Ketones, methyl with hypohalites

Aryl methyl ketones give generally high yields of acids on treatment with hypohalites [6SS, 696,698, 736. The reaction of 1,3,5-triacetylbenzene and sodium hypochlorite results in a 94% yield of trimesic acid [655], and that of methyl p-naphthyl ketone and sodium hypochlorite gives an 87-88% yield of p-naphthoic acid [695]. 4-Acetyl-4 -methoxybiphenyl is converted... 

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. 

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]. 

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). 

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... 

The oxidation of a methyl ketone to a carboxylic acid can be effected by the use of the haloform reaction. This involves treatment of the methyl ketone with an alkaline hypohalite reagent. A trihalomethyl ketone is initially formed which then undergoes hydrolysis under the basic conditions used. 

The hypohalite oxidations are easy to carry out. The methyl ketones, pure or dissolved in dioxane, are added to cooled or warm solutions of hypohalites in water. The reverse order of addition has also been used [736], An exothermic reaction ensues, and the haloform starts forming a heavy organic layer. The excess hypohalite is destroyed by sodium bisulfite, the heavy layer is separated, the residual haloform is removed by steam distillation, and the aqueous solution of the alkaline salt of the carboxylic acid is treated with sulfuric or hydrochloric acid (equation 420). 

Diraethyldihydroresorcinol (dimedone) is converted into 3,3-di-methylglutaric acid on treatment with sodium hypochlorite or sodium hy-pobromite. As a p-diketone, it suffers alkaline hydrolysis to 3,3-dimethyl-5-ketohexanoic acid, which undergoes regular hypohalite degradation of the methyl ketone end (equation 429) [735. Both the hydrolytic opening of the ring and the hypohalite reaction are accomplished in one step [699],... 

The oxidation of a methyl ketone to a carboxylic acid with one less carbon by oxidants other than hypohalites is exemplified by the oxidation of 2-acetylfluorene with sodium dichromate. In addition to the methyl keto group, the methylene group is also oxidized (equation 432) [626]. 

Alkali cleaves, a ,a>trihalomethyl ketones to trihalomethanes and carboxylic acids. This haloform reaction 714 also occurs directly if alkaline hypohalite solution is allowed to react with a methyl ketone and has preparative importance as a method of obtaining carboxylic acids from methyl ketones. 

In order to get this compound, we reacted B with NaOCl, which is a hypohalite. Hypohalites oxidize methyl ketones in the general reaction ... 

The seventh item in Table 8.6 is the sodium salt of the enolate ion of acetone. When any methyl ketone (i.e., a ketone of the form R-CO-CHj) or any secondary alcohol that can be oxidized to a methyl ketone (i.e., an alcohol of the form R-CH(0H)CH3) is treated with excess sodium hypochlorite (or any hypohalite), the haloform reaction occurs, resulting in the loss of the methyl group as chloroform (trichloromethane, CHCh) (or any haloform) and the formation of the salt of the... 

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