Hydrogen induced polarization-nuclear-spin hyperpolarization in catalytic hydrogenations without the enrichment of para- or orthohydrogen

Article abstract of DOI:10.1002/adsc.200404058

During the last 40 years, Prof. Dr. Joachim Bargon, to whom several articles in this issue are dedicated, has contributed more than 90 scientific publications to the understanding of NMR hyperpolarization phenomena such as chemically induced dynamic nucle

Full text of DOI:10.1002/adsc.200404058

FULL PAPERS
Hydrogen Induced Polarization--Nuclear-Spin Hyperpolarization
in Catalytic Hydrogenations without the Enrichment of Para- or
Orthohydrogen
a
b,
Thorsten Jonischkeit, Klaus Woelk *
a
Institute of Physical and Theoretical Chemistry, University of Bonn, Wegelerstrasse 12, 53115 Bonn, Germany
Fax: (þ49)-228-739424, e-mail: jonisch@thch.uni-bonn.de
b
Department of Chemistry, University of Missouri-Rolla, 131 Schrenk Hall, 1870 Miner Circle, Rolla, MO
65409-0010, USA
Fax: (þ1)-573-341-6033, e-mail: woelkk@umr.edu
Received: March 1, 2004; Accepted: May 26, 2004
th
Dedicated to Professor Dr. Joachim Bargon (University of Bonn) on the occasion of his 65 birthday and in
recognition of his numerous contributions to chemically induced hyperpolarized NMR.
Abstract: During the last 40 years, Prof. Dr. Joachim tion and emission patterns of PHIP not only if the hy-
Bargon, to whom several articles in this issue are drogen for the catalytic reactions is enriched in one of
dedicated, has contributed more than 90 scientific its nuclear spin states (parahydrogen or orthohydro-
publications to the understanding of NMR hyperpola- gen) but also if it is at its thermodynamic equilibrium.
rization phenomena such as chemically induced dy- Thermally equilibrated gaseous hydrogen is obtained
namic nuclear polarization (CIDNP) or parahydrogen from commercially available hydrogen gas bombs or
induced polarization (PHIP). Both techniques are ex- from electrolytic hydrogen generators. The new find-
tremely useful for elucidating the mechanisms and ki- ing is explained with the quantum mechanical proper-
netics of chemical reactions involving radicals or cat- ties of the small, highly symmetric hydrogen mole-
alytic hydrogenations, respectively. To honor Joachim cule.
Bargon×s scientific achievements, we dedicate to him
an additional, newly discovered and somewhat unex-
pected twist to the PHIP methodology. Accordingly, Keywords: homogeneous catalysis; hydrogenation;
NMR spectra exhibit the unique, enhanced absorp- NMR spectroscopy; parahydrogen; spin polarization
Introduction
(a) the two hydrogen atoms must be transferred in
pairs,
NMR is a superior tool for investigations with catalytic (b) the nuclear spin relaxation of the transferred hy-
reactions, because the parameters chemical shift, cou-
pling constant, and relaxation time yield much informa-
drogen atoms must be slower than the overall ki-
netics of the chemical reaction,
tion about chemical structures, as well as mechanisms (c) the symmetry of the transferred hydrogen atoms
and kinetics of the reactions. However, NMR is inher-
ently insensitive when compared with other methods
must be broken during the reaction.
such as infrared (IR) or ultraviolet/visible light (UV/ The conditions (a) and (b) enable the nuclear spin align-
Vis) spectroscopy. The macroscopic magnetization gen- ment of parahydrogen (p-H ) to remain ± at least parti-
2
erated by the nuclear spins at thermal equilibrium in the ally ± intact during the reaction and to be transferred to-
magnetic field of a typical NMR spectrometer is only gether with the hydrogen atoms to the reaction inter-
À5
about 10 of what it could be if all spins were aligned mediates and products. Condition (c) is necessary to ob-
in parallel. In 1986, it was predicted that molecular hy- tain NMR-observable magnetization from the inter-
drogen (H ) enriched in its nuclear singlet state (parahy- mediates or products× hyperpolarization. NMR spectra
2
drogen) can induce nuclear spin hyperpolarization in recorded in situ during or shortly after a catalytic hydro-
the products of hydrogenation reactions, which can genation with p-H exhibit the largely enhanced signals
2
[
1]
lead to largely enhanced NMR signals. The prerequi- in unique absorption and emission patterns. The phe-
sites for observing the spin hyperpolarization in the nomenon was independently termed PASADENA
NMR spectra of hydrogenation products are:
(parahydrogen and synthesis allow dramatically en-
960
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI:10.1002/adsc.200404058
Adv. Synth. Catal. 2004, 346, 960±969

Hydrogen Induced Polarization±Nuclear-Spin Hyperpolarization
FULL PAPERS
[
2]
hanced nuclear alignment) and PHIP (parahydrogen position. Hence, the symmetry of the rotational wave
[
3]
induced polarization) unfolding an extremely useful function alternates with the quantum number such
method to elucidate mechanisms and kinetics of cataly- that even rotational quantum numbers (J¼0, 2, 4, ...)
