Synthesis of Ketones from Carboxylic Acids

Alternatively, the thioacetal can be alkylated once more to give a thioketal. Hydrolysis of the thioketal gives a ketone. (Acetals and ketals are discussed in more detail in Section 18-18.) 

In each of these sequences, dithiane is alkylated once or twice, then hydrolyzed to give a carbonyl group bearing the alkyl group(s) used in the alkylation. We often consider dithiane to be a synthetic equivalent of a carbonyl group that can be made nucleophilic and alkylated. 

Show how you would use the dithiane method to make the following ketones and aldehydes, (a) 3-phenylpropanal (b) 4-phenyl-2-hexanone 

Ycxj can think of dithiane as a masked carbonyl group. To make an aldehyde or ketone, add to dithiane whatever alkyl groups are on the carbonyl group of the target compound. 

Organolithium reagents can be used to synthesize ketones from carboxylic acids. 18-9 Organolithiums are so reactive toward carbonyls that they attack the lithium salts of . x  

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One reaction that is quite efficient for lithium reagents but poor for Grignard reagents is the synthesis of ketones from carboxylic acids.112 The success of the... 

One reaction that is quite efficient for lithium reagents but poor for Grignard reagents is the synthesis of ketones from carboxylic acids.91 The success of the reaction depends upon the stability of the dilithio adduct that is formed. This intermediate does not break down until hydrolysis, at which point the ketone is liberated. Some examples of this reaction are shown in Section C of Scheme 7.4. 

Structure of the Carbonyl Group 817 18-3 Nomenclature of Ketones and Aldehydes 818 18-4 Physical Properties of Ketones and Aldehydes 820 18-5 Spectroscopy of Ketones and Aldehydes 822 18-6 Industrial Importance of Ketones and Aldehydes 828 18-7 Review of Syntheses of Ketones and Aldehydes 829 18-8 Synthesis of Ketones from Carboxylic Acids 833 18-9 Synthesis of Ketones and Aldehydes from Nitriles 833... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

Synthesis of ketones from carboxylic acids RCOR ... 

Lithium-halogen exchange. The direct synthesis of ketones from carboxylic acids, organic chlorides and LN is quite useful. The cyclization of 1,4-diiodobutane derivatives is the basis of an approach to cyclobutyl ketones. ... 

Ketone synthesis. Italian chemists have developed a synthesis of ketones from carboxylic acids. The first step involves reaction of the acid with 2-mercapto-phenol (1) to form 1,3-benzoxathiolium perchlorates (2). The products react with Grignard reagents to afford 2,2-disubstituted 1,3-benzoxalhioles (3). One of... 

It is not necessary to use phosphorus oxychloride complexes of formamides, because Roh and Kochendorfer in 1937 demonstrated that the iminium chlorides themselves react similarly and Bosshard and Zollinger have shown that comparable yields can be obtained using chlorodimethylformiminium chloride as the reagent. However, in the synthesis of diarylketones good yields are only obtained when the phosphorus oxychloride complex of the corresponding arylcarboxylic acid amide has been used The synthesis of ketones from carboxylic acid amides, phosphorus oxychloride and suitable substrates predates the aldehyde synthesis by approximately 40 years but it is of only limited usefulness because side reactions are very often encountered... 

The same group also reports an alternative method of generating the intermediate ( )-vinyloxyboranes from diazo-ketones and trialkylboranes. Isomerization of (E) - to (Z) -intermediates can be effected simply, and both isomers are again used in stereoselective aldol syntheses. Interestingly, hydrolysis of the intermediates leads directly to ketones, and hence constitutes a synthesis of ketones from carboxylic acid derivatives (Scheme 77). Evans etal. have reported similar results from the use of boron enolates in the stereochemical control of aldol reactions. ... 

Chikashita, H. Ishihara, M. Takigawa, K Itoh, K. (1991). Synthetic ap>phcation of benzothiazole ring system as an on-off type of leaving group. Synthesis of ketones and carboxylic acid derivatives from 2-(l-substituted 1-hydroxyalkyl)- and 2-(l-hydroxyalkyl)benzothiazoles. Bidl. Chem. Soc. Jpn. Vol. 64, pp. 3256-3261, ISSN. 

Li-thiophenoxide in tetrahydrofuran-hexane added at 25 to a stirred suspension of Cul in tetrahydrofuran, after 5 min. tert-butyllithium in pentane injected dropwise at -78 followed after 5 min. by a soln. of 2-cyclohexen-l-one in tetrahydrofuran, warmed to 0 , and the product isolated after 2 hrs. -> 3-tert-buiyl-cyclohexanone. Y 72%.-Li-(phenylthio)organocuprates are easily prepared, stable up to 0 , and allow easy work-up. They are particularly useful for the prepn. of a-subst. ketones from a,a -dibromoketones and of ketones from carboxylic acid chlorides. F. e., syntheses, and Li-heterocuprates(l) s. G. H. Posner, C. E. Whitten, and J. J. Sterling, Am. Soc. 95, 7788 (1973) convenient prepn. of Li-phenylthio-(alkyl)cuprates s. Synthesis 1974, 662 mixed Li-dialkylcuprates s. W. H. Mande-ville and G. M. Whitesides, J. Org. Chem. 39, 400 (1974). 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

A convenient way of six-carbon homologation of aldehydes and ketones is the nucleophilic addition of the dianion generated from sorbic acid, (2 ,4 )-hexa-2,4-dienoic acid and subsequent dehydration to form the corresponding trienoic acid (equation 43)81. The 3-methyl analogue of sorbic acid has been used in a similar fashion for a short synthesis of vitamin A carboxylic acid (equation 44)82. 

Synthesis of aromatic ketones from carboxylic acid derivatives (Expts 6.126 and 6.127). 

MnClj. The chloromanganese reagents can be used in THF, a more satisfactory solvent for the synthesis of ketones from mixed carbonic-carboxylic anhydrides (prepared by the reaction of carboxylic acids with ethyl chloroformate). 

Methyl ketonesfrom carboxylic acid chlorides (3,112). Posner e/n/. report that the synthesis of ketones from acid chlorides and organocopper reagents is applicable to acid chlorides containing iodo, cyano, acyl, and carboalkoxy groups. The reaction, however,... 

Syntheses with diazomethane Synthesis with addition of 1 C-atom Diazomethyl ketones from carboxylic acid chlorides... 

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