Indole hydrogen exchange

Indoles have been shown by ultraviolet and nmr spectroscopy to be protonated predominantly at the 3-position, giving the conjugate acids [172] (Hinman and Whipple, 1962). Hydrogen exchange at... 

Irradiation of tryptophan and related compounds is well known to result in hydrogen exchange at the 4-position of the indole nucleus and the side chain amino group is implicated In the process. This exchange reaction has now... 

Partial rate factors of hydrogen exchange of azulene, cycl(2.2.3)azine, indolizine, A-methyl-isoindole, and indole have been compared <87JCS(P2)591>. 

A number of kinetic studies on hydrogen exchange of derivatives of furan, thiophene,pyrrole,selenophene, imidazole, oxazole, thiazole, and indole have been reported. The kinetic picture is the same as for benzene derivatives reactions follow pseudo first-order kinetics and the values increase markedly as the acidity of the medium increases. 

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

We chose the microwave-enhanced Raney Nickel catalyzed hydrogen isotope exchange of indole and N-methylindole as our substrates and D20, CD3COCD3, CD3OD and CDC13 as the solvents. The thermal reaction had already been the subject of a recent study [44], The microwave-enhanced method was some 500-fold faster than the corresponding thermal reaction (at 40 °C). Furthermore the pattern of labeling (Scheme 13.3) varied with the choice of solvent. Thus in the case of indole it-... 

It can be assumed that the azoles are deprotonated by the interfacial exchange mechanism, but it is noteworthy that it has been suggested that the rate of alkylation of indole under liquiddiquid two-phase conditions decreases with an increase in the concentration of the sodium hydroxide [8]. The choice of catalyst appears to have little effect on the reaction rate or on the overall yields of alkylated azole. Benzyltriethylammonium chloride, Aliquat, and tetra-n-butylammonium hydrogen sulphate or bromide have all been used at ca. 1-10% molar equivalents (relative to the concentration of the azole) for alkylation reactions, but N-arylation of indole with an activated aryl halide requires a stoichiometric amount of the catalyst [8]. 

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