Undergraduate Organic and Polymer Lab Experiments that Exemplify Structure Determination by NMR T. Viswanathan, F. Watson, and D.T.C. Yang University of Arkansas at Little Rock, Little Rock, AR 72204 During the past 20 years, the NMR spectrometer has rivaled and surpassed the infrared spectrometer as the premier tool for molecular structure elucidation. Only the most impoverished academic chemistry departments do not have an NMR spectrometer. Since NMR analysis has hecome such an integral part of being a chemist, it is essential that undergraduate students be introduced to the measurement and interpretation of NMR spectra. Chemistry majors are first introduced to interpretation of NMR spectra during the second general organic lecture course (usually taken during the spring semester of the sophomore year). At this stage of development of their experimental capabilities, students are not usually expected t o operate an NMR spectrometer. Adequate introduction of experimental NMR techniques (involving 'H and '3C) requires at least a 1M)-MHz instrument. Where in the curriculum is the best place to teach experimental NMR methods that are so essential t o chemists and chemistry? Most chemistry curricula include a course in instrumental analvsis that addresses uroduction and analysis of N M R spectra. The instrumental course usuallv involves a single N M H exoeriment since it deals with a &ety of spectr&opic and klectrochemical methods. At UALR we are of the opinion that NMR is so essential to chemistry that the students must be given more than a cursory introduction involving a single experiment. Hence, i t is suggested that students be firmly schooled in NMR methodology through a series of experiments performed in the laboratory portions of three senior-level courses: Qualitative Organic Analysis (Chemistry 4250 a t UALR), Introduction to Polymer Chemistry (4380), and Or~~~
ganic Preparations (4251). Chemistry majors are required to take the qualitative analysis course and are expected to take a t least one of the other two. Currently, 10 different (synthetic) experiments are carried out in these senior-level lab courses. Even though NMR can be used for the identificationlcharacterization of most of the macromoleculessynthesized in the oolymer lab, it is felt that its use in at least three selected experiments should suffice to exemplify the technique's utility in structure elucidation. Since the FT-NMR in a small department must he used in other courses and faculty research projects, its availability in any one course is usually limited. The following lists 10 experiments that can be used to illustrate the use of NMR in organic laboratory courses. They have been chosen to demonstrate some classic as well as novel reactions. the utilitv of which is evident after spectroscopic analysis'of the prdducts. Most of the experiments have been oerformed in the UALR Chemistry Department. ~ x ~ e r i m e d1,2, t s and 3 can be in a polymer lab; 4through 7 in the qual lab; 8 through 10 in the preparations lab. They work well, especially when interpretation of results can be facilitated by NMR analysis. Laboratory Experiment #1
Characterization of Polymer Tacticity by NMR Analysis This experiment involves the synthesis of three types of polymethyl methacrylate (PMMA)-two by stereoregdm addition of and one by stereoirregular (random) addition of monomers-and the products investigated by NMR.
Isotactic PMMA
Syndiotactic PMMA
Atactic PMMA
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The experimental aspects of the preparation and purification of the polymer are simple enough ta he carried out in an undergraduate lab. The 'H- and 'W-NMR of the monomer and polymer are run and the spectra interpreted. The interpretation of the high-resolution spectra of the polymer can pose some problems due to fine structures caused by restricted rotation about N-COEt, hut may be eliminated by use of high temperatures (6) ( 5 80 OC). Low-temperature (-78 "C) ionic initiation (n-BuLi) in anonpolar solvent (toluene) causes the formation of a highly isotactic polymer (1).If instead an ether solvent (THF or 1,2-dimethoxyethane) is used, a highly syndiotactie polymer is formed (2).High-temperature (70 OC), free radical polymerization results in stereorandom addition, producing an atactic polymer ( 3 , 4 ) . The W N M R spectrum of the different tactic forms of PMMA, show slightly different absarhances for the ester methyl group, the methyl group an the polymer backbone, and for the methylene group. For example, the -CHrprotons in the syndiotactic polymers show one absorption peak at 1.86 6 while the -CH2- signal for the isotactie polymer shows four peaks a t 1.4, 1.6, 2.1, and 2.3 6. The atactic polymer shows both types of -CHs- absorption due to presence of both syndiotactic and isotactic regions in the polymer.
