Deuterated acetic acid

The earliest attempts to prepare deuterated steroids were carried out by exchange reactions of aliphatic hydrogens with deuterium in the presence of a surface catalyst. Cholesterol, for example, has been treated with platinum in a mixture of deuterium oxide and acetic acid-OD, and was found to yield... 

The isotopic purity of the product is usually about 48-62%, the rest of the material being mainly undeuterated. (An alternate preparation of a-mono-deuterio ketones of high configurational and isotopic purity is the mild oxidation of cis- or tra 5-deuterated alcohols under Jones conditions, see sections V-D and VII-A.) Treatment with zinc in acetic acid-OD has also been applied to the deiodination of 2a-iodoandrost-4-ene-3,17-dione. In a slightly modified version the iodine in 19-iodocholesterol acetate has been replaced with tritium by using tritium oxide as the isotope source/... 

Displacement of aromatic halogen in 2,4-diiodo-estradiol with tritiated Raney nickel yields 2,4-ditritiated estradiol. Aromatic halogen can also be replaced by heating the substrate with zinc in acetic acid-OD or by deuteration with palladium-on-charcoal in a mixture of dioxane-deuterium oxide-triethylamine, but examples are lacking for the application of these reactions in the steroid field. Deuteration of the bridge-head position in norbornane is readily accomplished in high isotopic purity by treatment of the... 

Deuteration at C-9 by Treatment of a 9a-Bromo-11 -keto Steroid with Zinc in Acetic Acid-OD... 

Deuteration at C-9 by treatment of a 9a-bromo-ll-keto steroid with zinc in acetic acid-OD, 204... 

A kinetic isotope effect, kH/kD = 1.4, has been observed in the bromination of 3-bromo-l,2,4,5-tetramethylbenzene and its 6-deuterated isomer by bromine in nitromethane at 30 °C, and this has been attributed to steric hindrance to the electrophile causing kLx to become significant relative to k 2 (see p. 8)268. A more extensive subsequent investigation304 of the isotope effects obtained for reaction in acetic acid and in nitromethane (in parentheses) revealed the following values mesitylene, 1.1 pentamethylbenzene 1.2 3-methoxy-1,2,4,5-tetramethyl-benzene 1.5 5-t-butyl-1,2,3-trimethylbenzene 1.6 (2.7) 3-bromo-1,2,4,5-tetra-methylbenzene 1.4 and for 1,3,5-tri-f-butylbenzene in acetic acid-dioxan, with silver ion catalyst, kH/kD = 3.6. All of these isotope effects are obtained with hindered compounds, and the larger the steric hindrance, the greater the isotope... 

A relative reactivity of ferrocene benzene of 105-106 has been quoted557 following a kinetic study of the deuteration of ferrocene in acetic acid-trifluoroacetic acid mixtures at 25 °C, but the value is entirely in error, being based on two faulty assumptions. The data are given in Table 166 and a linear plot of log Art versus —H0 was extrapolated to — H0 = 5.0, a rate coefficient of 1.3 x 10 1 being obtained. This was compared to the Gold and Satchell value for dedeuteration... 

The alcohol 3) , 28-diacetoxy-6 -hydroxy-18i -12-oleanene was oxidised in an aqueous acetic acid medium Deuteration at the six position had no effect on the rate in solvents of high (> 80 %) acetic acid content, but the isotope effect reached 2 in 60 % acetic acid. Increasing the acetic acid content of the medium produced a much larger effect on the oxidation rate of cyclohexanol than of the polycyclic alcohol. 

The resolution of the overall reaction into steps implied by the steric effect (above) has been achieved" for the oxidation of isopropanol. In 97% aqueous acetic acid a rapid reaction, ic2 x 1.25x10 l.mole . sec (15 °C, p = 0.183 Af NaC104), which is unaffected by deuteration, precedes the oxidation. Evidence for an intermediate has been reported for the oxidation of 1,1,1-tri-fluoro-2-propanol at very high acidities . 

