3412 lab 5 Benzocaine Synthesis Fischer Esterification PDF

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CHEM3412 Lab Synthesis of Benzocaine by Fischer Esterification O

O OH H2 N

+

EtOH

H2SO4 

OEt

+

H2O

H2 N

Benzocaine

Introduction Benzocaine is a local/topical anesthetic related to procaine (Novocain) and lidocaine. Benzocaine is the ethyl ester of para-aminobenzoic acid (PABA), a compound used in some sunscreens. In this lab, you will prepare benzocaine from PABA by a Fischer esterification, which is one of the classical methods to make an ester from a carboxylic acid. The Fischer esterification involves reaction of a carboxylic acid with an alcohol using an acid catalyst, with water formed as a byproduct. The reaction is reversible, and thus the ester and carboxylic acid actually end up being in equilibrium at the end of the reaction. To drive the reaction/equilibrium to the ester, we can take advantage of Le Chatelier’s principle by removing water as it is formed (using a drying agent or Dean Stark trap) or by using excess starting alcohol (only feasible when the alcohol is low boiling and thus easily removed, or is water soluble). With cheap and water soluble alcohols (such as MeOH, EtOH, etc.), the latter approach is most commonly employed. With higher boiling, non-water soluble and/or expensive alcohols, the removal of water approach would be preferred. Note: in addition to the Fisher esterification, esters can also be made from acids by other methods (which we will cover in lecture). Before you come to lab Complete pre-lab as usual, with safety data on the reactants including sulfuric acid (which is very corrosive to soft tissue, skin, and eyes). Review mixed solvent recrystallization in Zubrick. Procedure To 1.0 g of para-aminobenzoic acid (PABA) in a 50 or 100 ml RB flask is added ~10-12 ml of absolute EtOH. While stirring, 1.0 ml of H2SO4 is then added dropwise to the flask (Caution: strong mineral acid). The mixture is then refluxed for 40 minutes with stirring. At the end of the reaction, transfer the contents to a large E-flask (125 ml or greater) and add, in small portions with swirling, enough 10% sodium carbonate solution to make the mixture slightly basic according to pH paper (about 10-15 ml needed). Caution: addition of Na2CO3 may cause frothing as CO2 is formed from the carbonic acid. Once the solution is basic, add 40 mL of water to precipitate the product as a white solid. The product is then filtered by suction, washed with water to remove sodium carbonate and sulfate, and recrystallized. Recrystallization The crude benzocaine should be recrystallized from a mixture of MeOH and water. This is done by dissolving the product in the smallest amount of hot MeOH, hot-filtering, and 1

adding water to the hot solution until is just becomes cloudy. The solution is allowed to cool slowly to room-temperature to give crystals. If the compound “oils out”, it should be redissolved with heat and allowed to cool again, this time adding a few seed crystals (impure crystals) when cooling. Benzocaine is known to be difficult to recrystallize, so careful attention to details is necessary. Once recrystallized benzocaine is obtained, determine the mp and mass of products. Several literature mps have been reported, with the lowest and one of the highest given here: 76 oC [Helv. Chim. Acta. 1980, 63,456] and 89-90 oC [J. Org. Chem. 1981, 46, 653] [this last paper can be found on our webct site]. Perhaps your product mp will confirm one of these. Reports Write the results such as m.p. and mass of products on your lab notebook. Turn in everything electronically on D2L. You should draw the step-by-step mechanism and give the conclusion. Show your calculation.

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