PK values for carbon acids

A table of some pK values for carbon acids is appended for convenience, before going on to discuss the factors that can contribute to the relative stabilisation of carbanions ... 

Many pK values for nitrocarbon acids are in the compilations of Palm and colleagues182. A comprehensive study of the ionization of many carbon acids in DMSO has been made by Bordwell and colleagues and many of them are nitro compounds183. 

In considering relative acidity, classically it is only the thermodynamics of the situation that are of interest in that the pK value for the acid (cf. p. 54) can be derived from the equilibrium above. The kinetics of the situation are normally of little significance, as proton transfer from atoms such as O, N, etc., is extremely rapid in solution. With carbon acids such as (1), however, the rate at which proton is transferred to the base may well be sufficiently slow as to constitute the limiting factor the acidity of (1) is then controlled kinetically rather than thermodynamically cf. p. 280). 

As carbonic acid is a weak acid with pKi = 6.2 [106], the presence of CO2 in any measurement system may influence the results. If the pK value for the acid or conjugate acid is less than that of carbonic acid, little or no influence will occur. However, for ionizable systems where the pKa value is greater than that of carbonic acid, the presence of dissolved CO2 will have marked effects, giving apparent values that are lower than the true values. This is especially so where potentiomet-ric titrations with sodium or potassium hydroxides are used. This is because the concentrations of protonated and deprotonated forms required for the Henderson-Hasselbalch equation [Eqs. (3), (4), and (9)] are calculated from the volumes of acid or base added to the titration system. The presence of dissolved CO2 (in either the titrant or titrated solution) will alter the volume required. Spectrophotometric and other methods of pfCg measurement are free from the influences of dissolved CO2, if the pH-dependent phenomenon is insensitive to its presence. Cases where this must be taken into account include drugs where the absorption spectra overlap... 

A great number of acidities have also been measured in solution. In such cases, the common value reported is the pfCg. Recall (or skip ahead to Chapter 5) that pK is the negative log of the acid dissociation constant in water. As such, a smaller pK value implies a stronger acid, and each pfCa unit represents a factor of 10 in equilibrium acidity. Table 2.10 lists a number of pfCa values for carbon acids. 

It is noteworthy that the kinetics indirectly provided the evaluation of the basicities of these enamines [Eq. (4)]. The pK values for 4-(2-methyl-propenyl)morpholinc, l-(2-methylpropenyl)piperidine, and l-(2-methyl-propenyl)pyrrolidine are 5.47, 8.35, and 8.84, respectively (27). Since the protonation of the j8-carbon atom does not possess the character of a real equilibrium at pH 7 and up [for compound 1 even at pH 1 and up] the basicity must be fully ascribed to the equilibrium between enamine and the corresponding nitrogen-protonated conjugate acid. 

Enolates and related carbanionic nucleophiles are routinely generated by removal of an acidic proton in a molecule with a base. Carbonyl groups acidify their a protons somewhat and make dieir removal by a base a common process. However, structural features other than carbonyl groups can also acidify protons bound to carbon and thus facilitate dieir removal by bases. For example, pK values for structurally acidified C-H protons include the ones given below. 

The pK values for the nitro and aci-nitro form show that at high pH (>7) in aqueous solution the first equilibrium predominates. At low pH (<3) the equilibrium is between nitroethane and the aci-nitro isomer and only low concentrations of the latter are present, (aci-nitroethane)/(nitroethane) = 9 x 10 5. When acid is added to a solution of ethane nitronate in alkali, aci-nitroethane forms more rapidly than nitroethane (proton transfer to oxygen is fast compared with proton transfer to carbon) and the second equilibrium may be studied before any nitroethane has formed. The first equilibrium may be studied in equilibrated solutions at pH 7—11 [99]. 

The protons on the carbon between the two carbonyl groups of a (3-dicarbonyl compound are especially acidic because resonance delocalizes the negative charge on two different oxygen atoms. Table 23.2 lists pK values for (3-dicarbonyl compounds as well as other carbonyl compounds and nitriles. 

Strong acids have low pK values weak acids have high pK values. For example, formic acid is moderately strong pfC = 3.75. The pK values for other adds and proton-donating compoimds are phosphoric acid (H3PO4), 2.14 acetic acid (CH3COOH), 4.76 carbonic acid (H2CO3), 3.8 ammonium ion (NH ), 9.25 and bicarbonate ion (HCOj), 10.2. The values for K and pK refer to reactions that are reversible in aqueous solution and have attained a condition of equilibrium. 

The second pK value for lysine is 8.95. This is a fairly typical value for the second p T of amino acids and likely corresponds to proton removal from the nitrogen on ihe a carbon. The species that results is the predominant one at pH 9. 

The reported pKi values range from 3.9 to 5.7 (21,48). For our considerations it is essential that the pK value of uric acid is lower than that of bicarbonate, the latter being 6.1. All acids with a pK value of less than 6.1 are able to release carbon dioxide from bicarbonate. Our gasometric measurements showed a slow but clear release of carbon dioxide after addition of uric acid to sodium bicarbonate. A prolonged overproduction of acids (even weak acids such as uric acid inevitably impairs the alkali reserve if this is not compensated for. 

The position of the equilibrium in these acid-base reactions wUl depend on the relative acidity of the carbon acid and of the species BH (or, conversely, the basic strengths of and the carbanion). Some approximate pK values for typical carbon acids and the conjugate acids of some species commonly employed as bases are shown in Table 1.1. The numerical values recorded are approximate, since there is no method of accurately establishing absolute acidity in a single solvent medium for... 

The hydrogen bonded to the carbon of a terminal alkyne, called an acetylenic hydrogen atom, is considerably more acidic than those bonded to carbons of an alkene or alkane (see Section 3.8A). The pK values for ethyne, ethene, and ethane illustrate this point ... 

A hydrogen bonded to an sp carbon that is adjacent to a carbonyl carbon, however, is much more acidic than hydrogens bonded to other sp carbons. For example, the pK value for dissociation of a proton from the a-carbon of an aldehyde or a ketone ranges from 16 to 20, and the pK value for dissociation of a proton attached to the a-carbon of an ester is about 25 (Table 18.1). A compound that contains a relatively acidic hydrogen bonded to an sp carbon is called a carbon acid. 

If the a-carbon is between two carbonyl groups, the acidity of its a-hydrogen is even greater (Table 18.1). For example, the pK value for dissociation of a proton from the a-carbon of 2,4-pentanedione, a compound with an a-carbon between two ketone carbonyl groups, is 8.9. And the pK value for dissociation of a proton from the a-carbon of ethyl 3-oxobutyrate, which is between a ketone carbonyl group and an ester carbonyl group, is 10.7. Ethyl 3-oxobutyrate is classified as a j8-keto ester because the ester has a carbonyl group at the j8-position 2,4-pentanedione is a jS-diketone. 

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