Preparation of Propyl N,N-Diethylsuccinimate: An Insect Repellent Robert Caudle, Gretta Siegel, a n d William F. Wood' Humboldt State University Arcata, CA 95521 Finding chemicals that repel blood-sucking insects has been a n area of interest to researchers for many years. Of the thousands of chemicals synthesized and tested, only a few have proven to be useful insect repellents (1).Commercially available repellent substances include N,N-diethyl-m-toluamide (Deet, Off), I; dimethyl phthalate, 11; 2-ethyl-1,3-hexanediol (Ethohexadiol, 6-12), 111.
confirms the compound'8 purity; n~~~= 1.4505, literature (16) no25 = 1.4509. Preparation of the intermediate propyl hydrogen sucrinate requires about 2 hr. Conversion of VI to the acid chloride and subsequent reaction with diethylamine requires about 3 hr. These experiments were designed so they would onlv require equipment normally used in undergraduate organic chemistry courses. Experimental
Propyl Hydrogen Succinate ( Vi) A mixture of 0.10 mole of succinic anhvdride and 0.20 mole of 1fitted with .orooanol . was olaced in a IW-mL round-hottomed flask.~~.~~~~ ~. a condenier and then refluxed for 30 mln. After cooling, excess 1 propanul wad removed hy reduced pressure distillation using distil. lation apparatus fitted with a Claisen head and capillary tube air bleed (prevrnts humping],a steam bath and an aspirator. 'l'ornuurr removal for 5 min after the last of all I-propanol,distillation was ~ont~nued of the distillate entrred the receiving flask. The r,rodurt in the diatillation flask was essentiallvoure as i%vIl7 analvsis showed onlv those ahsorotions exoected for ?I: Yield 15.9 e (99%)of a clear lioiid: .~ IR r~a(.i~lates), h M K O , I:', 1:10,14tl;i, i Iw. 106,and 1020rm-1: NMR rnmt.71MS internal~twdard)6 1 l.Ots,IIII. I.O(t.2H). 2I,ts,4Hj, 1,6(multipIet,2H),and 0.9(t,3H). ~~
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I
II
CH3CHPH24-CCHICHIC-N(CH2CH3h IV
Propyl N,N-diethylsuccinimate, IV, was shown to be a relatively safe (2-4) and effective repellent (4-15). yet i t is not used to a great extent today. T h e synthesis of this compound as an experiment for the undergraduate organic chemistry laboratory is the subject of this communication. T h e first step in the synthesis of this insect repellent was reaction of succinic anhydride, V, with l-propanol to give the intermediate, propyl hydrogen succinate, VI. Removal of excess 1-propanol from the product was done by a reduced pressure distillation using an aspirator and a steam bath. The yield of VI was essentially quantitative and NMR spectroscopy showed no absorptions other than those expected for \I1 ,A.
Compound VI was converted to the acid chloride, VII, with thionyl chloride containing a catalytic amount of NJV-dimethylformamide. The acid chloride was then added dropwise to a stirred solution of diethylamine to give the desired product, IV.
After the reaction mixture was worked uo, NMR s w c t r w c o o ~ showed the product to be essentially purewith other than those expected for IV. The refractive index of 1V
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Propyl3-Chloroformylpropanoat ( VIfj To 0.20 mole of SOClz (CAUTION: Noxious vapors. Make transfers of this material in a fume hood) containing one drop of Nfl-dimethylformamide in a 100-mL round-bottomed flask fitted with a reflux condenser was added 0.10 mole of VI. The mixture was kept at room temperature for 20 min with the escaping gases being vented into a trap. The mixture was then refluxed on a steam bath for 15 min, after which excess SOClz was removed by distillation. Traces of SOClzwere removed from the reaction mixture by addition and subseauent distillation of 25 mL of hexane. This final step was reppated &e. The crude acid chloride, an amber liquid, was used svithoul further purification: IH (NaCI plate.! 30uu-'HStl, lalu. 1720, 1.1'75. 1400, 1180, 1060,and 9x0 rm-'.
Propyl N,N-Diethylsuccinimate (Ill A 500-mLthreenecked round-bottomrdflask n,ntainini:O:X mmolr ofdicthylamine (CAIII'IOX Noxious vapors. Make transfers of this material in a fume hood, in st1 mL ofCH2(:12 was fitted w ~ t h a condenser, a separatory funnel, and a glass stopper. The crude acid chloride, VII, was dissolved in 50 mL of CHzCIz and then added dropwise via the separatory funnel to the stirred reaction mixture (CAUTION:EXOTHERMIC). Themixture was stirred for 15 min after all f theacid chloride had heen added, then 100mL of Hz0 was add
