Reaction with hydroxamic acid

The reaction with hydroxamic acid chlorides has been extensively used recently by Italian chemists to synthesize di- and poly-isoxa-zolyls, as exemplified by 5-substituted 3,3 -diisoxazolyIs (29). °... 

McReady, R. M., and Reeve, R. M. (1955). Test for pectin based on reaction of hydroxamic acids with ferric iron. /. Agric. Food Chem. 3 260-262. 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

Lead tetraacetate oxidizes oximes to various products. For exanqrle, the oxime of cyclohexanone gives a-acetoxynitrosocyclohexane in 35% yield.Aldoximes react with lead tetraacetate to give nitrile oxides which then yield acetyl hydroxamates 1 reaction with acetic acid. ... 

Recently, Kibayashi s group (85JA5534) elegantly carried out the stereo-controlled total synthesis of gephyrotoxin (skin extracts of neopropical poison dart frog) based upon an intramolecular nitroso Diels-Alder reaction. The hydroxamic acid 365 was treated with tetrapropylammonium periodate... 

Hoare, D. G., Olson, A., Koshland, D. E., Jr. The reaction of hydroxamic acids with water-soluble carbodiimides. A lessen rearrangement. J. 

Amides and ureas The sulfonamides undergo functional group exchange on reaction with thiolacetic acid, hydroxamic acids, and R2NC(=S)SH, in the presence of cesium carbonate. Reaction of the sulfonamides with dithioacids affords thioamides. 

Although the reaction of hydroxamic acids with diaryliodonium salts affords the 0-phenyl derivatives, (see Section 5.1.1.3.3) the reaction of the closely related iV-hydroxycarbamates led exclusively to the N-aryl derivatives. 127... 

Formation from reaction of tetracovalent P(V) chlorides with alcohols 5, 3.3.5.2 Formation from reaction of tricovalent P(Ill) compounds with alcohols 5, 3.3.5.S.3 Formation from the reaction of C6H5PCI4 with CHjCOjH 5, 3.3.5 2 Formation from the reaction of PCI, with hydroxamic acids 5, 3.3.5.2 Formation from the reaction of PCI, with [CHjCfOlljCH, 5, 3.3.5.2 Formation from the reaction of RPCI2 compounds with H0C(CH,)2C02H 5, 3.3.5.2 Formation in reactions of tetracovalent P(V) chlorides with phosphoric acids 5, 3.3.5.5.1 Formation of H2 from 1, 1.2.2.1, 1.2.3.1,... 

A reaction occurs with hydroxamic acids to produce spirophosphoranes which can exist in equilibrium with a phosphite form... 

A stopped-flow method has been used to study the reactions of the [Fe(H20) ] ion with the a-hydroxy-carboxylic acids glycolic, DL-lactic, DL-malic, and benzilic acids. The main pathway involves reactions of [Fe(H20)5(0H)] + ion with HL, and an 7d mechanism is proposed. A similar study involves reactions with acetohydroxamic acid, hydroxyproline hydroxamic acid, tryptophane hydroxamic acid, and histidine hydroxamic acid. The second-order rate constants at 25 °C fall in the range (1.14—5.90) x 10 s. ... 

Table 6.5. Rate Constants (25°C) and Activation Parameters for the Reaction of Fe and FeOlP with Hydroxamic Acids RxCO.N(OH)Rf ...

In these reactions the tested organic substance and an inorganic salt give a more or less stable strong color due to a complex salt. In Part 2 of this monograph a series of such reactions is described, such as, for example, the reaction of hydroxamic acids with ferric salts (p. 276), the reaction of phenols with ferric chloride (p. 188), the reaction of molybdenum with o-dihydro-xybenzenes (p. 191), of diacetyl dioxime with nickel salts (p. 227), of phenols with Millon s reagent (p. 196), alcohols with ceric ammonium nitrate (p. 170), alcohols with vanadium-hydroxy quinoline complex (p. 171), and the reaction of cis-enols of )5-dicarbonylic compounds and a-dicarbonyl compounds with ferric chloride, (p. 294.)... 

