Recyclization of (2-Aminophenyl)bis(5-tert-butyl-2-furyl)methanes into Indole Derivatives: Unusual Dependence on Substituent at Nitrogen Atom

Abstract

R e c y c l i z a t i o n o f ( 2 -A m i n o a r y l ) b i s ( 5 -t e r t -b u t y l -2 -f u r y l ) m e t h a n e s Abstract: The recyclization of (2-aminophenyl)bis(5-tert-butyl-2-furyl)methanes under acidic conditions was studied. It was found that the extent of reaction of these substrates depends on the substituent at the nitrogen atom of the aniline moiety. N-Tosyl derivatives were converted into the corresponding 3-(5-tert-butyl-2-furyl)-2-(4,4-dimethyl-3-oxopentyl)-1-tosyl-1H-indoles. Indole formation was followed by furan ring opening in the case of N-unsubstituted substrates leading to 3-(5,5-dimethyl-1,4-dioxohexyl)-2-(4,4-dimethyl-3-oxopentyl)-1H-indoles. The same products were obtained from N-acetyl derivatives. However, the behavior of the N-benzoyl analogues depends on the reaction conditions: at room temperature 1-benzoyl-3-(5-tert-butyl-2-furyl)-1H-indoles were formed, but debenzoylation and furan ring opening proceed with heating. These data and results of control experiments showed that the reaction mechanism consists of three successive steps: recyclization itself, deacylation of the resulting N-acylindole, and furan ring opening in N-unsubstituted 3-(2-furyl)indoles. The last step can be realized for N-unsubstituted indoles only, but the furan ring is stable for Nacylindoles. This was explained by transformation of N-unsubstituted 1H-indoles under the reaction conditions into 3H-indole tautomers. These tautomers can be considered as 2,5-dialkylfurans, which have much lower stability against acids than 2-aryl-5-alkylfurans. This tautomerization is impossible for N-acylindoles. The high acidic stability of 2-(5-tert-butyl-2-furyl)indoles supports this conclusion.

Synthesis of tetracyclic system of 2,4‐di(tert‐butyl)‐6,7‐dihydrofuro[2′,3′:3,4]cyclohepta[1,2‐b]indole

“…The increase of reaction time leads, however, to triketone 16 but not to 15a (Scheme 5). This triketone was a single isolated product when reaction was performed for 9 h what is in a good accordance with the earlier obtained data [10].…”

“…The obtained results stimulated us to investigate carefully recyclization of [2-(benzoylamino)phenyl]bis(5-tert-butyl-2-furyl)methanes 12 in the mixture of acetic and hydrochloric acids [10]. We used compound 12a as a model substrate.…”

“…Condensation of these reagents in dioxane in the presence of catalytic quantity of perchloric acid gave rise to (2-nitroaryl)bis(5-tert-butyl-2-furyl)methanes 10a,b, which were further reduced by the treatment with hydrazine hydrate in the presence of Raney nickel [10]. The resulting anilines 11a,b were acylated with the corresponding benzoyl chlorides leading to benzamides 12a-e (Scheme 3).…”

“…The resulting anilines 11a,b were acylated with the corresponding benzoyl chlorides leading to benzamides 12a-e (Scheme 3). The reactions of 11 with tosyl chloride in pyridine yielded the corresponding N-tosylanilines 13a,b (Scheme 3) [10]. (Fig.…”

“…In particular, we have shown that the treatment of [2-(benzoylamino)phenyl]bis(5-tert-butyl-2-furyl)methanes 5 with HCl/AcOH at room temperature leads to ketones 6. However, at 45 C, this reaction is accompanied by debenzoylation followed by the second furan ring opening resulting in triketoindoles 7 (Scheme 2) [10].…”