1,2-Hydroxyamino oximes

An acid-catalyzed autocondensation of 1,2-hydroxyamino oximes (24) (obtained from olefin-dinitrogen trioxide by isomerization, followed by partial reduction of the 1,2-nitroximes with hydrogen over palladium-charcoal) with concentrated sulfuric acid gave 2,3 5,6-bistetra(or hexa)methylenepyrazine 1,4-dioxides (25) (556a). 

These reactions are catalyzed by ammonium acetate, the function of which is to generate protonated imines (322). Under mild reaction conditions, condensation of a- hydroxyamino-oximes with acetone dialkylketals takes place. The procedure can be successfully applied in cases where direct condensation with acetone... 

Benzenediamine (148) and frani-l-chloro-l,2-bis(hydroxyimino)ethane (149) gave 2(177)-quinoxalinone oxime (150), perhaps better formulated as 2-hydroxyaminoquinoxaline (151) (EtOH, 20°C, 3 h 71%) 6,7-dibromo-l,2-benzenediamine likewise gave 6,7-dibromo-2-hydroxyamino-quinoxaline. ... 

Oxime reduction is a very efficient procedure for obtaining racemic A7-hydroxy ami no acids in good yields. 19 31-361 TV-Hydroxylamine and O-protected A-hydroxylamines react smoothly and rapidly with a-oxo acid derivatives 23 to give the corresponding oximes 24. Acids 24 (R2= OH) can be reduced with NaBH3CN or LiBH3CN (Scheme 7) to give TV-hydroxyamino acids 25 (R2= OH)/31 but reaction yields are unsatisfactory for esters 24 (e.g., R2= OEt) or... 

Scheme 7 Synthesis of N-Hydroxyamino Acid Derivatives by Oxime Reduction131"331...

Hydroxylamines and Oximes. For RNH—OH compounds, prefix the name of the radical R to hydroxylamine. If another substituent has priority as principal group, attach the prefix hydroxyamino- to the parent name. For example, C6II5NIIOII would be named A-phenylhydroxylamine, but HOC6H4NHOH would be (hydroxyamino)phenol, with the point of attachment indicated by a locant preceding the parentheses. 

A derivative of the almost fully reduced imidazo[4,5-c]pyridine ring system, 3,3a,4,5,6,7-hexa-hydro-2//-imidazo[4,5-c]pyridine (357) has been prepared (Equation (29)) <88IZV409>. Cyclization of l-hydroxy-3-hydroxyamino-2,2,6,6-tetramethyl-4-piperidone oxime acetate (356) with benz-aldehyde or formalin at — 20°C for 3 d gave the reduced bicyclic compound (357). 

Hydroxyamino-2-butanone oxime (185) and diacetyl (186) gave 2,3,5,6-tetramethylpyrazine 1,4-dioxide (187) (MeOH, 20°C, 8 h 72%).423 Variations in the substitution pattern of synthon (185) led to dihydro- or even tetrahy-dropyrazine oxides.414,437,1163... 

The preparation of the requisite methyl ketone 67 starts from mesityl oxide (62) and hydroxylamine hydrochloride utilizing a known protocol (98BC1808) (Scheme 15). As correctly formulated in the original paper, hydroxylamine hydrochloride does not form the oxime but affords a low yield (11%) of the conjugate adduct, 4-(hydroxyamino)-4-methylpentan-2-one (63), which in solution is predominantly present as the hemiacetal cyclotautomer, 3,3,5-trimethylisoxazolidin-5-ol (64). Oxidation of 64 with mercuric oxide in chloroform furnishes a blue solution of 4-methyl-4-nitrosopentan-2-one (65) and its dimer 66 (ratio 85 15), which was isolated as colorless crystals 67 (54%). Condensation of nitroso ketone 65 with aniline in the presence of acetic acid provides / -phenyldiazenyl-a -methyl ketone 67 as a yellow oil (49%) (Scheme 15). 

Phosphonsaure 1-Hydroxyamino-3-methylthio-propan- E16a, 47 (Oxim-Red./P-Add./C,N-Spalt.)... 

Methyl-2-oxo- E21e, 5260 6-[n(Acyl) —SR] — en Cyclisier. 8-Aza-bicycIo]4.3.0]non-3-en 8-Hydroxy- E16a, 188 (N-OH —phthalimid-Red.) Azetidin 4-Ethenyl-3-isopropyl-2-oxo- E16b, 246 (Imin + R-C-COOR) Bicyclo 2.2.1]bept-2-en S-endo-(Hydroxyamino-methyl)- E16a, 26 (Oxim-Red.)... 