tic hydrogenations. The method is also utilized to identi- correspond to symmetric rotational states and odd num-
fy reactive intermediates that are not seen with other bers (J¼1, 3, 5, ...) to antisymmetric states. In addition,
1
methods. Several reviews with different emphasis on protons bear a spin quantum number of I¼ ³
2
and, in H ,
2
[
4±9]
methodical or chemical aspects are available.
couple to a total spin quantum number of either I¼0
Similar but inverted signal patterns and somewhat (p-H ) or I¼1(o-H ). Of these two possibilities, p-H
2
2
2
weaker NMR signal enhancements are achieved with is antisymmetric with respect to the interchange of the
H enriched in its nuclear triplet state (i.e., enriched in two protons, while o-H is symmetric (Fig. 1).
2
2
[10]
orthohydrogen). Since the acronym PHIP, however,
Because protons are fermions, the total wave function
is commonly used to cover all nuances of hydrogen in- of H is antisymmetric, i.e., changes sign when the indis-
2
duced polarization including the effects of orthohydro- tinguishable protons are interchanged (Pauli principle).
gen (o-H ), it might just be interpreted as ™polarized∫ Consequently, and as a result of the D symmetry of
2
1h
[
11]
hydrogen induced polarization. The acronym PASA- homonuclear diatomic molecules, the rotational sym-
DENA is nowadays frequently used to characterize an metry dictates the symmetry of the nuclear-spin wave
experimental procedure, namely the one in which the function and vice versa. While one of the wave functions
hydrogenation and NMR measurement are both carried (rotational or nuclear-spin) is symmetric, the other one
out in the static magnetic field of an NMR spectrometer. must be antisymmetric. Accordingly, p-H with its anti-
2
[
12]
Alternatively, the acronym ALTADENA (adiabatic symmetric nuclear-spin wave function occurs exclusive-
longitudinal transport after dissociation engenders net ly with even rotational quantum numbers, while o-H ex-
2
alignment) is used to describe the procedure in which clusively occupies energy levels with odd rotational
the hydrogenation is conducted outside of the NMR quantum numbers.
magnet and the sample is subsequently transported
The diagram in Figure 2 shows the six lowest rotation-
into the magnetic field for the NMR analysis. PHIP pat- al energy states of H (J¼0 to J¼5) with the relative
2
terns vary substantially with the experimental proce- horizontal location proportional to their energy. The
dure, and PASADENA and ALTADENA are alter- numbers posted above the states represent the numbers
nately used to optimize PHIP results for the elucidation of degeneracy, which are calculated from the product of
and analysis of catalytic reactions.
rotational and nuclear-spin degeneracy, (2I þ1)Â
In this article, we report that similar nuclear-spin hy- (2J þ1). In the representation of Figure 2, no external
perpolarization effects are obtained even without the magnetic field is assumed for it would lift the threefold
enrichment of p-H or o-H . Hydrogenation reactions nuclear-spin degeneracy of o-H . The energy difference
2
2
2
conducted with H at the thermal equilibrium of its nu- between adjacent rotational states, (J ±1 )! J, in linear
2
clear spin states (t-H ) can likewise lead to PHIP molecules is given by
2
NMR signal patterns in absorption and emission. The
new modification (thermal hydrogen induced polariza-
tion) was observed with both the PASADENA and the
ALTADENA experimental procedure.
ð1Þ
Quantum-Mechanical Properties of Molecular
Hydrogen
The total wave function of the small and highly symmet-
ric molecule H is easily separated into sub wave func-
2
tions for which the cross products are negligible (e.g.,
electronic, vibrational, rotational, and nuclear-spin
wave function). Since vibrational and electronic modes
are not activated in gaseous H at room temperature
2
[13]
or below, only the vibrational and electronic ground
states are populated and contribute to the partition
function of H . Consequently, energy transitions in H
Figure 1. Very much simplified representation of the spin
2
2
symmetry of p-H and o-H . The arrows in the H ball-and-
2
2
2
occur only between rotational and nuclear-spin states.
stick models symbolize effective magnetic moments. While
this representation is probably a quantum mechanist×s night-
mare for it particularly violates Heisenberg×s uncertainty re-
A rotation of (2nþ1)Â1808 (where n is a positive in-
teger including n¼0) about an axis perpendicular to the
molecular axis of H interchanges its two protons, while lation, it still helps visualizing the antisymmetric (p-H ) and
2
2
a rotation of 2nÂ1808 brings them back to their original symmetric (o-H ) nuclear-spin wave function of H .
