Deuterium incorporation

For a typical HX experiment, the most basic, and yet essential, measurement value is the average number of deuterium incorporated into each peptide. Because the mass of the peptide increase by 1.006 Da for every replacement of a proton with a deuteron, the average number of deuterium uptake in a peptide at a exchange time t can be calculated from Equation 7.1, 

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Oxidation of ethylene in alcohol with PdCl2 in the presence of a base gives an acetal and vinyl ether[106,107], The reaction of alkenes with alcohols mediated by PdCl2 affords acetals 64 as major products and vinyl ethers 65 as minor products. No deuterium incorporation was observed in the acetal formed from ethylene and MeOD, indicating that hydride shift takes place and the acetal is not formed by the addition of methanol to methyl vinyl etherjlOS], The reaction can be carried out catalytically using CuClj under oxygen[28]. 

Penicillin sulfoxides can be epimerized by heat to afford thermal equilibrium mixtures of a- and /3-sulfoxides, the position of the equilibrium depending on the C(6) side chain (Scheme 5). Deuterium incorporation studies support a sulfenic acid, e.g. (18), as the intermediate in these transformations. This mechanism is also supported by the finding that when an a-sulfoxide epimerizes to a /3-sulfoxide there is a simultaneous epimerization at C(2) (71JCS(C)3540). With irradiation by UV light it is possible to convert a more thermodynamically stable /3-sulfoxide to the a-sulfoxide (69JA1530). 

After completion of the reaction, the mixture is diluted with water, extracted with ether and the residue from the ether phase purified by chromatography and/or recrystallization. If the substrate contains aromatic protons, the reduction procedure is repeated in protic medium to back exchange deuteriums incorporated into the aromatic ring. 

The preparation of 7,7-d2-cholesterol in 1950 was the first example of deuterium incorporation into steroids via desulfurization of mercaptals with deuterated Raney nickel. A substantially modified version of this reaction subsequently became the first widely used method for site-specific insertion of two deuteriums in place of a carbonyl oxygen. This conversion consists of the preparation of a mercapto derivative (84 85), which usually... 

However, such an explanation was not convincing for other authors. Maeda and Kojima found that the irradiation of 2-phenylthiazole in ethanol at 80°C led to the same products described before but in a different ratio. Under the same reaction conditions, 5-phenylthiazole gave 4-phenylisothiazole, while 4-phenyl-thiazole was converted into 3-phenylisothiazole. The most important observation those authors made was that deuterium incorporation occurred when the reaction was carried out in benzene at 80°C in the presence of deuterium oxide. In fact, 2-phenylthiazole furnished deuterated 3-phenyl-4-deuteroisothiazole and... 

Neither deuterium incorporation nor double bond migration occurred when 6-cyano-2,3,4,8,9,9n-hexahydropyrido[2,l-Z)][l,3]oxazine (44) was... 

Reaction of acetone with D30+ yields hexadeuterioacetone. That is. all the hydrogens in acetone are exchanged for deuterium. Review the mechanism of mercuric ion-catalyzed alkyne hydration, and then propose a mechanism for this deuterium incorporation. 

The experiment was carried out with (i )-(-)-2[l-(methoxycarbonyl)ethyl]benzene-diazonium chloride (6.80). The product, methyl 3-methyl-3-//-indazole-3-carboxylate (6.81), was racemic. With regard to the inconclusive H/D exchange experiments one therefore has to conclude that the cyclization of the diazo-methylene intermediate 6.75 is faster than the rate of deuterium incorporation. 

The photo-Kolbe reaction is the decarboxylation of carboxylic acids at tow voltage under irradiation at semiconductor anodes (TiO ), that are partially doped with metals, e.g. platinum [343, 344]. On semiconductor powders the dominant product is a hydrocarbon by substitution of the carboxylate group for hydrogen (Eq. 41), whereas on an n-TiOj single crystal in the oxidation of acetic acid the formation of ethane besides methane could be observed [345, 346]. Dependent on the kind of semiconductor, the adsorbed metal, and the pH of the solution the extent of alkyl coupling versus reduction to the hydrocarbon can be controlled to some extent [346]. The intermediacy of alkyl radicals has been demonstrated by ESR-spectroscopy [347], that of the alkyl anion by deuterium incorporation [344]. With vicinal diacids the mono- or bisdecarboxylation can be controlled by the light flux [348]. Adipic acid yielded butane [349] with levulinic acid the products of decarboxylation, methyl ethyl-... 

The general acid catalysis, the deuterium solvent isotope effects, and the lack of deuterium incorporation upon partial hydration in D2 0 are particularly convincing evidence for a rate-determining protonation and the discrete intermediacy of a vinyl cation such as 6. 

Solvolyses of these cyclic vinyl triflates at 100 in 50% aqueous ethanol, buffered with triethylamine, lead exclusively to the corresponding cyclo-alkanones. Treatment of 176 with buffered CH3COOD gave a mixture of cyclohexanone (85%) and 1-cyclohexenyl acetate (15%). Mass spectral analysis of this cyclohexanone product showed that the amount of deuterium incorporation was identical to that amount observed when cyclohexanone was treated with CH3COOD under the same conditions. This result rules out an addition-elimination mechanism, at least in the case of 174, and since concerted elimination is highly unlikely in small ring systems, it suggests a unimolecular ionization and formation of a vinyl cation intermediate in the solvolysis of cyclic triflates (170). The observed solvent m values, 174 m =. 64 175 m =. 66 and 16 m =. 16, are in accord with a unimolecular solvolysis. 

