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A proton-magnetic-resonance study of the complex formed between actinomycin D and 10,11-dihydro-3H-naphth[1,2-g]indazol-7-ol strongly suggests that the indazole lies above the phenoxazine ring of actinomycin D. The complex can be destroyed by addition of dimethyl sulphoxide or dimethylformamide. The actinomycin D–indazole complex inhibits growth of Pseudomonas fluorescens and raises the thermal denaturation response of DNA. These data support the hypothesis that a molecular complex is formed which readily inhibits cell growth and interacts with DNA.

Some phosphorylated derivatives of 10-[(β-hydroxyethyl)carbamoyl]phenoxazine and the phenothiazine derivative were obtained.

This chapter discusses the nomenclature, general methods of synthesis, properties, typical reactions and stereochemical aspects of the oxazines, benzoxazines, phenoxazines, thiazines, benzothiazines, and phenothiazines and their derivatives. Oxazines are studied as 1,2-Oxazines, 1,3-Oxazines, 1,4-Oxazines and related compounds, such as morpholines and morpholones. Nominally there are nine possible benzoxazines; some are readily interconverted by tautomerism. These include 1,2-Benzoxazines, 1,3-Benzoxazines, 1,4-Benzoxazines and their hydro derivatives. The study of phenoxazine is important because some of its derivatives are highly colored and are used as dyes and also because certain phenoxazines show pharmacological activity. The simple derivatives of phenoxazines include the nitrophenoxazines, aminophenoxazines, 3-methoxyphenoxazines, phenoxazinecarboxylic acids, halogenophenoxazines, N-alkylphenoxazines and N-arylphenoxazines, acylphenoxazines, phenoxazinones and phenoxazonium salts, naturally occurring phenoxazine derivatives, such as actinomycins, cinnabarine and so on, benzophenoxazines and benzophenoxazinones. The isomeric forms of thiazines, having one sulfur and one nitrogen atom in a six-membered ring, and their hydro- and benzo- derivatives correspond with structures in the oxazine series, and are named and numbered in the same way. They include 1,2-thiazines and their hydro derivatives, 1,3-thiazines and related compounds, 1,4-thiazines, and their hydro derivatives. Phenothiazines represent an important class of drug substances, which show activity against numerous disorders. Some examples include phenothiazine homologs, halogenophenothiazines, nitrophenothiazines, aminophenothiazines and so on.

Publisher Summary This chapter presents the properties of the azine dyes such as phenazine, oxazine, thiazine, and sulfur dyes, and also their applications. Cyclocondensation of an o -aminophenol with an o -chloronitrobenzene leads to the formation of oxazine derivatives. Substituted 5 H -benzo[a]phenoxazin-5-ones are formed when o -aminophenol is condensed with 2,3-dichloro-1,4-naphthoquinones. The ratio of the isomers formed varies with the nature of R but the 4-substituted derivatives tend to predominate. Oxazine dyes are applied as indicators in bromatometry, for the titrimetric determination of ascorbic acid, redox indicators in inorganic analysis, and in the photometric determination of nitrates and nitrites in water. Some of the oxazine dyes discussed are triphenodioxazines and spirooxazines. The electrical oxidation converts bromide ion into bromine which in turn oxidizes the leuco compound to a dye itself. The reaction of 3,7-bis(diethylamino)phenoxazine with phosgene gives the 10-chlorocarbonyl derivative which is converted into an ester on treatment with potassium t -butoxide. Basic dyes for use in dye diffusion thermal transfer include the phenoxazine derivative.

The oxidation mixture of 3-hydroxykynurenine (1), treated with aqueous acetic anhydride and, subsequently, with acidic methanol, yields the 1-hydroxy-3-carbomethoxy-5-methoxy-11-(β-aspartoyl-N-acetyl-methyl ester)pyrido[3,2-a]phenoxazine (5), the 1-hydroxy-11-(β-aspartoyl-N-acetyl-methyl ester)-5.H-pyrido[3,2-a]-phenoxazin-5-one (6), the 1-methoxy-11-(β-aspartoyl-N-acetyl-methyl ester)-5H-pyrido[3,2-a]phenoxazin-5-one (6a), the l,5-dimethoxy-11-(β-aspartoyl-N-acetyl-methyl ester)pyrido[3,2-a]phenoxazine (7) and the 1-methyl-1(1′-[11-(β-aspartoyl-methyl esterimino)]ethenyl)ketal-1H,5H-pyrido[3,2-a]phenoxazin-5-one (8). A probable scheme, for the compound formation, is reported.

