Acridine nucleophilic addition

An alternative approach to the tetracyclic systan forms the heterocyclic ring by nucleophilic addition of an amine to a carbonyl group. Application of the Friedlander quinoline synthesis to various methoxy-1-tetralones yields the methoxy-5,6-dihydrobenz-[c]acridines, which are dehydrogenated to the aromatic compound by distillation from palladium-charcoal (M. Croisy-Delcey et al. J. med. Chem., 1983, 26, 303). 

X. Huang, T. Zhang, Cascade nucleophilic addition-cyclic Michael addition of arynes and phenols/anilines bearing ortho a,p-unsaturated groups fecile synthesis of 9-functionalized xanthenes/acridines, J. Org. Chem. 75 (2010) 506-509. 

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. ... 

Nucleophilic Reactions of Aromatic Heterocyclic Bases Heterocyclic aromatic compounds containing a formal imine group (pyridine, quinoline, isoquinoline, and acridine) also react readily with nucleophilic reagents. A dihydro-derivative results, which is readily dehydrogenated to a new heteroaromatic system. Since the nucleophile always attacks the a-carbon atom, the reaction formally constitutes an addition to the C=N double bond. An actual localization of the C=N double bond in aromatic heterocyclic compounds is incompatible with molecular orbital theory. The attack of the nucleophilic reagent occurs at a site of low 77-electron density, which is not... 

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. 

Air oxygen can also play the role of oxidant in the amination reactions. It is well known that 1,4-benzoquinone reacts with aliphatic amines in the presence of copper acetate to give 2,5-bis(dialkylamino)-l,4-benzoquinones in good yields [64]. The reaction mechanism involves nucleophilic 1,4-addition followed by oxidation of intermediate aminohydroquinones with air oxygen. The reactions of this type, which are also inherent to ort/io-quinones, have been reviewed earlier [65, 66]. It is interesting that amination is also possible in case of some heterocyclic phenols, which are first converted in situ into the corresponding ort/io-quinones. This approach has successfully been exploited to aminate ort/io-quinones generated from quinolines, indoles, acridines, isoquinolines, quinoxalines, benzofurans, and benzothiazoles (Scheme 15) (for review, see [65, 66]). 

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