Section 17.20 Synthesis of Carboxylic Acid Derivatives 711A cyclic ether can also be prepared by an intramolecular electrophilic addition reaction.
The product obtained from the intramolecular reaction can undergo further reac-
tions allowing for the synthesis of many different compounds. For example, the alkyl
bromide could undergo an elimination reaction, could undergo substitution with a
wide variety of nucleophiles, or could be converted into a Grignard reagent that could
react with many different electrophiles.
PROBLEM 35Design a synthesis for each of the following compounds, using an intramolecular reaction:a. c. e.b. d. f.17.20 Synthesis of Carboxylic Acid Derivatives
Of the various classes of carbonyl compounds discussed in this chapter—acyl halides,
acid anhydrides, esters, carboxylic acids, and amides—carboxylic acids are the most
commonly available both in the laboratory and in biological systems. This means that
carboxylic acids are the reagents most likely to be available when a chemist or a cell
needs to synthesize a carboxylic acid derivative. However, we have seen that car-
boxylic acids are relatively unreactive toward nucleophilic acyl substitution reactions
because the OH group of a carboxylic acid is a strong base and therefore a poor leav-
ing group. In neutral solutions (physiological ), a carboxylic acid is even
more resistant to nucleophilic acyl substitution reactions because it exists predomi-
nantly in its unreactive negatively charged basic form (Sections 1.20 and 17.14).
Therefore, both organic chemists and cells need a way to activate carboxylic acids so
that they can readily undergo nucleophilic acyl substitution reactions.
Activation of Carboxylic Acids for Nucleophilic Acyl Substitution
Reactions in the Laboratory
Because acyl halides are the most reactive of the carboxylic acid derivatives, the easi-
est way to synthesize any other carboxylic acid derivative is to add the appropriate nu-
cleophile to an acyl halide. Consequently, organic chemists activate carboxylic acids
by converting them into acyl halides.
pH=7.3O CH^2 CH^2 CH^2 OHCH 3 COOHO CH^2 CH^3 O CH^2 CH CH^2AlCl 3
∆/peroxideCH 2 CH 2 CH 2 CH 2 Cl NBSBrHCl
CH 2 CHCH 2 CH 2 CH 2 CHCH 3 CH 3 CHCH 2 CH 2 CH 2 CHCH 3
+O
HCH 3 CH 3O++ H+
CH 3 CH 3OH OH