Substitution deuterium

Substitution of D for H on a carbon results in a dramatic diminution of the height of the 13C signal in a broadband-decoupled spectrum for the following reasons. Since deuterium has a spin number of 1 and a magnetic moment 15% that of 1H, it will split the 13C absorption into three lines (ratio 1 1 1) with a J value equal to 0.15 X /CH. Furthermore, 7 for 13C—D is longer than that for 13C—H because of decreased dipole-dipole relaxation. Finally, the NOE is lost, since there is no irradiation of deuterium. A separate peak may also be seen for any residual 13C—H, since the isotope effect usually results in a slight upheld shift of the 13C—D absorption ( 0.2 ppm per D atom). The isotope effect may also slightly shift the absorption of the carbon atoms once removed from the deuterated carbon. 

The definition of chemical shift equivalence given for protons also applies to carbon atoms interchangeability by a symmetry operation or by a rapid mechanism. The presence of equivalent carbon atoms (or coincidence of shift) in a molecule results in a discrepancy between the apparent number of peaks and the actual number of carbon atoms in the molecule. 

13C atoms of the methyl groups in /-butyl alcohol (Fig. 5.3) are equivalent by rapid rotation in the same sense in which the protons of a methyl group are equivalent The, 3C spectrum of /-butyl alcohol shows two peaks, one much larger than the other, but not necessarily exactly three times as large the carbinyl carbon peak (quaternary) is much less than the intensity of the peak representing the carbon atoms of the methyl groups. 

In the chiral molecule 2,2,4-trimethyl-l,3-pentane-diol (Fig. 5.4), we note that CH3a and CH3b are not equivalent, and two peaks are seen. Even though the two methyl groups labeled c are not equivalent, they coincidently show only one peak. Two peaks may be seen at higher resolution. 

In Section 4.12.3 we noted that the CH3 protons of (CH3)2NCH=0 gave separate peaks at room temperature, but became chemical shift equivalent at about 123°. Of course, the 13C peaks show similar behavior. 

---

The high depth resolution, nondestructive nature of thermal neutrons, and availability of deuterium substituted materials has brought about a proliferation in the use of neutron reflectivity in material, polymer, and biological sciences. In response to this high demand, reflectivity equipment is now available at all major neutron facilities throughout the country, be they reactor or spallation sources. 

Fig. 4.9. DifiBoing zero-point energies ofprotium- and deuterium-substituted molecules as the cause of primary kinetic isotope effects.

The distribution of a-bromoketones formed in the reaction of acetylcyclopentane with bromine was studied as a function of deuterium substitution. On the basis of the data given below, calculate the primaiy kinetic isotope effect for enolization of... 

Mixtures of EE Cl and [EMIMjCl have also been studied [9, 10]. By analysis of the first order differences by hydrogen/deuterium substitution both on the imidazoli-um ring and the EE Cl, two intramolecular peaks were observed. These indicated the presence of [EECI2] as an asymmetric species, which, coupled with analysis of the second order differences, allowed the structure in Figure 4.1-3 to be proposed. 

THE EFFECT OF RING-DEUTERIUM SUBSTITUTION ON THE RATE AND PRODUCTS OF THE REARRANGEMENT OF HYDRAZOBENZENE IN 90% ETHANOL AT 0 °C... 

The methyl groups were then deuterium-substituted. Ethanolysis of (CD3)2CHBr gave a mixture of CD3CH = CD2 and (CD3)2CHOC2H5. The elimination pathway had hAd = 6.7, whereas the substitution pathway showed no measurable kie. Clearly, these observations imply nearly complete proton abstraction in the one transition state and the lack of C-H involvement in the other. 

