Relative Basicities of Some Endo and Exo Norbornylamines

Abstract

A series of endo- and exo-norbornylamines were synthesized and their relative basicities determined in acetonitrile and dimethylformamide solvents. The exo isomer is always more basic than the corresponding endo isomer in either solvent. All of the bicyclic amines studied have higher pK(a)'s in acetonitrile solvent than in dimethylformamide except for the 2-morpholinonorbornanes which are just the reverse. This effect is explained by the ability of the morpholine group to disperse a positive charge and the relative polarizabilities of the solvents. Semiempirical AM1 and PM3 methods along with ab initio HF/STO-3G, HF/3-21G, and HF/6-31G methods were used to calculate proton affinities and dipole moments for each of the amines. The results of the theoretical calculations correspond well with the experimental observations.

Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease

“…These values are lower than free morpholine and thiomorpholine (p K a morpholine = 8.36, thiomorpholine = 9.0) as has been previously reported in similar systems. 29 , 34 – 36 Overall, each ligand was found to be neutral at physiological pH 7.4, which is optimal for passive diffusion across the BBB. To further investigate the drug-like properties of the phenol–triazoles, several physicochemical parameters were calculated.…”

Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

“…A specific example of structural activation for electrophilic cyclopropanes was described in the works of Cook,70,71 wherein the reactions of tricyclo[2.2.1.0 2,6 ]heptan-3-one 25 with cyclic secondary amines were investigated (Scheme 11). Full conversion of 25 into amino ketones 26a-d was already detected after 2 hours, even though additional thermal and catalytic activation took place.…”

“…Full conversion of 25 into amino ketones 26a-d was already detected after 2 hours, even though additional thermal and catalytic activation took place. 71 Spiro-activation of cyclopropanes proved to be a more universal technique for additional structural activation of these compounds. This term was introduced in the mid1970s by Danishefsky, who employed electrophilic cyclopropane 27 in his research, 72 basing the initial structure upon Meldrum's acid (27 was subsequently named 'Danishefsky's cyclopropane').…”