Dimeric quinolins

The first dimeric quinoline alkaloid, pteledimerine, was isolated recently from the root bark of Ptelea trifoliata (cf. Vol. 10, p. 80). Several related compounds have now been found in the same species, and the structure of one of them, pteledimeridine (16), was elucidated mainly by means of H n.m.r. and mass spectroscopy.9 The two dimeric alkaloids are isomeric and differ only in the nature of the furoquinolone portion, which has angular annelation (2-quinolone) in pteledimeridine and linear annelation (4-quinolone) in pteledimerine. 

Table 24.10 Occurrence of dimeric quinolin-2(l//)-one/4(l//)-one alkaloids in Rutaceae species ...

No data is available oti the biosynthesis of dimeric quinoline alkaloids, which have been found in Rutaceae (Table 24.10) the proposed biogenetic pathway represents modes of Diels-Alder addition of prenyl dienes, as summarized for vepridimerine A (26, a-Ha) and B (26, p-Ha) in Scheme 24.6 [112]. These isomers suggest that dimerization of a quinoline diene takes place during isolation or that dimerization occurs nonenzymaticaUy in the plant tissue. 

These alkaloids constitute two small groups, and only a few derivatives occur sporadically in microorganisms and higher plants. For example, 8-hydroxyquino-line-4-carbaldehyde oxime (J.3.1) and broussonetine (J.2.1), a dimeric quinoline, were isolated from B. zeylanica (Moraceae) (151), (+)-tuberosine B (J.1.2) from... 

Selenium dioxide oxidation of 7,8-dihydro-5(6//)-quinolinone semicarbazone gave, in addition to the expected 4,5-dihydro selenadiazoloquinoline 95 (analogous to sulfur derivative 76), the oxidized l,2,3-selenadiazolo[4,5-/]quinoline 96, which, when heated to 210°C for 30 min, gave the dimeric [l,4]diselenino [2,3-/ 5,6-/ ]diquinoline (95JHC177). 

CN/CC replacements were also observed when the pyrimidine ring is part of a bicyclic system. Reaction of quinazoline with active methylene compounds, containing the cyano group (malonitrile, ethyl cyanoacetate, phenylacetonitrile) gave 2-amino-3-R-quinoline (R = CN, C02Et, Ph) (72CPB1544) (Scheme 12). The reaction has to be carried out in the absence of a base. When base is used, no ring transformation was observed only dimer formation and SnH substitution at C-4 was found. 

Unlike quinoline A -oxide, which yields a mixture of quinolin-2(l//)-one and 4-(4-quinolyl)quinolin-2(l//)-one, 7-methoxy-4-phenylquinoline A -oxide (47) with phenylsulfonyl chloride and dimcthylsulfoxonium metliylide affords the l//-l-benzazepine 48 (a rare example of an 7V-unsubstituted l//-l-benzazepine), together with small amounts of the dimeric 1//-1-benzazepine 49 and 2,2-bis(7-methoxy-4-pheny]-2-quinolyl) (8% mp 276 C).166... 

Irradiation of the dimers 1 of quinoline 1-imines 2 gives stable 1H-1,2-benzodiazepines. Selected examples are given.122... 

With radical ions, the dimerization equilibrium is strongly influenced by the solvation and association of radical ions with counter ions. It has been shown that the free ions dimerize much more slowly than do the respective contact ion pairs e.g., the quinoline radical anion does not dimerize in the powerfully solvating hexamethylphosphoramide, but it does dimerize rapidly in tetra-hydrofuran (160). Thus, two equilibria should be distinguished (160), viz. 

In the reaction of di-(5 -0-monomethoxytrityhmdine-3 -/ -nitrophenylethyl)-pyro-phosphate with a 5 -OH nucleoside component, simultaneous addition of quinoline-8-sulfochloride and 3-nitro-1,2,4-triazole is recommended to obtain a high yield of the fully protected dimer. 1521... 

Both chloro ligands of [Pt2Cl2(/u-dppm)2] are replaced by quinoline, 1-methylimidazole, and 4-t-butylpyridine, but only one is replaced by 2,4,6-trimethylpyridine.109 All of these platinum(I) dimers and pt2(PPh3)2(/i-dppm)2] display solid-state luminescence at room temperature and long emission lifetimes at 77 K.109... 

