G. R. Jurch, Jr..' M. D. Johnston, Jr., J. W. Perry, and T. E. Detty University of South Flor~da Tampa. FL 33620
I
II
The Synthesis and Proton NMR Spectrum of ~ e iI-~yc~ohepttatrieny~a~etate ~ l An advanced undergraduate laboratoty experiment
During their senior year, the BS chemistry majors in our department take a 3-quarter sequential laboratory course. The objective of this sequence is to acquaint (or reacquaint) the student with methods and techniques for the investigation of chemical systems and then to apply these methods to the examination of an actual chemical problem. The first two quarters and the first two weeks of the third quarter are devoted to the discussion (lecture) and mastering (laboratory) of techniques such as spectroscopy (ultraviolet, infrared, NMR), statistical analysis of data (including the use of a computer), polarography, potentiometric titrations, mass spectrometry, chromatography (TLC, column, gas-liquid, liquid, gel), fractional distillation, and other methods of purification. The remainder of the third auarter is then used for the application of as many of these techniques as possible to a n actual chemical prohlem. A wide variety of projects are available to the student, and they try to simulate as much as possible actual problems which mav he encountered later a h e n the student has become a practicing professional chemist. One such problem which has met with success is the synthesis and proton NMR study of the title compound, methyl 7-cvclohentatrienvlacetate (1. . . 2 .) . This oroblem eives the student Ln opeort"unity to apply several synthetic and purification techniques and then provides several possibilities for the application of NMR spectroscopy. The project is excellent in that i t can be done in its entiretv. .. as shown here. or can be done only partially. I n the latter case, it is still very profitable to the student's training.
Synthetic Methods The first step of the synthetic part of the project involves the synthesis of an organic salt, tropenium fluorohorate, from 1,3,5-cycloheptatriene.
This reaction provides experience in handling hydrascopic materials, and in spectroscopicexamination of the product. The students are reouired to take NMR. infrared, or ultraviolet spectra after each step in a synthetic procedure. The spectra are used ticonfirm the S ~ N C ~ U I ~ and ouritv of each oroduct. T& next synthetic step involves formation of the cycloheptatrienylacetic acid from the organic salt. CCOH
Ffgwe I The NMR Spectrdm 01 memyl 7cycloheptatroenylacemtelneatl at 60 Mhz The Speclrm shown YraS Ootalned an a Varm A-60 speclrameler Table 1. NMR Spectral Parameters of Methyl 7Cyeloheptatrienylace(ate in CCI, Chemical Shins (pprn)=
Coupling Constants (Hz)b
6. = 6.50
J~~ = 3.3 J&,= 3.3 J~ = 9.2
6,
= 6.02 6, = 5.10 6d = 2.1e5 6. = 2.52 6, = 3.58
J,c
-
0
J , ~= 5.6 J& = 7.4
Accurate la *a01 ppm unless omerw8se indicated. 'Accurate to i 0 . 2 HZ. Accurate fa i 0 . 0 3 ppm. a
The final step in the preparation involves the formation of the ester.
The product is purified by vacuum distillation. The purity of the ester is checked by mass spectrometry and a earbon-hydrogen analysis; the former method is also used to check the product structure. At this point, the student is ready to proceed with the NMR part of the project. The Basic NMR Spectrum The NMR spectrum of the ester is shown in Figure 1 and the chemical shifts and discernible coupling constants are listed in Table 1. The soectrum is of intermediate character between fint and second order. k 1 six resonances are far enoueh .. anart . to enable their inteerals to brsrpnmrrd. Tofnctlirntr hnhrrdisrussion the protonsare Istwlrd by the letrrrs o - / , as riven in the structure below.
~COH
This reaction provides experience in handling- and purifying a product whose melting point is near room temperature. The next reaction gives the student experience in running a reaction where some of the oroduets are "eases which should not he allowed to eaenne into the ntmosnhere. This reaction involves the conversion of ~
~
~
to contain the carbon monoxide produced. This reaction should be done in a hood, or the gases can be removed hy aspiration or can be trapped in a basic solution.
Preliminary assignmentsare relatively easy from the spectrum itself; however, confirmation must follow from further experiments. First, the olefinic resonances lie between 5 and 7 6-units and the shapes of the splitting patterns allow one to distinguish a from b and c. However, theidentitiesof b and c are only tentatively identifiable at this point-some extra information is needed to nail down which 1 Author
to whom correspondence should he addressed. Volume 57, Number 10, October 1980 1 743
tains a t least one "surprise."It turns out that decoupling andlor shift reaeent exneriments are the easiest wav to confirm the assienments a n i .. hence: ~~.the identitv, of the final ordduct. An attractive fiature of this project is that enheror hoth ufthcseoddirionnl typrsotraperimmrr; can k performed. Thus. the rvperiment can hradapted readily t o the particular aptitude of the students and to the equipment available.
