A set of good solvents for synthesis - Andrew Lang

The ideal situation when performing a synthesis is for the product to precipitate at room temperature from a solvent that is easy to get rid of. To this end we have performed a clustering analysis on solvents with known Abraham parameters with boiling points less than 80C. We also have performed a cluster analysis on the complete set of solvents with Abraham parameters.

SolventOptimization.png

Sets

The following sets should have similar solvation behaviour. Thus by performing a synthesis in one solvent from each of the sets, it is likely that the product will precipitate in at least one of the solvents. The eventual goal is to derive a model that predicts the best single solvent to maximize the likelihood of precipitation.
A = {benzene, 1-chlorobutane}
B = {dichloromethane, chloroform}
C = {carbon disulfide}
D = {pentane, hexane, carbon tetrachloride}
E = {methanol}
F = {ethanol, 2-propanol}
G = {acetonitrile}
H = {acetone, butanone, ethyl acetate, methyl acetate, diethyl ether, methy tert-butyl ether, THF}

Suggested set of solvents: benzene, chloroform, carbon disulfide, hexane, methanol, ethanol, acetonitrile, THF
[Very useful analysis Andy - for Ugi reactions hexane is too poor a solvent and carbon disulfide cannot be used for NMR SAMS solubility measurements so that leaves 6. It is interesting that methanol and ethanol form 2 different categories JCB]