Furazan N-oxides Research Articles

Halogenation of Aldoximes. A Versatile Reaction for the Synthesis of Highly Functionalized Hydroximoyl Chlorides and Furazan N-Oxides

Halogenation of Aldoximes. A Versatile Reaction for the Synthesis of Highly Functionalized Hydroximoyl Chlorides and Furazan N-Oxides

Chemical and Biochemical Reactions of Aromatic Furazan Compounds

Aromatic furazan has numerous pharmacologic and industrial applications. As part of our work on aromatic furazan chemistry and biochemistry, benzofurazan N-oxides, on irradiation using a high-pressure mercury lamp with a Pyrex filter in acetonitrile containing a little water, afforded 1H-azepine-2,7-dione. Mechanistic studies on the photoreaction using a low-pressure mercury lamp and photosensitizer suggest that photosensitized formation of 1H-azepine-2,7-dione with the aromatic hydrocarbon may be carried out by reabsorption of fluorescence. Quinoxaline 1,4-dioxide, phenazine 5,10-dioxide, and pyrido[2,3-b]pyrazine derivatives were synthesized from the corresponding aromatic or heteroaromatic furazan N-oxides by silica gel or molecular sieves under solvent-free conditions using microwave irradiation. The toxicities of some benzofurazans were examined on Escherichia coli; these may due to their reduction within the E. coli cell and their reoxidization by molecular dioxygen to form superoxide and hydrogen peroxide. The formation of 4,7-dicyanobenzofurazan anion radical in the E. coli cell suspension-4,7-dicyanobenzofurazan-glucose system in the absence of O2 was followed by ESR spectroscopy. 4,7-Dimethylbenzofurazan was transformed by 1O2 produced by irradiation of C60 into 4,7-dimethylbenzofurazan 4,7-endoperoxide. The endoperoxide decomposed back to 4,7-dimethylbenzofurazan at room temperature. 4,7-Dimethylbenzofurazan was transformed by irradiation with the third harmonic of a Quanta-Ray Nd:YAG laser (355 nm) into (2Z,4Z)-2,5-dimethylhexa-2,4-dienedinitrile monoxide. Irradiation of 4,7-dimethylbenzofurazan yielded a photoproduct with a quantum yield 0.48 and chemical yield 99%.

3,4-Bis(4-fluorophenyl)-1,2,5-oxadiazole 2-oxide

The title compound, C14H8F2N2O2, also known as di(4-F-phen­yl)furazan N-oxide, was found as a side product in the synthesis of isoxazole derivatives. The are two molecules in the asymmetric unit. The bond length of the dipolar N—O unit is 1.107 (7) A. X-ray analysis confirmed the compound to have the desired structure

Nitration of the 6-Methyl-1,3,5-Triazine Derivatives, 6-Methyl-1,3,5-Triazine-2,4(1H, 3H)-Dione and 2,4-Dimethoxy-6-Methyl-1,3,5-Triazine

Nitration of 6-methyl-1,3,5-triazine-2,4(1 H, 3 H)-dione (III) gave 2,4,6-trihydroxy-1,3,5-triazine (cyanuric acid, V) and tetranitromethane, whilst nitration of 2,4-dimethoxy-6-methyl-1,3,5-triazine (IV) gave 2,4-dimethoxy-6-trinitromethyl-1,3,5-triazine (VII) or a furazan N-oxide derivative (IX), depending upon the nitration medium.

Generation and cycloadditions of 4,5-dihydrooxazole- and oxazolidine-4-carbonitrile N-oxides

A route to 2-phenyl-4,5-dihydrooxazole-4-carbonitrile N-oxide 7 has been developed starting from (S)-serine methyl ester and involving dehydration of the 4-nitromethyl derivative 13 using m-tolylene diisocyanate and triethylamine. Cycloaddition of the nitrile oxide to styrene afforded a 55:45 mixture of diastereoisomeric dihydroisoxazoles 21 and 22; furazan N-oxides 19 and 20 were also formed in a competing dimerisation. The analogous (R)-oxazolidine-4-carbonitrile oxide 8, also prepared from (S)-serine methyl ester, reacted similarly with styrene, oct-1-ene and diethyl fumarate to afford ca. 1:1 mixtures of adducts. The structures of the dihydrooxazole–dihydroisoxazole adduct 21 and furazan N-oxide 20 were determined by X-ray crystallography.

