N-Alkylation hydroxylamines

The reaction is thought to occur by nucleophilic addition of the N-alkyl-hydroxylamine to the keto acid as if forming an oxime (Section 19.8), followed by decarboxylation and elimination of wrater. Show the mechanism. 

Die Reduktion von Hydroxylaminen mit Hydriden lauft analog der Reaktion von Nitro-so-Verbindungen bzw. Oximen. N-Alkyl-hydroxylamine werden durch Lithiumanalanat in der Regel zu prim. Aminen umgesetzt8, doch konnen auch Umlagerungen zum sek. Amin ablaufen9. 

Table 2.5 Formation of optically active functionalized fS-hydroxy-nitroncs 95 by reaction of aldehydes 93 with activated carbonyl compounds 94 and substituted N -alkyl hydroxylamine hydrochloride in the presence of L-proline as the catalyst...

N-Nitroso-N-alkylhydroxyl-amine, N-Alkyl-hydroxylamine Anwesenheit von H-Donator NO y-NH-OH 106, 119) H... 

Aldoxime lassen sich nicht zu N-Alkyl-hydroxylaminen zu hydrieren, vielmehr erhalt man z. B. mit Platin in alkoholischer Salzsaure unter Verbrauch von 1,5 Mol Wasserstoff 1,1-Dialkyl-hydroxylamine1. Diese entstehen wahrscheinlich durch Hydrierung in-termediar auftretender Nitrone (s. S. 253 f.), die sich leicht aus N-Alkyl-hydroxylamin und durch Hydrolyse entstandenem Aldehyd bilden ... 

Aliphatische Nitro-Verbindungen werden nur langsam und unvollstandig durch Natrium/fl. Ammoniak redu-ziert. Die entstehenden N-Alkyl-hydroxylamine werden als 4-Nitro-benzoesaure-amide isoliert2 ... 

Reactions of alkylperoxyl radicals with N-alkyl hydroxylamines... 

Reactions at the Hydroxylamine Nitrogen. These reagents have been used as 0-protected forms of hydroxylamine for synthetic transformations involving the unprotected nitrogen. Thus O-silylhydroxylamines have been used to prepare iV-hydroxy- 8-lactams and substituted dihydro-3-hydroxy-l,2,3-benzotria-zines, as weU as N-alkylated hydroxylamines for use as leuko-triene biosynthesis inhibitors. ... 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Thus the structure of the oxazirane must formally involve elimination of water from one molecule each of the carbonyl compound and of an alkyl hydroxylamine. (In the synthesis of oxazirane from N-methylhydroxylamine-O-sulfonic acid and benzaldehyde, this method... 

Aromatische O-Alkyl-oxime ergeben in ahnlicher Weise mit Natrium-cyano-trihydrido-borat die entsprechenden 0,N-Dialkyl-hydroxylamine z. B.2 ... 

Silylation of hydroxylamine or N-alkyl or N-ethoxycarbonyUiydroxylamines is usually accomphshed, in 52-84% yield, by silylation with TCS 14/NEt3 [63, 161, 162]. Whereas the reaction of N,0-bis(trimethylsilyl)methylhydroxylamine 952 with aldehydes such as benzaldehyde, or with ketones, with to adducts such as 953, has already been mentioned at the beginning of Section 7.3 thermal and other reactions of N,0-bis(trimethylsilyl)hydroxylamine 1141 or N-substituted N,0-bis(trimethylsi-lyl)hydroxylamines 1121, 1128, 1131 are discussed in this section. 

Action of the appropriate alkyl bromide on N-cyanourethane 130 affords the N-alkyl cyanourethanes 131 that, under the action of the hydroxylamine, through the intermediate formation of unstable hydroxyguanidines 132, yield the final products 133. These products have been found to display antithrombotic properties after... 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

Many of the 3-hydroxytriazene derivatives produced by diazo-coupling onto N-alkyl or A-aryl hydroxylamines decompose explosively above their m.p.s. However, the heavy metal derivatives are stable and used in analytical chemistry. 

N-Alkylation of hydroxylamines through ring opening of epoxides... 

Changing the base to triethylamine improves the yield of benzoylhydroxamic acid (96a) up to 91% the purification required column chromatography. Independently of the substituent in both Af-acylbenzotriazole and hydroxylamine, the desired O-alkyl, N-alkyl and 0,A-dialkyl hydroxamic acids were obtained as sole products as a result of nucleophilic displacement of the benzotriazolyl moiety by the hydroxylamine nitrogen. 

