Oxidation with hypohalite

Since aldehydes are notoriously polymerizable and difficult to manipulate, the products of periodate oxidation are oftentimes further oxidized, with hypohalite, to carboxylic acids, or are reduced to the corresponding alcohols. Oxidation has been more usually employed than reduction, since acids frequently form crystalline salts and other conveniently prepared derivatives. A process of oxidation of these aldehydic products by hypo-bromite, in the presence of barium carbonate or strontium carbonate, was developed and used extensively by Hudson and his coworkers.107 110 194-199,90s Their method can best be illustrated by an example the further oxidation of the dialdehyde, VI, shown previously (see p. 16) to be obtained by the oxidation of the methyl a-D-aldohexopyranosides. The isolation of... 

An interesting reaction, giving an acid with the same number of carbon atoms, takes place when some ketones (having a and a hydrogens) are stirred for 10-60 min at 25-80 °C with powdered potassium hydroxide, carbon tetrachloride, water, and ten-butyl alcohol [954] (equation 418). Ketones with a hydrogens but not a hydrogens give the same product as that obtained by oxidation with hypohalites [954. ... 

Oxidation with Hypohalites in Alkaline Solutions. In alkaline solution the halogens exist as hypohalous acid and hypohalite ions. The oxidation is likely to be more drastic than for the free halogens. Thus, whereas free iodine will not act as an oxidant, hypoiodite is a powerful oxidizing agent. Hypobromite and hypochlorite particularly are likely to produce oxidation of primary and secondary alcoholic groups and cause cleavage of carbon-carbon bonds. As noted above, the processes are complicated by the tendency of hypohalite to be converted to halate ions. 

The traditional method of oxidizing hydrazine derivatives makes use of halogens or hypohalites as oxidizing agents. The techniques range from the preparation of l,l -azobis(l-cyclohexanenitrile) by the addition of bromine to an alcoholic hydrochloric acid solution of the corresponding hydrazine [89], through the use of bromine water [90, 91] to oxidations with sodium hypo-bromite [64] or sodium hypochlorite [92]. 

The oxidation with halogens and hypohalites is a complicated reaction, as it depends strongly on the conditions of temperature, acidity, and concentration of the reacting species. The halogens show considerable differences in the positions of the various equilibria and the speed with which the equilibria are attained (see Table I). In acidic solution, the equilibrium between free halogen and hypohalous acid [Eq. (7. )] lies far to the left, and the concentration of hypohalous acid is very low. When alkali is added to the system, the concentration of hypohalite ion increases, according to Eq. (14). 

A related reaction occurs on irradiation of a hypochlorite (Scheme 2). The alkoxyl radical can again abstract a hydrogen atom in a l,S-shift, and the final chloro alcohol can be cyclized to form a tetrahydro-furan. Some processes lead directly to the cyclic product For instance, an alcohol with an accessible 8-hydrogen can be directly converted to a tetrahydrofuran on refluxing with lead tetraacetate. In a related reaction, treatment of an alcohol with silver carbonate and bromine can lead to the cyclic ether by initial formation of a hypohalite. The cyclization occurs when the rearranged radical is converted to a cation, either by oxidation with Pb(OAc)4 or by silver-assisted loss of halide ion. Hypoiodites are also fiequent-ly used, generated in situ. ... 

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. 

The anion of this acid results from the oxidation of red phosphorus with hypohalites in alkaline solution ... 

Contaet of this oxidant with readily oxidisable materials may lead to explosions. See Chlorine(l) trifluoromethanesulfonate See related HYPOHALITES... 

Quinoxaline-2-carboxamides have been used in the preparation of 2-aminoquinoxalines these derivatives are converted into the corresponding amines by treatment with sodium hypohalite under normal Hofmann-type conditions. 2-Aminoquinoxalines have been prepared by the reduction of aminoquinoxaline N-oxides with hydrogen and a Raney Ni catalyst, and 2-anilinoquinoxaline has been obtained from hydrolysis of... 

