acetonitrileSection 17.18 Hydrolysis of Nitriles 709PROBLEM 33Primary amines can also be prepared by the reaction of an alkyl halide with azide ion, fol-
lowed by catalytic hydrogenation. What advantage do this method and the Gabriel synthe-
sis have over the synthesis of a primary amine using an alkyl halide and ammonia?17.18 Hydrolysis of Nitriles
Nitriles are even harder to hydrolyze than amides. Nitriles are slowly hydrolyzed to
carboxylic acids when heated with water and an acid.
In the first step of the acid-catalyzed hydrolysis of a nitrile, the acid protonates the
nitrogen of the cyano group, making it easier for water to attack the carbon of the
cyano group in the next step. Attack on the cyano group by water is analogous to at-
tack on a carbonyl group by water. Because nitrogen is a stronger base than oxygen,
oxygen loses a proton and nitrogen gains a proton, resulting in a product that is a pro-
tonated amide (whose two resonance contributors are shown). The amide is immedi-
ately hydrolyzed to a carboxylic acid—because an amide is easier to hydrolyze than a
nitrile—following the acid-catalyzed mechanism shown in Section 17.15.
Because nitriles can be prepared from the reaction of an alkyl halide with cyanide
ion (Section 10.4), you now know how to convert an alkyl halide into a carboxylic
acid. Notice that the carboxylic acid has one more carbon than the alkyl halide.
PROBLEM 34Which alkyl halides form the following carboxylic acids after reacting with sodium
cyanide and the product heated in an acidic aqueous solution?a. butyric acid c. cyclohexanecarboxylic acid
b. isovaleric acidCH 3 CH 2 Br CH 3 CH 2 C
CH 3 CH 2 OHN−CN
DMFHCl, H 2 O
∆ CO+
CH 3 CH 2 CN+ H 2 O +
CH 3 CH 2 OHNH 4HCl
∆ COCH 3 CH 2 CH 2 Br CH 3 CH 2 CH 2 NCHNN 3 CH 2 CH 2 NH 2 + N 2−N 3 + − H 2
Pta carboxylic acid a protonated amideRNCH 2 ORNHOH
HOH 2RNHC CRNHCmechanism for acid-catalyzed hydrolysis of a nitrile++ +++OHOHHRNHC 2OHRNH 2H 2 OCOROHC+H^ OH 2H 2 O+(several steps)