Preparation of N,N-Diethyl-m-toluamide The Insect Repellent “OFF”

Reaction 1: Production of acid chloride + SOCl2 + HCl + SO2 m-toluic acid thionyl m-toluoyl chloride chloride

Reaction 2: Production of N,N-Diethyl-m-toluamide “OFF” + +HCl m-Toluoyl chloride Diethylamine N,N-Diethyl-m-toluamide

Special concerns All glassware must be dry! Be sure you are using anhydrous ether.

safety concerns for using thionyl chloride and diethylamine Dispense thionyl chloride and diethylamine in the hood. Keep the bottles closed when not in use Stopper test tubes when transferring chemicals to your hood Cool diethylamine prior to using

Procedure Assemble apparatus in the hood Add 1.81 g m-toluic acid (3-methylbenzoic acid) into a dry RBF Use a dry graduated pipette to transfer 2.0 mL of thionyl chloride into a test tube. STOPPER THE TEST TUBE BEFORE BRINGING IT TO YOUR HOOD. Remove the rubber septum and use a Pasteur pipet to add thionyl chloride to the RBF Add a boiling stone, reattach the rubber septum them reflux the mixture for 15 minutes Raise the apparatus from the heating mantle and let flask cool to RT

Procedure continued Remove septum and add 25.0 mL of anhydrous ether to the reaction flask Reattach septum and swirl mixture until it is homogeneous Put 4.5 mL of ice-cold diethylamine in a small Erlenmeyer flask with 8 mL of anhydrous ether Use a dry syringe to draw up diethylamine mixture and inject the solution into the RBF dropwise over 10-15 minutes through the rubber septum Swirl mixture occasionally Once all the diethylamine is added swirl the mixture occasionally for 10 minutes. Remove septum and add 14 mL 10% aqueous sodium hydroxide to the reaction flask in small portions. Swirl the flask occasionally for 15 minutes

Procedure continued: Extraction of product Disassemble glassware and transfer liquid to a separatory funnel Invert funnel for 2-3 minutes Remove and discard aqueous layer Add another 14 mL of 10% sodium hydroxide to the funnel, shake for 2-3 minutes, remove and discard aqueous layer Add 14 mL 10% HCl to the separatory funnel, shake, remove and discard aqueous layer Add 14 mL water to the separatory funnel, shake, remove and discard aqueous layer Transfer ether layer to a dry Erlenmeyer flask and dry with granular anhydrous sodium sulfate Decant ether into another dry preweighed flask. Use a small amount of ether to rinse the drying agent. Evaporate ether Weight flask with product to determine yield

Column chromatography

How does column chromatography work?

Column chromatography Clamp column vertically to wall of hood Weigh out 7.3 grams of alumina Place 14 mL hexane into a 125 mL Erylenmeyer flask Swirl hexane while incrementally adding the 7.3 g alumina Stir mixture with pipette then quickly pipette or pour slurry onto the column Collect hexane in a flask Preweigh collection beaker Dissolve product in 2 mL hexane When solvent level begins to enter alumina carefully add solution of N,N-diethyl-m- toluamide and hexane with a Pasteur pipette Once mixture in on column add rinse product flask with 4 mL hexane and add to the column with pipette Once wash mixture is on column add 14 mL hexane in small portions to the column to elute the N,N-diethyl-m- toluamide Collect all the eluting liquid in the preweighed beaker Evaporate hexane using a stream of air and heat Determine yield and obtain an FTIR

Additional information Remove a small amount of crude product prior chromatography for a back up FTIR. Do not let column run dry! Dispose of N,N-Diethyl-m-toluamide in the container provided.