Acridine A-oxides

During photolysis of acridine A-oxides 54, two isomeric indolotro-pones (56a,b) are formed, among other products (Scheme 14 75CL401, 75CPB2818 79T1273). As confirmed by UV spectra, the isomerization of 54 passes through intermediate 55. 

Cyano- and 10-chloro-acridine A-oxides yield 1,2-oxazepines on photolysis in benzene (Scheme 237). When the 10-substituent is methyl the unstable 1,2-oxazepine undergoes electrocyclization to a benzisoxazoline (320). Secondary photoproducts may be formed by direct irradiation of N- oxides or by rearrangement of the primary photoproduct. 

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. 

Pyridine, the quinoline and acridine A-oxides readily form salts (e.g. hydrochlorides (27) and picrates) which have been used for their characterization. Basic salts of the type (ArNO)2HX are also known the structure (28) is indicated for 2-picoline 1 -oxide hemihydro-bromide based on IR evidence. A list of these salts has been compiled (B-71MI20500). 

The nitration of acridine (9 R = H) in sulfuric acid is an unsatisfactory reaction in that the mixed isomers produced are difficult to separate. The main product is 2-nitroacridine (9 R = N02) the order of reactivity being 2>4>1>3 and product ratio 130 25 5 1 respectively (B-66MI20600). Acridine A-oxide, however, undergoes nitration at 0°C to produce 9-nitroacridine A-oxide (10) (60JCS3367). 

Acridine, halogenation, 59, 295 Acridine A-oxide, halogenation, 59, 295 Acridine, 9-benzyl-, nitration, 58, 251 Acridine, 9-phenyl-, nitration, 58, 251 Acridin-9(10//)-ones, see Acridones Acridizinium ion, see... 

For some time Tanasescu held the view that a group of compounds obtained by reaction of o-nitrobenzaldehydes with aromatic compounds in concentrated sulfuric acid, containing one oxygen atom more than the arylanthranils formed concurrently, were anthranil-A-oxides (e.g., 172).2QQ 201,206 Lehmstedt opposed this, and put forward the A-hydroxyacridone structure (173),213 312 which Tanasescu himself later adopted, although he preferred the tautomeric hydroxy-acridine- A-oxide structure (174).195 198 199 313... 

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... 

Attempts failed to prepare 9-azatriptycene (304) analogously from acridine or acridine A -oxide. However, the targeted compound can be readily obtained, in 54% yield, by treating 9-(2-chlorophenyl)-9,10-dihydroacridine with potassium amide for 90 min in refluxing liquid ammonia (Scheme 1-237). 9-Azatriptycene (304) shows all attributes of a basic amine. For example, it combines with acids and with methyl iodide, whereas the noncaged analogue triphenylamine even resists protonation by concentrated sulfuric acid. 

Epoxidation of propene and oct-l-ene was effected with tran5-Ru(0)j(TMP)/ O ll atm)/water-CH2Cl2. After some 40 turnovers in a day, the deactivated form of the complex, Ru(C0)(TMP).H20 was detected (vide infra). Use of (l-( C)-oct-l-ene suggest that, in part at least, the carbon atom of the Ru(CO)(TMP) formed derives from the first C atom of the octene [591]. For styrene epoxidation by trans-Ru(0)2(TMP)/(LN0)/CgH (LNO=N-oxides of 2,3,5,6-tetramethylpyrazine, acridine, 2-methylquinoline and 3,6-dichloropyridazine) the mono- and bis-A-oxides of tetramethylpyrazine were the most effective co-oxidants [586]. 

Quinoline 1-oxide undergoes nucleophilic attack by ozone to yield a hydroxamic acid (128), and 40% of the starting iV-oxide is recovered (Scheme 74). When an excess of ozone is employed the aldehydes (129) and (130) are obtained. Formation of these products has been attributed to electrophilic attack by ozone rather than further oxidation of (128), because in a separate experiment (128) yielded carbostyril on treatment with ozone. Isoquinoline 2-oxide yields 2-hydroxyisoquinolin-l-one, and acridine 10-oxide gives 10-hydroxyacridone and acridone in a similar manner to the above. Likewise, phenanthridine 5-oxide affords mainly 5-hydroxyphenanthridone. Quinoline 1-oxide undergoes oxidation by lead tetraacetate as shown (Scheme 75). 

Irradiation of acridine A7-oxide takes a different course depending on the solvent system, as shown in Scheme 121 (69LA(723)95, 68TL4519). 

The unstable dibenz[c,/][l,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous Af-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

A number of studies have been directed specifically at the acridine nucleus. The effect of substituents in the 9-position in acridine (V-oxides on Rf values for thin-layer chromatography (TLC) is measured by ap,198 and there is also a relation between this parameter and the N—O stretching frequencies. The effect of substituents on the basicity of acridine and the possibility of amine-ketimine tautomerism in 9-aminoacridines have been evaluated, taking quinoline as a model... 

Apart from investigations of the mechanism of the Clemmensen reaction ensuing from the formation of 3, work on the reactivity of nitrenes (Section IV,A,4), as well as studies of photochemical rearrangements of acridine Af-oxides (Section IV,B), have led to 4-azaazulenes. 

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). 

A number of different Ar-oxides have been investigated polaro-graphically, such as the A-oxides of quinoline,252 acridine,244 pyra-zine,254 quinoxaline,243 phenazine,246 and adenine,248 and the influence of substituents has been discussed. 

A number of different A-oxides have been investigated polarographically, such as N-oxides of quinoline [421], acridine [422], pyrazine [423], benzimidazole [424], quinoxaline [415], phenazine [416], and adenine [425], and the influence of substituents was discussed. 

Anthranil (119) and benzyne (from oxidation of 9 with lead tetraacetate) afford acridine (5%)81 depending on the sequence of bond forming and breaking, an oxygen-bridged cycloadduct and/or acridine N-oxide (120) may be intermediates in this reaction (Scheme 15), although 120 is known to react with benzyne in a different sense (Section IX). The addition of benzyne to oxazoles leads, ultimately, to anthracene derivatives in high overall yield.82b... 

The reaction of 2-fluoro-5-nitrobenzaldehyde with a wide variety of aryl-amines gives mixtures of the corresponding 2-arylamino-5-nitrobenzaldehydes and the related anils. Both aldehydes and anils underwent acid-catalysed cyclization to the corresponding 2-nitroacridines (80). The acridine N-oxide (81) was obtained as the major product by the reaction of < -fluorobenzyl cyanide with p-chloronitrobenzene in methanolic potassium hydroxide. ... 

We have prepared pyrido[3,2-a]acridines, 20 and 21 (96TH1), by Lewis acid-catalyzed cyclization of enamines 18, formed by the condensation of 6-aminoquinoline 16 with 2-cyano- 17a (Z = CN) or 2-ethoxycarbonylcyclo-hexanone 17b (Z = COaEt), to give the tetrahydropyrido[2,3-a]acridines 19. Oxidation of these tetrahydro derivatives, with palladium on charcoal, gave the fully aromatic systems 20 (Scheme 5). Oxidation of the amino derivative 19a also resulted in the formation of some of the deaminated product 21. 

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) ... 

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