Substituent effects on acidity

The listing of pK values shown previously in Table 20.3 indicates that there are substantial differences in acidity from one carboxylic acid to another. For example, trifluoroacetic acid K = 0.59) is 33,000 times as strong as acetic acid (Xa = 1.75 X 10 ). How can we account for such differences  

Because inductive effects operate through a bonds and are dependent on distance, the effect of halogen substitution decreases as the substituent moves farther from the carboxyl. Thus, 2-chlorobutanoic acid has pKa = 2.86, 3-chlorobutanoic acid has = 4.05, and 4-chlorobutanoic acid has pfCa = 4.52, similar to that of butanoic acid itself. 

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Because it s much easier to measure the acidity of a substituted henzoic acid than it is to determine the relative reactivity of an aromatic ring toward electrophilic substitution, the correlation between the two effects is useful for predicting reactivity. If we want to know the effect of a certain substituent on electrophilic reactivity, we can simply find the acidity of the corresponding benzoic acid. Worked Example 20.1 gives an illustration. 

Predicting the Effect of a Substituent on the Reactivity of an Aromatic Ring toward Electrophilic Substitution 

The pfifa of p-(trifluoromethyl)benzoic acid is 3.6. Is the trifluoromethyl substituent an activating or deactivating group in electrophilic aromatic 

Decide whether p-(trifluoromethyl)henzoic acid is stronger or weaker than benzoic acid. A substituent that strengthens the acid is a deactivating group because it withdraws electrons, and a substituent that weakens the acid is an activating group because it donates electrons. 

Assume you have a mixture of naphthalene and benzoic acid that you want to separate. How might you take advantage of the acidity of one component in the mixture to effect a separation  

The Ka for dichloroacetie acid is 3.32 x 10. Approximately what percentage of the acid is dissociated in a 0.10 M aqueous solution  

Since the dissociation of a carboxylic acid is an equilibrium process, any factor that stabilizes the carboxylate anion relative to undissociated carboxylic add will drive the equilibrium toward increased dissociation and result in increased addity. For example, an electron-withdrawing group 

Relative strengths of acetic add and chlorosubstituted acetic acids. Electrostatic potential maps of CHjCOj and CCI C02 show that the electron-withdrawing effect of the chlorine atoms makes the oxygen atoms in CCIjCO/ less negative and less basic than those in 

What is true for acetic acid is also true for other carboxylic acids at the physiological pH that exists inside cells, carboxylic acids are almost entirely dissociated. To reflect this fact, we always refer to cellular carboxylic acids by the name of their anion—acetate, lactate, citrate, and so forth, rather than acetic acid, lactic acid, and citric acid. 

Calculate the percentages of dissociated and undissociated forms present in the fol- 

Because the dissociation of a carboxylic acid is an equilibrium process, any factor that stabilizes the carboxylate anion relative to undissociated carboxylic acid will drive the equilibrium toward increased dissociation and result in increased acidity. An electron-withdrawing chlorine atom, for instance, makes chloroacetic acid (K = 1.4 x 10 ) approximately 80 times as strong as acetic acid introduction of two chlorines makes dichloroacetic acid 3000 times as strong as acetic acid, and introduction of three chlorines makes trichloroacetic acid more than 12,000 times as strong. 

Electron-withdrawing group stabilizes carboxylate and strengthens acid 

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Table 20,4 Substituent Effects on Acidity of p-Substituted Benzoic Acids...

A related comparison of remote substituent effects on acidities is provided by the data in Table 6-20. Here, the acidities of/ -substituted benzoic acids complexed to chromium tricarbonyl are related to the acidity of the parent compound. 

The discovery of Brauman and Blair in 1968 [34] that the acidities of aliphatic alcohols are completely reversed on going from bulk solution to the gas phase was a landmark in the interpretation of solvent and substituent effects on acid/base equihbria. The gas-phase acidity of alcohols increases in the following order [34, 125, 126] ... 

Generally, it has been found that substituent effects on acidity or basicity are significantly attenuated by the transfer of the substituted reactant from the gas phase into solution [235, 237, 240, 241]. Substituent effects are smaller in solution and this attenuation is different for different classes of substituted organic compounds [241]. 

Studying substituent effects on acidity is the standard method of determining whether a group is donating or withdrawing by induction and resonance,... 

Six-membered rings are considered before five-membered ones because they have been studied in greater detail and consequently their reactions are better understood. Because rate constants for quater-nization reactions have been correlated with values pertaining to the conjugate acids of heteroaromatic nucleophiles, substituent effects on acidities will be discussed prior to kinetic results. Acidity investigations suffer from fewer complications than N-alkylation and therefore provide results that offer considerable insight into the electronic effects of substituents on reactivity. Our review mentions only incidentally such related reactions, as oxidation - and acylation at an annular nitrogen atom. 

Generally speaking, photoacids behave similarly to ground-state acids as far as the solvent effect and the substituent effect on acidity and photoacidity is concerned. 

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