Toluene is a volatile, non-polar solvent, commonly used throughout the chemical industry, which is facing increasing scrutiny due to its reprotoxicity and production from petroleum. Therefore, replacements which are safe and bio-based are required. A solvent selection method has been developed which involved solubility tests, solvent modelling computer-aided molecular design and chemical intuition to find new, potentially bio-based solvents. Five candidates were identified: 2,2,5,5-tetramethyltetrahydrofuran (TMTHF), methyl butyrate, ethyl isobutyrate, methyl pivalate and pinacolone. TMTHF is one of a new class of ethers, called quaternary ethers, which were identified not to possess the same issues of peroxide formation as traditional ethers due to a key structural difference. In addition, TMTHF has been synthesized from potentially renewable feedstocks where it was found to have similarly non-polar solubility properties (able to dissolve synthetic rubber), and a similar boiling point (112 °C), melting point (< 90 °C) and autoignition temperature (417 °C) to toluene. Application testing showed that TMTHF was able to facilitate radically-initiated polymerisations for the production of vinyl polymers suitable for use as pressure-sensitive adhesives (high Mw), and behaved more like toluene than traditional ethers in esterification, amidation and Grignard reactions. As such, it is an ideal candidate to replace toluene in the polymerisation and coating industry, as well as in many other applications. In addition, four secondary candidates (methyl butyrate, methyl pivalate, ethyl isobutyrate and pinacolone) were also identified to be of low-polarity, like toluene. Methyl pivalate and pinacolone were the best of the four secondary candidates as ethyl isobutyrate could not produce sufficiently high Mw polymers and the odour of methyl butyrate was too unpleasant for large-scale use. Testing in a Menschutkin reaction confirmed that each candidate had similar solubility properties to toluene. Finally, TMTHF, methyl pivalate, pinacolone and methyl butyrate were found to be non-mutagenic in the Ames test (ethyl isobutyrate not tested), but full toxicity testing is required before registration with REACH.