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Updated: Aug 9, 2026

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate
Published on: April 24, 2018
Insight into the lipophilicity of the aromatic N-oxide moiety
G Caron1, P A Carrupt, B Testa
1Institut de Chimie Thérapeutique, Université de Lausanne, Switzerland.
Purpose:
A systematic study to assess the influence of N-oxygenation on the lipophilicity of aromatic weak bases was performed.
Methods:
The methods used were experimental (CPC and shake-flask techniques) and computational (AMI semi-empirical method).
Results:
The intrinsic increment in the log P(oct) system for an oxygen atom added to form an aromatic N-oxide, designated as diff(log PN(O) -N), was -1.91, but the presence of para-substituents markedly affected this value. The good linear relationship (r2 = 0.92) between diff(log PN(O) - N), and the electronic density on the oxygen atom suggests that H-bond acceptor basicity is the main structural factor responsible for the variations in lipophilicity of aromatic N-oxides. Partition coefficients of aromatic N-oxides in dodecane/buffer and chloroform/buffer systems also support this hypothesis.
Conclusions:
The solvent-dependent polarity of the N-oxide moiety is mainly due to its marked H-bond acceptor basicity.
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