Phenanthridines, formation

Photochemical dehydrogenation of azomethines 43 42 (Scheme 20) dihydro compounds are initially formed and aromatization is effected with either oxygen or iodine. Phenanthridine formation by this method is improved by the presence of BF3 <1988TL5213>. 

The acyl residue controls the formation and stability of the carbonium ion. If the carbonium ion is destabilized (by electron withdrawing groups), then cyclization to the phenanthridine nucleus will be sluggish. The slower the rate of cyclization, the greater the chance of side reactions with the cyclization reagent. Therefore, the yield of the phenanthridine will depend on the relative rates of cyclization and side reactions, which is controlled by the stability of the carbonium ion. 

The first compound containing a telluroazepine ring, ll-(4-methylphenyl) dibenzo[d,/][l,4]telluroazepine 62 was obtained in 21% yield upon heating p-xylene solution of 9-azido-9-(4-methylphenyl)telluroxanthene at 130-140°C (87KGS279). Other products of this pyrolitic process are the imine 63 (32% yield) and phenanthridine 64 (21% yield). Formation of the latter implies extrusion of the tellurium atom from dibenzotelluroazepine 62. 

It would be expected that the stabilization of the adsorbed species by an extended conjugated system should increase with the number of aromatic rings in the adsorbed azahydrocarbon. However, data suitable for comparison are available only for phenanthridine, benzo-[/]quinoline, and benzo[h] quinoline. The large difference in the yields of biaryl obtained from the last two bases could be caused by steric interaction of the 7,8-benz-ring with the catalyst, which would lower the concentration of the adsorbed species relative to that with benzo[/]quinoline. The failure of phenanthridine to yield any biaryl is also noteworthy since some 5,6-dihydrophenanthridine was formed. This suggests that adsorption on the catalyst via the nitrogen atom is possible, but that steric inhibition to the combination of the activated species is involved. The same effect could be responsible for the exclusive formation of 5,5 -disubstituted 2,2 -dipyridines from 3-substi-tuted pyridines, as well as for the low yields of 3,3, 5,5 -tetramethyl-2,2 -bipyridines obtained from 3,5-lutidine and of 3,3 -dimethyl-2,2 -... 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

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). 

A six-membered ring is formed in the reduction of 2-nitrobiphenyl-2 -carboxylic acid68 or 6,6 -dinitrobiphenyl-2,2 -dicarboxylic acid.69 In the former case a phenanthridine is formed, in the latter a 4,9-diazapyrene. Similarly, a seven-membered ring is obtained when 2-nitro-2 -isothiocyano-biphenyl (15) is reduced in acidic solution with the formation of 6-mercapto-dibenzo[d/]-l,3-diazepine 3-oxide (16)70 [Eq. (28)]. 

Certain aromatic imines undergo a similar cyclodehydrogenation to the phenanthridine. Benzylideneaniline (330) yields phenanthridine (331) only in sulfuric acid,355 whereas diphenylmethyleneaniline cyclizes in the presence of oxygen or iodine.356 Cyclizations have also been reported in Schiff s bases formed from a- and /J-naphthylamine357 and from 4-aminoquinoline,358 and in the mesomeric betaine 4,5-diphenyl-2-mercapto-l,3,4-thiadiazolium hydroxide.359 Irradiation of the anil of 2-aminonaphthalene (332) in ethanol, however, leads to incorporation of ethanol and the formation of 3-phenylbenzo[/]-quinoline (333).860 Additional photoproducts are obtained when the photolysis is carried out in w-hexanol.361... 

The formation of a-naphthylamines 140 and 153 in reactions of 2-benzopyrylium salts with ammonia and primary amines is not always an undesirable process. The synthetic application of a-naphthylamines is connected with the chemistry of benzo[c]phenanthridine alkaloids 132 (78MI1 81H474). 

