Investigating ethyl lactate as a green solvent - processes, performance and air quality impacts

Solvents have long been recognised as comprising most of the waste produced in the
pharmaceutical industry.
There is a need to move to more sustainable solvents, as judged considering factors
including VOC emissions, aquatic impact, health hazard exposure potential, flammability and
explosivity and more. Mindful that most solvents today are still derived from fossil fuels there
is also a desire to move towards bioderived solvents.
Ethyl lactate is a bioderived solvent with several promising features. Ranked "green" by the
GSK solvent guide it is water miscible and has a boiling point of 154 degrees C, putting it in a similar
range to many undesirable reprotoxic solvents (DMF, DMAc, and NMP). It is also potentially
available in a bioderived manner, on a significantly larger scale than many other putative
"greener" solvents, thanks to commercial fermentation of glucose to lactic acid for PLA
production.

Modelling using HSPiP (Hansen Solubility Parameters in Practice) suggests that ethyl
lactate is similar in solvent space to isoamyl alcohol and hexafluoroisopropanol (HFIP). It
would be interesting to benchmark the performance of ethyl lactate in processes currently
using isoamyl alcohol - and especially HFIP, a solvent which has seen a remarkable
increase in use in academia in recently years, especially in solubilising peptides, and in
photo and electrocatalysis, and which as a perfluorinated species is a solvent whose use is
under increasing scrutiny. The special properties of HFIP are well known, but it is far from
clear if it is essential for all the purposes for which it is currently being put to use.
Further work would involve a literature study of cases where DMAc, DMF and NMP are
being used for their high boiling but where their aprotic nature is not essential. It would be
particularly interesting to explore how ethyl lactate compares with DMSO - both as a general
solvent for biological screening purposes, and more specifically as an aqueous solution for
appropriate (i.e. no esterases) enzymatic transformations. Comparison of the performance of
ethyl lactate in these instance (using a variety of metrics - including yield, process mass
intensity, cost, carbon footprint etc.) may highlight future opportunities.
In addition, modelling would be undertaken to see where binary (or ternary) mixtures of ethyl
lactate with other solvents would give favourable solvent properties.
Finally, the potential to further modify ethyl lactate, by alkylation, or otherwise capping of the
free hydroxyl group would be explored to access other areas of solvent space, and
compatibility with other reaction types.
One key, often neglected factor, in assessing solvent suitability is the impact of volatile
organic compounds (VOC) on air quality. Improved regulation of e.g. the transport sector,
has led to significant air quality improvements over the past two decades, but VOC
emissions from solvents remain high. Little is known of the fate of ethyl lactate upon release
to the atmosphere. Recent work on similarly oxygenated VOC revealed complex gas-phase
reaction mechanisms with consequently unpredicted impacts on air quality.

As such this project will also identify and quantify the most efficient gas-phase breakdown
routes for ethyl lactate and so determine air quality impacts; predict and test both the solvent
properties and the air quality impacts of related compounds. Gas phase studies will be
undertaken at the Wolfson Atmospheric Chemistry Laboratories (WACL) and at partner labs
across Europe. Techniques include pulsed laser photolysis, fast flow and smog chambers,
coupled to a variety of analytical techniques, e.g. UV-vis. and FTIR spectroscopy, mass-
spectrometry and laser induced fluorescence. Impacts will be assessed via computational
simulations based on master chemical mechanism protocols.