of the desired compound, effectively addressing potential side reactions and enhancing the overall efficiency of the synthesis process.
Handling of Anhydride Impurities: The present invention also includes innovative strategies to manage the formation of anhydride impurities during the reaction process. By implementing specific controls and monitoring techniques, the invention significantly reduces the impact of these impurities, ensuring they do not interfere with subsequent conversion steps. This proactive approach enhances the purity and efficacy of the final product while minimizing the need for additional purification steps, thereby streamlining the overall process.
Use of Mild Base and Catalyst for the Final Conversion: The conversion of LC Acid Chloride to Bifenthrin is achieved using a mild base, such as sodium bicarbonate (NaHCO3), in conjunction with a catalyst like 4-Dimethylaminopyridine (DMAP). This method represents an advancement by enabling the reaction to proceed under milder conditions while maintaining efficiency. The careful optimization of base and catalyst concentrations ensures that the reaction proceeds to completion, resulting in high yields of Bifenthrin with minimal formation of undesirable side products. This optimization process not only enhances yield but also simplifies the overall purification requirements, contributing to a more efficient synthesis pathway.
The present disclosure addresses longstanding challenges by introducing a novel and optimized method for the preparation of Bifenthrin via the LC Acid Chloride route within the same media. This process is designed to improve safety, reduce environmental impact, and enhance efficiency, making it more suitable for large-scale industrial production.
The key innovation of the present disclosure lies in its optimized use of reagents and solvents, which minimizes the reliance on chemicals while maintaining high yields and product purity. The process utilizes thionyl chloride in a carefully controlled manner.. By optimizing the reaction conditions, the present disclosure ensures that the LC Acid Chloride is produced with minimal risk, allowing for safer handling and storage of the intermediate.
One of the most critical improvements introduced by the present disclosure is the simplification of pH control. Rather than relying on strong bases like sodium hydroxide, which require continuous monitoring, the present disclosure utilizes weaker bases such as sodium carbonate. These weaker bases maintain the reaction's pH within the desired range without the need for constant adjustment or monitoring, simplifying the overall process and reducing the likelihood of human error.
The process is further optimized to reduce the number of extraction and purification steps, making it more efficient and cost-effective. By minimizing the number of steps required to achieve high-purity Bifenthrin, the present disclosure reduces both the time and resources needed for production, making it more suitable for industrial-scale applications.
In summary, the present disclosure solves the problems associated with conventional Bifenthrin synthesis by providing a safer, more efficient, and environmentally friendly method. The process is designed to meet the demands of industrial-scale production while addressing the safety, environmental, and efficiency challenges that have historically plagued the synthesis of Bifenthrin. Through these improvements, the present disclosure offers a significant advancement over prior art processes, providing a more sustainable and scalable solution to produce Bifenthrin.
OBJECTIVEOFTHEDISCLOSURE
The main objective of the disclosure is to provide an improved method for the synthesis of Bifenthrin using the LC Acid Chloride route that enhances process efficiency and product purity.
Another important object of the present disclosure is to outline the two-step reaction process for synthesizing Bifenthrin from LC Acid.
In Step 1, LC Acid is converted to LC-Acid Chloride by reacting with Thionyl Chloride (SOCl2), in LC acid chloride media careful management of reaction conditions, including precise temperature control and the gradual addition of Thionyl Chloride, to ensure complete conversion and to limit the formation of undesired by-products.
Yet another object of the present disclosure is to develop a method for the synthesis of solid Bifenthrin, by reacting LC Acid Chloride of step 1 with Bifenthrin alcohol, symbiotically in presence of catalytic amount of organic bases and inorganic bases.
Yet another object of the present disclosure is to utilize organic base catalysts such as Triethylamine (TEA), pyridine, guanidine, pyrimidine, triazine, N,N-Diakyl benzene derivatives, 1,8-diazabicycloundec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), 4-dimethylaminopyridine (4-DMAP), tetramethylguanidine (TMG), N-methyN,N-Diisopropylethylamine, lpyrrolidine, N-methylmorpholine, N,N-dimethylpiperazine, and ethanolamine to facilitate the reaction.
Yet another object of the present disclosure is toemploy inorganic mild bases such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, barium hydroxide, zinc hydroxide, calcium hydroxide, aluminium hydroxide, Magnesium Hydroxide, Iron(II) Hydroxide, and potassium bisulfate to maintain reaction stability.
