Hydrazine-mediated one-pot amination-oxidation reaction: facile synthesis of 4-amino-.beta.-carbolines and 4-aminoisoquinolines

Abstract

The conversion of the 4-oxo-2-benzoyl-l,2,3,4-tetrahydro-|8-carbolines la and lb, respectively, into their corresponding 4-amino-(3-carbolines 2a and 2b was effected in 70% yield in refluxing hydrazine. In contrast, phenylhydrazine, when heated with the 4-oxo derivative lb, gave the pyridodiindole 18a. This compound derives its origin from an initial Fischer indole cyclization, followed by loss of the 2-benzoyl group and aromatization to the /3-carboline. During investigation of the scope and mechanism of this new amination-oxidation reaction, it was found that an acidic hydrogen atom (position 2, NH) to the carbonyl group (C-4) was necessary to drive the reaction to completion. Although phenylhydrazones such as 20b and 20c, which carry electron-withdrawing groups, led to the formation of 2b at the expense of the Fischer indole products 18b and 18c, respectively, the yields in this sequence were only moderate. Hydrazine, consequently, appears to be the reagent of choice to effect this amination-oxidation reaction since Fischer indole cyclization cannot compete in this process.

Structure, synthesis and application of azines: a historical perspective

“…Compound 23 was then heated in reuxing ethanolic hydrogen chloride for several hours to obtain 24. 18 2.1.3. Synthesis by reaction of phenyldiazomethane with 1diazo-1-phenylethane.…”

Reactions of hydrazones and hydrazides with Lewis acidic boranes

“…refluxing in ethanolic hydrogen chloride for several hours. 16 More interesting is that, in our case, the borane adduct of hydrazone 4 is also generated in the reaction. Previously, the hydrazine bisborane N 2 H 4 (BH 3 ) 2 has been postulated as a good hydrogen storage material containing 16.9 wt% hydrogen.…”

Synthesis of substituted 7,12-dihydropyrido[3,2-b:5,4-b']diindoles: rigid planar benzodiazepine receptor ligands with inverse agonist/antagonist properties

“…Since the pyridodiindoles (3,4-indolo-d-carbolines) are similar in structure to the ß-carbolines (Scheme II), 6ethylpyridodiindole 33 and methylated indole derivatives 34-3636 (Table I) were prepared for comparison to the SAR of the d-carbolines.30 Similar to trends in the SAR of d-carbolines, an ethyl group at position 6 (33) resulted in a net reduction of ligand potency. Moreover, 7-methylpyridodiindole 34 was found to be significantly less potent than dihydro analogue "All dihydropyridodiindoles were tested as the hydrochloride salt.…”

“…This afforded the 7,12-dihydropyridodiindole 2 as the sole product in 88% yield, which resulted from an acid-mediated Fischer indole cyclization (Scheme I). 33 The 1-substituted and 3-substituted pyridodiindoles were readily prepared by heating 1 in a 5-10-fold excess of the appropriately substituted phenylhydrazine for 4-6 h at 160 °C. This usually furnished the intermediate benzamide derivative 3 via a thermally mediated Fischer indole cyclization (Scheme I).…”

“…' Analyzed for C, H, and N. dPreviously cited in ref 31. 'See ref 33 for experimental details. 1 Measured against [3H]flunitrazepam, and Ro 15-1788 (10 µ ) was used to define nonspecific binding.…”