Hydroxamic acids ethers

A further type of nitro-group rearrangement gives rise to a cyclic hydroxamic ether. Noland e.t aL describe the action of cold, dilute sulfuric acid on the sodium salt of 5-nitronorbornene (98), which results in conversion to the oxazinone (101). This complex rearrangement is rationalized by the sequence 98 101 involving intermediate formation of the nitrile oxide (99) and the hydroxamic acid (100). 

There has as yet been no systematic work on the mass spectra of cyclic hydroxamic acids, but from the limited information available the direct loss of 0 or OH from the molecular ion is to be expected. The fragmentation behavior of the 0-alkyl derivatives is rather unpredictable, although again processes involving fission of the N—0 bond are generally important. Table II shows the prominent first-generation fragment ions from a few hydroxamic acids and their ethers. 

NITRILE OXIDES. Nitrile oxides are a well known class of compds represented by R.C N- 0, and are usually prepd by treating hydroxamic acid chlorides with a mild alkali, thus eliminating HQ (Ref 2). Wieland (Refs 1 3) was responsible for the first isolation of free nitrile oxides. These compds are somewhat unstable, showing a marked tendency to dimerize to (he corresponding furoxanes (1,3-dipolar addition) (Refs 2 3). The nitrile oxides add to a considerable number of carbenes, as benzonitrUe oxide (for example) to a large number of olefins in ether at 20° (Ref 3)... 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid in polyphosphoric acid, though the scope is essentially limited to phenolic ethers. 

As early as 1899, 8tieglitz proposed a tetrahedral intermediate for the hydrolysis of an imino ether to an amide. Thns it was clear qnite early that a complicated overall transformation, imino ether to amide, would make more sense as the result of a series of simple steps. The detailed mechanism proposed, althongh reasonable in terms of what was known and believed at the time, wonld no longer be accepted, but the idea of tetrahedral intermediates was clearly in the air. 8tieglitz stated of the aminolysis of an ester that it is now commonly snpposed that the reaction takes place with the formation of an intermediate prodnct as follows referring to work of Lossen. (Note that the favored tautomer of a hydroxamic acid was as yet unknown.)... 

As second example for the scale-up of solid-phase reactions directly on solid support, we chose an arylsulfonamido-substituted hydroxamic acid derivative stemming from the matrix metalloproteinase inhibitor library (MMP) of our research colleagues (Breitenstein et al. 2001). In this case, there was already a solution-phase synthesis available for comparison (see Scheme 4). The synthesis starts with the inline formation of a benzaldehyde 18 with the glycine methyl ester, which is then reduced to the benzylamine 20 using sodium borohydride in methanol/ THF (2 1). The sulfonamide formation is carried out in dioxane/H20 (2 1) with triethylamine as the base and after neutralisation and evaporation the product 21 can be crystallised from tert. butylmethyl ether. After deprotection with LiOH, the acid is activated by treatment with oxalyl chloride and finally converted into the hyroxamic acid 23 in 33.7% yield overall. 

Two derivatives of a cyclosilyl ether 148 have been synthesized by a German team <1994TL4335>. The enolizable cyclic hydroxamic acid 147 when treated with 2equiv of lithium diisopropylamide followed by reaction with di-fert-butyldichlorosilane in toluene yielded the stable [l,3,4,2]dioxazasilolo[5,4-c][l,4]oxazine derivative 148. 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

Electrochemistry of hydroxylamines, oximes and hydroxamic acids 503 Also, primary Af-alkoxyalkylamines afforded the corresponding oxime ethers (equation... 

Photoexcited nitrobenzene may be used for benzylic hydroxylation (at C-9) of 17/3-acetoxy-3-methoxyoestra-l,3,5(10)-triene. The photochemistry of the 17/3-nitro-steroid (217) is markedly solvent dependent, the major products being in ether the 17-desnitro-compound (218), in propan-2-ol the hydroxylamine (219), and in EtOH-NaOEt the hydroxamic acid (220) and the cyclopropane (221). The hydroxamic acid (220) is probably formed through the oxaziridine (Scheme 7). Although there are analogies to this in the photochemistry of nitrones and oximes, the photoreduction of a nitroalkane in propan-2-ol to an alkyl-hydroxylamine appears to have no precedent. Further studies of photochemistry of conjugated... 

Formation of hydroxamic acids has been reported during the photolysis of steroidal C-17 fl-nitrite esters,227 of ether dl-bornyl ether, and of dl-isobornyl nitrite.144... 

Bodenant and coworkers [387] have taken advantage of the affinity of protons for the nitrogen lone pair of hydroxamate in the design and synthesis of 53 and 54. Two hydroxamic acids, each bearing a pyrene, were covalently attached at the 1,3-positions of the lower rim of calix[4]arene. Methanol and diethyl ether solutions of 53 exhibit signatures of both pyrene monomer and excimer fluorescence. As is the case for 37 through 40, the intensity ratio of... 

Ketones, aldehydes Carboxylic acids, carbox-amides Alcohols Ethers Water C=0, HC=0 Vanillin COOH, CONH Alanine, cysteine, hydroxamic acid C-OH, C-N-O Ethanol C-O-C, O-C-N Diethylether h2o 2s-n 2s-n li-O li-O 1 s-o 530.6-531,3b 532.0-532.7a,b c,e 534.1e,g 535.4-535.6e,g 535,537-542d,f... 