Yet another object of the present disclosure is to ensure the reaction maintains a stable pH in the range of 8-14, supporting efficient conversion and product purity throughout the synthesis process.
Yet another object of the present disclosure is to achieve high yields and purity of the final Bifenthrin product, exceeding 95% yield and 98% purity, through a meticulous crystallization, filtration, and drying process.
Yet another object of the present disclosure is to reduce environmental impact and improve safety by minimizing the use of hazardous reagents and solvents and ensuring efficient handling and disposal of by-products.
Yet another object of the present disclosure is to provide a scalable and industrially viable process for Bifenthrin production that ensures consistency, cost-effectiveness, and environmental sustainability.

SUMMARY
The present disclosure introduces an innovative method for synthesizing Bifenthrin using the LC Acid Chloride route, aimed at enhancing efficiency, reducing environmental impact, and ensuring high product purity.
In an aspect of the present disclosure, the process defines in a critical initial stage: LC Acid is meticulously combined with Thionyl Chloride (SOCl2) in an LC acid chloride medium. The reaction is conducted under temperature control, with Thionyl Chloride being gradually added over a 2-3 hour period. It is essential to maintain the reaction temperature between 58-60°C for an additional 2-3 hours, which is crucial for achieving LC Acid content below 0.5%. Following this period, controlled distillation is employed to remove residual Thionyl Chloride, ensuring that both Thionyl Chloride and LC Acid levels meet the prescribed thresholds through rigorous testing.
In an aspect of the present disclosure, the subsequent stage focuses on the synthesis of solid Bifenthrin, initiated by introducing water, sodium carbonate, Bifenthrin alcohol, 4-DMAP, and hexane into the reaction vessel. Stirring for 15 minutes at 40°C precedes the gradual addition of LC Acid Chloride (TC < 0.5%) over a 4-hour period at 40-42°C. Post-addition, pH levels are meticulously monitored to ensure they remain above 7-12, adjusting with excess sodium carbonate as needed. The resulting product undergoes layer separation, solvent recovery,meticulous cooling and crystallization, achieving a yield exceeding 95% and purity exceeding 98% through filtration, drying, and distillation of hexane.
Another aspect of the present disclosure promises to revolutionize Bifenthrin production by prioritizing safety, efficiency in agricultural and industrial applications.

DETAILED DESCRIPTION OF THE DISCLOSURE
With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results. Throughout this specification, the word “comprise”, or variations such as “comprises” or “comprising” or “containing” or “has” or “having”, or “including but not limited to” wherever used, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
Reference throughout this specification to “some embodiments”, “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment may be included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases “in some embodiments”, “in one embodiment” or “in an embodiment” in various places throughout this specification may not necessarily all refer to the same embodiment. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.
The term “about” as used herein encompasses variations of +/-5% and more preferably +/-2.5%, as such variations are appropriate for practicing the present disclosure.The nature of the disclosure and the manner in which it is performed is clearly described in the specification. The disclosure has various components, and they are clearly described in the detailed description.
For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected 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.
a) Crystallization: A purification step involving controlled cooling of the organic layer to form crystalline Bifenthrin.
b) Loss on Drying (LOD): A parameter used to measure the moisture content in the final product. The goal is to achieve LOD = 0.5% in the dried Bifenthrin.
c) Reaction Vessel: The container (such as a round-bottom flask or reactor) used to carry out chemical reactions under controlled conditions.
Abbreviations:
a) LC: Long-chain (refers to the type of acid involved in the preparation of LC Acid Chloride).
b) DMF: Dimethylformamide, a solvent used in organic synthesis.
c) TC: Thionyl Chloride, the reagent used for chlorination.
d) RBF: Round-bottom flask, a type of laboratory glassware used in chemical reactions requiring heating or mixing.
e) 4-DMAP: 4-Dimethylaminopyridine, a catalyst used in the esterification process.
f) LOD: Loss on Drying, a measure of the moisture content in the final product.
g) RPM: Revolutions per minute, a measure of the speed at which the reaction mixture is stirred.
All processes described in this disclosure may be performed in any suitable sequence, unless explicitly stated otherwise or clearly contradicted by the context. The use of examples or exemplary language (e.g., “such as”) in relation to specific embodiments is solely for the purpose of illustrating the disclosure and should not be interpreted as limiting the scope of the disclosure as defined by the claims. No part of this specification should be construed to imply that any non-claimed element is essential to the implementation of the disclosure.