Scheme 14 Deuterium incorporation into acetophenone catalyzed by [Fe3(CO)i2]/terpy/PPh3/ PrONa/PrOD system...

Early experiments [1] using (+)-apopinene and deuterium showed, however, that in the isomerized molecules the deuterium content was very low and the isomerization was much faster than deuterium incorporation into the allylic position. Therefore it seemed probable that isomerization takes place through an intramolecular hydrogen shift. A sigmatropic 1,3-hydrogen shift was suggested, in which the allylic endo-H shifted top shift) [2]. 

It should be noted that the selective reduction of phenylacetylene and diphenylacetylene to either the ds-alkene or the alkane was achieved using LiAlH4 in the presence of FeCk or NiCk as a catalyst [90, 91]. However, deuterolytic workup of the reaction mixtures gave deuterium incorporations <26%, indicating that these reagent systems are not well suited for the synthesis of vinyl- or alkylaluminum compounds from alkynes. 

C21 in ketone 3. No deuterium incorporation at C17 was observed and only one of the two possible diastereomeric monodeutero ketones was observed. 

Diastereoselective reductive coupling of MVK and p-nitrobenzaldehyde performed under an atmosphere of elemental deuterium provides an aldol adduct incorporating a single deuterium atom at the former enone f>-pos-ition [69]. Deuterium incorporation at the a-carbon is not observed, excluding Morita-Baylis-Hillman pathways en route to product. Incorporation of a single deuterium atom suggests irreversible enone hydrometallation (Scheme 5). 

The analogous decomposition process was observed for related germylide-nephosphanes.32 Although the thermolysis of 12a was carried out in deuterated solvents, no deuterium incorporation was observed. Further work is needed in order to explore the reaction mechanism. In contrast to 12a, the thermolysis behavior of phosphasilenes 15 is quite different. 

The stereochemistry of dienes has been found to have a pronounced effect in the concerted cyclo-additions with benzyne 64>65h A concerted disrotatory cyclo-addition of tetrafluorobenzyne, leading for example with trans- (3-methylstyrene to (63, R = Me), is likely and in accord with the conservation of orbital symmetry 68>. However while the electro-cyclic rearrangement of (63, R = H) to (65, R = H) is not allowed, base catalysed prototropic rearrangement is possible. A carbanion (64, R = H) cannot have more than a transient existence in the reaction of tetrafluorobenzyne with styrene because no deuterium incorporation in (65) was detected when either the reaction mixture was quenched with deuterium oxide or when the reaction was conducted in the presence of a ten molar excess of deuteriopentafluorobenzene. 

When we allowed pentafluorophenyl-lithium to decompose in ether in the presence of an excess of N, ZV-dimethy laniline we obtained the compounds (92) 70, X = F), (94), the latter as the major compound, and a product which was shown to be (97). That this latter compound did not arise by metallation of 2V,lV-dimethylaniline followed by addition to tetrafluorobenzyne was shown by quenching the reaction mixture with deuterium oxide. No deuterium incorporation was detected. The compound (97) provides a rare example of a product derived by a Stevens rearrangement in which aryl migration has occurred b>. 

The research involved the use of deuterium gas as a tracer to follow the incorporation of hydrogen into coal. Neither donor solvent nor catalyst was used in those experiments. The liquefaction product was solvent fractionated, and the fractions were examined for deuterium incorporation in each structural position. 

Two significant results of that investigation were that deuterium incorporation was found to vary with product fraction and that preferential incorporation of deuterium was found in benzylic structural positions. The purpose of this research is to extend the use of the deuterium tracer method to donor solvent reactions. 

The main part of this research deals with the reaction of deuterium gas and Tetralin-d12 with a bituminous coal. In a separate experiment, naphthalene-d8 was used for investigating the chemistry of hydrogen transfer between coal and a nondonor solvent. In each experiment, the coal products and spent solvent were analyzed for toal deuterium content and for deuterium incorporation in each structural position. 

The atom % 2H values of the solvent-fractionated products are also shown in Table I. In previous hydrogenation experiments conducted without the use of a donor solvent (1,18), deuterium incorporation increased from the most soluble oil fraction to the insoluble residue. In E10 and El9, contact of the coal with Tetralin resulted in a uniform incorporation of deuterium in almost all of the four product fractions. In El9, the BMI fraction s high value of 61 atom % 2H may be due to direct gas-phase exchange and deuteration. 

However, the soqrce of the uranium hydride in the reaction of benzophenone with U wasn t clear. When the reaction was worked up with D90, no deuterium incorporation in TPA or DPM was seen, nor was any seen when using toluene-dg as a solvent. All of the naphthalene could be recovered, which led us to conclude that TMEDA (presumably coordinated to uranium) was reacting with the low valent uranium generating a uranium hydride which became incorporated into the TPA or DPM. 

Scrimgeour, C. M., Begley, I. S. and Thomason, M. L. (1999) Measurement of deuterium incorporation into fatty acids by gas chromatography/isotope ratio mass spectrometry. Rapid Communications in Mass Spectrometry 13, 271. 

Under the experimental conditions dehalogenation proved to be extremely rapid and was complete within 1 min. This contrasts with the 90-270 min at 100 °C required for thermal debromination of 2-bromonapthalene. No dehalogenation takes place in the absence of the formate donor and when the deuterium is located in the cosolvent rather than the donor (i. e. HCOOK + D20) hardly any deuterium incorporation takes place. Another interesting observation was that the amount (%) deuterium incorporation was always lower when protic solvents such as alcohols were used than aprotic solvents such as dimethyl sulfoxide (DMSO). These are both interesting and useful findings which are valuable for proposed tritiation studies. 

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