Deuteration studies with acetic acid-d4 (99.5% atom D) as the carboxylic acid building block, ruthenium(IV) oxide plus methyl iodide-d3 as catalyst couple and 1/1 (C0/H2) syngas, were less definitive (see Table III). Typical samples of propionic and butyric acid products, isolated by distillation in vacuo and glc trapping, and analyzed by NMR, indicated considerable scrambling had occurred within the time frame of the acid homologation reaction. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

The cartridge was preconditioned with 0.5 mL toluene and each of the above benzodiazepine solutions passed through it. Analytes retained on the MIP were eluted with 0.5 mL of 15% acetic acid in acetonitrile. Internal standard (corresponding deuterated benzodiazepine) was added and subjected to LC/MS/MS. The results obtained for recovery, limit of detection (LOD), and quantitation (LOQ) are shown in Table 1.22. The binding capacity of diazepam to the templated MIP was found to be 110 ng/mg polymer. The same results were obtained for postmortem hair samples. 

A different kind of host consisting of a peptide-based bicyclic structure has been described.118 In this case, the chemical shifts changes were followed by HSQC spectra in deuterated acetic acid and in water, when titrated with cellobiose. In any case, a low but measurable binding affinity constant was found. 

A large inverse secondary deuterium KIE of 0.64 was observed in acetic acid at 25°C when the perdeutero (d2o) compound was the deuterated substrate. This large inverse deuterium KIE was attributed to the KIE for the rate-determining formation of the bromonium ion (62). Although a portion of this KIE is undoubtedly due to the inductive effect (deuterium is more electron-donating than hydrogen and the deuterated bromonium ion would... 

Mitulovic et al. [Ill] presented a procedure for the preparation of a-carbon deuterium-labelled a-amino acids from native amino acids via a Schiff-base racem-ization protocol in deuterated acetic acid involving a preparative chromatography step of the obtained Z-protected deuterium-labeled amino acid derivatives on the tBuCQN-CSP [ill]. The analytical control of the enantiomeric products after DNP, Z, or DNZ derivatization showed a high enantiomeric excess (97-98%) and also a high isotopic purity (99%) by MS. 

Acetic acid (CH3COOH)2 and per-deuterated acetic acid (CDjCOOD dimer... 

Figures 3a and 3an show fs DFWM spectra of acetic acid (CH3COOH) and per-deuterated acetic acid (CD3COOD) vapor from a gas cell experiment (300K). In contrast to formic acid, acetic acid shows only J-type recurrences from dimeric species in the fs DFWM spectra at room temperature. The difference of 45 ps between the position in time of the recurrences from (CH-)C00H)2 and (CD3COOD)2 is determined by the smaller rotational constants B, C of (CD3COOD)2. From the non-linear fitting (Fig 3b, 3bo) the rotational constants A=5,7 0.3GHz B+C=1657.2 1.2MHz of the acetic acid dimer (CH3COOH)2 and...

A=5.4+0.4GHz B+C=1445.2 0.5MHz of the per-deuterated acetic acid dimer (CD3COOD)2 were extracted. It was not possible to determine the rotational constants B and C independently due to the symmetric prolate top nature of the dimeric structure (Ray s asymmetry parameter k=-0.965). More detailed consideration of the fs DFWM spectra taken in the gas cell and in a supersonic expansion for the acetic acid dimer are under way in our laboratory and will be presented in a forthcoming publication. 

Of the two competing pathways (44 -+ 45) and (44 -> 46) the one leading to C-23 deuteration (44-+45) is favored. Thus, when 5a-spirostan (44) is heated under reflux for 1 hour in acetic acid-OD or in ethanol-OD solution containing deuteriochloric acid, the 23,23-d2-analog (47, R = D) is obtained containing 90% of d2-species.78 Prolonged heating leads to the trideuterated... 

When 2,4,6-trimethylpyrylium perchlorate is heated with [0-2H]acetic acid, the 3- and 5-hydrogens are deuterated. This substitution is unlikely to occur by direct electrophilic displacement in the cyclic compound but may proceed through an acyclic dienone formed by prior addition of acetate ion at C-2 (69RRC247). 

A halo atom may be replaced by deuterium by the action of deuterium oxide on the Grignard reagent,83 87 121 or by reduction of the bromo compound with zinc and deuterated acetic acid.89 It has been shown that the first method does not give completely specific deuteration.87... 

Several reports deal with the action of heterocycle-chromate agents such as quinolin-ium dichromate on five-membered heteroaldehydes340 and quinolinium bromochromate on benzaldehydes,341,342 all in acetic acid solution. The latter studies show a second-order dependence on proton concentration, acceleration by electron-withdrawing para-substituents, and a substantial kinetic isotope effect for the deuterated aldehyde. 

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