Hydroxylamines O-alkylation

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... 

Both O-alkyl hydroxylamines and, especially, arylhydrazines, are slightly oxidized compounds. The presence of any oxidizers in the reaction mixtures must be excluded. Nevertheless, in real practice, these mixtures very often contain some by-products (e.g., ArNH2, ArOH, ArH, etc.). Usually, there are no problems to reveal their chromatographic peaks, because aU of them have lower retention parameters than those for the initial reagents and, moreover, all target derivatives. The condensation reaction of the considered type can be characterized by statistically processed differences of retention indices of products and initial substrates. This mode of additive scheme permits us to estimate these analytical parameters for any new derivatives on standard nonpolar polydimethyl siloxanes. For the simplest reaction scheme, Ah— —>Bh—, AMW = MW(B) -MW(A) and ARl, = RI(B) RI(A) ... 

AU considered condensation reactions have some anomalies for the a,j8-unsaturated carbonyl compounds. Most reagents with active hydrogen atoms can react not only with carbonyl groups but also with polarized conjugated double bonds C = C. As a result of this regularity, three products, instead of the estimated one target derivative, are formed in the reactions of a,)8-unsaturated carbonyl compounds with O-alkyl hydroxylamines ... 

A-Nitrosohydroxylamine (3.9) gives dinitrogen oxide in the usual way (3-13) via the hydroxydiazonium ion. At a very early time, this mechanism was investigated using N-labeled nitrous acid and O-alkylated hydroxylamines (Leffler and Bottner-By, 1951). 

Isoxazoies.—Formation. O-Alkyl-hydroxylamines react with diketen to yield... 

Fig. 3 Anomalous interaction of a, 3-unsaturated carbonyl compounds with O-alkyl hydroxylamines.

The N-alkoxyamines R R NOR, also called O-alkyl hydroxylamines, consist of a large family of compounds, even if the most... 

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 ... 

O-Alkyl-7 und O-Aryl-hydroxylamine8 lassen sich mit Lithiumalanat in die Komponenten spalten bzw. re-duktivumlagern , O-Acyl-10bzw. N-Sulfonyl-hydroxylamine11 imerstenSchritt zum Hydroxylamin und Al-kohol bzw. Sulfonamid reduzieren. 

Recently, a new method for synthesis of tertiary amines 326 from iV,iV-dialkyl O-benzoyl hydroxylamines 325 was proposed.425 The protocol is based on the copper-catalyzed reaction of hydroxylamines 325 with dialkyl- and diarylzinc reagents (Scheme 166). It is noteworthy that alkyl- and phenylzinc halides also reacted with compounds 325, however, yields were significantly lower than those for ZnR2 (18-29% vs. 69-98%). 

A broad range of compounds can be O-alkylated with carbene complexes, including primary, secondary, and tertiary alcohols, phenols, enols, hemiaminals, hydroxylamines, carboxylic acids, dialkyl phosphates, etc. When either strongly acidic substrates [1214] and/or sensitive carbene precursors are used (e.g. aliphatic diazoalkanes [1215] or diazoketones) etherification can occur spontaneously without the need for any catalyst, or upon catalysis by Lewis acids [1216]. 

Polynitroarylenes containing a variety of leaving groups are very susceptible to nucleophilic displacement (Section 4.8), and so, treatment of such substrates with hydroxylamine or an alkoxyamine usually generates the corresponding arylhydroxylamine or its O-alkyl derivative. 

Hydroxylamines and alkylhydroxylamines possess high nucleophilicity and can react with a variety of primary and secondary alkylating agents. The reactivity of hydroxylamines in the majority of these reactions resembles that of primary and secondary amines. While hydroxylamine and Af-alkylhydroxylamines 1 are ambident nucleophiles, under neutral or weakly basic reaction conditions alkylation proceeds exclusively on nitrogen atom to give products of type 2 (equation 1). Deprotonation of the OH group of hydroxylamines results in O-alkylation products. 

Because of their lower hydrophilicity and higher stability to oxidation, O-protected hydroxylamines are more convenient substrates for alkylation than hydroxylamine itself. Commercially available 0-benzylhydroxylamine was successfully alkylated with alkyl halides and alkyl sulfonates ". ... 

Due to a much lower danger of dialkylation, alkylation of iV-alkyl- and Ai-alkyl-O-protected hydroxylamines (e.g. 8, equation 6) with primary alkyl halides proceeds substantially more selectively giving high yields of Al,Al-disubstituted products " of type 9. 

Selective O-alkylation of hydroxylamines and their derivatives can be done through deprotonation of the OH group. O-Alkylation (equation 14) of iV-substituted hydrox-amic acid ° (e.g. 21) followed by hydrolysis of the resultant O-alkylation product 22 is the most commonly used approach. Since alkylation of Af-unsubstimted hydrox-amic acid results in a mixture of O- and A-alkylation products, the corresponding O-alkylhydroxylamines are better prepared through alkylation of Af-hydroxysuccinimide or Af-hydroxyphthalimide followed by hydrolysis. 

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. 

O-Alkyl- and O-arylhydroxylamines and their A-substituted derivatives have been the most extensively used reagents for amination of C-nucleophiles (Table 1). O-Methyl hydroxylamine la is the most extensively used O-organylhydroxylamine-type reagent. 

Enehydroxylamine 0-derivatives 149 and 151, prepared from the reactions of A-alkyl-3-(hydroxyamino)cyclohex-2-enone (148, R = H) and iV-alkyl-3-(hydroxyamino)-5,5-dimethylcyclohex-2-enone (148, R = Me) with MsCl (equation 41) and Mc2NC(S)Cl (equation 42), respectively, in the presence of base rearrange spontaneously providing the corresponding [3,3]-sigmatropic rearranged products 150 and 152 in moderate to excellent yield . However, the diethyl phosphate 153 (equation 43) and the O-benzoyl hydroxylamine 154 rearrange under reflux in toluene (equation 44). 

Hoffman and coworkers have extensively studied the reactions between amines and sulfonyl peroxides. When primary amines reacted with arylsulfonyl peroxides at —78 °C in ethyl acetate, A-alkyl-O-arylsulfonyl hydroxylamine derivatives were obtained (equation 8), whereas when various primary and secondary amines reacted with sulfonyl peroxides, oxidative deamination was observed. ... 

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. 

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). 

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