Aqueous S <sub>N</sub> Ar Reactions without a Surfactant: A Scalable Method That Uses Only Water from Start to Finish

Six nucleophilic aromatic substitution (SNAr) reactions were efficiently scaled to 10–20 g batch sizes in water without the use of organic solvents or surfactants. Each reaction reached completion within 6 h through simple heating above the melting points of the reactants. The workup involved filtration with pure water, eliminating the need for organic extraction. This streamlined, solvent- and surfactant-free protocol consistently delivered high-purity crystalline products in excellent yield, offering a significantly more sustainable alternative to traditional SNAr methods that rely on polar aprotic solvents or aqueous surfactant additives.

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Publication Details

Journal
Organic Process Research & Development
Published
2025-12-08
DOI
https://doi.org/10.1021/acs.oprd.5c00113
Primary Topic
Sulfur-Based Synthesis Techniques
Type
article
Field-Weighted Citation Impact
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article

Aqueous S N Ar Reactions without a Surfactant: A Scalable Method That Uses Only Water from Start to Finish

Organic Process Research & Development
Sulfur-Based Synthesis Techniques
article

Aqueous S N Ar Reactions without a Surfactant: A Scalable Method That Uses Only Water from Start to Finish

article en

Abstract

Six nucleophilic aromatic substitution (SNAr) reactions were efficiently scaled to 10–20 g batch sizes in water without the use of organic solvents or surfactants. Each reaction reached completion within 6 h through simple heating above the melting points of the reactants. The workup involved filtration with pure water, eliminating the need for organic extraction. This streamlined, solvent- and surfactant-free protocol consistently delivered high-purity crystalline products in excellent yield, offering a significantly more sustainable alternative to traditional SNAr methods that rely on polar aprotic solvents or aqueous surfactant additives.

Organic Process Research & DevelopmentVol. 29(12)
Central Oregon Community College (US)
Responsible consumption and production
Openalex Percentile: Top 43%
Sulfur-Based Synthesis Techniques
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