Phenanthridines nucleophilic

Quinoline 1-oxide undergoes nucleophilic attack by ozone to yield a hydroxamic acid (128), and 40% of the starting iV-oxide is recovered (Scheme 74). When an excess of ozone is employed the aldehydes (129) and (130) are obtained. Formation of these products has been attributed to electrophilic attack by ozone rather than further oxidation of (128), because in a separate experiment (128) yielded carbostyril on treatment with ozone. Isoquinoline 2-oxide yields 2-hydroxyisoquinolin-l-one, and acridine 10-oxide gives 10-hydroxyacridone and acridone in a similar manner to the above. Likewise, phenanthridine 5-oxide affords mainly 5-hydroxyphenanthridone. Quinoline 1-oxide undergoes oxidation by lead tetraacetate as shown (Scheme 75). 

Phenanthridine with DMAD in dry methanol yields 471, but if water is present related compounds are also formed.439 In benzene the expected quinolizine 472 and also the oxazine 473 are obtained.440,441 Nucleophilic attack at the carbonyl group of DMAD is uncommon. 

Similar types of nucleophilic substitutions have also been carried out when PIFA is activated by two equivalents of Lewis acids such as trimethylsilyl triflu-oromethanesulfonate (TMSOTf) and BF3 Et20 or heteropolyacid in standard solvents such as CH2C12 and MeCN. These reactions were applied to intramolecular reactions by the same authors leading to biaryls (49) [54-57], quinone imine derivatives (50) [58], and dihydrobenzothiophens (51) [59], which are important structures of bioactive natural products [Eqs. (7)-(9)]. Dominguez and co-workers have expanded the above biaryl coupling reaction to the syntheses of benzo[c]phenanthridine system (52) [60] and heterobiaryl compounds (53) [61] [Eqs. (10,11)]. 

Calculated reactivity indices are at one with qualitative electronic theory in accounting for ready nucleophilic attack at C-6 in the phenanthridine molecule. However, the limited data available on positional reactivities in electrophilic substitutions is not accounted for satisfactorily by any of the available treatments (see later) and it has been pointed out that the simple Hiickel treatment used by some authors,223, 220 is generally inapplicable in heteroaromatic systems.228... 

Although, predictably, C-6 of the phenanthridine ring is susceptible to nucleophilic attack, until recently only qualitative reactivity data were available. New examples of both direct substitutions (hydride ion extrusion) and nucleophilic replacements, notably of halogen atoms, have been reported since the last review.6... 

Ease of nucleophilic attack at C-6 has recently been demonstrated by the virtually quantitative conversion of phenanthridine into 6-methylphenanthridine by means of methylsulfinyl carbanion in dimethyl sulfoxide.316... 

Aminative replacement in compounds other than those bearing halogen atoms are uncommon, but 6-aminophenanthridine is easily prepared by heating 6-phenoxyphenanthridine with urea296 and 6-anilinophenanthridine has been obtained by the action of aniline on the 6-phenoxy compound.268 The formation of 6-anilinophenanthridine from phenanthridine iV-oxide and phenyl isocyanate probably proceeds via an initial 1,3-dipolar addition, followed by nucleophilic substitution and decarboxylation (Scheme 4).309... 

The decreasing reactivity of the most familiar aromatic heterocyclic compounds with nucleophilic reagents may be illustrated by the following sequence quinoxaline > acridine > phenanthridine > isoquinoline > quinoline > pyridine. Acridine is alkylated in the 4-position, phenanthridine and quinoxaline in the a-position, isoquinoline in the 1-position, and quinoline and pyridine in the 2- or 4-positions. Weaker nucleophilic reagents seem to enter the 4-position of the pyridine and quinoline rings. If the addition occurs readily and in good yield, the intermediate dihydro derivative may sometimes be isolated otherwise, the product of the subsequent oxidation results. In synthetic work the dihydro derivative is usually directly oxidized. 

Nucleophilic substitution of phenanthridine always takes place at the 6-position with organolithium compounds, as in the Chichibabin amination and Ziegler reaction. 

The major adducts formed when phenanthridine is allowed to react with dimethyl acetylenedicarboxylate have been reformulated. - An initial Michael-type reaction gives the zwitterion (206) and succeeding reactions depend on the nature of the solvent. Adduct (207) is formed in anhydrous methanol by the addition of a proton and methoxide ion, while in benzene nucleophilic attack on the carbonyl group of a second ester molecule and subsequent cyclization provides 208. Alternatively, reaction at the triple bond of a second molecule of ester followed by ring closure of the new zwitterion gives 209. Other products related to 207 arise if the methanol contains water. 6-Methylphenanthridine with dimethyl acetylenedicarboxylate in benzene gives a mixture of the azepine (210) and tetramethyl 9a-methyl-9aA-dibenzo[a,c]quinolizine-6,7,8,9-tetracarboxylate. The... 

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