2
2
Adv. Synth. Catal. 2004, 346, 960±969
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Thorsten Jonischkeit, Klaus Woelk
ð4Þ
where Espin(I¼0) is the nuclear-spin energy of the anti-
symmetric coupling in p-H , which is smaller than
2
Espin(I¼1), the energy of the symmetric coupling in
[
15]
o-H2. The frequency difference of 276 Hz [Eq. (4)] is
1
known as the J(H,H) coupling constant of H and is in-
2
dependent of external magnetic fields. A comparison of
1
J(H,H) with the smallest rotational transition frequen-
cy [Eq. (2)] shows that the partition function of p-H and
2
o-H at thermal equilibrium is solely governed by the oc-
2
cupation of rotational states. The o-H /p-H ratio at ther-
2
2
mal equilibrium is calculated from the energies of the ro-
tational states and their numbers of degeneracy accord-
ing to the Boltzmann distribution:
ð5Þ
Figure 2. Lower rotational states of H separated into col-
2
where k is Boltzmann×s constant, T is the absolute tem-
umns of p-H states (left) and o-H states (right). The rota-
2
2
perature, and DE is the energy difference between the
J
tional quantum number (J) of each state is shown to the right
of the columns, and the number of degeneracy is posted
above each state.
rotational levels EJ¼0 and E . At about room temperature
J
(
T¼295 K), Eq. (5) yields 25.09% p-H and 74.91%
2
o-H . Thus, H at its thermal equilibrium of 295 K (ther-
2
2
mal hydrogen or t-H ) consists of 99.88% non-polarized
2
where h is Planck×s constant, c is the speed of light in free
H (3:1mixture reflecting the threefold spin degeneracy
2
space, and B is the rotational constant of the molecule.
of o-H ) and 0.12% spin-polarized p-H . Hence, t-H
2
2
2
À1 [14]
With the rotational constant of H (B¼60.864 cm ),
À3
2
carries a 1.2Â10 excess of p-H or, put another way,
2
the energy difference between the lowest rotational lev-
À3
has a thermal spin polarization of 1.2Â10 compared
el of p-H (J¼0) and the lowest level of o-H (J¼1)
2
2
with the equal population of all energy levels achieved
only at infinite temperature.
yields
In standard PHIP experiments, p-H is typically en-
2
riched up to the ratio of its thermal equilibrium at li-
quid-nitrogen temperature (T¼77 K) yielding 52%
p-H and 48% o-H . This enrichment still consists of
ð2Þ
2
2
6
4% non-polarized H (o-H /p-H ratio of 3:1) but leads
2 2 2
Thus, the lowest-energy rotational transition in H is
2
to 36% spin-polarized p-H . Figure 3 shows histograms
2
quite large exhibiting a transition frequency in the far-
infrared spectral range. It is noted, however, that this en-
ergy transition is forbidden because of the different ro-
tational and spin symmetries. Because the spacing be-
tween rotational states increases with the rotational
quantum numbers (Figure 2), the next transition be-
tween (J¼1) and (J¼2) yields the even higher transi-
tion frequency
of the thermally equilibrated partition between H rota-
2
tional states at liquid-nitrogen temperature (T¼77 K)
and at room temperature (T¼295 K).
In the static magnetic field of an NMR spectrometer,
the nuclear-spin states of o-H loose their degeneracy
2
and split into three states that are equidistant in energy,
each with the rotational-state degeneracy of (2J þ1) re-
maining. The different nuclear spin states are now la-
beled T , T , T reflecting the triplet symmetry. The
þ1
0
À1
ð3Þ energy spacing between o-H
spin states depends on
2
the external magnetic field (B ) and is calculated with
0
the magnetogyric ratio (g) according to
In contrast with the large rotational energy splitting in
H , the energy difference between the spin couplings
2
ð6Þ
in p-H and o-H is only
2
2
962
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Hydrogen Induced Polarization±Nuclear-Spin Hyperpolarization
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Results and Discussion
Signal Enhancement
If pure p-H (spin polarization of DN/N¼1) is used for
2
catalytic hydrogenations, and spin relaxation is negli-
gible during the catalytic cycles, only those energy levels
are populated in the intermediates and products of the
reactions, which share ± at least partially ± the singlet
symmetry of p-H . For simplicity, we assume at first
2
that hydrogenation products are formed in which the
transferred hydrogen atoms couple only with each other
but not with other nuclei. However, the concept exem-
Figure 3. Partition histograms for the six lowest rotational plified here is used similarly for hydrogenation products
states of H at thermal equilibrium of (a) T¼77 K and (b) with more complex coupling patterns. Furthermore, it is
2
T ¼ 295 K. Dark grey bars represent states of p-H , while
2
supposed that the chemical-shift difference between the
transferred hydrogen atoms in the product is large com-
pared with the coupling constant. Then, the high-field
approximation for a loosely coupled spin system applies
light grey bars refer to the states of o-H . At 77 K, only the
2
lowest two states (ground states for p-H and o-H ) and, at
2
2
2
95 K, only the lowest four rotational states are substantially
[16]
populated.
