Reactivity of carboxylic acid

The order of reactivity of carboxylic acid derivatives toward nucleophilic acyl sub stitution can be explained on the basis of the electron donating properties of sub stituent X The greater the electron donating powers of X the slower the rate... 

Section 20 2 The structure and reactivity of carboxylic acid derivatives depend on how well the atom bonded to the carbonyl group donates electrons to it... 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

The sequence in Figure 12-32 not only represents the general reactivity of carboxylic acid derivatives but also gives information on the ease of synthesis. The more reactive a species is, the more difficult it is to prepare it (and vice versa). From this series, you can see that synthesizing a less reactive acyl compound from a more reactive acyl compound is always possible. 

The Influence of Fluoro Substituents On the Reactivity of Carboxylic Acids, Amides, and Peptides in Enzyme-Catalyzed Reactions ... 

Derivatives and Reactivity of Carboxylic Acids Commonly Used in Amide Formation... 

Many of these reactions an1 reversible, but equilibrium will prefer the more stable products. In other words, since a strong base makes a poor leaving group, the equilibrium will favor the formation of the compound whose leaving group is a stronger base. This explains the order of reactivity of carboxylic acid derivatives. 

A is correct. This question may require a little too much knowledge for the MCAT. It is more likely that a question like this will he associated with a passage that explains reactivity of carboxylic acid derivatives. To find the answer, we look at the strengths of the leaving groups ... 

Based on the above factors, the order of reactivity of carboxylic acid derivatives is... 

Butyl benzyl phthalate is a mixed carboxylic acid ester formed by the condensation of phthalic acid with two different alcohols. No literature values could be found nor any directly applicable QSARs. Based on known reactivity of carboxylic acid esters, any acid hydrolysis should be very slow. Neutral hydrolysis, while reported in the literature for certain reactive esters, is not likely for the phthalate esters. The carboxylic acid esters are most labile to alkaline hydrolysis (Mabey and Mill, 1978). 

The reactivity of carboxylic acid derivatives that react with nucleophiles according to the mechanism in Figure 6.4 cannot he measured via the rate of formation of the substitution product. Instead, the decrease in the concentration of the starting material serves as a measure of the reactivity. 

B Relative Reactivity of Carboxylic Acids and Their Derivatives... 

Sections 22.8-22.14 are devoted to specific examples of nucleophilic acyl substitution using heteroatoms as nucleophiles. There are a great many reactions, and it is easy to confuse them unless you learn the general order of reactivity of carboxylic acid derivatives. Keep in mind that every reaction that begins with an acyl starting material involves nucleophilic substitution. 

Compare the reactivity of carboxylic acids and esters towards nucleophiles and electrophiles, respectively. 

Acid halides are among the most reactive of carboxylic acid derivatives aiv can be converted into many other kinds of compounds. For example, we already seen the value of acid chlorides in preparing aromatic alkyl ketono by the Friedel-Crafts acylation reaction (Section 16.4). 

Skonberg, C. Sidenius, U. Olsen, J. Hansen, S.H. In Vitro Reactivities of Carboxylic Acid-CoA Tliioesters with Glutathione, Drug Metab. Rev. 35(S2), 105 (2003). 

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