Reactivity of carboxylic acid derivatives

Carboxylic acid derivatives are similar to carboxylic acids, but the OH group has been replaced with a different group (Z), 

The chemistry of carboxylic acid derivatives is different from the chemistry of ketones and aldehydes, because carboxylic acid derivatives possess a built-in leaving group, which allows the carbonyl group to re-form after being attacked  

The identity of the leaving group will determine how reactive the compound is. For example, acid chlorides are extremely reactive because the built-in leaving group (chloride) is very stable  

Chloride is a great leaving group because it is a weak base. For this reason, acid halides (also called acyl halides) are the most reactive of the carboxylic acid derivatives. This is very useful, because it means that we can use acid halides to form any of the other carboxylic acid derivatives. 

Carboxylic acid derivatives can be viewed as having a wild card next to the carbonyl group. I am calling it a wild card, because it can be easily exchanged for a different group  

If the nitrogen atom bears alkyl groups, these groups are placed at the beginning of the name, and the letter N is used as a locant to indicate that they are attached to the nitrogen. 

Nitriles are named as derivatives of carboxylic acids by replacing the suffix ic acid or oic acid with onitrile.  

This eflfect renders the carbonyl group even more electrophific when compared with the carbonyl group of a ketone. 

The relative order of reactivity of carboxylic acid derivatives. 

Now let s consider resonance effects. An acid halide has three resonance structures. 

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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. 

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... 

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. 

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. 

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). 

Relative Stability and Reactivity of Carboxylic Acid Derivatives... 

Reactivity of carboxylic acid derivatives versus carboxylic acids... 

At this point we want to consider the relative reactivity of carboxylic acid derivatives and other carbonyl compounds in general terms. We return to the subject in more detail in Chapter 7. Let us first examine some of the salient structural features of the carbonyl compounds. The strong polarity of the C=0 bond is the origin of its reactivity toward nucleophiles. The bond dipole of the C-X bond would be expected increase carbonyl reactivity as the group X becomes more electronegative. There is another powerful effect exerted by the group X, which is resonance electron donation. 

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