(
AX spin system) leading to four spin states (Figure 4)
two of which are mixed states of 50% singlet and 50%
where ꢀh ¼h/2p. The p-H levels (I¼0, J¼0, 2, 4, ...) are triplet symmetry (jab>and jba>), while the others
2
usually labeled S (or S ) to reflect the singlet symmetry, are pure triplet states (jaa>and jbb>). If the hydroge-
0
but they remain unaffected by an external magnetic nation reaction occurs instantaneously (i.e., fast with re-
field. The single line that is observed in the NMR spec- spect to the spin-spin relaxation of the transferred hy-
trum of H originates from transitions between the o-H
drogen atoms) and within the NMR magnetic field (PA-
2
2
levels only, whereas p-H is NMR inactive. Even in the SADENA procedure), the two mixed states, jab>and
2
field of the strongest NMR magnets currently available jba>, are exclusively and equally populated because of
commercially (B ¼21T, resonance frequency of
their singlet character (Figure 4a). Accordingly, a hyper-
00 MHz¼9Â10 Hz), the splitting of the o-H spin lev- polarization of all NMR transitions (1±4 in Figure 4) is
0
8
9
2
els is three to four orders of magnitude below the energy achieved in the product, each carrying DN/N¼0.5. This
difference between the rotational states; thus, NMR hyperpolarization leads to both the large signal en-
magnetic fields do not influence the H partition func- hancement of PHIP and the distinct absorption and
2
tion.
emission pattern schematically shown in the NMR spec-
For the hydrogenation experiments described below, trum of Figure 4a. If, however, the catalytic hydrogena-
we used a 200 MHz Bruker Avance DRX NMR spec- tion is conducted outside of the spectrometer×s magnetic
trometer (B ¼4.7 T). In this field, the population differ- field (ALTADENA procedure), only the state that, in a
0
ence, DN, between a lower and upper resonant level magnetic field, converts to jba>shares the singlet sym-
1
of H NMR (a and b, respectively) is calculated from metry of p-H and, thus, is the only one populated (Fig-
2
[
12]
the Boltzmann distribution at 295 K using Eq. (6) and ure 4b). Accordingly, transitions 1and 4 are the only
7
the proton×s magnetogyric ratio (g¼26.752Â10 rad ones seen in the spectrum. However, since only one state
À1
À1 [17]
s
T ):
is populated, the hyperpolarization is DN/N¼1, and the
transitions occur with twice the intensity of the PASA-
DENA signals. After relaxation of the hyperpolariza-
tion, the remaining thermal polarization leads to the
standard thermal spectrum (Figure 4c).
ð7Þ
The theoretical (i.e., maximum) enhancement factor
j) is calculated from the ratio of the product×s PHIP hy-
(
where N and N are the populations of the levels a and perpolarization to the thermal polarization. According-
a
b
b, respectively.
ly, with pure p-H and our 200 MHz NMR spectrometer
2
(
B ¼4.7 T), the theoretical enhancement factor is [cf.
0
Eq. (7)]
ð8Þ
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Thorsten Jonischkeit, Klaus Woelk
PASADENA experiment. To match ALTADENA hy-
perpolarization, the field must even approach infinity.
Enhancement factors also depend on the temperature.
An increased temperature generally decreases the ther-
mal polarization [Eq. (7)] and, thus, increases the en-
hancement factor.
Experimentally, enhancement factors are determined
from the ratio of PHIP signal intensities to the intensi-
ties of the corresponding signals at thermal equilibrium
(
thermal signals). Mainly because of relaxation phe-
nomena and J-couplings to further protons in the prod-
uct molecules, however, experimentally derived en-
hancement factors are typically smaller than their theo-
retical values [Eq. (8) or (9)].
Because of the exclusive occupation of, and the large
energy difference between, the rotational states in H2
(
1
vide supra), t-H already carries a spin polarization of
.2Â10 [cf. Eq. (3)]. This value is about two orders
2
À3
Figure 4. Spin-state diagram of hydrogen nuclei in an AX of magnitude larger than the thermal polarization in a
-
5
spin system (left). The populations are depicted by the line typical hydrogenation product [1.63Â10 , Eq. (5)]. Ac-
width of the states and yield the NMR spectra schematically cordingly but initially much to our surprise, a p-H PHIP
2
shown on the right; (a) population and spectrum expected for
pattern with an enhancement factor of
PASADENA hydrogenation with pure p-H , (b) population
2
and spectrum expected for ALTADENA hydrogenation
with pure p-H , (c) population and spectrum expected after
relaxation to thermal equilibrium.
