Laboratory Syntheses of Insect Pheromones Russell A. Cormier and J a m e s N. Hoban Metropolitan State College, Denver, CO 80204
Insect pheromones have been the subject of several recent ( I ) . Our interest in this area inarticles in THIS JOURNAL volves development of laboratory ~ynthesesof these interestina substances which utilize straiahtforward and familiar chemical transformations and whichalso employ a variety of important laboratory techniques. With these objectives in mind, we earlier descrihed a synthesis of the housefly sex attractant (2). In this article we wish toreport syntheses of the sex attractants of the tiger moth and the boll weevil. The tiger moth pheromone was first isolated in 1971 and identified as 2methylheptadecane (I) (3). This fatty acidrelated alkane is well known in the chemical literature, and reports of its preparation have appeared previously (3.4). As shown in the reaction scheme helow, the synthesis of the tiger moth sex attractant begins with acid-catalyzed esterification of the fatty acid palmitic acid (11) to give methyl palmitate (111) in 92% yield. Reaction of this ester with an excess of methylmagnesium iodide yields 92% of 2-methyl-2-heptadecanol (IV). This tertiary alcohol is dehydrated readily in 91% yield when heated with a catalytic amount of p-toluenesulfonic acid. The dehydration product, 2-methyl-2heptadecene (V), is contaminated with about 8% of the exnected disubstituted alkene. 2-methvl-l-hentadecene. Finallv. catalytic hydrogenation of the alkene minkre affords an 87% yield lfi7% overall) of 2-methylhepradecnne (1).
Each of the steps in the above synthetic scheme utilizes fundamental reactions which are often illustrated in an introductory organic chemistry laboratory course. Only the hydrogenation step requires comment. Alkene (V) is reduced rapidly at room temperature and one atmosphere pressure in ethanol solution using a palladium catalyst. Because most undergraduate laboratories are not equipped with a hydrogenation apparatus (5),the reduction of alkene (V) employs the Fieser modification (6) of an in situ hydrogenation method introduced hy H. C. Brown. Thus, a platinum catalyst is formed in the uresence of activated charcoal bv reduction of platinum chloiide with sodium borohydride, anh hydrogen pas is generated by acidification of sodium borohvdride. In ahdition to the above sequence, we have also~developed the synthesis outlined below of rhe ter~enoidcvclohexane derivatives which t'unrtion as prindpal co&ituen& of the boll weevil sex attractant (7-9). The alcohol (IX)and aldchvde (X) pheromones are formed as mixtures of geometric isomers whose relative amounts are estimated by gas chromatography and NMR spectroscopy. The preparation of the startingmaterial, 3,3-dimethylcyclohexanone(VII), from 5,5-dimethyl1,3-cyclohexanedione (VI), is descrihed elsewhere (10). Detailed procedures for synthesis of the boll weevil pheromones may be obtained upon request.
CHCHPH
M
CHCHO
X
The two multi-step syntheses described here require several laboratory periods. 1n general, each step, including purification and characterization of each intermediate oroduct. requires a separate laboratory period. The reactions and tkchniques required for synthesis of the tiger moth pheromone are intended for an introductory organic chemistry laboratory. However, the reagents and reaction conditions involved in the synthesis of the boll weevil pheromones are more sophisticated, and, therefore, this scheme may he considered more appropriate for an advanced lahoratory course. Experlmenial Section Methyl Palmitate (111) A mixture of 8.55 a (33 mmol) of ualmitic acid, 1 mL of concentrated sulfuric&id, and 25 ml."f anhydrous methanol is refluxed for 30 min. Afrer cooling the reaction mixture in ice water, 2 g of sodium mcthoxide added to neutralize the acid, and the rmulting mixture is dried over anhydrous sodium sulfate. The solvent is removed in uacuo, and short-path distillation of the residue affords 8.46 g (92%) of colorless methyl palmitate, hp 132-134° (0.4 mm) {lit. (11) bp 14S0 (2 mm)). Gas chromatographic analysis (12) reveals only a single peak. The following spectral characteristics are found: IR (neat) 1735 cm-1; NMR (CC4) 6 0.7-1.7 (m, 29 H, aliphatic protons), 2.22 (t, J = 7 Hz, 2 H, -CH2-C=O), 3.58 (s, 3 H, -0-CH3). 