And the Structure Is.. .? S. S. Stradling St. Lawrence University. Canton, NY 13617 The tradition of the qualitative (organic) unknown can be pictured as the transfer of an unlabeled vial containing a suspiciously obscure-looking liquid or solid from a knowledgeable professor to an apprehensive student. Much useful learning can follow that transfer as the student accumulates physical and chemical information and matches it with spectral data to reach a conclusion of the unknown's structure. Although an occasional completely anonymous unknown will appear in this manner during one's professional life, much more is usually known about the origin of the material. To recognize this reality, we have adapted several experiments from the literature as unknowns for students in our junior and senior advanced laboratory program. These experiments involve the reaction of known starting materials under conditions which yield products offering varying degrees of challenge to a student's ingenuity as a determiner of structure. Except for provision of a rather complete presentation of the reaction and work-up conditions, these exercises, requiring 2-6 afternoons of laboratory work, provide a typical challenge to a laboratory researcher. Our experience in providing these unknowns suggests that the course of reaction is not immediately obvious to students and the task of analyzing the data is both productive and rewarding. Five reactions producing "unknowns" are presented herein: (1) base treatment of citral, (2) camphor plus acid, (3) acid treatment of limonene oxide, (4) carvone oxime with acid, and (5) a Grignard reaction with ethyl phenylacetate.
Experlrnental Organic starting materials were obtained from Aldrich Chemical Co. Gas chromatographic analyses were performed on a Perkin-Elmer Sigma 2000 using Supelco column packings and conditions indicated in the individual experimental sections. Citral Plus Base ( 1)
Reflux a mixture of citral (about 7.0 g), potassium carbonate (about 7.0 e). and water (ahout 70 mL) for aooroximatelv 48 b Cool andseparate the l'ayers. Dry theorgan'ic layer with anhvdrous sodium sulfate. decant. and distill under reduced pre&ure (reported b.p. 108-110 OC1100 mm and 75 OCf18 mm) (1, 2) collecting as many fractions as appropriate. Yields ranging between 40-72% are expected. The purity of the product is determined by gas chromatography using a SP2100 column a t 125 " C for 5min, then rising to 175 O C at 3 deg/min. This experiment also has been performed with success on a microscale by refluxing citral(1 g), potassium carbonate (1 g), and water (10 mL) in a 25-mL round-bottomed flask for 24 h, drawing off thelower aqueous layer, drying the residual organic materials with anhydrous sodium sulfate, decanting into a 3-mL conical vial, and distilling into a Hickmann still under reduced pressure. Camphor Plus Acid (3, 4) In a hood, cautiously stir (magnetic) amixture of camphor (10 g) and conc. sulfuric acid (65 mL) maintained a t 110 O C for 1 h. Cool the solution, and pour it cautiously into ice water (200-300 mL). Extract the aqueous solution with three 40 mL portions of hexanes or pentanes. Wash the combined hydrocarbon portions three times with 5% sodium hydroxide, then dry with anhydrous sodium sulfate. Rotary evaporate the hydrocarbons, and chromatograph 3-3.5 g of the crude product (yellow oil) on silica gel (75 g) (40-140 mesh) using methylene chloride as eluant. Both gravity and flash chromatography have been used to accomplish successfully the required separation. Collect 50 mL fractions (perhaps 10). After solvent removal, analyze the fractions (and the original crude product) using gas~chromatography (SP2100; 125°C for 5 min, rising to 150 "Cat 2OCImin). The resulting two major products are separated adequately by the column chromatography. Llrnonene Oxide Plus Add Reflux (+).limonene oxide (10 g) and formic acid (75 mL) for 24 h, then cautiously pour into ice water (about 200 mL). Extract the aqueous s&tion with four, 40 mL ponions of methylene chloride. The combined extracts are washed successively with 50 mL each of 5% sodium hydroxide, water, and saturated salt solution. Dry the methylene chloride solution with anhydrous sodium sulfate, decant, and evaporate the solvent. Vacuum distillation produces a purified product (reported bp 104 "C, 10 mm Hg) (5).Purity is checked by gas chromatography (SP2100; 160 OC). This experiment has also been run successfully in smaller quantities in refluxing toluene using a Nafion catalyst.
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Journal of Chemical Education
Carvone Oxime Plus Acid (6) The carvone oxime is prepared by refluxing carvone (8 mL, 7.7 g), hydroxylamine hydrochloride (4.7 g), 95% ethanol (50 mL), and pyridine (10 mL) for 1h. The mixture is concentrated hv rotarv evaporation to a svrup. then mixed : precipitate of"ca&one oxime is with ice water (100 m ~ ) hep collected by suction filtration and recrvstallized from ethanol-water (mp 70-71 OC). The unknown is prepared by refluxing the carvone oxime (2.0 g) with 6 M hydrochloric acid (20 mL) for 10 min, then reducing the heat to allow warmingfor an additional 50 min. The cooled solution is extracted once with diethyl ether (20 mL) and the ether portionis washed successively with 10mL each of water, 5%sodium bicarbonate, and saturated eodium chloride. The ether is dried with anhydrous sodium sulfate, decanted. and eva~orated.The hrownish-red crude ~ r o d u c t 1s determined by &schromatography (SP1000,200 O'C) to be quire pure (>90 90)and is analyzed w~thoutfurther purification.
