Phenanthridines, reduced

Thermolysis of 2,2 -bis(azidomethyl)biphenyl (33) in an inert solvent produces a mixture of phenanthridine (21 %) and 5//-dibenz[c,e]azepine (29% bp 138—140°C/0.08 Torr). The yield of dibenzazepine is increased to 57% by carrying out the thermolysis under reduced pressure over glass beads.86 The mechanism of this unique reaction has been discussed. 

Reaction conditions used for reduction of acridine [430,476, partly hydrogenated phenanthridine [477 and benzo f]quinoline [477 are shown in Schemes 38-40. Hydrogenation over platinum oxide in trifluoroacetic acid at 3.5 atm reduced only the carbocyclic rings in acridine and benzo[h]quinoline, leaving the pyridine rings intact [471]. 

A similar approach using N- vinylisoquinuelidines has led to stereospecific syntheses of reduced isoquinolines and phenanthridines (e.g. Scheme 51) (79JOC124, 81JOC4643). 

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)]. 

Hydroxy-8,9-methylenedioxyphenanthridine, [10]. The method developed by Kessar et al. [11] for phenanthridines and related compounds was applied to the synthesis [10] of 3-hydroxy-8,9-methylenedioxyphenanthridine (22) (Scheme 5). Thus, the benzylidene aniline 23, prepared from 6-chloropiperonal and 3-benzyloxyaniline, was reduced to the secondary amine 24. Treatment of 24 with excess lithium diisopropylamide furnished, on work-up, the benzyl ethers 25 (22%) and 26 (6%) respectively. Catalytic debenzylation of the former generated 22. 

Successful cyclizations involving attack on reduced rings have also been reported in the presence of polyphosphoric acid the originally formed hexahydrophenanthridines (15) all undergo spontaneous partial dehydrogenation to the corresponding 7,8,9,10-tetrahydro-phenanthridines (16).48... 

In the case of phenanthridine itself, this has been achieved by reduction with lithium aluminum hydride211 presumably stoichiometric quantities were employed since the hydride can reduce phenanthridine to its 5,6-dihydro derivative.212 In a procedure which has been adopted more widely, an excess of lithium aluminum hydride is employed and the resultant 5,6-dihydrophenanthridine is dehydrogenated catalytically or,213 better, with an excess of chlor-anil.102, 200 Oxidation with aqueous potassium permanganate has been employed for the second stage,139 but the method does not appear to be general.22... 

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... 

RuHCl(PPh3)3] and [RuH2(PPh3)2(PPh2C6H4)] can reduce polyaromatic compounds under hydrogen. Quinoline (67) and phenanthridine (69) are converted to 1,2,3,4-tetrahydroquinoline (68) and 9,10-dihy-drophenanthridine (70). ... 

Heteroaromatic cations undergo reduction when treated with 1,4-dihydronicotinamide. An early study showed that the 10-methylacridinium ion (87) was rapidly reduced in a redox reaction to the 9,10-dihydro adduct by 1,4-dihydronicotinamides (M Scheme 18). A variety of systems including py-ridines, isoquinolines, quinolines and phenanthridines have been studied using this and related procedures. The selective reduction of pyridinium and quinolinium salts with 1-benzyl-1,2-dihydro-isonicotinamide (89) has been achieved. The selective conversion to the thermodynamically more stable 1,4-dihydro species (90 Scheme 18) is rationalized by the reversibility in the formation of the kinetic products (i.e. the 1,2-adducts) in the presence of pyridinium ions. In the pyridinium case 1,6-di-hydro adducts were also observed in some cases. Reactivity in such systems is sometimes hindered due to hydration of the dihydropyridine system. This is particularly so in aqueous systems designed to replicate biological activity. Dihydroazines derived from isoquinolines and 3,5-disubstituted pyridines have been reported to overcome some of these difficulties. ... 

Additional evidence for photomodified toxicity in plants is provided by Wieg-man et al. s azaarene phototoxicity work with the diatom species, Phaeodactylum tricornutum [25,93,118]. Wiegman et al. irradiated azaarenes with environment-ally-realistic intensities of UVR. The EC50 values (for reduced photosynthesis) for quinoline, isoquinoline, acridine, and phenanthridine were reduced when exposure solutions were irradiated prior to the introduction of diatoms. The reduction of EC50 concentrations ranged from a factor of three to a factor of 300. Effect concentrations for these azaarenes ranged from approximately 230 gg to 1 mg 1 [... 

On acid catalysis, 2-aminobiphenyl-2 -carboxylic acids 31 cyclize affording phenanthridones 32, which are reduced by zinc or LiAlH4 to phenanthridines 34. The aminobiphenylcarboxylic acids 31 are accessible from the corresponding nitro compounds 33 by reduction. 

A common intermediate in the synthesis of benzo[c]phenanthridines is the 2-aryl-l-tetralone, which provides rings A, B, and D of the alkaloid nucleus. In 1973, two independent research groups reported the synthesis of nitidine via the 3,4-dihydro-2-(3,4-dimethoxyphenyl)-6,7-methylenedioxy-(2/7)-naphthalone 29 (Scheme 2). The synthesis of this intermediate was arrived at by two different routes. Kametani ei al. (73JHC31) reduced 3-(3,4-methylenedioxyphenyl)proprionate 21 to the corresponding alcohol 22 with lithium aluminium hydride, which was then converted to the chloride 23 with thionyl chloride. After production of the nitrile 24 by reaction with sodium cyanide and subsequent hydrolysis to the carboxylic acid 25, Friedel-Crafts cyclization of the acid chloride 26 afforded the tetralone intermediate 27. Reaction with l-bromo-3,4-dimethoxybenzene 28 in the presence of sodium amide yielded the tetralone intermediate 29 in an overall yield of 4%. 

Reduced phenanthridines have been prepared from anilines and derivatives of cyclohexanone. In the first reported example, Borsche obtained 6,9-dimethyl-7,8,9,I0-tetrahydrophenanthridine (130a) in 15% overall yield by condensing 6-acetyl-3-methylcyclohexanone with aniline and cyclizing the resultant anil (129a) with sulfuric acid. Although the anil (129b) of 2-acetylcyclohexane-l,3-dione cyclizes in... 

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