title: The application of design of experiments (DoE) reaction optimisation and solvent selection in the development of new synthetic chemistry.
abstract: This article outlines the benefits of using 'Design of Experiments' (DoE) optimisation during the development of new synthetic methodology. A particularly important factor in the development of new chemical reactions is the choice of solvent which can often drastically alter the efficiency and selectivity of a process. Whilst solvent optimisation is usually done in a non-systematic way based upon a chemist's intuition and previous laboratory experience, we illustrate how optimisation of the solvent for a reaction can be carried out by using a 'map of solvent space' in a DoE optimisation. A new solvent map has been developed specifically for optimisation of new chemical reactions using principle component analysis (PCA) incorporating 136 solvents with a wide range of properties. The new solvent map has been used to identify safer alternatives to toxic/hazardous solvents, and also in the optimisation of an S(N)Ar reaction.
authors.affiliation: Paul Murray Catalysis Consulting Ltd, 67 Hudson Close, Yate, BS37 4NP, UK. paul.murray@catalysisconsulting.co.uk.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Murray
authors.forename: Fiona
authors.initials: F
authors.lastname: Bellany
authors.forename: Laure
authors.initials: L
authors.lastname: Benhamou
authors.forename: Dejan-Krešimir
authors.initials: DK
authors.lastname: Bučar
authors.forename: Alethea B
authors.initials: AB
authors.lastname: Tabor
authors.forename: Tom D
authors.initials: TD
authors.lastname: Sheppard