H-NMR Chemical Shifts of Protons Adjacent to Nitrogen

The Aae criterion was applied to the problem of the piperidine equilibrium (10 11) by examining the H-NMR spectrum of the deutero derivatives 12, 13, and 14 at — 85°C when ring inversion is slow on the NMR time scale.37 The Aae values are recorded in Table I. The preferred conformation for the N-substituted piperidines 13 and 14 was assigned as lone-pair axial because for these compounds Aae values were similar to those in quinolizidine. However, in piperidine (12), where the Aae value is similar to that in cyclohexane, the lone pair was assumed to occupy the equatorial position in the preferred conformation. In support of this contention, protonation of 

The Aae values (at 60 MHz) observed for 3-azabicyclo[3.3.1]nonane and its Af-methyl derivative were 0.08 and 0.67 ppm respectively, a decrease of 0.5-0.6 ppm compared to the Aae values for the corresponding piperidines. On this evidence the conformations 15 and 16 were assigned to these compounds.37 

However, there are two assumptions implicit in this treatment (a) that a small isotropic substituent (e.g., methyl) would have the same effect on both 

Booth and Little40 observed a chemical shift difference (Aae) of about 0.4 ppm for the C-2 and C-6 methylene protons in 4-methylpiperidine, which was assumed to exist as an equilibrium containing 95% of the C-methyl equatorial conformation. N-Methylation of 4-methylpiperidine caused an upfield shift of 0.22 ppm for the C-2 equatorial proton and of 0.68 ppm for the C-2 axial proton. Comparison of these values with those observed for the proton adjacent to methyl groups in cyclohexane led these authors to the 

The Aae in piperidine of 0.48 ppm is increased to 0.66 ppm (for the 6-methylene protons) in 3,3-dimethylpiperidine (measurements in CH2C12 solution below coalescence temperature for ring inversion). This was taken as an indication of an increase in N-Heq conformer in the latter compound.42 Measurements on decahydroquinolines however, showed43 the insensitivity of this parameter to N-H orientation (e.g. 19 and 20 gave Aae values of 0.61 and 0.54 ppm, respectively). 

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