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Description  |
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FIELD OF THE INVENTION
This invention relates to the spectral analysis of organic compounds having
a conor group by nuclear magnetic resonance (NMR). In one aspect, it
relates to a composition which, when added to a compound to be identified
by NMR, facilitates the interpretation of the compound's spectrum. In
another aspect, it relates to a composition which, when analyzed by NMR,
has a spectrum which is readily interpreted.
BACKGROUND OF THE INVENTION
NMR spectroscopy has been used for many years in the identification of
compounds by comparing the spectra of known compounds with those of the
compounds to be analyzed. The techniques employed in this method of
spectral analysis are described in the literature, and NMR spectrometers
are commercially available. For a discussion of the theory of nuclear
magnetic resonance and a decription of the basic components of an NMR
spectrometer and its operation, reference may be made to Van Nostrand's
Scientific Encyclopedia, 4th Ed., D. Van Nostrand Company, Inc.,
Princeton, New Jersey. Briefly, in the operaton of a spectrometer, a tube
containing a sample to be analyzed is positioned between the pole faces of
a direct current electromagnet whose gap can be varied. An oscillating
radio frequency field is imposed at right angles to the magnetic field. A
separate radio frequency coil in the form of a few turns of wire wound
tightly around the sample tube serves as the receiver coil to pick up the
resonant signal from the sample. When nuclear transitions are induced,
energy is absorbed from the receiver coil, causing the voltage across the
receiver coil to drop. After this voltage change is amplified and
detected, the resulting direct current voltage is placed on an
oscilloscope. The NMR spectrum, a pattern of intensity as a function of
frequency, is thereby produced. An interpretation of the spectrum makes it
possible to determine the nuclei present in molecules and their relations
to the remainder of the molecule.
Since the beginning of NMR spectroscopy in the late 1940's, the effects of
paramagnetism on nuclear magnetic resonances have been the subject of
considerable study. The object of the study has been to provide means to
simplify and clarify the NMR spectrum, thereby rendering compound
identification more certain as well as increasing the scope of the
applicability of NMR spectroscopy. The results of the study have been the
development of so-called shift reagents which, when added to a sample of a
compound subjected to NMR, will cause frequency shifts that desirably will
result in a high resolution spectrum without objectionable peak
broadening. Although large frequency shifts caused by several paramagnetic
chelates have been observed, up to the present time much of the work has
revolved around the question of which metal will permit the observation of
such high resolution spectra of its complexes. It has been reported [J.
Amer. Chem. Soc., 91, 5160 (1969)] that the dipyridine adduct of
tris(2,2,6,6-tetramethyl-3,5-heptanedionato) europium(III) produces
relatively large concentration-dependent paramagnetic shifts in
cholesterol monohydrate without serious peak broadening. Subsequently, it
was reported [(Chem. Commun., 422 (1970)] that the coordinating
effectiveness of the europium was significantly improved by elimination of
the pyridine using the unsolvated europium chelate of
2,2,6,6-tetramethyl-3,5-heptanedione[Eu(thd).sub.3 ].
While the above-mentioned chelates are useful as shift reagents for
specific classes of compounds, their effectiveness is drastically reduced
when used with weak Lewis bases. Moreover, the solubility of the thd
chelates is relatively low in nonalcoholic solutions. As a result free
ligand and complexed ligand are present, a condition that limits the
spectral shifts obtainable.
It is an object of this invention, therefore, to provide superior
paramagnetic shift reagents for nuclear magnetic resonance spectral
clarification.
Another object of the invention is to provide shift reagents that can be
effectively used with organic compounds having a donor group, such as weak
Lewis bases.
A further object of the invention is to provide shift reagents that are
highly soluble in nonalcoholic solutions.
Still another object of the invention is to provide an improved method of
spectral analysis of an organic compound having a donor group by nuclear
magnetic resonance.
A still further object of the invention is to provide a composition which,
when added to a compound, greatly simplifies and clarifies its spectrum.
Yet another object of the invention is to provide a composition which, when
subjected to NMR, has a spectrum that can be readily interpreted.
