Malathion Purification via Sodium Bisulfite Extraction

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Malathion preparations for pharmaceutical use contain significant levels of toxic impurities like isomalathion, which increase during storage, posing toxicity risks and stability issues due to instability at elevated temperatures.

Innovation Solution

A process involving the preparation of O,O-dimethyldithiophosphoric acid in an organic solvent, extraction into water, reaction with diethyl maleate, and treatment with a sulfur reagent at a pH less than 7 to produce a highly purified malathion with reduced impurities, ensuring stability and low toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional malathion preparation methods are used, then production cost and simplicity are maintained, but toxic impurities like isomalathion are present at significant levels

Engineering Contradiction:

Improvepurity of malathionVSAvoidcomplexity of purification process

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies extraction by treating malathion with aqueous sodium bisulfite solution, which selectively extracts and removes toxic impurities such as isomalathion and O,O,S-trimethyl phosphorodithioate from the malathion preparation, achieving high purity while maintaining process simplicity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent utilizes parameter changes by controlling the pH of the aqueous sodium bisulfite solution (pH 3-6) and the temperature (0-25°C) to optimize the removal of toxic impurities while preserving malathion integrity, thereby achieving high manufacturing precision through controlled chemical conditions

Inventive Principle:

Principle #35Parameter changes

2Stability of the object's composition

If malathion is stored at elevated temperatures, then storage conditions are relaxed, but toxic impurities increase and stability decreases

Engineering Contradiction:

Improvestorage stability of malathionVSAvoidtoxicity of impurities

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by removing toxic impurities such as isomalathion through sodium bisulfite treatment before storage, preventing their formation and accumulation during storage even at elevated temperatures, thereby maintaining stability and reducing harmful factors

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies preliminary anti-action by using sodium bisulfite to chemically neutralize and remove toxic impurities before they can cause harm during storage, creating a stable preparation that resists degradation and maintains low toxicity under various storage conditions

Inventive Principle:

Principle #9Preliminary anti-action

3Manufacturing precision

If conventional purification methods are used, then process simplicity is maintained, but toxic impurities cannot be effectively removed

Engineering Contradiction:

Improveremoval of toxic impuritiesVSAvoidsimplicity of purification process

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent converts the harmful toxic impurities into removable substances by reacting them with sodium bisulfite, which selectively binds to and removes impurities like isomalathion and O,O,S-trimethyl phosphorodithioate, achieving effective purification through a simple aqueous treatment process

Inventive Principle:

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

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 malathion with significantly lower toxic impurities and improved storage stability, maintaining purity and reducing isomalathion levels even at elevated temperatures and humidity.

Implementation Method 1

extracting the O,O-dimethyldithiophosphoric acid into water to generate an aqueous solution of O,O-dimethyldithiophosphoric acid

Methodology Applied

Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

reacting the aqueous solution of O,O-dimethyldithiophosphoric acid with diethyl maleate to form malathion

Methodology Applied

Scientific EffectChemical reaction: Chemical Bonding

Implementation Method 3

treating the malathion from step (c) with a sulfur reagent, wherein the sulfur reagent has a pH less than about 7.0

Methodology Applied

Scientific EffectChemical purification: Purification

Data Source

PatentUS8957238B2Process for preparing malathion for pharmaceutical use

Publication Date: 2015.02.17 TARO PHARMA INDS

AI summary

The present invention provides a process for preparing a highly pure form of malathion having a reduced level of toxic impurities. In addition, the malathion prepared by the process of this invention is storage stable. The level of toxic impurities in the malathion, e.g., isomalathion, O,O,S-trimethyl phosphorodithioate (MeOOSPS), O,O,S-trimethyl phosphorothioate (MeOOSPO), O,S,S-trimethyl phosphorodithioate (MeOSSPO), malaoxon, isomalathion, diethyl fumarate, methyl malathion, dimethyl malathion, O,O-methyl,ethyl-S-(1,2-dicarboethoxy)ethyl-phosphorodithioate are lower than that of any other commercial preparation of malathion that may be used for pharmaceutical purposes.