2-Methyl-2-heptanol (IV) The following reaction is carried out in a 250-mL, threeneck flask provided with a reflux condenser, drying tube, dropping funnel and magnetic stirrer. Alternatively, a oneneck flask with a Claisen head may be substituted. A 1.46-g (60 mmol) portion of magnesium turnings is placed in the flask and covered with 10 mL of anhydrous ether. While the reaction mixture is stirred and cooled as necessary, a solution of 8.52 g (60 mmol) of methyl iodide in 25mL of anhydrous ether is added dropwise during a 20-min period at a rate which maintains a vigorous but controllable reflux. The reaction mixture is then heated a t reflux for an additional 10 miu. While the methylmagnesium iodide solution is cooling in an ice water bath, a solution of 6.76 a (25 mmol) of methyl palmitate in 25 mL of anhydrous ether is added dropwise k t h stirring during 15min. The reaction mixture is heated at reflux for 15 min more, and then cooled in ice water. The reaction mixture is hydrolyzed by dropwise addition of 10 mL of saturated aqueous ammonium chloride followed by 25 mL of 10% hydrochloric acid to dissolve the resulting gummy precipitate. The organic layer is dried over anhydrous sodium sulfate and Volume 61 Number 10 October 1984
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concentrated in uacuo. The vield of colorless oil is 6.21 e (92%). This material is not purifieb further. GC analysis (125 shows onlv one neak. The followine s~ectralnro~ertiesare found:
2-Methyl-Zheptadecene ( V)
A 5.20-g (20 mmol) portion of crude alcohol (IV) is placed in a 50-mL round-bottomed flask together with 0.1 g of ptoluenesulfonic acid. The flask is equipped with a magnetic stirrer and a short-~athstillhead. The reaction mixture is heated to 15&160° &an oil bath during a l-h period. The rate of heatimg is adiusted as necessary to control the vigor of water vapor ev&tioi. After cooling the reaction mixtire to room temperature, short-path distillation under vacuum yields 4.61 g (91%)of colorleas alkene, hp 123-126" (0.4 mm). GC analysis (12)indicates about 8%of a single impurity of shorter retention time, presumed to he 2-methyl-l-heptadecene. The alkene mixture displays the following NMR spectrum in carbon tetrachloride: 6 0.7-2.1 (m, 37 H, aliphatic hydrogens, two hroad CH3 singlets at 6 2.54 and 6 2.66), 5.08 (hroad t, J = 7 Hz, 1H, C=CH); a hroad singlet at d 4.63 is assigned to the vinyl protons of 2-methyl-l-heptadecene. The following reaction is carried out in a 50-mL filter flask with pipet hulh or balloon wired onto the sidearm and containing a magnetic stirring bar. A l-mL portion of a solution of 1g of platinum chloride in 20 mL of water is placed in the reaction flask together with 0.5 g of activated charcoal and 10 mL of water. A 3-mL portion of a solution containing 1.6 g of sodium horohvdride and 0.3 e of sodium hvdroxide in 40 mL of water is then added, and the reaction mixture is stirred for 5 min to allow for formation of the catalyst. This is followed
928
Journal of Chemical Educafion
by addition of 4 mL of concentrated hydrochloric acid and a solution of 1.00 g of alkene (V) in 15mL of hexane. A rubber seDtum can is then wired onto the neck of the reaction flask. ~i.5-m portion ~ of the above sodium horohydride solution is added by syringe dropwise with stirring during about 10 min. The evolved hydrogen causes the pipet hulh to inflate, and this slowly deflates as the reaction mixture is stirred. After stirring for about 20 min, an additional 1.5 mL of sodium borohydride solution is added. After 15min more, the reaction mixture is suction-filtered through Celite to remove the catalyst and charcoal. The organic laver of the filtrate is dried over sodium sulfate and co&entra&d in uacuo. Bulh-to-bulb distillation of the residue at 120-125° (0.5 mm) gives 0.88 g (87%)of colorless alkane (I), which exhibits a single peak by GC (12). This material has the following NMR spectrum in carbon tetrachloride: 6 0.7-1.7 (m, 40 H, CH3 doublet at 6 0.87, J = 6.5 Hz). Literature Cited (1)Wood, William F.,J. Cm. EDuc.,69.35
(2)
andreferenaseited therein. Cziz R. A. Phan, M. D.. Gmddis, T., (1982): and S'lu,R, J. C W . EDuC.. 66,345
(8) Tum1inson.J.H., Gue1dner.R. C.,Hdee.D.D..Thompaon,A. C..HedIm.P.A,and Minyard. J. P.,J.Org. Chem., 36,2616 (1971). (9) Rlkticr. S. W., and M d y , N. V.. J. Org Chem., 41,1069 (1916). (10) Cormier,R.A.,Synth.Commun.. 11.295(1981). (11) "HandbookofChemisUyand Physirs,"SGthed.,TheChsmidRubkCa,Cbveland. OH.1 W S 7 R . 0. C-321% (12) Gas chmmatographie a n d p i s wa8 performed wing an OV-1 dieone m l m (%in. ~
~
OD.).