Most students are quite familiar with the important nucleophilic properties of Grignard reagents in preparing various types of alcohols from carbonyl compounds, including esters. In this reaction, however, presumably for steric reasons, the Grignard reagent utilizes its powerful basic properties to effect a Claisen condensation of the ester. The molar ratio of reactants is also chosen to not impede, if not promote, the base condensation. The product is ethyl p-oxo-aphenylbenzenebutanoate (Chem. Abstr. designation). Our experience, as well as others who have worked with the methyl ester (9,101, suggest that any en01 tautomer must be in low concentration, a t least in CDC12, since it does not appear in the NMR as a complication to structure analysis. This reaction can also be run using methyl phenylacetate instead of the ethyl ester.
Ethyl Phenylacetate Plus Grignard (7)
Slowlv add, with mametic stirring, an ether solution of ethyl phenylacetate to ;cooled solution of isopropylmagnesiumchloride inether. We usuallv work with ahout 2 cot the ester in 20 mL of dry diethyl eiher and use a 506molar excess of a commercially available (Aldrich Chemical) 2M Grignard solution. [Grignard solutions that have been stored are tested for efficacy before use, and the amount used is adjusted depending on the actual concentration (8j.1The reaction mixture is stirred at room temperature for 10 min and refluxed "eentlv" for an additional 10 min. After cooline. -, the reaction mixture is poured slowly into a 10%ammonium chloride solution (perhaps 20 mL) and transferred to a separatory funnel. Additional wash ether is added, if necessarv, and the lavers seoarated. The lower. aaueous laver is exGacted with &her (20 mL) and the ethdr layers arecombined and washed successivelv with 20 mL each of 5% sodium hicarhonate and saturatedsodium chloride solution. The ether is dried with anhydrous maanesium sulfate, decanted. and evaporated on a steam bath & a hood. The solid can bd purified by trituration in cold ethanol or by recrystallization from ethanol as indicated by Conant and Blatt (7). Dlrcusslon Infrared and proton nuclear magnetic resonance spectra are obtained for all the unknowns and remesent the most useful data for performing structure anaiyses. Ultraviolet soectrosco~vwould assist in some of the structure evaluations but isgenerally omitted. Physical data, such as bp, mp, no,are also collected, and find use when comparing possible structures with known information. Most products are subiected to pas . chromatoera~hic - - analvsis as a -eauee - of ~.u r i .t v . The reaction of citral with aqueous base causes a retroaldol process producing 6-methyl-5-heptene-2-one. The reaction of sulfuric acid with camphor causes complex rearraneements leadine to the two isolated ~roducts.carvenin about a 6:4 rstio. one and3,4-dimethy~a~eto~henone, Rearrangements subsequent to the opening of the epoxide ring in limonene oxide leads to carvenone as the isolated product from this reaction. Oximes plus acids, though rarely with aqueous hydrochloric, often lead to Beckmann rearrangement products. This does not occur here; in fact, the preparation of the oxime is a bit of a ruse, since in aqueous acid the carvone oxime almost surelv hvdrolvzes hack to the ketone. which then aromatizes t h r ~ ; ~ h d o u k ebond migration and tautomerization. The product is carvacrol.
h carvenone
carvacrol
ethyl 8-oxo-a-phenylbenzenebutanoate ethyl 2,4-diphenylacetoacetate Acknowledgment Considerable gratitude is extended to the many St. Lawrence University students who undertook these experiments with enthusiasm and dedication. Special thanks are extended to G.V. Henderson, K. Rehehn, D. Bymark, M. Masley, and R. Decker, all of whom worked on initial smoothing of procedural rough edges. Thanks also to the Shell Corporation which orovided fundine for summer stipends for Maslev and ~ e c k e and ; to ~ u ~ o n c faogift r of ~ a k o catalyst. n ' Presented at the 199th American Chemical Societv Meetinm-. Boston. MA, April 1990.
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Llterature Cited 1. Dennison, N. R.;Mirringt0n.R. N.; StL!srf,A. D. A w l . J. C h e m 1975.28.1339-1343. 2. Aldrich Caialog.Hondbook olFine Chemiroia. Aldrich Chemical Co.. Inc., 1990. 3. Lutr.R. P.;Rober~%J.D . J . Am. Chem.Snc 1962.84.3715-3721. 4 . Radig. 0. R.;Sysko,R. J. J . A m Chrm.Sor. 1912.94. 5475.6479, 5. Weest. R. C.. Handbook 01 Chmiarry and Physics, 56th ed.; CRC: Cieveland. OH.
man: England. 1989; pp 442-445. 9. Ainswoifh,C.: Chen. F.:Kuo Y-N.J. Or8onomet. C h e m 1972.46.59-71. 10. Rochi. G.:Hechsfres~er,V.; Pswlak. W. J.Or#. C h m . 1973,33.4348-4350.
Volume 68 Number 5 May 1991
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