The work of Melander and Carter (1964) on 2,2 -dibromo-4,4 -di-carboxybiphenyl-6,6 -d2 (1) has been referred to above in the introductory and theoretical sections, where it was pointed out that the availability of two detailed theoretical computations of the inversion barrier (Westheimer and Mayer, 1946, Westheimer, 1947 Hewlett, 1960) made this system especially attractive for the study of steric isotope efifects. Furthermore, in the preferred initial-state conformation the two bromines are probably in van der Waals contact (cf. Hampsoii and Weissberger, 1936 Bastiansen, 1950), and thus initial-state steric effects are unaffected by deuterium substitution in the 6 and 6 positions. The barrier calculations provided two different theoretical values for the non-bonded H Br distance in the transition state which, together with the corresponding H Br potential function, could be inserted in equation (10) to yield values for A AH. For... 

Deuterium Substitution. The a and P secondary isotope effects affect the rate in various ways (p. 298). The measurement of a secondary isotope effects provides a means of distinguishing between SnI and Sn2 mechanisms, since for Sn2 reactions the values range from 0.95 to 1.06 per a D, while for S l reactions the values are higher. This method is especially good because it provides the minimum of perturbation of the system under study changing from a H to a D hardly affects the reaction, while other probes, such as changing a substituent or the polarity of the solvent, may have a much more complex effect. 

Thus, identification of all pairwise, interproton relaxation-contribution terms, py (in s ), for a molecule by factorization from the experimentally measured / , values can provide a unique method for calculating interproton distances, which are readily related to molecular structure and conformation. When the concept of pairwise additivity of the relaxation contributions seems to break down, as with a complex molecule having many interconnecting, relaxation pathways, there are reliable separation techniques, such as deuterium substitution in key positions, and a combination of nonselective and selective relaxation-rates, that may be used to distinguish between pairwise, dipolar interactions. Moreover, with the development of the Fourier-transform technique, and the availability of highly sophisticated, n.m.r. spectrometers, it has become possible to measure, routinely, nonselective and selective relaxation-rates of any resonance that can be clearly resolved in a n.m.r. spectrum. 

Another separation method in using nonselective relaxation-rates is based on deuterium substitution, and utilizes the fact that the efficiency with which a nucleus contributes to the relaxation of a neighboring nucleus is proportional to the square of the magnetogyric ratio of the donor nucleus, that is, Phd/PHH = /3(yo/yn) - Because yo/yn — l/, replacement of a proton by a deuterium nucleus would be expected to contribute to the... 

The second separation method involves n.O.e. experiments in combination with non-selective relaxation-rate measurements. One example concerns the orientation of the anomeric hydroxyl group of molecule 2 in Me2SO solution. By measuring nonselective spin-lattice relaxation-rat s and n.0.e. values for OH-1, H-1, H-2, H-3, and H-4, and solving the system of Eq. 13, the various py values were calculated. Using these and the correlation time, t, obtained by C relaxation measurements, the various interproton distances were calculated. The distances between the ring protons of 2, as well as the computer-simulated values for the H-l,OH and H-2,OH distances was commensurate with a dihedral angle of 60 30° for the H-l-C-l-OH array, as had also been deduced by the deuterium-substitution method mentioned earlier. 

However, the relaxation contributions obtained from Eq. 22 were not satisfactorily compared with those obtained from specific, deuterium-substitution experiments and single- and double-selective relaxation-rates. Moreover, the errors estimated for the triple-pulse experiments were very much larger than those observed for the other techniques. This point will be discussed next. 

Combinations of non-selective and/or single-selective relaxation-rates, or both, with n.0.e. values may conveniently be performed with reliable results, especially when other methods seem impractical. However, these experiments are time-consuming, as they entail the determination of a rather large number of experimental values. Moreover, the n.O.e. parameters carry their own systematic and random errors, which are magnified in the calculation of interproton distances. The deuterium-substitution method requires specific deuteration at a strategic position, which, in many cases, may be inconvenient or impractical. Also, this technique is valid only when the relaxation rates obtained after deuterium substitution are at least 5% enhanced, relative to the relaxation rates of the unsubstituted compound, and it requires that, for a meaningful experiment, the following condition " be satisfied. 

The main difficulty in obtaining the vinyl radical is that the species easily loses the hydrogen atom and is converted into acetylene. Nevertheless, a very low concentration of the radical H2C=CH has been achieved (Shepherd et al., 1988) by vacuum UV photolysis of ethylene frozen in an argon matrix, and a Fourier transform IR study of this intermediate has been carried out. A variety of and deuterium-substituted ethylene parent molecules were used to form various isotopomers of vinyl radical. On the basis of its isotopic behaviour and by comparison with ab initio... 

