Amides restricted rotation effects

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

The extent of restricted rotation about the amide band of (38) was used to compare the electron-withdrawing process of phosphonium salts (38, Y = alkyl) and chalcogenides (38, Y = O or S) with the more conventional electron-withdrawing groups. These phosphorus groups were found to exert a — A7 effect comparable with that of a nitro-group. 

Presumably the ketone experiences less rotational restriction than the amide, but any enhancement in flexibility had little apparent effect on efficacy in this case. The relatively poor inhibitory capacity of the ether 109 was explained in terms of the energy penalty created by differences between the bound and solution conformation of the dihydropyran ring. 

To bias the direction the macro cycle takes at each of the transformations, temporary barriers would be required in order to restrict Brownian motion in one particular direction. Such temporary barriers are intrinsically present in [3]catenane 20 (Fig. 8 and Scheme 10). Irradiation at 350 nm of , -20 causes counter-clockwise rotation of the light-blue macrocycle to the succinic amide ester (orange) station to give Z,E-20. The light-blue macrocycle cannot rotate clockwise because the purple macrocycle effectively blocks that route. 

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