Phenanthridone, preparation

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. 

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. 

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). 

Following the original report that hydrazoic acid converts phen-anthraquinone into phenanthridone,87 Stephenson has shown that a 10 M excess of hydrazoic acid is required to avoid increasing the amount of diphenamic acid at the expense of phenanthridone.88 Even this excess of acid converts 4-nitrophenanthraquinone into a mixture of nitrodiphenamic acids, with only a trace of 5-nitrophenanthridone.89 Both 3,4-benzophenanthridone (48) and 7,8-benzophenanthridone (49) have been prepared from chrysenequinone (47) by the scheme outlined below.90... 

Examples of the preparation of hydrogenated phenanthridones via the Beckmann rearrangement have also been reported. Thus, the action of thionyl chloride on the oxime (57) gives a hexahydrophen-anthridone which must be 58, since on dehydrogenation 4-methyl-phenanthridone (59) is formed.103 Perhydrofluorenone is a minor... 

Hydrazoic acid attacks the carbonyl and carboxy groups of fluorenone-l-carboxylic acid simultaneously giving mainly 4-amino-phenanthridone together with some acidic material, presumably phenanthridone-4-carboxylic acid.89 The latter is best prepared by prior protection of the carboxy group with pyrrolidine.106 112 The increase in strain associated with the conversion of 4,5-dimethyl-fluorenone into 1,10-dimethylphenanthridone is reflected in the relatively low yield (50%) obtained under Schmidt conditions.22... 

Derived diazonium compounds, in general, undergo the usual interconversions although yields are often rather low. Reference has already been made (see p. 404) to an unsuccessful attempt to prepare 3-hydroxy-6-methylphenanthridine from the amine.11 1-Amino-phenanthridone gives only impure 1-hydroxyphenanthridone on diazotization in sulfuric acid followed by heating,127 but the method is more satisfactory in the case of 2-amino-iV-methylphenanthri-done.126 Phenanthridones are usually more readily available than the corresponding 6-amino compounds, but as a structural proof phenan-thridone itself has been obtained by the action of nitrous acid on 6-aminophenanthridine.150... 

Photolysis of styrylquinolones (130) affords benzo-[k]phenanthridones whilst the benzylidene lactones (131), from which the styrylquinolones may be prepared, give 6-oxobenzo[k]phenanthridine-7-carbo3 1ates on irradiation in methanol (V. Arisvaran et al,. Synthesis, 1981, 821). 

Cycloaddition reactions are not only used to construct quinoline derivatives, but also used to elaborate them. Phenanthridone derivatives were prepared by Diels-Alder reactions with 2(l )-quinolones and butadiene derivatives <01CPB407>. The synthesis of pyranoquinolines via a formal [3 + 3] cycloaddition was also reported. For example, aldehyde 66 was treated with piperidine and acetic anhydride to afford the corresponding iminum ion which undergoes a [3 + 3] cycloaddition with 4-hydroxyquinolone (67) to give pyranoquinoline 68. Intermediates such as pyranoquinoline 68 were used in the total syntheses of simulenoline and huajiaosimuline <01JOC1049>. 

The phenanthridone alkaloid, lycoricidine 64 fScheme 12.32). is known to possess cytotoxic activity. Based on the retrosynthetic analysis as discussed in Section 12.3.2 f Scheme 12.18T the Chida group reported the total synthesis of lycoricidine starting from d-glucose in which the Ferrier carbocyclization reaction was enployed as the key reaction. For the preparation of the cyclohexene unit in lycoricidine, d-glucose was converted into 2-azido-d-altropyranoside derivative 122 via epoxide 121 fScheme 12.31T Protection of the diol moiety in 122 afforded 68, which was transformed into 5-enopyranoside 67 by the action of DBU. Ferrier carbocyclization of 67 with 1 mol% of Hg(OCOCF3)2, followed by p-elimination,... 

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