Hydroxamic acids methods

Succinyl coenzyme A trisodium salt [108347-97-3] M 933.5. If it should be purified further then it should be dissolved in H2O (0.05g/mL) adjusted to pH 1 with 2M H2SO4 and extracted several times with Et20. Excess Et20 is removed from the aqueous layer by bubbling N2 through it and stored frozen at pH 1. When required the pH should be adjusted to 7 with dilute NaOH and used within 2 weeks (samples should be frozen). Succinyl coenzyme A is estimated by the hydroxamic acid method [J Biol Chem 242 3468 1967]. It is more stable in acidic than in neutral aqueous solutions. [Methods Enzymol 128 435 7956.]... 

An iron-hydroxamic acid method was used by Andronov and Yudina, who measured air concentrations of vinyl acetate in the presence of butyraldehyde, acetaldehyde, and hydrogen chloride (9.). 

Fig. 151). The hydroxamic acid method is satisfactory for colorimetric determination of lipid esters [47, 204, 213]. Sugar esters can be treated with resorcinol-hydrochloric acid and determined colorimetrically [46, 93]. Mono-, di- and triglycerides may be quite accurately estimated by alkaline hydrolysis and titrimetric determination of the glycerol [76].

The hydrogenolysis of hydroxamic acids (22) and hydra2ides (23) has also been used to synthesi2e amides. One of the earliest methods for the preparation of amides consists of treating acid chlorides with dry ammonia or an amine (24). 

In 2000, an efficient three-step procedure for the synthesis of 5-substituted 3-isoxazolols (without formation of undesired 5-isoxazolone byproduct) was published. The method uses an activated carboxylic acid derivative to acylate Meldrum s acid, which is treated with A,0-bis(ten-butoxycarbonyl)hydroxylamine to provide the N,0-di-Boc-protected P-keto hydroxamic acids 14. Cyclization to the corresponding 5-substituted 3-isoxazolols 15 occurs upon treatment with hydrochloric acid in 76-99% yield. 

The cyclic hydroxamic acid (104) obtained by this route had previously been prepared by the two methods illustrated. These exemplify well the variants possible within route (ii). 

The following discussion of hydroxamic acids includes saturated systems, e.g., 2, compounds such as 3, derived from aromatic systems, 7V-hydroxyimides such as 7V-hydroxyglutarimide (78), and certain of their derivatives including thiohydroxamic acids. Naturally occurring cyclic hydroxamic acids are discussed to show the range of structural types that has been found, hut macrocyclic polyhydroxamic acids are mentioned very briefly, because several comprehensive reviews of these compounds are already available. The main purpose of this review is to summarize the methods available for the synthesis of cyclic hydroxamic acids, to outline their characteristic reactions, and to present some useful physical data. Their synthesis and some biological properties have previously been reviewed by Coutts. ... 

Because of the great range of structures containing cyclic hydroxamic acid functions it is difficult to give a concise summary of the available synthetic methods. Nevertheless, the vast majority of published syntheses depend on condensation reactions involving only familiar processes of acylation or alkylation of hydroxylamine derivatives. The principles of such syntheses are outlined in a number of typical examples in Section III, A but no attempt has been made to cover all reported cases. 

By this method, Chauveau and Mathis have prepared cyclic hydroxamic acids (41) containing a sulfur atom in the ring. The acyclic precursors (40) were formed by alkylation of a thiol anion. 

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

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 method which has been of most preparative value is that established by Panizzi el and Di Maio and Tardella. Benzene-sulfonhydroxamic acid (74), known as Piloty s acid, reacts with a cyclic ketone (73) in alkaline media at 0 , to produce the ring-expanded hydroxamic acids (75 and 76) in approximately equal yield. 

Reduction of cyclic hydroxamic acids generally leads to lactams or the corresponding amines. Chemical methods have frequently been preferred to catalytic hydrogenation, probably because the choice of... 

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. 

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

Dehydration of O-silylated hydroxamic acids is used as a general method in the synthesis of nitrile oxides (95) in the presence of trilluoromethanesulfonic anhydride and triethylamine. 

A general synthetic method for acyclic a-alkoxynitrones (196) involves the alkylation with triflates of hydroxamic acids (195) in neutral conditions (Scheme 2.69) (352). Similarly, the synthesis of cyclic methoxynitrone of pyrrolines (197) has been carried out (353). 

