Indigo Carmine Preparation Process Segmentation and Purification

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Solution Overview

Problem

Current methods for preparing Indigo carmine fail to achieve high purity and are either complex, environmentally unfriendly, or require hazardous and expensive reagents, making them inefficient and industrially impractical.

Innovation Solution

A novel process involving the reaction of indole with hydrogen peroxide in an alcoholic solvent, followed by treatment with sulfuric acid and purification in ester solvents, and finally conversion using a sodium source in aqueous media with ketonic solvents to achieve Indigo carmine with >99.5% purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to prepare Indigo carmine, then the process is simpler, but the purity cannot achieve >99.5%

Engineering Contradiction:
Improvepurity of Indigo carmineVSAvoidcomplexity of preparation process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The preparation process is divided into multiple distinct stages: oxidation of indole to indigo using hydrogen peroxide and catalyst, sulfonation of indigo to form indigodisulfonic acid, and final conversion to Indigo carmine using sodium source. Each stage includes specific purification steps, allowing incremental achievement of high purity while maintaining manageable process complexity through systematic breakdown.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The process employs preliminary purification actions at each stage: filtration after oxidation, washing with ester solvents after sulfonation, and washing with ketonic solvents after final conversion. These preliminary actions remove impurities early in each stage, preventing carryover to subsequent stages and enabling final purity >99.5% without requiring excessively complex final purification.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If hazardous reagents are used in the preparation process, then the reaction efficiency may be improved, but environmental safety and cost increase

Engineering Contradiction:
Improveyield of Indigo carmineVSAvoidenvironmental harm and safety risks
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The process converts potentially harmful reagents into beneficial or neutral substances. Hydrogen peroxide oxidizes indole to indigo and decomposes into water and oxygen. Sulfuric acid performs sulfonation and can be recovered. The use of these reagents with controlled decomposition or recovery transforms them from hazards into useful, environmentally acceptable components.

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

Solution Approach 2:

The process uses reagents that are either inexpensive, readily available, or easily decomposed into harmless substances. Hydrogen peroxide decomposes into water and oxygen, sulfuric acid can be recovered and reused, and the washing solvents (ester and ketonic) are chosen for their ability to remove impurities effectively while being relatively safe and economical. This approach maintains high yield without requiring expensive, hazardous, or persistent reagents.

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

3Manufacturing precision

If conventional purification methods are used, then the process is faster, but the purity cannot meet ICH guidelines

Engineering Contradiction:
Improvepurity of Indigo carmineVSAvoidpurification time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The process uses intermediate purification steps with specific solvents as mediators: ester solvents wash the indigodisulfonic acid intermediate, and ketonic solvents wash the final Indigo carmine product. These intermediary washing steps efficiently remove specific impurities at each stage, achieving cumulative purification effect that meets ICH guidelines without requiring excessively long final purification procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

Purification actions continue throughout the entire process rather than being concentrated at the end. Each reaction stage is followed by its dedicated purification step (filtration, washing), maintaining continuous removal of impurities. This continuous purification approach achieves high purity more efficiently than batch purification, reducing total time while ensuring ICH compliance.

Inventive Principle:
Principle #20Continuity of useful action

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

The process results in high-purity Indigo carmine with a simplified, environmentally friendly, and industrially applicable method, reducing the use of hazardous reagents and improving yield while meeting industrial standards.

Implementation Method 1

Indole of compound formula (II) treating with hydrogen peroxide in presence of catalyst in alcoholic solvent to give indigo of compound formula (III)

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

Indigo of compound formula (III) react with sulfuric acid and adding organic solvent then wash or purification in ester solvent to given to indigodisulfonic acid of compound formula (IV)

Methodology Applied
Scientific EffectSulfonation: Chemical Bonding

Implementation Method 3

reacting indigodisulfonic acid of Formula (IV) using aqueous media in sodium source of compound and wash with ketonic solvent to give title compound formula (I)

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Data Source

PatentEP3383956B1An improved process for the preparation of indigo carmine
Publication Date: 2023.08.09 DISHMAN CARBOGEN AMCIS LTD

AI summary

The present invention relates to an improved process for preparation of Indigo carmine of Formula (I), in high purity more than 99.5%.