2
ð10Þ
for the PASADENA procedure and
is still expected for t-H PASADENA hydrogenations,
and
2
ð9Þ
for the ALTADENA procedure. In contrast, p-H spin
ð11Þ
2
polarization is only 36% (vide supra) in a H gas sample is expected for t-H ALTADENA. Because t-H is di-
2
2
2
that was enriched to its thermal equilibrium at liquid-ni- rectly obtained from standard gas bombs or electrolytic
trogen temperature (77 K). The maximum hyperpolari- H generators, the result of Eqs. (10) and (11) means that
2
zation achieved with 36% spin-polarized p-H in an AX everyone with access to standard laboratory equipment
2
hydrogenation product is therefore DN/N¼0.36 for AL- and an NMR spectrometer should be able to observe
4
TADENA (leading to j¼2.20Â10 ) and DN/N¼0.18 PHIP signals from appropriate and efficient catalytic
4
for PASADENA (j¼1.10Â10 ).
hydrogenations without going through a procedure of
Because thermal polarization of spin states depends p-H or o-H enrichment.
2
2
on the B field [Eqs. (6) and (7)], enhancement factors
0
also depend on B . An increased magnetic field leads
0
to an increased thermal NMR signal, which, in turn, de- In situ NMR of Homogeneously Catalyzed
creases the enhancement factors [Eqs. (8) and (9)]. In Hydrogenations
the temperature range that is suitable for catalytic reac-
tions, the hyperpolarization with p-H , however, is inde- To observe PHIP hyperpolarization in NMR spectra,
2
pendent of the B field. This makes the enhancement the hydrogen atoms of H must be transferred in pairs
0
2
factor a relative measure. For example, the factor is re- to the product. This particular mechanism is most likely
duced to about half the value of Eqs. (8) or (9), if the with homogeneous hydrogenations using organometal-
1
magnetic field is increased to 9.4 T (400 MHz H reso- lic complexes as the catalyst. Because the reaction
5
nance frequency). However, a B field of 1.6Â10 T is must break the singlet symmetry of the transferred hy-
0
needed to reduce the enhancement factor of PASADE- drogen atoms [condition (c), vide supra], an asymmetri-
NA experiments to j¼1. Put another way, only a field of cally substituted acetylene, i.e., ethyl propiolate (pro-
5
B ¼1.6Â10 T leads to a thermal polarization that is as piolic acid ethyl ester, H-C¼C-COOEt), was chosen as
0
high as the hyperpolarization achievable with p-H in a the substrate. It is noted, however, that reactions with
2
964
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Hydrogen Induced Polarization±Nuclear-Spin Hyperpolarization
FULL PAPERS
[
12]
symmetrically substituted olefins and acetylenes also intensities. In first approximation and for loosely cou-
exhibit PHIP signals, namely if the transferred hydrogen pled spin systems, maximum PHIP intensities are ob-
atoms in the product are chemically equivalent but mag- servedwiththe458pulsesofstandardNMRsignalsrather
netically different (e.g., hydrogenation into an AA’BB’ than with 908 pulses. Actually, most PHIP intensities van-
[8]
system). Even if the hydrogen atoms are transferred ish at the 908 pulse of the standard intensities. Further-
into chemically and magnetically equivalent positions, more, at 1358, PHIP signals show another intensity max-
13
naturally abundant C breaks the symmetry in 1.1% imum but with inverted signal patterns. Accordingly, the
of the product for every carbon atom that exhibits a periodicity of PHIP intensities as a function of pulse
1
13
measurable H/ C J-coupling to the transferred hydro- width (or pulse intensity) is twice the periodicity of regu-
[18]
gen atoms.
lar NMR signals. Thus, it is possible to observe PHIP sig-
Still, for optimum results, we picked a catalytic reac- nals while suppressing thermal signals with a difference
tion with hydrogen transfer into chemically different po- spectroscopy of a 458 and a 1358 pulse experiment, which
sitions and selected appropriate reaction conditions ac- efficiently co-adds PHIP intensities but cancels thermal
cording to:
signal intensities. Alternatively, the addition of a 458
a) The hydrogenation must be fast, so that much spin- and a 2258 pulse experiment leads to the same result.
polarized product is formed in a given time span. Typical PHIP spectra recorded in situ from PASADE-
b) None of the substances in the solution should carry NA and ALTADENA experiments of our catalytic
nuclear quadrupole moments that increase nuclear- model hydrogenation are shown in Figures 5a and 6a, re-
spin relaxation. For example, palladium with its spectively. The PHIP patterns at 6.3±5.8 ppm are easily
strong quadrupole moment was not selected, al- assigned to the vinyl moiety of the product ethyl acry-
though its reactivity is very high and palladium-or- late, which was formed by the reaction. In the ALTA-
ganic catalysts are still known to generate PHIP hy- DENA spectrum, PHIP signals are also observed at
perpolarization in the products of hydrogenation 2.4 ppm and 0.8 ppm originating from the subsequent
(
(
reactions.
