Experiment # 45: Benzocaine
The local anesthetic, benzocaine, was synthesized via the esterification of p-aminobenzoic acid with ethanol. The percent yield of crude product was determined to be 21% and the melting point was recorded at 86.2°C ± 0.2°C, with a 6.3% error from 92°C, the literature melting point of pure benzocaine. The crude product was then recrystallized to improve the purity of benzocaine and 57.4% was recovered. The new melting point range was measured at 89.1°C ± 0.3°C, which has a 3.15% error. The infrared spectrum of the recrystallized product was measured to further verify that the synthesized product was benzocaine. Introduction
The discovery of benzocaine as a local anesthetic came out of necessity to find a replacement for other anesthetic compounds with high toxicity levels such as cocaine and similar synthetic drugs. Cocaine has been used for its pain relief and stimulant effects for centuries, specifically by the Amerindian population in the Peruvian Andes, in the form of chewing the coca leaf (Erythroxylon coca) (Pavia et al, 283). The pure crystalline tropane alkaloid and active component of the coca leaves, cocaine, was isolated in 1862, and was used as an anesthetic in surgical and dental procedures in the 1880’s (Pavia et al, 284). However, it was soon realized that the use of cocaine was not safe because the lethal dose was very close to the treatment dose and because of the toxic effects on the central nervous system, including addiction (McMaster University). As a result, scientists began to make substitute synthetic compounds similar in structure to cocaine, which consists of an aromatic residue, an intermediate chain, and a basic tertiary amino group, shown in figure 1. Figure 1: Structure of Cocaine
All of the synthetic drugs that derived from the structure of cocaine had similar functional groups including an aromatic ring at one end, which is typically an ester of an aromatic acid, a basic tertiary amino group at the other end (which increases the compound’s solubility in the injection solvent), and a central chain of atoms one to four units in length that connects the two ends (Pavia et al, 284). Benzocaine does not possess the tertiary amino group and thus is not used for injection, but only as a topical anesthetic.
To synthesize an aromatic ether involves the esterification of a benzoic acid in the presence of acid. The benzoic acid is not reactive enough to undergo nucleophilic addition so a strong acid is required to protonate the carbonyl oxygen, which gives it a positive charge, thus making the molecule more reactive. The tetrahedral intermediate then loses a water molecule to yield the ester product for an overall substitution of a hydroxide group (-OH) by an alkyl group (-OR) (McMurry, 796). The general mechanism for esterification is shown in figure 2. Figure 2: Mechanism of Esterification Reaction.
1. Protonation of carbonyl & Nϋ attack
2. Formation of good leaving group
3. Loss of water and another deprotonation forms the ester
(Organic Chemistry Help)
In this experiment, Ethyl p-aminobenzoate, or benzocaine, was synthesized by the esterification reaction mechanism of p-aminobenzoic acid and ethanol in the presence of sulfuric acid. The general reaction is shown in figure 3.
Figure 3: Esterification of p-aminobenzoic Acid to Synthesize Benzocaine
An analytic balance was used to measure 0.1212g of p-aminobenzoic acid. The p-aminobenzoic was transferred to a 3mL conical vial along with 1.2mL of absolute ethanol, and a magnetic spin vane was added to dissolve the solid. Next, 1.0mL of concentrated sulfuric acid was added drop-wise to the vial while the solution was still being mixed by the spin vein, and a white precipitate formed in the vial. The mixture was then refluxed; a water cooled condenser was attached to...
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