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

The Friedel-Crafts cyclization of the acid chloride (19a) occurs normally at — 70°, with the formation of the azacycloheptenone (20), but the sole product at 5° is 5,6-dihydro-5-tolylsulfonylphenanthridine (21). Similarly, the related acid (19b) gives phenanthridine when heated with polyphosphoric acid at 60°.53 Presumably a 5,6-dihydro-phenanthridine is formed which undergoes dehydrogenation in the reaction medium (cf. Das Gupta et aZ.48). 

The formation of a phenanthridine lactone by the persulfate oxidation of 2 -cyanobiphenyl-2-carboxylic acid is interesting in that little is known of the addition of radicals to the C=N system. The mechanism proposed below (Scheme 1) also accounts for the occurrence of fluorenone as a by-product.64... 

The decomposition of 2,2,-bis(azidomethyl)biphenyl in boiling biphenyl ether gives a mixture of phenanthridine and 5/7-dibenz[c,e]-azepine (46). Hydrazoic acid is evolved and the following mechanism has been proposed (Scheme 2) (although attempts to confirm carbene formation were not successful).93... 

The conversion of 9-methylfluorenol into 6-methylphenanthridine proceeds in abnormally low yield owing to the formation of a neutral by-product (25%),117 which has been identified as the phenanthridine... 

Treatment of 2-(l-naphthylaminomethylene)-l-tetralone (143) with formic acid provides 7,8-dihydro-3,4 9,10-dibenzophenanthri-dine (144),177 although the simpler 2-anilinomethylene-l-tetralone (145) does not give a phenanthridine derivative under similar conditions.30 177 The observation30 that ring closure of 145 with hot formic acid, followed by treatment with ammonia, gives 5,6,8,9-tetrahydro-dibenz[c7t]acridine has been confirmed, and is rationalized in terms of an intermediate xanthylium formate. The nitrogen atom in the final product comes from the ammonia used in the reaction.177... 

The formation of the adduct (218) from phenanthridine-5-oxide and dimethylketene in benzene is accompanied by deoxygenation... 

Aminative replacement in compounds other than those bearing halogen atoms are uncommon, but 6-aminophenanthridine is easily prepared by heating 6-phenoxyphenanthridine with urea296 and 6-anilinophenanthridine has been obtained by the action of aniline on the 6-phenoxy compound.268 The formation of 6-anilinophenanthridine from phenanthridine iV-oxide and phenyl isocyanate probably proceeds via an initial 1,3-dipolar addition, followed by nucleophilic substitution and decarboxylation (Scheme 4).309... 

The carbon-nitrogen double bond of phenanthridine can be reduced selectively by hydrogenation over Raney nickel, and attempted reductive dechlorination of 6-chloro derivatives in the presence of this catalyst normally results in the formation of the corresponding 5,6-dihydro compounds.106 Hydrogenations over palladium catalysts are more successful.203 325 Desulfurization of phenanthridinthione... 

Synthetic and degradative use has been made in several instances of the easy decarboxylation of phenanthridine-6-carboxylio acids.30, 80, 324 The corresponding iV-oxide is decarboxylated by heating in aqueous sulfuric acid.77 Phenanthridine-3,8-dicarboxylic acids are more resistant to decarboxylation, which can be achieved (in poor yield) by heating with copper powder in quinoline.194 The usual carboxyl derivative inter con versions (esterification, amide formation, ester and amide hydrolyses, etc.) proceed normally with both phenanthridine-6-carboxylic acid and its A-oxide,77, 232, 352 although an unsuccessful attempt to prepare 6-acetylphenanthridine from the acid with methyllithium has been reported.232... 

The oxidation of chars prepared from nitrogen-containing precursors has been investigated. Chars produced from the nitrogen-containing compounds acridine and phenanthridine were oxidized at atmospheric pressure at temperatures of 773-873 K. The relative rates of nitrogen and carbon release and the formation of NO have been determined in relation to char nitrogen content and precursor type. 

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