Deuterated alcohol

Tanaka has recently reviewed the hydrogenation of ketones with an emphasis on the mechanistic aspects of the reaction.233 Numerous references related to this subject can be found in his article. Deuteration of cyclohexanones and an application of NMR spectroscopy to the analysis of deuterated products have revealed that on ruthenium, osmium, iridium, and platinum, deuterium is simply added to adsorbed ketones to give the corresponding alcohols deuterated on the Cl carbon, without any deuterium atom at the C2 and C6 positions, while over palladium and rhodium the C2 and C6 positions are also deuterated.234 A distinct difference between rhodium and palladium is that on rhodium deuterium is incorporated beyond the C2 and C6 positions whereas on palladium the distribution of deuterium is limited to the C2 and C6 carbons.234,235 From these results, together with those on the deuteration of adamantanone,236 it has been concluded that a Tt-oxaallyl species is formed on palladium while deuterium may be propagated by an a, 3 process237 on rhodium via a staggered a, 3-diadsorbed species. 

The aluminum isopropoxide is not only a catalyst but is actually the reducing agent.322 Experiments with aluminum alkoxides derived from alcohols deuter-ated on carbon323 showed that the hydrogen is transferred to the carbonyl group directly from the alkoxide without participation of the solvent thus the reaction can be carried out also in the absence of 2-propanol, by using aluminum isopropoxide in the molten state or in toluene or other hydrocarbon. 

During the course of base-catalyzed exchange in O-deuterated alcohols, the vinylic hydrogen in the a position to the ketone is replaced by deuterium, in addition to the hydrogens activated by enolization. Thus, under these conditions the exchange of androst-l-en-3-one (16, R = H) gives a trideuterio derivative (18) instead of the expected 4,4-d2 analog (16, R = D). " (For other examples see compounds 13, 19, 21, 23, 26 and 27.) Incorporation of this deuterium is due to rapidly reversible alcohol addition (16 -+17) and elimination (17 18) which competes with the enolization step. " ... 

Reduction with metal deuteride complexes (section Ill-A) is undoubtedly the most convenient way to convert carbonyl compounds into the corresponding deuterated alcohols. For stereochemical reasons, however, it is sometimes necessary to resort to reductions with alkali metals in O-deuterated alcohols, or in liquid deuterioammonia-O-deuterioalcohol mixtures. 

There are ample precedents for reductions of double bonds in conjugated enones with lithium in deuterioammonia (see section V-C). Examples of the reduction of saturated ketones in deuterated media appear only as side reactions (over reductions) during the above mentioned conversions. For experimental details, therefore, one should consult the literature for the analogous reductions in protic medium (see also chapter 1). The use of deuterioammonia is essential for labeling purposes since by using liquid ammonia and methanol-OD the resulting alcohol contains no deuterium. For the preparation of deuterioammonia see section IX-D. 

This reaction provides a wide variety of products since decomposition of the deuterated alkylborane intermediate (164) can be achieved with hydrogen peroxide to yield labeled alcohols (165), with hydroxylamine-O-sulfonic acid leading to deuterated amines (166), as well as with boiling propionic acid or propionic acid-OD, to form mono- (167) or dideuterio (168) hydrocarbons, respectively. Furthermore, if a monodeuterium label at the sterically more accessible position (170) is sufficient, the use of expensive metal deute-... 

There are three methods which are commonly used in the steroid field to replace a halogen atom by deuterium. These methods involve treatment of the halides— generally chloride, bromide or iodide—(a) with lithium aluminum deuteride, (b) with deuterium gas and a surface catalyst or (c) with zinc in O-deuterated acids or alcohols. 

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/... 

Aliphatic sulfonyl chlorides that have a-hydrogen substituents, react with simple tertiary amines, such as trimethylamine, to generate sulfenes or perhaps their amine adducts 446). These species are suggested by the incorporation of one (but not more) deuterium atoms on reaction of sulfonyl chlorides with deuterated alcohols and triethylamine (447-450). A 2 1 adduct of sulfene and trimethylamine with proposed sulfonyl-sulfene structure could be isolated (451). 

Ri = N3, R.2 = H), and an equilibrium is observed in the case of the deuterated compound (59 Ri = R2 = N 02). Certain secondary amino-substituted compounds (59, 60 Rj =RNH, R2 = H) show solvent dependence of their equilibria solutions in dimethyl sulfoxide contain mainly form 59, whereas alcohols as solvents favor form 60. ... 

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. ... 

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 equatorial allylic alcohol 3)S-hydroxyandrost-4-ene is oxidised by Cr(Vl) 310 times faster than the saturated 3)3-hydroxy-5a-androstan-17-one, 5.7 times faster than the axial 3a-hydroxyandrost-4-ene and 6.9 times faster than its 3-deuterated analogue . The greater speed of oxidation of the equatorial isomer is in contrast to the pattern observed for saturated alcohols and probably arises from resonance between the double bond and the incipient carbonyl group. 

A concerted four-center cis addition leads to (52) and a trans adduct a trans addition, possibly via protonium species, leads to (53) and a cis adduct a stepwise cationic addition leads to (54) and a mixture of cis and trans adducts. Recent studies by Marshall and Wurth strongly indicate that intermediate (54) is correct. Irradiation of octalin (55) in aqueous /-butyl alcohol (DaO)-xylene results in formation of the equatorially deuterated alcohols (56) and (57) and the equatorially deuterated exocyclic olefin (58) ... 

Fig. 29. Decrease in intensity of nitroxide ESR signal npon addition of deuterated ethanolamine to ethanolamine ammonia lyase containing spin labeled cobinamide coenzyme. The two curves are for different concentrations of coenzyme to enzyme. The arrows indicate the point at which alcohol dehydrogenase and NADH was added to remove acetaldehyde from the enzyme. Note that full intensity is regained...

The reaction of carbenes with alcohols can proceed by various pathways, which are most readily distinguished if the divalent carbon is conjugated to a tt system (Scheme 5). Both the ylide mechanism (a) and concerted O-H insertion (b) introduce the alkoxy group at the originally divalent site. On the other hand, carbene protonation (c) gives rise to allylic cations, which will accept nucleophiles at C-l and C-3 to give mixtures of isomeric ethers. In the case of R1 = R2, deuterated alcohols will afford mixtures of isotopomers. 

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