Protonation Deuteronation Studies

In principle, the estimation of conformational equilibrium in a piperidine derivative by protonation is very simple. If nitrogen inversion is slow compared to deuteronation, if H+/D+ exchange does not occur in the salts, and if H+/D+ exchange is unimportant in the mixing process, then the relative proportion of the salts corresponds to that of the conformers. Thus the spectrum of pure dry cis-3,5-dimethylpiperidine in deuterotrifluoroacetic acid (unchanged after 2 days) showed a septet at 8 2.70 for the 2,6-axial protons in 112 and 113. This was interpreted as a triplet for 112 and a quartet for 113 and analysis of the multiplets gave 54% 112 and 46% 113 (AG  

This work was criticized165 because the time of mixing may be long compared to that of proton transfer and nitrogen inversion, but the validity of the original experiment has been defended by studies on model compounds.166 

Attention, however, has been drawn to the problem of H/D scrambling at the liquid-liquid interface.167 In the spectrum of a solution obtained by extraction of cis-3,5-dimethylpiperidine from a dilute solution in cyclohexane with D2S04, the triplets due to 112 show a clear additional coupling 

The kinetically controlled protonation method may also be applied to the determination of the conformational free energy of C-methyl groups in piperidines. For example, protonation of 1,5-dimethylpiperidine (in which 13C is located in the /V-CH3 group) in dodecane and estimation of the ions produced by 13C-NMR spectroscopy gives AG20° of 1.5 0.1 kcal mol-1 for the 3-methyl group.169 

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X-rays, often used in radiation chemistry, differ from y-rays only operationally namely, X-rays are produced in machines, whereas y-rays originate in nuclear transitions. In their interaction with matter, they behave similarly—that is, as a photon of appropriate energy. Other radiations used in radiation-chemical studies include protons, deuterons, various accelerated stripped nuclei, fission fragments, and radioactive radiations (a, /, or y). 

The Truhlar group has reported an interesting theoretical study of H/D kinetic isotope effects for conversion of 2 phospho-D-glycerate to phosophoenolpyruvate catalyzed by the yeast enolase enzyme. The proton transfer step (first reaction step in Fig. 11.10) is the rate limiting step and was chosen for theoretical study. The KIE for proton/deuteron transfer is kn/kD = 3.3 at 300 K. 

We thought it preferable not to include in the discussion the electrophilic aromatic photosubstitution since well-studied examples 3ie still scarce (proton-deuteron and proton-triton exchange in acidic media protodeboronation). From our experience we have the feeling that many electrophiles are very efficient quenchers and that moreover it is not easy to choose systems where the concentrations of the potentially reacting electrophiles can be made high enough to react efficiently with the short-lived excited species. 

The NHC class of nucleophilic carbenes are also bases. The proton-deuteron exchange of NHCs attached to macromolecules has been studied and the influence of counterion has been explored.99 Substitution, both directly on the imidazolium unit and on the pre-orientating calixarene backbone, was also studied. The results showed that substitution of the imidazolium salts has a large influence on the H-D exchange rates in wet methanol. These results were presented as having implications for Suzuki coupling. 

Since about 1930 a great number of papers concerned with radiation effects on catalysts have been produced, but very little work in comparison has been done with ion bombardment. The great majority of the papers dealt with 7-, X-ray, electron or thermal neutron irradiations. Some of the later studies using protons, deuterons and a-particles are to some extent comparable to irradiations with ions . In some cases enhancement of the catalytic activity was found, in others in-... 

Proton-deuteron exchange reactions are most easily studied by n.m.r. Examples are the exchange of aromatic protons in phenols under alkaline conditions, exchange of the a-protons in methoxy-acetone in aqueous solution, exchange of NH protons in triethyl-ammonium ion, exchange of the nuclear protons of hydroxy-indoles in deuterium oxide under mildly basic conditions and exchange of aromatic protons of substituted benzophenones in deutero-sulphuric acid. ... 

The resonant reactions of alpha particles with boron have been very fully studied by Shire et al., who observ- ed protons, deuterons, neutrons and gamma rays from and protons from B. Their yield curves for B are shown in Fig. 45 that for gamma radiation is extended to higher energies by Talbott and Heydenburg [43] and that for neutrons by Walker with low resolution, using a polonium alpha particle source. 

Millburn et al. in their studies on the reaction cross-sections for protons, deuterons, He, and He particles measured the protons produced from bombardment of various targets by I60 Mev deuterons. They found the cross-section for carbonisO.43 barns which is about three times the value predicted by Eq.(35.4). They also found that the A dependence was closer to then Ak Heckrotte attempted to explain this discrepancy by modifying Berber s simple assumptions so that the nucleus had a potential well with a parabolic shape and an effective radius of = 1.6 X 10 . This is an empirical model that is specific to the reactions of D, He, and He and has no bearing on other nuclear phenomena. 

An excellent way of measuring the material loss at the surface is use of thin-layer activation. A thin layer of radioactive tracer is produced on the surface by irradiation with charged particles. This technique can be applied to all types of iron, steel, nonferrous metals and alloys. It is particularly suitable for metal wear studies, because, if done carefully, the charged-particle activation little alters the mechanical properties of the surfaces of specimens. As the charged particles for irradiation, protons, deuterons, a particles, and occasionally He-particles accelerated by a cyclotron or other accelerators are used. Choosing the kind and energy of the charged particles, a radioactive layer of 10-1,000 pm thickness is produced. Typical nuclear reactions used are as follows. 

Unlike photochemistry that acts on a substance by using only photons of a relatively low, some 1—10 eV energy, the radiation chemistry makes use of high energy particles (10 to eV). These comprise y-quanta, fast electrons, fast nuclei, protons, deuterons, tritons, a-particles, fission fragments and neutrons. (For a detailed description of ionizing radiation sources and of their use in radiation-chemical studies see [60, 502].)... 

Thus, as a bonus, this approach allows the rational design of selectively mono- or dideuterated amino acids and analogues. These chirally labeled molecules can be used to study the mechanistic details of biosynthetic pathways involving amino acid precursors. This approach has been recently extended (14) to allow the synthesis of chiral methyl lactic acid in which the three methyl hydrogens are replaced by a proton, deuteron, and triton. 

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