Understanding the Exceptional Properties of Nitroacetamides in Water: A Computational Model Including the Solvent

Proton transfer in water involving C–H bonds is a challenge and nitro compounds have been studied for many years as good examples. The effect of substituents on acidity of protons geminal to the nitro group is exploited here with new p K a measurements and electronic structure models, the latter including explicit water environment. Substituents with the amide moiety display an exceptional combination of acidity and solubility in water. In order to find a rationale for the unexpected p K a changes in the (ZZ ′ )NCO- substituents, we measured and modeled the p K a with Z=Z ′ =H and Z=Z ′ =methyl. The dominant contribution to the observed p K a can be understood with advanced computational experiments, where the geminal proton is smoothly moved to the solvent bath. These models, mostly based on density-functional theory (DFT), include the explicit solvent (water) and statistical thermal fluctuations. As a first approximation, the change of p K a can be correlated with the average energy difference between the two tautomeric forms (aci and nitro, respectively). The contribution of the solvent molecules interacting with the solute to the proton transfer mechanism is made evident.

Synthesis of Methyl-5,6,11,12-tetrahydrodibenzo[a,e]cyclooctenols and a conformational study by proton nuclear magnetic resonance

A series of methyl-5,6,11,12-tetrahydrodibenzo[a,e]cycloocten-5-ols were synthesized, and their conformations assigned by means of proton nuclear magnetic resonance. Placing substituents in three of the four available sites on the eight-membered ring enabled the chemical shifts of the geminal proton to be observed. It was found that the three sites have intrinsic chemical shifts. The compounds studied were found to populate a twist-boat conformation, with bulky substituents preferentially populating the axial site.

Hétérobicycles oxygénés. Synthèse d'alkyl-3,6,8-trioxabicyclo[3.2.1]octanes et d'alkyl-3,7,9 et -4,7,9-trioxabicyclo[4.2.1]nonanes

The cyclization in a basic medium of 2 (or 4)-chloroalkyl-4 (or 2) -hydroxyalkyl-1,3-dioxolanes leads to bicyclic acetals, the 3,6,8-trioxabicyclo[3.2.1]octanes, which are useful intermediates for synthesis, yielding notably functionalized 1,4-dioxanes. The nmr spectra of these heterobicyclics were studied. The geminal proton coupling constants permit oneto distinguish between five- and six-membered rings and the determination of couplings over several bonds (4J and 5J) yields information concerning the conformation of the model bicyclics.Two isomeric series of alkylated bicyclic acetals (3,7,9- and 4,7,9-trioxabicyclo[4.2.1]nonanes) are accessible by the following routes: (a) the intramolecular addition of a 4-hydroxy-alkyl group to the ethylenic double bond on the carbon atom a to C-2 in the 1,3-dioxolanes; (b) the dechlorohydration of 2-chloromethyl-4-hydroxyalkyl-1,3-dioxolanes; (c) the dehydration of dioxolane-diols. The main interest in these heterobicyclics is to prepare a seven-membered ring and to be able to prepare functionalized 1,4-dioxepanes. [Journal translation]

The effect of substituents on geminal proton–proton coupling constants. III

The effect of substituents at the 3-position in a series of N-methyl 5,6-dihydro-7H,12H-di-benzo[c,f]azocines on the geminal coupling constants of the C-12 methylene protons has been determined. The slope of the Hammett plot of 2J vs. σ has been found to be +0.20. The orientation of the methylene protons with respect to the π orbitals of the benzene ring bearing the substituent is such that no hyperconjugative effect should be present. The value of +0.20 is in contrast to a previously measured slope of −1.9 for compounds having a geometry ideal for hyperconjugative effects and substantiates the predictions of theoretical MO calculations. As a result, the reliability of this conformational dependence of ρ for use in conformational analysis has been strengthened.A comparison of the data for the azocines with those in the literature indicates the difference between the minimum and maximum effects of a phenyl substituent on a geminal coupling constant of an attached methylene group is 5.5 Hz.