Laboratory Experlment #3 Ring-Forming Polymerization of Diallyldimethylammonium Chlorlde (This emeriment was also develoned hv Viswanathan (5) with LO" ath hi as of Department of ~dlyme; Science. ~ n i v e k t yof Southern hlississippi.1 The unequivocal structure of pulg(dial1ydimethglammoniumJ chloride (shown below) has been proven in an excellent paper (7)by comparison of the W-NMR of the polymer with some model compounds. They were able to prove that the polymer did not have the expected six-membered ring structure in the backbone ('H-NMR alone was shown to he insufficient for arriving at the correct structure). This example demonstrates the power of W-NMR spectroscopy in the structure elucidation of
/'\
In the 'H-NMR spectrum of a sample of PMMA, the total area under the single -CHz- peak (that corresponding to syndiotactic isomer) and the four peaks due to isotactic - C H r , can be taken as being proportional to the total -CH2- content in the polymer. The ratio of the area of the -CH2- protons (isotactie or syndiotactic) to the total -CHr area may thus he used to represent the relative abundance of a particular type of tacticity in a given sample of PMMA. Laboratory Experlment #2 Ring-Openlng Polymerization of 2-Substituted Oxazolines (This is one of the experiments developed by Viswanathan (5), along with Lon Mathias of Department of Polymer Science, University of Southern Mississippi.) Ring-opening polymerization represents an important method for the synthesis of several commercially important polymers (e.g., polyoxyethylene (POE), poly(propylene oxide) (PPO), nylon 6 and poly(ethy1eneimiue) (PEI)). PEI itself can he prepared hy acid hydrolysis of poly(2-ethyloxazoline) whose synthesis is discussed below. The ring-opening polymerization of the monomer 2-ethyloxazoline is interesting because the heterowelic monomer opens during nucleophilic attack generating an amide functionality.
molecules that are not otherwise amenable for easy analysis by 'HNMR spectroscopy. Laboratory Exparlment #4 Use of Lanthanide Shift Reagents in Deducing and Distinguishing the Structures of Longchain lsomerlc Alcohols Proton NMRspectra oflong-chain (2five carbons) alcohols yield broad multiplets for -CHr protons further removed from the -OH group in the high-field region (1.2-2.2 6), making structure elucidation by hulk integration of these shapeless peaks very difficult. In some cases, the prohlem can he overcome by the use of lanthanide shift reagents (LSR's). Far general purposes, Eu(fod)~can be used because of its relatively high solubility, chemical inertness, and its ability to improve the solubility of some compounds in some nonaqueous solvents (8). T h practical use of LSR for problem solving is demonstrated in distinguishing the structure of isomeric alcohols. An example is to distinguish the two compounds below.
Without the use of shift reagents, it would he impossible to distinguish these compounds based on their 'H- or 'V-NMR spectrum. However, the problem is solved by use of LSR. A plot of the shifts of the signals against different amounts of Eu(fod)a added will yield a graph with lines of different slope for each of the protons. The steever the s h e of a vroton. the closer it must he to the site of compl~xation&, the OH group). For 'C-YMR spectroscopy, low concentratiun of Ybtdpm), is LSR of choice since it gives exrellenr r e i u l t ~for aliphatir alcohols t9). ~~
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~
~~~~~~
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2.2-Azobls(2-amldinopropane-2HCl)-a water soluble free-radlCaI initiator available from Polysciences. Inc., Warrlngton. PA 18976.
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51%. The structures of the intermediate and final products can be identified by proton NMR (13)
Laboratory Experiment #5 NMR Spectroscopy of Racemlc Phenylethylamine Using Chirai Lanthanlde Shift Reagents Enantiomeric forms of a-phenylethylamine cannot be distinguished by 'H- or 'T-NMR, because the groups attached to the stereocenter are in an enantiotopie environment. However, the chemical shifts of the proton and carhon groups attached to the stereoeenter can he differentially altered so as to become clearly distinguishable in the 'H- or 'T-NMR spectrum. This is accomplished by use of one of several chiral lanthanide shift reagents. One of the most useful af these is tris (d,d-dicampholylmethanato)europium(II1). The addition of the c h i d shift reagent results in the formation of two diastereomeric forms of an acid-base complex, thereby creating s diastereotopie environment for the groups attached to the stereocenter. This would result in distinct resonance peaks for the 'H's and ' V s of the two enantiomeric forms of a-phenylethylamine. Eu(dcm)a resonances themselves occur at high fields and move to still higher fields upon addition of a coordinating substrate (mine). An excellent paper dealing with the determination of enantiomeric purity using chiral lanthanide shift reagents has been puhlished 110). Chemical shift owitions of various 'H's in a-ohenvlethvlamine . . . in Eu(dcm)?aregiven in this article. In this experiment, a sample of the racemic mixture can he resolved using (R)(R)-tartaricacid (11).The optical rotation of one of the enantiomeric forms may he determined using apolarimeter. The NMR using the chiral shift reagent is then studied and compared with the spectrum of the racemic sample with the chiral reagent.
Laboratory Experiment #9 The Effect of Solvent on Bromlnation of 5-MBA by NBromosuccinimlde(NBS)(13) Bromination of 5-MBA with NBS in CCL, furnishes 5-hromomethylbenz(o)anthracene in 92% yield. When hromination is earried out using dimethylformamide as the solvent, 7-hromo-5-methylhenz(a)anthraeene is formed as the exclusive product. This dramatic solvent effect is best appreciated by NMR analysis of the products formed.