A Novel Synthesis of Pyrazolo[3,4- c]furazan Derivatives

The first derivatives of pyrazolo[3,4-c]furazan N-oxide have been synthesized from the corresponding 3-amino-4-(hydroxyiminomethyl)furazan by treatment with bromine followed by DBI.

1,3-dipolar cycloaddition reactions of levoglucosenone

The cycloaddition reactions of levoglucosenone with various 1,3-dipoles have been examined. Benzonitrile oxide underwent regiospecific and face-selective cycloaddition yielding isoxazoline 2a as the major product. D-Glyceraldehyde-derived nitrile oxide 6 was less selective and afforded furazan N-oxide dimer 8 in addition to a mixture of isoxazolines. C,N-Diphenylnitrone and N-benzyl- C-phenylnitrone reacted similarly yielding isoxazolidines 9 and 10. In each case the major adduct resulted from attack at the less hindered face of the dipolarophile anti to the 1,6-anhydro bridge, and with the oxygen of the nitrile oxide or nitrone becoming attached to the β-carbon of the enone. In contrast benzonitrile N-phenylimide added to levoglucosenone to give a regioisomeric mixture of pyrazoles 11 and 12, resulting from dehydrogenation in situ of the initially formed pyrazolines. No reaction was observed with p-methoxybenzonitrile sulphide. The structures of isoxazoline 2a and isoxazolidine 9 were confirmed by X-ray crystallography.

Correlation of 13C Shifts with Substituent Parameters in 3,4-Diphenyl-1,2,5-oxadiazole 2-Oxides Substituted at the Para-Positions of Either or Both Phenyl Rings

Abstract C-1′, C-1″, C-3, and C-4 13C shifts in 3,4-di(4′-or/and 4″-X)phenyl-1,2,5-oxadiazole 2-oxides (3,4-diarylfurazan 2-oxides; three series: X=NMe2, OMe, Me, Cl, H, and NO2) were correlated vs. seven different divided substituent parameter sets. Results have implied that i) the C-3–C-4 bond does not transmit mesomeric effects efficiently; ii) no effects can be specifically attributed to the possibility that the C-3 aryl maintains a higher dihedral angle with respect to the furoxan ring than the C-4 aryl; iii) there appears to be a directionality to the propagation of localized π-polarization due to lesser ability of C=N(O)→O to convey effects compared with C=N(O); and, iv) the furazan N-oxide ring, being generally an electron acceptor, transmits substituent effects nonlinearly.

ChemInform Abstract: Structural and Molecular Orbital Study of the Furazan N‐Oxide System. Structures of 3‐Amino‐4‐methylfurazan N‐Oxide and 4‐Amino‐3‐methylfurazan N‐Oxide, and Molecular Orbital Calculations

The molecular structure of the two title furazan oxide isomers has been determined by three-dimensional X-ray analysis from diffractometer data. Molecular orbital calculations at ab-initio level, using minimal and spilit valence basis sets and at semiempirical level using the MINDO/3 approach, have been performed on 3-amino-4-methylfurazan N-oxide, 4-amino-3-methylfurazan N-oxide, 3-methyl-4-aminofurazan, 3,4-diaminofurazan, and unsubstituted furazan and furazan N-oxide. The influence of the amino substituent on the five-membered ring has been analysed; all results show that significant electronic effects are present.

Structural and molecular orbital study of the furazan N-oxide system. Structures of 3-amino-4-methylfurazan N-oxide and 4-amino-3-methylfurazan N-oxide, and molecular orbital calculations

The molecular structure of the two title furazan oxide isomers has been determined by three-dimensional X-ray analysis from diffractometer data. Molecular orbital calculations at ab-initio level, using minimal and spilit valence basis sets and at semiempirical level using the MINDO/3 approach, have been performed on 3-amino-4-methylfurazan N-oxide, 4-amino-3-methylfurazan N-oxide, 3-methyl-4-aminofurazan, 3,4-diaminofurazan, and unsubstituted furazan and furazan N-oxide. The influence of the amino substituent on the five-membered ring has been analysed; all results show that significant electronic effects are present.

