Location
Stephen F Austin State University, Baker Pattillo Student Center, Twilight and Grand Ballrooms
Start Date
10-4-2012 4:00 PM
End Date
10-4-2012 8:00 PM
Description
The multi-step synthesis of Lidocaine is traditionally a low-yielding reaction mainly due to its second step, formation of a-chloro-2,6-dimethylacetanilide. Students often question the use of an acid (acetic acid) as the solvent for the reaction of a base (2,6-dimethylaniline, 1) with the acyl chloride (a-chloroacetyl chloride, 2), (Reaction Scheme) but they follow the procedure as directed.
Students, if treated as scientists in training, should be able to form a hypothesis before an experiment, design experiments to test the given hypothesis, and evaluate the results. A typical laboratory class was assigned to synthesize a-chloro-2,6-dimethylacetanilide using the procedure in the textbook, with acetic acid. This allowed everyone to learn from mistakes and correct their technique. A post-lab discussion including mechanistic evaluation (Mechanism: Equation 1) required the students to form a hypothesis and develop a series of experiments that could test it. If the problem was the acidity of the solvent, a less acidic solvent (ethanol) (Mechanism: Equation 2) was chosen to test this hypothesis. Acetone, ethyl acetate, and tetrahydrofuran (THF) were chosen to represent aprotic solvents to test the hypothesis that an aprotic solvent would work better than the protic solvents.
The second experiment was done similarly, with the students assigned to use one of the five solvents by drawing cards from a hat. The amount of solvent was consistent (2 mL) with each experiment. Each procedure used a fifteen minute reaction time prior to quenching the reaction in 2 equivalence of sodium acetate in 10 mL of water. The resulting mixture was cooled in an ice water bath for 10 minutes prior to collecting the white solid by vacuum filtration. The resulting white solid was dried to determine the percent yield, melting point, and obtain NMR samples. Verification was conducted by performing the experiment once more with students using a different solvent than before.
Research in the Teaching Laboratory: Improving the Synthesis of Lidocaine
Stephen F Austin State University, Baker Pattillo Student Center, Twilight and Grand Ballrooms
The multi-step synthesis of Lidocaine is traditionally a low-yielding reaction mainly due to its second step, formation of a-chloro-2,6-dimethylacetanilide. Students often question the use of an acid (acetic acid) as the solvent for the reaction of a base (2,6-dimethylaniline, 1) with the acyl chloride (a-chloroacetyl chloride, 2), (Reaction Scheme) but they follow the procedure as directed.
Students, if treated as scientists in training, should be able to form a hypothesis before an experiment, design experiments to test the given hypothesis, and evaluate the results. A typical laboratory class was assigned to synthesize a-chloro-2,6-dimethylacetanilide using the procedure in the textbook, with acetic acid. This allowed everyone to learn from mistakes and correct their technique. A post-lab discussion including mechanistic evaluation (Mechanism: Equation 1) required the students to form a hypothesis and develop a series of experiments that could test it. If the problem was the acidity of the solvent, a less acidic solvent (ethanol) (Mechanism: Equation 2) was chosen to test this hypothesis. Acetone, ethyl acetate, and tetrahydrofuran (THF) were chosen to represent aprotic solvents to test the hypothesis that an aprotic solvent would work better than the protic solvents.
The second experiment was done similarly, with the students assigned to use one of the five solvents by drawing cards from a hat. The amount of solvent was consistent (2 mL) with each experiment. Each procedure used a fifteen minute reaction time prior to quenching the reaction in 2 equivalence of sodium acetate in 10 mL of water. The resulting mixture was cooled in an ice water bath for 10 minutes prior to collecting the white solid by vacuum filtration. The resulting white solid was dried to determine the percent yield, melting point, and obtain NMR samples. Verification was conducted by performing the experiment once more with students using a different solvent than before.
