Enolates carboxylic acids

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins with reaction of the carboxylic acid with PBr3 to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an cr-substitution reaction to give an cv-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the a-bromo carboxylic acid product. 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

The heteroatoms most commonly encountered by the organic chemist are oxygen, nitrogen and sulphur. The position of absorption of protons attached to these atoms is not normally sufficiently reliable for interpretative purposes, although there are exceptions to this general rule (e.g. carboxylic acids, enols,... 

In the presence of an electrophile, tautomerization of a substrate with a C=0 double bond to its enol only takes place when catalyzed by either a Bronsted- or a Lewis acid. The proton-catalyzed mechanism is shown for the ketone — enol conversion B — iso-B (Figure 12.4), the carboxylic acid —> enol conversion A — E (Figure 12.6), the carboxylic acid bromide — enol conversion E —> G (Figure 12.7) and the carboxylic acid ester — enol conversion diethyl-malonate —> E (Figure 12.9). Each of these enol formations is a two-step process consisting of the protonation to a carboxonium ion and the latter s deprotonation. The mechanism of a Lewis acid-catalyzed enolization is illustrated in Figure 12.5, exemplified by the ketone —> enol conversion A —> iso-A. Again, a protonation to a carboxonium ion and the latter s deprotonation are involved the Lewis acid-complexed ketone acts as a proton source (see below). 

Enolization of carboxylic acids. Enolates including that from acrylic acid are formed. Alkylation leads to useful synthetic intermediates. 

Bis(trimethylsilyl)acetamide (1). Mol. wt. 203.44, b.p. 71-73735 mm. Prepared in 80% yield by reaction of acetamide with trimethylchlorosilane with triethylamine as catalyst, the reagent effects trimethylsilyUuion of amides, ureas, amino acids, phenols, carboxylic acids, enols. ... 

Concerning drugs, both cationic and anionic compounds are commonly used (protonated basic side chain, protonated aza heterocycles, deprotonated carboxylic acids, enolic species, and acidic sulfonamides) (Figure 21.1). 

Subsequent deprotonation to afford the carboxylic acid enolate requires the formation of a doubly deprotonated species, which is disfavored relative to the formation of an ester enolate. In fact, activated esters such as phenyl esters1291 or thioesters1301 are especially prone to racemization, since enolization is easier than for simple esters. 

This compound is called ketene hydrate by Barra et al. (1992), but carboxylic acid enol by Andraos et al. (1993). 

A seemingly simple approach to a-hydroperoxy-acids is the direct addition of oxygen at low temperatures to carboxylic acid enolates (see also ref. 62). 

It has been found that carboxylic acid enolates, generated under thermodynamic control (25 C for three days), condense with aldehydes to form a preponderance of... 

There are two major areas of use for nonaqueous acid-base titrations. The first is the direct determination of compounds that have definite acidic or basic properties. This includes many thousands of organic compounds. For example, many amines are basic and can be titrated. There are also numerous acidic compounds, such as sulfonic acids, phosphonic acids, carboxylic acids, enols, imides, phenols, sulfur compounds, and others which can be titrated. The second largest and most important use of nonaqueous acid-base titrations is the indirect deter-... 

Lithiated oxazolines (22) are asymmetric carboxylic acid enolate equivalents, allowing quite reasonable optical induction in many cases. Organolithium reagents add to vinyloxazolines such as (23) [obtained by reaction of (22 R = H) with 3-methoxypropanal], and this approach has been applied to the synthesis of chiral lactones. ... 

Andraos, J., Chiang, Y., Huang, C.-G., Kresge, A. J., and Scaiano, J. C., Flash photolytic generation and study of ketene and carboxylic acid enol intermediates formed by the photolysis of diazonaphthoquinones in aqueous solution,/. Am. Chem. Soc., 115, 10605,1993. 

Chiang, Y., Jefferson, E.A., Kresge, A.J., and Popik, V.V., Flash Photolytic Investigation of 4-Diaz-oisothiochroman-3-One in Aqueous Solution Observation of a Short-Lived Carboxylic Acid Enol,... 

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