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The 13C NMR spectra of 17 methyl- and ethyl-substituted tetrahydrofurans and 58 alkyl- and aryl- substituted 1,3-dioxolanes are reported. For the cases in which substituents recur, additive substituent parameters are calculated and compared with similar parameters in cyclopentanes and in 6-membered rings. Considering the conformational flexibility of 5-membered ring systems, additivity of the parameters is surprisingly good.

The 13C n.m.r. spectra of 53 thianium, S-methylthianium, S-alkylthianium and S-methyl-1-thiadecalinium salts, most of them substituted with methyl groups in the ring, have been recorded. The chemical shifts of the ring carbons in these thianium and S-methylthianium salts and the S-methyls in the S-methylthianium salts have been analyzed in terms of additive parameters of the methyl substituents which are compared to those previously determined for the parent thianes. Comparison is also made with other charged species.

17O chemical shifts of axial hydroxyl groups in cyclohexanols are upfield of those of corresponding equatorial groups, but in 5-hydroxy-1,3-dioxanes the opposite is observed: the axial OH resonates downfield of the equatorial OH. The situation is the same in the corresponding methyl ethers and is, thus, not a result of intramolecular hydrogen bonding in the axial 5-hydroxy-1,3-dioxane, but appears to parallel the effect on 13C and 19F shifts observed in corresponding equatorial and axial 5-methyl- and 5-fluoro-1,3-dioxanes, which has been attributed to an upfield shifting effect of the antiperiplanar γ-located heteroatoms. Surprisingly, the reciprocal effect is not seen in the ring 17O shifts of the 5-hydroxy-1,3-dioxanes. A δ compression shift is seen in the 17O spectrum of trans-3,3,5-trimethylcyclohexanol (syn-axial OH and CH3), analogous to the effect earlier reported in 13C spectra. Conversion of four of the alcohols to methyl ethers produces a large upfield effect on the 17O shift, larger in the cyclohexanols than in the 1,3-dioxane-5-ols. Similar upfield shifts have been recorded in the literature; their extent depends on whether the alcohols are primary, secondary or tertiary.

The extreme similarity (except in the vicinity of the nitrogen atom) of the 13C spectra of the agonist-antagonist pairs oxymorphone-naloxone and morphine-nalorphine and their respective hydrochlorides suggests that the N-methyl and N-allyl compounds have analogous conformations. This makes unlikely an interpretation of the agonist-antagonist dichotomy in terms of confonnational differences. Both morphine hydrochloride and nalorphine hydrochloride exist as mixtures of two diastereomers: ca 83% of the isomer with equatorial N-alkyl and 17% of the isomer with axial N-alkyl (ΔG°=O.95 kcalmol−1).

The 13C NMR spectra of cyclobutane and seven methylated homologs and of ethyl cyclobutanecarboxylate and five isomeric diethyl cyclobutanedicarboxylates are reported and substituent parameters for methyl groups in methylcyclobutanes are calculated. Of note is a sizeable and nearly configuration-independent upfield shifting γ-effect.

The 13C NMR spectra of 62 oxanes (tetrahydropyrans) with and without methyl substituents at various ring positions, some of them bearing in addition (or instead) ethyl, vinyl, ethynyl, carbomethoxy and methylol substituents at C-2, have been recorded, and the 294 resulting chemical shifts have been correlated by multiple linear regression analysis. Axial and equatorial α-, β-, γ-, δ-, gem- and vic-parameters for shifts caused by methyl groups at all ring positions, and similar parameters for Et,—CHCH2,—CCH, CO2Me and CH2OH groups at C-2, are reported. Standard deviations of the parameters are, in most cases, within 0.3 ppm and the agreement of calculated and experimental shifts is excellent. This is probably the largest parameter set of this type extant. 13C NMR spectra of a number of additional substituted tetrahydropyrans, and of 3,6-dihydro-2H-pyrans and 3,4-dihydro-2H-pyrans, are tabulated and discussed.