Hydroxamic acids aldehydes

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)... 

When primary nitro compounds are treated with sulfuric acid without previous conversion to the conjugate bases, they give carboxylic acids. Hydroxamic acids are intermediates and can be isolated, so that this is also a method for preparing them. Both the Nef reaction and the hydroxamic acid process involve the aci form the difference in products arises from higher acidity, for example, a difference in sulfuric acid concentration from 2 to 15.5 M changes the product from the aldehyde to the hydroxamic acid. The mechanism of the hydroxamic acid reaction is not known with certainty, but if higher acidity is required, it may be that the protonated aci form of the nitro compound is further protonated. 

When the compound for identification fails to respond to test 4 (aldehyde or ketone), the next class reactions to apply are the hydroxamic acid test and saponification, i.e., hydrolysis in alkaline solution. These are the class reactions for esters and anhydrides the rarely-encountered lactones react similarly. 

Aldehyde 54 and the hydroxamic acids 55 were generated together in an acid-catalysed elimination reaction (Scheme 7 pathway (ii)). A crossover experiment indicated that esters are formed in a concerted rearrangement concomitant with the likely formation of the hydroxynitrene 57 (Scheme 7 pathway (iii)) while there is no evidence to date for the formation of hydroxynitrene, joint solvolysis of equimolar quantities of /V-acetoxy-/V-butoxy-/>-chlorobenzamide 26e and N- acetoxy-/V-benzyloxybenzamide 27a afforded significant quantities of butyl p-chlorobenzo-ate (36%) and benzyl benzoate (54%) as the only esters. This is an example of a HERON reaction, which has been identified in these laboratories as a characteristic rearrangement of bisheteroatom-substituted amides.32,33,42 43 155 158 Since ester formation was shown to prevail in neutral or low acid concentrations, it could involve the conjugate anion of the hydroxamic acid (vide infra).158... 

Nitrosobenzenes react with the carbonyl group of aldehydes to yield hydroxamic acids 73, according to reaction 20. Recently, the reactions between some X-substituted nitrosobenzenes (X = H, p-Me, p-C 1, m-Cl, p-Br) and formaldehyde were reported194 in order to investigate the mechanism of the hydroxamic acid formation. The mechanism reported in Scheme 9 involves a first equilibrium yielding the zwitterionic intermediate 74 which rearranges (by acid catalysis) into hydroxamic acid 75. The presence of a general acid catalysis, the substituent effect (p values of the Hammett equation equal —1.74),... 

A very simple chiral Lewis acid, prepared by mixing optically pure BINOL with 3 equiv of Me3Al, catalyzes the [4+2] cycloaddition of A-hydroxy-A-phenylacry-lamine with cyclopentadiene at 0°C in high yield (>96%) and a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful (Scheme 12.14). ... 

Formally, they can all be viewed as derivatives of hydroxylamine, H2N—OH indeed, oximes can be prepared by the addition of hydroxylamine to aldehydes and ketones (equations 1 and 2), and hydroxamic acids by its reactions with acetyl halides and esters (equations 3 and 4). ... 

Formation of hydroxamic acids via the reaction of the carbonyl group of aldehydes and a-oxo acids with the aromatic or aliphatic C-nitroso group belongs to the small number of nucleophilic reactions of the C-nitroso group. ... 

Angeli and Rimini discovered that A-hydroxybenzenesulfonamide 211 formed hydroxamic acids in fair to good yields if treated with aldehydes in the presence of sodium methoxide in MeOH (Scheme 9i) 6 69 Unfortunately, the acidic worknp afforded the desired hydroxamic acid together with the benzenesnlfinic acid 212 as a byprodnct. 

Recently, Porcheddu and Giacomelli have reported a convenient one-step procednre for the synthesis of hydroxamic acids 215 starting from aldehydes 213 and solid-snpported A-hydroxybenzenesulfonamide 214 (Scheme 92). The hydroxamates are isolated in good to high yields and purities by simple evaporation of the volatile solvents, after treatment of the crude reaction mixture with sequestering agents (216 and 217). 

Aldehyde (106) and the hydroxamic acids (107) were generated together in an acid-catalysed elimination reaction (Scheme 20, pathway (i)). 

