Anodic oxidation of 5,10-dihydro-5,10-dimethylphenazine

Summary The compound 5,10-dihydro-5,10-dimethylphenazine (DMPZ) exhibits two succesive reversible, 1-electron oxidation-reduction steps in acetonitrile and propylene carbonate as solvents. This system has been tested by most of the known diagnostic criteria of electrochemical reversibility and found to adhere to all of them unambiguously. This model system provides a reference for comparison of other multi-stage electrochemical processes.When DMPZ is oxidized in solvents or additives which are strong nucleophiles demethylation accompanies the second stage of oxidation. Since this chemical follow-up reaction occurs in aqueous media it is of significance in the biological redox reactions of N-alkylated phenazines.

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Zusammenfassung Die Verbindung 5,10-Dihydro-5,10-dimethylphenazin (DMPZ) weist in Acetonitril und Propylencarbonat als Lösungsmittel zwei aufeinanderfolgende reversible einelektronige Oxydations-Reduktions-Stufen auf. Dieses System wurde mit Hilfe der meisten Kriterien für elektrochemische Reversibilität untersucht und in allen Fällen ein eindeutiges Verhalten festgestellt. Das System kann als Bezug zum Vergleich anderer vielstufiger elektrochemischer Prozesse dienen. Wird DMPZ in Lösungsmitteln oder in Gegenwart von Zusätzen, die stark nucleophil sind, oxydiert, so begleitet eine Demethylierung die zweite Stufe der Oxydation. Da diese Reaktion in wäßrigem Medium verläuft, ist sie von Bedeutung bei biologischen Redoxreaktionen von N-alkylierten Phenazinen.

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Dedicated to Prof. Dr. M. von Stackelberg on his 70th birthday.     

UV spectra of some derivatives of 5,10-dihydrophenarsazine and 5,10-dihydrophenoxarsine

The long-wave band with a maximum above 300 nm in the UV spectra of substituted 5,10-dihydrophenarsazines is interpreted as a transition with intramolecular charge transfer in which the trivalent arsenic atom acts as an electron acceptor. The unshared pair of electrons of As(III) apparently makes its own contribution to the transitions at 240–280 nm.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 768–770, June, 1974.     

Crystal structure of 5,10-(diphenyl)-5,10-dihydrophenarsazine

The crystal structure of the title compound 1 , the first phenarsazine possessing a 10-phenyl substituent to be synthesized, has been determined by single crystal x-ray methods. The crystals are monoclinic, space group P2₁/c with four molecules in a cell of dimensions a = 10.737(3), b = 8.561(4), c = 20.523(7)Å, β = 91.91(3)° and V = 1885(1)ų. The structure has been refined by full matrix least-squares to R = 0.046 using 2087 observed reflections. The folding angle between the two benzo planes is 151.7(4)° indicating that 1 is significantly more puckered than phenarsazines substituted with 5-aryl groups. Moreover, although both phenyl groups adopt a boat-axial conformation, the planes of the aryl rings are nearly perpendicular to each other with the 10-phenyl group adopting the usual conformation (i.e. in the plane bisecting the phenarsazine ring which contains As(5) and N(10)) and the 5-phenyl group assuming the a typical conformation (i.e. very nearly perpendicular to the plane bisecting phenarsazine ring). The bond distance between As and the carbon atom of the 5-phenyl ring is approximately the same as that found in other 5-arylphenarsazine compounds indicating little resonance interactions between As and the aromatic ring in 1 .     

Facile synthesis of 5,10-diaryl-5,10-dihydrophenazines and application to EL devices

[structures: see text] An efficient method for the synthesis of 5,10-diaryldihydrophenazine was developed using a recently developed Pd(0)-mediated cross-coupling reaction. The products 1k and 3c showed excellent properties as hole injection materials in electroluminescent (EL) devices.     

Synthesis of 5,10-dideazaminopterin

The synthesis of 5,10-dideazaaminopterin by two independent routes is described. Condensation of the piperidine enamine of 4-p-carbomethoxyphenylbutyraldehyde ( 4 ) with ethoxymethylenemalononitrile followed by treatment of the resultant arylethylenaminomalononitrile ( 5 ) with methanolic ammonia produced 2-amino-3-cyano-5-p-carbomethoxyphenethylpyridine ( 6 ). Cyclization of the aminocyanopyridine with guanidine afforded 4-amino-4-deoxy-5,10-dideazapteroic acid ( 8 ). Coupling of the pteroate intermediate with glutamate yielded the target 5,10-dideazaaminopterin ( 10 ). Alternatively, reduction of 2,4-diamino-6-formyl-5-deazapteridine ( 11 ) with sodium borohydride gave the 6-hydroxymethyl compound 12 . Conversion to the bromide was followed by alkylation of dimethyl homoterephthalate to afford methyl 4-amino-4-deoxy-10-carbomethoxy-5,10-dideazapteroate ( 14 ). Decarboxylation with ester cleavage (sodium cyanide in dimethyl sulfoxide at 180°) also gave the diaminopteroic acid ( 8 ). 5,10-dideazaaminopterin ( 10 ) was an effective growth inhibitorof folate dependent bacteria, S. faecium and L. casei.     

Formyl substituted phenazine 5,10-dioxides

Two new formyl-substituted phenazine 5,10-dioxides were prepared, 2-formylphenazine 5,10-dioxide and 7-hydroxy-2-phenazinecarboxaldehyde 5,10-dioxide. Nitrones of these aldehydes were prepared as potential antibacterial agents but evaluation in vitro and in vivo did not disclose significant antibacterial activity.     

