Base-Promoted Hydrolysis of Amides

The aqueous sodium hydroxide soiution is caustic. Wear iatex gloves when handling it. Shouid it contact the skin, immediately flood the area with water. 

Preparation Sign in at www.cengage.com/logln to read the MSDSs for the chemi-cais used or produced in this procedure. 

Hydrolysis. Equip a smaii round-bottom fiask containing 10 ml of 3 Af sodium hydroxide soiution for shortpath distiiiation into a receiver containing a few miiii-iiters of diiute hydrochioric acid. Heat the mixture to boiiing and note changes, if any, in the appearance of the contents of the receiver. After the mixture is homogeneous, aiiow the soiution to cooi to room temperature. 

Neutraiize the acidic soiution in the receiver, perform the Hinsberg test (Sec. 25.14A), and prepare derivatives of the amine (Sec. 25.14). If the amine is not voiatiie enough to distiii, and thus is not found in the receiver, use small portions of diethyl ether to extract it from the aqueous layer contained in the stillpot. Dry the combined ethereal extracts over potassium hydroxide pellets, decant the solution, and then remove the solvent by one of the techniques described in Section 2.29. Prepare derivatives of the amine from the residue remaining after solvent removal (Sec. 25.14). 

Acidify the alkaline solution from which the amine has been extracted and isolate the carboxylic acid by either vacuum filtration or by extraction with diethyl ether followed by drying over sodium sulfate and removal of solvent as before. Characterize this acid by preparing suitable solid derivatives (Sec. 25.13). 

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Example 2.14. A rationale for the involvement of different leaving groups in the acid- and base-promoted hydrolysis of amides. 

Brown RS, Bennet AJ, Slebocka-Tilk H. Recent perspectives concerning acid and base promoted hydrolysis of amides. Aa Chem Res. 1992 25 481-488. 

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