~.~~
~
Spin Decoupling Experiments Decounled snectra are shown in Fieure 2: the nresentation used is adanted &m ihat of Eeeer and ~ o s~i lrd l.. ' ~ h. &is done is. simolv. ,. tosurressivrly irradiatr rach rrsonancr and watch what happens to thr others (Fig. 2A is the unirradiatcd spectrumi. Weshall concentrate on the high points here. First, irradiation in the region of e (Fig. 2B) causes thequanet tentativrly ass~gnrdt o r torollnpse ton doublet. This wcurrrnce immrdiatrly confirms the identity o t t h e lnrter re+ onance and hence. by inference. c,f 0.Irradiation c $Fir.2Ei causes b to collapse t o a fin; multiplet-much more like a hioadsinglet than a clearly discernible doublet. Thus, we have confirmed 6 being coupled t o e. I t is of equal importance to note that this irradiation of e does not affect a, which should he the case if a and e are not coupled. This latter finding is moderately surprising since o and e are allylically disposed toward each other. The fact that they are not strongly coupled is confirmed by subsequent irradiation of o (Fig. 2D) leaving the resonance of c totally unaffected. However, b collapses t o a simple doublet upon this irradiation. Also, irradiation of b (Fig. 2E) is the only thing which has any effect on the o peaks. Yet a appears as a triplet in the original spectrum; i.e., it must he coupled t o two protons rather than one. The answer to this riddle lies in the fact that a is coupled to both the other b protons. In one case, the coupling is vicinal (three-bond) and in the other case allylic. The two coupling constants are nearly equal and thus cause a t o appear as a triplet rather than a pair of doublets. Thus, spin decoupling has allowed us t o resolve what would probably, otherwise, have resulted in an error in assigning splitting6 if these measurements had not been performed. - - - ~ ~ ~ ~ Further irradiations are straightforward hut give little additional information. No irradiation has any effect on the methyl V) resonance, as expected. I t is of particular importance t o note that d and e are too close together for the coupling between them to he decoupled effectivelv. a t least a t 60 MHz. The latter fact should he nointed out t o the stud& as one of the shortcomings and difficulties often encountered in decoupling experiments.
~.~ ~~~
~
~
~
--~ ~
~
~~
. .
Shift Reagent NMR Experiments It often happens that suitable decoupiing equipment ia not available even th f > d > c > b > a. In the case of Pr(fod)s the d resonance was obscured too much of the time to he of more than qualitative use. However, this poses no difficulties in nailing down the required assignments. I t can he seen that the ambiguity in the b and c assignments is immediately resolved and that the other assignments are confirmed just as readily. All this follows from the simple rule of "what is closest to the carhonyl is shifted the most." Plots of shift versus shift are extremely easy todo and give gratifying straight lines. I t should he noted that &-values (values of the shifts in the absence of LSR) are also ohtained. In this case, it allows a check of the values in Table 1.In other cases, 60's can be ohtained even if the shift is obscured in the regular spectrum. Students should, however.. weieh .. all their sam~lesand have a mod idea of their reagent eunrenrrati~ms.A t high doping lev&, the atmple rtraight line rrlatimrhip can break down. If the time allows, both shift reagent should he used. Ifhowever, Volume 57, Number 10, October 1980 1 745
Results of Prffodh Exoerlrnents
Table 2. Raw Shins ( ~ p m ) : ~ pa 6. 6a 0.0 0.029 0.064 0.107 0.204 0.236 0.254
6.50 6.425 6.27 6.06 5.55 5.37, 5.31
6,
SdE
61
6.
1A6d
6.02 5.92 5.72 5.43 4.74 4.52
~~-
-
Linear regression r e s ~ i t s : ~ Relative rhin slopes
Proton a b C
-0.140 f 0.001 -0.187 0.002 -0.503 f 0.002
d
-
*
accuracy: *O.OI ppm. Relative concentration (molar) of LSR versus substrate:substrate concentrationsare
'Mean
tixedat0.20 M. S h l t I s of this proton obscured throughout the run. d R e 5 0 n m of ~ ~Other ~ proton^ are ploned v e r w the incremental rhin at I.
'By definition.