Quinoline 1-oxide undergoes nucleophilic attack by ozone to yield a hydroxamic acid (128), and 40% of the starting iV-oxide is recovered (Scheme 74). When an excess of ozone is employed the aldehydes (129) and (130) are obtained. Formation of these products has been attributed to electrophilic attack by ozone rather than further oxidation of (128), because in a separate experiment (128) yielded carbostyril on treatment with ozone. Isoquinoline 2-oxide yields 2-hydroxyisoquinolin-l-one, and acridine 10-oxide gives 10-hydroxyacridone and acridone in a similar manner to the above. Likewise, phenanthridine 5-oxide affords mainly 5-hydroxyphenanthridone. Quinoline 1-oxide undergoes oxidation by lead tetraacetate as shown (Scheme 75). 

The starting material for the tricyclic NSAID meseclazone (69-5) consists, appropriately, of chlorosalicylic acid (69-1), which has NSAID activity in its own right. Reaction of the acid with hydroxylamine gives the hydroxamic acid (69-2). Treatment of that product with the diethyl acetal from 4-chlorobutyraldehyde (69-3) gives the derivative (69-4), which is in effect a carbinolamine derivative of the aldehyde. Exposure to a mild base results in the formation of the final ring by displacement of the terminal side chain chlorine by the hydroxylamine oxygen [71]. It is not at all unlikely that the product, meseclazone (69-5), is actually converted back to the salicylate (69-1) in vivo. 

Reduction of hydroxamic acids. Buffered TiC lj can reduce simple hydroxamic acids (equation I). Yields are high when R1 is an alkyl group when it is hydrogen, aldehydes are obtained as by-products. The reagent also reduces substituted N-hydroxy-2-azetidinones to /Mactams (equation 11). 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

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... 

Hydroxamic Acids by Interaction of Aldehydes and Sodium Nitto-... 

Preparations of hydroxypyrazine A-oxides by primary syntheses have been included in Chapter III and are summarized briefly as follows Section 1II.3, 2-hydroxypyrazine 1-oxides from a-aminohydroxamic acids and 1,2-dicarbonyl compounds or a,/l-unsaturated a-bromo aldehydes (545-548) Section III.4, 2-hydroxy-3,6-dimethylpyrazine 1-oxide from the bisulfite derivatives of pyruvo-hydroxamic acid and aminoacetone (548) and Section III.5, ring closure of the C-C-N-C-C-N-0 system (545, 546, 548-553). In addition to these preparations... 

The enzyme 2-C-methyl-D-erythritol-4-phosphate synthetase appears to catalyse a Bilik reaction (Figure 6.10) the substrate l-deoxyxylulose-5-phosphate is converted to the title compound via an intermediate aldehyde, whose carbonyl derives from C3 of the substrate. The first step is thus a Bilik reaction and the aldehyde is subsequently reduced by the enzyme using NADPH as reductant, The X-ray crystal structure of the Escherichia coli enzyme in complex with the promising antimalarial Fosmidomycin (a hydroxamic acid) reveals a bound Mn " coordinated to oxygens equivalent to the substrate carbonyl and 03. The stereochemistry and regiochemistry follow the normal Bilik course, although the crystallographers favour an alkyl shift rather than a reverse aldol-aldol mechanism. The intermediate aldehyde has been shown to be a catalytically competent intermediate. 

Synthesis of hydroxamic acids from aldehydes and N-sulfonylhydroxylamine also used as a color test for aldehydes (see 1st edition). 

The interaction of phenyl isocyanodichloride (120) with 2,4-dithiobiurets (121) affords the 2,4,6-triimino-l,3,5-dithiazines (122) (Equation (26)) <84JIC149>. The hydroxamic acid derivatives (123) are capable of forming cyclic acetals with an aldehyde, thus giving rise to the 1,5,2-dioxazinone... 

The most significant synthetic route to these compounds is the condensation of A-(a-hydroxy-acyl)hydroxamic acids with carbonyldiimidazole (Equation (23)) or aromatic aldehydes (Equation... 

The formation of the hydroxamic acids (213) by cyclization of the nitroso-aldehydes (212), which are intermediates in the photolysis of 17/3-yl nitrites, was shown not to involve electronically excited species. Further studies relevant to the photochemistry of veratr-13(17)-enin-ll/8-yl nitrites (214) have been reported photolysis of the etiojerva-5,13(17)-dien-ll/S-yl nitrite (215) gave the parent alcohol, the nitrone (216), and the iV-oxide (217). Although this reaction is more complex than that reported for the 12a-analogue (214), the... 

Syrup. Shows mutarotation. (a)g1 + ]° — —14.5" (3 days, c = 11). Sol in water. Slowly reduces cold Fehling s sola-Sodium amalgam reduces it to natural, inactive erythrito). No aldehyde reaction with ben zen esu I f hydroxamic acid. Not fermented by yeast. 

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