Hydroxylamines addition reactions

The hydroxylamine addition reaction was used for the preparation of P-N-hydroxyaminophenylpropionic acid (115) (Scheme 26) from cinnamic acid 148). Prolonged heating of a mixture of (115) and hydroxylamine gives the appropriate P-amino acid 150). 

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). 

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. 

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... 

The reaction of different substituted hydrazines (or hydroxylamines) with the a,/3-unsaturated ketones 210 gives pyrazolines 211 (or isoxazolines 212), as the result of a Michael addition reaction followed by an intramolecular Mannich reaction (Scheme 12) <2001FAR32>. 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Starting material which, upon oxidation with PSP, gave aldehydes. These were in turn condensed with primary hydroxylamines, promoted by polymer-bound acetate, to produce nitrones. The nitrones assembled using either method then underwent 1,3-dipolar cyclo-addition reactions with various alkenes to give the corresponding isoxazolidines (Scheme 2.46 and 2.47). 

The main first part of the review (Section HI) summarizes preparation of hydroxylamine derivatives through alkylation, arylation, and addition reaction of hydroxylamine, or its derivatives such as hydroxamic acids and A-oxysulfonamides. The second main part (Sections IV-VIII) describes methods of creation of hydroxyamino groups de novo from other functionalities. Due to easy interconversion outlined in Section II, syntheses of hydroxylamines and hydroxamic acids are considered together. For the same reason, the chapter also relates to synthesis of A-oxysulfonamides and V-oxyphosphonamides as far as these methods are of interest for the preparation of hydroxylamines. 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

The reductive NO chemistry will cover some new developments on the electrophilic reactions of bound nitrosyl with different nucleophiles, particularly the nitrogen hydrides (hydrazine, hydroxylamine, ammonia, azide) and trioxodinitrate, along with new density functional theoretical (DFT) calculations which have allowed to better understand the detailed mechanistic features of these long-studied addition reactions, including the one with OH-. The redox chemistry of other molecules relevant to biochemistry, such as O2, H2O2 and the thiolates (SR-) will also be presented. 

The mesomeric quinonemethides and 0-quinonemethides described above are somewhat more stable than the simple p-quinonemethides whose properties are already well known even from classical studies. The o-quinonemethides XX and XVII do not add on water even in solution in aqueous organic solvents their solution in dioxane/water is stable for months. They do not add on methanol or higher alcohols and react only slowly with phenols and organic acids. The addition of water is not catalyzed by mild alkalies the red color of the phenoxide ion (XVIII) prevails for weeks in soda solution. Addition of water occurs more rapidly in strongly alkaline solution. The addition of mineral acids and reduction by sodium borohydride are instantaneous. The addition of HC1 is rapid even at pH 4.0, the conditions used for determining the carbonyl content of lignin by the hydroxylamine hydrochloride reaction 13). 

Dihydropyrimidines 296 react very easily with water, forming 6-oxy derivatives 297 even during storage of 296 in solvents containing water and special catalysts [248]. There are examples of other addition reactions with water [326, 327, 328, 329, 330, 331], alcohols [82, 332], hydrazine and hydroxylamine [333]. 

The cyano group in 160 underwent addition reactions with sulfuric acid and with hydroxylamine to give the amide 161 and the amidoxime 162, re-... 

Although there is ample evidence for nucleophilic additions to benzyne la> and some other unstable angle strained cycloalkyne intermediates 15,27,31,205 207), only a few addition reactions to isolable angle strained cycloalkynes are known which can be classified as nucleophilic. Hydroxylamine and hydrazine add to (31) to yield the corresponding oxime and hydrazone, resp. 208). 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

A less restrictive implementation of the procedure, find-all-pathways, on the initial chemical species set, would employ the. operators K or K and would generate several additional reactions of interest. Among these additional reactions of particular interest are, the decomposition reaction of nitrobenzene and the disproportionation of nitrobenzene with N-phenyl hydroxylamine forming aniline and nitrobenzene ... 

Fig. 2. Important reactions involved in the generation of thiol-maleimide links. All of these reactions proceed under neutral conditions. (A) Free sulfhydryl groups undergo additional reactions with maleimide groups. (B) Thioacetate protection groups may be hydrolyzed with hydroxylamine. (C) 2-Pyridyldisulfide protecting groups are reduced by DTT.

Treatment of synlanti mixtures of aldoximes (69) with allylboronates generates N-(homoallyl)hydrox-ylamines (70) in good yield (Scheme 6). - The anti oxime reacts faster than the syn isomer. N-(Ho-moallyl)hydroxylamines (70) have been converted to homoallylamines (71) (with iron(II) dihydrolipoate) and have been treated with aldehydes to generate highly functionalized nitrone intermediates (72) for use in 1,3-dipolar addition reactions. 

There are four preparation methods for S-acyl sulfenamides 96 (1) RC(0)SX (X=Cl,Br,I)+R NH [20,284] (2) M(RCOS) (M=Na,K)+R NCl [78,229,262] (3) M(RCOS) (M=Na, K) + sodium hydroxylamine-0-sulfonate (see Scheme 13) [262] (4) addition reaction of RCOSH to activated N=N double bond [67]. The cyclic compounds 97, such as benzoisothiazolinones, have also been obtained by oxidizing the corresponding isothiazolthiones with KMn04 [198] or iso-propylethylenoxide [82] and by heating bis(o-aminobenzoyl) disulfide in acetic acid [64]. 

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