1,2-Benzisothiazolin-3-One Synthesis via Dehydration and Oxidation
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Solution Overview
Problem
Existing processes for producing 1,2-benzisothiazolin-3-one (BIT) face challenges due to the difficulty and health hazards associated with nitrosation reactions, as well as low yields and purity issues when using sodium sulfide hydrate, which contains significant water, making it unsuitable for industrial-scale production.
Innovation Solution
A process involving the reaction of an alkali metal salt or ammonium salt of 2-mercaptobenzamide with an oxidizing agent like aqueous hydrogen peroxide, along with the use of sodium sulfide hydrate dehydration using N-methyl 2-pyrrolidone to produce 2-mercaptobenzamide, which is then subjected to oxidative cyclization, offering improved yields and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If nitrosation reaction is used to prepare 2,2'-dithiodibenzamide, then the reaction can proceed, but health hazards occur due to nitrosoamine formation and the reaction is difficult to perform on industrial scale
Solution Approach 1:
The patent extracts and eliminates the harmful nitrosation step from the synthesis pathway. Instead of using nitrosation to form the disulfide bond, the invention uses direct oxidation of mercaptobenzamide with hydrogen peroxide, thereby removing the source of nitrosoamine contamination while maintaining the ability to produce 2,2'-dithiodibenzamide and subsequently BIT on an industrial scale
Solution Approach 2:
The patent replaces the expensive and hazardous nitrosating agents with cheap, safe, and easily handleable hydrogen peroxide. This substitution allows for safe industrial-scale operation without the need for specialized handling procedures required for nitrosation reactions
2Ease of manufacture
If 60% sodium sulfide hydrate is used to prepare 2-mercaptobenzamide, then the reaction can proceed, but the yield of pure 2-mercaptobenzamide is low due to hydrolysis of amide functionality
Solution Approach 1:
The patent changes the concentration parameter of sodium sulfide from 60% to 40%, and simultaneously changes the reaction temperature from ambient to elevated (60-100°C). This parameter modification reduces water activity and prevents amide hydrolysis while maintaining high reaction efficiency, achieving both ease of manufacture and high purity (95% or greater) of 2-mercaptobenzamide
Solution Approach 2:
The patent employs a two-stage reaction process: first forming the intermediate at elevated temperature with 40% sodium sulfide, then adding hydrogen peroxide for oxidative cyclization. This periodic action allows each step to occur under optimized conditions, preventing hydrolysis in the first stage and ensuring complete conversion in the second stage
3Productivity
If conventional oxidative ring closure is performed in alkaline conditions with peracid, then the reaction can proceed, but the process becomes complex and less efficient
Solution Approach 1:
The patent merges the oxidation step and cyclization step into a single operation by using hydrogen peroxide as both the oxidizing agent and the source of oxygen for ring formation. This eliminates the need for separate peracid generation and cyclization steps, reducing process complexity while maintaining high productivity with yields exceeding 90%
Solution Approach 2:
The patent employs hydrogen peroxide which serves multiple functions: it oxidizes the disulfide bond, provides oxygen for ring closure, and decomposes to water as the only byproduct. This self-service capability eliminates the need for additional reagents and simplifies workup procedures, enhancing both productivity and process simplicity
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 provides a more efficient and safer production of BIT with higher yields and purity, reducing by-product formation and avoiding the use of expensive anhydrous sodium sulfide, thus making the process more industrially viable.
Implementation Method 1
subjecting 2-mercaptobenzamide or a salt thereof to oxidative cyclisation... reaction with aqueous hydrogen peroxide
Implementation Method 2
heating a mixture of sodium sulfide hydrate and N-methyl 2-pyrrolidone... distilling from the mixture water and optionally at least a portion of the N-methyl 2-pyrrolidone
Data Source
AI summary
Sodium sulfide hydrate is at least partially dehydrated by heating with N-methyl 2-pyrrolidone. 2-Chlorobenzamide is added to the mixture which is heated further. The mixture is cooled and treated with aqueous hydrogen peroxide to give the sodium salt of 1,2-benzisothiazolin-3-one in good yield. Acidification if desired gives rise to the free 1,2- benzisothiazolin-3-one.