Quinolines, isoquinolines and quinoxalines

N-heterocycles (quinolines, isoquinolines and quinoxalines) when a Cp lr catalysts was employed for their reduction in FA/TEA [108]. 

Ketenes are mostly used as common starting materials for structurally diverse mono-spiro- and fused six-membered heterocycles such as lactones, pyrans, pyronones, pyridines, quinolines, isoquinolines, oxazine, quinoxalines, thiazines, oxathines, etc. 

The compounds to be discussed are the quinolines, isoquinolines, cinnolines, quinazolines, quinoxalines, and phthalazines. Once again, this is a family of compounds for which much qualitative, but little quantitative information is available. 

When two fused six-membered rings (naphthalene analogues) are considered, possibilities become very numerous, partly on account of the reduced symmetry of naphthalene, compared with benzene, and also because of the larger number of positions available for substitution. Thus, there are two monoazanaphthalenes, quinoline (8) and isoquinoline (9), four benzodiazines [cinnoline (10), phthalazine (11), quinazoline (12) and quinoxaline(13)], with the two nitrogen atoms in the same ring, and six naphthyridines (e.g. (14), named and... 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Mono- and dilithio derivatives of p-tosylmethyl isocyanide 297a were shown to display interesting reactions. Reaction of the monoanion with unsaturated esters was shown to give pyrrole derivatives . Dianion 297b was found to add to the carbon-nitrogen double bonds of isoquinoline, quinoline and quinoxaline affording compounds 298, 299 and 300, respectively. In the reactions with pyridine iV-oxide and pyridazine iV-oxide, unstable open-chain products 301 and 302 were obtained . 

The ethyl radical directly attacks the heteroaromatic base, while the acetaldehyde acts as a source of acetyl radical. Photochemical oxy-alkylation has also been tried with ethers. The reaction has been successfully carried out with pyridines, quinolines, isoquinolines,cinno-lines, and quinoxalines. Particularly good yields were obtained with caffeine (16) (Scheme 14). ... 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

The H(D) atom abstraction rate constants in durene crystals by the impurity molecules quinoline, isoquinoline, quinoxaline, and quinozaline in their excited triplet state were measured by Hoshi et al. [1990] using the phosphorescence method described above. The transfer occurs in the fragment CH N formed by a methyl group of durene and a nitrogen atom of the impurity molecule. In the interval 300-100 K the activation energy drops from 3.5 kcal/mol to 1.6 kcal/mol. Deuteration reduces the... 

The decreasing reactivity of the most familiar aromatic heterocyclic compounds with nucleophilic reagents may be illustrated by the following sequence quinoxaline > acridine > phenanthridine > isoquinoline > quinoline > pyridine. Acridine is alkylated in the 4-position, phenanthridine and quinoxaline in the a-position, isoquinoline in the 1-position, and quinoline and pyridine in the 2- or 4-positions. Weaker nucleophilic reagents seem to enter the 4-position of the pyridine and quinoline rings. If the addition occurs readily and in good yield, the intermediate dihydro derivative may sometimes be isolated otherwise, the product of the subsequent oxidation results. In synthetic work the dihydro derivative is usually directly oxidized. 

Isoquinoline is more reactive at the 1-position than quinoline is at the 2-position by approximately the same factor by which the 1-position of naphthalene is more reactive than the 2-position this is true also for the N-oxides. Comparison of the rate data for quinoline and quinoxaline (11.15), and the data in 11.59, suggests that replacement of =CH— by =N— accelerates the exchange at the 2- and 3-positions by factors of 135 and 20, respectively. The low reactivity of quinoxaline N-oxide seems anomalous and may be in error. 

A large variety of chloride or sulfonate-substituted heteroarenes can be subjected to iron-catalyzed cross-coupling. This holds true for pyridines, pyrimidines, triazines, quinolines, isoquinolines, carbazoles, purines, pyridazines, pyrazines, quinoxalines, quinazolines, uracils, thiophenes, and benzothiazoles. In the pyridine system the presence of leaving groups of different reactivity has been demonstrated to allow for sequential introduction of different alkyl groups (Scheme 4—220). ... 

The dioxygenase-catalyzed oxidation of heterocyclic arenes occurs predominantly in a carbocycHc ring of the substrate [7], exemplified by the conversion by P. putida UV4 of quinoline, isoquinoline, quinoxaline, and quinazoline to the cw-diol products shown in Fig. 35 [57], but a recent report of the formation of cw-diol 46 (Fig. 36) by oxidation of 2-chloroquinoline by P putida [58] suggests the possibility that furtber products of this t) may become available as new chiral starting materials for synthetic applications. 

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