Halogenated Substrate Reductive Amination Catalyst Poisoning

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Solution Overview

Problem

Metal catalyzed reductive amination reactions of halogenated substrates face challenges with the formation of undesirable by-products that can lead to operational issues such as clogging and catalyst poisoning, due to their low solubility and impact on selectivity and activity.

Innovation Solution

Maintaining a nitrogen-containing compound at a molar ratio below 1.2 relative to the first functional group during the reaction, and using a composition comprising at least 98% o-chloro-benzyl-dimethylamine with controlled levels of stereoisomers to minimize by-product formation and maintain catalyst performance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If metal based catalysts are used for reductive amination of halogenated substrates, then the desired reaction product is formed, but by-products are formed that have low solubility and cause operational problems

Engineering Contradiction:
Improvereaction efficiencyVSAvoidby-product formation
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the reaction system by introducing a specific additive that modifies the reaction pathway. This additive alters the by-product formation kinetics without significantly affecting the main reaction, thereby reducing harmful by-products while maintaining productivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary substance (additive) that mediates between the catalyst and substrate. This intermediary selectively interacts with the catalyst to prevent unwanted side reactions, reducing by-product formation while preserving the desired reaction efficiency

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If reductive amination is performed on halogenated substrates, then the desired amine product is obtained, but the halogen-containing by-products act as catalyst poisons

Engineering Contradiction:
ImproveselectivityVSAvoidcatalyst stability
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent applies preliminary anti-action by adding a protective agent before the harmful interaction occurs. This agent preemptively binds to potential catalyst poison sites or prevents the formation of halogen-containing by-products that would otherwise deactivate the catalyst, thereby maintaining both selectivity and catalyst stability

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The additive serves as an intermediary that protects the catalyst from harmful interactions. It selectively modulates the catalyst's reactivity toward the desired substrate while preventing unwanted interactions with halogen-containing compounds, thus maintaining high selectivity and catalyst reliability simultaneously

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If conventional reductive amination conditions are used, then the reaction proceeds, but precipitate formation causes clogging of filters and piping

Engineering Contradiction:
Improvereaction rateVSAvoidoperational smoothness
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent introduces an intermediary additive that modifies the physical properties of by-products in the reaction mixture. This additive prevents precipitate formation by improving by-product solubility or preventing crystallization, thereby maintaining operational smoothness without compromising reaction rate

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The additive changes the physical-chemical parameters of the reaction system, specifically affecting the solubility and phase behavior of by-products. This parameter modification prevents precipitate formation and clogging while maintaining the desired reaction productivity

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 significantly reduces the formation of undesirable by-products, preventing operational problems and extending the life and selectivity of the catalyst, resulting in a more efficient and stable reductive amination process.

Implementation Method 1

metal catalysed reductive amination

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 2

reductive amination... in the presence of hydrogen

Methodology Applied
Scientific EffectHydrogenation: Hydrogenation

Data Source

PatentEP3374344B1Improved process for the reductive amination of halogen-containing substrates
Publication Date: 2023.10.04 TAMINCO BV
  • EP3374344B1 patent drawingFigure 1
  • EP3374344B1 patent drawingFigure 2

AI summary

Disclosed is a process for performing a reductive amination of a first functional group in an organic feed substrate, which feed substrate comprises at least one further functional group containing a halogen atom, in the presence of hydrogen, a nitrogen-containing compound, and a catalyst, wherein the presence of the nitrogen-containing compound, expressed in a molar ratio relative to the first functional group in the organic feed substrate, at least during the reaction as long as the conversion of the organic feed substrate has not yet reached 80%, is maintained below a level of 1.3. Further disclosed is a composition of the invention comprising at least 98.0%wt of 2-chloro-benzyl-dimethylamine, at most 0.60%wt of the meso-o- CI-BDMA dimer and at least 1 ppm wt of the (+/-)-o-CI-BDMA dimer and any use therefor.