Alcohols, secondary conversion into ketones

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

Chromium(VI) oxide is used for chromium plating copper stripping as an oxidizing agent for conversion of secondary alcohols into ketones (Jones oxidation) as a corrosion inhibitor in purification of oil and in chromic mixtures for cleaning laboratory glassware. 

Conversion of saturated, primary alkyl and aryl alkyl alcohols into the corresponding aldehydes can be achieved by this method provided that the alcohols are entirely dissolved in the organic phase. Relatively unstable protective groups are not affected, as in the oxidation of the acetonide of 1,2,6-hexanetriol, whereas conjugated and isolated double bonds give rise to side reactions which considerably decrease selectivities and yields.4 Some examples of aldehydes synthesized with this method are reported in Table 1. Under the same conditions, secondary alcohols are oxidized to ketones. Addition of catalytic amounts of quaternary onium salts allows fast and total conversion of primary alcohols and aldehydes into carboxylic acids making this methodology very versatile 4... 

An excellent method for the conversion of ether-soluble secondary alcohols to the corresponding ketones is by chromic acid oxidation in a two-phase ether-water system. The reaction is carried out at 25-30 °C with the stoichiometric quantity of chromic acid calculated on the basis of the above equation, and is exemplified by the preparation of octan-2-one and cyclohexanone (Expt 5.86). The success of this procedure is evidently due to the rapid formation of the chromate ester of the alcohol, which is then extracted into the aqueous phase, followed by formation of the ketone which is then extracted back into the ether phase and is thus protected from undesirable side reactions. 

Other oxidations with singlet oxygen are conversions of alkenes into epoxides [43, of secondary alcohols into ketones via alcohol hydroperoxides [44, 45] (equation 9) and the oxidative degradation of tertiary amines to secondary amines [46] (equation 10). 

The main applications of oxidation with chromium trioxide are transformations of primary alcohols into aldehydes [184, 537, 538, 543, 570, 571, 572, 573] or, rarely, into carboxylic acids [184, 574], and of secondary alcohols into ketones [406, 536, 542, 543, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584]. Jones reagent is especially successful for such oxidations. It is prepared by diluting with water a solution of 267 g of chromium trioxide in a mixture of 230 mL of concentrated sulfuric acid and 400 mL of water to 1 L to form an 8 N CrOj solution [565, 572, 579, 581, 585, 556]. Other oxidations with chromic oxide include the cleavage of carbon-carbon bonds to give carbonyl compounds or carboxylic acids [482, 566, 567, 569, 580, 587, 555], the conversion of sulfides into sulfoxides [541] and sulfones [559], and the transformation of alkyl silyl ethers into ketones or carboxylic acids [590]. 

Sodium dichromate hydroxylates tertiary carbons [620] and oxidizes methylene groups to carbonyls [622, 623, 625, 626, 631] methyl and methylene groups, especially as side chains in aromatic compounds, to carboxylic groups [624, 632, 633, 634, 635] and benzene rings to quinones [630, 636, 637] or carboxylic acids [638]. The reagent is often used for the conversion of primary alcohols into aldehydes [629, 630, 639] or, less frequently, into carboxylic acids or their esters [640] of secondary alcohols into ketones [621, 629, 630, 641, 642, 643, 644] of phenylhydroxylamine into nitroso-benzene [645] and of alkylboranes into carbonyl compounds [646]. 

Potassium ferrate, K2Fe04, which is prepared from ferric nitrate and alkaline hypochlorites [916], is a selective oxidant for the conversion of primary alcohols into aldehydes (not acids), of secondary alcohols into ketones, and of primary amines into aldehydes [917, 918]. 

Primary alcohols are oxidized to aldehydes or acids, and secondary alcohols are oxidized to ketones. Tertiary alcohols resist oxidation, unless they are dehydrated in acidic media to alkenes, which are subsequently oxidized. The conversion of alcohols into carbonyl compounds can be achieved by catalytic dehydrogenation or by chemical oxidation. Catalytic dehydrogenation is especially of advantage with primary alcohols, because it prevents overoxidation to carboxylic acids. Examples are tabulated in equations 223-227 and 265-268. 

Several biochemical oxidations can be applied to the conversions of secondary alcohols into ketones. In a complex system containing horse liver alcohol dehydrogenase, ( )-trans-3-methylcyclohexanol and ( )-cis-2-methylcyclopentanol are dehydrogenated to (-)-(5)-3-methylcyclohex-anone (yield 50% ee 100%) and to (+ )-(5)-2-methylcyclopentanone (yield 55% ee 96%), respectively [1036]. 

Over the past 30 years, metal orthophosphates have been used as catalysts for a variety of organic processes [1]. Most are active in the gas-phase dehydration of alcohols and some such as Caio(OH)2(P04)6 [2], Zn3(P04)2 [3] and calcium nickel phosphate [4] exhibit a dehydrogenating ability in the conversion of secondary alcohols into ketones. More recently, mixed orthophosphates including NaZnP04 [5] and NaMgP04 [6] have been used as catalysts for the dehydrogenation of alcohols. 

Use of polymer-bound chlorite 11 was shown to be more efficient for the oxidation of secondary alcohols to the corresponding ketone [23c]. The method was applied to a series of complex synthetic intermediates and gave excellent results. Immobilized chlorite was shown to be also a very efficient co-oxidant in the conversion of primary alcohols into the corresponding carboxylic acid [24]. This method is particularly attractive due to the ease of purification, the excellent yields and purity obtained also on more complex structures. What makes these techniques particularly interesting is that they have found applications in the synthesis of complex molecules. It was the method of choice for the synthesis of intermediate 13, the core of azadirachtin, in studies towards the synthesis of this natural product by the Nicolaou group [25]. This bicyclic aldehyde was obtained very cleanly using this method (Scheme 4.2). 

The conversion of secondary alcohols (R2CHOH) into ketones (RCOR) is Oxidation levels can be used to... 

Alkyl hydroperoxides oxidize some sugar alcohols to the corresponding ketones under molybdenum-salt catalysis. Ruthenium tetroxide oxidizes secondary alcohols to ketones in neutral or basic media permitting, under the latter conditions, direct conversion of y-lactones into y-ketoacids. ... 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

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