Acridines, 9-substitution oxidative

The nitrations of a wide range of substituted quinoline N-oxides under various conditions [82HC(382)447] show the usual pattern of substituent effects superimposed upon the pattern resulting from the use of nitric acid/sulfuric acid at low temperature (5,8-positions), weaker mixtures of these acids at high temperature (4-position), or acyl nitrates (3-position). Nitration of acridine N-oxide by nitric acid/sulfuric acid occurs in the 5-position (60JCS3367). 

Related 1,3-oxazepines have been obtained from irradiation of many other heterocyclic A-oxides including pyridine A-oxides, isoquinoline A-oxides, quinoxaline A-oxides, quinazoline A-oxides, phenanthridine A-oxides, benzophenazine A-oxides, and acridine A-oxides.4 However, the reported yields are variable and have generally been higher for phenyl and other aryl-substituted derivatives. 

Dibenz[c/][l,2]oxazepines (81) are obtained as the principal products from the photolysis of the substituted acridine A-oxides (80) in benzene. The electron-withdrawing substituents help stabilize the antiaromatic 1,2-oxazepine moiety. On refluxing in benzene, (81b) is converted mainly back to the starting A-oxide, while on heating (81a) in aqueous acetonitrile at 60 °C, the main product is an... 

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 most frequently reported oxidation reaction of isatins is the oxidation with alkaline hydrogen peroxide to give anthranilic acids. This procedure has been both as a proof of structure of isatins and as a method of synthesis of anthranilic acids. The oxidation has been applied to alkyl 8"10 11 23 33>38-40>46 49>50>118halo n.18.35.36-38-40.47.10 .11 . 119,136,240 alkoxy,26,a8 39,47,75.io7,ii8,i36 trifluoromethyl,33,38,137 and nitro8,120,217 isatins. Use of N-substituted isatins led to N-substituted anthranilic acids.66,71,125,158,169,243 In the oxidation of 5-bromo-l-(y-carbethoxypropyl)-7-ethylisatin, 60 was isolated after treatment with ethanol and acid.11 Oxidation of isatin derivatives 61 led, after treatment with diazomethane, to the acridine derivatives 62.67 Application of this oxidation method to 7-hydroxyisatins gave rise to benzoxazo-lones (63).2,41... 

In the case of terpyridine and acridine derivatives, the bis(methylamines) are the most convenient intermediates. Substituted 4/-phenyl-2,2/ 6/,2"-terpyridines were prepared by reacting (ii)-propenons and iV-[2-(pyrid-2 -yl)-2-o octln l p ridinium iodide with ammonium acetate in acetic acid or in methanol. The terminal pyridine moieties were oxidized with 3-chloroperbenzoic acid to iV, A" -dio idcs followed by modified Reisserty-Henze reaction to obtain 6,6"-dicarbonitriles. The bis(methylamines) were obtained by reduction of the 6,6"-dicarbonitriles withborane (scheme 8 (Mukkala et al., 1993)). 

Fluorescence studies of the commercially important l,3-diphenyl-2-pyrazoline derivatives have been extended to a wide range of phenyl- and methyl-substituted derivatives. The fluorescence yields in non-polar solvents are all close to unity, with the exception of l,3,5,5-tetraphenyl-2-pyrazoline. This is not the case in methanol, when a large variation in yields is observed.85 (See the section on oxidation for other photochemical processes in these compounds.) By an examination of the fluorescence spectra and fluorescence excitation spectra of 9-amino-acridine at 4.2 K, the fine-structure fluorescence spectrum of the neutral molecule has been identified and investigated using laser excitation.88... 

Reactions of dibenzopyridines show analogies with pyridine, quinoline and isoquinoline. Acridine and phenanthridine are A-protonated by strong protic acids, iV-alkylated by alkyl halides and A-oxidized by peroxy acids. Electrophilic substitutions of acridine often result in disubstitution at the 2- and 7-positions (e.g. nitration giving 3), whereas those of phenanthridine occur at different positions (e.g. nitration mainly at the 1- and 10-position yielding 4 and 5) ... 

A-Methylacridones are synthesized from 2-(A-methyl-A-phenylamino)benzaldehydes in DMF using Sc(OTf)3 as the catalyst and Na2S04 as additive via dehydrogenative cyclization. There are two primary processes in the transformation the aldehyde first coordinates with Sc(OTf)3 and induces the aromatic electrophilic substitution (5eAt) reaction to form the active intermediate Af-methyl-acridin-9-ol, which is then quickly oxidized in situ to afford the acridones. ... 

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