Richard A. Y. Jones

The conformational analysis of saturated heterocycles. Part XXXI. 1-t-Butylpiperidine-4-spiro-4′-(1′,3′-dioxolan) and 1,3-dioxan-5-spiro-4′-(1′,3′-dioxolan)

The use of dipole moment and n.m.r. measurements of spiro-1-t-butylpiperidines and spiro-1,3-dioxans is proposed as a general method for the investigation of intramolecular interaction in situations of defined geometry. The method is applied to the title compounds.

The conformational analysis of saturated heterocycles. Part XXXIII. 1-t-Butylpiperidine-4-spiro-4′- and -5′-(2′,2′-dimethyloxazolidine) and a discussion of steric compression effects on chemical shifts

The title compounds, and a 3′-methyl analogue of the former, have been prepared and their low-temperature n.m.r. spectra studied to elucidate their conformational equilibria and hence allow deductions regarding the steric requirements of the formally sp3-hybridised NH and NMe groups and the oxygen atom in comparison with a methylene group. Evidence for deshielding by steric compression is reviewed, and it is shown that this can cause protons attached to axial groups to resonate at lower field than the equatorial analogues

The conformational analysis of saturated heterocycles. Part XXXII. 1-t-Butylpiperidine-4-spiro-4′- and -5′-oxazolines and -4′- and -5′- thiazolines

Compounds of the type mentioned in the title have been prepared and their dipole moments and low-temperature n.m.r. spectra investigated to provide evidence on the position of the conformational equilibria of type (1a)⇌(1b) and hence of the relative steric interactions involving sp2-hybridised nitrogen, and of oxygen and sulphur attached to sp2-carbon, compared in each case with a methylene group.

cis–trans Equilibrium in meta-chlorophenyl aldehydes, ethers, ketones, and carboxylic esters from dipole moment studies

Comparison of dipole moments of meta-chloro-, para-chloro-, and 3,5-dichloro-substituted compounds with parents enable the calculation of group dipole directions, of interaction moments, and of cis–trans conformational equilibria in the meta-substituted derivatives.

The conformational analysis of saturated heterocycles. Part XXXIV. The influence of lone pair orientation on the differential proton chemical shift of adjacent methylene groups and on Jgem values

The differential chemical shifts (Δae) and geminal coupling constants (Jgem) between axial and equatorial protons of the 2-position CH2 groups in hexahydropyrimidines, hexahydro-1,3,5-triazines, and tetrahydro-1,3-oxazines have been compared with the proportions of lone-pairs axial in these compounds. It is concluded that whereas Δae can provide a qualitative indication of the orientation of lone pairs, no simple quantitative correlation exists. The variations found in Jgem showed no systematic correlation with the conformational equilibrium of adjacent N-alkyl groups, in the compounds now studied.

The conformational analysis of saturated heterocycles. Part XXI. Dipole moment studies of 1-ethyl- and 1-isopropyl-piperidines and further studies of 1-methylpiperidines

Further measurements indicate a conformational free-energy difference of ca. 0·65 kcal./mole for an N-methyl group in the piperidine ring system in favour of the methyl group equatorial, and values of 0·9 and 1·4 kcal./mole, respectively, for N-ethyl and N-isopropyl groups. These values are discussed in comparison with literature data.

The conformational analysis of saturated heterocycles. Part XXII. Conformation of piperidine: evidence and conclusions from dipole moment studies

Electric dipole moments of suitably substituted piperidines indicate that the N-hydrogen atom prefers the equatorial position. A survey of the available evidence indicates that a value of ΔG°= 0·4 ± 0·2 kcal./mole favouring NH-equatorial for piperidine in the gas phase and non-interacting solvents is in agreement with all known facts. Reasons for the NH-equatorial preference are discussed.

The conformational analysis of saturated heterocycles. Part XXX. 3-Alkyl tetrahydro-1,3-oxazines

Tetrahydro-1,3-oxazine and its N-methyl, ethyl, isopropyl, and t-butyl derivatives have been prepared, and the dipole moments of the four last compounds measured. Provisional conclusions regarding the conformations of these compounds are presented.

The conformational analysis of saturated heterocycles. Part XXIII. Hexahydropyrimidines

The preparations of some N-substituted hexahydropyrimidines are described. Their electric dipole moments have been measured in cyclohexane solution and interpreted in terms of their conformations. The conformational free-energy differences between axial and equatorial N-methyl and N-ethyl groups are a little smaller than in the corresponding N-alkylpiperidines and accord with a repulsion between two axial lone electron pairs of about 0·3 kcal./mole. For N-isopropyl groups the conformational free-energy difference is surprisingly high; a possible explanation is suggested.

The conformational analysis of saturated heterocycles. Part XXVII. The orientation of quaternisation of piperidines: further studies

Previous work on the quaternisation of piperidines is reviewed, and the application of n.m.r. half-widths in the unambiguous determination of configuration is described. Together with the X-ray evidence this allows a reassessment of previous and new experimental evidence from reaction rates and product ratios. The effect of changing the leaving group in the alkylating agent cannot be simply explained. It is concluded that although simple piperidines generally are methylated by axial approach, equatorial methylation can occur when axial approach is subject to steric hindrance, and equatorial attack frequently occurs with quaternising groups larger than methyl. The reasons for this behaviour are considered.