Hydroxylamines, addition compounds

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Manganous salts form addition compounds with bases such as pyridine, quinoline, hydroxylamine. These are generally more stable than the true ammines. 

This means that, instead of one expected product with molecular weight (MW) = Mq + 29 (with O-methyl hydroxylamine as reagent), reaction mixtures may contain two additional compounds with MW = Mq + 47 and Mq + 76. This feature is negligible for analysis of individual compounds, but when samples are mixtures of components of interest, the analysis becomes impossible because of the complexity of the resultant interpretation. 

A number of addition derivatives may be used in the identification of the carbonyl compounds. Of these the crystalline derivatives formed with phenylhydrazine, C6H6NHNH2, and hydroxylamine, NH2OH, are the most important. The products formed with phenylhydrazine are called phenyUiydrazones, and have the general formula, RRiC=NNHC jls. The products formed with hydroxylamine are called oximes, and have the general formula, RRiC=NOH. Other crystalline addition compounds are formed with sodium bisulfite by aldehydes, and by those ketones which contain a methyl group. The addition compounds with ammonia, except in the case of acetaldehyde and a few other carbonyl compounds, are complex products. 

Aliphatic aldehydes, their trimers, or bisulfite addition compounds, when refluxed in 95% ethanol with hydroxylamine hydrochloride and a few drops of hydrochloric acid for 6 hrs., give the corresponding nitriles in practically quantitative yield.16... 

As an alternative to an olefination method, the Cope elimination can be used as a preparative method for unsymmetrical hydroxylamines. Addition of unsymmetrical secondary amine 41 to a,p-unsaturated compounds gave access to compound 42, which underwent oxidation and Cope elimination to yield the unsymmetrical hydroxylamine product 44.16... 

The utility of the organocatalytic hydroxylamine addition has been demonstrated with the preparation of a wide range of interesting enantioenriched compounds such as, P-antino acids [345,346], P-amino alcohols [345,346], 1,3-diamines [346], and different five- and six-membered nitrogen-containing heterocycles [347], as depicted in Schane 2.122 for the enantioselective synthesis of the alkaloid (+)-Angustureine... 

The effect of the amine on the overall equilibrium constants of condensation reactions of carbonyl compounds and amines has been discussed above (see section II.A) where it was pointed out that the thermodynamic stability of the C=N— linkage increases with the type of amine used, in the order NH3 < aliphatic amines < aromatie amines < amines containing an adjacent electronegative atom with a free electron pair. In contrast to the overall equilibrium constants, the rate and equilibrium constants for addition compound formation appear to be dependent on the basicity of the amine. In studies in which different amines have been reacted with the same earbonyl compound under the same conditions, the following observations have been made. The equilibrium constants for addition compound formation with -chlorobenzaldehyde were found to be 21 7, 9-11, 4 14 1/mole for hydroxylamine (pJiTa = 6-0) methoxyamine (pA =... 

Both aliphatic and aromatic isocyanates can be blocked by a variety of blocking agents. These include alcohols, phenols, oximes, lactams, j8-dicarbonyl compounds, bisulfite addition compounds, hydroxylamines and esters of p-hydroxybenzoic acid and salicylic acid. Perhaps the most widely used blocking agents at present are phenol, branched alcohols, 2-butanone oxime (methyl ethyl ketoxime) and 8-caprolactam. The use of blocked isocyanates in PU coatings has been comprehensively reviewed. ... 

Oximes, hydrazines and semicarbazones. The hydrolysis products of these compounds, t.e., aldehydes and ketones, may be sensitive to alkali (this is particularly so for aldehydes) it is best, therefore, to conduct the hydrolysis with strong mineral acid. After hydrolysis the aldehyde or ketone may be isolated by distillation with steam, extraction with ether or, if a solid, by filtration, and then identified. The acid solution may be examined for hydroxylamine or hydrazine or semicarbazide substituted hydrazines of the aromatic series are precipitated as oils or solids upon the addition of alkali. 

Compound (253) is formed from benzaldehyde and methylhydroxylamine-O-sulfonic acid in 35% yield. With ethyl-substituted chloramine or hydroxylamine-O-sulfonic acid yields do not exceed 10%, which is assumed to be due to steric hindrance and is foreseeable for both carbonyl addition and O —N bond formation. 

Nitro functions are easily reductively alkylated and a number of alkylated anilines are made industrially starting with the appropriate nitroaromatic in the ketone as solvent. The addition reaction can occur at the hydroxylamine intermediate as well as the aniline. A process step is saved by beginning with the nitro compound. 

Formation of azo-type products might be troublesome. These by-products, arising from reduction of aromatic nitro compounds, usually are assumed to be derived from the coupling of intermediate nitroso and hydroxylamine compounds. The coupling problem is accentuated in reduction of nitroso compounds because of much higher concentrations. It can be alleviated by dropwise addition of the substrate to the hydrogenation and use of acidic media. 

Hydroxamic acids are an important class of compounds targeted as potential therapeutic agents. A-Fmoc-aminooxy-2-chlorotrityl polystyrene resin 61 allowed the synthesis and subsequent cleavage under mild conditions of both peptidyl and small molecule hydroxamic acids (Fig. 14) [70]. An alternative hydroxylamine linkage 62 was prepared from trityl chloride resin and tV-hydroxyphthalimide followed by treatment with hydrazine at room temperature (Scheme 30) [71]. A series of hydroxamic acids were prepared by the addition of substituted succinic anhydrides to the resin followed by coupling with a variety of amines, and cleavage with HCOOH-THF(l 3). 

The five-coordinate complexes Ir(CO)(PPh3)2L, where HL = /3-diketone, A-benzoyl-A-phenyl-hydroxylamine, salicylaldehyde, 8-hydroxyquinoline, 2-hydroxybenzophenone, 2-hydroxy-8-methoxybenzophenone, were prepared from [Ir(CO)(PPh3)2Cl].632 The resulting compounds all underwent oxidative addition reactions with Br2. Reaction of [(cod)2IrCl]2 with N-substituted 3-hydroxy-2-methyl-4-pyridine gives the bichelated complex (389). 33... 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

Addition of organometalic compounds to nitrones is known as an efficient method of enantioselective synthesis of primary amines that can be easily obtained by the reduction of hydroxylamines which are the products of nucleophilic addition. 

Addition of 2-Alkyl-2-Oxazolines All of the above mentioned reactions of nucleophilic addition of nitrones give the corresponding hydroxylamines. In this chapter, the reactions of nitrones and nucleophiles and their conversions to compounds of other structures are considered. 

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