This picture has been broadly validated, and in some respects refined, by other work in which coal was depolymerized by acid-catalyzed transalkylation [as by interaction of coal with phenol and BF3 (23-27)] or by similar, less clearly defined, phenolation reactions (28-31), or selectively degraded by specific oxidants, such as dichromates (32-34), hypohalites (35-38), or peroxy-acids (39-43). But these studies have also revealed some previously unsuspected features. Buffer-controlled oxidation with Na2Cr207 (34) and KMn04 (44) have indicated an occasionally significant presence of straight-chain (up to C21) and branched-chain (up to C8) aliphatic compounds in coal. Oxidation with performic acid (41-43) has yielded substituted compounds that are clearly related to the microbial or chemical degradation products of lignin or flavonoids. And when applied to supposedly very similar coals, virtually identical depolymerization or oxidation procedures often furnished distinctly different product slates (45). 

The mechanism by which hypohalites oxidize alcohols probably involves initial formation of an alkyl hypohalite (Eq. 16.16). This product arises from reaction of the alcohol with the hypohalous acid that is in equilibrium with hypohalite ion in aqueous medium (Eq. 16.15). Base-promoted E2 elimination of the elements of H-X from the alkyl hypochlorite leads directly to either an aldehyde or ketone. The advantage of using hypohalite as an oxidant is immediately obvious upon examining Equation 16.16. The inorganic by-product derived from the oxidant is a halide salt that can be safely flushed down the drain. Reactions that do not produce toxic by-products are environmentally friendly and are now commonly referred to as "Green Chemistry." (See the Historical Highlight at the end of this chapter.)... 

One of the side reactions that may occur when hypohalite is used as an oxidizing agent for benzylic alcohols is halogenation of the aromatic ring. Although this side reaction is a problem when benzyl alcohol is oxidized with calcium hypochlorite, it is not observed in the oxidation of 4-chlorobenzyl alcohol. Explain this observation. 

The halogen oxoacids and oxoanions are produced by reactions of the halogens and their oxides with water. Most of the oxoacids are stable only in solution. Table 14.3 shows ball-and-stick models of the acids in which each atom has its lowest formal charge note the formulas, which emphasize that H is bonded to O. The hypohalites (XO ), halites (XO2 ), and halates (XOj ) are oxidizing agents formed by aqueous disproportionation reactions [see the Group 7A(17) Family Portrait, reaction 2]. You may have heated solid alkali chlorates in the laboratory to form small amounts of O2 ... 

Haloform reactions are generally performed with halogens in the presence of hydroxide [251] or directly with hypohalites [252]. Alternative methods affording carboxylic acids from methyl ketones (or other enolizable substrates) include the aerobic oxidation in the presence of a catalytic amount of dinitrobenzene [253] with a base in a dipolar aprotic solvent such as DMF [254] or HMPT (hexamethylphospho-ric triamide) [255, 256] and the use of stoichiometric quantities of hypervalent iodide derivatives [95, 257] or nitrosylpentacyanoferrate [258]. Furthermore, metal catalysts can be used, and systems such as tert-butyl hydroperoxide in the presence of rhenium oxide [259], oxygen in combination with a copper complex [260], heteropolyacids [261] and Mn"/Co" systems [262] were found to be applicable. Finally, aryl ketones are selectively oxidized to aliphatic carboxylic acids by treatment with periodate [81] in the presence of ruthenium trichloride [263]. 

Such solutions are necessarily contaminated with halide ions and with the products of any subsequent decomposition of the hypohalite anions themselves. Alternative routes are the electrochemical oxidation of halides in cold dilute solutions or the chemical oxidation of bromides and iodides ... 

Aldoximes can be oxidatively dehydrogenated to nitrile oxides using a variety of oxidants such as lead tetraacetate [16a], alkali hypohalites [lla],NBS in DMF followed by base treatment [16b], chloramine-T [11b], 1-chlorobenzotriazole [16c], mercuric acetate [ 16 d], etc. However, we employed either NaOCl or chloramine-T for most of our INOC reactions. For instance, a piperidine ring fused to an isoxazoline as in 14 was constructed using the INOC methodology (Scheme 3) [17]. Monoalkylation of N-tosylallylamine 10 with the bromoacetal... 

