Sodium Salt Synthesis via pH-Controlled Acidification

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Solution Overview

Problem

The existing method for preparing the sodium salt of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid has a low overall yield, not exceeding 32%, due to inefficient intermediate product yields and incomplete precipitation and purification processes.

Innovation Solution

Adjusting the acidification pH to 5-5.5 during the synthesis of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid and using acidified hydrochloric acid for washing, which enhances complete precipitation and purification, and maintaining the reaction conditions to improve the yield to 56%.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the reaction mass is acidified to a lower pH (3-4) as in the prior art, then the precipitation process is simpler, but the yield of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid is reduced to 40%

Engineering Contradiction:
Improveyield of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acidVSAvoidacidification process complexity
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The invention changes the pH parameter from the conventional range of 3-4 to a higher range of 5-5.5 during acidification. This parameter change optimizes the precipitation conditions for (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid, increasing its yield from 40% to 70% while maintaining process simplicity through the use of hydrochloric acid solution.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the reaction mass is acidified to a higher pH (5-5.5) as in the invention, then the yield of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid increases to 70%, but the purification process becomes more complex

Engineering Contradiction:
Improveyield of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acidVSAvoidpurification process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention changes the pH parameter from the conventional range of 3-4 to a higher range of 5-5.5 during acidification. This parameter change optimizes the precipitation conditions for (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid, increasing its yield from 40% to 70% while maintaining process simplicity through the use of hydrochloric acid solution.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses acidified water (hydrochloric acid solution) as an intermediary medium for both acidification and washing. This intermediary serves dual purposes: it adjusts the pH to optimize precipitation and simultaneously washes the precipitate to remove excess pyridine, simplifying the overall purification process despite the higher pH requirement.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional washing with water is used, then excess hydrochloric acid remains in the product, but if acidified water is used for washing, then excess pyridine is completely removed

Engineering Contradiction:
Improvepurity of final productVSAvoidproduct loss during washing
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The invention uses acidified water (hydrochloric acid solution) as an intermediary medium for both acidification and washing. This intermediary serves dual purposes: it adjusts the pH to optimize precipitation and simultaneously washes the precipitate to remove excess pyridine, simplifying the overall purification process despite the higher pH requirement.

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

The adjusted process increases the yield of the sodium salt to 56% and ensures complete purification by removing excess pyridine and hydrochloric acid, resulting in a higher purity product.

Implementation Method 1

the mixture was acidified with hydrochloric acid to a pH of 5-5.5

Methodology Applied
Scientific EffectAcidification:

Implementation Method 2

The resulting precipitate of pentyl(4-(N-(2,6-dichlorophenyl)sulfamoyl)phenyl)carbamate was filtered off

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 3

washed with water acidified with a solution of hydrochloric acid to a pH of 5-5.5, until the odor of pyridine disappeared

Methodology Applied
Scientific EffectWashing:

Implementation Method 4

ensures complete purification of the product from the excess of pyridine

Methodology Applied
Scientific EffectPurification: Purification

Implementation Method 5

dried. The product yield was 2.1 g (80%)

Methodology Applied
Scientific EffectDrying: Desiccation

Data Source

PatentEP3351530B1Method of producing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulphanilic acid
Publication Date: 2020.08.12 TETS
  • EP3351530B1 patent drawingFigure 1
  • EP3351530B1 patent drawingFigure 2
  • EP3351530B1 patent drawingFigure 3

AI summary

The invention relates to the field of organic chemistry and medicine, and more particularly to a method of producing synthetic biologically active derivatives of carbopentoxysulfanilic acid. The present method of producing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid, which includes synthesizing (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid by mixing 2,6-dichloroaniline and pyridine, then adding carbopentoxysulfanilic acid chloride to the mixture, agitating the reaction mass in a medium acidified by a solution of hydrochloric acid, isolating the precipitate and washing and drying same, and also includes subsequently synthesizing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid by mixing ethanol solutions of caustic soda and (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid, agitating the resultant mixture, distilling off the ethanol and drying the precipitate, is characterized in that the reaction mass formed during the production of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid is agitated in a medium which is acidified with a solution of hydrochloric acid to pH 5-5.5, and the isolated precipitate may be washed with water acidified with a solution of hydrochloric acid to pH 5-5.5. This increases the yield of a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid to 70% (compared to a prior art yield of 32%) and also increases the purity of the target sodium salt.