Ian J. Ferguson

The conformational analysis of saturated heterocycles. Part 84. Conformational consequences of internal β-heteroatoms. Ring and nitrogen inversion in 3,5-dimethyl-1-oxa-3,5-diaza-, 5-methyl-1,3-dioxa-5-aza-, and 1,3,5-trimethyl-, -triethyl-, -tri-isopropyl-, and -tri-t-butyl-1,3,5-triaza-cyclohexanes

Variable temperature proton and carbon-13 dynamic n.m.r. spectroscopy has been used to study the inversion barriers and preferred conformations of 3,5-dimethyl-1-oxa-3,5-diaza-, 5-methyl-1,3-dioxa-5-aza-, and 1,3,5-trimethyl-1,3,5-triaza-cyclohexane. The conformational consequences of consecutively replacing O with NMe in passing from 1,3,5-trioxacyclohexane to 1,3,5-trimethyl-1,3,5-triazacyclohexane are discussed. The observed effects of increasing size of alkyl substituent on the 1,3,5-triazacyclohexane system are also discussed.

The conformational analysis of saturated heterocycles. N-inversion in hindered piperidines

Results from a new dynamic n.m.r. method, applicable to heavily biased equilibria, and kinetically controlled protonation studies agree when applied to 1,2,2,6-tetramethylpiperidine, giving the free energy difference for N-inversion [ΔG°(1E→1A)] as 1–9± 0·2 at 213 K (d.n.m.r.) and 1·95 ± 0·1 kcal mol–1 at 293 and 373 K (kinetic protonation); the free energy of activation [ΔG‡(1E→1A)] is 11·0 ± 0·3 kcal mol–1 at 213 K.

Studies in azole chemistry. Part 2. Nitration of 1,4,5-trimethylimidazole 3-oxide and 1-methylpyrazole 2-oxide, and some reactions of the products

In sulphuric acid, 1,4,5-trimethylimidazole 3-oxide and 1-methylpyrazole 2-oxide are nitrated as the free bases at C-2 and C-5, respectively. At high acidities the pyrazole gives 1-methyl-3,5-dinitropyrazole 1-oxide. With phosphorus trichloride the pyrazole oxides were deoxygenated, and with phosphoryl chloride, 1-methylpyrazole 2-oxide gave 5-chloro-1-methylpyrazole. 1-Methyl-5-nitropyrazole 2-oxide with acetyl chloride gave 5-chloro-1-methyl-4-nitropyrazole.

The conformational analysis of saturated heterocycles. Part 101. 1,3-Diazacyclohexanes and 1-thia-3-azacyclohexanes

Conformational equilibria and barriers to ring and nitrogen inversion, determined by 1H and 13C n.m.r. for the title compounds, are correlated with other recent work on ring-1,3-diheteroatom-substituted cyclohexanes.

Conformational analysis of saturated heterocycles. Part 78. Passing pyramidal nitrogen inversions in some perhydro-1,3-oxazines and -1,3-diazines

Variable temperature proton n.m.r. studies allowed the direct observation of pyramidal nitrogen inversion hindered by an adjacent equatorial alkyl group in some 2-alkyl-3-methylperhydro-1,3-oxazines and 2-alkyl-1,3-dimethylperhydro-1,3-diazines. The axial–equatorial free energy differences for the N-methyl groups and the conformer populations have been measured.

The conformational analysis of saturated heterocycles. Part 76. Ring and nitrogen inversion in cis- and trans-1, 4, 5, 8-tetramethyldecahydropyrazino[2,3-b]pyrazine

Variable-temperature protonand pulsed proton noise-decoupled carbon-13 Fourier transform n.m.r. have been used to determine the inversion barriers and conformations of cis- and trans-1, 4, 5, 8-tetra methyl decahydropyrazino[2,3-b]pyrazine. The rate processes causing the spectral changes are discussed.

Quantitive dependence of N-methyl inversion barriers in six-membered rings on electronic and steric effects. Direct observation of the conformational equilibria in tetrahydro-1,3-oxazines and hexahydropyrimidines

Low-temperature 1H n.m.r. spectra of N-methyl and N,C-polymethyl derivatives of tetrahydro-1,3-oxazine and hexahydropyrimidine allow calculation of conformational equilibria and the rationalisation of steric and electronic effects on N-methyl inversion barriers.

The conformational analysis of saturated heterocycles. Part 89. Conformational analysis of trans-1,2,3,4,5,6-hexamethyl-1,2,4,5-tetra-azacyclohexane

Variable-temperature 13C n.m.r. shows the title compound to be the trans-isomer which adopts a symmetric conformation with the C-methyl groups diequatorial and the N-methyl groups symmetrically diaxial diequatorial (aeae). The N-inversion barrier (ΔGc‡ 7.7 kcal mol–1) provides strong evidence for the three conformational sets previously postulated for 1,2,4,5-tetra-azacyclohexanes.

The conformational analysis of saturated heterocycles. Part 87. Carbon-13 nuclear magnetic resonance studies of 1,3-diazacyclohexanes and some bi- and tri-cyclic analogues

Variable temperature 13C n.m.r. studies elucidate the conformational equilibria and energetics of 1,3-dimethyl- and 1,2,3-trimethyl-1,3-diazacyclohexane, cis-1,3,4,7,8-pentamethyl-1,3,7-triazabicyclo[3.3.1]nonane, and 1,2,4,5,7,8-hexamethylperhydro-1,4,7,9b-tetra-azaphenalene. 13C N.m.r. shifts of the N-methyl carbon atoms in these compounds are correlated using the γ-gauche upfield shift criterion.

The conformational analysis of saturated heterocycles. Part 72. Tetrahydro-1,3,4-oxadiazines

Variable-temperature proton n.m.r. spectroscopy has been used to study the inversion barriers and conformations of 3.4-dialkyltetrahydro-1.3.4-oxadiazines. The predominant conformer of 3,4-dimethyltetrahydro-1.3,4-oxadiazine was found to be 3ax, 4eq.