Sucralose-6-acetate Biphasic System Reduces DMF Decomposition

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Solution Overview

Problem

Existing methods for preparing sucralose-6-acetate result in excessive decomposition of DMF, leading to high production costs and environmental concerns due to the use of harmful solvents and byproducts like sulfur dioxide and chlorine hydride.

Innovation Solution

A biphasic liquid-liquid system is employed using an inert non-polar solvent, such as a high-boiling-point alkane, and N,N-dimethylformamide (DMF), where sucrose-6-acetate undergoes chlorination with phosgene or solid phosgene, followed by hydrolysis and crystallization to minimize DMF decomposition and enhance yield.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If DMF is used as solvent for chlorination of sucrose-6-acetate, then the reaction can proceed, but DMF decomposes excessively due to chlorine hydride production, increasing production cost

Engineering Contradiction:
Improvereaction yieldVSAvoidDMF decomposition
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent extracts and removes the harmful byproduct chlorine hydride from the reaction system through a gas-liquid separator. This prevents chlorine hydride from attacking and decomposing DMF, thereby reducing DMF loss while maintaining reaction productivity. The separator continuously removes generated HCl gas, solving the contradiction between maintaining DMF as solvent and preventing its decomposition.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The gas-liquid separator acts as an intermediary device between the reaction system and the environment. It mediates the removal of chlorine hydride without interfering with the main chlorination reaction, allowing DMF to remain as solvent while protecting it from decomposition by the harmful byproduct.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If high temperature (90-98°C) is used to improve sucralose yield, then reaction efficiency increases, but DMF decomposition accelerates due to chlorine hydride production

Engineering Contradiction:
Improvesucralose yieldVSAvoidDMF decomposition
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent implements continuous removal of chlorine hydride through the gas-liquid separator during the entire reaction process. This continuous action allows the reaction to proceed at high temperature for extended periods without accumulating harmful byproducts, thereby maintaining both high productivity and low DMF decomposition.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent converts the harmful effect of chlorine hydride (which causes DMF decomposition) into a removable byproduct stream. By continuously separating and removing HCl gas, the system transforms a problematic side effect into a controlled output, allowing high-temperature reaction to proceed without excessive DMF loss.

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

3Productivity

If chlorinated ether is used as solvent, then sulfur dioxide and chlorine hydride depart quickly improving yield, but the solvent has higher toxicity, higher cost, and causes poor solubility of sucrose-6-acetate

Engineering Contradiction:
Improvereaction yieldVSAvoidsolvent toxicity and cost
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the expensive and toxic chlorinated ether with DMF, which can be continuously regenerated. Instead of relying on a single-use expensive solvent, the system uses a cheaper solvent (DMF) that can be recovered and reused, reducing both cost and environmental impact while maintaining high yield through continuous byproduct removal.

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

Solution Approach 2:

The patent changes the solvent parameter from chlorinated ether to DMF, and compensates for the difference in byproduct removal capability by introducing the gas-liquid separator. This parameter change reduces solvent toxicity and cost while maintaining reaction efficiency through the added separation device.

Inventive Principle:
Principle #35Parameter changes

4Productivity

If perfluorooctane is added as synergetic solvent, then reaction yield increases by 3%, but the solvent system becomes more complicated and requires sulfolane for DMF protection

Engineering Contradiction:
Improvereaction yieldVSAvoidsolvent system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts the function of byproduct removal from the solvent system itself and places it in a dedicated gas-liquid separator device. This eliminates the need for complex solvent combinations like perfluorooctane and sulfolane, achieving the same protective effect through a simpler physical separation approach.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The gas-liquid separator serves as an intermediary that handles the byproduct removal function, allowing the solvent system to remain simple (just DMF) while still achieving high yield and low DMF decomposition. The separator mediates between the reaction mixture and the harmful byproducts without requiring complex solvent additives.

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

This method significantly reduces DMF decomposition, achieves high reaction yields, and allows for the simple recycling of the non-polar solvent, thereby lowering production costs and environmental impact.

Implementation Method 1

a biphasic liquid-liquid system formed by an inert non-polar solvent and N,N-dimethylformamide (abbreviated as DMF)

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

proceeding with cooling, settling the solution to form layers upon completion of the reaction

Methodology Applied
Scientific EffectPhase separation: Density Gradient

Implementation Method 3

sucrose-6-acetate and chlorinating agent engaging in chlorination reaction through heating

Methodology Applied
Scientific EffectChlorination reaction: Chemical Bonding

Implementation Method 4

engaging in chlorination reaction through heating

Methodology Applied
Scientific EffectThermal heating: Heating

Implementation Method 5

proceeding with hydrolysis and neutralization of the DMF solution layer containing the product

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP3456728B1Method for preparing sucralose-6-acylate in biphasic liquid-liquid system
Publication Date: 2022.09.28 ZHEJIANG NHU CO LTD

AI summary

The present invention discloses a method for preparing sucralose-6-acetate in a biphasic liquid-liquid system. The method comprises slowly dropwise adding an inert non-polar solvent containing a chlorinating agent to an N,N-dimethyl formamide (DMF) solution of sucrose-6-acetate; then reacting the biphasic liquid-liquid mixture at a certain temperature for 9-20 hours; cooling the system to room temperature after stopping heating, and settling the solution to form layers, an upper layer being an inert non-polar solvent layer, and a lower layer being a DMF solution layer containing the product; hydrolyzing, neutralizing, and filtering the lower layer to obtain a filtrate, and then concentrating the filtrate to obtain a concentrate; dissolving the concentrate in water, and obtaining the product by extraction using ethyl acetate and crystallization, the inert non-polar solvent being an alkane solvent containing 8-18 carbon atoms that is not mutually soluble with DMF. The method has a high product yield, and can significantly reduce the decomposition of DMF, thereby reducing costs.