Water

Mechanism + Description

Simple SN2 displacement of alcohol.

General comments

Many activated esters e.g. trifluoroethyl, benzoyl, trifluoroacetate etc can be hydrolysed with water or water-solvent mixtures alone or added to an organic solvent if needed for solubility. This should always be tried as a first line of investigation.

Key references

J.Am.Chem.Soc., 1958, 80, 2985 - Hydrolysis of t-Alkyl Trifluoroacetates

Relevant scale up example

None found

Green Review

  1. Atom efficiency (by-products Mwt)
    High – produces product and corresponding alcohol, negligible waste and water can be used as the solvent.
  2. Safety Concerns
    None prominent. Higher temperatures may be required to push reaction to completion (stability of SM/product).
  3. Toxicity and environmental/aquatic impact
    Minimal.
  4. Cost, availability & sustainable feedstocks
    Cheap and readily available.
  5. Sustainable implications
    Sustainable. Aqueous waste can potentially be directly bio-treated.
© 2015 Green Chemistry Institute Pharmaceutical Roundtable. All rights reserved.