Crystalline Pyraclostrobin Synthesis via Solvent Parameter Shift
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Solution Overview
Problem
Current methods for producing crystalline methyl N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]-N-methoxycarbamate (pyraclostrobin) require additional crystallization steps and are hindered by side reactions with alcohols and ketones, making them unsuitable for large-scale synthesis.
Innovation Solution
A process involving the reaction of a compound of formula II with an alkylating agent in the presence of a base and a polar solvent selected from alcohols and ketones, with the addition of water, which allows for the direct production of crystalline pyraclostrobin without the need for further solvent crystallization, using preferred solvents like methanol and acetone, and bases such as potassium hydroxide, and optimizing reaction conditions to achieve high yields.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If alcohols are used as polar solvents in the alkylation reaction, then the reaction can proceed, but unwanted side-reactions between DMS and the alcohol occur
Solution Approach 1:
The patent changes the solvent parameter from alcohol to ketone, fundamentally altering the chemical environment to eliminate side-reactions while maintaining reaction feasibility. This parameter change transforms the problematic alcohol solvent into a non-interfering ketone solvent.
Solution Approach 2:
The patent converts the previously harmful alcohol solvent into a beneficial ketone solvent by recognizing that ketones undergo self-condensation rather than side-reactions with DMS. This transforms a harmful interaction into a beneficial process that maintains reaction conditions without unwanted by-products.
2Ease of manufacture
If ketones are used as polar solvents in the alkylation reaction, then the reaction can proceed, but self-condensation (aldol-reaction) occurs
Solution Approach 1:
The patent optimizes the ketone solvent parameters by selecting specific ketones (acetone, methyl-ethyl ketone, butanone) and controlling reaction conditions (temperature, base concentration) to minimize self-condensation while maintaining reaction feasibility.
Solution Approach 2:
The patent introduces a base as an intermediary that facilitates the main alkylation reaction while controlling ketone self-condensation. The base mediates between the ketone solvent and the reaction components, enabling the desired transformation while suppressing unwanted side-reactions.
3Manufacturing precision
If additional crystallization steps are added to produce crystalline material, then crystalline pyraclostrobin can be obtained, but the process complexity and time increase
Solution Approach 1:
The patent merges the reaction and crystallization steps into a single integrated process. The crystalline product precipitates directly from the reaction mixture during the alkylation reaction, eliminating the need for separate crystallization steps and reducing process complexity.
Solution Approach 2:
The reaction system performs self-crystallization, where the product automatically precipitates in crystalline form during the reaction process. This self-service mechanism eliminates the need for external crystallization intervention, reducing both time and process complexity.
4Object-generated harmful factors
If polar aprotic solvents are used instead of alcohols and ketones, then side-reactions are minimized, but the production of crystalline material requires additional steps
Solution Approach 1:
The patent changes the solvent class from polar aprotic to polar protic (ketones), which paradoxically enables both minimal side-reactions and self-crystallization. This parameter change allows the system to achieve multiple objectives simultaneously that were mutually exclusive with polar aprotic solvents.
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 method effectively produces crystalline pyraclostrobin at high yields without additional crystallization steps, minimizing side reactions and water content, and is suitable for large-scale synthesis, particularly in solvent-free formulations like suspension concentrates.
Implementation Method 1
reacting a compound of formula II with an alkylating agent in the presence of a base
Implementation Method 2
the addition of water... direct production of crystalline pyraclostrobin without the need for further solvent crystallization
Data Source
AI summary
The present invention relates to a process for preparing crystalline methyl N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]-N-methoxycarbamate (I), comprising a) reacting a compound of formula (II) with an alkylating agent in the presence of a base in the presence of a polar solvent selected from alcohols and ketons; b) the addition of water.