Grignon-Dubois and coworkers have shown that reduction of a quinoline using zinc and acetic acid in THF gives the dimeric compound 3-177 via intermediate 3-176 (Scheme 3.47) [70J. Usually, a mixture of the syn- and anti-products is formed the substituent has some influence on the regioselectivity of the dimerization and cydization step. With R = H and R = 6-Me, only the benzazepine 3-177 were produced, by a head-to-head dimerization. 

Clark et al. [81] determined the time course of A-acetylation of primaquine by Streptomyces roseochromogenous and Streptomyces rimosus by quantitative high performance liquid chromatographic analyses of the culture broths. The A-5-bistri-fluoroacetyl derivative of primaquine was used as an internal standard in the analysis for the quantitation of primaquine A-acetate in microbial culture broths. S. roseochromogenous forms the highest level of primaquine A-acetate at 24—36 h after substrate addition, while S. rimosus is slower in its acetylation, peaking at 3 days after substrate addition. The formation of a novel dimeric compound from the reaction of primaquine with 8-(4-phthalimido-l-methylbutylamino)-6-methoxy quinoline is also reported. 

A kinetic study has been carried out in order to elucidate the mechanism by which the cr-complex becomes dehydrogenated to the alkyl heteroaromatic derivative for the alkylation of quinoline by decanoyl peroxide in acetic acid. The decomposition rates in the presence of increasing amounts of quinoline were determined. At low quinoline concentrations the kinetic course is shown in Fig. 1. The first-order rate constants were calculated from the initial slopes of the graphs and refer to reaction with a quinoline molecule still possessing free 2- and 4-positions. At high quinoline concentration a great increase of reaction rate occurs and both the kinetic course and the composition of the products are simplified. The decomposition rate is first order in peroxide and the nonyl radicals are almost completely trapped by quinoline. The proportion of the nonyl radicals which dimerize to octadecane falls rapidly with increase in quinoline concentration. The decomposition rate in nonprotonated quinoline is much lower than that observed in quinoline in acetic acid. 

Br oxH = quinolin-8-ol) suggests that both complexes exist as magnetically isolated dimers in the solid state. The complexes [Fe(met)(OH)X],2MeOH (X = Cl or NO, met = DL-methioniney" have been isolated and evidence... 

The equilibrium between radical-anion and dimer for pyridine and quinoline has been examined in a number of aprotic solvents. Radical-anions of pyridine dimer-ise rapidly in liquid ammonia in tire presence of alkali metal ions [15] In hex-amethylphosphoramide with alkali metal counter ions, the monomer is detectable in an equlibrium concentration [16], The monomeric species can be stabilised by substituents and 2- or 4-cyanopyridines give radical-anions which persist in liquid ammonia while 3-cyanopyridine radical-anion dimerises with a rate constant of 2 x 10 [17], Quinoline radical-anion is stable in hexamelhylphosphoramide [16] but in liquid ammonia it dimerises irreversibly [18]. 

Reduction of quinolines in acid solution at a lead cathode or by dissolving zinc leads to attack on the heterocyclic ring with the formation of 4,4-coupled products, together with the tetrahydroquinoline [82,83]. In the case of 2- and 4-methyl substituted quinolines, dimeric products are obtained in 10 90 % yields. In these processes, dimerization of the one-electron addition product is in competition with further reduction to give the 1,4-dihydroquinoline, The latter is an enamine and it... 

Quinolines are reduced in alkaline solution at a lead cathode or by sodium and alcohol to another cla.s.s of dimeric product [85,86]. The meso-4,4 -hydrodimer is again an intermediate in the process. It undergoes slower conversion to the imine tautomer under alkaline conditions and the intramolecular aldol condensation between one imine function and the remaining enamine function leads to the product 23 [86]. 

Closely related to solvent effect, and governed by the same or similar factors, are the phenomena of dimerization via self-association, and association with other species present in solution, such as cations or anions, in definite stoichiometric proportions. Studies of such associations lead to further knowledge of such interactions involving the more complex bases in nucleic acid structures. One of the earliest workers to study dimerization systematically was Shindo (59CPB407), who examined the broad N—H stretch region 3300-2400 cm-1 in the IR spectra of a variety of substituted pyridin-2-ones and quinolin-2-ones in perfluorocarbon mulls and CC14 solution. 

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