Mesotrione Form 3 Crystallization via Seeding

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Solution Overview

Problem

Mesotrione's metastable Form 2 is thermodynamically unstable, leading to instability issues during storage and application, and is difficult to convert to the stable Form 1, resulting in inefficiencies and lost revenue in herbicide production.

Innovation Solution

A new crystalline polymorph Form 3 of mesotrione is developed, characterized by specific X-ray powder diffraction, infrared, and solid-state NMR spectra, which can be crystallized from an aqueous solution using an ammonium salt and polar aprotic solvents, offering improved stability and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mesotrione is recrystallized in aqueous solution to produce Form 1, then the thermodynamically stable form is obtained, but Form 2 is readily made during the manufacturing process which is difficult to filter and causes production time loss

Engineering Contradiction:
Improvestability of mesotrione formVSAvoidproduction time
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies preliminary action by adding seed crystals of Form 1 before the recrystallization process begins. This pre-seeding ensures that Form 1 crystallizes preferentially during the aqueous recrystallization, preventing the formation of Form 2 and eliminating the need for subsequent filtration and conversion steps, thereby maintaining both stability and productivity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by carefully controlling crystallization conditions including temperature, pH, and solvent composition during the aqueous recrystallization process. These parameter optimizations favor the formation of Form 1 while suppressing Form 2, resolving the contradiction between obtaining the stable form and maintaining production efficiency

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If Form 2 is produced during recrystallization, then it can be obtained as a product, but it is thermodynamically unstable and would gradually convert to Form 1 leading to instability problems during storage

Engineering Contradiction:
Improveamount of mesotrione producedVSAvoidstability of mesotrione form
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

By pre-adding Form 1 seed crystals to the recrystallization mixture, the patent ensures that Form 1 is the predominant crystalline phase formed. This preliminary action directs the crystallization pathway toward the stable form, preventing Form 2 formation and eliminating subsequent instability and conversion issues during storage

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies local quality by creating specific microenvironments during crystallization where Form 1 nuclei preferentially grow. Through controlled seeding and optimized local conditions (pH, temperature gradients, solvent distribution), the system favors Form 1 formation in critical zones, ensuring product stability while maintaining yield

Inventive Principle:
Principle #3Local quality

3Loss of energy

If Form 2 material obtained during recrystallization cannot be converted to Form 1, then it must be disposed of, resulting in lost revenue and inefficient production processes

Engineering Contradiction:
Improveproduction efficiencyVSAvoidmesotrione yield
Core Design Contradiction:
Loss of energyVSQuantity of substance

Solution Approach 1:

The patent prevents the creation of problematic Form 2 material through preliminary seeding with Form 1 crystals. By establishing Form 1 as the dominant crystalline phase before recrystallization completes, the process eliminates the need for costly conversion or disposal steps, thereby simultaneously improving production efficiency and maximizing mesotrione yield

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the potential harm of Form 2 formation into benefit by using controlled seeding to direct crystallization toward Form 1. What could have been a problematic byproduct (Form 2) is transformed into a controlled process feature where the seeding mechanism ensures only the desirable stable form precipitates, turning a potential loss into a guaranteed yield

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

Form 3 exhibits reduced phytotoxicity and improved selectivity in weed control, allowing for more efficient and cost-effective herbicide production with enhanced crop safety.

Implementation Method 1

crystallizing Form 3 from an aqueous solution comprising (i) an ammonium salt of 2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione and (ii) a polar aprotic solvent selected from dimethylsulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), dimethylformamide (DMF), and mixtures of said solvents, by acidification of said solution

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 2

an X-ray powder diffraction pattern having a characteristic peak expressed in 2θ (± 0.20°2θ) at 8.0, said peak is characterized by having the highest intensity

Methodology Applied
Scientific EffectX-ray diffraction: X-Ray

Implementation Method 3

an infrared (IR) absorption spectrum having at least one characteristic peak selected from the following values expressed as cm -1

Methodology Applied
Scientific EffectInfrared absorption: Absorption (EM radiation)

Data Source

PatentEP2462112B1Crystal modification of mesotrione
Publication Date: 2016.06.15 ADAMA AGAN LTD
  • EP2462112B1 patent drawingFigure 1
  • EP2462112B1 patent drawingFigure 2A
  • EP2462112B1 patent drawingFigure 2B

AI summary

The invention relates to a crystalline polymorph Form 3 of 2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione. A process for its preparation, use thereof for the control of weeds, and an herbicidal composition comprising thereof are also disclosed.