2004 Chem 2OB3 Lab Manual – Experiment 4. Reactions of Carboxylic Acids.
Experiment 4. Reactions of Carboxylic Acids & TheirDerivatives.
References: Brown & Foote, Chapters 17, 18
This experiment is in two parts. The first is a synthesis of Benzocaine, in which you convert acarboxylic acid to one of its derivatives, an ester. The second part consists of a couple of simpletest tube reactions that illustrate some of the properties of carboxylic acids and variousderivatives.
Part A: History of Benzocaine
The scientific work that led to the discovery of the local anaesthetic "benzocaine", is typical of how many biologically active synthetic drugs have been developed from naturally occurringsubstances. For centuries the Amerindians of the Andes have been using the leaves of the 'Coco bush' (
) as a mild stimulant. They would (and still do) chew the leaves to helpthem cope with the exigencies of life in a harsh environment altitude, hunger, inclement weather,and a precipitous terrain make several demands on endurance. In due course, chemistsinvestigated the components of the coco leaves, and finally the active component, the alkaloid"cocaine", was isolated pure in 1862. In the following years its properties were investigated, and by the 1880's it was in use as an anaesthetic in surgery and dentistry, one of the first such drugs toalleviate pain in medical procedures.However, it was quickly realized that cocaine also had two major disadvantages, first, the lethaldose was not a great deal more than the therapeutic dose, and so safe administration of the drug insurgery was unreliable. Secondly, cocaine causes serious problems, like potentially irreversibledamage to the central nervous system. Consequently, as soon as the structure of cocaine wasestablished (in 1910), chemists began preparing analogues, in the hope of finding one that wouldhave lower toxicity but equivalent efficiency. This search was based on the assumption thatcertain structural features were important for activity. As the list of successful analogues grew, it became apparent what these were: that there should be an aromatic acid derivative, with thecarbonyl group separated from a tertiary amine nitrogen by a chain of two to four atoms. Anexample is
, which is one of the most successful synthetic drugs in this family in use.A simplier analogue is the ethyl ester of
aminobenzoic acid, called "
". Clearlythis lacks the tertiary amine component, so not surprisingly, it is less active as an injectable drug. Nevertheless, it retains anaesthetic properties, and is used extensively as a topical pain reliever,Page 1