5H-Oxazolo[4,5-b]phenoxazine (5) was synthesized by the reaction of 3-amino-2-hydroxyphenoxazine hydrochloride (2) with formamide. A series of styryl-oxazolophenoxazines (9) were prepared by condensation of 2-methyl-5-acetyloxazolo[4,5-b]phenoxazine methiodide (8) with aromatic aldehydes. By contrast, 2-aryl-oxazolophenoxazines (14) were synthesized by reaction of 3-aminophenoxaz-2-one (1) with the appropriate aldehydes in the presence of an acid–base catalyst. The biological activities of some of these compounds were tested.

Summary(1) S-phenylamino-9-dialkyl-aminobenzo[a]phenoxazine dyes stained fat in vivo when administered to mice in their food. (2) The fat staining properties of the dyes were not materially altered by substituents on the phenyl nucleus other than those of highly acidic nature, or by substitutions of the naphthyl group and certain nitrogen heterocyclic rings for the phenyl group. The 5-phenylamino-9-morpholinyl derivatives also stained fat in vivo. (3) S-benzylamino-9-di-methylamino- and diethylaminobenzo[a]phenoxazine dyes did not stain fat in vivo, al-though they did stain tumor tissue. The corresponding dyes in which the alkyl group on the 9-nitrogen contained more than 2 carbon atoms stained fat in vivo. These dyes also stained tumor tissue in vivo.

1. 1. The object of the present investigation has been to show that the optical absorption(s) produced by mixing phenothiazine, or related compounds, with certain electron-acceptor species is the result of an intermolecular charge-transfer transition in an electron-donor-acceptor complex. Observation of a new absorption in a single mixture is not in itself a strong criterion for such complex formation. However, it has previously been shown that linear correlations of frequencies of charge-transfer bands often exist for related groups of complexes. 2. 2. Such correlations are observed between many of the systems: phenothiazine, 3,7-dimethylphenothiazine, 10-methylphenothiazine, chlorpromazine, phenoxazine and thianthrene with various electron acceptors compared with the corresponding complexes of hexamethylbenzene. 3. 3. With certain very strong electron acceptors, the new optical absorptions observed on mixing cannot be assigned to intermolecular charge-transfer transitions. It appears that, in these cases, ionisation to the corresponding radical cation of the donor by single electron transfer occurs. These radicals are unstable in neutral solution, though stable at low pH. 4. 4. In the further reaction which occurs in the case of phenothiazine, it is suggested that a dimer is formed.

Publisher Summary In azine, oxazine, and thiazine dyes, described in this chapter, the basic onium chromophore is normally substituted in position 3 or in positions 3 and 7 by auxochromic groups capable of donating electrons via mesomerism, for example, amino, substituted amino and hydroxyl. The positive ions of dyes so substituted exist as resonance hybrids, and their deep and intense colors are due to electronic transitions within the charged form. Methods of synthesis and commercial uses of phenazine, oxazine, thiazine and sulfur dyes are examined along with examples of individual members of these groups. Phenazine dyes include eurhodines and eurhodols, aposafranines, safranines, fluorindines, indulines and nigrosines, and aniline black. Phenoxazine dyes include basic type, gallocyanines, and triphendioxazines. The bright blue fiber-reactive triphendioxazine dyestuffs for cotton— for example, PROCION Blue H-EGN (C.I. Reactive Blue 198)—have gained considerable commercial importance at the expense of the more traditional anthraquinonoid products. Phenothiazine dyes are mostly salts of the oxidized form of 3,7-diaminophenothiazine with substituents on the amino groups, for example, Methylene Blue, Brilliant Alizarin Blue G, and Leuco-Methylene Blue. The sulfur dyes constitute a wide range of coloring matters cheaply produced by the introduction of sulfur into a variety of organic substances, for example, Immedial Black, Immedial Pure Blue, Hydron Blue R.

Phenoxazine (I), phenothiazine (II), and phenoselenazine (III) form solid iodine complexes of a 2:3 mole ratio when the components dissolved in benzene are mixed (1,2). They are all black polycrystalline powder.