Umsetzung von 1-Brom-alkanen mit N-Benzyl-hydroxylamin in Phosphorsaure-tris-[di-methylamid] (HMPT), Dehydratisierung des so gebildeten N-Alkyl-N-benzyl-hydroxyl-amins mit 2-Fluor-l-methyl-pyridinium-(4-methyl-benzolsulfonat) und saure Hydrolyse des entstandenen N-Benzyliden-amins ergibt 1-Amino-alkane in guten Ausbeuten3. 

Die Umsetzung der (Methyl-lithium)-(N-alkyl-0-methyl-hydroxylamin)-Komplexe mit Alkyl- oder Phenyl-lithium fiihrt in einigen Fallen zu guten Ausbeuten an Alkyl-methyl-aminen3 ... 

Die Reaktion von Formaldehyd-(O-benzyl-oxim) mit einem Alkyl-lithium bei tiefer Tem-peratur fiihrt zum N-Lithium-Derivat eines N-Alkyl-O-benzyl-hydroxylamins, das bei der Umsetzung mit einem weiteren Alkyl-lithium das N-Lithium-Derivat eines Dialkylamins ergibt dieses wird ohne Isolierung mit einem Alkyl-halogenid zu einem Trialkylamin al-kyliert1. 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

Hydroxylamines and hydrazines can be acylated on insoluble supports using the same type of acylating agent as is used for the acylation of amines [146-149]. Because of their higher nucleophilicity, hydroxylamines or hydrazines can be acylated more readily than amines, and unreactive acylating agents such as carboxylic esters can sometimes be successfully employed (Table 13.10). Polystyrene-bound O-alkyl hydroxamic acids can be N-alkylated by treatment with reactive alkyl halides and bases such as DBU (Entry 5, Table 13.10). 

Oxidation of secondary hydroxamic acids with performic acid affords the N-alkyl residue as a carboxylic acid (136). A most useful oxidative reaction is that obtained by action of periodate on hydroxamic acids and hydroxylamines (41, 43, 121, 122). Primary hydroxamic acids give ni-... 

Isoxazolidines display properties consistent with their cyclic hydroxylamine structures. Thus, isoxazolidines behave as nucleophiles and thus can be N-alkylated or N-acylated. Isoxazolidines are also strong bases (p5.05) and undergo other reactions such as hydrogenolysis, oxidation, thermolysis, photolysis, and decomposition by bases. 

N-Alkylation may require careful selection of experimental conditions when several reactive moieties are present in the reactants. Thus, when a Mannich ketobase is allowed to react with hydroxylamine, it is preferable to use the iodomethylate of the base, since it is more easily decomposable, in order to reduce the extent of the concurrent oximation... 

Path a can be considered as a C-alkylation by the Mannich base of enamine or enol derivatives the latter acts in the presence, for example, of hydroxylamine, followed by intramolecular condensation leading to ring closure and formation of the aromatic nucleus 340. " By contrast, path b involves amino group replacement by arylamine (N-alkylation by the Mannich base) producing the P-arylaminoketone 341, directly obtainable also by Mannich synthesis. " ... 

Primofy amines. A new method for preparation of primary amines involves N-alkylation of this derivative of hydroxylamine, dehydration of the product, 2, to 4, and finally acid hydrolysis of the N-benzylidenealkylamine (4) to the amine 5. HMPT is the solvent of choice for the alkylation step. 2-Fluoro-l-methylpyridinium p-toluenesulfonate (3) is superior to tosyl chloride for the second step. 

Hydroxylamin N-Propyl-N-(3-sulfo-propyl)- - El6a, 115 (N-Alkyl.)... 

Hydroxylamin N-Decyl- E16a, 5 (N-Alkyl.), 36 (Oxim-Red.) Octanol 8-Dimethylamino-Vl/la, 1, 522 f. 

Thermolysis of aporphine A -oxides (184), easily obtained by peracid oxidation of aporphines, gives variable yields of yV-phenanthrylethyl hydroxylamines (185). These may be transformed by reduction and N-alkylation into the corre-... 

A similar rate expression has also been established for N-methyl hydroxylamines, and is known in the nitrosation of aromatic amines. With O-alkyl hydroxylamines the expression has the more usual form... 

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