Phenanthridine reduction

Phenanthridine (74) was converted by NBS into the 2-bromo derivative (40%) (55JA6379), but the bromine-sulfuric acid-silver sulfate reagent gave low yields of 1-, 4-, and 10-bromophenanthridines in the ratio (1 6.4 9.5), a reactivity order which contrasts with that found in nitration (1 > 10 > 4 > 2) (69AJC1105). Phosphoryl chloride converted phenanthridine 5-oxide into the 6-chloro derivative, but when that position was blocked by a phenyl substituent, the reductive chlorination process gave a 2-chloro compound (84MI2). 

Reductive cyclization of 2-formyl-2 -nitrobiaryl compounds gives phenanthridine derivatives.136 The Stille coupling of nitroarylstannanes with 2-bromobenzaldehyde are used for the preparation of the requisite 2-formyl-2 -nitrobiaryls. Subsequent treatment of biphenyl derivatives with zinc dust in acetic acid gives the phenanthridine derivatives as shown in Eq. 10.80.137... 

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]. 

The hydrogenation of phenanthridine at 250 °C under pressure in the presence of a sodium-rubidium catalyst in benzene is reported to give octahydrophenanthridines. Acridine similarly forms a variety of reduction products (71JOC694). 

The cyclic borates (758) are useful alternatives to benzanilides in the photochemical synthesis of phenanthridines. Irradiation, followed by reduction with lithium aluminum hydride, gives phenanthridines in good yield, the borate ring maintaining the correct stereochemistry (78CC884). 

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)]. 

Chlorophenyl)-l-phenylpyrazole (65) affords a good yield of pyra-zolo[l,5-/]phenanthridine (66) on reduction [Eq. (55)] in DMF containing... 

Mol. wt. 181-233, m.p. 124°. The reagent is prepared by reduction of phenanthridine with lithium aluminum hydride in refluxing ether (75% yield).1... 

The iV-methylamine (160) (R = Me) gives a complex mixture of products when treated under the same conditions.186 It was shown subsequently that prior reduction of the anils used as starting materials is, in fact, unnecessary since in the presence of potassamide in liquid ammonia (o-chlorobenzylidene)aniline forms phenanthridine in excellent yield, and the analogous anils from p-toluidine and a-naphthylamine undergo ring closure under similar conditions. In view of the known trans geometry of the anils and the unlikelihood of trans-cis equilibration under these conditions this reaction deserves further study.187 Potassamide in liquid ammonia also converts 2-bromo-iV-ethyl-3 -hydroxybenzanilide (162) into a mixture of iV-ethyl-3-(164) and N-ethyl-1 -hydroxyphenanthridone (165), probably via the aryne (163).188... 

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... 

Phenanthridine was reported initially to exhibit a single (probably two-electron)272 reduction wave in dimethylformamide containing tetraalkylammonium salts as supporting electrolytes.272-274 Polaro-graphic half-wave potentials for the reduction of A-heteroaromatics in dimethylformamide (DMF) are controlled by electron transfer... 

The first reduction wave for phenanthridine jV-oxide in dimethyl-formamide (at 25°) appears at — 1.774 (vs. s.c.e.) in good agreement with the HMO energy of the lowest vacant orbital277 a mechanism for the reduction has been proposed.278 No esr signal could be detected during controlled-potential electrolysis at the appropriate potential, perhaps because of the relative instability of the anion radical. This behavior, which is paralleled by isoquinoline, contrasts sharply with that of the oxides of other polynuclear N-heteroaromatic systems (e.g., quinoline and acridine).277... 

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... 

Further examples of the reduction of the carbon-nitrogen link by means of lithium aluminum hydride have been reported,90, 332 and sodium borohydride has been used for the same purpose in the reduction of a number of 6-alkyl-l,2,3,4,4a,10b-hexahydrophenanthri-dines.42 Quaternary phenanthridinium salts form IV-alkyldihydro-phenanthridines on treatment with lithium aluminum hydride.333... 

The reduction of phenanthridine to 5,6-dihydrophenanthridine (90, R = H) was readily accomplished by reaction with lithium aluminum hydride in ethereal solution.118 The same dihydrophenanthridine resulted from the lithium aluminum hydride reduction of 6-chloro-phenanthridine or phenanthridone,1180 thus confirming the position of saturation of the product.119 It is of interest to note that molecular complexes of phenanthridine and dihydrophenanthridine were not observed as products in this reduction as was the case in the metal hydride reduction of phenazine.119... 

Phenanthridine methiodide underwent a facile reduction to N-methyl-5,6-dihydrophenanthridine (90, R = CHS) with lithium aluminum hydride in ethereal solution.120 It was found that the use of... 

Electroreduction of l-(4-fluorophenyl)-5-(2-halogenophenyl)tetrazoles (89), when the halogen substituent is Cl, Br or I, leads to cleavage of the carbon-halogen bond to give a phenyl radical (equation 52). Competition then follows between intramolecular radical substitution giving 7-fluorotetrazolo[l,5-f]phenanthridine (90). Further reduction of the... 

The proportion of the liberated nitrogen which was converted to N0X was also lower for the phenanthridine than the acridine char. It is believed that the balance of nitrogen is released as N2 due to the reduction of N0X by C and/or CO. A high concentration of carbon... 

Reduction of the cis lactam 61 with LAH afforded the cis amine 60, which was also obtained from either oxidative photocyclization of the enamide 56 or nonoxidative photocyclization of the bromoenamide 56, followed by successive reductions. Oxidative photocyclization of the enamide 56 in the presence of iodine afforded the corresponding dehydrolactam 59 in good yield, which is a useful intermediate for further conversion to various aromatized benzo[c]phenanthridines, the basic structure of many aromatic alkaloids (19,20). 

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. ... 

On reduction of aryl halides the initially formed ion radical decomposes to halide ion and aryl radical [13-16]. In appropriate substituted compounds the radical may in an intramolecular attack effect a ring closure. This is exemplified in the reductive cyclization of 5-(2-chlorophenyl)-l-phenylpyrazole to pyrazolo[l, 5-/]phenanthridine [13] and iV-allyl-... 

Keay, J. G., The Reduction of Nitrogen Heterocycles with Complex Metal Hydrides, 39, 1. Keene, B. R. T., Tissington, P., Recent Developments In Phenanthridine Chenustry, 13, 315. 

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