In an embodiment, the LC Acid content is reduced to less than 0.5%, including ranges such as 0.4% LC Acid content, 0.3% LC Acid content, 0.2% LC Acid content, 0.1% LC Acid content, 0.05% LC Acid content.
In an embodiment, the Hexane is distilled outranging from 35-60°C, including possible distillation temperature ranges such as 35-40°C, 35-45°C, 35-50°C, 35-55°C, 35-60°C, 40-45°C, 40-50°C, 40-55°C, 40-60°C, 45-50°C, 45-55°C, 45-60°C, 50-55°C, 50-60°C, and 55-60°C.
In a specific embodiment, the present disclosure provides a process for the preparation of Bifenthrin via the LC Acid Chloride route. The process involves charging Hexane, DMF or DMA, and LC Acid into a reaction flask (rbf), heating the mixture to35-58°C, and add Thionyl Chloride while maintaining the temperature at 35-58°C. After the addition, the reaction mixture is maintained at a certain temperature
In another embodiment, the synthesis of Bifenthrin (solid form) includes charging water and mild inorganic base into a reaction flask, followed by the addition of Bifenthrin alcohol, 4-DMAP, and hexane. The reaction mass is stirred for 15-17 minutes and warmed to35-58°C. The LC Acid Chloride
In an embodiment, the temperature during the addition of LC Acid Chloride is maintained between 35°C and 70°C.

In an embodiment, the time for the addition of LC Acid Chloride is 1-12 hours
In an embodiment, the pH of the reaction mixture is maintained above pH 5-14.
In an embodiment, the pH is maintained in the range of pH 6 to pH 14, maintaining continue till completion of BFN alcohol NMT 0.5%.
In another embodiment, after reaching the desired alcohol content (< 0.5%), the layers are separated at a temperature of 38°C to 40°C. The aqueous layer is extracted with hexane, and the organic layer is separated. The organic layer BFN-AQL-01 undergoes washing with 2-7% sodium bicarbonate solution at 30°C, followed by separation BFN-AQL-02 and another wash with water at 35°C to 40°C.
In an embodiment, the gradual cooling of the organic layer is carried out over 5 hours, including a cooling pattern of:
• Cooling from 35°C to 25°C over 60 minutes;
• Cooling from 25°C to 15°C over 60 minutes;
• Seeding at 15°C, followed by cooling to 10°C over the next 60 minutes;
• Allowing heat from crystallization, if observed, to subside before cooling the mixture further from 10°C to 0°C over the next 60 minutes, and finally cooling from 0°C to -5°C over 60 minutes.
In some embodiments, the cooling pattern may vary, including cooling from:35°C to 20°C, 25°C to 15°C, 15°C to 5°C, or cooling from 30°C to 15°C over different periods to control crystallization effectively.
In another embodiment, the process includes filtration of the solid product (without washing), followed by drying under vacuum at 50°C until the loss on drying (LOD) is = 0.5%. The yield is expected to exceed 95%, with the purity of the final crystalline Bifenthrin product being greater than 98%.

In yet another embodiment of the present disclosure, the two stages of Bifenthrin synthesis, namely Stage 1 (Preparation of LC Acid Chloride) and Stage 2 (Synthesis of Bifenthrin in Solid Form), are closely interrelated to optimize the overall efficiency and product quality.
In Stage 1, the LC Acid Chloride is prepared by first charging LC Acid into a reaction vessel having LC acid chloride media, Thionyl Chloride (SOCl2) is then gradually added while carefully controlling the temperature between 35°C and 58°C. The reaction is maintained at this temperature range for an additional 2-3 hours to ensure optimal conversion of LC Acid to LC Acid Chloride. Following this, Hexane is distilled out under mild vacuum at a temperature range of 35-60°C, with specific temperature combinations such as 35-40°C, 40-50°C, or 55-60°C, depending on the required conditions. This precise control over the distillation process ensures that both Thionyl Chloride and LC Acid levels meet the required thresholds for purity, resulting in a high-quality LC Acid Chloride.
In Stage 2, the LC Acid Chloride from Stage 1 (Thionyl Chloride content < 0.5%) is directly used for the synthesis of Bifenthrin. The LC Acid Chloride is added into a reaction mass containing water, sodium carbonate, Bifenthrin alcohol, 4-DMAP, and hexane, which is stirred and warmed to 40°C. The addition of LC Acid Chloride over 4 hours at a temperature between 40°C and 42°C is critical to maintaining the purity achieved in Stage 1. The pH of the reaction mass is monitored after 50% of the LC Acid Chloride is added, ensuring that it remains above pH 8-12. If necessary, sodium carbonate is added to restore the pH, ensuring the reaction proceeds efficiently without the formation of unwanted by-products.
