Deprotonation of carboxylic acids

Enolates prepared by deprotonation of carboxylic acid derivatives can also undergo elimination to yield ketenes. This is rarely seen with amides, but esters, thiolesters, imides, or N-acylsulfonamides can readily decompose to ketenes if left to warm to room temperature (Scheme 5.58). At -78 °C, however, even aryl esters can be converted into enolates stoichiometrically without ketene formation [462, 463],... 

The addition of alcohols to nitrilium salts gives rise to formation of alkoxymethyleneiminium salts, which react with bases to yield imido esters (231 Scheme 33). - By deprotonation of carboxylic acid amides ambident anions are formed, which can be alkylated in the presence of silver ions to give imido esters, e.g. (232). " Secondary amides react with trifluoroacetic acid anhydride or trifluorosulfonic acid anhydride to give mixed anhydrides of imidic acids (233). ... 

The carboxylate anion is formed on deprotonation of carboxylic acids. The anion is stabilised by resonance (i.e. the charge is spread over both oxygen atoms) but can also be stabilised by the R group if this has a -I effect. 

Examples of amino acid and peptide coordination to a metal ion. Deprotonation of carboxylic acid and amide groups is required for efficient coordination potential donor groups are highlighted in the free hgands. 

So now we can expand our chart of acid and base strengths to include the important classes of alcohols, phenols, and carboxylic acids. They conveniently, and memorably, have piCa values of about 0 for the protonation of alcohols, about 5 for the deprotonation of carboxylic acids, about 10 for the deprotonation of phenols, and about 15 for the deprotonation of alcohols. The equilibria above each piCa shows that at approximately that pH, the two species each form 50% of the mixture. You can see that carboxylic acids are weak acids, alkoxide ions (RO ) are strong bases, and that it will need a strong acid to protonate an alcohol. 

Tetramethylammonium hydroxide (TMAH) is the most commonly used reagent for THM, and TMAH thermochemolysis has been extensively applied to the characterization of organic natural materials [98,103,104,107,108,124,127,134-138]. Py with TMAH involves the deprotonation of carboxylic acids and the hydrolysis of ester and ether bonds, followed by the formation of tetramethylammonium salts, which are subsequently subjected to thermal dissociation and leads to the formation of the corresponding methyl derivatives. 

Under thermodynamic control, the formation of cis-enolates is generally favored, except for the 4- to 10-membered rings of cyclic ketones, lactones, and lactams that necessarily form fcraws-enolates for geometrical reasons. It is obvious that a twofold deprotonation of carboxylic acids does not give rise to diastereomeric enolates. 

In the discussion of the relative acidity of carboxylic acids in Chapter 1, the thermodynamic acidity, expressed as the acid dissociation constant, was taken as the measure of acidity. It is straightforward to determine dissociation constants of such adds in aqueous solution by measurement of the titration curve with a pH-sensitive electrode (pH meter). Determination of the acidity of carbon acids is more difficult. Because most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. Any strong base will deprotonate the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, tetrahydrofuran (THF), and dimethoxyethane (DME) are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as DMSO and cyclohexylamine are used in the preparation of strongly basic carbanions. The high polarity and cation-solvating ability of DMSO facilitate dissociation... 

The reaction of Bi2HnNH22 with chlorides of carboxylic acids proceeds not to carboxamides, as would have been expected, but to carboximido acids. Reaction of the amine takes place only when deprotonated with strong base. The high p KR value of the ammonium group makes reactions with CH-acidic compounds difficult, as the latter might be stronger acids than the Bi2HiiNH3. ... 

Recently the group of D. W. Armstrong exploited the enantiopure ionic liquid 76 in the photoisomerization of dibenzobicyclo[2.2.2]octatrienes, and up to 12% ee was reported (Scheme 83). The obtained ee was possible due to the addition of base in order to deprotonate the carboxylic acid function of 74 resulting in a strong anion-chiral cation interaction. In the absence of a base, lower values of ee were obtained, and in the case that ester functions instead of carboxylic acid groups were present in the molecule, only racemic product was found. Ionic liquid 77 gave up to 6.8% ee. 

The adsorption behaviour of 1,2,4,5-tetra carboxylic and 2,3-dihydroxybenzoic acids most closely simulated that of NOM (Evanko and Dzombak, 1998). Another modelling study, this time with CD-MUSIC, suggested that adsorption of carboxylic acids on goethite involved two complexes located on different crystal planes, viz. a deprotonated outer sphere complex (pH 3-9) and an inner sphere mononuclear chelate present at ca. pH 6 (Boily et al., 2000). 

Carboxylic acids are more acidic than alcohols and acetylene. Strong aqueous bases can completely deprotonate carboxylic acids, and salts of carboxylic acids are formed. Strong aqueous mineral acids readily convert the salt back to the carboxylic acids. Saits are soluble in water but insoluble in nonpolar solvents, e.g. hexane or dichloromethane. 

In the reaction of Figure 12.19, the alkoxide formed in this step deprotonates a carboxylic acid (cis-1 —> K), whereas in Figure 12.18 an iminium ion is deprotonated (B — C). Accordingly, different chemoselectivities are observed Figure 12.19 shows an enamine-mediated aldol addition, and Figure 12.18 presents an enamine-mediated aldol condensation. Hydrolysis of the iminium ion K in Figure 12.19 leads to the formation of the aldol addition products B and the amine which, together with the still unconsumed substrate A, forms the new enam-ine C, to start the catalytic cycle anew. 

For every rule, there is an exception or so they say. Sometimes this is also true in chemistry. It appears, for example, that the pvalues of carboxylic acid esters vary more widely than is allowed or acknowledged by Table 13.1. This does not justify, though, the abandonment of the above mentioned rules of thumb for estimating the position of the deprotonation equilibrium of C,H-acidic compounds. As it were, one structural effect on the C,H acidity of carboxylic acid esters has so far been totally ignored, namely the effect of the conformation that the substructure C-0-C=0 adopts in relation to the highlighted bond (printed in boldface), i.e., which dihedral angle occurs between the C-O and the C=0 bond. 

The parent acids and alcohols, on the other hand, are not expected to display any significant mesomeric stabilisation, because this would involve the participation of some rather unreasonable Lewis structures with separated positive and negative charges. As a consequence, the tt-delocalisation in 1 and 2 is a factor that lowers the deprotonation energy of carboxylic acids and enols, thus reinforcing their acidity, according to standard organic-chemistry textbooks. 

The basicity of LDA is so high that it is even possible to generate bisenolates from /3-diketones and /3-ketoesters (Figure 10.7). Even carboxylates can be deprotonated at the a carbon if the strongest organic bases are employed (Figure 10.8). In contrast, the twofold deprotonation of phenylacetic acid by ethylmagnesium bromide is not com-... 

With these estimates for the pKa values of the CH-groups of malonic acid and the corresponding carboxylates on the one side and the known pKa values of the two carboxyl groups of malonic acid (Figure 10.49, top row) on the other, all equilibrium constants are available that are required to estimate the relative amounts of all conceivable products B-F of the deprotonation of malonic acid with pyridine using Equation 10.4. Figure 10.50 gives the mole ratios of products B-F, relative to one mole of malonic acid dissolved in pyridine. 

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