Deuterated phenol

Early mechanistic studies have indicated that the oxypalladation step in the Wacker process proceeds through an <37z/z-pathway,399 although recent deuterium-labeling experiments have shown the viability of a yy/z-mechanism involving insertion of a metal-coordinated oxygen into the alkene.400,401 For example, with excess chloride ion present, the Wacker-type cyclization of a deuterated phenol system occurred in a primarily //-pathway, whereas the oxypalladation step favored a yy/z-mode in the absence of excess chloride ion (Scheme 16). Thus, either mechanism may be operative under a given set of experimental conditions. 

Figure 7. SANS signal from PNIPA in fully deuterated water ( ) at 20 °C and in contrast matched conditions (18% D20 82% H20) with different amounts of deuterated phenol (O 0 mM, 20 mM, and A 40 mM).

When sludge samples are spiked with internal standard prior to the extraction steps, low recoveiy of especially the deuterated phenol is observed. Similar effects are not observed in spiked natural sediments. Consequently, we postpone the addition of internal standard until the extraction steps have been performed. The concentrations in the final report are thus given as total metl lenechloride extractable concentrations. 

Besides, it seems that lignin is simply dissolved in phenol rather than covalently linked to. This result was confirmed by experimenting with deuterated phenol, even though the analysis is quite complex due to exchanges of deuterium with hydrogen of sulphuric acid and water. 

The rearrangement is found to be of intramolecular nature. The radical pair remains in the solvent cage and their recombination in the cage affords the acyl migration products, while hydrogen abstraction by the phenoxy radical from the solvent leads to the formation of phenol as by-product. When the reaction of phenyl acetate was carried out with deuterated phenol in methanol, the major products were ortho- and para-hydroxy acetophenones and phenol. Only trace amounts of crossover products were obtained [42]. The presence of methoxy substiment at meta- and para-positions increases the yield of ortho-Vries product [43]. For example, 39 gives 40. 

Reactions (6)-(10), formally, involve hydrogen atom abstraction. The lower rate constant observed by Maclachlan et al., when 0-deuterated phenols were used instead of normal phenols, was consistent with a rate-determining hydrogen atom abstraction in reaction (6) [21]. Reactions (7)-(10) have not been studied mechanistically as yet all are sufficiently fast to preclude observable radical dimerization. Rate constants of reactions (5) and (6) (with variously substituted phenols and hydroquinones) were found to be several orders of magnitude greater than that for radical dimerization. 

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. 

From the point of view of the synthetic organic chemist, the importance of aromatic thallation, and the remarkable degree of orientation control which can be exercised over this process, lies in the ease with which the resulting ArTlXj compounds can be converted into substituted aromatic derivatives in which the new substituent group has entered the ring at the position to which thallium was originally attached. Syntheses of phenols, nitroso compounds, biaryls, aromatic nitriles, thiophenols, and deuterated aromatic compounds have all been achieved these results are summarized briefly below. 

Partial reduction of polyarenes has been reported. Use of boron trifluoride hydrate (BF3 OH2) as the acid in conjunction with triethylsilane causes the reduction of certain activated aromatic systems 217,262 Thus, treatment of anthracene with a 4-6 molar excess of BE3 OH2 and a 30% molar excess of triethylsilane gives 9,10-dihydroanthracene in 89% yield after 1 hour at room temperature (Eq. 120). Naphthacene gives the analogously reduced product in 88% yield under the same conditions. These conditions also result in the formation of tetralin from 1-hydroxynaphthalene (52%, 4 hours), 2-hydroxy naphthalene (37%, 7 hours), 1-methoxynaphthalene (37%, 10 hours), 2-methoxynaphthalene (26%, 10 hours), and 1-naphthalenethiol (13%, 6 hours). Naphthalene, phenanthrene, 1-methylnaphthalene, 2-naphthalenethiol, phenol, anisole, toluene, and benzene all resist reduction under these conditions.217 Use of deuterated triethylsilane to reduce 1-methoxynaphthalene gives tetralin-l,l,3-yielding information on the mechanism of these reductions.262 2-Mercaptonaphthalenes are reduced to 2,3,4,5-tetrahydronaphthalenes in poor to modest yields.217 263... 

