Fluopicolide Preparation Using Chelation to Remove Nickel
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Solution Overview
Problem
Existing processes for preparing substituted pyridylmethylbenzamide derivatives are inefficient, costly, and unsuitable for industrial scale due to the formation of side products and contamination with nickel during Raney-Nickel hydrogenation.
Innovation Solution
A process involving reacting substituted 2-(aminomethyl)pyridine derivatives with a compound in a solvent and base at controlled temperatures, followed by acidification, phase separation, and filtration to yield pyridylmethylbenzamide derivatives with reduced nickel content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If Raney-Nickel hydrogenation is used to prepare substituted 2-(aminomethyl)pyridine derivatives, then the hydrogenation reaction proceeds efficiently, but nickel contamination occurs in the final product making it unsuitable for agricultural use
Solution Approach 1:
The patent extracts and removes nickel from the reaction system by introducing a chelating agent (EDTA or DTPA) that selectively binds nickel ions, forming water-soluble complexes that can be separated from the organic product phase. This allows the beneficial hydrogenation reaction to proceed while removing the harmful nickel contamination in the final agricultural product.
Solution Approach 2:
The patent introduces chelating agents (EDTA, DTPA) as intermediary substances that mediate between the nickel catalyst and the final product. These intermediaries bind to nickel ions during and after the hydrogenation reaction, preventing nickel transfer to the organic product while allowing the reaction to proceed efficiently.
2Ease of manufacture
If conventional multi-step processes are used to prepare pyridylmethylbenzamide derivatives, then the reaction can proceed with standard catalysts, but the process is inefficient and costly for industrial scale
Solution Approach 1:
The patent merges the hydrogenation reaction and the subsequent purification steps into a streamlined process. By using chelating agents that work in the same reaction medium and can be removed in a single purification step, the patent combines multiple operations into fewer steps, improving overall production efficiency while maintaining ease of manufacture.
3Ease of manufacture
If palladium on charcoal is used for hydrogenation, then the reaction can proceed, but dehalogenated side products are formed reducing the yield
Solution Approach 1:
The patent changes the catalyst parameter from palladium on charcoal to Raney-Nickel, and further optimizes by controlling reaction conditions (temperature, pressure, solvent) and introducing chelating agents. These parameter changes maintain reaction feasibility while preventing dehalogenation side reactions, thereby improving product purity.
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
The process enables large-scale production of pyridylmethylbenzamide derivatives suitable for agricultural use by minimizing nickel contamination and side product formation.
Implementation Method 1
The preparation of substituted 2-(Aminomethyl)pyridine derivatives by hydrogenation of the corresponding substituted 2-Cyanopyridine derivatives in the presence of palladium on chorcoral
Implementation Method 2
WO 2004/046114 discloses the catalytic hydrogenation of substituted 2-cyanopyridine derivatives to the corresponding 2-(Aminomethyl)pyridine derivatives in the presence of Raney-Nickel
Implementation Method 3
separating the phases and discarding the aqueous phase
Implementation Method 4
acidifying the reaction mixture with a suitable acid to a pH value of 0 to 3
Data Source
AI summary
The present invention relates to an improved process for the preparation of substituted pyridylmethyl- benzamide derivatives of formula (I), in particular 2,6-Dichloro-N-{[3-chloro-5-(trifluoromethyl)-2- pyridyl]methyl}benzamide (Fluopicolide), from substituted 2-(Aminomethyl)pyridine derivatives which are obtained by Raney-Nickel hydrogenation.