Acid-catalysed hydrogen exchange

The reaction of an acid with an aromatic leading to hydrogen exchange, viz. 

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Kinetic studies of the mechanism of acid-catalysed hydrogen exchange... 

C.D. Johnson and K. Schofield, A Criticism of the Use of the Hammett Equation in Structure-Reactivity Correlations, J. Am. Chem. Soc., 1973, 95, 270 T.J. Gilbert and C.D. Johnson, Acid-Catalysed Hydrogen Exchange of Acetophenones. Evidence for the Inapplicability of the Reactivity-Selectivity Principle, J. Am. Chem. Soc., 1974, 96, 5846. 

Figure 7. Isotope effects for acid-catalysed hydrogen exchange of indoles at 25°C ( ) H30, ...

Electrophilic Reactions. Further studies aimed at the correlation of the reactivity of five-membered heteroaromatic rings towards electrophiles have been reported. Acid-catalysed hydrogen exchange rates were measured (n.m.r.) for isoxazole, isothiazole, and their 3- and 5-methyl derivatives. Extrapolated values for the rate constants at 100 °C and pH 0 were obtained and compared with those for other ring systems. Quantitative effects of the methyl groups reflect the relative degree of bond fixation, and indicate that the aromaticity increases in the series isoxazole, pyrazole, and isothiazole. ... 

Two papers dealing with HMO calculations of the chemical reactivity of substituted thiophens should be noted one on the acid-catalysed hydrogen exchange" and the other on the transmission of substituent effects across the thiophen ring" Gol dfarb et al." have studied another problem in chemical reactivity electrophilic substitution of thiophen-2-carbaldehyde occurs in the 5-position but at the 4-position when this compound is protonated, and substitution in protonated 2-amino-thiophens occurs at the 5-position despite the m-directing property of the ammonium group. They found the chemical reactivity to be related to the CNDO/2 valence-electron densities." ... 

The rate coefficients obtained with hydrogen iodide show that the effectiveness of halogen acids in catalysing hydrogen exchange is HF > HBr > HI and, as noted above, this was attributed to the difference in dielectric constant of the media. 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

Acid-catalysed hydrogen-deuterium exchange in norcamphor has also been investigated by Werstiuk and Banerjee (1977) (DOAc—D20—DC1 medium). It was observed that exo-deuteron addition to the enol is also preferred, but with a slightly smaller selectivity (x 190). This would mean that, if torsional factors cause preferential base-catalysed exo-exchange, they also occur for acid-catalysed keto-enol tautomerism. However, the absence of important torsional strain effects on the rate constants of acid-catalysed enolisation of cyclic and bicyclic ketones contradicts this assumption. 

GS-MS and H NMR analysis of the selectively deuteriated intermediate product 2-amino-5,2 -dichloro-3,4, 6 -trideuteriobenzophenone, 46, have shown that in the first acid-catalysed key exchange reaction one deuterium has been incorporated into the triply substituted A ring and two deuterium atoms into the doubly substituted aromatic ring B Hydrogens a , b and c have been deuteriated in 99%, 98% and 92%, respectively. 

Indoles, like pyrroles, are very weak bases typical p a values are indole, -3.5 3-methylindole, -4.6 2-methylindole. -0.3. This means, for example, that in 6M sulfuric acid two molecules of indole are protonated for every one unprotonated, whereas 2-methylindole is almost completely protonated under the same conditions. By NMR and UV examination, only the 3-protonated cation (3//-indolium cation) is detectable it is the thermodynamically stablest cation, retaining full benzene aromaticity (in contrast to the 2-protonated cation) with delocalisation of charge over the nitrogen and o-carbon. The spectroscopically undetectable A -protonated cation must be formed, and formed very rapidly, for acid-catalysed deuterium exchange at nitrogen is 400 times faster than at C-3, indeed the A -hydrogen... 

Electrophilic aromatic hydrogen exchange reactions fall into two classes, namely those reactions catalysed by acid and those reactions catalysed by base. Of these the former are by far the most common and have been subjected to the most extensive and intensive kinetic studies. 

The intermediacy of enols or enolate anions may be demonstrated by hydrogen exchange reactions (see Section 4.11.2). Both acid-catalysed and base-catalysed tautomerism mechanisms involve removal... 

Two mechanisms are shown above. The base-catalysed mechanism proceeds through the enolate anion. The acid-catalysed process would be formulated as involving an enol intermediate. Note that the terminal hydrogens in pentan-3-one are not exchanged, since they do not participate in the... 

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