Acetic deuterated

Singleton, D. L., G. Paraskevopoulos, and R. S. Irwin, Rates and Mechanism of the Reactions of Hydroxyl Radicals with Acetic, Deuterated Acetic, and Propionic Acids in the Gas Phase, J. Am. Chem. Soc., Ill, 5248-5251 (1989). 

Into the previously reported transition-metal catalyzed intermolecular hydroalk-oxylations of alkenes, gold catalysts showed to be the most active catalysts, with divergent reactivity with respect to PtCl2, leading to the formation of aUylethers [156]. Opposite to monosubstituted allenes, disubstituted aUenes yield no aliphatic acetals. Deuteration studies support the hypothesis of a zwitterionic Pt carbene as... 

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... 

Another example of selective deuteration in homogeneous solution is saturation of the sterically more accessible A -double bond in ergosterol acetate (142 143). The a-configuration of the incorporated deuteriums... 

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... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

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

Bromination of 3 -hydroxy-B-homo-5a-cholestan-7-one acetate (54b) in the presence of hydrobromic acid gives a single thermodynamically stable monobromo ketone. To determine the position of the bromine atom, the sequence of reactions was repeated with compounds selectively deuterated in the 5a-position. 

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... 

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

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 . 

The decarboxylation of carboxylic acid in the presence of a nucleophile is a classical reaction known as the Hunsdiecker reaction. Such reactions can be carried out sometimes in aqueous conditions. Man-ganese(II) acetate catalyzed the reaction of a, 3-unsaturated aromatic carboxylic acids with NBS (1 and 2 equiv) in MeCN/water to afford haloalkenes and a-(dibromomethyl)benzenemethanols, respectively (Eq. 9.15).32 Decarboxylation of free carboxylic acids catalyzed by Pd/C under hydrothermal water (250° C/4 MPa) gave the corresponding hydrocarbons (Eq. 9.16).33 Under the hydrothermal conditions of deuterium oxide, decarbonylative deuteration was observed to give fully deuterated hydrocarbons from carboxylic acids or aldehydes. 

Further studies by Spenser demonstrated that l,2-13C-labeled acetate (13) was incorporated into lycopodine but gave a distribution of the labels that did not account for the pelletierine-route that was hypothesized (Scheme 6.2) [11]. An intact 3-carbon unit was desired for testing, but labeled acetoacetate (l,2,3,4-13C-acetoacetate (14), which could undergo decarboxylation to provide an intact 3-carbon unit) was found to give the same incorporation pattern as acetate (and therefore must have been cleaved to acetate prior to uptake). In addition, feeding studies using deuterated, 13C-labeled acetate provided a loss or washout of deuterium at the C16 methyl group. This could only occur if an intermediate had formed that would provide for facile enolization. Both the equal distribution of the 13C labels and loss of the deuteriums led the researchers to propose that the intermediate was symmetric, such as acetone dicarboxylic acid (15). 

For a number of benzylformic acids we used N-ethylmorpholine as catalyst and D20 as solvent/donor. Once again decarboxylation/deuteration occurs very rapidly and is complete within 4 min. The range of compounds that can be labeled in this manner has been further widened by the recent observation [75-77] that tributylpho-sphine and other trivalent phosphorus compounds (R3P, R= Bu, Ph, Me2N, OEt) catalyze the decarboxylation of a-iminoacids. By using deuterated/tritiated acetic... 

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. 

Deuterated and tritiated tin hydrides have been used to prepare deuterated saccharides93 and tritiated steroids46 from alkyl bromides, (equations 68 and 69). It is important to note that isomerization has occurred at the chiral reaction centre in the saccharide reaction (equation 68). For the steroid, the tin hydride reaction is regiospecific, i.e. it only reacts at the more reactive bromide rather than the less reactive chloride site and does not react with the keto group, the hydroxyl group or the acetal group. 

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