It is an easy mistake to make that, because the list of indole syntheses on Wikipedia is long, surely it includes the easiest and most practical
methods. But in 1965, Bellamy and Guthrie published a method from nitrosobenzenes and alkylamines via the phenylazoalkane, which is converted to the
phenylhydrazone with H2SO4 in EtOH, and this is a substrate for the Fischer synthesis. This avoids the conventional prep of phenylhydrazine by the
reduction of a phenyldiazonium with bisulfite (a moderately frightening process).
Nitrosobenzenes, on the other hand, usually require simpler preparations, and the corresponding amines may be easier to obtain and are usually more
stable than the aldehydes. So the nitroso + amine version is easier on both sides than the hydrazine + aldehyde one.
They carried out the Fischer indole synthesis using BF3*Et2O, but surely there are other catalysts for this part. A quick search finds many examples
using Brønsted acids.
Attachment: bellamy1965.pdf (689kB) This file has been downloaded 279 times
Boffis - 13-5-2025 at 12:48
c_n_a, I have read the attached paper and can't quite see your point. The authors, in the experimental section, shown that the the use of BF3-ether
gives no better yield that the same reation without. So that in their example of cyclohexanone phenylhydrazone they get 86% yield with just sulphuric
acid as the condensing agent and 76% with BF3. Or are you refering to the use of phenylazoalkanes as starting materials?
Are phenylazo-alkane more accessible that hydrazones?clearly_not_atara - 13-5-2025 at 13:21
Boffis: I think you read the paper just fine, but you should reread the post.
Actually, I didn't read the paper that well, or I would have realized that they did the cyclization with sulfuric acid, too.
But that wasn't my point at all.
Quote:
Are phenylazo-alkane more accessible that hydrazones?
The point of the original post was precisely this, yes. The phenylazoalkane is produced by the reaction of a nitrosobenzne with an alkylamine.