Furazan N-oxides. Part 3. Synthesis of di-isocyanates from strained norbornane furazan N-oxides

Thermolysis, at ca. 110 °C, of the strained norbornane furazan N-oxides (5)–(8) in toluene, saturated with sulphur dioxide, affords the isomeric 1,3-di-isocyantocyclopentanes (14)–(17). Product formation is explained by a mechanism involving cleavage of the furazan ring to cyclopentane-1,3- bis(nitrile oxides)[e.g.(9)], followed by 1,3-dipolar cycloaddition with SO2 to form bis-1,3,2,4-dioxathiazol-2-ones [e.g.(12)]. Subsequent extrusion of SO2 and rearrangement yields di-isocyanates [e.g.(14)] which were identified spectroscopically and by preparation of urethane and/or urea derivatives on reaction with alcohols and aniline. Compound (8) with aniline gives the cyclic biuret (20) rather than a bis-urea, the structure of the product being established by X-ray crystallography. In the absence of SO2 polymeric furoxans are formed.

Furazan N-oxides. Part 2. Synthesis and structure of some strained furazan N-oxides

The strained furazan N-oxides (5) and (6) have been synthesised from norbornene and dicyclopentadiene by treatment with N2O3, thermal isomerisation of the resulting nitronitroso-adducts to the nitro-oximes [e.g.(9)], and subsequent dehydration at ambient temperature using SO3–DMF or CISO3H–DMF. Characterisation of the products is based on analytical and spectroscopic evidence by comparison with the known analogues (2) and (3), and in the case of (6) by X-ray crystal structure analysis. Compound (6) has endo-stereochemistry and is shown by 13C n.m.r. spectroscopy to be, like (2), a mixture of isomers, (6A) and (6B). X-Ray crystal structure analysis also showed that (3) has exo-stereochemistry and that for both (3) and (6) the O1–N2 bond of the oxadiazole is long (1.47 and 1.54 A).

Sulphur dioxide mediated conversion of strained furazan N-oxides into di-isocyanates

Thermolysis of strained furazan N-oxides of the norbornane series results in fragmentation of the oxadiazole ring, the isolated products being di-isocyanates when the reactions are carried out in the presence of sulphur dioxide, while in its absence unstrained polymeric furoxans are formed.

Furazan N-oxides: a convenient source of both nitrile oxides and isocyanates

Thermolysis of furazan N-oxides results in ring cleavage to nitrile oxides which may be trapped in good yield as 1,3-dipolar cycloadducts; in the absence of dipolarophiles the intermediate nitrile oxides rearrange to isocyanates.

Furazans and furazan oxides. Part I. Synthesis and reactions of some strained furazan N-oxides

Furazan N-oxides with a strained ring bridging the 3- and 4-positions are progressively deoxygenated by trialkyl phosphites, forming furazans, which can in some cases be isolated, and dinitriles. Heating in the presence of an acetylene forms bis(nitrile oxide) adducts (isoxazoles), with the more highly-strained types.

Investigations on steroids. IV. Syntheses of androstano[2,3-c]furazans and related compounds.

Steroids with a furazan ring fused to the 2, 3-positions were synthesized. 2, 3-Dihydroxyiminoandrostanes (III) prepared from androstan-3-ones (I), via 2-hydroxyimino-3-ketones (IV), or 2, 3-diketones (II), were cyclized directly to androstano[2, 3-c]furazans (XVII) by means of alkali, succinic anhydride or thionyl chloride. Alternatively, 2, 3-dihydroxyimino compounds (III) were treated with sodium hypochlorite or lead tetraacetate to afford the corresponding furazan N-oxides (furoxans)(XXI), which were deoxygenated to the furazans (XVII) by heating with triethyl phosphite. Similarly, androst-4-eno and androsta-4, 6-dieno[2, 3-c]furazans (XVII, XIX) were prepared. Syntheses of their derivatives were also described.