The interrelationship between the two stages is essential for achieving enhanced efficacy in the final product. The highly pure LC Acid Chloride produced in Stage 1 directly contributes to the efficiency and yield of Stage 2. By minimizing impurities in Stage 1, the reaction in Stage 2 proceeds smoothly, requiring less pH adjustment and producing a final Bifenthrin product with a purity greater than 98% and a yield exceeding 95%. The optimized reaction conditions ensure that the two stages work in synergy, reducing overall reaction time, minimizing the use of additional reagents, and ensuring a high-quality final product with minimal waste.
The present disclosure offers several distinct advantages in optimizing the synthesis of Bifenthrin, particularly through the interrelation of both stages for enhanced efficiency and product quality. One of the key benefits is the production of highly pure LC Acid Chloride in Stage 1, where precise control over the reaction parameters—such as the careful addition of Thionyl Chloride, temperature management, and reduction of LC Acid content—ensures minimal impurities. This purity directly translates to Stage 2, enabling a more efficient synthesis of Bifenthrin with fewer by-products and requiring less pH adjustment during the process.
A major advantage is the improved yield and purity of the final Bifenthrin product, with yields exceeding 95% and purity above 98%. By using highly pure LC Acid Chloride from Stage 1, the reaction in Stage 2 proceeds smoothly, reducing the need for additional reagents and minimizing reaction time. This staged approach maximizes the efficiency of the entire process, resulting in higher-quality output with minimal waste.
Furthermore, the ability to maintain the pH above 8-12 throughout the addition of LC Acid Chloride in Stage 2 ensures optimal reaction conditions, leading to better conversion rates and less degradation of the product. The careful control of temperature and pH significantly enhances the overall effectiveness of the process, contributing to a cleaner, safer, and more sustainable method.
In summary, the present disclosure’s integrated and staged approach delivers key advantages such as improved yield, higher purity, reduced reagent consumption, shorter reaction times, and lower environmental impact. This makes it not only a highly efficient process but also a more sustainable and cost-effective solution for large-scale Bifenthrin production.
It is to be understood that the foregoing descriptive matter is illustrative of the disclosure and not a limitation. While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. Those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein. Similarly, additional embodiments and features of the present disclosure will be apparent to one of ordinary skill in art based upon description provided herein.
Descriptions of well-known/conventional methods/steps and techniques are omitted so as to not unnecessarily obscure the embodiments herein. Further, the disclosure herein provides for examples illustrating the above-described embodiments, and in order to illustrate the embodiments of the present disclosure certain aspects have been employed. The examples used herein for such illustration are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the following examples should not be construed as limiting the scope of the embodiments herein.
EXAMPLES
Example 1: Preparation of Bifenthrin (Stage 1-LC Acid Chloride Formation)
The first stage in the preparation of Bifenthrin involved the formation of LC Acid Chloride, a crucial intermediate in the synthesis process. This stage followed the reaction scheme depicted in Figure 1, which illustrates the conversion of LC Acid to LC Acid Chloride using thionyl chloride as the chlorinating agent in presence of LC acid chloride media.
In the synthesis of LC Acid Chloride, as depicted in Figure 1, the reaction employs hexane as a solvent along with N,N-Dimethylformamide (DMF) or N,N-Dimethyl acetamide (DMA) serving as a catalyst. The process initiates with the charging of 250 g of LC Acid into a reaction flask (RB), where it is combined with hexane and 3.01 g of DMF. The reaction mass is stirred at a controlled temperature of 50°C to facilitate the interaction between the reactants. Following this, 125.5 g of thionyl chloride (TC) is added to the reaction mixture gradually over a span of 60 to 75 minutes while maintaining the temperature at 50°C. Upon the completion of this addition, the temperature of the reaction mixture is raised and held steady between 58°C and 60°C for a period of 2 to 3 hours to ensure thorough reaction and conversion of LC Acid to LC Acid Chloride.
