MCAT Organic Chemistry Review 2018-2019

Figure 8.8. Synthesis   of  a   Carboxylic  Acid    via Oxidation   of  a   Primary Alcohol

There are many other methods of generating carboxylic acids, including organometallic reagents
(Grignard reagents) and hydrolysis of nitriles (–C≡N), but these are outside the scope of the MCAT.

NUCLEOPHILIC ACYL SUBSTITUTION

Many of the reactions in which carboxylic acids (and their derivatives) participate proceed via a
single mechanism: nucleophilic acyl substitution. This mechanism is similar to nucleophilic addition
to an aldehyde or ketone, which was discussed in Chapters 6 and 7 of MCAT Organic Chemistry
Review. The key difference, however, focuses on the existence of a leaving group in carboxylic acids
and their derivatives. In this case, after opening the carbonyl via nucleophilic attack and forming a
tetrahedral intermediate, the carbonyl can reform, thereby kicking off the leaving group. This
reaction is shown in Figure 8.9.

Figure 8.9. Nucleophilic    Acyl    Substitution

Step    1:  Nucleophilic    addition;   Step    2:  Elimination of  the leaving group   and reformation of  the

carbonyl.

In these reactions, the nucleophilic molecule replaces the leaving group of an acyl derivative. Acyl
derivatives encompass all molecules with a carboxylic acid-derived carbonyl, including carboxylic
acids, amides, esters, anhydrides, and others. These reactions are favored by a good leaving group.
Remember, weak bases, which are often the conjugate bases of strong acids, make good leaving
groups. These reactions are also favored in either acidic or basic conditions, which can alter the
reactivity of the electrophile and nucleophile.