Carboxylic acid inductive effects

Solution The 2-chloro substituent increases the acidity of butanoic acid substantially, due to its inductive effect. In fact, the effect is about the same as for chloroacetic and acetic acids. The 3-chloro substituent exerts a similar hut much smaller effect, because the C—Cl bond is now farther away from the carboxylate group. Inductive effects fall off rapidly with distance. 

ACIDITY OF CARBOXYLIC ACIDS Resonance Stabilization of the Carboxylate Ion Inductive Effect on Acidity Acidity of Aromatic Carboxylic Acids... 

The p/Q value for butanoic acid is entirely typical of a carboxylic acid. The effect of the chloro substituent is to withdraw electron density inductively, and its influence in stabilizing the carbox-ylate anion is greatest when it is closest to the site of the anion. The effect of the 2-oxo substituent indicates that this is a stronger electron withdrawer than -CHCIR. 

Carboxylic acids are weak acids and m the absence of electron attracting substituents have s of approximately 5 Carboxylic acids are much stronger acids than alcohols because of the electron withdrawing power of the carbonyl group (inductive effect) and its ability to delocalize negative charge m the carboxylate anion (resonance effect)... 

For many years, resonance in caiboxylate ions was emphasized when explaining the acidity of carboxylic acids. Recently, however, it has been suggested that the inductive effect of the carbonyl group may be more important. It seems clear that, even though then- relative contributions may be a matter of debate, both play major roles. 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

Because inductive effects operate through cr 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 p/chlorobutanoic acid has p/chlorobutanoic acid has p/C., = 4.52, similar to that of butanoic acid itself. 

Indolmycin, biosynthesis of, 864 Inductive effect. 37, 562 alcohol acidity and. 604 carboxylic acid strength and. 758 electronegativity and, 37 electrophilic aromatic substitution and, 562... 

As suggested by Roberts and Moreland many years ago (1953), the acidity constants of 4-substituted bicyclooctane-l-carboxylic acids provide a very suitable system for defining a field/induction parameter. In this rigid system the substituent X is held firmly in place and there is little possibility for mesomeric delocalization or polarization interactions between X and COOH (or COO-). Therefore, it can be assumed that X influences the deprotonation of COOH only through space (the field effect) and through intervening o-bonds. On this basis Taft (1956, p. 595) and Swain and Lupton (1968) were able to calculate values for o and crR. 

H02C(CH2) C02H it was found that beyond a certain point the increment in the rate coefficient for an increases of one in n is constant at 5.2 x 10 l.mole . sec which compares with a value of 5.73 x 10 1.mole . sec for n-paraffin oxidation (p. 293). It is clear that carboxylic acids behave as paraffins except that a slight retardation due to the inductive effect of -CO2H is apparent. Permanganate behaves in much the same way and some examples of carboxylic acid oxidation have been cited in the section on hydrocarbons. 

Finally, since besides the inductive effect of the sulfoxide and the sulfone functional groups, hydrogen bonding, field effects and steric effects to solvation may or may not work in the same direction, the pK values can be useful in assigning configurations of suitable pairs of stereoisomeric sulfoxide and sulfone carboxylic acids ... 

The use of ethanol as an achiral auxiliary gave the adduct 53 with 55% ee, while neopentyl alcohol and methanol gave 96 and 87% ee, respectively. These results suggested that the achiral alcohol might exert a steric effect on the stereoselectivity. However, the increase in enantioselectivity from 55% to about 96% when 2,2,2-trifluoroethanol (TFE) was used instead of ethanol indicates a possible significant inductive effect also. Good enantioselectivities were also obtained with carboxylic acids and phenols. 

Introduction of 3,5-dimethyl and 4-substituent on the Phebox skeleton revealed a weak substituent effect on the degree of asymmetric induction (Scheme 15) [28,29]. When trimethylsilyl acrylate was used as enolate source, the (3-hydroxy carboxylic acid was obtained directly upon mild acid hydrolysis. In the production of carboxylic acid 49, an enantiomeric excess of 96% ee was attained using the NC -substituted Phebox-Rh catalyst. 

As the carboxyl group itself has an electron-withdrawing inductive effect, the presence of a second such group in an acid might be expected to make it stronger, as shown by the following pKa values ... 

Only a small number of substances have so far been investigated, and the available results are given in Table 2. These compounds should be more suitable than carboxylic acids for correlating acidity with inductive effects, since the negative charge is concentrated on one oxygen atom. 

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