Mass spectra of 5,10-dihydrophenarsazines, 5,10-dihydrophenarsazine and phenophosphazine oxides,and related heterocycles

The electron-impact-induced fragmentation of eight 5,10-dihydrophenarsazines and three 5,10-dihydrophenarsazine oxides proceeds by loss of the exocyclic arsenic substituents to give the stable ion (II) as the base peak followed by loss of arsenic to give a carbazole species (III). The fragmentation pattern is independent of substituents at either hetero-atom in the cases examined. Dihydrophenophosphazine oxides behave similarly but give as the base peak an ion in which the phosphoryl grouping is retained. 10,11-Dihydro-5-phenyl-5H-dibenzo[b, f][1,4]azarsepine and 2,3-dihydro-1,2-diphenyl-1H-benz [c]azarsole fragment by different pathways. It is suggested that the ability of arsenic and phosphorus to sustain a positive charge by dπ-pπ bonding is the dominating factor in these fragmentations.     

Oxidation of 2-alkyl-5,10-dihydrophenazines

Oxidation of 2-alkyl-5,10-dihydrophenazines afforded 1:1 molecular complexes of the initial compounds with the corresponding 2-alkylphenazines.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004, pp. 1544–1545.Original Russian Text Copyright © 2004 by Bidman.This revised version was published online in April 2005 with a corrected cover date.     

Synthetic access to 5,10-disubstituted porphyrins

A simple acid-catalyzed condensation of unsubstituted tripyrranes with pyrrole and various aldehydes affords 5,10-disubstituted-β-unsubstituted porphyrins by the ‘3+1’ approach in low to moderate yields. A complementary synthesis of similar compounds involves reaction of unsubstituted porphyrin (porphine) with organolithium reagents in good yields.     

A Conveniet Approach to 5,10-Diazasteroids

Dienamine I is a versatile intermediate for the total synthesis of modified steroids, Several examples of its application have been recently communicated from this laboratory³,⁴. We now wish to report the conversion of dienamine I into a 5,10-diazasteroidal system via a sequence of simple steps which are of general application to the total synthesis of this class of steroids⁵.     

A stable radical-substituted radical cation with strongly ferromagnetic interaction: nitronyl nitroxide-substituted 5,10-diphenyl-5,10-dihydrophenazine radical cation

A stable radical-substituted radical ion with strongly ferromagnetic intramolecular interaction (J) between the radical and radical ion sites is an attractive spin building block of organic magnets. We prepared 2-nitronyl nitroxide-substituted 5,10-diphenyl-5,10-dihydrophenazine radical cation, 1+. The 1+ salt was stable under aerated conditions at room temperature and had a large J/kB value (>/=+700 K).     

Polarographic oxidation of some 5,10-dihydrophenazine derivatives

The polarographic anode oxidation of 5-substituted dihydrophenazines in an aprotic medium and an aqueous acetone solution has one-electron or two-electron character. It was shown by means of the electronic and ESR spectra that the intermediates in the anode oxidation of dihydrophenazine and 5-methyldihydrophenazine are cation radicals and that the products of one-electron oxidation of 1,3-dinitro-5-aryl-substituted dihydrophenazines are phenazyl radicals. The final products of anode oxidation are phenazinium salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 548–551, April, 1976.     

Electron-impact induced fragmentation of some 5,10-di- hydrophenazastannines

The electron-impact induced fragmentation of four 5,10-dihydrophenazastannides [(I)-(IV)] was studied by low and high resolution mass spectrometry. Two of the compounds contain tin in the spiro position. To identify energetically favorable reaction paths, low electron-energy scans (12 eV) were taken along with 70 eV ones. The molecular ions fragment by consecutive ejection of the 10-substituents or, alternatively, by loss of R₂Sn. Subsequent fragmentation is accompanied by complex skeletal rearrangements and hydrogen migrations. An example of SnBr bond formation has been discovered. Ions of the phenanthridine type (m/e 179, C₁₃H₉N) are formed via enlargement of the center heterocyclic ring and rearomatization. Tentative mechanistic pathways are derived for all major fragmentation sequences on the basis of computer-aided correlation of metastable peaks, accurate mass measurements (elemental composition) and shifts resulting from specific deuterium labelling.     

Intramolecular hydrogen bonding in 1-nitro-5,10-dihydrophenazine derivatives

The formation of free radicals only for derivatives with a nitro group in the 1 position was observed in the oxidation of a number of 5-substituted 5,10-dihydrophenazines with lead dioxide. A long-wave absorption band was observed in the electronic spectra of the derivatives with a nitro group in the 1 position. The assumption of the formation of an intramolecular hydrogen bond in dihydrophenazines with a nitro group in the 1 position was confirmed by quantum-chemical modeling of the three structures of the 1,3-dinitro-5-phenyl-5,10-dihydrophenazine molecule. By comparison of the integral intensities of the bands of the stretching vibrations of the N-H bond in 5-substituted dihydrophenazines it was concluded that this bond is depolarized in derivatives with an intramolecular hydrogen bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 2, pp, 263–265, February, 1978.     

Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones,benzo[g] isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione

Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydro-furan leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.     

Hydrobromic acid-dimethyl sulfoxide reagent for dealkylation of 5,10-dialkyl-5,10-dihydrophenazines: Synthesis of 10-alkyl-2(10H)-phenazinones

By the reaction of 5,10-dialkyl-substituted 5,10-dihydrophenazine with hydrobromic acid in dimethyl sulfoxide at 90–110°, 10-alkyl-2(10H)-phenazinone was obtained as a major product. Brominated dihydrophenazine was isolated in the case of 1,6-dichloro-5,10-dimethyl-5,10-dihydrophenazine.