hydrogenation of ethyl acrylate forming ethyl propio-
nate (propionic acid ethyl ester). The experimental en-
Among the many reactions that comply with the above- hancement factors for the signals of the vinyl moiety
3
4
mentioned conditions, we selected [Rh(DPPB)(COD)] are j¼1.8Â10 (PASADENA) and j¼1.2Â10 (AL-
BF (Scheme 1), where DPPB¼1,4-bis(diphenylphos- TADENA) compared with thermal signal intensities re-
4
phino)butane, and COD¼1,5-cyclooctadiene, as a sim- corded from the same samples but after the hyperpola-
ple but efficient, commercially available catalyst precur- rization has completely relaxed. Compared to the theo-
sor for the hydrogenation of the electron-deficient sub- retical maximum, the experimental PHIP signals are di-
strate ethyl propiolate to form ethyl acrylate (acrylic minished by a factor of 6.1for PASADENA and 1.8 for
acid ethyl ester).
ALTADENA. The diminishment is caused by the acety-
To determine the efficiency of generating hyperpola- lenic proton of the propiolic acid ester, which, in the
rization in the chosen hydrogenation, we compared ex- product, couples to both of the transferred hydrogen
perimental enhancement factors of PHIP spectra with atoms. In the high-field approximation, the additional
the corresponding theoretical factors (ALTADENA: J-couplings split each of the nuclear spin states of Fig-
4
4
j¼2.20Â10 , PASADENA: j¼1.10Â10 , vide supra). ure 4 into two equally populated states, thus, reducing
The PHIP spectra were recorded in situ during catalytic the hyperpolarization of each transition to DN/N¼
hydrogenations with H enriched in p-H up to the ther- 0.25 for PASADENA and DN/N¼0.5 for ALTADENA.
2
2
mal equilibrium at liquid-nitrogen temperature. Details Thermal polarization, however, is largely independent
of the reactions and the p-H enrichment procedure are of additional J-couplings. In the PASADENA experi-
2
given in the experimental section.
ment, relaxation of the hyperpolarization or an incom-
It is noted that PHIP signal intensities depend differ- plete reaction at the time of recording the spectra ac-
ently on NMR pulse widths than regular, thermal signal counts for further diminishment. In PASADENA ex-
periments, we sometimes observed increasing PHIP in-
tensities in a spectrum recorded several seconds after
the first spectrum. This indicates that the reaction was
still incomplete at the time of the first spectrum. Since
it takes substantially longer to transport the sample
tube into the magnetic field of the NMR spectrometer,
we did not observe this effect with ALTADENA. In
summary, the experimental enhancement factors show
that the reaction we selected works very efficiently for
the transfer of hyperpolarization via p-H and that an ex-
2
Scheme 1. [1,4-Bis(diphenylphosphino)butane](1,5-cyclooc-
tadiene)rhodium(I) tetrafluoroborate.
clusive reaction mechanism of pairwise transfer of hy-
drogen atoms is most likely.
Adv. Synth. Catal. 2004, 346, 960±969
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Thorsten Jonischkeit, Klaus Woelk
For the quantitative determination of the enhance-
ment factors, integrated signal intensities of both the
PHIP hyperpolarization signals and the signals recorded
after the population of nuclear-spin states has complete-
ly relaxed were calibrated with the solvent×s signal inten-
sity. This calibration is advisable because the receiver
gain setting of the NMR spectrometer must inevitably
be changed when switching from recording largely en-
hanced PHIP signals to recording thermal signals that
are up to four orders of magnitude smaller.
The same experiments (PASADENA and ALTADE-
NA) were repeated with t-H taken directly from an H
2
2
gas bomb. To ensure that the gas bomb×s H did not ac-
2
cidentally carry spin hyperpolarization, the measure-
ments were repeated with H obtained from an H gen-
2
2
erator that electrolyzes water. By electrolyzing water,
H is always generated at the current temperature×s ther-
2
1
Figure 6. 200 MHz H ALTADENA NMR spectra recorded
from the catalytic hydrogenation of ethyl propiolate to
form ethyl acrylate (a) during the reaction with 36% spin-po-
larized p-H , (b) during the reaction with t-H , and (c) after
2
2
the reaction with t-H and complete relaxation of the hyper-
2
polarization. The vertical scales of (b) and (c) are enlarged
versus (a) by the factors posted. NMR signals are assigned
as explained in the legend to Figure 5. In addition, however,
PHIP signals from the subsequent hydrogenation of ethyl
acrylate to form ethyl propionate are observed in (a) and
(
b) at 2.4 ppm and 0.8 ppm for the methylene and methyl
group of the propionate, respectively.
