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Once Upon a Time Without DMF: Greener Paths in Peptide and Organic Synthesis
Antonia Scognamiglio1, Elisa Magli2, Giuseppe Caliendo1
1Department of Pharmacy, School of Medicine, University of Naples Federico II, Via D. Montesano, 49, 80131 Napoli, Italy.
Molecules (Basel, Switzerland)
|February 13, 2026
Summary
N,N-Dimethylformamide (DMF) is a widely used solvent facing restrictions due to toxicity. This review analyzes safer alternatives for peptide and organic synthesis, guiding future research toward sustainable chemistry.
Area of Science:
- Organic Chemistry
- Green Chemistry
- Chemical Safety
Background:
- N,N-Dimethylformamide (DMF) is a vital solvent in synthesis.
- DMF presents significant health and environmental risks.
- Regulatory bodies classify DMF as a substance of very high concern (SVHC).
Purpose of the Study:
- To review and analyze existing literature on DMF alternatives.
- To identify current research gaps and challenges in DMF replacement.
- To provide recommendations for future research directions.
Main Methods:
- Comprehensive literature search on DMF alternatives.
- Analysis of reported properties and applications of alternative solvents.
- Identification of research trends and limitations.
Main Results:
- Several alternative solvents show promise for DMF replacement.
- Gaps exist in understanding the long-term safety and scalability of alternatives.
- Current alternatives may not fully match DMF's performance in all applications.
Conclusions:
- Safer and sustainable alternatives to DMF are crucial for modern synthesis.
- Further research is needed to validate and optimize alternative solvents.
- Transitioning away from DMF requires a multi-faceted approach considering efficacy, safety, and environmental impact.
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