Computational Study of Selected Amine and Lactam N-Oxides Including Comparisons of N-O Bond Dissociation Enthalpies with Those of Pyridine N-Oxides

Abstract

A computational study of the structures and energetics of amine N-oxides, including pyridine N-oxides, trimethylamine N-oxide, bridgehead bicyclic amine N-oxides, and lactam N-oxides, allowed comparisons with published experimental data. Most of the computations employed the B3LYP/6-31G* and M06/6-311G+(d,p) models and comparisons were also made between the results of the HF 6-31G*, B3LYP/6-31G**, B3PW91/6-31G*, B3PW91/6-31G**, and the B3PW91/6-311G+(d,p) models. The range of calculated N-O bond dissociation energies (BDE) (actually enthalpies) was about 40 kcal/mol. Of particular interest was the BDE difference between pyridine N-oxide (PNO) and trimethylamine N-oxide (TMAO). Published thermochemical and computational (HF 6-31G*) data suggest that the BDE of PNO was only about 2 kcal/mol greater than that of TMAO. The higher IR frequency for N-O stretch in PNO and its shorter N-O bond length suggest a greater difference in BDE values, predicted at 10–14 kcal/mol in the present work. Determination of the enthalpy of sublimation of TMAO, or at least the enthalpy of fusion and estimation of the enthalpy of vaporization might solve this dichotomy. The “extra” resonance stabilization in pyridine N-oxide relative to pyridine was consistent with the 10–14 kcal/mol increase in BDE, relative to TMAO, and was about half the “extra” stabilization in phenoxide, relative to phenol or benzene. Comparison of pyridine N-oxide with its acyclic model nitrone (“Dewar-Breslow model”) indicated aromaticity slightly less than that of pyridine.

Predicted Reversal in N-Methylazepine/N-Methyl-7-azanorcaradiene Equilibrium upon Formation of Their N-Oxides

“…8 kcal/mol (33 kJ/mol) destabilization in the amine oxide (N + -O − ) linkage flanked by two vinyl groups. This appears to be the source of the 8 kcal/mol destabilization in N-methylazepine N-oxide (8) which causes it to be less stable than its azepine N-oxide isomer 9 and reduces its N−O BDE by about 8 kcal/mol compared to its isomer as vinyl groups are destabilized by electroN-withdrawing substituents [49,50]. While a very thorough computational study on the effects of substituents on the 1H-azepin/-7-azanorcaradiene system has been published [51], the study focuses on substitution at the 3-and 4-positions of azepine but not on N-substitution.…”

“…In order to further investigate this dramatic crossover, it is worthwhile to explore a variety of comparisons with other measures of stability including N-O BDE values, thermochemical measures of aromaticity as well as calculated structural and nucleus-independent chemical shift (NICS) [11][12][13] data. While the experimental [14] and computational data [8] indicate a BDE for pyridine N-oxide (10) of 62-64 kcal/mol (eqn 1), the corresponding value for pyrrole N-oxide (11, eqn 2, see Table 3) is far lower, reflecting resonance energy of ca. 20-25 kcal/mol in the aromatic N-methylpyrrole, as described below.…”

“…Figure 1 depicts the enthalpy relationships among 6-9. The largest effects appear to arise from two factors: the relative stability of N-methylazepine (6) relative to its 7-azanorcaradiene valence isomer ( 7) and the relatively low N-O BDE of N-methylazepine N-oxide (8). Both the 7-azanorcaradiene ( 7) and its N-oxide (9) appear to exhibit no unusual destabilization or stabilization effects on enthalpy.…”

“…This very large energy difference may come as a surprise at first. However, if one compares the enthalpy of expulsion of 3 O from trans-1,2-dimethylethylene oxide (+88 kcal/mol) with the BDE of even a relatively strong N−O bond (61.5 kcal/mol, pyridine N-oxide, Table 3), epoxidation is favored by about 26 kcal/mol [8,37]. Comparison with the considerably weaker N−O bond in 8 (BDE ca 41-42 kcal/mol, Table 3) predicts epoxidation to form 22 is favored by about 47 kcal/mol.…”

“…What change is there in the energy and equilibrium relationship with the 7-azanorcaradiene valence isomer? Experimental and computational data indicate a bond dissociation enthalpy (BDE) of 62−64 kcal/mol for pyridine N-oxide with a value 8−14 kcal/mol lower for trimethylamine N-oxide [8]. How do the N-O BDE values for azepines and their 7-azanorcaradiene valence isomers relate to the thermochemistry of these molecules?…”