SYNTHESIS OF ALDEHYDES AND KETONES

We have already seen, in previous chapters, several ways to prepare aldehydes and ketones. One of the most useful is the oxidation of alcohols. 

Oxidation of a primary alcohol gives an aldehyde, and oxidation of a secondary alcohol gives a ketone. Chromium reagents, such as pyridinium chlorochromate (PCC), are commonly used in the laboratory for this purpose (review Sec. 7.12). 

PROBLEM 9.3 Give the product expected from treatment of 

Write an equation for the oxidation of an appropriate alcohol to (CH3)2CHCH2CH0 (3-methylbutanal). 

Solution Aldehydes are prepared by oxidation of 1 alcohols (RCH2OH) with PCC. First, find the carbonyl carbon in 3-methylbutanal (marked with an asterisk). Convert this carbon to a primary alcohol. A proper equation is  

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The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

This method has several common features with the dithiane method5 that is useful for the synthesis of aldehydes and ketones.4 This latter method is illustrated by the synthesis of cyclobutanone (page 76). 

Synthesis of aldehydes and ketones.1 The carbanion of 1 can be generated by aqueous NaOH and can be alkylated with use of methyltrioctylammonium chloride as phase-transfer catalyst. A second alkylation is possible using NaH in DMF as base. The dialkylated product (3) can be hydrolyzed to a ketone by HC1 or H2S04 in CH3OH (equation I). 

Hydroboration of an alkyne followed by treatment of the alkenylborane with basic peroxide provides a method of synthesis of aldehydes and ketones. 

The Corey-Kim Oxidation allows the synthesis of aldehydes and ketones from primary alcohols and secondary alcohols, respectively. 

In the past, Darzens methodology was primarily used for the synthesis of aldehydes and ketones, as a homologation reaction without any consideration of stereocontrol in the epoxide formation. For this sequence, saponification of the a,P-epoxy ester followed by decarboxylation gives the substituted carbonyl compound ... 

A mixed oxide of ruthenium, copper, iron and alumnium has been developed as a catalyst for the synthesis of aldehydes and ketones from alcohols.258 Oxidation of chiral secondary 1,2-diols with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone under ultrasound wave promotion leads to the selective oxidation of benzylic or allylic hydroxyl group. The configuration of the adjacent chiral centre is retained.259 The kinetics of oxidation of ethylbenzene in the presence of acetic anhydride have been studied.260... 

Oxidative dehydrogenation of alcohols is a new approach in the development of industrial processes for the synthesis of aldehydes and ketones [103-105], In this regard, the technologically most suitable is the method of acetaldehyde synthesis in the presence of melted vanadium oxide, alkaline metals with promoting additives, alkaline metal sulfates or chlorides as catalysts [105], The target product yield equals 65.9% per used alcohol at 69.2% conversion. The disadvantage of the method is the relatively low yield of the target product... 

Synthesis of Aldehydes and Ketones from Acid Chlorides... 

Synthesis of aldehydes and ketones by reactions of organomagnesium compounds... 

Table 22 Synthesis of aldehyde- and ketone-functionalized phospholes...

Synthesis of aldehydes and ketones. This substance can function as a protected cyanohydrin of formaldehyde in an extension of Stork and Maldonado s synthesis of ketones from aldehydes, RCHO —> RCOR, by way of cyanohydrins (4, 300-301). Thus the anion of 1, generated with LDA, does not undergo self-condensation, but can be alkylated the product on hydrolysis gives the homologous aldehyde of the alkyl halide. Thus the reagent serves as the latent anion of formaldehyde, HC=0. An example is shown in equation (I). 

Synthesis of aldehydes and ketones. Trityl ethers disproportionate to triphenyl-methane and aldehydes or ketones in the presence of small amounts of trityl salts trityl hexafluorophosphate, trityl hexafluoroantimonatc, (CsHjIjC AbFft , or trityl hexafluoroarsenate, (C H 5)jC AsFj,". 

The development of the synthesis of peptides on solid supports has also had a strong impact on other areas of organic synthesis. From the very beginning, some research groups tried, with some success, to export the idea from peptide synthesis to, for instance, the monoalkylation and monoacylation of carboxylic acids,the synthesis of aldehydes and ketones, or to the use of resin-bound dienes or dienophiles to trap reactive intermediates.PI This pioneering work has been fundamental to the much more recent explosion of combinatorial chemistry on solid supports. Synthesis on solid supports has also found application in the synthesis of oligonucleotides, PI oligosaccharides,PI peptide-DNA hybrids,P°l and peptide nucleic acids (PNAs).P l... 

Ganem, B., Boeckman, R. K., Jr. Silver-assisted dimethyl sulfoxide oxidations. Improved synthesis of aldehydes and ketones. Tetrahedron Lett. 1974, 917-920. 

Steliou, K., Poupart, M. A. Reagents for organic synthesis. 5. Synthesis of aldehydes and ketones from nitro paraffins. J. Org. Chem. 1985,... 

Ghera42d has now found that the reaction can be applied to acyclic diol acetates and thus affords a general synthesis of aldehydes and ketones. The diol acetates must be pure and activated zinc is essential. 

For the solid phase synthesis of aldehydes and ketones, various linkers based on diols 48 have been used (Figure 14.16) [110-112]. Loading of this type linker with carbonyl compound is generally achieved by treatment of the resin with pTsOH in benzene with azeotropic removal of water. Products are released upon treatment with HC1 or pTsOH in aqueous dioxane. 

The latter is thermodynamically favorable because of the very strong carbon-oxygen double bond that is formed. It is kinetically rapid because the enol O—H bond is acidic and readily deprotonated, allowing the proton eventually to find its way to the nearby carbon. More details concerning the process will be upcoming when carbonyl compounds are discussed. Note that the hydration of alkynes is a new synthesis of aldehydes and ketones. 

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