Phenanthridones

The major product of this reaction is the yellow, labile, 1 2 molar adduct (134) corresponding to the pyridine series, along with a small amount of a colorless compound (139) which is discussed later and some phenanthridine oxalate. The labile adduct is converted to the stable isomer (135) on heating in quinoline or pyridine. Oxidation of both these adducts with potassium permanganate in acetone gives phenanthridone as the major product. In the case of the labile adduct. 

The system 35a + 35b is in equilibrium in solution the interconversion formally involves migration of the benzoyl group from an oxygen to a nitrogen atom. Benzoylation of the sodium salt of phenanthridone at — 20° gives rise to the 0-benzoyl derivative 35a, which is stable at low temperatures. When heated alone or in CH2C12 solution, 35a converts to the JV-benzoyl derivative 35b, the form that is obtained directly by benzoylation at room temperature. The compounds with X = p-MeO or p-Cl show similar melting behaviors (80). 

More recently Wege and coworkers synthesized the Nifedipine analogue Af-hydroxy-phenanthridone (50) from Af-benzyloxybiphenyl-2-carboxamide (48) by cyclization to Af-benzyloxyphenanthridone (49) followed by catalytic reductive removal of the benzyl group (Scheme 9). ... 

A vinylogous indole derivative like 264 reacts with DMAD to give a phenanthridone derivative (267) (Scheme 42). An interesting case of the reaction of an enamine system is observed in the case of the 2H-pyrrolizine (268), which gives a mixture of the azepino[2,l,7-crflpyrrolizine derivative (271) and the 1 1 adduct (275) (Scheme 43) 164,165 reaction of 3-ethoxycarbonylmethylene-3 -pyrrolizine, on the other hand, yields a pyrrolo[2,l,5-croom temperature, the primary adduct (278) is isolated and undergoes thermal cyclization to 281 (Scheme 44). ... 

Ozonolysis of phenanthridine in methylene chloride followed by alkaline peroxide oxidation gives quinoline-3,4-dicarboxylic acid (2%) and phenanthridone (39 23%) as the main product (Scheme 27) (64JA38). 

Oxidation of 6-methylphenanthridines with potassium dichromate in acetic acid results in oxidative loss of the methyl group, the product being the phenanthridone (e.g. 67 Scheme 62) (61JCS3771). If a second methyl group is present it remains unchanged. Selenium dioxide oxidizes the 6-methyl group to the aldehyde. 

Nuclei for tricyclic antidepressants and tranquilizers, for example clomacran (89) (64USP3131190), almost invariably contain the three rings fused in a linear array. An exception to this general rule is fantridone (90), an antidepressant obtained by alkylation of the anion of phenanthridone with 3-chloro-iV,iV-dimethylpropylamine (68BRP1135947). Similar activity is shown by a relatively simple quinoline derivative (91), which is derived from 2-chloroquinoline and piperazine (70GEP2006638). 

Preparative routes to 5/7-dibenz[6,e]azepine-6,11 -diones (morphanthridinediones) are based mainly on the cyclization of 2-aminobenzophenone-2 -carboxylic acids and their derivatives (55LA(594)89). Studies on a-aminodiphenyImethane-2 -carboxylic acid reveal that cyclization to 5,11 -dibenz[6,e ]azepinone (188) is much slower at room temperature than the cyclizations of the analogous 2-aminobiphenyl-2 -carboxylic acid and the 2 -aminobiphenylacetic acid (189), which at room temperature cyclize spontaneously to phenanthridone and dibenz[f>,d]azepin-6-one (190) respectively (61JOC1329). The hydrogen bromide-induced cyclization of dinitriles (Scheme 16) is adaptable to the synthesis of 2-amino-7-bromo-3//-azepines and 5H-dibenz[c,e]azepin-7-ones (67JOC3325). Apparently, for unsymmetrical dinitriles cyclization is such as always to give the azepine with the bromo substituent attached to the carbon of the a,j8-unsaturated nitrile as exemplified in Scheme 16. 

Similar transformations have been reported for quinoline 1-oxide and 3-, 4-, 5-, 6-, 7-, and 8-methylquinoline 1-oxides in aqueous solution,151 for quinoxaline 1-oxide,152 for adenine 1-oxide,153 and for phenanthridine 5-oxide (181 R = H) which yields phenanthridone (182 R = H).154... 

A number of related reactions are worthy of mention. Benzanilide (334) is converted into phenanthridone (335) by irradiation in benzene in the presence of iodine.362 Cyclodehydrogenation is also observed in the anilides of indole-2-carboxylic acid and indole-3-carboxylic acid on irradiation in acetone.363 Irradiation of diphenyl-amine304 and certain of its JV-substituted derivatives365 yields the corresponding carbazole. The mechanism of this reaction differs from... 

Nonoxidative photocyclization also occurs in 2-diphenyl isocyanate (367) to form carbazole (368) and phenanthridone (369).390 The mechanism of this transformation is uncertain, and, in fact, little attention has been given to the photochemistry of isocyanates. Carbazole is also the principal product of nonsensitized photolysis of 2-azidobiphenyl391 the reaction presumably involves the cyclization of an intermediate nitrene. 

Crinasiadine, N-Methylcrinasiadine. Two simple phenanthridone alkaloids, crinasiadim (27) [12] and N-methylcrinasiadine (28) [13] (Scheme 6) were prepared [9] from a commor intermediate, the chloro compound 21. 

It was shown by monitoring the reaction by NMR spectroscopy that the overall process to involve the following steps firstly, a ring closure of 125 to the phenanthridone 126 (Scheme 17), secondly, the formation of 127 by thermal loss of the N-protecting group, thirdly, diaxial opening of the oxirane 127 to the triolbenzoate 128, fourthly, hydrolysis of 128 to the tetrol 129 and finally, a slow dealkylation of the O-benzyl ether 129 to (+)-pancratistatin (94). 

Several syntheses of phenanthridone derivatives related to the aromatization products of narciclasine and lycoricidine and apparently designed to further support the structural revision have been completed. In a photochemical synthesis starting from 368 the compound 360 was obtained yielding on debenzylation narciprimine (356), whereas from 369 in an analogous way arolycoricidine (361) was prepared. Also, starting from the amide 370 through photocyclization to 362 via 363 a compound identical with natural permethylisonarciprimine (357) was obtained (81). 

More recently, a detailed paper discussed the synthetic problems presented by the syntheses of the substituted phenanthridones of the narciprimine-isonarciprimine series along with the synthesis of per-methylisonarciprimine 357 (79). The potential pharmacological interest of narciclasine and other Amaryllidaceae metabolites has been suggested (79a, 79b). 

Phenanthridone has been obtained by the action of carbon dioxide on 2-lithioaminobiphenyl49 and by cyelizing 2-biphenylyl isocyanate with aluminum chloride,50 the latter reaction appearing to be a general one. Thus, cyclization of 5-bromo-2-biphenylyl isocyanate gives 2-bromophenanthridone,51 while reaction of the isocyanate (17) with trifluoroacetic acid is a key stage in the synthesis of dihydroxy-crinene (18).52... 

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