Oxidation hydroxamic esters

While the silver and zinc salts were effective Lewis acids for these cyclizations, Kikugawa and coworkers reported that the alkoxynitrenium ions could be generated directly from hydroxamic esters (4) using hypervalent iodine oxidants such as hydroxy(tosyloxy) iodobenzene (HUB) and phenyliodine(lll)bis(trifluoroacetate) (PIFA) . Presumably, with such reagents the reactions proceed through A-(oxoiodobenzene) intermediates (54), which can themselves be regarded as anomeric hydroxamic esters and sources of alkoxynitrenium ions (55) (Scheme 11). 

Oxidation of hydroxamic esters in an alcoholic solvent may prove to be useful in certain cases. Phenyliodine(III)bis(trill uoroacetate) (PIFA) oxidation of the proline derivative (185) in trifluoroethanol afforded a 26% yield of the A-methoxy-Af-trifluoroethoxy derivative (187), presumably via an intermediate Af-methoxy-A-acylnitrenium ion (186) (equation 23). ... 

Oxidations of the hydroxamic esters have been carried out in good yields using lead tetraacetate ammonium hexachloroplumbate(IV), peroxides and silver oxide ". Cooley and coworkers reported that only iV,Al -diacyl-iV,A -dialkoxyhydrazines... 

Mixtures of isomeric di-ALoxides are generally obtained when 5(6)-substituted benzofurazan 1-oxides (51) are used in the Beirut reaction52-54 however, only 7-substituted 2-cyano-3-phenylquin-oxaline 1,4-dioxides (52) were isolated from benzoylacetonitrile (PhCOCH2CN).55 The di-AAoxide mixtures obtained from reaction with acetonyl methyl sulfide (MeCOCH2SMe) were analyzed by H nuclear magnetic resonance (NMR) analysis of the mixed hydroxamic esters (53) formed by hydrolysis and methylation of the primary products.52... 

From the variation in the ratios of 6- and 7-hydroxamic esters formed in the last reaction, it was concluded that benzofurazan 1-oxides react in their o-dinitrosobenzene form 5 lb, which are intermediate between the rapidly interconverting tautomers 5 la and 51c. 

Cyclic sulfites (68) also are opened by nucleophiles, although they are less reactive than cyclic sulfates and require higher reaction temperatures for the opening reaction. Cyclic sulfite 77, in which the hydroxamic ester is too labile to withstand ruthenium tetroxide oxidation of the sulfite, is opened to 78 in 76% yield by reaction with lithium azide in hot DMF [82], Cyclic sulfite 79 is opened with nucleophiles such as azide ion [83] or bromide ion [84], by using elevated temperatures in polar aprotic solvents. Structures such as 80 generally are not isolated but as in the case of 80 are carried on (when X = N3) to amino alcohols [83] or (when X = Br) to maleates [84] by reduction. Yields are good and for compounds unaffected by the harsher conditions needed to achieve the displacement reaction, use of the cyclic sulfite eliminates the added step of oxidation to the sulfate. 

Alternatively, the oxidation may occur by coupling to a suitable reactant. In 1997, Miyashita explored the scope of oxidative aroylations with nitrobenzene (Scheme ll.lO)." With the same oxidative reagent, nitrobenzene, benzoin reactions had already been developed back in 1982 using cyanide or thiamine. The combination of an aldehyde and nitrosobenzene, in the presence of an NHC, led to the formation of 7V-phenyl hydroxamic acids in good yields. These can be further converted into hydroxamic esters via a one pot reaction in the presence of a second (o,p-unsaturated) aldehyde. Furthermore, the oxidative coupling of aldehydes with carbodiimides in air allowed access to Af-acyl urea derivatives with IMes HCl 19 as the NHC precursor. Related thioesterifications reactions have also been reported using... 

The formation of the latter compounds can be attributed to the result of the direct attack of the nucleophile R on the a- or p-carbon atoms of SENAs after elimination of the corresponding protons. However, it is most likely that the reaction proceeds through nitrile oxides or conjugated nitrosoalkenes (see Scheme 3.93). This interpretation is evidenced by generation of silyl esters of hydroxamic acids R CONHOSi as by-products. The reactions with more saturated solutions give the latter compounds as the major products. 

Electrochemical oxidation of hydroxamic acids in the presence of amines, alcohols or water afforded the corresponding amides, esters or carboxylic acids (equation 19) . ... 

