Synthesis and ring closure reactions of pyrido[3,2,1-jk]carbazol-6-ones

Abstract

4-Hydroxy-5-phenylpyrido[3,2,1-jk]carbazol-6-ones (4, 5), which were obtained from carbazoles 1 and malonates 2 or 3, were converted to reactive intermediates such as 4-chlorides 9 or 4-tosylates 10, which gave in turn 4-azido-5-phenyl derivatives 11. 5-Alkyl-4-azides 11 were not obtained in this manner; however a new one-pot azidation reaction was developed starting from 4-hydroxy derivatives 4 which gave azides 11 in good yields. 4-Azido-5-phenyl derivative 11f cyclized on thermolysis to the indole 12. The thermal behaviour of the azides 11 was studied by thermoanalytical methods (DSC).J. Heterocyclic Chem., 42, 85 (2005).Pyrido[3,2,1-jk]carbazol-6-one is part of the heterocyclic skeleton of many natural products (e.g., strychnos alkaloids such as strychninolones and brucinolones [2], picrasidin Q [3] and olivacine alkaloids [4]). It possesses the biologically interesting combination of indole and 2-pyridone structures. Moreover, some derivatives have found interest in pharmacological [5] or in dye chemistry [6]. Our interest is focused to 4-hydroxy-5-substituted pyrido[3,2,1-jk]carbazol-6-ones (4, 5) which possess 2 reactive positions: the hydroxy group at C-4, which can be substituted by various nucleophiles, and the CH-acidic proton at C-5, which reacts with a large number of electrophiles. In this contribution we want to report an improved synthesis of 4-hydroxy-5-substituted pyrido-[3,2,1-jk]carbazol-6-ones, the acetylation, tosylation and the nucleophilic exchange of the hydroxy groups.The synthesis of some 4-hydroxy-5-substituted pyrido[3,2,1-jk]carbazol-6-ones 4 is described in the literature in a few cases either by thermal condensation of malonates 2 with carbazole 1a at about 300 °C with moderate yields [7], or by thermal condensation of dichlorophenylmalonates with carbazole 1 at 260 °C with good yields [8]. We adopted the cyclocondensation methods of malonates with 1,3-dinucleophiles earlier described for quinolones and related compounds [9] for the synthesis of 4-hydroxy-5-substituted pyrido[3,2,1-jk]carbazol-6-ones 4 and 5. The first reaction step leads in a condensation reaction at about 200 °C to the monoanilides of the carbazole 1a with the malonates 2; the end of this reaction step can be easily observed by the end of ethanol evolution; further thermolysis at higher temperatures (300-350 °C) gives, by elimination of the second equivalent of ethanol, an intermediate α-oxo ketene which attacks in an electrophilic reaction the ortho-position of the aromatic ring to cyclize to the pyrido[3,2,1-jk]carbazol-6-ones 4. The yields of this reaction type are within 60-90% except with the octadecyl malonate 2j; in this case only 24% of 4j was obtained. It was also possible to carry out this reaction in one step without interruption when a 1:1 mixture of the malonate and the carbazole 1a was heated for 12 hours in refluxing diphenyl ether solution which limits the thermolysis temperature to 253 °C. The yields are within 60-80% comparable to the stepwise reaction; the workup however is easier and the purit...

One-Pot Conversion of 1-Bromo-β-carboline and 1-Bromocarbazole into Pentacyclic­ Compounds by Suzuki Cross-Coupling Followed by Spontaneous Cyclization

“…11 Further approaches utilized heteroannulation reactions on 5,6-dihydrocanthin-4-one 14 for the preparation of pyrimidino and quinolino congeners of C and thermolysis of an azidoarene to generate a indolo-canthin-6-one. 15 Isoxazole-and pyrrole-annulated canthin-4-ones were obtained by intramolecular 1,3-dipolar cycloadditions, 16 whereas an attempted intramolecular hetero-Diels-Alder cycloaddition of a vinylindole failed to give the desired pentacyclus of type C. 17 Markgraf et al 11 reported an unsuccessful attempt to prepare benzocanthin-6-ones of type C starting from 1-chloro-β-carboline and 2-methoxycarbonylphenylboronic acid, which should comprise a Suzuki cross-coupling 18 and subsequent intramolecular N-acylation at the pyrrole nitrogen. In a project aimed at the synthesis of pentacycles of types C and D with high flexibility in ring E and without the problems associated with obtaining poorly separable isomeric mixtures, we reinvestigated the latter approach.…”

Syntheses, Substitution and Cyclization Reactions of 7a,8,9,10,11a-Hexahydro-pyrido[3,2,1-jk]carbazoles With a Strychnos Alkaloids Partial Structure

“…The exchange of the chloro against an azido group forms 4-azido-5-nitro compound 14 in moderate yields (Scheme 4). In the last years we investigated a series of cyclization reactions of azides with reactive orthosubstituents [19][20][21][22]. The conditions for the thermolysis reaction of 4-azido derivative 14 was investigated by differential scanning calorimetry (DSC) to obtain the information on the cyclization temperature to obtain the planned furoxane 15 and get information for possible further decomposition reactions.…”

Syntheses and Reactions of 5-Unsubstituted 11b-Methyl-1,2,3,11b-tetrahydro-pyrido[3,2,1-jk]carbazoles Having a Strychnos Alkaloids Partial Structure

“…Found: C,48.91;H,3.48;N,3.51. 4-Chloro-11b-methyl-1,2,3,11b-tetrahydro-6H-pyrido[3,2,1-jk]carbazol-6-one (18): A solution of 4-hydroxy-pyridocarbazolone 9 (1.00 g, 40 mmol) in phosphoryl chloride (15 mL) was heated under reflux for 15 minutes. After cooling, the reaction mixture was poured onto ice/water (100 mL) and brought to pH = 4-6 with 2 M aq.…”

“…The thermal cyclization of ortho-phenyl azides in pyridocarbazoles proceeds via nitrene intermediates [17] and is known to produce indolo products [18]. The conditions of the ring closure reaction of the 4-azido derivative 22 was investigated by differential scanning calorimetry (DSC) to obtain the information on the cyclization temperature to furoxane 23 and possible further decomposition.…”