Acidity of carboxylic acids

Carboxylic acids are the most acidic class of compounds that contain only carbon, hydrogen, and oxygen. With ionization constants on the order of 10 (p/fa 5), they are mnch stronger acids than water and alcohols. The case should not be overstated, however. Carboxylic acids are weak acids a 0.1 M solution of acetic acid in water, for example, is only 1.3% ionized. 

To understand the greater acidity of carboxylic acids compared with water and alcohols, compare the structural changes that accompany the ionization of a representative alcohol (ethanol) and a representative carboxylic acid (acetic acid). The equilibria that define are 

Free energies of ionization are caicuiated from equiiib-rium constants according to the reiationship 

Positively polarized carbon attracts electrons from negatively charged oxygen. 

CH2 gronp has negligible effect on electron density at negatively charged oxygen. 

The melting points and boiling points of carboxylic acids are higher than those of hydrocarbons and oxygen-containing organic compounds of comparable size and shape and indicate strong intermolecular attractive forces. 

In aqueous solution intermolecular association between carboxylic acid molecules is replaced by hydrogen bonding to water. The solubility properties of carboxylic acids are similar to those of alcohols. Carboxylic acids of four carbon atoms or fewer are miscible with water in all proportions. 

Hydrogen bonding between two acetic acid molecules. 

The acidity can be increased by adding electron-withdrawing groups to the R (electron donors have the opposite effect). For example, the acidity of acetic acid increases as chlorine atoms replace hydrogen atoms. Acetic acid has Ka = 1.76 x 10-5, chloroacetic acid has Ka = 1.40 x 10-3, dichloroacetic acid has K = 3.32 x 10-2, and trichloroacetic acid has K = 2.00 x 10 l. 

The distance the electron-withdrawing group is from the carboxylic acid group is also important. For example, butanoic acid has Ka = 1.5 x 10-5, 4-chlorobutanoic acid has K = 3 x 10-5,3-chlorobutanioic acid has K = 8.9 x 10-5, and 2-chlorobutanoic acid has Ka = 1.4 x Hr. This shows that the chlorine is more effective the closer it gets to the carboxylic acid group. 

For the aromatic carboxylic acids, substituents on the aromatic ring may also influence the acidity of the acid. Benzoic acid, for example, has Ka = 4.3 x 10-5. The placements of various activating groups on the ring decrease the value of the equilibrium constant, and deactivating groups increase the value of the equilibrium constant. Table 12-2 illustrates the influence of a number of para-substituents upon the acidity of benzoic acid. 

Para-Substituted Benzoic Acid, Activating Groups K Value a 

Solubilities Carboxylic acids form hydrogen bonds with water, and the lower-molecular-weight carboxylic acids (up through 4 carbon atoms) are miscible with water. As the length of the hydrocarbon chain increases, water solubility decreases until acids with more than 10 carbon atoms are essentially insoluble in water. The water solubilities of some simple carboxylic acids and diacids are given in Tables 20-1 and 20-Z 

Carboxylic acids are very soluble in alcohols because the acids form hydrogen bonds with alcohols. Also, alcohols are not as polar as water, so the longer-chain acids are more soluble in alcohols than they are in water. Most carboxylic acids are quite soluble in relatively nonpolar solvents such as chloroform because the acid continues to exist in its dimeric form in the nonpolar solvent Thus, the hydrogen bonds of the cyclic dimer are not disrupted when the acid dissolves in a nonpolar solvent 

A carboxylic acid may dissociate in water to give a proton and a carboxylate ion. The equilibrium constant for this reaction is called the acid-dissociation constant. The p/(a of acid is the negative logarithm of A a 2nd we commonly use p Ta as an indication of the relative acidities of different acids (Table 20-3). 

Values of pK are about 5( a = 10 ) for simple carboxylic acids. For example, acetic acid has a p/i a of 4.7(ATa = 1.8 X 10 ). Although carboxylic acids are not as strong as most mineral acids, they are still much more acidic than other functional groups we have studied. For example, alcohols have pATa values in the range 16 to 18. 

Acetic acid (p/C = 4.74) is about lO times as acidic as the most acidic alcohols In fact, concentrated acetic acid causes acid burns when it comes into contact with the skin. 

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For many years resonance m carboxylate 10ns was emphasized when explaining the acidity of carboxylic acids Recently however it has been suggested that the indue tive effect of the carbonyl group may be more important It seems clear that even though their relative contributions may be a matter of debate both play major roles... 

The effect of structure on acidity was introduced m Section 1 15 where we developed the generalization that electronegative substituents near an lomzable hydrogen increase Its acidity Substituent effects on the acidity of carboxylic acids have been extensively studied... 

Another example of the effect of resonance is in the relative acidity of carboxylic acids as compared to alcohols. Carboxylic acids derived from saturated hydrocarbons have ipK values near 5, whereas saturated alcohols have pA values in the range 16-18. This implies that the carboxylate anion can accept negative charge more readily than an oxygen on a saturated carbon chain. This can be explained in terms of stabilization of the negative charge by resonance, ... 

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... 

Sections Electronegative substituents, especially those within a few bonds of the 19.6-19.7 carboxyl group, increase the acidity of carboxylic acids. 

Reactant and product structures. Because the transition state stmcture is normally different from but intermediate to those of the initial and final states, it is evident that the stmctures of the reactants and products should be known. One should, however, be aware of a possible source of misinterpretation. Suppose the products generated in the reaction of kinetic interest undergo conversion, on a time scale fast relative to the experimental manipulations, to thermodynamically more stable substances then the observed products will not be the actual products of the reaction. In this case the products are said to be under thermodynamic control rather than kinetic control. A possible example has been given in the earlier description of the reaction of hydroxide ion with ester, when it seems likely that the products are the carboxylic acid and the alkoxide ion, which, however, are transformed in accordance with the relative acidities of carboxylic acids and alcohols into the isolated products of carboxylate salt and alcohol. 

The polar solvent effect on relative acidities of carboxylic acids and enols was studied by Wiberg et al.179 by means of the DFT(B3LYP)/SCRF and MP2/SCRF calculations. Both methods well reproduced experimental solvent effects. 

The reactivity of the carbonyl group is enhanced by resonance, which stabilizes the carboxylate ion (see Figure 9-16). This increased stability of the carboxylate ion means that it s easier for a hydrogen ion to leave the Ccirbox-ylic acid. Thus the resonance is one factor in accounting for the acidity of carboxylic acids. 

Physical properties of carboxylic acids and derivatives include solubility, melting point, boiling point, and a few other characteristics. In this section we examine each class and discuss the most important physical properties. (In the upcoming section Considering the Acidity of Carboxylic Acids, we discuss the most important chemical property of Ccirboxylic acids — acidity.)... 

Figure 6-12 6-311+G vs. Experimental Aqueous-Phase Relative Acidities of Carboxylic Acids... 

Resonance effects. Resonance that stabilizes a base but not its conjugate acid results in the acid having a higher acidity than otherwise expected and vice versa. An example is found in the higher acidity of carboxylic acids compared with primary alcohols. 

G. V. Calder and T. J. Barton, "Actual Effects Controlling the Acidity of Carboxylic Acids," J. Chem. Educ. 48, 338 (1971). 

Table 1 Secondary deuterium IEs on acidity of carboxylic acids...

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