Trifluoroacetylation of Unknown Alcohols An Integrated Microscale Organic Experiment Using Spectroscopic Methods Kenneth Piers1 and Richard Hsung2 Calvin College, Grand Rapids, MI 49506 Recently, we have converted our oraanic chemistry lahoratory program from macro- to microscale, along the lines pioneered by Mayo, Pike, and B ~ t c h e rThis . ~ conversion has ;equired the revision of all of the experiments formerly performed in our macroscale laboratory program. We have found that trifluoroacetylation of unknown alcohols is a fast, clean, easily performed microscale experiment that inteerates a number of a s ~ e c t of s laboratorv work. viz. svnthesis " (including a nontrivial yield calculation), isolation (extraction), characterization (boiling point, refractive index), spectroscopic measurement and interpretation (IR, 'HNMR), and unknown identification. Trifluoroacetylation of alcohols has several advantages over traditional acetylation experiments involving alcohols. Trifluoroacetylation requires no strong acid catalyst, involves a simplified workup procedure, and produces the product esters in higher isolated yield than does acetylation. A similar, though somewhat less complex, macroscale acetylation experiment was recently described in this Journal.4 The Experlmenl
Each student begins with an equal volume of an unknown alcohol. The task is to identifv the alcohol they were given from a list of 18 possible candidates. The identification is accomplished by conversion of the alcohol into its trifluoroacetate derivative. The preparation of the ester involves the reaction of the unknown alcohol with a measured quantity of trifluoroacetic anhvdride. The ouantities used in the svnthesis of the ester are such that, with low molecular weight alcohols. the anhvdride is the limitine reaeent: - . with hieher molecular weight alcohols, the alcohbl is the limiting reagent. Once the student has isolated the ester, it is characterized and identified. The student must measure the boiling point (ultra-micro techniquePand refractive index of the product and compare the measured values with those in the table provided. Generally comparison of these measured values with the known values does not allow an uuambiguuus identification ofthe compound. The student completes the idrn-
tification by running an IR spectrum of the product and interpreting it and by interpretation of a proton NMR spectrum of the ester, which, in our case, is provided by the instructor. Obviously, additional data (carbon-13 NMR, mass spectrum) could he obtained in order t o further characterize the product. However, we have found that the data we use provides the students with sufficient evidence for reliable identification and provides a good introduction to spectral interpretation in the laboratory and especially imDresses them with the utilitv of NMR swectroscowv . for struc&a1 elucidation. After identifvina the ester, the student infers the identitv of the unknown aicohol. T O complete the experiment, thk student must calculate a percent yield for the svnthesis of the ester. This calculation requires that the student determine which r e a c t a n t t h e alcohol or the anhydride-was the limiting reagent in the experiment. Thus, volume, density, and molecular mass data (CRC Handbook) must he handled correctly for each of the reactants. This calculation turns out to he nontrivial for most students. Procedure Outfit a clean, dry 5-mL reaction vial6 with an air condenser, and add a boiling chip. Cool the vial in an ice beth for a few minutes, and then using an automatic pipet transfer 775 rrL of ice-cold trifluoroacetic anhydride into the vial in the fume hood. Then carefully add (auto-pipet), without agitation, 500 p L of the unknown alcoh01.~ Quickly replace the air condenser, and carefully swirl the contents of the vial in order to mix the two layers. A vigorous reaction ensues that is sufficiently exothermic so as to hring the contents of the vial to a boil. When spontaneousreflux stops, cool the vial in an ice bath. When the vial is cold, carefully remove the condenser, and using a disposahle Pasteur pipet add about 1 mL of 25%aqueoussalt (NaCI) solution to it. Cao the vial securelv. and mix thorouehlv .. ,hv.shakine. All~wthe layem to separate, and using a Pa9teur pipet remove and discard the lowpr aqueous layer.' Repeat this extraction procedure Physlcal Constants of TrlfluoroacetateEsters Trlll~~roa~etale
b.
l"Cle
Ally1
Author to whom correspondenceshould be addressed. Calvin College undergraduate, 1984-1988. Mayo, D. W.; Pike. R. M.; Butcher. S. S. Microscale Organic Laboratory. 1st ed.; Wiley: New York. 1986. Branz. S. E. J. Chem. Educ. 1985. 62.899-900. s.;. Meredith. M. L. J. Chem. M&O,D.~ . : ~ l k eR.. M.; ~ u t c h e r ; ~ Educ. 1985, 62, 1114-1115. We use the microscale glassware kits manufactured by Ace Glass Inc.. Vineland, NJ. 'The alcohol may be at room temperature. If the alcohol is added carefully, it floats on the surface of the much more dense trifluoroacetic anhydride (density = 1.495 glrnL). and no reaction takes place until the layers are mixed. This workup procedure works well wlth all unknowns except the following: propyl, isopropyl, and allyl alcohols. With these three aicohols, the reaction should be wo&ed up by addition of water instead of salt solution. In these cases, the ester layer is on the bottom, the water layer on top when the layers separate.
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90
Journal of Chemical Education
Benzyl rrB"ty1 lsobutyl seoButy t-Butyl
Cyclohexyl ~Heptyl rrHexyl 2-Methyl-I-butyl
BOCVl 2-octy1 lsopentyl *Pentyl seoPentyl 3-PentyI ~Propyl ~SDO~ODV~
Measurements made on crude reaction prcduu.
%a
%
Yield'
with one additional 1-mL portion of salt solution. Dry the product over anhydrous Na2S04 (200 mg), and when it is dry transfer the nroduct into a oreweiehed s s m ~ l vial. e Reweieh the vial. and record the mass of p;oduct"ohtained. Measure t h e boiling point (ultramicro method), refractive index, and infrared spectrum of the prod. ~ interuct. Obtain the protun XMR spectrum of your p r ~ d u c r Ry pretation of th? spectral data and by compariwnof the boiling point and refractive index uith those of known esters ,see table), identify
.~~~~~~~~~~~ ~~
~
the ester and, hence, the unknown alcohol. When the alcohol has heen identified, Look up its density (CRCHandbook) and determine which reactant was the limiting reagent in the synthesis of the ester. Then calculate a percent yield-for the reaction lnteresled persons may receive c o p e s of the 'ti-NMR spectra of the trift~oroacelates of the unknown alcohols upon request.
Volume 66
Number 1 January 1989
91
