7-Nonanoic Lactone: Synthesis of a Fragrance and Flavor Enhancer in the Undergraduate Laboratory Richard A. Bunce' and Henry D. Reeves Oklahoma State University, Stillwater, OK 74078 The flavor and fragrance industry is an important branch of commercial chemical manufacture. While many flavor and framance comnounds are readilv acauired from natural sourcecthe difficilty and expense i f isolating and processine sufficient ouantities of rare natural extracts often makes it ~ommercial&viableto develop a laboratory preparation of a substance exhibiting similar gustatory and olfactory properties. The high profitability of these chemicals makes them attractive targets for synthesis and easily rationalized as experiments in the organic laboratory. The current experiment describes the synthesis of y-nonanoic lactone, an unnatural compound having the odor and flavor of coconuts, and is a modification of an earlier procedure outlined by Ault ( I ) . The synthesis, depicted in the sequence below, begins with the Knoevenaeel condensation of malonic acid with heptanal(2). The use oftriethylamine for thisstep results in formation of the unsaturated acid with >95q selectivity for the 0.7 double-bond isomer. I t has been suggested (3)that the formation of the kinetic dehydration product in this reaction derives from the steric requirements of the base. Purification of this product is most easily accomplished by means of an extraction orocedure-the acid is extracted into mild base, neutral contaminants are removed by ether extraction. and the aaueous laver is reacidified and extracted. This procedure is more convenient than vacuum distillation and gives a product that is highly pure. Lactonization of the 3-nonenoic acid is then carried out using Amberlyst-15 in refluxing heptane (4). The temperature at which thelactonization was performed proved to he very important; heptane (bp 98 "C) was found to be the solvent of choice, while in hexane (bn . . 69 OC) the reaction was slow. Finallv. ..workuo of the reaction simply involves filtering the catalyst, concentratine the crude reaction mixture and vacuum distilline the product using a shurt-path apparatusz under aspirator vacuum (28-30 mmHr). The experiment can be easily carried out by students in t i o 3-h laboratory periods.
This appears to he the first use of Amberlyst-15 as a heterogeneous catalyst in the undergraduate laboratory. Amberlyst-15 is a porous sulfonated polystyrene resin3 that serves as an excellent source of strong acid in nonaqueous media (5). I t is easy to measure, safe to use, and readily removed a t the end of the reaction. An additional advantage is that the catalyst can be regenerated and used several times. Pedaeoeicallv. the exneriment introduces students to several impokan&oncepts and techniques. Beyond affording exposure to the Knoevenagel condensation and electrophilic addition to an alkene, the experiment demonstrates the use of chemically active extraction and vacuum distillation as
' Amor to whom correspondence should be addressed.
Short paih distillations were carried out using an inexpensive (less than $20 for materials) apparatus fabricated in our glass shop. The one-piece semi-microdistillation head consists of a 25-mL roundbottomed flask (AceNo. 7015-04),a threaded connector with bushing (Ace Nos. 5027-05 and 5029-35, respectively) to hold the thermometer, a condenser fabricated in our glass shop, and a 19/22joint (Ace No. 7585-32, matches our current glassware kits) with vacuum takeoff. We have found these setups to be quite effective for distillations at aspirator pressure. Amberlyst 15 is a registered trademark of the Rohm and Haas Co.
Volume 67
Number I
January 1990
69
NMR demupllng experiment on 3 m o k
acid (3).
purification techniques. Theexperiment also lends itself toa discussion of kinetic vs. thermodynamic control in organic reactions, heterogeneous vs. homogeneous catalysis, polymer-supported reagents (6)and ring size effects on lactonization (7).all of whichare i m ~ o r t a ntto ~ i c s i nmodernoraanic s&diis. Additionally, iihigh-resoiution NMR is available. the e x ~ a n d e dalkene reaion of 3-nonenoic acid analyzes as two overiapping doublego€ triplets (see figure). ~ e c o u pling experiments can be used t o unequivocahly establish the trans stereochemistry of the double bond. Upon irradiation of each allylic C H 2 group - in the molecule, half of this complex pattern collapses to a doublet having a coupling constant (Jt,..,) of 15.3 Hz. In a further exercise, students can monitor their lactone closure reaction hv observing changes in the carbonyl absorption in the infrared or h i thin-laver chromatoara~hvwhere the lactone is observed to have a iower Rit h a n t h e s k i n g acid.