After 3 hours of reaction, the mass is analyzed to confirm that the LC Acid content is less than 0.5%. If the content meets this criterion, the reaction mixture is cooled to a temperature range of 40°C to 45°C, and a vacuum is applied for 30 minutes to remove any residual thionyl chloride from the mixture. Subsequently, the sample is tested again to ensure that the free thionyl chloride content is below 0.5%. Once confirmed, the reaction mass is further cooled to a temperature range of 25°C to 30°C, completing the preparation of LC Acid Chloride with minimal by products.then move forward for next step. LC acid chloride 366 g with purity >98%

Figure: 1

Example 2: Preparation of Bifenthrin (Stage 2 - Esterification)
The second stage in the preparation of Bifenthrin involved the esterification reaction between LC Acid Chloride and Bifenthrin alcohol, as illustrated in Figure 2. This crucial step resulted in the formation of the final Bifenthrin product, a potent insecticide widely used in agriculture and pest control.

Figure: 2
As depicted in Figure 2, the reaction utilized Bifenthrin alcohol and LC Acid Chloride as the primary reactants. The esterification was carried out in a biphasic system, with hexane serving as the organic solvent and an aqueous sodium carbonate solution providing the basic environment. 4-Dimethylaminopyridine (4-DMAP) was employed as a catalyst to enhance the reaction rate and efficiency.
The preparation method for Bifenthrin, following the reaction scheme in Figure 2, involved several carefully controlled steps. Initially, water and sodium carbonate were charged into a reaction vessel to create the basic aqueous layer. Bifenthrin alcohol, 4-DMAP, and hexane were then added to form the organic layer. The reaction mixture was warmed to 40°C, creating optimal conditions for the esterification process.
LC Acid Chloride, prepared in the previous stage with less than 0.5% thionyl chloride content, was gradually added to the reaction mixture over 4 hours, maintaining the temperature between 40°C and 42°C. As shown in Figure 2, this addition resulted in the nucleophilic attack of the Bifenthrin alcohol on the carbonyl carbon of LC Acid Chloride, forming the ester linkage characteristic of Bifenthrin.
Throughout the reaction, the pH was carefully monitored and maintained 7-14by adding sodium carbonate as needed. This basic environment, as indicated in Figure 2, was crucial for neutralizing the hydrochloric acid byproduct and driving the reaction to completion. After the complete addition of LC Acid Chloride, the reaction was maintained at 40-42°C for an additional hour to ensure maximal conversion.
The progress of the reaction was monitored by analyzing the Bifenthrin alcohol content, with additional LC Acid Chloride added if necessary to achieve less than 0.5% residual alcohol. Once the desired conversion was achieved, the reaction mixture was cooled and the layers separated. The organic layer containing the Bifenthrin product was washed with sodium bicarbonate solution and water to remove any residual impurities.
Following the reaction scheme in Figure 2, the purified organic layer underwent a controlled cooling process to induce crystallization of the Bifenthrin product. The cooling pattern involved gradual temperature reduction from 35°C to -5°C over 5 hours, with seeding at specific temperatures to promote crystal formation. The resulting crystalline Bifenthrin was then filtered, dried under vacuum at 50°C, and analyzed for purity and yield.
Example 3: Specific Synthesis of Bifenthrin
In this step, 1343 g of water and 282.24 g of sodium carbonate are charged into a reaction flask (RB) and stirred for 5-10 minutes to ensure proper mixing. Following this initial preparation, 800 g of Bifenthrin alcohol, 8.38 g of 4-Dimethylaminopyridine (4-DMAP), and 2086 g of hexane are added to the stirred mixture. The reaction mass is then stirred for an additional 15 minutes before being warmed to 40°C.
At this point, the addition of 1085 g of LC Acid Chloride (with thionyl chloride content less than 0.5%) is initiated, performed over a period of 4 hours while maintaining the temperature between 40°C and 42°C and the pH within the range of 6-12. The mixture is stirred for 1-2 hours to facilitate the reaction. After this period, the pH of the reaction mass is checked, and a sample is sent for analysis to determine the Bifenthrin alcohol content.
If the Bifenthrin alcohol content is found to exceed 0.5%, additional LC Acid Chloride is added based on the quantity of unreacted Bifenthrin alcohol, and the mixture is maintained for an additional 0.5 hours. After the completion of the reaction, the layers are separated at a temperature of 38°C to 40°C. The aqueous layer is extracted with hexane, leading to the collection of the organic layer, designated as BFN-AQL-01. This organic layer is then washed with a 2% sodium bicarbonate solution at 30°C, resulting in a second separated layer, BFN-AQL-02.