mal equilibrium. For the reproducibility of the hydroge-
nation experiments with H from the electrolytic gener-
2
ator, however, it is important that the H gas is carefully
2
dried (i.e., over silica gel) before it is used in the catalytic
reaction. Still, no differences were detected in the NMR
spectra from the experiments with H from the electro-
Figure 5. 200 MHz H PASADENA NMR spectra recorded lytic generator compared with the experiments with H2
in situ from the catalytic hydrogenation of ethyl propiolate from the gas bomb.
2
1
to form ethyl acrylate (a) during the reaction with 36%
Spectra recorded in situ during the catalytic hydroge-
spin-polarized p-H , (b) during the reaction with t-H , and
2
2
nations with t-H are shown is Figures 5b and 6b, respec-
2
(
c) after the reaction with t-H and complete relaxation of
2
tively. They exhibit the same qualitative information
the hyperpolarization. The vertical scales of (b) and (c) are
enlarged versus (a) by the factors posted. NMR signals are as-
signed as follows: 4.2 ppm, acetylene proton of ethyl propio-
late; 3.8 and 1.2 ppm, ester group of ethyl propiolate;
(
the same signal pattern) as observed from the hydroge-
nations with p-H enriched gas samples. However, the
2
enhancement factors of the t-H PHIP signals are only
2
j¼6 for PASADENA and j¼29 for ALTADENA com-
6
2
.5±5.8 ppm, vinyl moiety of ethyl acrylate; 4.6 and
.4 ppm, ester group of the product ethyl acrylate; 2.0 ppm pared with the thermal signals that were recorded after
residual protons of the solvent acetone-d6.
complete relaxation (Figures 5c and 6c, respectively).
966
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 960±969

Hydrogen Induced Polarization±Nuclear-Spin Hyperpolarization
Table 1summarizes the theoretical and experimental
FULL PAPERS
An investigator who wishes to analyze catalytic hydro-
NMR enhancement factors of the hydrogenations con- genations with respect to the pairwise mechanism, its ki-
ducted with (a) H thermally equilibrated at room tem- netics, and the positions into which the hydrogen atoms
2
perature (t-H ), (b) H enriched in p-H to the thermal are transferred, or who tries to identify intermediates in
2
2
2
equilibrium at liquid-nitrogen temperature (77 K, i.e., the catalytic cycle, will always strive to use the largest
6% p-H ), and (c) with 100% (i.e., pure) p-H . NMR signal enhancement achievable at a reasonable
The ratio between the theoretical enhancement fac- expense. Since it is neither expensive nor much time-
tors of 36% p-H and t-H is 299 (Table 1d). This ratio consuming to enrich p-H up to the thermal equilibrium
3
2
2
2
2
2
is most accurately reproduced experimentally by the at liquid-nitrogen temperature (cf. experimental sec-
PASADENA experiments. In the ALTADENA experi- tion), the 36% spin-polarized p-H provided by this pro-
2
ment, a ratio of 410 was determined, which is far more cedure is usually a good compromise even for investiga-
than expected from the theory. However, unlike PASA- tors that do not use the technique on a daily basis. How-
DENA, where the experimental conditions are highly ever, for preliminary experiments and demonstrations,
reproducible (cf. experimental section), ALTADENA in situ NMR spectra from catalytic hydrogenations
is prone to many experimental uncertainties such as with the H taken as is from a standard gas bomb may al-
2
the time frame of hydrogen insertion and sample-tube ready be sufficient to reveal the desired results, as shown
shaking, and the transport from the earth magnetic field in this article. The ALTADENA procedure is usually
under which the reaction is conducted into the NMR preferred over the PASADENA procedure for such pre-
main magnetic field.
liminary experiments, because it is easily conducted out-
side of the NMR magnet, intrinsically shows stronger
enhancement factors, and is conducted with slightly en-
Conclusion
hanced H pressure (up to 3 bar), if needed, in a simple
NMR tube with a septum screw cap.
2
PHIP investigations are an established NMR technique
for the elucidation of hydrogenation reactions. If largely
enhanced PHIP patterns are recorded in the NMR spec-
tra of catalytic hydrogenations, much information is di-
rectly revealed about the reaction under investigation.
