Acidifying Effect of an N-Oxide Group – A Useful Motif in Enhancing Acidity towards Superacidic Values*

DFT calculations carried out on trans-decahydronaphthalene and 4b,8b-dihydronaphthalene, important structural features of many alkaloids, revealed that they are moderately acidic carbon acids in the gas-phase and in DMSO solution. Substitution with a nitrogen atom of a neighbouring C(sp)–H fragment bonded to an acidic centre reduces the corresponding acidity in both phases. Following that, oxidation of the nitrogen atom to an N–oxide group enhances the acidity significantly. This acidifying effect of an N–oxide moiety in the vicinity of a deprotonation centre was estimated to be around 9−17 kcal mol in the gas-phase deprotonation enthalpy and about 5−11 pKa units in DMSO. Therefore, this electronic effect could be applied in the design of novel strong acids and superacids. Such acidity enhancement is identified through triadic analysis to be a consequence of the final state effect of anion, where compounds bearing an N–oxide group benefit from the favourable charge-dipole interaction between the negative charge and an N–O group. A dramatic increase in acidity is observed upon multiple cyanation. For example, octacyanoquinolizine N–oxide is an extremely strong superacid as seen by the gas-phase ΔHacid = 254.8 kcal mol and pKa,DMSO = −20.2, and its synthesis is highly desirable and strongly recommended. Triadic analysis suggests that this huge acidifying effect takes place because of strong resonance in anions of polycyano compounds, efficiently assisted by multiple CN groups, which stabilizes the corresponding principal molecular orbitals.