A new reagent, 7,7,8,8-tetracyanoquinodimethan (TCNQ), is introduced for the colorimetric determination of free radical precursors, such as cysteine, proline, hydroxyproline, the phenoxazine family and mercaptans. TCNQ is also useful in the location and characterization on paper or thin-layer chromatograms of proline, hydroxyproline, cysteine, polynuclear compounds, mercaptans, thiocarbonyl amides and thiosemicarbazones. In addition, aminoacid derivatives, such as the N-(phenylthiocarbamyl) amino-acids and the 3-phenylthiodantoins, can be located and characterized on chromatograms. TCNQ has been applied to the location and characterization of atmospheric proline, carbazole and 11H-benzo[a]carbazole. For characterization purposes absorption spectra were obtained directly from glass-fibre, paper, or thin-layer chromatograms from about 300 to 900 mmu.

Musso's demonstration of the amino- and hydroxyphenoxazone structure of synthetic orcein suggested trial of simpler mixtures and isolated pure dyes of the phenoxazine phenoxazone series. It was further thought that explorations of this sort might reveal which of the hitherto demonstrated 14 chromatographic components of orcein might take part in or even be chiefly responsible for the elective staining of elastin.

N-Phenylaza-15-crown-5 3 reacts with phenothiazine 1a, 2-chlorophenothiazine 1b, or phenoxazine 1c in the presence of mild oxidizing agents (I2, Fe 3+ or Cu 2+ ) affording new Wurster aza-crown-ethers 4a–4c. Homolytic processes for the formation of compounds 4a-4c were discussed. Redox properties of these compounds were investigated by cyclic voltammetry. In concentrated sulfuric acid as solvent and oxidant, these compounds give stable radical-cations as proved by electron paramagnetic resonance (EPR). Ionophoric properties of the new compounds 4a-4c were evidenced by cyclic voltammetry with lithium and sodium cations. The relative hydrophobic/hydrophilic character of these compounds was determined by reverse-phase thinlayer chromatography (RP-TLC). Redox and ionophoric properties of the new compounds 4a–4c may lead to analytical and bioanalytical applications.

Three classes of p-type redox active molecules, i.e. triarylamine derivatives, phenothiazine/phenoxazine derivatives, and transition metal complexes are presented in this paper. Their structures, redox potentials and applications for molecular wiring and redox targeting of carbon-free insulating battery materials are discussed in detail.

A novel photochromic compound with NH-N intramolecular H-bond (1-p-toluenesulphonylazo- 2,4,6,8-tetrakis(tert-butyl)phenoxazine) and the corresponding model structures (1-oxo-2,4,6,8-tetrakis(tertbutyl) phenoxazine, 2,4,5,7-tetrakis (tert-butyl )-1-( veratroylazo ) phenoxazine, 2,4,5,7-tetrakis ( tert-butyl )-Nacetyl- 1-(p-toluenesulphonylazo)phenoxazine) have been synthesized and their spectral and photochemical properties are studied. The photochromic transformations observed are found to be conditioned by ESIPT (as a primary step) followed by E-Z isomerisation about N–N-bond.

A new class of complex cation-radical salts is formed by the reaction of phenothiazine bromide with phenoxazine, phenothiazine, its benzo derivatives, and phenoselenazine.

A TLC procedure was developed for the separation of phenoxazinone-type pigments. By employing silica gel G as the adsorbent and a solvent system of benzene-ethyl acetate-glacial acetic acid-formic acid (12:6:1:1), the separation of the following reference compounds was accomplished: cinnabarinic acid (Rf 0.35), cinnabarin (0.47), 2-amino-3-oxo-3H-phenoxazine (0.57), tramesanguin (0.67), and phenoxazine (0.99). Examination of the individual acetone extracts of Pycnoporus cinnabarinus (Jacq. ex Fr.) Karst., P. coccineus (Fr.) Bond. and Sing., and P. sanguineus (L. ex Fr.) Murr. by this technique revealed that all three species contained the same pigments. In addition to cinnabarinic acid, cinnabarin, and tramesanguin, two additional phenoxazinone-type pigments (Rf 0.53 and 0.90) were found in the respective carpophores.