Experimental Sectlon 3-Nonenoic Acid (3) A mixture of 1.04g (0.01mol) of malonic acid and 1.34 mL (1.14 g, 0.01 mol) of h e p t a d in a 25-mL round-bottomed flask was treated with 2 mL of triethylamine. A boiling stone was added, and the mixture was refluxed for 1h or until the evolution of carbon dioxide ceased. At the end of the heating period, the reaction was caoled to room temperature and transferred to a separatory funnel using 1020 mL of ether. The mixture in the separatory funnel was washed once with 10 mL of ice cold 10%HCI, the layers were separated and the aqueous layer discarded. The organic layer was then washed with 10 mL of 5%NaOH, the layers were separated, and the organic layer was discarded in the waste solvent bottle. The aqueous layer was returned to the separatory funnel and extracted once with 10 mL of ether. The layers were separated, the organic layer was discarded and the aqueous layer was returned to the separatory funnel. The aqueous layer was reacidified with 10 mL of 10% HCI and extracted with 10 mL of ether; the aqueous layer was discarded. The organic layer was washed with saturated aqueous sodium chloride, dried over MgSO4, filtered, and concentrated in a tared flask using a rotary evaporator. The spectral data far 3-nonenoie acid were: IR (thin film) 3500-2450,1720,1645,975 em-'; NMR (CDC13 6 11.30
70
Journal of Chemical Education
(bs, IH), 5.64 (dt, IH, J = 15.3, 6.4 Hz), 5.52 (dt, IH, J = 15.3, 6.4 Hz),3.08Id, 2H, J = 6.4 Hz), 2.02 (q,2H, J = 6.4 Hz), 1.32 (m, 6H1, 0.89 (6.RH. J = 6.4 Hz); '"C-NMR (CDCM6 178.9,1:~5.5,120.6,37.Y, 32.4.31.3.28.8. 22.5. 14.0. The tvpieal rance of yields obtained by
y-Nonanolc Lactone (4) In a 25-mL round-bottomed flask was plac=dthe 3-nonenoicacid isolated from the first step, an equal weight of Amberlyst-15 and 2 mL of heptane. The miature was refluxed vigorously for 1 h, then cooled. The Amberlyst-15 was removed by filteringthrough a funnel containing a cotton plug, and the filtered catalyst is rinsed with 5 mL of ether. The solution was concentrated on the rotovap, and the resulting ail was vacuum distilled at aspirator pressure ( 2 a 0 mm Hg) where y-nonanoic lactone was collected between 138 and 145 "C. The spectral data were: IR (thin film) 1775,1180em-'; 'H-NMR (CDC13 6 4.51 (quintet, lH, J = 6.0 Hz), 2.54 dd, 2H, J = 9.5, 7.0 Hz),2,33(m,lH),1.88(m,lH), 1.70(m, lH),1,60(m,lH),1.50-1.22 (eamplex,liH),0.89 (m,3H);I3C-NMR6177.4,81.2,35.6,31.5,28.9, 28.0,24.9, 22.5, 14.0. The range of yields obtained by students was 48-76s. Acknowledgment The authors wish to acknowledge NSF Grants DMB8603864 and CHE-8718150 for partial support in the upgrade of our NMR facility.
Literature Clted I. Ault,A.T~rhnigu~aondE~patimrnfs/arOrgonicChaMalry,SU~ed.:AllynandBacon: Boston, 1987,pp46-9.Kwuyoahi,F.NipponKogakuZosahi 1961,82.627 (Chem. Absfr. 1%2,56,85491. 2. Jone8.G. Or8.ReocLions 1 9 6 7 . 1 5 . ~ . 3. Ysmanaka, H.; Yokoysma, M.; Saksmoto, T.: Shiraishi, T.: Sagi, M.; Mizugaki. M. H~larocyclea1383,20,1541. Borer.S. E.:Linatead,R.P. J. Chem.Soc. 1931,740. 4. Bortnick, N. M. (Rohm and Haas Col. U S . Patent 3,037,052 (May rJ, 1962) (Cham. A b ~ f r .1962. 57. 6125s). Monsanto Co. (Jpn Kokai Tokkyo. Kohol. Jp. Patent 57,134,471 (Aug. IS, 19821 (Cham. Abslr. 1982.98,71909nl. Bun-, R. A.: Drwnright R. E.:Tsylor, V.L.Syn. Commun. 1389.19.2423. 5. "Amberlyst15,SynfheticResinCatalysC';TechnicalBulletin:FluidPm-Chsmicals; Rohm and Heas Co.: Philadelphia, PA, 1980. 6. Ford. W.T. InPolymoricRelipontaond Cololysls:Ford, W.T.,Ed.;AmeriiiChhmiiiI Society: Washington. OC, 1986; p. I. Sherrington, D.C. In Polymer S v p p o n ~ d R ~ a ~ . flow in Organic Synthpria; Hodg% P.: Shcrrington, D.C., Ed..: Wiley: New York, 1980; p 157. 7. Winnik, M. Chem. Re". 198l.81.491. and references cited therein.
