Oxidation of hydrazides

Oxidation of hydrazides. Acid hydrazides are oxidized to carboxylic acids by several Cu(I I) salts, particularly Cu(OH)2 and Cu(OH)CI. The salt can be used in calulytic amounts if oxygen is available to convert Ou(I) to Cu(II). For this purpose the most convenient salt is Cu(OAc), in THF or CH,OH (equation I). 

Peptide synthesis by in situ activation Anodic oxidation of hydrazides... 

Facile formation of esters occurs on oxidation of hydrazides in the presence of alcohols regardless of the oxidant involved the hydrazides are oxidized via diimide intermediates to the corresponding acyl radicals which are prone to nucleophilic acyl substitution in polar aprotic methanol but do not undergo further oxidation to acylium ion even by the strong oxidants." ... 

The activation of acids by oxidation or dehydration of their derivatives has been studied by a German school. Oxidation of an acid diphenylhydrazide by JV-bromosuccinimide yields the azonium ion (96), which functions as a highly activated acid derivative, azobenzene being eliminated on nucleophilic attack. A related activation by oxidation has been performed in the solid phase by production of the polymer-bound azo-compound (97), nitrogen being expelled on amide-bond formation. Dehydrative activation is exemplified by conversion of the ester (98), prepared from the acid and 1,1-diphenylethylene glycol, into the enol ester (99). The generation of azo-compounds by anodic oxidation of hydrazides has been reported. All of these procedures have been utilized successfully in peptide synthesis. 

The available studies indicate that diimide has been used as a reducing agent for the preparation of HNBR. It has been used mainly as an alternative for hydrogenation of nitrile rubber latex. The use of diimide to hydrogenate low-molecular weight olefines is well known in the organic literature [93]. Diimide can be conveniently generated in situ by thermal treatment of solutions of p-tolu-enesulfonyl hydrazide or oxidation of hydrazine. 

Van Zyl JM, BJ van der Walt (1994) Apparent hydroxyl radical generation without transition metal catalysts and tyrosine nitration during oxidation of the anti-tubercular drug, isonicotinic acid hydrazide. Biochem Pharmacol 48 2033-2042. 

The 3f/-pyrazole-3,5(4//)-diones (7), prepared by lead tetraacetate,29,30 or tert-butyl hypochlorite31,32 oxidation of malonic acid cyclic hydrazides, are generally less stable than the triazoles 5, and are not isolable. The monocarbonyl derivatives (8-10) have been reported.33-36 The unstable 1,3,4-thiadiazole-2,5-dione (11) has been generated and reacted in situ.31,3 ... 

Six-membered ring ADC compounds can be generated by oxidation of the corresponding cyclic hydrazides. Pyridazine-3,6-dione (12) and phthalazine-1,4-dione (13, R = H), often called diazaquinones,4 are stable in solution only at low temperature, but can be generated, and intercepted at higher temperatures.39-43 Fusion of an extra benzene ring increases stability44 and the tetracyclic compound 14 is relatively stable.45 Substituted phthala-zine-l,4-diones have been widely studied because of their involvement in... 

Figure 1.107 The N-terminal aldehyde group on a peptide formed from periodate oxidation of serine or threonine residues can be conjugated with a hydrazide-containing molecule to produce a hydrazone bond.

Figure 9.31 The side-chain hydrazide group of this BODIPY derivative can be used to label aldehyde-containing molecules. Glycoconjugates may be labeled after oxidation of carbohydrates with sodium periodate to produce the required aldehydes.

The following protocol describes the oxidation of carbohydrate (glycans) on antibody molecules to form aldehydes and the subsequent coupling to hydrazide particles. 

The following protocol describes a method for the periodate oxidation of a glycoprotein followed by biotinylation of the resultant aldehydes using hydrazide-PEG4-biotin. Chapter 1, Section 4.6 describes an alternative protocol for the modification of glycans at their reducing ends with hydrazide compounds. 

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

The emission spectra match the fluorescence of the corresponding acid. Methane was detected as a major product in the chemiluminescent oxidation of 57 a and it was suggested that it resulted from the decomposition of methyl-diimine formed after dehydrogenation of the hydrazide 57a ... 

That a bridged peroxide 68 (for a more detailed discussion, see 1>, p. 84) arises from the intermediate open-chain peroxide formed either by recombination of hydrazide radical ion with. 02( > radical ion, such as 66, or by nucleophilic attack of ion on a carbonyl group of a diazaquinone, such as 67, appears to be very plausible. One of the most important experimental reasons for this assumption has been put forward by E. H. White and M. M. Bursey 106> who, on oxidation of luminol with... 

---