Other and further objects and advantages of the invention will become
apparent to those skilled in the art upon consideration of the
accompanying disclosure and the drawing, in which:
FIG. 1 shows the spectra of ethyl propionate without a shift reagent and
with a shift reagent of this invention;
FIG. 2 shows the spectra of di-n-butyl ether with Eu(thd).sub.3, with
varying amounts of a shift reagent of this invention, and without any
shift reagent;
FIG. 3 is a graph that shows induced contact shifts of methylene resonances
of ethyl propionate as a function of added shift reagent; and
FIG. 4 is a graph that shows induced contact shifts of methyl resonances of
ethyl propionate as a function of added shift reagent.
SUMMARY OF THE INVENTION
The present invention resides, in the discovery that lanthanide chelates of
fluorinated ligands, when used as paramagnetic shift reagents, result in
easily interpreted high resolution spectra of their complexes with organic
compounds having a donor group. The lanthanide chelates that can be used
in the practice of the present invention can be represented by the
following structural formula:
##STR1##
wherein M is a rare earth element of the lanthanide series; R.sub.1,
R.sub.2 and R.sub.3 are individually selected from the group consisting of
hyddrogen, deuterium, alkyl and fluoroalkyl, at least one of the R.sub.1,
R.sub.2 and R.sub.3 groups being fluoroalkyl; or R.sub.1 and R.sub.2
together are d-camphor and R.sub.3 is fluoroalkyl; X is an organic
compound contaning a donor group; and a is a numeral from zero to 4,
inclusive. The alkyl and fluoroalkyl groups contain from 1 to 10,
inclusive, preferably from 1 to 4, inclusive, carbon atoms.
As indicated in the foregoing paragraph, the letter "X" represents an
organic compound containing a donor group, which combines in molecular
form with the lanthanide chelate. Examples of such compounds include
water, methyl alcohol, acetone, dimethylformamide, dimethoxypropane, and
the like.
The lanthanide chelates defined by the above formula that are operable in
the practice of the present invention are those in which the letter "M"
represents the paramagnetic trivalent rare earth ions. These ions and
their symbols in the order of their atomic numbers are cerium (Ce),
praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu),
gadolinium (Gd), terbium (Tb), dysposium (Dy), holmium (Ho), erbium (Er),
thulium (Tm), and ytterbium (Yb). Of the chelates it is preferred to
utilize those according to the above formula in which M is Eu or Pr.
Examples of lanthanide chelates as defined by the foregoing formula include
tris
(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)europium(III)
[Eu(fod).sub.3 ];
tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)praseodymium
(III) [Pr(fod).sub.3
]tris(1,1,1,2,2,3,3,7,7,7-decafluoro-4,6-heptanedionato)europium(III)dihyd
rate;
tris(1,1,1,2,2,3,3,7,7,7-decafluoro-4,6-heptanedionato)praseodymium(III)di
hydrate;
tris(1,1,1,2,2,3,3,7,7,7-decafluoro-4,6-heptanedionato)ytterbium(III);
tris(1,1,1,2,2,3,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)ytterbium(
III); dimethylformamide adduct of
tris(1,1,1,5,5,5,-hexafluoro-2,4-pentanedionato) europium(III);
perdeuterated
tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)europium(III
); perdeuterated
tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)praseodymium
(III); tris(trifluoroacetyl-d-camphorato)europium(III); and the like.
The lanthanide chelates represented by the above formula (except for those
in which R.sub.1 and R.sub.2 together are d-camphor) and methods for their
synthesis are described in the literature. In this regard attention is
directed to Inorganic Chemistry, 6, 1105 (1967) and Inorganic Chemistry,
10, 498 (1971), which are incorporated herein by reference. The chelates
in which R.sub.1 and R.sub.2 together are d-camphor and R.sub.3 is a
fluoroalkyl, can be synthesized by preparing an alcohol solution of
trifuloroacetyl-d-camphor [H(facam)] and adding this solution to an
aqueous solution of a chloride of one of the aforementioned rare earth
elements. For example, in the synthesis of
tris(trifluoroacetyl-d-camphorato)praseodymium(III) [Pr(facam).sub.3 ], a
first solution is prepared by stirring 15 millimols (3.70 grams) of
H(facam) into 100 milliliters of a 50 percent alcohol solution. A 10
percent ammonium hydroxide solution is slowly added until all of the
H(facam) is dissolved. A second solution is prepared by adding 5
milliliters of a 1 molar aqueous solution of praseodymium chloride (5
millimols) to 20 milliliters of alcohol. The first solution is then added
dropwise to the second solution while stirring vigorously. The precipitate
that forms is stirred in the mother liquor for an additional time, e.g.,
for about one hour, after all of the first solution has been added. The
mixture is then filtered and the precipitate is washed with 100
milliliters of a 50 percent alcohol solution. After the precipitate is air
dried overnight, it is recovered and the product obtained is determined by
analysis to be Pr(facam).sub.3.
In one embodiment the present invention resides in an improvement in the
spectral analysis by nuclear magnetic resonance of an organic compound
having a donor group. The improvement comprises the step of mixing with
the organic compound to be analyzed a shift reagent which is a lanthanide
chelate of a fluorinated ligand as defined hereinabove, the shift reagent
and the organic compound being in solution in a common solvent. The shift
reagent can be in solution in the solvent in which case the compound to be
analyzed is added to the solution. Alternatively, the compound to be
analyzed can be in solution, and in this case the shift reagent is added
to the solution. Furthermore, the shift reagent and the compound to be
analyzed can be in separate solutions in which event the two solutions are
mixed.
Conditions for resonance are expressed in terms of a difference (chemical
shift) between the field necessary for resonance in the sample and in an
arbitrarily chosen reference material. Thus, samples to be subjected to
nuclear magnetic resonance conventionally contain a reference material
having only a single resonance line, which serves to locate the resonant
frequency of a sample in a magnetic field. Examples of suitable reference
compounds include tetramethyl silane (TMS), chloroform, cyclohexane and
benzene. The reference material can be added to the compound to be
analyzed, to the shift reagent or to the solution or solutions containing
these materials.
In general, solvents suitable for use are compounds in which both the shift
reagent and the compounds to be analyzed are soluble. Also, the compounds
useful as solvents are those that either do not absorb, or if they do
absorb, the absorption occurs in a region that does not interfere with the
sample spectrum. Examples of suitable solvents include carbon
tetrachloride, chloroform, deuterated methylene chloride, benzene,
deuterated benzene, and the like.
In another embodiment, the invention resides in a composition which
comprises a solution of a lanthanide chelate of a fluorinated ligand, as
defined above, in a solvent therefor. Generally, the solution contains
about 0.01 to 0.5 mol of the chelate per 1000 milliliters of the solvent.
The composition may also contain a reference compound, the amount usually
being in the range of about 0.1 to 1 weight percent, based on the weight
of the solution.
In still another embodiment, the invention resides in an adduct of a
lanthanide chelate of a fluorinated ligand, as defined above, and an
organic compound having a donor group. The adduct is in solution and is
formed when the chelate and the organic compound are mixed in the solvent
prior to subjecting the sample to NMR. The mol ratio of chelate to organic
compound to achieve complete coordination will vary with the particular
chelate and organic compound employed. However, this ratio can be readily
determined by one skilled in the art by observing the point where further
addition of the chelate causes no further spectral shift. It is to be
understood, however, that the adduct is present in solution prior to the
addition of the amount necessary to cause a maximum spectral shift.
In general, the paramagnetic shift reagents of this invention can be used
in the spectral analysis by nuclear magnetic resonance of organic
compounds having a donor group. Classes of such compounds include ethers,
esters, ketones, alcohols, amines, acids, amino acids, oximes, sulfides,
sulfoxides, nitriles and amides as well as various natural products and
compounds that can be classified as pollutants. Specific examples of
compounds of the aforementioned classes include the following: ethyl
ether, di-n-butyl ether, methyl n-propyl ether, methyl tert-propyl ether,
n-propyl ether, tert-butyl ether, 1-chloroethyl ethyl ether, vinyl ether,
vinyl methyl ether, vinyl ethyl ether, allyl ether, ethynyl ethyl ether,
benzyl methyl ether, benzyl ethyl ether; 2-ethylhexyl acetate, hexyl
acetate, isoamyl acetate, ethyl propionate, ethyl acetate, butyl acetate,
cellulose acetate, isopropyl acetate, dibutyl phthalate, di-n-octyl
phthalate, diethylene glycol monolaurate, 1,2-propylene glycol
monolaurate, butyl oleate, butyl stearate, benzyl acetate, benzyl
benzoate, benzyl propionate, methyl benzoate, methyl salicylate, methyl
formate, triethyl orthoformate, ethyl acetoacetate; methyl n-propyl
ketone, acetone, methyl ethyl ketone, diethyl ketone, diisobutyl ketone,
methyl vinyl ketone, methyl propenyl ketone, acetol, acetoin,
acetopropanol, chloroacetone, chloropentanone, cyclohexanone, isophorone,
acetophenone, benzophenone, acrylophenone, benzoin, xanthone; ethyl
alcohol, isopropyl alcohol, methylethyl carbinol, pentanol, tertiary butyl
carbinol, n-hexyl alcohol, n-octyl alcohol, n-decyl alcohol, lauryl
alcohol, cetyl alcohol, eicosyl alcohol, cyclohexanol, allyl alcohol,
propargyl alcohol, ethylphenyl alcohol, benzyl alcohol, menthol, glycerol,
erythritol; methylamine, isopropylamine, n-butylamine, allylamine,
dimethylamine, diisopropylamine, di-n-amylamine, methylethylamine,
trimethylamine, tri-n-butylamine, triisoamylamine, ethylenediamine,
hexamethylenediamine, cyclohexylamine, aniline, .alpha.-naphthylamine,
o-chloroaniline, m-toluidine, diphenylamine, o-phenyldiamine,
p-toluenediamine, benzidine, 2-aminopyridine, 2-aminothiazole; formic,
acetic, butyric, acrylic, methacrylic, propiolic, valeric, caproic,
caprylic, lauic, palmitic, stearic, oleic, lanoleic, oxalic, malonic,
succinic, adipic, sebacic, maleic, fumaric, acetylenedicarboxylic,
aconitic, glycolic, lactic, malic, citric, glyoxylic, acetoacetic,
bromoacetic, and thioglycolic acids; alanine, arginine, citrulline,
glutamic acid, glycine, hastidine, lysine, methionine, proline, tyrosine,
valine, isoleucine, phenylalanine, ornithine, proline; acetaldoxime,
propionaldoxime, acrylaldoxime, choral oxime, .alpha.-benzadoxime,
.beta.-benzadoxime, phenylacetaldoxime, o-tolualdoxime, m-tolualdoxime,
p-tolualdoxime, glyoxime, acetoxime, diisopropyl ketoxime, cyclopentanone
oxime, .alpha.-d-carvoxime, .beta.-d-carvoxime, acetophenone oxime,
dimethylglyoxime, quinone dioxime; dimethyl sulfide, methylene sulfide,
diethyl sulfide, divinyl sulfide, diallyl sulfide, dichloro ethyl sulfide,
dibenzyl sulfide, diphenyl sulfide, carbonyl sulfide, acetyl disulfide,
benzoyl disulfide, allyl trisulfide; phenyl sulfoxide, dimethyl sulfoxide,
dibenzyl sulfoxide, diphenyl sulfoxide; acetonitrile, butyronitrile,
isobutyronitrile, acrylo nitrile, succinonitrile, dodecanedinitrile,
cyclohexanecarbonitrile, benzonitrile, phenylacetonitrile; formamide,
acetamide, stearamide, acetanilide, acetoacetanilide, benzanilide, urea,
thiourea, cyanamide, sulfamide, trifluoroacetyl amides derived from amino
acids (e.g., trifluoroacetylalanine); and the like. Examples of natural
products include camphor, lanosterol, lanolin, testosterone, DDE
(metabolite of DDT), androsterone, cholesterol, and etiocholanoline.
Examples of pollutants that can be identified by the practice of the
present invention include peroxyacylnitrate, acetaldehyde, benzaldehyde,
formaldehyde, isoamyl alcohol, ethyl acetate, n-propanol, isopropanol,
heptachlor epoxide, dieldrin, and butyric acid.
The shift reagents of this invention are greatly superior to the prior art
reagents, e.g., tris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium(III)
[Eu(thd).sub.3 ], when used with weak Lewis bases. This superiority is
based upon the discovery that the lanthanide chelates of fluorinated
ligands as defined above are more highly soluble in nonalcoholic solutions
and possess a higher Lewis acidity. Thus, it has been found that
substitution of fluorocarbon moieties in .beta.-diketonate ligands
increases the solubility of the metal complex while the
electron-withdrawing fluorines increase the residual acidity of the
cation, making it a better coordination site for weak donors. Because of
these properties they are effective in forming adducts with organic
compounds containing a donor group. And by forming adducts, the shift
reagents cause the NMR spectra to be shifted greatly relative to the
spectra of the organic species alone. The resulting spectra are thereby
more easily interpreted than the cluttered and often indecipherable
spectra of the organic compounds along.
A better understanding of the invention can be obtained from a
consideration of the following examples which are not intended, however,
to be unduly limitative of the invention.
EXAMPLE I
Two experiments were conducted in which NMR spectra were obtained at 60 MHz
with carbon tetrachloride solutions containing 0.1 m mol of ethyl
propionate. A Varian HA-60-IL spectrometer was used and tetramethyl silane
(TMS) was employed as the internal reference. In the first experiment a
shift reagent was not used while in the second experiment Eu(fod).sub.3
was employed as a shift reagent. The sample for the first experiment was
prepared by adding the TMS and 10 mg of ethyl propionate to 0.5 ml of
CCl.sub.4 in the sample tube. In the second experiment, the sample was
prepared in the same manner except that 25 mg of Eu(fod).sub.3
(2.5.times.10.sup.-5 mol) was added to the solution of ethyl propionate in
CCl.sub.4.
The results obtained in the two experiments are shown in FIG. 1 of the
drawing. The lower trace shows the spectrum of ethyl propionate alone
while the upper trace shows the spectrum of ethyl propionate with added
Eu(fod).sub.3. As seen from a comparison of the two spectra, the presence
of a shift reagent of this invention caused the NMR spectrum to be shifted
(down-field) greatly relative to the NMR spectrum of ethyl propionate
alone. As a result the spectrum with Eu(fod).sub.3 is spread out, making
it much easier to interpret than the spectrum of ethyl propionate alone.
EXAMPLE II
A series of experiments was conducted in which NMR spectra were obtained at
60 MHz with CCl.sub.4 solutions containing 0.1 m mol of di-n-butyl ether.
The spectrometer used was the same as the one mentioned in Example I and
TMS was employed as the reference material. In one of the experiments a
shift reagent was not used while in the other experiments varying amounts
(10, 25, 50 and 75 mg) of Eu(fod).sub.3 were added to the solution of the
ether in CCl.sub.4. The samples were prepared in the same manner as
described in Example I.
The results obtained in the series of experiments are shown in the lower
portion of FIG. 2. In the lower portion of the figure, the lower trace
shows the spectrum of the ether alone, while the upper four traces in the
same portion of the figure show the spectra of the ether with added
amounts of Eu(fod).sub.3. The amount of added Eu(fod).sub.3 is shown to
the right of the trace of the spectrum of the sample containing that
amount. As seen from a comparison of the five spectra, the presence of
Eu(fod).sub.3 caused the NMR spectra to be shifted relative to the NMR
spectrum of ether alone. Also, increasing the amount of added
Eu(fod).sub.3 resulted in the attainment of progressively larger induced
shifts. As shown by the top trace, addition of 75 mg of Eu(fod).sub.3
resulted in a greatly simplified spectrum that could be easily interpreted
to identify the ether.
An esperiment was conducted in which the NMR spectra was obtained with a
CCl.sub.4 solution of di-n-butyl ether, following the same procedure as
described above except for the differences noted hereinafter. Thus,
Eu(thd).sub.3 was used as the shift reagent instead of Eu(fod).sub.3.
Also, upon adding Eu(thd).sub.3 to the ether solution, the latter was
heated in order to dissolve as much of the Eu complex as possible.
Therefore, the shifts induced in the ether were the maximum obtainable
with Eu(thd).sub.3. The spectrum obtained is shown in the upper part of
FIG. 2. From a consideration of this spectrum and those obtained with
Eu(fod).sub.3, it is seen that Eu(thd).sub.3 is by comparison ineffective
as a shift reagent. The superiority of Eu(fod).sub.3 as a shift reagent
can be attributed to its higher solubility and its greater Lewis acidity.
EXAMPLE III
A series of experiments was conducted in which the NMR spectra were
obtained with solutions containing 10 mg of ethyl propionate in 0.5 ml of
CCl.sub.4. TMS was used as the internal reference. A spectrum was obtained
for the ester alone, and spectra were also obtained for the ester after
adding Eu(fod).sub.3 in increments of 25 mg. The induced contact shifts of
the methylene resonances of the ester as a function of Eu(fod).sub.3 were
measured in hertz from TMS (internal). The results were plotted and the
graphs obtained are shown in FIG. 3. The induced contact shifts of methyl
resonances of the ester as a function of Eu(fod).sub.3 were also measured
in hertz from TMS (internal). The results obtained are shown graphically
in FIG. 4.
The graphs of FIGS. 3 and 4 demonstrate that at lower concentrations there
is an essentially linear dependence of the paramagnetic shifts on added
Eu(fod).sub.3. However, in the case of both methylene and methyl groups, a
point was reached where further additions of the shift reagent caused no
further spectral shifts. These data indicate that the shift is due to
bonding of the organic donor groups with the coordinatively unsaturated
europium chelate and that the spectrum in which there are no further
spectral shifts is essentially that of a coordinated ligand rather than
that of the average of the free ligand and complexed ligand.
Furthermore, because the shift reagents of this invention are highly
soluble, it is possible to use rare earth ion to organic donor ratios that
are high enough to permit the assignment of a constant value to a given
compound. This is of great assistance in compound identification, a
technique that was not possible with prior art shift reagents because of
their low solubility. To establish with certainty the identity of
compounds with similar spectra, it is only necessary to add a large excess
of the shift reagent, e.g., Eu(fod).sub.3, and observe the spectrum of the
resulting complexed ligands. The formation constant can be determined from
data of the type shown in FIGS. 3 and 4. The large molar ratio of
Eu(fod).sub.3 to organic compound needed to reach the saturation point as
shown on the graphs is indicative of the low basicity of the organic
compounds and the extreme solubility of the fod complex. For example, in
the case of ether, 2.0 mol equivalents of the chelate was required to
achieve complete coordination of the ether. This represents a solubility
of over 200 mg of the europium complex in a 0.5 ml CCl.sub.4 solution of
the ether. An important function of the fod ligand is, therefore, to
impart extremely high solubility to the resulting complex, thereby making
it possible to attain larger induced shifts.
EXAMPLE IV
An experiment was conducted in which Eu(fod).sub.3 was added to a solution
of trifuloroacetyl-d-alanine in CCl.sub.4. The procedure followed was
essentially the same as that described in Example I. A comparison of the
spectra with and without the Eu(fod).sub.3 indicated that the addition of
the shift reagent resulted in the methyl resonance being shifted downfield
by 0.66 ppm(.delta.).
EXAMPLE V
Experiments were conducted in which Pr(fod).sub.3 and
tris(1,1,1,2,2,3,3,7,7,7-decafluoro-4,6-heptanedianato) praseodymium (III)
dihydrate [Pr(dfhd).sub.3.(H.sub.2 O).sub.2 ] were separately added to a
solution of di-n-butyl ether in CCl.sub.4. The procedure followed was
essentially the same as that described in Example I. A comparison of the
spectra indicated that the resonances of the ether with added
Pr(fod).sub.3 or Pr(dfhd).sub.2.(H.sub.2 O).sub.2 were shifted upfield to
new positions relative to the resonances of the ether alone.
