Phenanthroline-9,10-diones

Unexpectedly strong intermolecular hydrogen bonding has been reported by IR spectroscopic studies for tetrahydro-4,7-phenanthroline-l,10-dione-3,8-dicarboxylic acids, which exist in the oxo-hydroxy form 165 in both solid state and in solution [78JCS(CC)369].Tlie conclusion was based on comparison of B-, C-, and D-type bands for 165 and their dimethyl esters (detection of hydrogen bonding) and on analysis of IR spectra in the 6 /xm region (pyridine- and pyridone-like bands). 

Fig. 43.4 Pentamethylcyclopentadienyl(1,10-phenanthroline-5,6-dione)chloro rhodium (111) hexafluorophosphate (11).

The oxidation of 1,7-phenanthrolines containing a hydroxy, methoxy, or amino group in the 5- or 6-position to 1,7 phenanthroline-5,6-dione (51) by nitric acid has been patented.249 250 Its monosemicarbazone has also been patented.251 l,7-Phenanthroline-5,6-dione (51) gives the diepoxide (52) on reaction with diazomethane.226... 

Phenanthroline is oxidized by alkaline potassium permanganate to 2,4 -bipyridyl-3,3 -dicarboxylic acid14 and to l,8-phenanthroline-5,6-dione in 28% yield by nitric-sulfuric acid mixtures.252 The latter reaction also yielded some nitrated products and 2,5-diazafluorenone. 

The well documented oxidation of 1,10-phenanthroline (4) to 2,2 -bipyridyl-3,3 -dicarboxylic acid (53) by alkaline permanganate has been repeated. It is now found that 4,5-diazafluoren-9-one (54) is consistently a coproduct of the reaction in 20% yield.253 This provides a convenient route to this hitherto difficultly accessible compound. The formation of 4,5-diazafluoren-9-one almost certainly occurs by way of the intermediate, but not isolated, l,10-phenanthroline-5,6-dione, which is known to undergo a benzilic acid type rearrangement in the presence of hydroxide ions to give the diazafluorenone. This rearrangement of l,10-phenanthroline-5,6-dione has recently been studied further.115 Under some conditions 5,6-dihydro-5,6-dihydroxy- 1,10-phenanthroline can be isolated with the diazafluorenone. 

There has been considerable interest in the preparation of 4,7-phenanthroline-5,6-dione and its relatives due to their antibacterial activity. Patents225,249, 250,256,257 have appeared covering the oxidation of 5- or 6-substituted hydroxy-, methoxy-, or amino-4,7-phenanthrolines to... 

Reactions of 4,7-phenanthroline-5,6-dione have been the subject of considerable study. It is reduced to 5,6-dihydroxy-4,7-phenanthroline by Raney nickel hydrogenation226,249 or by aromatic thiols in benzene,262 and oxidized by permanganate to 3,3 -bipyridyl-2,2 -dicarboxylic acid.263 It forms bishemiketals with alcohols226 and diepoxides with diazomethane.226 The diepoxides by reaction with hydrochloric acid form diols of type 57, R = Cl, which on oxidation with lead tetraacetate give 3,3 -bipyridyl diketones of type 58, R = Cl. Methyl ketones of type 58, R = H, are also obtained by lead(IV) acetate oxidation of the diol 57, R = H, obtained by lithium aluminum hydride reduction of 57, R = Cl. With phenyldiazomethane and diphenyldiazomethane the dione forms 1,3-dioxole derivatives,264,265 which readily hydrolyze back to the dione with concomitant formation of benzaldehyde and benzophenone, respectively. 

As a 1,2-diketone, 4,7-phenanthroline-5,6-dione reacts readily with ethylenediamine258 and 5,6-diamino-4,7-phenanthroline266 to give pyrazine derivatives. Several related condensations have also been reported.258,267,268 It also condenses with enamines,269 trialkyl and dialkyl phosphites,262 and guanidine carbonate.270... 

Phenanthroline-5,6-dione forms a dioxime that is advocated as a derivative suitable for its analytical estimation.271 It reacts with / -piperidinoethoxyamine to form the corresponding monooxime, which has useful biological properties.272,273... 

The radical anion of 4,7-phenanthroline-5,6-dione has been prepared electrolytically, and its ESR spectrum was recorded.274... 

Unlike 1,7-, 1,10-, and 4,7-phenanthrolines, which give nitrated products, the predominant product of the reaction of 1,8-phenanthroline (2) with mixed nitric and sulfuric acids is the 5,6-dione (59) (28%). Both the 5-nitro- (60) and 6-nitro-1,8-phenanthrolines (61) are formed, but in much lower yield ( 6-7%). 2,5-Diazafluorenone (62) is also present (6%).252 Bromination of 1,8-phenanthroline affords the 5- and 6-bromo derivatives and the 5,6-dibromo analog.275... 

The nitration of l,4-dihydro-5-methoxy-2-trifluoromethyl-4-oxo-l,10-phenanthroline gives a nitrated product, presumably the 6-nitro derivative, along with the corresponding 5,6-dione.38... 

The most important biologically active 4,7-phenanthroline is 4,7-phenanthroline-5,6-dione (112), known as phanquone, Entobex, which is used medicinally as an amoebicide. It is active also against bacteria, protozoa, and other parasites.390 Several closely related derivatives are also highly active.224, 250, 251,258-261, 390,538,539 Phanquone is used particularly in treating amoebic dysentery and is often used in combination with other antibiotics.540-542 The effect of 4,7-phenanthroline-5,6-dione and its relatives on cell metabolism has been investigated.543 It has also been reported to be mutagenic.544... 

Perrhenyl chloride, see Rhenium chloride trioxide, 4039 Perylenium perchlorate, 3784 1,10-Phenanthroline-5,6-dione, 3572 Phenethyl alcohol, see Benzeneethanol, 2978 Phenoxyacetylene, 2915... 

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