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

NNN Rat Liver microsomes assay for a-hydroxylation and the effect of a-deuterium substitution 33... 

The effects of deuterium substitution on the rates of a-hydroxylation of NNN have been measured. The results obtained in vitro, with rat liver microsomes, showed only a small deuterium isotope effect of 1.2 for 2 -hydroxylation, whereas a significant effect of 2.4-2.7 was observed for 5 -hydroxylation (33). Analogous results were obtained 2n vivo when the urinary metabolites... 

The structure of [TpBut]ZnH has been determined by x-ray diffraction, although the hydride ligand was not located (Fig. 38). However, definitive evidence for the presence of the hydride ligand is provided by NMR and IR spectroscopies. Specifically, the hydride resonance is observed at 8 5.36 ppm in the H NMR spectrum, and p(Zn-H) is observed as a strong absorption at 1770 cm-1 in the IR spectrum, which shifts to 1270 cm 1 (vhIpd = 1.39) upon deuterium substitution (Fig. 39). 

Shifts due to either a- or (3-deuterium substitution are also quite significant, usually leading to well resolved fluorine signals for the deu-terated and undeuterated species, which can be useful in characterization of deuterium labeled fluorinated compounds. An example of the a-effect is shown in Figure 2.11, which depicts the fluorine NMR spectrum of F—CH2CH2CH2CH2CH2CD2—F, a molecule that has... 

For the ds-l-chloro-2-fluoroethylene, an a-deuterium isotope effect (one D) of 0.6 ppm is observed, along with a trans-P-deuterium isotope effect of 0.4 ppm. Looking at the /rau.v-l -chloro-2-fluoroethylcnc system, the a-deuterium isotope effect is 0.5 ppm and the c/s-P-isotope effect is 0.2 ppm. For the 1-chloro-l-fluoroethylene system, trans-P-isotope effect is 0.5 ppm, with the ds-(3-isotope effect being 0.4 ppm. From these results, it appears that trans-deuterium substitution transmits its isotope effect better than ds-deuterium substitution, the same trend as is observed in transmission of coupling constants. 

Data from microwave spectra on the centrifugal effect of rotational transitions of selenophene and its deuterium-substituted derivatives have been determined experimentally and compared with the calculated theoretical values of the centrifugal stretching constants by means of the force constants determined from the solution of the inverse vibrational problem.26 The two sets of values show good agreement, indicating that the system of force constants obtained for selenophene correctly reflects the characteristic features of the force field of the molecule. 

Mass spec analysis of the peptide fragments formed by this process yields pairs of MS peaks differing only by the mass change caused by the substitution of deuterium atoms for hydrogen atoms in half of the crosslinks. Thus, searching for MS peaks in the data that differ by the number of deuterium substitutions immediately will identify peptides from the interacting proteins that have been captured by the crosslinking process. 

The role of a-electrons in the stabilization of aromatics has been repeatedly emphasized by Shaik and Hiberty48 and has recently received experimental confirmation after a study of the effects of deuterium substitution of annulenes with internal hydrogens, such as the anti-aromatic [16] annul ene and the aromatic [18]annulene.49 50... 

The Ru-catalyzed cyclocarbonylation of a-allenic sulfonamides proceeds in the presence of Et3N under a CO atmosphere (20 atm) to yield ,/funsaturated lactams (Scheme 16.32) [36], In order to gain an insight into the reaction mechanism, a deuterium-substituted a-allenic sulfonamide was subjected to the carbonylation. The deuterium was found to be totally transferred to the methyl group. Based on this observation, a mechanism has been proposed which involves a ruthenacycle derived from addition of the Ru-H to the terminal double bond of allene (Scheme 16.33). 

Deuterium substitution for the migrating 4/ proton demonstrates that the enzyme transfers it by a stereospecific intramolecular path... 

---