Fulminic acid can be regarded as the simplest oxime. A number of compounds with an oxime group C=NOH can form salts which possess initiating properties, for example salts of nitroformoxime (methylnitrolic acid) (I) which can be obtained in a known way by the action of nitrous acid on nitromethane. Salts of form-hydroxamic acid (II), particularly the mercuric salt, also possess initiating properties [66]. Formhydroxamic acid can be obtained by the action of hydroxylamine on formic acid esters or by oxidation of methylamine. 

The teichoic acid shows an infrared absorption band at 1751 cm.-1, characteristic of carboxylic ester groups, which is not observed in samples from which the D-alanine residues have been removed. Removal of the u-alanine was readily effected with ammonia or hydroxylamine, when D-alaninamide or D-alanine hydroxamate were formed. The kinetics of the reaction with hydroxylamine reveal the high reactivity of its D-alanine ester linkages, which, like those in most other teichoic acids, are activated by the presence of a neighboring phosphate group. That the D-alanine residue is attached directly to the ribitol residues, instead of to the d-glucosyl substituents, was also shown by oxidation with periodate under controlled conditions of pH, when it was found that the D-alanine residues protect the ribitol residues from oxidation. Under the same conditions, all of the ribitol residues were oxidized in a sample of teichoic acid from which the D-alanine had been removed, and it is concluded that the ester groups are attached to C-2 or C-3 of the ribitol residues. 

Peptide a-oxo acids, a-oxo esters, and a-oxoamides are also potent inhibitors of cysteine and serine proteases. Oxidation of peptide a-substituted carboxylic acid derivatives provides a general route to these compounds (Section 15.1.5). Peptide hydroxamic acids have been shown to be inhibitors of metalloproteinase and some have been reported to have antibiotic, anticarcinogenic, and antiviral activities. Peptide hydroxamic adds may be prepared by solution and solid-phase methods using a variety of resins (Section 15.1.6). a-Aminoboronic acids may be prepared by several routes and are reported to be inhibitors of aminopepti-dases. Procedures have been developed for their incorporation into peptides (Section 15.1.7). 

The protein is treated with hydroxylamine which splits any ester linkages forming a hydroxamic acid. The amount of hydroxamic acid present may be determined colorimetrically by (a) foimation of a ferric complex, (6) oxidation to nitrous acid which is then reacted with sulfanilic acid and a-naphthylamine to give a diazo dye, or (c) hydrolyzing off the hydroxylamine which then reacts with indole. In methods (6) and (c) excess hydroxylamine must be removed before the determination. This is normally achieved by dialysis. 

Alternatively (Fig. 2, route B), a nitrile group in principle could serve as a precursor of the final hydroxamic acid function via oxidation to the nitrileoxide and its hydrolysis. This strategy would be based on the nitrile ester 10 as a key intermediate and its racemic resolution. While the resolution step could be achieved enzymatically, the oxidation experiments failed and this approach was finally abandoned. 

Other methods, among which thermolysis or photolysis of tetrazene [59], photolysis of nitrosoamines in acidic solution [60], photolysis of nitrosoamides in neutral medium [61], anodic oxidation of lithium amides [62], tributylstannane-mediated homolysis of O-benzoyl hydroxamic derivatives [63, 64], and spontaneous homolysis of a transient hydroxamic acid sulfinate ester [65] could have specific advantages. The redox reaction of hydroxylamine with titanium trichloride in aqueous acidic solution results in the formation of the simplest protonated aminyl radical [66] similarly, oxaziridines react with various metals, notably iron and copper, to generate a nitrogen-centered radical/oxygen-centered anion pair [67, 68]. The development of thiocarbazone derivatives by Zard [5, 69] has provided complementary useful method able to sustain, under favorable conditions, a chain reaction where stannyl radicals act simply as initiators and allow transfer of a sulfur-containing... 

Acylphosphoranes are oxidized to Q ,/3-dicarbonyl compounds in fair yields using aqueous NaI04 (eq 20). This method complements other methods such as the Potassium Permanganate or Ruthenium(VIII) Oxide oxidation of alkynes. NalOa is also used for the oxidation of hydroxamic acids and N-hydroxycarbamic esters at pH 6 to generate highly reactive ni-troso conqiounds. The oxidations are usually conducted in the presence of conjugated dienes so that the nitroso intermediates are trapped as their Diels-Alder cycloadducts (eq 21). 

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