Hypochlorite reactions with carboxylic acids

Methyl ketones are degraded to the next lower carboxylic acid by reaction with hypochlorite or hypobromite ions. The initial step in these reactions involves base-catalyzed halogenation. The a-haloketones are more reactive than their precursors, and rapid halogenation to the trihalo compound results. Trihalomethyl ketones are susceptible to alkaline cleavage because of the inductive stabilization provided by the halogen atoms. 

We have found that carboxylic acids are obtained advantageously from methyl ketones by reaction with hypochlorites in an aqueous medium... 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

The reaction can also be effected with hypochlorite ion, and this constitutes a useful method for converting methyl ketones to carboxylic acids. 

Nickel(lll) oxide, prepared from a nickel(ii) salt and sodium hypochlorite, is used for the oxidation of alkanols in aqueous alkali [46]. Residual nickel(Ii) oxide can be re-activated by reaction with sodium hypochlorite. Nickel oxides have also long been used in the manufacture of the positive pole in the Edison nickel-iron rechargeable battery, now largely superseded by die lead-acid accumulator, and in the Jungner nickel-cadmium batteries used as button cells for calculators [47]. Here, prepared nickel oxide is pressed into a holding plate of perforated nickel. Such prepared plates of nickel(lli) oxide have been proposed as reagent for the oxidation, in alkaline solution, of secondary alcohols to ketones and primary alcohols to carboxylic acids [48]. Used plates can be regenerated by anodic oxidation. 

Immobilized TEMPO has been used for the one-pot oxidation of alcohols to carboxylic acids as well.26 For this purpose TEMPO resin 1 was combined with two ion-exchange resins loaded with chlorite anions and hydrogen phosphate in the presence of catalytic amounts of potassium bromide and sodium hypochlorite in solution. The reaction required work-up for the removal of salts, but tolerated several protecting schemes and afforded pure products in good to excellent yields. The reaction is initiated by catalytic TEMPO oxidation of alcohols to aldehydes driven by dissolved hypochlorite followed by oxidation to the carboxylic acids effected by chlorite. 

Benzisoxazole-3-carboxylic acid, 6-nitro-, reaction with methanolic hypochlorite, 59, 273... 

It is known from Houben-Weyl, Methoden der organischen Chemie, volume 8, pages 415-416, that carboxylic acids can be manufactured by oxidation of methyl ketones with hypohalites in an aqueous medium. The publication recommends dispersing the ketone by means of oxidation-resistant emulsifiers or carrying out the reaction in the presence of dioxane all the examples were carried out in this way. In most cases the reaction only takes place satisfactorily with hypobromite solutions, which are more expensive and less stable than hypochlorite solutions. For this reason alone, industrial utilization of the reaction is confined to special reactions with aromatic ketones. 

There are a variety of stoichiometric oxidants that can be used in conjunction with 2,2,6,6-tetramethylpiperdine 1-oxyl (TEMPO), including TCCA, iodobenzene diacetate, meto-chloroperbenzoic acid (wi-CPBA), sodium bromite, sodium hypochlorite, and /V-chloi osuccinirnide. TEMPO can be used to oxidize primary alcohols to aldehydes or carboxylic acids, based on reaction conditions. A particularly attractive feature is that the product is usually isolated quite pure after concentration of the organic layer. 

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