Methanal Extrusion in ipso-Substitution Reactions of Hydroxymethylindoles

Abstract

A range of 3-hydroxymethylindoles undergo acid-catalysed reactions involving ipso-electrophilic substitution with the extrusion of methanal and the formation of diindolylmethane moieties. Both inter-and intramolecular processes lead to macrocyclic compounds 10 and 14.

Comparative reactivity of 5,7-dimethoxyindoles with aldehydes and ketones

“…Presumably the intermediate bromomethyl compound undergoes further combination with the indole 17. However, many cases have been reported where 7-hydroxymethyl-4,6-dimethoxyindoles undergo acidcatalysed ipso-substitution reactions with elimination of formaldehyde to give 7,7'-diindolylmethanes, 8,9,15 (e.g. the conversion of indole 16 to diindolylmethane 15) so the two 4-hydroxymethylindoles 16 and 17 were further investigated.…”

“…This product was confirmed by comparison with the other product obtained from this reaction using thin layer chromatography and 1 H NMR spectroscopy. (15). Method A.…”

“…UV/Vis (λmax, nm, ε, cm -1 M -1 ): 216 (49,000), 228 (54,000), 272 (22,000), 295 (17,000), 306 (14,000). 1 515 (100), 500 (22), 394 (18), 393 (65), 258 (15), 204 (17). Anal.…”

Indole macrocycles formed by diindolylmethane ring closure

“…[9][10][11][12][13] Another major approach to indole containing macrocycles involves the construction of indolylmethylene cyclic oligomers, the calixindoles, formed by acid-catalysed reactions of activated indoles with aryl aldehydes, 14,15 activated indoles with hydroxymethylindoles, 16,17 or hydroxymethylindoles alone with extrusion of formaldehyde. 18 In special circumstances, direct oxidative dimerization of 2,7'-biindolyl compounds can generate macrocyclic tetraindolyls, the indorphyrins. 19…”

Celebrating RACI and Academy of Science Awards

“…Both inter-and intramolecular processes lead to macrocyclic compounds. [8] The second paper describes the construction of 21-membered macro-heterocycles containing three indole units linked through imine and amine moieties. [9] Michela Mitchell (Monash University) won an Early Career Investigator Award and best student oration at the 2016 RACI Peptide User Group Winter Symposium.…”