Phenanthridinium salts

An attempt to generate an amino-aryl carbene 154 from the alkylated phenanthridinium salt 153 (Equation 78) <2006TL531> was unsuccessful due to steric interactions. The actual reaction with a variety of strong, sterically hindered bases/nucleophiles is shown (Equations 79-81). The mesityllithium products proved that a carbene intermediate is not possible. Unlike /-butyl alcohol and hexamethyldisilazane, trimethylbenzene, the conjugate acid of mesityllithium, is not prone to carbene insertion reactions. Electronically this is explained by the planar nature of 153 which serves to lower the lowest unoccupied molecular orbital (LUMO) energy of the iminium moiety. 

Although phenanthridine was discovered in the late nineteenth century1, 2 neither the parent base nor its derivatives attracted attention until useful therapeutic activity was established in certain quaternary phenanthridinium compounds.3 A substantial number of substituted phenanthridines (and many phenanthridinium salts) have now been described and lists of compounds appearing in the literature from 1884 until 1955 are available.4, 6 Phenanthridines have attracted surprisingly little systematic attention, although the system is of considerable theoretical interest and, with its nine nonequivalent carbon atoms, may be expected to provide a rigorous test of molecular orbital reactivity correlations. Naturally occurring derivatives include several Amaryllidaceae and Papaveraceae alkaloids, notably, lycorine, haemanthamine, and chelidonine the chemistry of the phenanthridine alkaloids has been reviewed.6... 

A large number of quaternary phenanthridinium salts have been prepared in the search for biological activity279 and many further examples have been reported since the last review, some obtained by... 

This aspect of the chemistry of phenanthridinium salts has been well reviewed see, e.g., B. A. Newton, Advan. Chemother. 1, 35 (1964). 

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... 

Phenanthridine. Phenanthridine is hydrogenated to the 5,6-dihydro derivative quantitatively over Raney Ni at 20°C and 1 atm H2.105 Phenanthridinium salts were also hydrogenated to the corresponding 5,6-dihydro derivative over platinum oxide or Pd-C in ethanol with addition of a small amount of sodium acetate (eq. 12.53)106 or over platinum oxide in ethanolic hydrogen chloride.107... 

Several JV-(quinonylalkyl)enaminones have served as model compounds for an intramolecular Nenitzescu reaction demonstrating the ambident reactivity of both the enaminone and the quinone. The compounds cyclized unexpectedly, mainly to heterocyclic spiro-compounds146,147. A phenanthridinium salt and benzofuranoazocine are also obtained, depending on the length of the chain connecting the quinone and the enaminone moieties (equation 95). 

The amide (39) affords a low yield of the 6-ary1-5-methyl phenanthridinium salt on treatment with t-butyl lithium (D. Hellwinkel, R. Lenz and F. Lammerzahl. Tetrahedron, 1983, 2073). Formanilides yield phenanthridines on treatment with phosphorus pentachloride (N.S. Narasimhan, toa, ait. )... 

Previous reports have indicated that 2-phenylquinoline A-oxide nitrates at the 4-position. However, it is now clear, although for reasons not yet understood, that the site of nitration varies with the reaction conditions. For example, 2-(3-nitrophenyl)quinoline iV-oxide is always produced, albeit in variable yield (27— 78%), in 80— 95% sulphuric acid regardless of the reaction temperature. In contrast, 4-nitro-2-phenylquinoline JV-oxide is the main product (19—35%) in more dilute (70—75%) sulphuric acid. N-Amino-quinolinium, -isoquinolinium, and -phenanthridinium salts, with base, give not the anticipated N-imides but their dimers, e.g. (106). ° Despite the fact that the 7V-imide monomers cannot be... 

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