Catalytic Protodecarboxylation of Alpha-Halo-Acrylic Acids

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Solution Overview

Problem

The synthesis of terminal halo olefins, particularly through protodecarboxylation of α-halo-acrylic acid derivatives, is limited by the need for excessive heating, stoichiometric metal usage, and restricted substrate scope, which hampers widespread application and efficiency.

Innovation Solution

A method involving the protodecarboxylation of α-halo-acrylic acid derivatives using catalytic amounts of copper and/or silver, allowing for stereospecific formation of halo olefins under mild conditions, with silver(I) oxide and copper(I) salts proving highly efficient, enabling high yields and purities without the need for excessive heating.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If protodecarboxylation is performed using conventional methods, then halo olefins can be synthesized, but excessive heating and stoichiometric metal usage are required, reducing efficiency and increasing cost

Engineering Contradiction:
Improvereaction efficiencyVSAvoidheating energy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The invention changes the temperature parameter from excessive heating (conventional methods) to mild heating conditions (50-150°C). This is achieved by optimizing the catalyst system (silver salts, copper salts, or their combinations) and reaction conditions, allowing the protodecarboxylation to proceed efficiently at lower temperatures, thus reducing energy consumption while maintaining high productivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces stoichiometric metal usage with catalytic amounts of metal salts. The metal catalysts (silver salts, copper salts) are used in sub-stoichiometric quantities (typically 5-50 mol%), significantly reducing metal consumption and waste generation while maintaining high reaction efficiency and productivity

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Productivity

If protodecarboxylation is performed using conventional methods, then halo olefins can be synthesized, but stoichiometric metal usage is required, increasing cost and waste

Engineering Contradiction:
Improvereaction efficiencyVSAvoidmetal consumption
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The invention replaces stoichiometric metal usage with catalytic amounts of metal salts. The metal catalysts (silver salts, copper salts) are used in sub-stoichiometric quantities (typically 5-50 mol%), significantly reducing metal consumption and waste generation while maintaining high reaction efficiency and productivity

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention changes the metal loading parameter from stoichiometric amounts to catalytic amounts. This parameter change, combined with optimized catalyst selection and reaction conditions, enables the reaction to proceed efficiently with minimal metal consumption, reducing both cost and environmental impact

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If protodecarboxylation is performed using conventional methods, then halo olefins can be synthesized, but the substrate scope is restricted, limiting application

Engineering Contradiction:
Improvesubstrate scopeVSAvoidreaction reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The invention employs a universal catalyst system that can accommodate diverse substrates including electron-withdrawing groups (ester, amide, nitrile, sulfone) and various R1 substituents (alkyl, aryl, heteroaryl). The catalyst system (silver salts, copper salts, or their combinations) functions reliably across this broad substrate scope, enabling the synthesis of various halo olefins with different functional groups without compromising reaction reliability

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention optimizes reaction parameters (temperature 50-150°C, catalyst loading 5-50 mol%, reaction time 1-24 hours) to achieve reliable results across a broad substrate scope. These parameter optimizations allow the reaction to tolerate various functional groups and substituent types while maintaining high yields and stereoselectivity

Inventive Principle:
Principle #35Parameter changes

4Manufacturing precision

If protodecarboxylation is performed to improve stereoselectivity, then halo olefins with high E/Z selectivity can be obtained, but reaction conditions must be precisely controlled, increasing complexity

Engineering Contradiction:
ImprovestereoselectivityVSAvoidprocess control complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention achieves high stereoselectivity (E/Z selectivity) by optimizing reaction parameters including temperature (50-150°C), catalyst loading (5-50 mol%), and reaction time (1-24 hours). These parameter optimizations enable precise control over the stereochemical outcome without requiring overly complex process control systems, as the reaction proceeds reliably under mild and easily controllable conditions

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

This approach enables the synthesis of halo olefins with improved stereoselectivity and yield, reducing reaction time and metal usage, thus overcoming the limitations of existing methods by allowing for the formation of halo olefins under milder conditions and broader substrate compatibility.

Implementation Method 1

a method for the synthesis of a halo olefin of formula (I) wherein Hal, R 1 The present description relates also to the intermediates comprised in the method according to this invention

Methodology Applied
Scientific EffectCatalysis: Catalysis

Data Source

PatentEP3589606B1Transition metal-catalyzed protodecarboxylation of alpha-halo-acrylic acid derivatives
Publication Date: 2023.09.20 BOEHRINGER INGELHEIM INT GMBH
  • EP3589606B1 patent drawingFigure 1
  • EP3589606B1 patent drawingFigure 2
  • EP3589606B1 patent drawingFigure 3

AI summary

The present invention relates to a method for the synthesis of a halo olefin of formula (I) wherein Hal, R1, R2, R3, R4, X and Y are defined according to claim 1, or a salt thereof comprising the step of protodecarboxylation of an a-halo-acrylic acid derivative in the presence of a catalytic amount of copper and/or silver.