A convenient synthesis of 2‐amino‐6‐methoxy‐1‐methyl (and 1,4‐dimethyl)carbazole derivatives and their 6‐aza analogues

Abstract

2,6‐Diaminotoluene (3a) and 2,6‐diamino‐p‐xylene (3c) led to 2‐methyl (and 2,5‐dimethyl)‐3‐acetylamino‐phenylhydrazines 5a,b. Fischer indolization of their hydrazones 6a,b and 7a,b derived from 4‐methoxycy‐clohexanone and 4‐piperidone, and subsequent aromatization of intermediate tetrahydrocarbazole derivatives 8a,b and 9a,b allowed us to work out a convenient route to the title compounds.

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

“…In the general case the nature of substitution at the nitrogen atom of the carbonyl component does not have a significant effect on the cyclization process: Both piperid-4-one [41] itself and its N-alkyl [32][33][34][35][36][37][38][39][40][42][43][44][45][46][47][48][49][50] and N-acyl [51,54] derivatives can also take part in the transformation, as can be demonstrated by the synthesis of the C 14 -labeled medical product Alosetron [67]. Of substantial importance for the Fischer reaction is the spatial structure of the piperidine carbonyl component.…”

“…).In this case there is no need to isolate the hydrazone that is formed in situ in the pure state, and this makes possible to achieve a one-pot synthesis of the carboline[39][40][41].…”

γ-Carbolines and their hydrogenated derivatives. 1. Aromatic γ-carbolines: methods of synthesis, chemical and biological properties (review)

“…Heating of γ-carboline 2-oxide with phosphorus oxychloride at 80-90°C leads to the formation of 1-chloro-γ-carboline, the chlorine in which can be substituted by a primary, secondary, or tertiary amino group. Boiling the N-oxide in acetic anhydride leads to 1-acetoxy-γ-carboline, the hydrolysis of which gives 1-hydroxy-γ-carboline [83,89]. The reaction of γ-carboline 2-oxide with phenyl isocyanate at 40°C only leads to the formation of 1-phenylamino-γ-carboline; the process presumably takes place as 1,3-addition of the isocyanate to the N-oxide [91].…”

“…Aromatization is most often realized by heating the respective γ-carboline derivative over metallic palladium [82,83]. Thus, 8-methyl-γ-carboline was first obtained from 2-benzyl-8-methyl-1,2,3,4-tetrahydro-γ-carboline by joint dehydrogenation and debenzylation.…”

Carbolines. Part I: Comparison of some methods for the synthesis of α-, γ-, and δ-carbolines (a review)

“…The ability to convert 1,2,3,4-tetrahydropyrido [4,3-b]indoles (22) obtained from the Fischer reaction into pyrido [4,3-b]indoles (23) by dehydrogenation in decalin in the presence of 10% Pd/C has been demonstrated [58] (Scheme 3).…”