The presence in the heterocycle of additional basic centers or those open to alkylation can lead to a change in reaction directions. It essentially limits the application of this method in the formation of a-methoxy nitrones. In such cases, it is reasonable to use diazomethane and, depending on the structure of hydroxamic acid (198-201) the yields of a-methoxy nitrones (197), (202-204) can rise from 17% up to 62% (Scheme 2.70) (353). 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

In 1983, Prasad et al.12 first reported the condensation of chloromethyl polystyrene with /V-hydroxyphthalimide to give the ester, hydrazinolysis of which yielded the desired resin-bound hydroxylamine. However, the sole purpose of this reagent was to react with, and hence extract ketones from, a complex steroidal mixture, and its use for the solid-phase synthesis of hydroxamic acids was not explored. Recently, the exploitation of the above solid-phase approach for the synthesis of hydroxamic acids was independently reported by three groups,7-9 all of which differ only in the method for the initial anchoring of TV-hydroxyphtha-limide to an 4-alkoxybenzyl alcohol functionalized polystyrene or trityl chloride polystyrene. Subsequent /V-deprotection was... 

TOA were determined, in the supernatant prepared as described by Hissett et al (25), by the method of Montgomery et al (26). The organic acids were esterified with acidified ethylene glycol. The esters were then reacted with hydroxylamine and the hydroxamic acids thus formed were converted to their ferric complexes and their concentrations were determined by optical density measurements at 500u. 

The HDAC inhibitors TSA and TPX (Fig. 2) have been utilized as structural leads in the early stages of the quest for new and more selective small molecule inhibitors of the HDAC enzyme family. In order to investigate the function of the individual HDAC members, Schreiber et al. synthesized a library of 7200 potential HDAC inhibitors based on the structural features of TSA and TPX [93]. The members of this library were prepared on solid support by means of split pool methods. The key characteristics of these compounds consist of a dioxane-containing capping region and a zinc binding motive, connected via an aliphatic chain. Three different zinc binders, i.e., carboxylic acid, o-aminoanilide and hydroxamic acid were used. 

Although some of this early work was based on N nuclei which are of special interest for studies of hydroxylamines, oximes and hydroxamic acids, a variety of reasons led to a concentration of work on F and, particularly, H nuclei. These include the sensitivity of these nuclei to the method, the advent of commercially available instrumentation to allow exploitation of this sensitivity, the abundance of H compounds and the unfavorable spectral characteristics of N. ... 

The main first part of the review (Section HI) summarizes preparation of hydroxylamine derivatives through alkylation, arylation, and addition reaction of hydroxylamine, or its derivatives such as hydroxamic acids and A-oxysulfonamides. The second main part (Sections IV-VIII) describes methods of creation of hydroxyamino groups de novo from other functionalities. Due to easy interconversion outlined in Section II, syntheses of hydroxylamines and hydroxamic acids are considered together. For the same reason, the chapter also relates to synthesis of A-oxysulfonamides and V-oxyphosphonamides as far as these methods are of interest for the preparation of hydroxylamines. 

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... 

Conversion of hydroxamic acids into hydroxylamines is usually performed by hydrolysis or alcoholysis under acidic"" or basic catalysis , although other methods like reaction with trimethylsilyl iodide have also been sparingly used. 

Other 0-aUcylation methods are exploited less frequently. 0-Allylation of Af-substituted hydroxamic acids of type 25 with allyl carbonates such as 26 and related compounds has been achieved through palladium catalyzed addition-elimination (equation 16). 

The A-hydroxycarboxamide group is a key fragment of many siderophores so that a convenient synthesis of this group is crucial for further progress. A variety of methods have been attempted for the preparation of hydroxamic acids starting from carboxylic acids. Although some of these methods are quite efficient for the preparation of substituted hydroxamic acids, the preparation of the parent compound is still a problem and yields are often moderately unacceptable, in part due to the low solubility of the parent hydroxylamine hydrochloride in organic solvents. 

Although the simplest route to prepare hydroxamic acid derivatives remains the reaction of hydroxylamine with acid chlorides, this last method cannot be apphed to all Af-protected-a-amino acids. The synthesis of Fmoc-protected amino acid hydroxamates represents the only exception to this rule . In fact, Fmoc-amino acid hydroxamates 98 can be synthesized by the acylation of hydroxylamine using Fmoc-amino acid chlorides 97 in the presence of MgO (Scheme 52). The route is simple, efficient, and affords good yields of products. 

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