Another method of detection of oximes is based on the oxidation with benzoyl peroxide nitrous acid is liberated, which can be detected by reaction with sulfanilic acid and 1-naphthylamine. The reaction is also given by hydroxamic acids. 

Corbett, M. D. and B. R. Corbett. 1993. Studies on the nitroso-glyoxylate reaction. Relative hydroxamic acid production by glyoxylate, pyruvate, and formaldehyde in reactions with 4-nitrosobiphenyl. Chem. Res. Toxicol. 6 82-90. 

Fig. 2. Functional groups on modified polyacrylamides (a) formed by reaction with dimethylamine and formaldehyde (Mannich reaction) (b), quatemized Mannich amine (c), carboxylate formed by acid or base-cataly2ed hydrolysis or copolymerization with sodium acrylate and (d), hydroxamate formed by...

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

Ring substituents show enhanced reactivity towards nucleophilic substitution, relative to the unoxidized systems, with substituents a to the fV-oxide showing greater reactivity than those in the /3-position. In the case of quinoxalines and phenazines the degree of labilization of a given substituent is dependent on whether the intermediate addition complex is stabilized by mesomeric interactions and this is easily predicted from valence bond considerations. 2-Chloropyrazine 1-oxide is readily converted into 2-hydroxypyrazine 1-oxide (l-hydroxy-2(l//)-pyrazinone) (55) on treatment with dilute aqueous sodium hydroxide (63G339), whereas both 2,3-dichloropyrazine and 3-chloropyrazine 1-oxide are stable under these conditions. This reaction is of particular importance in the preparation of pyrazine-based hydroxamic acids which have antibiotic properties. 

Indirect detection of an intermediate. The overall reaction of hydroxylamine with a carboxylic acid derivative yields a hydroxamic acid as the product, Eq. (3-176). 

When Jencks reacted hydroxylamine with p-nitrophenyl acetate, p-nitrophenolate ion was released at a rate faster than that at which acetohydroxamic acid was formed. This burst effect is evidence for a two-step reaction. In this case the intermediate is O-acetylhydroxylamine, which subsequently reacts with hydroxylamine to form the hydroxamic acid. 

R = CH3 and AR = C6H4NO2.) Actually Scheme XXV and Eq. (3-176) both take place, with some of the hydroxamic acid being formed directly and some via the intermediate. (Note that each of these reactions is itself complex, presumably occurring via a tetrahedral intermediate as shown in Scheme XXII for ester hydrolysis.)... 

A variety of condensation processes can lead to cyclic hydroxamic acids. These involve either the condensation of two molecules or the intramolecular cyclization of a single compound. In some cases, a primary hydroxamic acid function is already present and formation of a cyclic compound can arise by suitable reaction on nitrogen. These processes will be dealt with first. 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

During a study of azonitrones (70), Forrester and Thomson showed that reaction with toluene-p-sulfinic acid resulted in nitrogen evolution and formation of the hydroxamic acid (66) together with the pyrrolidone (71) and the amidine (72). These workers suggested the following reaction course. Although the yield of hydroxamic acid was high, the method is not likely to be of preparative value. 

The reaction is based on an early observation by Angeli and Ahrens that Piloty s acid converted aldehydes to hydroxamic acids, and this has formed the basis of the Angeli-Rimini aldehyde test. Di Maio and Tardella propose the above reaction sequence, consistent with the observed second-order kinetics. The possibility that benzenesulfon-hydroxamic acid would decompose in alkali to give nitroxyl (HNO)... 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

The hydroxamic acid function in most alicyclic and aromatic compounds is stable to hot dilute acid or alkali, and derivatives cannot undergo normal base-catalyzed Lessen rearrangement. Di Maio and Tardella," however, have shown that some alicyclic hydroxamic acids when treated with polyphosphoric acid (PPA) at 176°-195° undergo loss of CO, CO.2, or H2O, in a series of reactions which must involve earlj fission of the N—0 bond, presumably in a phosphoryl-ated intermediate. Thus, l-hydroxy-2- piperidone(108) gave carbon monoxide, 1-pyrroline (119), and the lactams (120 and 121). The saturated lactam is believed to be derived from disproportionation of the unsaturated lactam. 

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