A number of new 10-(O,O-dialkylphosphonoformyl) derivatives of phenoxazine and phenothiazine were obtained.

1. N-(Bromoacetyl)phenoxazines react with trialkyl phosphites with the formation of N-(O, O′-dialkylphosphonoacetyl)phenoxazines. 2. Arbuzov rearrangement of N-(bromoacetyl)phenoxazine with trialkyl phosphites yielded a series of N-(O, O′-dialkylphosphonoacetyl)phenoxazines, which have not been described in the literature.

The free radical cations of phenothiazine, 10-methylphenothiazine, and phenoxazine have been formed by chemical oxidation of their parent compounds. The radicals all possess complex, intense visible absorption bands which allow excitation of their resonance Raman spectra throughout the visible region. The point-group symmetries of the parent compounds in solution have been determined as Cs for both phenothiazine and 10-methylphenothiazine, and C2v for phenoxazine. A partial assignment of the Raman bands has been made for each radical cation studied. The relative intensities of Raman bands and the parent-to-radical frequency shifts observed have been interpreted in terms of the structural changes which occur on radical formation. An analysis of the phenothiazine radical cation visible absorption band, supplemented by resonance Raman data and excitation profiles, has yielded information on the excited-state geometry.

La lithiation de la phenoxazine N-protegee par lithiooxycarbonyl se fait sur le C1; reactions avec divers electrophiles

The one-equivalent oxidations of phenothiazine and phenoxazine (Ar2NH) in neutral and acidic CH3CN solution by CeIV and FeIII have been analysed kinetically into the sequence Ar2NH [graphic omitted] Ar2NH˙+ [graphic omitted] Ar2N+→ product and values (or limits) for the relevant rate constants, including those for the oxidant–cation radical reaction, obtained by stopped-flow or rapid-scanning spectrometry. The latter technique has provided u.v.–visible spectra of all the intermediates involved, of which some are described for the first time.

Rate and equilibrium constants have been determined by a microwave temperature-jump method for the reactions of trichloroacetic acid and picric acid with the basic indicator phenyl diethyl Nile Blue base (5-phenylimino-9-diethylamino-benzo[α]phenoxazine), over a range of temperature in five solvents—1-chlorobutane, 1-chloropentane, chlorobenzene, bromobenzene and iodobenzene. The rate constants are inversely correlated with the viscosities of the solvents; they are 8–24 times smaller than the values calculated for diffusion-controlled reactions by simple diffusion theory (Debye-Smoluchowski equation), and are more sensitive to viscosity. The results can be explained by preliminary formation of a weak complex, within which the reactant molecules can rotate into positions favourable to reaction.The question whether the viscosity-dependence of the rate is attributable to the first step (encounter) or the second (rotation) is discussed.

We were able to develop a convenient method for the oxidation of phenoxazine (I) that makes it possible to isolate the perchlorate salt (II) of the phenoxazine cation radical, the existence of which in solutions has been demonstrated by EPR spectroscopy. For this, we carefully ground an equimolar mixture of phenoxazine with ferric perchlorate nonhydrate in a small amount of 57% perchloric acid. The dark-red precipitate of II was removed by filtration and washed with the minimum amounts of acetone and ether to give the product in 53% yield. The results of elementary analysis of the salt are in agreement with the empirical formula. Treatment of a solution of perchlorate II in acetonitrile with zinc dust gives phenoxazine. The EPR spectrum of a solution of II in acetonitrile (i0 -4 mole/liter) consists of a quartet of lines (aHNH ~ a N ~ 7.6 Oe). The absorption spectrum in the visible region contains a band with %max 383, 409, and 530 nm.

The e.s.r. spectra of the series of cation radicals and nitroxide radicals derived from phenoselenazine, phenothiazine, and phenoxazine have been measured, together with the e.s.r. spectra of the neutral radicals from phenothiazine and phenoxazine. The proton and nitrogen hyperfine splittings in these radicals are compared with those calculated by a variety of molecular orbital methods. In some cases hyperfine splittings from 33S and 77Se have been observed and these are employed in the evaluation of the unpaired electron density distributions. From a study of the phenoselenazine cation radical, we conclude that spin–rotation relaxation causes an appreciable contribution to the line-width of the e.s.r. spectrum of this species in solution at room temperature.