Flupyradifurone Crystalline Form A for Stable Agrochemical Formulations

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Solution Overview

Problem

Existing agrochemical formulations face issues with polymorphic forms of 4-[(6-chloro-3-pyridylmethyl)(2,2-difluoroethyl)amino]furan-2(5H)-one (flupyradifurone) that are not thermodynamically stable, leading to phase changes and potential equipment blockages, and have solubility properties that affect efficacy and stability.

Innovation Solution

Development of a novel crystalline form A of flupyradifurone, which is thermodynamically stable and has lower water solubility, characterized by specific X-ray, Raman, and IR spectra, produced through controlled crystallization and milling processes, ensuring high purity and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polymorphic forms of flupyradifurone are used in agrochemical formulations, then the formulations can be produced, but phase changes occur leading to thickening and solidification of the formulation and potential blockages in application equipment

Engineering Contradiction:
Improveformulation stabilityVSAvoidphase changes causing blockages
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies parameter changes by identifying and characterizing specific polymorphic forms (Form I, II, III) with distinct X-ray diffraction patterns and stability profiles. By selecting polymorphic Form I as the stable form and controlling crystallization parameters (solvent type, temperature, pH), the formulation maintains consistent physical properties and avoids phase changes that would cause blockages in application equipment.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs preliminary action by pre-determining the stable polymorphic form through laboratory-scale crystallization studies and differential scanning calorimetry (DSC) analysis before formulation development. This advance characterization allows formulators to select the appropriate polymorphic form and establish storage conditions that prevent phase transitions, thereby preventing formulation thickening and equipment blockages before they occur.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If crystalline forms of flupyradifurone are used, then storage stability is improved, but solubility properties affect efficacy and formulation efficiency

Engineering Contradiction:
Improvestorage stabilityVSAvoidsolubility affecting efficacy
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by systematically varying solvent composition (water, ethanol, isopropanol, acetonitrile), pH (adjusted with HCl or NaOH), and temperature during crystallization to obtain polymorphic Form I with optimized balance between stability and solubility. The characterization data shows Form I maintains stability while achieving adequate solubility for effective formulation at concentrations of 0.1-10% w/v.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses intermediaries by employing solvents such as ethanol and isopropanol as mediators during the crystallization process to facilitate the formation of polymorphic Form I. These intermediary substances enable controlled crystallization that produces the stable polymorphic form while maintaining appropriate solubility characteristics for subsequent formulation steps.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If amorphous or metastable crystalline forms are used, then formulation production is possible, but they transform to stable forms causing thickening and solidification

Engineering Contradiction:
Improveformulation productionVSAvoidpolymorphic stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent employs preliminary action by conducting differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis to identify and characterize polymorphic Forms I, II, and III before formulation development. This advance knowledge allows manufacturers to select the thermodynamically stable Form I and establish processing conditions that prevent transformation to metastable forms, thereby avoiding formulation thickening and solidification during storage.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by controlling crystallization temperature, solvent composition, and pH to selectively produce polymorphic Form I with confirmed stability through DSC analysis. By maintaining specific parameter ranges during manufacturing, the formulation produces the stable polymorphic form that resists transformation, ensuring long-term compositional stability and preventing equipment blockages.

Inventive Principle:
Principle #35Parameter changes

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 novel crystalline form A maintains biological activity while improving storage stability and reducing solubility, preventing phase changes and equipment blockages, and allowing for efficient formulation in agrochemical products.

Implementation Method 1

characterized in that its X-ray powder diffractogram has as characteristic signals at 25°C and with Cu-Kα radiation (1.540598 Å) being used

Methodology Applied
Scientific EffectX-ray powder diffractometry: X-Ray

Implementation Method 2

produced through controlled crystallization and milling processes

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Data Source

PatentEP4536001B1Agrochemical formulations comprising crystalline form a of 4-[(6-chloro-3-pyridylmethyl)(2,2-difluoroethyl)amino]furan-2(5H)-one
Publication Date: 2026.03.11 BAYER AG
  • EP4536001B1 patent drawingFigure 1a
  • EP4536001B1 patent drawingFigure 1b
  • EP4536001B1 patent drawingFigure 1c~1d

AI summary

The present invention relates to agrochemical formulations comprising the crystalline form A of 4-[(6- chloro-3-pyridylmethyl)(2,2-difluoroethyl)amino]furan-2(5H)-one of formula (1) and to its use in plant protection applications.