Tertiary Amine Synthesis via Transfer Hydrogenation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The existing methods for preparing tertiary amines through the reduction of nitriles often suffer from poor selectivity, low conversions, and high secondary amine loading, particularly when using high temperatures and pressures, and lack a viable method for reductive amination with secondary amines via transfer hydrogenation.

Innovation Solution

A method for preparing tertiary amines via reductive amination of nitriles using transfer hydrogenation in the presence of a catalyst, a secondary amine, and a hydrogen donor, which can be performed at atmospheric pressure and lower temperatures, utilizing Group VIII metals like palladium or platinum on supports, with hydrogen donors such as formic acid or its salts, and optionally water, in solvents like alcohols or aprotic solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If high temperatures and high hydrogen pressures are used for reductive amination of nitriles, then conversion to tertiary amines is achieved, but selectivity deteriorates and secondary amine loading increases

Engineering Contradiction:

ImproveconversionVSAvoidselectivity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent changes the physical state parameters of hydrogen from gaseous (high pressure) to liquid (ambient pressure) by using formic acid as a hydrogen donor. This parameter change allows the reaction to proceed at ambient pressure and temperature while maintaining high conversion and improving selectivity, resolving the contradiction between productivity and manufacturing precision

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces formic acid as an intermediary hydrogen donor that mediates the hydrogen transfer process. Instead of using direct hydrogen gas under high pressure, formic acid serves as a safe intermediary that decomposes to provide hydrogen in-situ, enabling high conversion while maintaining selectivity and eliminating the need for high-pressure equipment

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If high pressure hydrogen gas is used for reduction, then conversion is achieved, but safety hazards and equipment costs increase

Engineering Contradiction:

ImproveconversionVSAvoidsafety hazards

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

Formic acid serves as an intermediary hydrogen donor that eliminates the need for high-pressure hydrogen gas. It decomposes under mild conditions to provide hydrogen in-situ, maintaining high conversion while completely avoiding the safety hazards associated with storing and handling high-pressure hydrogen gas

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses formic acid as a disposable, safe alternative to expensive and dangerous high-pressure hydrogen gas. Formic acid can be handled at ambient pressure and temperature, eliminating the need for specialized high-pressure equipment and reducing both capital and operational costs while maintaining high conversion

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Productivity

If high temperatures are used for reductive amination, then conversion is improved, but energy consumption and decomposition issues increase

Engineering Contradiction:

ImproveconversionVSAvoidenergy consumption

Core Design Contradiction:

ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent changes the temperature parameter from high (120°C or above) to ambient or mild conditions by using formic acid as a hydrogen donor. Formic acid decomposition provides sufficient hydrogen under mild conditions, achieving high conversion while dramatically reducing energy consumption and avoiding thermal decomposition of sensitive compounds

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Formic acid acts as an intermediary that enables hydrogen transfer at low temperatures. Its decomposition provides hydrogen in-situ under mild conditions, eliminating the need for high-temperature heating and thus reducing energy consumption while maintaining high conversion rates

Inventive Principle:

Principle #24Intermediary (Mediator)

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 achieves high selectivity and conversion to tertiary amines at reduced energy costs, avoiding the hazards of high-pressure hydrogen gas and decomposition issues, while allowing for the use of less expensive reaction vessels and milder conditions.

Implementation Method 1

reductive amination of nitriles using transfer hydrogenation

Methodology Applied

Scientific EffectTransfer hydrogenation: Hydrogenation

Implementation Method 2

in the presence of at least one catalyst

Methodology Applied

Scientific EffectCatalysis: Catalysis

Implementation Method 3

with a hydrogen donor molecule such as isopropanol, cyclohexene, cyclohexadiene, formic acid, formic acid salts, hydrazine, hydrazine salts, and amines

Methodology Applied

Scientific EffectHydrogen donation: Redox Reactions

Data Source

PatentUS9469595B1Reductive amination of nitriles using transfer hydrogenation

Publication Date: 2016.10.18 EASTMAN CHEM CO

AI summary

This disclosure describes a low temperature process for the preparation of tertiary amines from nitriles and secondary amines via reductive amination using transfer hydrogenation. The process can use a nitrile and a dialkylamine and proceeds under surprisingly mild conditions using a palladium catalyst and the corresponding dialkylammonium formate as the hydrogen donor, and show a pronounced acceleration in the presence of water.