Conversion to carboxylic acids

Fig. 11. The metal sites in D. gigas hydrogenase (Hase) (A) and aldehyde oxidore-ductase (AOR) (B). The figure emphasizes the relative positioning of the metal sites Emd their proximity, suggesting an attractive electron transfer pathway. The arrows indicate electron trsmsfer for hydrogen evolution requiring an electron donor (A) Emd aldehyde conversion to carboxylic acid, the electrons being transferred to Em electron acceptor (B).

Reduction of saturated carboxylic acids with the borane derivative, thexylchloro-borane, provides a direct route to aldehydes without their prior conversion to carboxylic acid derivatives. The aldehydes initially formed were isolated either as their bisulfite adducts or as their hydrazones, from which the aldehydes were regenerated. 

Acid. Conversion to carboxylic acid and alcohol takes place. The sulphonate group may be on either of these. Thus acyl isethionates yield a fatty acid and isethionate ions, mono- and di-alkyl sulphosuccinates yield fatty alcohols and sulphosuccinic acid, and a-sulphonated fatty esters yield the a-sulphonated fatty acid and a low-molecular-weight alcohol. 

TABLE 27.16 Substituted Benzenes Deprotometalation Using a Lithium-Zirconium Base and Subsequent Conversion to Carboxylic Acids... 

We will consider nitriles and their subsequent conversion to carboxylic acids and amines again in Chapter 18, page 231. 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

Because cyano groups may be hydrolyzed to carboxylic acids (Section 20 19) the Sand meyer preparation of aryl nitriles is a key step m the conversion of arylammes to sub stituted benzoic acids In the example just cited the o methylbenzomtnle that was formed was subsequently subiected to acid catalyzed hydrolysis and gave o methylbenzoic acid in 80-89% yield... 

Some of the more common reagents for the conversion of carboxylic acids to trimethylsilyl esters are listed below. For additional methods that can be used to silylate acids, the section on alcohol protection should be consulted since many of the methods presented there are also applicable to carboxylic acids. Trimethylsilyl esters are cleaved in aqueous solutions. 

The Arndt-Eistert synthesis allows for the conversion of carboxylic acids 1 into the next higher homolog 4. This reaction sequence is considered to be the best method for the extension of a carbon chain by one carbon atom in cases where a carboxylic acid is available. 

Succinic acid, 2,2-difluoeo-, 42, 44 SuCCINIMIDE, N-IODO-, 42, 73 Sulfonation of pyridine, 43, 97 Sulfur tetrafluoride, in conversion of carboxylic acids to 1,1,1-trifluoro compounds, 41, 104/ toxicity of, 41,105 / ... 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

Note Such conversions of carboxylic acid derivatives into nuclear or extra-nuclear primary aminoquinoxalines appear to be almost unrepresented in recent literature, apart from one partial Curtins procedure. 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Most resolution is done on carboxylic acids and often, when a molecule does not contain a carboxyl group, it is converted to a carboxylic acid before resolution is attempted. However, the principle of conversion to diastereomers is not confined to carboxylic acids, and other groupsmay serve as handles to be coupled to an optically active reagent. Racemic bases can be converted to diastereomeric salts with active acids. Alcohols can be converted to diastereomeric esters, aldehydes to diastereomeric hydrazones, and so on. Even hydrocarbons can be converted to diastereomeric inclusion... 

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0")2 ] by treatment with a strong base such as LDA. The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCH2COOH and RR"CHCOOH. This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 458),... 

Conversion of Alkyl Halides, Alcohols, or Alkanes to Carboxylic Acids and Their Derivatives... 

The Conversion of Carboxylic Acid Salts to Ketones With Organometallic Compounds... 

Among other oxidizing agents that have been used to accomplish the conversion of ArCHs to ArCHO are ceric ammonium nitrate, ° ceric trifluoroa-cetate, and silver(II) oxide.Oxidation of ArCHa to carboxylic acids is considered at 19-11. 

Esters can be formed when the hydrocarbonylation reaction is carried out in an alcohol.242 Although hydrocarbonylation is the basis for conversion of alkenes to carboxylic acids on an industrial scale, it has seen only limited application in laboratory synthesis. 

Another reaction that can be used for conversion of carboxylic acids to the corresponding amines with loss of carbon dioxide is the Hofmann rearrangement. The classic reagent is hypobromite ion, which reacts to form an A-bromoamide intermediate. Like the Curtius reaction, this rearrangement is believed to be a concerted process and proceeds through an isocyanate intermediate. 

A related method for conversion of carboxylic acids to bromides with decarboxylation is the Hunsdiecker reaction.276 The usual method for carrying out this transformation involves heating the carboxylic acid with mercuric oxide and bromine. 

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