Oxidation reactions aldehyde/ketone preparation

Oxidative reactions frequently represent a convenient preparative route to synthetic intermediates and end products This chapter includes oxidations of alkanes and cycloalkanes, alkenes and cycloalkenes, dienes, aromatic fluorocarbons, alcohols, phenols, ethers, aldehydes and ketones, carboxylic acids, nitrogen compounds, and organophosphorus, -sulfur, -selenium, -iodine, and -boron compounds... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

The formation of a-acetoxyketones by oxidation of enamines with thallic acetate has been studied in detail (27) and found to be of preparative value (80 % yields) particularly in five- and six-membered-ring ketone derivatives. Enamines of linear or seven-membered-ring ketones were oxidized also, but at very much slower rates. Enamines of aldehydes with a-hydrogen substituents underwent self-eondensations during the oxidation reactions. Lead tetraacetate was less satisfactory as an oxidizing agent. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

A synthesis of A-substituted a-aminobenzylphosphinic acids starts from ammonium hypophosphite this is allowed to react with primary amines together with aldehydes or ketones in the presence of HC1.60 The nature of the products and general success of the Atherton-Todd reaction for the preparation of dialkyl- and diaryl-phosphinic amides from secondary phosphine oxides depends on the order in which reactants are mixed and on the choice of polyhalogen reactant.61... 

Diastereoselective metallo-Claisen reactions can be used to prepare aldol-type products if the 1,1-dimetallic reagents 91 obtained are oxidized to aldehydes or ketones (equation 43)37f. 

Carboxylic acids can be converted to symmetrical ketones by pyrolysis in the presence of thorium oxide. In a mixed reaction, formic acid and another acid heated over thorium oxide give aldehydes. Mixed alkyl aryl ketones have been prepared by heating mixtures of ferrous salts.1717 When the R group is large, the methyl ester rather than the acid can be decarb-methoxylated over thorium oxide to give the symmetrical ketone. 

The Oppenauer oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation,95 This is the reverse of the Meerwein-Pondorf-Verley reaction (6-25), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum f-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the preparation of ketones, it has also been used for aldehydes. 

Monosubstituted and 1,2-disubstituted olefins can be oxidized to aldehydes and ketones by palladium chloride and similar salts of noble metals.367 1,1-Disubstituted olefins generally give poor results. The reaction is used industrially to prepare acetaldehyde from ethylene... 

Aluminum methoxide Al(OMe)3 is a solid which sublimes at 240 °C in vacuum. Aluminum isopropoxide melts in the range 120-140 °C to a viscous liquid which readily supercools. When first prepared, spectroscopic and X-ray evidence indicates a trimeric structure which slowly transforms to a tetramer in which the central Al is octahedrally coordinated and the three peripheral units are tetrahedral.162,153 Intramolecular exchange of terminal and bridging groups, which is rapid in the trimeric form, becomes very slow in the tetramer. There is MS and other evidence that the tetramer maintains its identity in the vapour phase.164 Al[OCH(CF3)2]3 is more volatile than Al[OCH(Me)2]3 and the vapour consists of monomers.165 Aluminum alkoxides, particularly Al(OPr )3, have useful catalytic applications in the synthetic chemistry of aldehydes, ketones and acetals, e.g. in the Tishchenko reaction of aldehydes, in Meerwein-Pondorf-Verley reduction and in Oppenauer oxidation. The mechanism is believed to involve hydride transfer between RjHCO ligands and coordinated R2C=0— A1 groups on the same Al atom.1... 

In the reactions listed in Table 3, Michael addition of a primary aromatic amine to an a, (3-unsaturated aldehyde or ketone (prepared in situ) is followed by cyclization and oxidation of the intermediate dihydroquinoline to a quinoline (138 — 141). 

Aldehydes, ketones and quinones are important most of the methods of preparing them come into this section. The reactions on which these methods are based are chiefly of two kinds—purely oxidising reactions (Preparation 440), and reactions involving hydrolysis followed by oxidation (Preparation 156). 

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 industrial preparation of simple aldehydes and ketones usually involves an oxidation reaction of the related alcohol. Thus, formaldehyde is prepared by oxidation of methanol, and acetone is prepared by oxidation of 2-propanol. 

Many enzymes are both active and stable in carbon dioxide and have been used to conduct a number of reactions. Several different types of reactions have been examined, including hydrolysis (Lee et al., 1993 Randolph et al., 1985 Zheng and Tsao, 1996), oxidation (Hammond et al., 1985 Randolph et al., 1988), and esterification/transesterification (Kamihira et al., 1987 Nakamura et al., 1986 Rantakyla and Aaltonen, 1994), but there are other types of reactions that would make worthwhile investigations in carbon dioxide. These include preparation of amides, reduction of ketones, preparation of cyanohydrins from aldehydes, aldol reactions, hydroxylation reactions, and Baeyer-Villiger oxidation. 

The Dakin Reaction allows the preparation of phenols from aryl aldehydes or aryl ketones via oxidation with hydrogen peroxide in the presence of base. The aryl formate or alkanoate formed as an intermediate is subsequently saponified to yield the substituted phenol product. 

The Swem Oxidation of alcohols avoids the use of toxic metals such as chromium, and can be carried out under very mild conditions. This reaction allows the preparation of aldehydes and ketones from primary and secondary alcohols, resp. Aldehydes do not react further to give carboxylic acids. A drawback is the production of the malodorous side product dimethyl sulphide. 

Oxidation. This reagent is prepared by reaction of CAN with K2C03 (2 equiv.) to form Ce(C03)2, which is then treated with trifluoromethanesulfonic acid (4 equiv.). This oxidant is effective for oxidation of benzylic alcohols to aldehydes (72-92% yield), and of alkylarenes to aldehydes or ketones (65-70% yield). 

This Chapter contains reactions which prepare the oxides of nitrogen, sulfur, and selenium. Included are N-oxides, nitroso, nitro compounds, nitrile oxides, sulfoxides, selenoxides, and sulfones. Oximes are found in Sections 60A (Protection of Aldehydes) and 180A (Protection of Ketones). Preparation of sulfonic acid derivatives are found in Chapter Two and the preparation of sulfonates in Chapter Ten. 

Liu and Zhou applied Roush s crotylboration to the stereoselective synthesis of the orostanal 70, a novel sterol that induces apoptosis in human acute promyelotic leukemia cells28 (Scheme 3.ly). The aldehyde 72, prepared from hyodeoxycholic acid methyl ester, underwent asymmetric reaction with crotylboronate (R,R)-43E to furnish 73. Hydrogenation of the terminal alkene followed by Swem oxidation gave the ketone 74. Methylenation of the ketone and removal of the protective groups afforded orostanal in 50% yield. 

This chapter includes not only nuclear and extranuclear pyrazinecarboxylic acids and anhydrides, but also the related esters, acyl halides, amides, hydrazides, nitriles, aldehydes, ketones, and any of their thio analogues a few rare isothiocyanatopy-razines and pyrazinecarbonitrile oxides are also included. To avoid repetition, interconversions of these pyrazine derivatives are discussed only at the first opportunity for example, the esterification of carboxylic acids is discussed as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, many cross-references have been inserted. 

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