As can be seen, the pathway from the cyclohexadienone to the ortho-rearranged phenol does not imply a jump over an energy barrier (34 kcal/mol), but a tunneling from the vibrational energy levels located at E(vo) = 0 kcal/mol and E(vi) = 3.9 kcal/mol (4.4 kcal/mol for the deuterated compound). Analogous results have been reported for the photo-Fries rearrangement of 2,4-dimethoxy-6-( ara-tolyloxy)-v-triazine (28) to give 2,4-dimethoxy-6-(2-hydroxy-5-meth-ylphenyl)-v-triazine (29) (Scheme 11) [43]. 

Deuterated standards (dio-xylene ds-phenol ds-acetophenone cfc-phenylethanol cfc-nitrobenzene ds-propiophenone dg-naphthalene cfe-acridine di2-perylene) accumulator column 9 55-93 78 4-21 10 d... 

The pyridine-catalyzed aromatic proton exchange with deuterium provides a simple indication of the ability of a phenol to participate in chromene formation. Only those phenols which undergo exchange react with the unsaturated carbonyl compound, the attack occurring at the positions of deuteration (64JA2084). 

Fig. 3. 2H NMR spectra of uncured (A) and (B, C) cured phenol/formaldehyde resins (I) deuterated [DJformaldehyde containing resin and (II) deuterated [3,5-DJphenol containing resin (adapted from Ref. )...

Hydrodesulfurization of certain hydroxy-437 and methoxy-sub-stituted615 alkybenzo[6]thiophenes is a useful means of preparing some otherwise inaccessible alkyl-substituted phenols [e.g., Eq. (15)].015 Various p-methoxyphenylbenzo[6]thiophenes have been employed similarly to prepare the corresponding hydroxydiphenyl-alkanes.464 Catalytic hydrodesulfurization of a-alkyl-/ -(3-benzo[6]-thienyl)propionic acids affords a convenient method of preparing a,y-disubstituted y-phenylbutyric acids.636 Treatment of / -(3-benzo[6]thienyl)acrylic acid with Raney nickel alloy, sodium meth-oxide, and deuterium oxide affords the deuterated acid (366).667... 

Specifically deuterated derivatives of phenols can be prepared conveniently by using appropriate combinations of acid- and base-catalyzed exchange reactions. Treating with NaOD (or NaOH) causes exclusive exchange in positions ortho and para to the phenolic group while D3P04 deuterates all available aromatic sites. As an example, the conversion of 4-hydroxy-3-methoxytoluene to 5-monodeutero- and 2,6-dideuteroderiva-tives is illustrated below. 

Selective Deuteration. Methods outlined earlier (6) were used. NaOD was used to deuterate selectively positions ortho and para to a free phenolic group, D3P04 to deuterate all aromatic sites, and NaOH to remove selectively deuterium from positions ortho and para to a free phenolic group. 

Bernasconi, Koch, and Zollinger measured the IEs on acidity due to ring deuteration in some anilinium ions.49 The results are listed in Table 4. Deuterium definitely decreases acidity, but it was not possible to distinguish whether the IE decreases with increasing distance of the isotope or whether meta deuterium is ineffective compared to ortho (and perhaps para). A tentative answer to this question comes from phenols (Table 3),32 where the IEs are large enough and the NMR titration method accurate enough to show that there is no decrease as the site of deuteration moves from ortho to meta to para. 

A deuterated species of phenol, C6H5OD35 has been investigated by far-IR and microwave spectroscopy and the first two Fourier coefficients determined as V2 = -16.1911.19 kJ/mol, V4 = 0.2410.24 kJ/mol. In the parent species of phenol36) a determination assuming only a V2 term yielded V2 = -14.439 kJ/mol. 

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