Abstract:A short new route to the pyrido[2,3,4-kl]acridine ring system has been developed from readily available quinoline precursors involving two key steps: ( i ) a palladium(0)-catalysed Suzuki cross-coupling reaction of 4-chloroquinolines with arylboronic acids, and ( i i ) an intramolecular nitrene insertion reaction of the nitrenes derived from 4-phenyl-5azidoquinolines.
“…The presence of strong IR absorption band in the υ max 2,110–2,119 cm −1 (asymmetric) and υ max 1,220–1,260 cm −1 (symmetric) regions further distinguished systems 3 from the amino derivatives 4 . The analogous 4-phenyl-5-azidoquinolines on the other hand, previously afforded in refluxing xylene pyrido[2,3,4- kl ]acridines via an intramolecular nitrene insertion reaction [ 25 ]. The 3-aryl-4-azido-7-methoxyquinolin-2(1 H )-ones prepared from the reaction of 3-aryl-4-(chloro/tosyloxy)-7-methoxy-quinolin-2(1 H )-ones with sodium azide in refluxing DMF were also found to undergo thermolytic ring closure to afford the 5-alkyl-3-methoxy-11 H -indolo[3,2- c ]quinolin-6(5 H )-ones [ 26 ].…”
Palladium-catalyzed Suzuki-Miyaura cross-coupling of 2-aryl-4-azido-3-iodo-quinolines with arylboronic acids afforded the corresponding primary 4-amino-2,3-diarylquinolines in a single-pot operation along with symmetrical biaryls and traces of the 2,3-diaryl-4-azidoquinolines. A plausible mechanism, which implicates palladium hydride species in the reduction of the incipient 2,3-diaryl-4-azidoquinolines to afford the 4-amino-2,3-diarylquinolines is proposed.
“…The presence of strong IR absorption band in the υ max 2,110–2,119 cm −1 (asymmetric) and υ max 1,220–1,260 cm −1 (symmetric) regions further distinguished systems 3 from the amino derivatives 4 . The analogous 4-phenyl-5-azidoquinolines on the other hand, previously afforded in refluxing xylene pyrido[2,3,4- kl ]acridines via an intramolecular nitrene insertion reaction [ 25 ]. The 3-aryl-4-azido-7-methoxyquinolin-2(1 H )-ones prepared from the reaction of 3-aryl-4-(chloro/tosyloxy)-7-methoxy-quinolin-2(1 H )-ones with sodium azide in refluxing DMF were also found to undergo thermolytic ring closure to afford the 5-alkyl-3-methoxy-11 H -indolo[3,2- c ]quinolin-6(5 H )-ones [ 26 ].…”
Palladium-catalyzed Suzuki-Miyaura cross-coupling of 2-aryl-4-azido-3-iodo-quinolines with arylboronic acids afforded the corresponding primary 4-amino-2,3-diarylquinolines in a single-pot operation along with symmetrical biaryls and traces of the 2,3-diaryl-4-azidoquinolines. A plausible mechanism, which implicates palladium hydride species in the reduction of the incipient 2,3-diaryl-4-azidoquinolines to afford the 4-amino-2,3-diarylquinolines is proposed.
“…1 This provides a simple and general synthesis of 2-cyanobenzothiazoles from anilines in two steps and, if desired, the cyano group can be cleanly removed in one step with concentrated hydrochloric acid. 3 By analogy with many earlier reactions, 1 5 would be the expected thermolysis product of the iminodithiazole 6 formed from 8-amino-6methoxy-4-phenylquinoline 12 and Appel salt 1. These highly cytotoxic marine natural products include the kuanoniamines and dercitins.…”
mentioning
confidence: 90%
“…2 We envisaged that kuanoniamine A 4 could be derived from the thiazoloquinoline 5 by nitration at the quinoline 5-position and conversion of the nitro group into an azide via the primary amine, followed by azide decomposition and nitrene insertion into the phenyl ring, as demonstrated for a closely related compound. 3 By analogy with many earlier reactions, 1 5 would be the expected thermolysis product of the iminodithiazole 6 formed from 8-amino-6methoxy-4-phenylquinoline 12 and Appel salt 1. This amine was prepared as shown in Scheme 1.…”
mentioning
confidence: 90%
“…The nitro compound 8 was reduced almost quantitatively with stannous chloride in ethanol to the amine 9 which was acetylated in high yield. Treatment of the 4-chloroacetamide 10 with phenylboronic acid under standard conditions, 3 but with 5 rather than 3 mol% of catalyst, gave 96% of the 4-phenyl-quinoline 11 which was hydrolysed with hot concentrated hydrochloric acid to give the amine 12 as a not very stable oil. Treatment of this (and other 8-aminoquinolines) with Appel salt 1 and pyridine in DCM at room temperature in the usual way 1 gave very low yields of the imino-1,2,3-dithiazoles like 6.…”
8-Aminoquinolines and 4,5-dichloro-1,2,3-dithiazolium chloride 1 give N- (quinolin-8-yl)iminodithiazoles 6 and 15a-c which undergo a novel thermal rearrangement to give imidazo[4,5,1-ij]quinoline-4-thiones 13 and 16a-c respectively. Normal cyclisation of the dithiazolo group onto the carbocyclic ring to form a benzothiazole (e.g. 6→5) is averted by peri-participation of the quinoline ring nitrogen. This participation results in formation of the imidazole ring and delivery of a sulfur atom to the quinoline 2-position; delivery of this sulfur appears to be intramolecular and possibly involves a [1,3] sigmatropic shift of a carbon-sulfur bond (Scheme 4). The same overall reaction is observed, at much lower temperature, on treatment of the quinolinyliminodithiazoles (15a and c) with sodium hydride in THF (Scheme 5), thus providing a ready route to imidazo[4,5,1-ij]quinoline-4-thiones. These thiones are rapidly oxidised to the corresponding 4-ones, such as 25; 25 was also formed, rapidly and quantitatively, from the analogous iminodithiazole derivative 23 of 8-aminoquinolin-2-one in boiling ethanol (Scheme 6). Mechanisms are proposed for all the new rearrangements reported.We have shown that thermolysis of 5-arylimino-1,2,3dithiazoles 2, easily prepared from primary aromatic amines and 4,5-dichloro-1,2,3-dithiazolium chloride † (Appel salt) 1,
“…These compounds often exhibit an array of biological activities and a particular chemical behavior that have attracted the interest of many natural product chemists and biochemists. Since 1983, when the structure of amphimedine, the first of these marine alkaloids was reported, many additional examples have been described, and a number of papers have appeared describing synthetic efforts toward and the total synthesis of pyridoacridine alkaloids. − 1 …”
1-BOC-2-lithio-1,4-dihydropyridines were condensed with 3,4-disubstituted cyclobutenediones to produce 1,2-adducts. Neat thermolysis under oxygen-free conditions produced substituted 1,4-dihydroquinoline hydroquinones in which the tert-butoxy residue of the BOC group was displaced by a phenolic residue, generating an oxazolone ring that functioned to protect both rings of the dihydroquinoline hydroquinone from untimely oxidation. Oxidative aromatization with concomitant loss of the oxazolone ring was achieved using 2 equiv of o-chloranil in acetic acid and provided substituted quinoline quinones in good yields. By use of this strategy, a concise synthesis of the pyridoacridine ring system was achieved.
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