In general, ketones don t undergo oxidation however, methyl ketones undergo a haloform reaction. In a haloform reaction, the oxidation converts the methyl group to a haloform molecule (usually iodoform (CHI3)), which leaves the Ccirbon backbone one carbon atom shorter. The oxidant in a haloform reaction is sodium hypohalite (NaOX), which forms by the reaction of sodium hydroxide (NaOH) with a halogen (X, where X = Cl, Br, or 1). 

Benzofuroxans can be prepared by oxidation of o-quinone dioximes with, for example, fer-ricyanide or hypohalite in a process which closely parallels the formation of monocychc furoxans from glyoximes. Its utility is restricted by the availability of the starting materials which are themselves often best made by reduction of the furoxan. However, it is a valuable approach when the parent quinone or its monooxime is accessible by other means. It was, for example, the route originally used for naphtho[l,2-c]furoxan, the first aromatic-fused derivative <1886CB176>, and it is the method of choice for acenaphthofuroxans (11). In other cases oxidation of o-nitroanilines or thermolysis of o-nitroaryl azides are more suitable. 

The most widely used, and often most convenient reagents for such one-pot reactions are sodium hypochlorite (45) or hypobromite (16). These reactions are performed in the presence of an organic base (generally triethylamine) that normally enhances the yield of cycloaddition products (45). This method was employed for many intermolecular reactions (71) and also seems especially suited for intramolecular ones (72-77) as well as for the solid-phase synthesis (78) of 2-isoxazolines. Hypohalite can also be replaced by sodium broruite in combination with a catalytic amount of tri-u-butyltin chloride (79). In a related method, O-tributylstannyl oximes were treated with tert-butyl hypochlorite to produce nitrile oxides that were trapped with aUcenes or alkynes to afford the corresponding isoxazolines or isoxazoles in moderate to good yield (80). 

A convenient procedure for the oxidation of primary and secondary alcohols was reported by Anelli and co-workers (8,9). The oxidation was carried out in CH2CI2 with an aqueous buffer at pH 8.5-9.5 utilizing 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 1) as the catalyst and KBr as a co-catalyst. The terminal oxidant in this system was NaOCl. The major disadvantage of using sodium hypochlorite or any other hypohalite as a stoichiometric oxidant is that for each mole of alcohol oxidized during the reaction one mole of halogenated salt is formed. Furthermore,... 

Hypohalites IRO-Hal) are similar to nitrates (see p. 155 in their photochemical behaviour. Ultraviolet irradiation gives an (n,Ji > excited state that cleaves to form an alkoxy radical and a halogen atom. The radical may undergo alpha-cleavage before recombination with the halogen atom occurs, and this accounts for the formation of 5-iodopentanal (5.69) from the hypoiodite of cydopentanol such hypoiodites are generated in situ from the alcohol. Iodine and merturyfll oxide. In open-chain systems the alkoxy radical can... 

The finely divided metal is soluble in hypohalites if an excess of alkali is present. At red heat, the metal combines with C z to form the dichlondc. Ruthenium(VIIl) oxide is formed when an alkaline ruthenium solution is treated with a strong oxidant, such as chlorine, or bromate ion when the Ru is in acid solution,... 

The most widely used routes to benzo[ >]thiophene-2-carboxylic acids are (a) successive lithiation and carbonation of the parent benzo[ >]thiophene,42,76 90 98,183,477, 481>487,521,685-687 (ft) oxidation of the corresponding aldehyde,90,91,106,189 424, 477,640 (c) hypohalite oxidation of the corresponding methyl ketone,82 °8,189,424 and (d) cyclization reactions (Section IV,D, and E). Acids prepared by these routes are listed in Table XV. Oxidation of aldehydes usually proceeds almost quantitatively with moist silver oxide,90,91,105, 189,424 hut potassium permanganate is satisfactory.477, 640... 

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