Sulfinylation of Pyrazole Derivative Using Stable Salts
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Solution Overview
Problem
Current industrial processes for producing fipronil, a crucial insecticide, face challenges such as low yield, impurity issues, and the use of toxic reagents, making it unsuitable for large-scale industrial production and posing environmental and health risks. Additionally, the instability of reagents like CF3S(O)Cl and difficulties in scaling up the process lead to inefficiencies and product contamination.
Innovation Solution
A novel process involving the sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile using trifluoromethylsulfinic acid, its anhydride, or sulfinate alkaline earth metal salts, in the presence of a tertiary amine acid complex, with a halogenating agent, to achieve high purity and yield while avoiding toxic substances and environmental hazards.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If CF3S(O)Cl is used as the sulfinylating agent, then the reactivity is high, but the stability is poor and it is extremely unstable
Solution Approach 1:
The patent uses CF3S(O)ONa or CF3S(O)OK as a stable intermediate compound that can be stored and handled safely. This intermediate then reacts in situ with the pyrazole derivative to deliver the sulfinyl group, replacing the need for unstable CF3S(O)Cl while maintaining high reactivity through the intermediate's controlled reaction with the substrate.
Solution Approach 2:
The patent prepares the stable salt CF3S(O)ONa or CF3S(O)OK in advance as a pre-formed reagent. This preliminary preparation allows the unstable CF3S(O)Cl to be avoided entirely, while the pre-formed salt is ready to react with the pyrazole derivative under controlled conditions to achieve the desired sulfinylation.
2Stability of the object's composition
If CF3S(O)ONa is used as the sulfinylating agent, then the stability is improved, but the reactivity is not high and the yield is relatively low
Solution Approach 1:
The patent introduces a catalyst (such as DMF, triethylamine, or pyridine) that mediates between the stable CF3S(O)ONa and the pyrazole derivative. This catalyst facilitates the reaction by forming a more reactive intermediate species in situ, thereby enhancing the reactivity and yield while maintaining the stability advantage of using CF3S(O)ONa.
Solution Approach 2:
The patent optimizes reaction parameters such as temperature, solvent type, and catalyst concentration to enhance the reactivity of CF3S(O)ONa. By adjusting these parameters, the reaction conditions are tuned to maximize the yield and rate of sulfinylation while retaining the stability benefits of using the salt form rather than the unstable acid chloride.
3Productivity
If toxic reagents are used in the current industrial process, then the production efficiency is maintained, but environmental and health risks increase
Solution Approach 1:
The patent replaces toxic reagents with less hazardous alternatives. Specifically, it substitutes unstable and toxic CF3S(O)Cl with the safer CF3S(O)ONa or CF3S(O)OK salts, and replaces corrosive POCl3 with milder reagents like SOCl2 or COCl2. This conversion maintains production efficiency while significantly reducing environmental and health risks.
Solution Approach 2:
The patent employs reagents that are easier to handle and dispose of safely. The use of stable salts like CF3S(O)ONa and milder chlorinating agents reduces the need for specialized handling equipment and reduces waste treatment complexity, thereby maintaining productivity while lowering the harmful impact on the environment and human health.
4Productivity
If the process is scaled up for large-scale production, then the productivity increases, but the process stability decreases due to reagent instability
Solution Approach 1:
The patent uses stable intermediate compounds (CF3S(O)ONa or CF3S(O)OK) that can be stored and handled safely during large-scale production. These intermediates provide process stability by eliminating the need to handle unstable CF3S(O)Cl, while still enabling high reactivity and yield through catalyzed reactions, thus supporting both high productivity and process reliability at scale.
Solution Approach 2:
The patent prepares stable reagent salts in advance before scaling up production. This preliminary preparation of stable, non-hazardous reagents ensures that the large-scale process can proceed with high reliability, avoiding the instability issues associated with CF3S(O)Cl while maintaining high productivity through efficient subsequent reaction steps.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This process enhances the yield and purity of fipronil, ensuring its suitability for large-scale industrial production while minimizing environmental and health risks, and allows for the production of a high-quality pesticide suitable for agricultural and animal health applications.
Implementation Method 1
The sulfinylation of a pyrazole-type compound refers to the substitution of a hydrogen atom on a pyrazole heterocycle carbon atom by an RS(=O)- group
Implementation Method 2
in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, p-toluenesulfonic acid, benzenesulfonic acid, xylene sulfonic acid, methanesulfonic acid and trifluoromethylsulfonic acid
Implementation Method 3
with the addition of a halogenating agent
Data Source
AI summary
The present invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3- carbonitrile (II) is reacted with a sulfinylating agent selected from trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a trifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent.