tion. Thus, to obtain more nearly valid thermodynamic data, determination of the retention profile for that system is a necessary step so as to be able to select the best range of sample size before using the methods such as those outlined by Condor and Purnell(2,3,33). The above procedure can also be applied in determinations of adsorption parameters, provided adequate determinations of the effective surface areas for each of the interfaces can be obtained. Both peak means and peak maxima have been used throughout this study. Peak means are often easier to obtain by computer techniques involving moment analysis and have also been reported (38, 39) to be more meaningful from a thermodynamic viewpoint. However, the true value of the peak mean is very difficult to obtain if there is bad peak tailing. Furthermore, peak means start to change rapidly a t
noticeably larger sample sizes than d o the peak maxima. In contrast, retention volumes based on peak maxima are much less infiuenced by peak shape so they show less scatter in the data. Therefore, retention volumes based on peak maxima may be more useful in actual practice. Wider use of pure stationary phases should help interlaboratory comparisons of data. The present approach of characterization should be useful if standard stationary liquids are adopted (13, 14) even though the smaller polymers are the easiest to obtain pure, but are also the most limited by their volatility.
(38) E. Kucera, J . Chromatogr., 19, 237 (1965). (39) 0. Grubner, “Advances in Chromatography,” J. G. Giddings and R. A. Keller, Ed., Marcel Dekker, New York, N. Y., Vol. 6, 1968, pp 173-246.
RECEIVED for review February 2, 1971. Accepted June 25, 1971. This work was supported in part by the U. S. Atomic Energy Commission under contract AT-(1 1-1)-1222.
ACKNOWLEDGMENT
The authors express their thanks to Dr. C. H. Lochmiiller for his assistance in preparing the pure oligomer phases.
Applications of Paramagnetic Shlift Reagents in Proton Magnetic Resonance Spectrometry Analysis of Alcohol Mixtures Dallas L. Rabenstein Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada Addition of tris(dipiva1omethanato)europium [Eu(DPM),] to CDCl, solutions of alcohols results in large downfield shifts in the resonance frequencies of the carbon-bonded alcohol protons. The shifts arise from complexation of the hydroxyl function to the paramagnetic europium(ll1). In this work, the shifts induced by Eu(DPM), in the proton NMR spectra of all the isomers of alcohols containing up to five carbons and selected isomers of alcohols of higher carbon numbers have been measured at 60 MHz. The shifting ability of Eu(DPM), has been applied to the problem of analyzing multicomponent alcohol mixtures by NMR. It has been demonstrated with a variety of mixtures that overlapping resonances due to formally nonequivalent protons can be resolved to yield analytical resonances for each component.
NUCLEAR MAGNETIC RESONANCE spectrometry (NMR) is inherently suited as a technique for quantitative analysis because the integrated intensity of a resonance is directly proportional to the concentration of nuclei giving the resonance. The basic requirement for its application t o the analysis of multicomponent mixtures is that a resolved analytical resonance be available for each component t o be analyzed. Mixtures of chemically similar compounds often give rise t o spectra characterized by overlapping resonances, however, which has severely limited the use of NMR as a technique for quantitative analysis. This limitation has been overcome t o some extent by the development of spectrometers utilizing magnets of high field strengths. Recently, Hinckley reported that the dipyridine adduct of the europium complex of dipivaloylmethane [Eu(DPM), .2Py] induces large downfield shifts in the proton magnetic
resonance spectra of molecules containing hydroxyl groups without collapsing multiplet patterns due t o spin-spin coupling (1). The shifts are probably due t o pseudocontact interactions arising from bonding of the hydroxyl group t o the paramagnetic europium (2,3). This was followed by the report that the pyridine free complex of dipivalomethane, EU(DPM)~, is a n even more effective “shift reagent” for simplifying the spectra of molecules containing hydroxyl groups and certain other functional groups bearing lone pairs of electrons (4). Briggs and coworkers have reported that the analogous praseodymium complex, Pr(DPM),, induces shifts that are opposite in direction and larger than those reported for EU(DPM)~ (5). These shift reagents are a n important discovery because they allow otherwise unresolved spectra to be resolved and interpreted without the loss of spin-spin coupling information. The shifting ability of these paramagnetic lanthanide complexes potentially provides a method for resolving overlapping resonances from the individual components of multicomponent mixtures. If this is the case, it would then be possible to analyze such mixtures by NMR. This would significantly increase the general applicability of N M R as a technique for quantitative analysis. We are presently involved in research (1) C. C . Hinckley, J. Amer. Chem. SOC.,91,5160(1969). (2) D. R. Eaton, ibid., 87, 3097 (1965). (3) J. Briggs, F. A. Hart, and G . P. Moss, Chem. Commun., 1970, 1506. (4) J. K. M. Sanders and D. H. Williams, ibid., p 422. ( 5 ) J. Briggs, G. H. Frost, F. A. Hart, G . P. Moss, and M. L. Staniforth, ibid., p 749.
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
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b
Figure 1. 60 MHz proton NMR spectra of 0.40 ml of CDC13solution containing 0.300M n-heptanol at various mole ratios [moles of Eu(DPM)~per mole of n-heptanol]: (a) 0.00, (b)0.19, (c) 0.78. Temperature, 3OoC aimed at first characterizing the europium-induced shifts for several functional groups, and then applying these shifts to the problem of analyzing multicomponent mixtures by NMR. The results of our studies on saturated straight chain and branched alcohols are reported in this paper. EXPERIMENTAL
Proton NMR spectra were obtained on a Varian A60D spectrometer equipped with a variable temperature accessory. Spectra were recorded at sweep rates of 2 Hz/sec using radiofrequency fields of 0.05 milligauss. All chemical shifts are reported in parts per million relative to internal tetramethylsilane. The homogeneity of the magnetic field was readjusted for each sample to compensate for changes in the magnetic field due to the paramagnetic europium. The alcohols either were analytical reagent grade or were purified by fractional distillation. There were no detectable resonances due to impurities. Eu(DPM)a was prepared from Eu(N03)3(Research Organic/Inorganic Chemical Corp.) and 2,2,6,6-tetramethylheptane-3,5-dione (Eastman Organic Chemicals) by the method of Eisentraut and Sievers, with the exception that oxygen was not excluded during isolation of the complex (6). Spectra were obtained of -0.3M solutions of the alcohols in CDCl3 to which varying amounts of E u ( D P M ) ~were added. All solutions were prepared determinately. At this alcohol concentration, it was only possible to reach a mole ratio of -0.8 because of insolubility of the complex. Mole ratio as used here is defined as moles of EU(DPM)~ per mole of alcohol. The CDC13 was thoroughly dried over 4A molecular sieves before use to remove traces of acid which decompose the complex. RESULTS
Characterization of the Paramagnetic Induced Shifts. The shifts for the carbon-bonded protons of all the isomers of alcohols containing up to five carbons and selected isomers (6) K. J. Eisentraut and 5254 (1965). 1600
R. E . Sievers, J. Amer. Chem. Soc., 87,
of alcohols of higher carbon numbers were measured as a function of the mole ratio. The dependence of the NMR spectrum of n-heptanol on the mole ratio is shown in Figure 1. At a mole ratio of zero (spectrum a), only the resonances due to the protons of the methylene group bonded to the hydroxyl group (HA) and the protons of the methyl group (Ha) are assignable. The other protons give rise to the featureless envelope between 1.0 and 2.0 ppm. Increasing the mole ratio, however, increasingly resolves the spectrum such that, at a mole ratio of 0.78 (spectrum c), the spectrum is first order. The broad singlet resonance ca. 0.72ppm on the high field side of TMS in spectrum b is due to the fert-butyl protons of the complex. The shoulder on the high-field side of this resonance increases in intensity as the concentration of Eu(DPM)3 is increased and is of an intensity consistent with its assignment to the vinyl protons of the complex. The chemical shift is a linear function of the mole ratio over the mole ratio ranges used in this work. This is illustrated in Figure 2 by the chemical shift behavior of the carbon-bonded protons of n-pentanol. Over these mole ratio ranges, the chemical shift of a particular alcohol proton in the presence of the shift reagent, bEu, is related to the mole ratio, R,by Equation l.
-k SR
~ E U= ~ C D C I ~
(1 1
where bCDCI, is the chemical shift of the particular alcohol proton in a CDCls solution of the alcohol (a mole ratio of 0.0) and S is the gradient of the chemical shift us. mole ratio plot. The experimental data were treated by standard least-squares techniques t o obtain 8cDcla and S for each of the carbonbonded protons of each of the alcohols studied (5). Slighi deviations from linearity occur for some protons at mole ratios less than 0.1 giving an extrapolated 8CDC13 that differs from the observed 8CDC13. Such differences are less than 2x ir every case. The extrapolated values are reported so that tht europium-induced shift can be calculated at a given molt ratio by Equation 1. The chemical shift gradients and the intercepts at a molt ratio of zero for the carbon-bonded protons of n-pentanol a
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
Table I. Paramagnetic Shift Parameters for n-Pentanob
Temperature, "C
4 18
30 42 55
HA 26.2b (3. 56Ic 24.3 (3.57) 22.4 (3.56) 21.2 (3.62) 19.4 (3.63)
Nomenclature:
HB 14.9 (1.58) 13.8 (1.54) 12.7 (1.56) 11.9 (1.59) 10.9 (1.60) H H
HD 5.02 (1.38) 4.70 (1.35) 4.31 (1.35) 4.06 (1.37) 3.75 (1.36)
Hc
10.2 (1.37) 9.45 (1.34) 8.72 (1.30) 8.15 (1.36) 7.39 (1.38)
HOCH~CH~CH~CH~CHS A B C D E
HE 2.80 (0.94) 2.56 (0.94) 2.36 (0.93) 2.22 (0.93) 2.05 (0.93)
I
240
I
H H H
I l l HO-C-C-C-C-C-H. I I I I
1 I
H H H H H A B C D E
Chemical shift gradient, in units of ppm/mole Eu(DPM)r/mole of alcohol. c I n parentheses, chemical shift at a mole ratio of 0.00, in ppm.
several temperatures are listed in Table I. These data indicate that the magnitude of the induced shift increases significantly as the temperature decreases over this temperature range. As the temperature decreases, however, information is increasingly lost because the multiplet patterns due to spinspin coupling are increasingly collapsed. Similar behavior was observed for the other alcohols. To facii1:aw comparison of the paramagnetic shifts for the different alcohols, the data will be reported at a standard temperature of 30' C. At this temperature, the multiplet structure due t o spin-spin coupling is not significantly collapsed. Results for the normal alcohols through n-heptanol are given in Table 11. Results for all the other isomers of alcohols containing up to five carbons are listed in Table 111. The standard deviation of the chemical shift gradients listed in Tables I, 11, and 111 averaged 1.4% of the chemical shift gradient while the standard deviation of the intercepts averaged 4.0 % of the intercept (7). -
(7) J. Mandel, "The Statistical Analysis of Experimental Data," Interscience, New York, N. Y., 1964.
I
0.0
0.2
0.4
0.6
0.8
1.0
MOLE RATIO Figure 2. Variation in chemical shift for carbon-bonded protons of n-pentanol in CDCls (0.40 ml of 0.300M solution) with increasing concentration of Eu(DPM)~. Temperature, 30°C. Straight lines obtained by least squares calculations Application to Analysis of Multicomponent Alcohol Mixtures. With the data in Tables 11 and 111, the proton NMR spectrum for a given mixture Of alcohols can be calculated at a particular concentration of E U ( D P M ) ~ .Thus, it should be possible to predict npriori whether a given mixture is amenable t o analysis by NMR. To test this approach, N M R spectra were predicted for a variety of alcohol mixtures. The
Table 11. Paramagnetic Shift Parameters for n-Alcohols., b
Alcohol Methanol Ethanol rz-Propanol n-Butanol n-Pentanol rt-Hexanol rz-Heptanol
HA 21.2= (3.64)d 23.0 (3.76) 22.8 (3,64) 22.6 (3.72) 22.4 (3.56) 22.7 (3.79) 23.0 (3.64)
HB
Hc
HD
HE
HF
HG
12.6 (1.30) 12.8 (1.65) 12.7 (1.80) 12.7 (1.56) 12.6 (1.84) 12.9 (1.68)
7.96 (0.98) 8.45 (1.58) 8.72 (1.30) 8.57 (1.56) 8.64 (1.49)
4.07 (0.99) 4.31 (1.35) 4.25 (1.46) 4.35 (1.40)
2.36 (0.93) 2.46 (1.41) 2.50 (1.37)
1.45 (0.94) 1.54 (1.34)
0.93 (0.90)
In CDCla at 30 "C. Nomenclature, as in Table I. Chemical shift gradient, in units of ppm/mole Eu(DPM)a/moleof alcohol. In parentheses, chemical shift at a mole ratio of zero, in ppm.
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
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Table 111. Paramagnetic Shift Parameters for Alcohols~
Alcohol
HA
HE
HE!
HE"
Hc
13.1 (1.46)
14.4 (1.69)
8.12 (0.96)
Hcl
Hc"
HD
HO
I (B) 1
24. 8b (3.92)~
13.5 (1.15)
(C)
24.3 (3.78)
13.2 (1.25)
HOCHz-C-CHs (A) (C)
22.4 (3.44)
13.4 (1.76)
Hac-C-CHs H (A)
(B") HO H
1 (B) I
1 1
HaC-C-C-CH3 H H (A) (B') CHa
8.17 (0.94)
(B) CH3
14.8 (1.31)
HO-C-CHs
I
CH3 (B)
I l l I I I
CHs-C-C-C-CHs
H H H
(C)
23.8 (3.70)
12.9 (1.15)
12.4 (1.36)
22.9 (3.49)
11.4 (1.74)
13.6 (1.46)
22.1 (3.52)
12.8 (1.56)
15.2 (1.15)
14.8 (1.34)
7.98 (0.95)
8.40 (0.96)
15.7 (1.38)
8.50 (0.92)
1
b c
23.2 (3.35)
Chemical shift gradient, in units of ppm/mole Eu(DPhb/mole of Alcohol. In parentheses, chemical shift at a mole ratio of 0.00, in ppm.
1602
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
8.01 (1 .24)
10.3 (1.23)
4.30 (0.92)
8.77 (0.90)
9.35 (1.91)
HO-CHz-C-CHj (A) 1 CH3 (C) a fn CDC13,at 30 "C.
3.59 (0.93)
8.15 (1.38)
9.06 (0.94)
4.52 (0.96)
F
E
I
I
D
I
C
I
B A
I I
Figure 3. 60 MHz proton NMR spectra of a CDCla solution containing 0.10M methanol, 0.091M ethanol, 0.095M n-propanol, 0.10M n-butanol, 0.11 M n-pentanol, 0.10M n-hexanol Lower: Spectrum of CDCla solution has been added Upper: Spectrum of 0.40 ml of solution to which 134.0 mg of E~I(DPM)~ Letters indicate the methyl groups of n-hexanol ( A ) , n-pentanol ( B ) , n-butanol (0,n-propanol (D), ethanol ( E ) ,and methanol (F)
HOCH~CH~CH~CH~CH~CH~CHS
1
HOCH,CH2CH,CH2CH&H 3 1
I
2.6
1
I
2.4
1
I
2.2
I
I
I
2.0
1
1.8
I
I
1.6
I
I
1.4
ppm, vs TMS
Figure 4. Portion of the 60 MHz proton NMR spectrum of 0.40 ml of CDC13solution containing 0.150M n-hexanol and 0.150M n-heptanol to which 63.0 mg of Eu(DPM), has been added
predicted spectra indicated that a sufficient number of analytical resonances could be obtained in many cases. Synthetic mixtures were then prepared for several systems to experimentally test the predictions. Some examples will be presented. In some cases, there were slight differences between the predicted and observed shifts indicating preferential complexation of certain components. The data in Table I1 predict that, in a mixture of n-alcohols, the resonances for the methyl protons of each component will be shifted less than the resonances for the methylene protons separated from the hydroxyl group by the same number of bonds in the presence of Eu(DPM)3. Thus, when the solution contains a sufficiently high concentration of EU(DPM)~, the methyl protons should provide a resolved analytical reso-
nance for each component. Spectra for a six-component mixture of methanol through n-hexanol are shown in Figure 3. The lower spectrum is for a CDCls solution of the alcohols. The resonances for the protons on the carbon bonded t o the hydroxyl group are in the envelope centered at 3.7 ppm. The resonances for the other protons are in the methylene-methyl envelope (0.8 t o 2.0 ppm) characteristic of compounds containing alkyl groups. An analytical resonance cannot be assigned t o each component of the mixture so that no quantitative information can be obtained from this spectrum. The upper spectrum is for a CDC13 solution of the same mixture to which E u ( D P M ) ~has been added. As predicted by the data in Table 11, the methyl group for each of the components gives a resolved resonance making it possible to quantitatively
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
1603
Figure 5. 60 MHz proton NMR spectra of a CDC13 solution containing 0.109Mn-pentanol, 0.106M 2-pentano1, and 0.0%3M 3pentanol Lower: Spectrum of the CDCla solution Upper: Spectrum of 0.40 ml of solution to which 67.4 mg of Eu(DPM) has been added
20.0
15.0
10.0 ppm, v t TMS
5.0
0.0
Figure 6. 60 MHz proton NMR spectra of a CDC13 solution containing 0.152M 2-methyl-1-butanol and 0.156M 2-methyl-2-butanol
A
Lower: Spectrum of CDCl3 solution Upper: Spectrum of 0.40 ml of solution to which 67.4 mg of Eu(DPM)s has been added
analyze this six-component mixture by proton N M R at 60 MHz. A portion of the spectrum for a CDCl, solution of n-hexanol and n-heptanol t o which Eu(DPM)3 has been added is shown in Figure 4. As predicted, approximately first-order triplets are resolved for the methyl groups of each alcohol. I n contrast, the spectrum for a CDCl, solution of the two alcohols consists of a triplet at 3.7 ppm due t o overlapping resonances from the methylene protons adjacent t o the hydroxyl groups and two envelopes between 0.8 and 2.0 ppm due to overlapping resonances from the other protons. The data in Tables I1 and 111 predict that, in a mixture of n-pentanol, 2-pentanol, and 3-pentanol, the resonances for the E protons of n-pentanol, the D protons of 2-pentanol, and the C protons of 3-pentanol will be resolved triplets at sufficiently high concentrations of Eu(DPM)3. Spectra are shown in 1604
Figure 5 for such a mixture. The lower spectrum is for a CDC& solution. This spectrum is again characterized by overlapping resonances for the different components from which no quantitative information can be obtained. The upper spectrum is for the same solution containing Eu(DPM)~. The resonances for the methyl groups are resolved, as predicted. A further example is shown in Figure 6 for a mixture of 2methyl-1 -butanol and 2-methyl-2-butanol. DISCUSSION Paramagnetic Shifts in Saturated Alcohols. The paramagnetic shifts in the proton magnetic resonance spectra of alcohols coordinated via the hydroxyl group to Eu(DPM)3 are probably dominated by the pseudocontact interaction
ANALYTICAL CHEMISTRY, VOL. 43, NO. 12, OCTOBER 1971
(2, 3). Pseudocontact shifts result from direct interaction between the magnetic dipoles of the unpaired electrons of the paramagnetic metal and the magnetic dipoles of the ligand nuclei (8-10). The pseudocontact interaction is transmitted through space, even when there is no covalent bonding (II), and is attenuated as the distance from the paramagnetic ion increases. Thus the magnitudes of the downfield shifts for the nonequivalent carbon-bonded protons of alcohols bonded to Eu(DPM)$ depend mainly o n the distance between t h e europium and the protons. The dependence of the shift gradient for a particular proton on the distance from the hydroxyl group should prove useful in structural studies (12). From the data in Tables I1 and 111, the average shift gradients at 30 “C are 23.0, 13.4, 8.6, 4.2, 2.4, 1.5, and 0.9 ppm for carbon-bonded protons separated from the hydroxyl group by one, two, three, four, five, six, and seven carbons, respectively.
