Der FISCHER'sche Indolringschluss mit 1, 3‐disubstituierten 4‐Piperidonen. 7. Mitteilung über synthetische Indolverbindungen [1]

Abstract

Sunzmavy. Treatment of the arylhydrazones of 1,3-disubstitutcd 4-piperidones with ethanolic hydrogen chloride (FISCHER reaction conditions) affords 1,2,3,4-tetrahydropyrimido [3,4-a]-indoles in good yields. During catalytic hydrogenation in the presence of protons these tetrahydropyrimido-indoles are split into 2-(2-mcthylamino-ethyl)-indoles. The formation of these tricyclic products can be explained by rearrangement immediately following the normal FISCI~ER reaction.If the substituent at the piperidine nitrogen is an acyl group, normal or rearranged products are formed, depending on the nature of the 3-substituent.Bei der FIscHER'schen Indolsynthese werden aus Phenylhydrazonen von Aldehyden oder Ketonen je nach Substitution der Carbonylverbindung Indole oder auch

γ-Carbolines and their hydrogenated derivatives 3.* Hydrogenated derivatives of γ-carbolines: chemical and biological poperties (Review)

“…In this case the cyclization takes place with the formation of the indolenines 19, which are transformed into the intermediates 20 with cleavage of the C(1)-C(9b) bond in a retroreaction of the Mannich type, and they subsequently rearrange to the pyrimido[1,6-a]indoles 21 [54]. In a number of cases 3-substituted isotryptamines 22 are formed in addition to the pyrimido[1,6-a]indoles 21 [55].…”

γ-Carbolines and their hydrogenated derivatives. 2.* Hydrogenated derivatives of γ-carbolines: methods of synthesis (review)

“…This is explained by steric hindrances in the N,Ndisubstituted hydrazones. For 1,3-disubstituted piperidines cyclization takes place with skeletal isomerization, leading predominantly to 1,2,3,4-tetrahydropyrimido[1,6-a]indoles [69].…”

“…Indolenine derivatives analogous with compound 56 can also be reduced with almost quantitative yields by LiAlH 4 in ether[69].…”

“…Electron-deficient substituents at the piperidine nitrogen atom (R 1 = Ac, CO 2 Et, etc.) must hinder the formation of pyrimido-[1,6-a]indole or make it impossible[69…”

Synthesis of the Indole Nucleus

“…Recent studies17s support the latter observation and point out that in both the solid state or in solution only the thermodynamically more stable hydrazone 127 is present. It has also been shownls0 that mild acid or alkaline conditions, as well as the presence of radicals, will 264 …”