# Synthesis of Fluoroquinolones: Revisiting the Grohe Route in DES-Based Media

**Authors:** Rúben Neto, Luis Domingues, Ana Rita Jesus

PMC · DOI: 10.3390/ph19020208 · Pharmaceuticals · 2026-01-25

## TL;DR

This paper explores using deep eutectic solvents to make fluoroquinolones in a more eco-friendly way, achieving good results with lower environmental impact.

## Contribution

The study demonstrates the use of DESs in the Grohe method for fluoroquinolone synthesis, improving sustainability and reducing hazards.

## Key findings

- Several synthesis steps using DESs achieved moderate to good yields under mild conditions.
- The overall yield reached up to 43% with reduced purification needs.
- Greenness assessment confirmed DESs' lower toxicity and energy use compared to traditional solvents.

## Abstract

Background: The development of greener synthetic routes to active pharmaceutical ingredients (APIs) is a key challenge in sustainable chemistry. Methods: In this work, we explored the use of deep eutectic solvents (DESs) in the multi-step synthesis of a fluoroquinolone following the Grohe method. Results: Several steps of the synthetic sequence were successfully carried out using DESs, achieving moderate to good yields, while operating under mild reaction conditions and reducing purification requirements. Overall, the use of DESs led to an overall yield of up to 43%. A comprehensive greenness assessment, combining EcoScale scoring and the GSK and CHEM21 solvent selection guides, confirmed the superior sustainability profile of DESs, reflecting their lower toxicity, biodegradability, and reduced energy demands. Conclusions: These findings establish DESs as promising, eco-friendly alternatives to volatile and hazardous organic solvents for the synthesis of quinolone derivatives, offering a valuable step toward more sustainable pharmaceutical manufacturing.

## Full-text entities

- **Genes:** GHS (Goldenhar syndrome) [NCBI Gene 7971]
- **Diseases:** injury to (MESH:D014947), carcinogenic (MESH:D011230), cytotoxicity (MESH:D064420)
- **Chemicals:** acids (MESH:D000143), p-TSA (MESH:C041343), benzoyl chloride (MESH:C013409), p (MESH:D010758), H3 (MESH:C012616), p-toluene sulfonic acid monohydrate (MESH:C029501), metal (MESH:D008670), methanol (MESH:D000432), 3H (MESH:D014316), acrylate (MESH:C036658), NaCl (MESH:D012965), cyclopropylamine (MESH:C067351), ester (MESH:D004952), triethylamine (MESH:C016162), ciprofloxacin (MESH:D002939), carbon (MESH:D002244), lactic acid (MESH:D019344), polyols (MESH:C024617), choline (MESH:D002794), carboxylic acid (MESH:D002264), C4 (MESH:C058899), dichloromethane (MESH:D008752), C6 (MESH:C117224), amide (MESH:D000577), NMA (MESH:D019323), LA (MESH:D007811), water (MESH:D014867), acetamide (MESH:C030686), 13C (MESH:C000615229), NaOH (MESH:D012972), Gly (MESH:D005998), -TSA (MESH:C481298), HCl (MESH:D006851), silica (MESH:D012822), Glycerol (MESH:D005990), betaine (MESH:D001622), Dioxane (MESH:C025223), H7 (MESH:D019307), ethyl acetate (MESH:C007650), H6 (MESH:C003027), ozone (MESH:D010126), 2H (MESH:D003903), APIs (-), K2CO3 (MESH:C037593), H9 (MESH:C044388), Fluoroquinolone (MESH:D024841), amine (MESH:D000588), quinolone (MESH:D015363), Na2SO4 (MESH:C012036), toluene (MESH:D014050), N-nitroso-N-methyl urea (MESH:D008770), urea (MESH:D014508), chloroform (MESH:D002725), U (MESH:D014501), acrylates (MESH:D000179), DMF (MESH:D004126), THF (MESH:C018674), C2 (MESH:C023714), diethyl ether (MESH:D004986), acyl-glycerol (MESH:D005989)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943312/full.md

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Source: https://tomesphere.com/paper/PMC12943312