EXAMPLE VI
Experiments were conducted in which Eu(fod).sub.3 was added to solutions of
2-pentanone in CCl.sub.4 and to a solution of hexyl acetate in CCl.sub.4.
The procedure followed was essentially that of Example I. A comparison of
the spectra of 2-pentanone and hexyl acetate with and without the
Eu(fod).sub.3 showed that the resonance peaks were all shifted downfield
to new values relative to each other. In many cases, peaks that were
superimposed in the spectra of the organic compounds alone appeared
separately so that they were easier to assign.
EXAMPLE VII
An experiment was conducted in which Eu(fod).sub.3 was added to a mixture
of acetone, methyl acetate, cyclohexane and tetramethyl silane (TMS). The
NMR spectrum of the mixture was greatly clarified as a result of the
addition of the shift reagent. Thus, the cyclohexane peak did not shift
relative to the TMS, which was used as a reference. The other peaks on the
other hand were all shifted downfield.
The data in the foregoing examples demonstrate that the addition of the
shift reagents of this invention to organic compounds containing a donor
group result in spectra that are greatly spread out, resulting in the
resolution of overlapping peaks. The spectra are thereby clarified so that
they can be more easily and accurately interpreted. Because the solubility
of the shift reagents in nonalcoholic solutions is much higher than that
of the prior art reagents, a shorter time is required in making a spectral
analysis and a much wider range of spectra can be clarified.
In the practice of the present invention, a mixture of rare earth shift
reagents can be employed as well as a single one. It is preferred to use
shift reagents that are prepared from the ligands
1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione [H(fod)];
1,1,1,2,2,3,3,7,7,7-decafluoro-4,6-heptanedione [H(dfhd)]; and
trifluoroacetyl-d-camphor [H(facam)]. The preferred shift reagents derived
from these fluorinated ligands are Eu(fod).sub.3, Pr(fod).sub.3,
Eu(dfhd).sub.3.(H.sub.2 O).sub.2, Pr(dfhd).sub.3.(H.sub.2 O).sub.2,
Eu(facam).sub.3, and Pr(facam).sub.3. The deuterated or partially
deuterated analogs of these chelates are also particularly desirable for
use as shift reagents. However, it is to be understood that other
lanthanide chelates of fluorinated ligands, as defined hereinbefore by the
structural formula, can be advantageously utilized in the practice of this
invention.
As previously indicated, the paramagnetic shift reagents of this invention
are applicable to the spectral analysis of organic compounds having a
donor group. The wide applicability of the shift reagents results from the
use of fluorinated ligands in preparing the rare earth chelates. The
presence of electron-withdrawing fluorine increases the residual acidity
of the cation of the rare earth chelates, making it a good coordination
site even for weak donors. Thus, the paramagnetic shift reagents are
outstandingly effective in clarifying the spectra of organic Lewis bases,
thereby facilitating their interpretation. A particularly important
application of the present invention is in the identification of
pollutants. Often the identity of an offending compound is unknown and is
present in admixture with other materials. In accordance with the present
invention, spectra can be obtained that are spread out and uncluttered by
overlapping NMR peaks. As a result it is possible to identify the unknown
pollutant in a minimum of time, the initial step to be taken in control of
the pollutant.
Another important specific application of the present invention resides in
the use of optically active facam chelates, e.g., Eu(facam).sub.3 and
Pr(facam).sub.3, as shift reagents to distinguish dextro and levo isomers
of various compounds such as amino acid derivatives. Furthermore, the
shift reagents of this invention can be employed to clarify the NMR
spectra of other nuclei such as .sup.13 C, .sup.19 F, .sup.15 N, and the
like.
In view of the foregoing disclosure, improvements and modifications of the
invention may be made by those skilled in the art. Such modifications and
improvements fall within the spirit and scope of the invention.
* * * * *
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