The Cycloaddition Reaction of 3-Alkylindoles with p-Benzoquinone

Wayland E. Noland, Frederic J. Baude

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


3-Alkylindoles, including skatole, 3-ethylindole, 1,3-dimethylindole, 2,3-dimethylindole, and 1,2,3-trimethylindole, react with p-benzoquinone in acetic acid at room temperature, giving 2:1 cycloadducts (- H2) which are shown to be 7b,14b-dialkyl-5a,7b,12a,14b-tetrahydrobisindolo[2,3-6:2ʹ,3ʹ-6ʹ]benzo[1,2-d:4,5-dʹ]difurans (1a-e). The cycloadducts derived from indoles unsubstituted in the 2 position (1a-c, but not 1d and e) undergo acid-catalyzed or thermal isomerization to 2,5-bis(3-alkylindol-2-yl)hydroquinones (2a-c), different (2a) from 2,5-bis(2-methylindol-3-yl)hydroquinone (7), and which (2a) are readily oxidized to the corresponding quinones (as with 2a → 3), different (3) from the known 2,5-bis(2-methylindol-3-yl)-p-benzoquinone (6). The structure of 2a was proved by a double Fischer indole synthesis of its O,Oʹ-dimethyl derivative (2g). Cycloadduct 1a (but not 1d) underwent facile hydrogenolysis in inert solvents to 2,5-bis(3-methylindolin-3-yl)hydroquinone (14a) or, in ethanol solution, to its N,Nʹ-diethyl derivative 14b, identical with a sample prepared by lithium aluminum hydride reduction and cleavage of the N,Nʹ,O,Oʹ-tetraacetyl derivative 14d of 14a. Pyrolysis of 14a either gave partial breakdown, to 2-(3-methylindolin-3-yl)hydroquinone (16) and skatole, or at higher temperatures 14a and b gave complete breakdown to hydroquinone and skatole or 1-ethyl-3-methylindole (17). Action of alkali on the methiodide (18) of 14b under attempted Emde conditions gave no reduction but instead dehydroiodination to a double zwitterion 19. Acetylation of 19 was accompanied by N,Nʹ-didemethylation, giving the O,Oʹ-di-acetyl derivative 14c of 14b. 2,2ʹ-(2,5-Dimethoxy-p-phenylene)dipropionaldehyde (21) and its diphenylhydrazone (22) were synthesized, but an attempted double Fischer indolenine synthesis to 3,3ʹ-(2,5-dimethoxy-1,4-phenylene)bis(3-methyl-3H-indole) (23), which upon hydrogenation should yield the O,Oʹ-dimethyl derivative of 14a, failed. The probable mechanisms of formation of the cycloadducts 1 and their derivatives are discussed, with particular reference to other reactions of 3-alkylindoles and of indolenines reported in the literature. The synthesis of 2,3,4-trimethylindole is described.

Original languageEnglish (US)
Pages (from-to)3321-3337
Number of pages17
JournalJournal of Organic Chemistry
Issue number10
StatePublished - Oct 1966


Dive into the research topics of 'The Cycloaddition Reaction of 3-Alkylindoles with p-Benzoquinone'. Together they form a unique fingerprint.

Cite this