Preparation of N,N-Diethyl-m-toluamide (DEET) and its Identification by IR and NMR SpectroscopyEim A. ChemistCHEM 304July 10, 2005INTRODUCTIONN,N-Diethyl-m-toluamide (DEET) is the active ingredient in many insect repellants.1 In this experiment, DEET will be prepared from m-toluic acid through the intermediate acid chloride and then identified by its IR and proton NMR spectra. The overall reaction is a series of two acyl substitutions and is shown in Scheme 1 below:Scheme 1Carboxylic acids can be converted to acid chlorides by treatment with a compound such as phosphorus trichloride (PCl3) or thionyl chloride (SOCl2).2 The reactive acid chloride can then be treated witha primary or secondary amine to give the amide along with HCl, which reacts with the excess amine to give an alkylammonium chloride salt. The mechanism of this process is shown on the following page in Scheme 22:Page 1Scheme 2Page 2To carry out this reaction, the apparatus shown in Figure 1 will be assembled. The apparatus must be dry, since thionyl chloride will react with water to give sulfur dioxide and hydrogen chloride.4Figure 13m-Toluic acid and thionyl chloride will be charged into the reaction flask (USE A HOOD!), then boiled gently to effect the formation of the acid chloride. The acid chloride will then be cooled to room temperature and dissolved in anhydrous ether. Ice-cold diethylamine will be added as a solution in anhydrous ether to form the amide. The resulting ether mixture will washed with aqueous sodium hydroxide (to remove any excess acid chloride), then washed with hydrochloric acid (to remove any excess diethylamine). The resulting ether solution of DEET will be dried and evaporated to yield the crude product, which will then be purified by column chromatography to afford pure DEET. The percent yield from m-toluic acid will be determined and the product will be analyzed by transmission infrared spectroscopy (IR) as a neat sample using NaCl plates5 to confirm its structure by (1) looking at the major absorptions and comparing them to a correlation table6 and (2) by comparing the spectrum to that of an authentic sample. The major IR absorption is expected to be the amide carbonyl at 1640 – 1700 cm-1.6 The product will also be analyzed by 1H-NMR spectroscopy as a solution in CDCl3. The 1H-NMR chemical shifts are expected to be a multiplet at  7 – 8 for the four aromatic protons, a singlet around  2 – 3 for the three protons on the benzylic methyl group, a quartet at  2 - 3 for the four CH2 protons in the ethyl groups, and a triplet at around  0.5 – 1 for the six CH3protons in the ethyl groups.7Page 3Table of Chemical Substances8Reagent Structure/Formula Role Mol.Wt.Mp Bp Density Amount Moles MoleRatiom-Toluic AcidC8H8O2Reactant 136.15108-112 oC236 oC1.05g/mL0.272 g 0.0020 1.000ThionylChlorideSOCl2Reactant 118.97 -105 oC 76 oC1.63g/mL0.492 g 0.0041 2.068Diethylamine (CH3CH2)2NH Reactant 73.13 -50 oC 55 oC 0.7 g/mL 0.462 g 0.0063 3.159Diethyl Ether (CH3CH2)2O Solvent 74.12 -116 oC 35 oC 0.7 g/mL --- ---SodiumHydroxide,10% aq.NaOHAqueousauxiliary--- --- --- --- --- ---HydrochloricAcid, 10%HClAqueousauxiliary--- --- --- --- --- ---SodiumSulfateNa2SO4Dryingagent--- --- --- --- --- ---N,N-Diethyl-m-toluamideC12H11NOProduct 191.27 --- 111 oC0.996g/mL--- ---Alumina Al2O3Adsorbent --- --- --- --- --- ---Hexane C6H14Solvent 86.18 -95 oC62 – 69 oC0.678g/mL--- ---Page 4Safety Information8Compounds:Material Toxic? Corrosive? Flammable? Carcinogenic?m-Toluic acid No No No NoThionyl chloride Yes (Inhalation, rat:LC50 = 500ppm/1H)Yes No NoDiethylamine No Yes Yes (Fp-28 oC ( -18.40 oF))NoDiethyl ether No No Yes (Fp:-45 oC ( -49 oF))NoSodium hydroxide, 10% aqNo Yes No NoHydrochloric acid, 10%No Yes No NoSodium sulfate No No No NoN,N-Diethyl-m-toluamideNo No No NoAlumina No No No NoHexane No No Yes (Fp: -15 oC ( 5 oF))NoNote: Fp is the abbreviation for Flash PointTechniques:Thionyl chloride is toxic and corrosive! Do not breath the vapors! Use in a hood!When heating a reaction apparatus, be sure that it is open to the air so that pressure build up and subsequent rupture of the apparatus does not occur.When heating liquids, make sure the liquid is stirred (or a boiling chip is added) to prevent “bumping”.When performing an extraction, make sure to vent the separatory funnel often to prevent pressure build-up.Page 5EXPERIMENTALThe apparatus shown in Figure 1 was assembled. The 10-mL reaction flask was charged with 0.275 g of m-toluic acid (0.0020 mol) and 0.30 mL of thionyl chloride (0.492 g, 0.0041 mol). The condenser water was started, and the mixture was gently heated with stirring on an aluminum block (block temp ~ 90 oC) untilboiling started. The reaction mixture was then gently boiled for about 15 minutes. After the boiling period was finished, the reaction mixture was cooled to room temperature. 4.0 mL of anhydrous ether were added, and the mixture was stirred at room temperature until a homogeneous mixture was obtained. To this solution was added (dropwise over a 15 minute period) a solution of 0.66 mL of cold (0 oC) diethylamine (0.462 g, 0.0063 mol) in 1.33 mL of anhydrous ether. During the addition, a thick white cloud of diethylamine hydrochloride was formed. After complete addition, the reaction mixture was stirred at room temperature forabout 10 minutes. 10% aqueous sodium hydroxide (2 mL) was then added, and the reaction mixture was stirred for an additional 15 minutes at room temperature, then poured into a separatory funnel and allowed to separate. The aqueous layer was discarded, and the organic layer was washed with an additional portion of 10% aqueous sodium hydroxide (2 mL), followed by a portion of 10% hydrochloric acid (2 mL). The organic layer was washed with water (2 mL), dried (Na2SO4) and evaporated to yield crude N,N-diethyl-m-toluamide as dark brown liquid. The crude product was filtered through a short alumina column using hexane as the eluent (~ 5 mL). The hexane solution was evaporated to give 0.340 g of pure N,N-diethyl-m-toluamide as a yellow liquid.RESULTS AND DISCUSSIONReaction of m-toluic acid with thionyl chloride, followed by diethylamine produced 0.340 g of a yellow liquid the IR spectrum of which unequivocally showed the presence of the amide carbonyl functional group at 1633 cm-1. In addition, absorptions due to aliphatic C-H (2980 – 2880 cm-1), and aromatic C=C (at 1585 cm-1). The IR spectrum is attached to this report. These