NMR integration progress for solubility measurements
In a previous post I reported about issues with using H NMR integrations for quantitative assessment of solute concentration to determine solubility. Using default parameters, a study by David Bulger revealed that integration of the methyl group on 2-phenylbutanoic acid lead to only 8.4% average error while the methine H gave an average of 26% under-integration.(ONSC-EXP102)
We have tried to select methyl or methylene groups whenever possible but obviously this won't work for many compounds, especially our series of aromatic aldehydes and carboxylic acids.
Khalid Mirza has just done a study using longer relaxation times and the results appear very promising (ONSC-EXP103). For 4-pyrenebutanoic acid using default parameters the integration of the aromatic vs. methylene hydrogens was off by 9-18% while extending the relaxation time (d1=50s) reduced the error to less than 1.2%.
Furthermore, Marshall Moritz used the new settings in a measurement of a known concentration of 4-nitrobenzaldehyde in acetonitrile and came within 3.2% using an aromatic hydrogen (ONSC-EXP111). Use of the aldehyde hydrogen was not as good, although much better than what we normally see with the default settings.
So I am cautiously optimistic that we are likely to get better data going forward.