Raw Shins (ppm): p 6.
Results of Eu(fod), Experlrnentsa
0.0 0.051 0.065 0.135 0.173 0.221 0.244
6.50 6.57 6.62 6.71 6.79 6.67 6.91
6b
60
6.03 6.10 6.19 6.31 6.41 6.53
5.10 5.34 5.58 5.93 6.21 6.54
-
-
6.
61
lA6t1
2.23 2.59 2.95 3.60 4.10 4.74 5.07
2.53
3.58 4.12 4.66 5.38 6.01 6.79 7.18
0.0 0.54 1.06 1.80 2.43 3.21 3.60
3.66 4.48 5.16 6.02 6.46
Linear regression results: proton
60
Relative shin slopes
a
6.50 f 0.00, 6.02 f 0.004 5.10f 0.01 2.16 f 0.03 2.52 f 0.01 (3581
0.11410.002 0.158 1 0.002 0.453 f 0.005 0.600 f 0.014 1.092f 0.004 111
b c
d e f
'See me tootnotes of Table 2 tor an explanation of me variouo quantities glven here.
it is deemed inappropriate to use hoth LSRs, Eu(fad)s is the prefemed one to use. Generally, the down field direction of its LIS gives spectra which are easier to obtain. Also, it has less tendency to broaden spectral lines than does Pr(fod)s (5). Summary T h e svnthesis a n d NMR studies of methvl l-cvclohentatrienylacetate afford a n excellent project for advanced undergraduate students. Several different svnthetic. nurification, a n d spectroscopic techniques a r e us&. ~ t u d e & a r e allowed a n opportunity to carry o u t three types of N M R experiments: obtaining a basic spectrum, spin decoupling t o confirm assignments, a n d t h e use of lanthanide shift reagents a s a n alternative method of making assignments a n d i n confirming t h e compounds structure. Experimental Materials The chemicals required are listed below. Most of these were reagent grade and readily obtainable from the usual commercial sources. In 746 / Journal of Chemical Education
To prepare samples for shift reagent studies, first make about 2 ml of -0.2 M solution of the substrate. Then place about 0.5 ml of this solution in a tared NMR tuhe. Take the spectrum, weigh the sample, add a small amount (-20 mg) of LSR to the tuhe, and then reweigh. Next take the shifted spectrum and repeat the above procedure until finished (generally 5 or 6 samples with relative concentrations of LSR to substrate ranging from 0 to -0.25 are sufficient.
~
66
3.11
p4010,
Instruments The NMR spectra were taken on Varian A-60 and EM-360 spectrometers; the latter was equipped with a Model EM-3630 spin decouder. Sweep widths correswndinr! - to 1Hzlmm and 2 Hzlmm were used. A Perkin-Elmer Model 710 soectrometer was used far the infrared spectra, a Cary Model 1 4 rpwtnmeter was used to ohtain ultravider spectra, and a Varinn EM-fi(lO wna used to obtain mass spectra.
* Measured directly.
Table 3.
most cases no further purification was required. Where a particular commercial source is more convenient or where special treatment is needed for a particular chemical it will be given when required. Chemicals used: triphenylcarhinol (Arapahoe), fluoroboric acid (J.T. Baker, purified, 4&50% aqueous solution), acetic anhydride, malonic acid, pyridine, pentane, petroleum ether (304O0C), methanol, cycloheptatriene, oxalyl chloride, and thionyl chloride. The SOClo was distilled from boiled linseed oil. usine 10 e of SOCL oer - milliliter of oil. The fraction removed for use b;iled"at 76%.-?he distillation was performed in a hood. The lanthanide shift reagents (LSR) employed were Eu(fod)s and Pr(fod)3. Both were Aldrieh "Gold Label" and were sublimed and stored for a t least 24 hr over PdOlo in uacuo. No impurities were observed in LSR NMR spectra; the only resonances observed for each were the tert-hutvl neaks of the fad lieand. The Aldrich "Gold Label" LSRs can be use2 without further n&fication. The onlv.. orecaution which need he taken is to store them in a vacuum desiccator over
~~
Tropenium fluoroborate (7). In a one liter Erlenmeyer flask protected with a drying tuhe. 33.38 (U.l'LX mole) of triphenylcarbinul was dirnrlved in :300 ml uf acetic anhydride. In ordcr rodissolve the alcohol the mixture was warmed un a steam bath until all the solid disappeared. After solution was completed, the mixture was cooled u, room temperature wnh tap water, carefully avoiding reprecipitation of the alwhol. Fluorohoric acid