N-[2-(2-Brom-phenyl)-ethyl]-0-methyl- E16a, 277 (Oxim-Red.) 0-[2-(2-Brom-phenyl)-ethyl]-N-methyl- Elba, 277 (Oxim-Red.) Propan l-(4-Brom-phenyl)-2-hydroxyamino- E16a, 54 (En —N02-Red.)... 

H-l-Benzothiin 6-Chlor-3-(N-ethyl-hydroxyamino)-4-oxo- E16a. 132 (Oxim + Diazo-Verb.)... 

Deoxy-a-furoallosid l,2 5,6-Di-0-isopropyliden-3-hydroxyamino-E16a. 32 (Oxim-Red.) Malonsaure... 

Propansaure 2-Hydroxyamino-3-(l-methyl-indol-3-yl)- -methylamid E16a, 37 (Oxim-Red.)... 

Incorporation of natural amino acids (114, 115,116, 117, 118) and homologs (119,120,121) without further chain lengthening (VII to XVI) proceeds with retention of the a-amino nitrogen (119, 120, 122). An enzyme catalyzing the oxidation and decarboxylation of the N-hydroxyamino acid VIII to the aldoxime XI (123,124) has been purified 1400-fold (125). It is stimulated by FMN, O2 uptake is observed, and the a-keto acid oxime V is not used as a substrate (124,125). Decarboxylation may occur via the a-nitroso acid IX. Incorporation of the nitro compound XIII (126) presumably occurs via the acf-nitro compound XII which was suggested by Ettlinger and Kjaer (72) as an intermediate. The addition of thiols to... 

Azapurin-2-one gave 62 and 85% yields of simple adducts, such as 46, with methoxyamine (NH20Me) and hydroxylamine, respectively, at pH 4 (room temp 18 h). However, 8-azapurine and its 2-amino and 2-thioxo derivatives underwent further reaction and produced 4-hydroxyamino-methylenamino- (47c), 4-diaminomethylenamino- (50), and 4-thioureido-1,2,3-triazole-5-carbaldehyde oxime (48c) (in 77,80, and 55 % yields, respectively). Similarly, 8-azapurine and methoxyamine gave 47(1. ... 

Hydroxamic acids react with diaryliodonium salts to afford the O-phenyl derivatives. number of heterocyclic compounds containing A -hydroxyamino groups were selectively arylated on the oxygen atom. 0 (Table 5.4) In the case of oximate anions, ambident behaviour was observed, with predominant 0-arylation. With heterocyclic oximes, the 0-aryl ethers were mainly formed and served as precursors to prepare unstable aryl fulminates, 19 (Table 5.5) In the reaction of quinolone derivatives with diaryliodonium salts, the products of O- or C-arylation were obtained.(Table 5.6)... 

Direct IV-oxidation of these heterocycles invariably fails (see Section 3.02.7.2.8), making ring synthetic methods the only viable alternative <93CHE127>. Although there has been considerable interest in the chemistry of compounds of this type, there are no new synthetic approaches of a general nature. The most common approach is to react a-oximinoketones with aldehydes and primary amines. With formaldehyde, however, the 2-unsubstituted 1-oxides rearrange to 2-imi-dazolones. Variations on this theme allow synthesis of 1-hydroxyimidazole 3-oxides. Thus, treatment of an a-dicarbonyl compound with an aldehyde and hydroxylamine, or reaction of the aldehyde oxime or aldehyde with a 1,2-dioxime are common approaches <898773 >. Similarly, a-hydroxyamino-... 

The hydroxyimino group attached to carbon (C=NOH) may be converted into an amino group by way of the intermediate hydroxyamino or imino group. The reduction of oximes can be conducted so as to yield (1) a synthesis of amines from carbonyl compounds, (2) introduction of amino groups into a compound containing active methylene groups (by way of the isonitroso compounds obtained by nitrosation), or (3) production of amines from the adducts of nitrogen oxides or nitrosyl chloride to olefins. 

Hydroxyamino groups are reduced to amino groups, in principle, by the same methods as are used for the oxime group. Aromatic hydroxylamines, which can rearrange to aminophenols in an acid medium, are advantageously reduced by aluminum amalgam.116... 

From D-ribose (d-16), a chiral oxime n-17 was derived which is a useful auxiliary in diastereose-lective 1,3-dipolar cycloadditions (Sections D.1.6.1.2.1. and D.8.). The oxime is in equilibrium with the hydroxyamino form which forms nitrones with carbonyl compounds. The preparation of d-I7 involves protection of the 2,3- and 5-positions ... 

---