Reduction hydroxylamine synthesis

Addition-reduction. The synthesis of Dt.-l3-amino-p-phenylpropionic acid (3) from cinnamic acid (1) involves 1,4-addition of hydroxylamine to the conjugated system followed by reduction of the hydroxylamine acid (2) by the hydroxylamine."... 

A series of 8-amlnopurine nucleosides and their N -substituted derivatives were prepared via direct brominatlon of the natural purine ribosides and deoxyribosides and subsequent nucleophilic displacement of the 8-bromo group with hydrazine or azide (followed by catalytic reduction), hydroxylamine or allqrlamines . A new synthesis of 2-fluoro-adenoslne was developed, starting from 2,6-diazido-9-(tri-0-acetyl-p-D-ribofuranosyl)purine which was reduced to the 2-amlno-adenosine derivati the latter was selectively diazotized in the presence of fluoroboric acid 2. 2-Fluoro-3 -deoxyadenpsine was prepared from the unprotected 2-amlno-3 -deoxyadenosine in an analogous manner . 2-Aminoadenosine was also prepared by Raney-nickel catalyzed reduction of 2,6-dihydroxylamino-... 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

Hydroxylamine can be prepared by a variety of reactions involving the reduction of nitrites, nitric acid or NO, or by the acid hydrolysis of nitroalkanes. In the conventional Raschig synthesis, an aqueous solution of NH4NO2 is reduced with HS04 /S02 at 0° to give the hydroxylamido-A ,A -disulfate anion which is then hydrolysed stepwise to hydroxylammonium sulfate ... 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

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. 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

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 lithium derivatives of acetylenides (Li—C=C-C02R) to chiral nitrones proceeds with high stereoselectivity, giving a-acetylene substituted hydroxylamines (410a,b) (656). This reaction has been successfully applied to the synthesis of y-hydroxyamino-a, 3-ethylene substituted acids (411a,b), formed in the reduction of (410) with Zn in the presence of acid (657, 658), and to chiral 5-substituted-3-pyrroline-2-ones (412a,b) (Scheme 2.184) (658). 

One of the processes most generally used for the synthesis of nitrones is based on reduction of AN to hydroxylamines followed by oxidation of the resulting intermediates. In this process, the nitrogen atom of the nitro group remains in the target nitrones. Another possible approach to the synthesis of nitrones from AN, which involves the replacement of the nitrogen atom that is present in AN, will be described later in this chapter. 

The effect of temperature on the reduction of nitro-alkanes has been extensively exploited in the synthesis of cp-ephedrine analogues [i5,21,22] starting from 1-aryl-2-nitropropenes which are easily converted to the substrates 2. Reduction of these nitrocompounds below 20° C affords the hydroxylamine. The amine is formed above 55° C. Neutralisation of either reaction mixture causes rapid intramolecular migration of the acetyl group from oxygen to nitrogen, a reaction which implies a... 

Hydroxylamine hydrochloride is used for controlled reduction reactions. It is used in organic synthesis as an antioxidant for fatty acids and in photographic developer solutions. 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

The reduction of aromatic nitro compounds is believed to proceed to an intermediate mixture of nitroso compounds and substituted hydroxylamines which are not isolated but condense to form an azoxy compound which, in turn, is reduced to an azo compound. Contributing evidence to substantiate this mechanism is that the reduction of a mixture of two aromatic nitro compounds leads to a mixture of azo compounds consistent with that predicted if each of the nitro compounds were reduced to a nitroso compound and a hydroxylamine and these, in turn, reacted with each other in all possible combinations. This observation also implies that the bimolecular reduction of nitro compounds is practical only from the preparative standpoint for the production of symmetrically substituted azo compounds. Spectrophotometric studies of the reaction kinetics of the reduction of variously substituted nitro compounds may, however, uncover reasonable procedures for the synthesis of unsymmetrical azo compounds. 

Intramolecular reductive amino cyclization.1 The key step in a synthesis of the ergot alkaloid aurantioclavine (3) from 3-formylindole (1) involves treatment of the nitro olefin 2 with amalgamated zinc in refluxing methanolic 2 N hydrochloric acid. Zn-HOAc, Fe-HOAc, SnCl2-HCl are not useful for this purpose. Cyclization is believed to involve an intermediate hydroxylamine, which can be isolated from short-term reactions. 

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