Trifloxystrobin Synthesis via Diazonium Coupling
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Solution Overview
Problem
Existing methods for synthesizing trifloxystrobin face challenges such as long synthetic routes, use of toxic reagents like sodium cyanide, expensive starting materials, and low yields, making them unsuitable for commercial-scale operations.
Innovation Solution
A four-step process starting from o-toluidine to selectively synthesize (E)-methoxyimino-o-tolyl-acetic acid, followed by conversion to trifloxystrobin, using inexpensive and easily sourced o-toluidine, avoiding hazardous reagents and optimizing conditions for high yield and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional multi-step synthesis routes are used, then trifloxystrobin can be prepared, but the synthetic route becomes long and complex with low yield
Solution Approach 1:
The synthesis is divided into two main segments: (1) preparation of (E)-2-methoxyimino-2-(o-tolyl)acetic acid from o-toluidine through diazotization and coupling reactions, and (2) conversion to trifloxystrobin through esterification and bromination. This segmentation allows each step to be optimized independently, achieving high yield (40.2%) while maintaining clarity in the synthetic pathway.
Solution Approach 2:
The patent performs preliminary actions by first synthesizing the diazonium salt from o-toluidine and then immediately coupling it with glyoxylic acid methoxime to form the imino acid. This preliminary preparation of reactive intermediaries avoids subsequent complex steps and directly leads to the desired product with high efficiency.
2Ease of manufacture
If toxic reagents like sodium cyanide are used, then certain synthesis steps can be achieved, but environmental safety and operational safety deteriorate
Solution Approach 1:
The patent converts the potentially harmful diazonium intermediate (which can be unstable and explosive) into a beneficial coupling reagent that forms the C-C bond in the imino acid. This transformation eliminates the need for toxic cyanide reagents while maintaining synthesis feasibility through the diazonium-glyoxylic acid coupling mechanism.
Solution Approach 2:
The patent uses readily available and safe reagents such as sodium nitrite, glyoxylic acid methoxime, and standard coupling conditions instead of expensive and toxic cyanide reagents. The synthesis employs disposable, easy-to-handle materials that can be safely managed in industrial settings, eliminating environmental and operational hazards.
3Manufacturing precision
If expensive starting materials and reagents are used, then specific synthesis steps can be performed, but manufacturing cost increases
Solution Approach 1:
The patent employs inexpensive and easily sourced reagents including o-toluidine, sodium nitrite, glyoxylic acid methoxime, and standard coupling agents. These reagents are readily available at commercial levels and can be easily disposed of or recycled, significantly reducing manufacturing costs while maintaining high chemical purity (>98%) of the final product.
Solution Approach 2:
The patent optimizes reaction parameters such as using copper sulfate as a catalyst, controlling pH levels, and selecting appropriate solvents to enhance reaction efficiency. These parameter changes allow the use of cheaper reagents while achieving the same or better manufacturing precision, eliminating the need for expensive specialized materials.
4Productivity
If multiple synthesis steps are used, then trifloxystrobin can be prepared, but the cycle time increases and effluent generation increases
Solution Approach 1:
The patent merges multiple functions into fewer steps: the coupling reaction simultaneously forms the C-C bond and creates the imino group, while the esterification and bromination steps are combined into a streamlined sequence. This merging reduces the total number of operations, decreasing cycle time and reducing effluent generation while maintaining high overall yield (40.2%).
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 achieves a high yield of 40.2% trifloxystrobin with high chemical purity (>98%), reducing the number of steps and eliminating the need for toxic reagents, making it commercially viable and environmentally friendly.
Implementation Method 1
preparing a 2-methyl benzene diazonium chloride of formula (2) by reacting I-amino-2- methylbenzene of formula (1) with alkali metal nitrite in presence of an acid
Implementation Method 2
obtaining a 2-methoxyimino-acetic acid of formula (4) by reacting 2-oxoacetic acid of formula (3) with methoxylamine hydrochloride in presence of a base in a solvent or mixture of solvents
Implementation Method 3
obtaining (E)-2-methoxyimino-2-(o-tolyl)acetic acid of formula (5) by reacting a compound of formula (2) with a compound of formula (4) in presence of salt of an acid or a base and a metal sulphate in a suitable solvent or mixture of solvents
Implementation Method 4
obtaining (E)-2-methoxyimino-2-(o-tolyl) acetic acid methyl ester formula (6) by reacting a compound of formula (5) with an acid and methanol with or without a solvent or mixture of solvents
Implementation Method 5
obtaining an intermediate of formula (7) by reacting a compound formula (6) with metal halogenate in presence of a base with or without catalyst in a solvent or mixture of solvents
Implementation Method 6
obtaining trifloxystrobin formula (1) by reacting a compound of formula (7) with a 1-(3-trifluoromethyl-phenyl)-ethanone oxime formula (8) in presence of a base and with or without phase transfer catalyst in a solvent or mixture of solvents
Data Source
AI summary
The present invention relates to an improved process for the preparation of trifloxystrobin of formula (I), which is simple, economical, efficient, user and environment friendly, moreover commercially viable with higher yield and chemical purity.