An antibiotic active against Mycobacterium phlei, S. aureus and other bacterial strains has been isolated from a Streptomyces sp. and named actinonin. It is obtained as fine, white needles or colorless rods from ethanol-ether, m. p. 148-149° (uncorr.). Soluble in water, alcohols, and pyridine stable in cold dilute alkali and acid. C19H35O5N3. Actinonin is apparently a primary hydroxamic acid (49, 93). 

We now turn to some rarities. 2-(Trimethylsilyl)ethyl ethers do not belong to the alkoxymethyl acetal clan but they are included here because the conditions used to cleave them resemble the conditions used to cleave SEM ethers. The 2-(trimethylsilyl)ethyl ethers in 300 1 en route to the siderophore Nannochelin A [Scheme 4.300] were impervious to trifluoroacetic acid in dichloromethane (1 1) for five hours at 0aC. thus allowing selective scission of the terr-butyl ester. The two hydroxamic acids were then liberated with trifluoroborane etherate in the final step.549... 

An interesting preparation of 128 involves the cycloaddition of carbon suboxide to the anil of cyclopentanone (129).87 Compound 129 also reacts with monosubstituted malonyl chlorides to give iV-aryl-2-oxo-3-alkyl-4-hydroxy-6,7-dihydro-5ff-1 -pyrindines (131) in fair yields.88 Similarly, the oxime ether of cyclopentanone (132) reacts to give the cyclic hydroxamic acid derivative (133),89 and benzylmalonyl chloride reacts with the A,A-dimethylhydrazone of cyclopentanone (134a) to give 134b in 90% yield.90... 

The nitrone of piperidine reacts with phenyl vinyl ether to yield a 1,3-dipolar cycloaddition product. Benzylation led to a ring-opened product which was converted to a hydroxamic acid. This is desired functionality in medicinal chemistry because it is a metal-binding ligand <03S1221>. 

Brief reports of cycloadditions with chiral acyl nitroso dienophiles have recently appeared. - In one study, acyl nitroso compound (101) derived from the corresponding hydroxamic acid was added to cy-clohexadiene to afford a 3.5 1 mixture of diastereomeric adducts (102) and (103). It was proposed that dienophile (101) reacts in the cyclic chelated form shown, since the related methyl ether which cannot internally hydrogen bond shows much lower diastereoselectivity. ... 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid (34) in polyphosphoric acid, but the scope is essentially limited to phenolic ethers.The reaction of an aromatic compound with aniline, BU4NF and KMn04 led to the diarylamine. The formation of hydroindole derivatives was accomplished by reaction of a A-carbamoyl phenylethylamine derivative with phenyliodine (III) diacetate, followed by Bu4NF. Direct amidation via ipso substitution by nitrogen was accomplished when a A -methoxy arylethylamide (35) was... 

Alternatively, DIBOA and DIMBOA in a THF solution have been methylated witii a solution of diazomethane in diethyl ether at their more acidic hydroxamic acid unit, regioselectively. 

Hydroperoxy-2-nitropropane, 256 p-Hydroquinone, 331,393,418 p-Hydroquinone dimethyl ethers, 432 Hydroquinones, 72 Hydrosilylation, 562 Hydroxamic acids, 204 2-Hydroximino-l-phenylpropane, 124 ai-Hydroxyacetophenone, 342 (3-Hydroxyacetylenes, 144-145 a-Hydroxy acids, 492 (5-Hydroxy acids, 301 1-Hydroxyadamantane, 126 a-Hydroxyaldehydes, 342 3o-Hydroxy-5a-androstene-17-one, 227-228... 

Molybdenum and tungsten have been separated on a chelating resin with thioglycolate groups. A mixture of these metals is sorbed from an acetate solution of pH 4.3, then Mo and W are eluted successively with 2 M HCl and a mixture of 0.1 M NaOH and 0.1 M NaCl [36]. The sorption of Mo and W on silicate sorbents, modified with hydroxamic acids, was also studied [37,38]. Mo was also preconcentrated on dibenzo-18-crown-6 ether columns from HCl [39] and HBr [40] media. 

The crown ether, 18-crown-6 [34—36], [2.2.2]-cryptand [37], and calixarene derivatives of hydroxamic acids have also been used for extraction of U(VI) [38]. 

Hydroxamic acids react with diaryliodonium salts to afford the O-phenyl derivatives. number of heterocyclic compounds containing A -hydroxyamino groups were selectively arylated on the oxygen atom. 0 (Table 5.4) In the case of oximate anions, ambident behaviour was observed, with predominant 0-arylation. With heterocyclic oximes, the 0-aryl ethers were mainly formed and served as precursors to prepare unstable aryl fulminates, 19 (Table 5.5) In the reaction of quinolone derivatives with diaryliodonium salts, the products of O- or C-arylation were obtained.(Table 5.6)... 

The route developed by Fowler and his associates (287) involved an ingenious application of the aza-Cope rearrangement, in which the bridged hydroxamic acid derivative 468, prepared as shown in Scheme 48, was subjected to flash vacuum thermolysis. The product, the enol ether 469, was not isolated but immediately hydrolyzed to the ketone 470, which was then hydrogenated and cyclized to the racemic ketone 466. This appears to be the first application of the aza-Cope rearrangement in synthetic chemistry, since the reaction is normally not thermodynamically favored when C-1 is replaced by nitrogen. However, it is clearly successful when the nitrogen is acylated, as in the present example. 

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