The organic layer is subjected to a final wash with water at a temperature between 35°C and 40°C, yielding another separated layer, BFN-AQL-03. The organic layer is gradually cooled to a temperature range of 0°C to 5°C, after which the reaction mass is filtered once crystal formation is observed. The final product is dried, resulting in a yield of 95% with a purity of 98%.
This meticulous process, guided by the reaction scheme in Figure 2, resulted in high-quality Bifenthrin with a yield exceeding 95% and purity greater than 98%. The product appeared as a white to off-white crystalline solid, ready for formulation into various insecticidal products. , Claims:1. A two-part process for preparing a solid Bifenthrin symbiotically, comprising part 1 and part 2, wherein part 1 comprising the steps of:
a) treating a LC Acid with chlorinating agents, specifically thionyl chloride in a media of LC acid chloride in presence of catalyst selected from the group consisting of DMF or DMA to form a mixture;
b) heating the resulting mixture to a temperature within the range of 30°C to 70°C;
c) adding thionyl chloride (TC) while maintaining the temperature within the range of 30 to70 °C
d) holding the reaction at a temperature in the range of 35°C to 75°C for a duration of 2 to 4 hours,
2. The process as claimed in claim 1, further comprises part 2, utilizing the prepared LC Acid Chloride of step a-e to synthesize Bifenthrin comprising the steps:
a) charging water and sodium carbonate in a reaction vessel, and adding Bifenthrin alcohol, 4-DMAP, hexane and solvents to the reaction vessel;
b) stirring the mixture for 10-15 minutes and warming it up to 35-70°C;
c) gradually adding the LC Acid Chloride while maintaining a pH above 7-14 and
d) isolating Bifenthrin.
3. The process as claimed in claim 1, wherein heating the mixture to a temperature in the range of 35-70°C.
4. The process as claimed claim 1, wherein the addition of thionyl chloride is performed over a period of 1 to 10hourswhile ensuring the reaction temperature remains above35 to 70°C or more.
5. The process as claimed in claim 1, wherein step e, further comprises a degassing step for 30 minutes, wherein the free thionyl chloride content is minimized.
6. The process as claimed in claim 2, wherein sodium carbonate is added to maintain the pH of the reaction mass above 7 to 14throughout the addition of LC Acid Chloride.
7. The process as claimed in claim 2, wherein the Bifenthrin alcohol content is monitored, and additional LC Acid Chloride is introduced when it exceeds 0.5%.
8. The process as claimed in claim 2, wherein the final washing step includes washing the organic layer with water at a temperature ranging from 35°C to 40°C9. The process as claimed in claim 2, wherein the crystallization process includes cooling the organic layer from 35°C to -5°C over a period of 5 hours, with temperature intervals.
9. The process as claimed in claim 2, wherein the solvents comprise non-polar solvents selected from the group consisting of toluene, xylene, and halogenated solvents selected from the group consisting of mono chloro difluoromethane (MDC) and ethylene dichloride (EDC).
10. The process as claimed in claim 2, wherein the solvents comprise ethereal solvents selected from the group consisting of hexane dimethyl formamide (DMF), tetrahydrofuran (THF), and 2-Methyltetrahydrofuran (2-MetTHF), and polar aprotic solvents selected from the group consisting of dimethylformamide (DMF) and dimethylacetamide (DMA).
11. The process as claimed in claims 1-11, wherein the solid Bifenthrin product is dried at a temperature of 50°C until the loss on drying is equal to or less than 0.5%.
12. The process as claimed in claim 1-12, wherein the Bifenthrin produced is characterized by its white to off-white crystalline appearance, and wherein the residue obtained after distilling hexane from the filtrate in Part 2 has a purity exceeding 95%.
13. The process as claimed in claim 1, wherein the heating and stirring conditions in both parts are continuously monitored to maintain optimal reaction conditions, promoting high yield and purity.
14. The process as claimed in claim 1, wherein the reaction is conducted under an inert atmosphere to enhance the formation of LC Acid Chloride.
15. The process as claimed in claim 2, wherein the mixing speed during the addition of LC Acid Chloride is maintained within a range of 100 to 300 RPM to ensure thorough mixing.
16. The process as claimed in claim 2, wherein the reaction time is optimized to ensure complete conversion of Bifenthrin alcohol to Bifenthrin.
17. The process as claimed in claim 1-16, wherein the hexane used is recycled after purification to reduce environmental impact.