Question

Synthesis of Lidocaine. Write out a scheme for each of the reactions with the mass of each reagent calculate the theoretical yield for each reaction. Use the theoretical yield of the first reaction as the starting material mass of the second reaction.

Answer 1

Experimental Procedure – Preparation of N-(2,6-Dimethylphenyl)chloroacetamide 1. First, get ~ 100 mL of water cooling in an ice-bath. You will use it soon. Wearing gloves, measure out 3.0 mL of 2,6- dimethylaniline into a 10-mL graduated cylinder and set aside in your hood. Using a larger graduated cylinder that your TA will have for you on the common bench, measure out 15-mL of glacial (concentrated) acetic acid (be very careful as it is corrosive) and add it to a 125 mL Erlenmeyer flask. Immediately rinse the graduated cylinder that held the acetic acid with acetone a few times and allow to air dry. You will use it again soon. Add the amine, via a Pasteur pipet, to the acetic acid in the Erlenmeyer flask. Rinse out your 10-mL graduated cylinder with acetone a few times and dry with the air jet. In this cylinder, measure out 2 mL of 2-chloroacetyl chloride and transfer to the Erlenmeyer flask containing acetic acid and 2,6-dimethylaniline. Add your thermometer to the Erlenmeyer. Using the larger graduated cylinder that you cleaned out a moment ago measure out 25 mL of 0.333 M aqueous sodium acetate. Add this directly to the Erlenmeyer. Note any observations and temperature changes! Next, remove the thermometer and rinse it into the flask with the cold water you previously prepared and add 60 mL directly to the flask (reserve the remaining cold water for use soon), stir thoroughly for 10 minutes using your glass stir rod. Isolate the product via vacuum filtration using a Buchner funnel on the common bench. Rinse with a few portions of the remaining cold water. Press as dry as possible with another piece of filter paper. Preparation of Lidocaine, AKA: 2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide – To a pre-weighed 50-mL round bottomed flask add the pressed-dry amide 1 and re-weigh the flask to get an exact amount of amide 1 used (record this mass). Sequentially add 7.5 mL diethylamine, 25 mL toluene and a few boiling stones. Special Note: The TA will add your diethyl amine for you from the reagent bottle to minimize the stench in the lab. Attach a water-cooled reflux condenser to the round bottomed flask (see section above for the proper hook-up of a water-cooled condenser). Turn water on very slowly. Your water going to the drain should just trickle out, not flow like white water rapids! Lower assembly into sand bath and reflux for 90 minutes (note any and all observations). Cool to room temperature, unaided. Transfer to a separatory funnel and wash the organic layer with 3x50 mL portions of water. Extract the organic layer with 3M HCl (2x20 mL). Remove aqueous layer into a new Erlenmeyer and wash organic layer in sep funnel with water (1x20 mL). Drain aqueous layer into the acidic extract just performed. Cool this flask in an ice-bath and add a thermometer to the solution. When it has reached 10 °C, add a small portion of 3M NaOH. Continue to add 3M NaOH, in portions, while keeping the temperature below 20 °C until the solution is strongly basic (green by pH paper). Note observations 5 upon additions of base. Isolate via vacuum filtration on a Buchner funnel and let air pass through as long as possible. Characterization and Purification – Recrystallize your Lidocaine from hexanes (follow the macroscale procedure on pages 65-66 of your lab manual. Run a TLC using 3:1 EtOAc:hexanes. Spot the plate as indicated in the picture below. This method of co-spotting allows one to determine how the compounds will run together. Sometimes compounds interact with one another. Circle your spots and turn your plate in with your report. You will notice that Lidocaine streaks on the TLC plate at any concentration. This is completely normal and you should not worry about it. Circle the darkest region of the streak.