One-Pot Sulfation and Acetylation for Stable Hydroxyl Compounds

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Solution Overview

Problem

Existing methods for producing compounds with carboxylate, sulfate, and acetate groups are inefficient, costly, and produce unstable products, particularly when used in aqueous solutions, and do not allow for the introduction of acetyl groups without altering the structure of sulfate and carboxylate groups.

Innovation Solution

A method involving a single reaction batch with SOs-DMF and CH2(CO)O(CO)CH2 in the presence of a hydrolyzing reagent, preferably a weak base, to sulfonate and acetylate compounds with hydroxyl groups, ensuring stability and purity without intermediate steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If multiple-step methods are used for carboxymethylation and sulfation, then substitution levels can be achieved, but the process becomes complex, time-consuming, and produces unstable intermediates

Engineering Contradiction:
Improvesubstitution level controlVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent combines carboxymethylation and sulfation reactions into a single simultaneous reaction step using a dual-functional reagent system. This eliminates the need for separate sequential steps, reducing process complexity while maintaining control over substitution levels through stoichiometric control of the reagents.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses pre-formed complexes or pre-mixed reagent systems that contain both carboxymethylating and sulfating agents in controlled ratios. This preliminary preparation allows both reactions to proceed simultaneously with controlled substitution levels without requiring multiple sequential steps.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If traditional sulfation methods are used, then sulfate groups are introduced, but acetyl groups cannot be introduced without altering sulfate and carboxylate groups

Engineering Contradiction:
Improvegroup introduction capabilityVSAvoidstructural integrity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs a hydrolyzing reagent as an intermediary that selectively hydrolyzes excess reagents and unstable intermediates after the simultaneous carboxymethylation and sulfation reactions. This intermediary step protects the structural integrity of the introduced sulfate and carboxylate groups while allowing acetyl groups to be introduced without alteration.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If known methods are used for producing compounds with multiple functional groups, then substitution can occur, but the products are unstable in aqueous solutions

Engineering Contradiction:
Improvefunctional group contentVSAvoidaqueous stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent optimizes reaction parameters including pH control, temperature, and reagent concentrations to produce stable compounds with multiple functional groups. The simultaneous reaction approach with controlled stoichiometry prevents the formation of unstable intermediates that would decompose in aqueous solutions, while still achieving high levels of functional group substitution.

Inventive Principle:
Principle #35Parameter changes

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 method enables quick and effective synthesis of stable compounds with sulfate and acetate groups, suitable for therapeutic use, without unstable intermediates or contaminants, and maintains the structural integrity of existing groups.

Implementation Method 1

the reaction of said compound with SOs-DMF and CH 2 (CO)O(CO)CH 2

Methodology Applied
Scientific EffectNucleophilic substitution: Chemical Bonding

Implementation Method 2

the reaction of said compound with SOs-DMF and CH 2 (CO)O(CO)CH 2

Methodology Applied
Scientific EffectNucleophilic acyl substitution: Chemical Bonding

Implementation Method 3

in presence of a hydrolyzing reagent, preferably an acid or a base

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP4703392A1A method for n-,o-sulfonation and acetylation of a compound
Publication Date: 2026.03.04 ORGANES TISSUS REGENERATION REPARATION REMPLACEMENT OTR3
  • EP4703392A1 patent drawingFigure 1a~2d
  • EP4703392A1 patent drawingFigure 3A~3D
  • EP4703392A1 patent drawingFigure 4a~4b

AI summary

The invention relates to a method for sulfation and acetylation of a compound having one or more hydroxyl group, wherein the method comprises, in a single reaction batch, the reaction of said compound with Sulphur trioxide/N,N-dimethylformamide (SOs-DMF) and CH2(CO)O(CO)CH2 in presence of a hydrolyzing reagent. The present invention has an application in particular in the therapeutic, pharmaceutical and chemical fields.