Analysis of Mixtures. The problem in the analysis of multicomponent alcohol mixtures by N M R is one of obtaining a resolved analytical resonance for each component to be analyzed. In some cases, analytical resonances can be resolved by using a spectrometer of a higher magnetic field strength. The examples in Figures 3-6 demonstrate that utilization of the shifting ability of E u ( D P M ) ~provides a n alternative method for resolving analytical resonances for the components. The amenability of other alcohol mixtures to analysis by NMR using this approach can be predicted with the data in Tables I1 and 111. Thus, many mixtures whose spectra were previously characterized by overlapping resonances are now susceptible to analysis by proton magnetic resonance spectrometry. We are also investigating the application of E U ( D P M )and ~ other paramagnetic shift reagents t o tne analysis of multicomponent mixtures of compounds containing other functional groups, including amines, esters, ethers, and ketones. ACKNOWLEDGMENT
(8) D. R. Eaton and W. D. Phillips, Aduan. Magn. Resonance, 1, 103 (1965). (9) P. J. McCarthy, “Spectroscopy and Structure of Metal Chelate
Compounds,” K. Nakamoto and P. J. McCarthy, Ed., John Wiley and Sons, Inc., New York, N. Y., 1968, p 309. (10) H. J. Keller and K. E. Schwarzhans, Angew. Chem., Int. Ed. Engl., 9, 196 (1970). (11) G. N. LaMar, J . Chem. Phys., 41, 2992 (1964). (12) D. R . Crump, J. K. M. Sanders, and D. H. Williams, Tetrahedron Lett., 4419 (1970).
It is a pleasure t o acknowledge the technical assistance of Mr. F. Baudais in several phases of this work. RECEIVED for review April 30, 1971. Accepted June 28, 1971. Presented before the Division of Analytical Chemistry, 161st National Meeting, American Chemical Society, Los Angeles, Calif., March 29, 1971. This work was supported, in part, by a grant from the National Research Council of Canada.
Small Computer, Magnetic Tape Oriented, Rapid Search System Applied to Mass Spectrometry L. E. Wangen, W. S. Woodward, and T. L. Isenhour Department of Chemistry, Uniaersity of North Carolina, Chapel Hill, N . C. 27514 A fast search procedure capable of searching a spectral library at a rate of 10000 16-bit words per second directly from magnetic tape has been developed for a small computer. No computer memory is devoted to library spectra. A library of 6652 low resolution mass spectra with 352 mass positions coded to peak/no peak information can be completely searched for nearest as well as perfect matches in 15 seconds. Statistical considerations and some principles of information theory are used to reduce to 48 the number of bits necessary to code a mass spectrum with minimal loss of pertinent information. Mass positions that consistantly correlate throughout the data set are combined such that all spectra are reduced in dimensionality by the same procedure. This makes it unnecessary to perform any decoding operations on library spectra prior to or during the search. Results are presented for searching 352 dimensional spectra as well as the same spectra reduced to 80 and 48 dimensions.
THEAVAILABILITY of large libraries of spectrometric data in computer compatible form has led t o an increasing use of spectral comparison as a n aid t o structure determination and compound identification. Powder diffraction files have been utilized i n mineral identification while the use of infrared and mass spectra in compound identification has become of
increasing import as spectra libraries (1-5) are made available. Several recent papers have dealt with the numeric representation of the data and methods for efficient search and comparison. Anderson and Covert ( I ) reported a system developed for infrared data on the IBM 7080 computer. As many as 20 spectral terms (adsorption maxima or no absorption) and 15 chemical classification terms together with melting or boiling point information could be compared with the library spectra to identify a compound. This system allowed for a *O.l-pm ambiguity in the wavelength of adsorption peaks and could search for five unknowns at a time giving up to the 100 best matches for each unknown. They achieved a rate of 167 spectral comparisons per second. Erley (2) compacted the ASTM infrared file into 10 16-bit words per spectrum and used logical operations to perform comparisons. The data coding included chemical group and elemental (1) D. H. Anderson and G. L. Covert, ANAL. CHEM.,39, 1288 (1967). (2) D. S. Erley, ibid., 40, 894 (1968). (3) D. S. Erley, Appl. Spectros., 25, 200(1971). (4) F. E. Lytle, ANAL.CHEM., 42, 355 (1970). ( 5 ) F. E. Lytle and T. L. Brazie, ibid., p 1532.
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