Laboratory Experlment #8 Demonstration of the Carbon-Nitmgen Double Bond Character in Amides In primary amides where R and R' are both protons, we can see them as two distinct broad signals (12). This is due to restricted rotation around the carhon-nitrogen hond. Secondary amides generally do not exhibit spectra that correspond to two rotameric forms. This is because the two Lareer ErouDs R and R" stay trans to each for tertiary amides when R' = other. A 50:50 ratio of rot&ers;xis& R".
In the W-NMR of N-ethyl-N-methylbenzamide, all eight types of carbons iincludine those in the ohenvl - rine) eive two lines each a t - 3 0 T (in CDCI~). ~ hpairs e of lines coalesce in turn as thetemperature is raised to 50 'C. This experiment is a good exercise for students in qualitative organic lab who prepare benzamide derivatives and try to interpret the NMR spectra.
.
Laboratory Experiment #7 SimplMication of 'H-NMR Spectra by Lbutemtion of Exchangeable Protons Protons attached to highly electronegative atoms such as 0 or N may be acidic enough that they can undergo exchange reactions in D20 solution. This could be an advantage in eases where these exchangeables are buried under a Large group of other signals. For example, in lang-chain (alkyl) alcohols, the -OH proton may be buried under the alkyl protons (1.2-2.0 6). In such cases, deuteration followed by reintegration can reveal its presence and can he quantified by the decrease in peak area, corresponding to the number of exchangeahles removed.
Laboratory Experiment # l o Deoxygenatlon of a$-Unsaturated Aldehydes and Ketones via the CatecholboraneReduction of the Corresponding Tosylhydrazones ( 1 4) The reduction of tosylhydrazones with boron hydrides offers a mild and convenient alternative to the Wolff-Kishner and Clemmensen reductions. In this experiment an a,8-unsaturated system is reduced with migration of the double hond. The structure of the final product is easily derived by NMR spectroscopy. NNHTs
Laboratory Experlmant #8 Synthesis of 5-Methylbenz(a)anthracene(13)(5-MBA) A three-step synthesis of 5-methylhenz(o)anthracene(noncarcinoeenic) is oerfomed. The first steo is a Friedel-Crafts acvlation of l&thvln6"hthalene . ~~~.~~~ ,.....with o h t h a k anhvdride to eive ketc-acid 1in 96%yield. The second a t e s s reduitionbi thi kirb-acid 2 (90~;)by %n/NaOH. The third step is cyclization and reduction of the result. ing ketone by HI in acetic acid to give 5-MBA. The overall yield is ~~~~~~~
Literature Clted
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1. McCsffery, E. M. L o b m t o r y Pmporafhn (or Morromolesulor Chemrsfry; MeCrawHili: New Yark, 1970:p 229.
2. Sorenson, W.R.;Campbel1.T. W.Pr~rp~rolio~M~lhads~fPoiy~~~Chhhiitry:Intersciencc: New York,1968;p 284.
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3. Collins, E. A,; Bares J.; Billmeyer, Jr., F. W. Exporimant8 i n Palymcr Science: lnterl~ ciencc: New York, 1973; p 313. 4. Pearco, E. M.: Wright C. E.;Bordoloi, B. K. Lobomlory Experiments in Polymer Synthesis and Chnrorterizotion, Educolionol Modules for Notconal Science and Engineering I E M M S E I Prajeel:The Pennsylvania State University, Materials Rerearch Laboratory: Univemity Park,P A 16802,1982; p 250 and references therein. 5. Mathias, L. J.; Viswansthsn,T. J. C h o n Edue 1981.64 639-641. 6. Ivin, K. J.; Kusn-Essig, L. C.:Lillio,E. D.; Wstf, P.Polymer 1976.17.658-664. 7. Lancaster. J. E.; Baeeei, L.: Panrer,H. P. Palym. Lett. 1976.14 549-554. 8. Silverstein. R. M.; Bassler. C. C.;Morrill.T. C. Spselromel~ieIdenlifirationofOlgonicCompoundr. 4th ed.: Wilav: New York, 1988.
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9. Williamson,K.L.;Clutter,D.R.;Enich,R.:Alexandcr,M.:Burroughr,A.E.:Chua,C.; Bogel, M. E. J.Am. Chem. Soc. 1974,96,1471-1479. 10. McCrearv. M. D.: Lewis.D. . W.:. Wermiek D. L.: Whitesides. G.M. J . Am. C k m . S o c . 1s7a.96, i o i 1 0 5 4 . 11. A u k A. Tzchniyues and Exp~rimenta/or Organic Ch~miatry,5th ed.: Allyn and Bacon: Newton. MA, 1987; p 339. 12. Richsrds.S. A.Loborolory0uide toPmtonNMRSpecfroscopy;Sciontifics:Paia Aka, CA, 1988: p 101. 13. Che. J.: Yang.D.T.C.P?or. Allonsoa A c d S c i . 1987.41. 24. . 14. Kaba1ka.G. W.; Yang,D.T. C.;Bsker, Jr., J.D. J. Org. C h ~ m 1976,41,574
