English and German Wikipedia give slightly different mechanisms on Fischer indole synthesis. The thing bugging me is the protonation of N and the source of the proton.

Look at the intermediates 8 (Ger) and 5 (Eng). In the German Wikipedia imines are not protonated, in the English they are. Or look at intermediates 10/11 (Ger) and 7 (Eng) - protonation occurs but on different N-atoms of the aminoacetal. Ammonia won't leave the molecule unless it is previously protonated, but how important is protonation in other steps? Aren't those molecules in an equilibrium with all their protonation variations anyway? And so does the reaction mechanism even specify the source of the proton? Do specific steps take a proton from the molecule, whereas other steps take it from the surroundings? I always thought the molecule simply grabs the most available proton (the closest and "loosest" one).

German Wikipedia: Fischersche Indolsynthese

English Wikipedia: Fischer indole synthesis


1 Answer 1


English Wikipedia is more correct. Under acidic conditions, carbonyl and imine additions should happen via the oxocarbenium and the iminium ions, respectively.

Also, the in German version, the step between 5 and 6 is not a step; that's a resonance structure. There's also sloppiness in 3 and 10. Those attacks should come from the lone pair. Technically, those steps should've happened before the addition anyway, as I've already pointed out. Bottom line is that, again, the English version looks better.

  • $\begingroup$ There's actually something happening from 5 to 6, namely a deprotonation. I agree the German one is sloppy, 5 shouldn't even be there if you use the N lone pair to expel water in 4. $\endgroup$ Dec 1, 2016 at 14:59

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