Electronic structure methods have been applied to calculate the gas and aqueous phase reaction energies for base-induced rearrangements of N-chloropiperidine, N-chloro-3-(hydroxymethyl)piperidine, and N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine. These derivatives have been selected as representative models for studying the chemical fate of environmentally relevant chloramines. The performance of different computational methods (MP2, MP4, QCISD, B3LYP and B2PLYP) for calculating the thermochemistry of rearrangement reactions was assessed. The latter method produces energies similar to those obtained at G3B3(+) level, which themselves have been tested against experimental results. Experimental energy barriers and enthalpies for ring inversion, nitrogen inversion and dehydrochlorination reactions in N-chloropiperidine have been accurately reproduced when solvent effects have been included. It was also found that the combined use of continuum solvation models (e.g.CPCM) and explicit consideration of a single water molecule is sufficient to properly describe the water-assisted rearrangement of N-chlorinated compounds in basic media. In the case of N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine, which represents the chlorinated metabolite of the antidepressant paroxetine, several different reactions (intramolecular addition, substitution, and elimination reactions) have been investigated. Transition state structures for these processes have been located together with minimum energy structures of conceivable products. Imine 4A is predicted to be the most stable reaction product, closely followed by imine 4B and oxazinane 8, while formation of isoxazolidine 7 is much less favourable. Calculated reaction barriers in aqueous solution are quite similar for all four processes, the lowest barrier being predicted for the formation of imine 4A.
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