Hydroxylamine carbonyl compounds

Cyclohexanone purity is most readily deteanined by gas-Hquid chromatography over DC-710 or carbowax 20M-on-chromosorb. Impurities such as cyclohexane, ben2ene, cyclohexanol, and phenol do not interfere. In the absence of other carbonyl compounds cyclohexanone may be deterrnined by treatment with hydroxylamine hydrochloride, which forms the oxime, as follows ... 

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. 

Certain reactions between carbonyl compounds and nucleophiles are catalyzed by amines. Some of these reactions are of importance for forming carbon-carbon bonds, and these are discussed in Chapter 2 of Part B. The mechanistic principle can be illustrated by considering the catalysis of the reaction between aldehydes and hydroxylamine by aniline derivatives. 

The Preparation of Oxaziranes from Carbonyl Compounds and Derivatives of Hydroxylamine and Chloramine... 

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... 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

It is much more common not to be able to isolate any intermediates at all, but this does not necessarily mean that none are formed, merely that they may be too labile or transient to permit of their isolation. Their occurrence may then often be inferred from physical, particularly spectroscopic, measurements made on the system. Thus in the formation of oximes from a number of carbonyl compounds by reaction with hydroxylamine (p. 219),... 

Dining preparation of an unspecified oxime, the carbonyl compound, pyridine, hydroxylamine hydrochloride and sodium acetate were heated in a stainless steel autoclave. At 90°C a sudden reaction caused a pressure surge to 340 bar, when the bursting disk failed. The reaction had been run previously and uneventfully on one-tenth scale in a glass lined autoclave. 

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. 

Nitrones have been generally prepared by the condensation of /V-hydroxylamines with carbonyl compounds (Eq. 8.40).63 There are a number of published procedures, including dehydrogenation of /V,/V-disubstituted hydroxylamines, / -alkylation of imines, and oxidation of secondary amines. Among them, the simplest method is the oxidation of secondary amines with H202 in the presence of catalytic amounts of Na2W04 this method is very useful for the preparation of cyclic nitrones (Eq. 8.41).64... 

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). 

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...

Bicyclic nitrones (132) were formed from the reaction of alkenyl carbonyl compounds (131) with hydroxylamine. The reaction requires the presence of the terminal olefinic electron withdrawing ester group CC Et. Also, the product(s) of reaction are shown to depend on the space filling capacity of substituents R1 — R4... 

Accordingly, diazobenzene and nitrous acid are related to each other in the same way as are phenylhydrazine and hydroxylamine the latter two substances, in fact, yield the same reaction products with carbonyl compounds as the former two do with the corresponding methylene derivatives. 

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. 

During the first month of this experiment, it was realized that this reaction is extremely variable. Thus, diverse amines (ammonia, primary and secondary amines, hydrazine derivatives, hydroxylamines) 13, carbonyl compounds (aldehydes, ketones) 14, acid components 15 or their anions (H2O, Na2S203, H2Se, R2NH, RHN-CN, HN3, HNCO, HNCS, RCO2H, RCOSH, ROCO2H, etc.), and the isocyanides could form the a-adducts 16 that rearrange into their products 17 (Scheme 1.5). 

If the addition of hydrogen takes place in a 1,2-mode the products are oximes, hydroxylamines, amines, and carbonyl compounds resulting from the hydrolysis of the oximes [567], Oximes and carbonyl compounds also result from reductions of a,/3-unsaturated compounds with iron [569, 570] and an oxime was prepared by catalytic hydrogenation of a )S-nitrostyrene derivative over palladium in pyridine (yield 89%) [571]. 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

Chemicals. The carbonyl compound standards 2-methylpropanal, 2-methylbutanal, 3-methylbutanal, pentanal, hexanal, furfural, methional, phenylacetaldehyde, and (E)-2-nonenal were purchased from Sigma-Aldrich (Milwaukee, Wl). A stock solution containing a mixture of the standard compounds in ethanol was prepared daily in a concentration of 100 ppb each. An aqueous solution of the derivatization agent 0-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBOA) (Sigma-Aldrich, Milwaukee, WI) was prepared at a concentration of 6 g/L. PFBOA solution was prepared every 3 months and kept refrigerated. 

The experimental conditions used to prepare oximes depend mostly on the nature of the parent materials and the basicity of the reaction medium usually, reactions proceed smoothly at pH close to neutral. In organic chemistry, it is generally beheved that reactions of RR C=0 and hydroxylamine at a pH close to neutral proceed through nucleophilic attack of the nitrogen electron pair on the electrophilically activated C=0 carbon. Usually, the preparation of oximes via condensation of the carbonyl compounds and hydroxylamine hydrochloride needs long reaction times . 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

The use of 0-acylhydroxylamine-type reagents for amination of a-metallated carbonyl compounds is limited. The use of 0-mesitoylhydroxylamine 2j or 0-(3,5-dinitromesitoyl) hydroxylamine 2k in the amination of the enolate derived from 3-methylbutanoic acid was unsuccessful ". 

There are a few reports on the amination of a-metallated carbonyl compounds with 0-(arenesulfonyl)hydroxylamine-type reagents. However, in recent years there has been substantial progress in Af-(alkoxycarbonyl) 0-(arenesulfonyl)hydroxylamine [alkyl N-(arenesulfonyloxy)carbamate]-type reagents for the amination of enolates and eniminates. 

A-Metal derivatives of A-(aUtoxycarbonyl) 0-(arenesulfonyl)hydroxylamines, [alkyl A-metal A-(arenesulfonyloxy)carbamates] 3i-o have been used in the amination of a-metallated carbonyl compounds to give A-Boc [N(COOBu-f)] or A-Alloc [N(COOCH2 CH=CH)] protected a-aminocarbonyl compounds. 

Oxaziridines unsubstituted at nitrogen (9, R =H) (in general used as aminating reagents, see Sections 3.5.4 and 3.5.6), are prepared by treatment of carbonyl compounds with chloramine or hydroxylamine-O-sulfonic acid in aqueous media (91S327). This method is, however, limited to certain carbonyl compounds with cyclohexanone, followed by butanone, benzaldehyde, and trichloroacetaldehyde giving the best results. 

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