Optically Active N-PINAP Salt Crystallization

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Solution Overview

Problem

Current methods for producing optically active [4-(2-diphenylphosphanylnaphthalen-1-yl)phthalazin-1-yl]-(1-phenylethyl)amine (N-PINAP) require complex separation processes like column chromatography, which are inefficient and costly.

Innovation Solution

A method involving the formation of a salt with an optically active organic sulfonic acid, such as camphorsulfonic acid, is used to produce N-PINAP, allowing for preferential crystallization and isolation without the need for column chromatography, using a solution containing N-PINAP and an optically active amine in a hydrophilic organic solvent with water, in the presence of a transition metal complex and a tertiary amine.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If column chromatography is used to separate diastereomixture, then optical purity is improved, but device complexity and production cost increase

Engineering Contradiction:

Improveoptical purityVSAvoidseparation process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent introduces an optically active sulfonic acid as an intermediary substance that forms diastereomeric salts with the racemic amine mixture. This intermediary enables selective crystallization of one enantiomer as a stable salt, while the other remains in solution, achieving separation without complex chromatographic equipment

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical state of the amine components by converting them into salt forms through reaction with optically active sulfonic acid. This parameter change (from free base to salt) creates significant differences in solubility and crystallization behavior between diastereomers, enabling simple filtration-based separation

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If column chromatography is used to separate diastereomixture, then optical purity is improved, but productivity decreases

Engineering Contradiction:

Improveoptical purityVSAvoidproduction efficiency

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent exploits phase transition (crystallization) as the separation mechanism. By controlling temperature and solvent conditions, one diastereomeric salt crystallizes preferentially from the solution, allowing rapid separation through filtration rather than slow chromatographic elution

Inventive Principle:

Principle #36Phase transitions

Solution Approach 2:

The separation process is designed to be self-organizing through selective crystallization. The diastereomeric salts automatically separate based on their inherent solubility differences in the chosen solvent system, eliminating the need for complex operational controls or lengthy chromatographic runs

Inventive Principle:

Principle #25Self-service

3Manufacturing precision

If column chromatography is used to separate diastereomixture, then optical purity is improved, but loss of substance increases

Engineering Contradiction:

Improveoptical purityVSAvoidmaterial loss

Core Design Contradiction:

Manufacturing precisionVSLoss of substance

Solution Approach 1:

The patent creates a copy of the target enantiomer in the form of a diastereomeric salt with the optically active sulfonic acid. This salt copy has different physical properties that enable easy separation, while the original amine structure is preserved and can be recovered by treating the isolated salt with base

Inventive Principle:

Principle #26Copying

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 enables the production of optically active N-PINAP with high optical purity (>95%) without the need for column chromatography, improving yield and reducing production costs.

Implementation Method 1

mixing a solution containing the optically active amine represented by the formula (1) and the optically active amine represented by the formula (3) with an optically active organic sulfonic acid

Methodology Applied

Scientific EffectSalt formation: Chemical Bonding

Implementation Method 2

allowing preferential crystallization and isolation without the need for column chromatography

Methodology Applied

Scientific EffectCrystallization: Crystallisation

Implementation Method 3

mixing a solution containing an optically active amine represented by the formula (1) and the optically active amine represented by the formula (3) in a hydrophilic organic solvent, with water

Methodology Applied

Scientific EffectSolvation: Solvation

Data Source

PatentEP2246356B1Process for production of optically active amines

Publication Date: 2013.04.03 SUMITOMO CHEM CO LTD

AI summary

Salts of optically active [4-(2-diphenylphosphanylnaphthalen-1-yl)phthalazin-1-yl]-(1-phenylethyl)amines represented by the formulas (1) to (4) with an optically active organic sulfonic acid, and a production method thereof.