Experimental Section
For example, the reaction mechanism is, at least for PASADENA Hydrogenation of Ethyl Propiolate with
the part that generates the hyperpolarization, such [Rh(DPPB)(COD)]BF4
that the hydrogen atoms are transferred in pairs from
In a standard 5-mm NMR sample tube, 2.17 mg (3 mmol)
the same H molecule. The positions of the transferred
2
of [Rh(DPPB)(COD)]BF were dissolved in 500 ml of ace-
4
hydrogen atoms in the product molecules are often iden-
tified easily from the signal patterns of PHIP, although, it
is sometimes advisable to run a computer simulation for tube temporarily sealed, and the solution thoroughly mixed
tone-d . Thereafter, 15.2 mL of ethyl propiolate (14.7 mg,
6
1
50 mmol, SCR¼50) were added to the solution, the sample
back up of the spectrum analysis.
by shaking. The 5-mm sample tube with the freshly made solu-
To record PHIP spectra from a catalytic hydrogena- tion was positioned in an NMR spinner and hooked up, at its
open end, to a 5-mm glass extension tube by a tightly fitting
tion, gaseous H is usually enriched in p-H up to the
2
2
rubber hose connection. The assembly with the extension
tube was lowered into the NMR magnet, whereby the spinner
ensures an optimum positioning in the sweet spot of the mag-
netic field. The length of the extension tube was chosen to
reach slightly above the upper end of the magnet bore. A
long glass capillary tube was lowered through the extension
tube into the sample tube reaching just above the reactive so-
thermal equilibrium at liquid-nitrogen temperature.
However, we found that even thermal H taken as is
2
from a gas bomb or obtained from an electrolytic H2
generator carries a spin polarization about three orders
of magnitude higher than the thermal polarization in
most reaction products. This spin polarization results
in similar PHIP signal patterns, although, with much lution. Thereafter, the capillary was hooked up to a magnetic
smaller signal enhancements. drive by a rope mechanism. The magnetic drive was positioned
Table 1. Calculated and experimentally derived PHIP enhancement factors.
Calculation
Experiment
PASADENA
6
±1 .8Â10
PASADENA
36.8
ALTADENA
73.6
ALTADENA
29
±1 .2Â10
(
(
(
(
a) t-H2
b) 36% p-H2
c) 100% p-H2
4
4
3
4
1.10Â10
2.20Â10
4
4
3.07Â10
6.13Â10
d) Ratio t-H /36% p-H
299
299
300
410
2
2
Adv. Synth. Catal. 2004, 346, 960±969
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
967

FULL PAPERS
Thorsten Jonischkeit, Klaus Woelk
further away from the NMR magnet to avoid interference of its
magnetic field with the NMR field but enabled the capillary
tube to be lowered into the solution for hydrogen addition
and to be removed from the solution for the NMR measure-
ments. The insertion of the capillary into, and its removal
from, the solution was controlled by the spectrometer console
via a special TTL gate line.
half an hour after initially flushing the charcoal reactor with
H from a standard gas bomb, a continuous flow of room-tem-
2
perature H gas enriched to 36% spin-polarized p-H was ob-
2
2
tained from one leg of the U-shaped reactor up to 100 mL/min.
The flow was controlled by adding fresh H from the gas bomb
2
into the other leg of the reactor.
The hydrogen gas for the reaction was either enriched in
p-H up to its thermal equilibrium at liquid-nitrogen tempera-
2
Acknowledgements
ture (77 K, 36% spin-polarized p-H ), taken as is from a stand-
2
ard H gas bomb, or generated with an electrolytic H genera-
2
2
The idea to obtain PHIP NMR signals without the enrichment of
para- or orthohydrogen (i.e., from reactions with hydrogen gas
at its room-temperature thermal equilibrium) was sparked in
tor. For 3 s, it was bubbled at a pressure of minimally more than
bar through the capillary glass tube into the reactive solution.
Thereafter, the capillary was raised and a waiting period of 2 s
was passed to allow excess hydrogen bubbles to part from the
solution before the NMR spectrum was recorded.
1
1
993 by a discussion that one ofthe authors (K. W.) had with
Prof. Simon B. Duckett (University of York, UK). Several years
later (1997), Dr. Johannes Natterer and Dr. Ralph Giernoth
In the homogeneous hydrogenations with the catalyst pre-
(
University ofCologne, Germany) were Ph.D. students of
cursor [Rh(DPPB)(COD)]BF , the COD must be hydrogena-
4
Prof. Dr. Joachim Bargon (University of Bonn). J. Natterer sug-
gested to K. W. that thermal hydrogen should yield PHIP pat-
terns; however, this was based upon density-matrix calculations
in the product-operator formalism. R. Giernoth succeeded to
obtain small PHIP signals during catalytic reactions with hydro-
gen from a standard hydrogen gas bomb. However, he was un-
able to decide whether the effect was real or due to parahydrogen
enriched residues in the supply lines. The contributions and pre-
liminary work ofS. B. Duckett, J. Natterer, and R. Giernoth are
greatly acknowledged. Finally, on a more amusing note, the mo-
tivational slogan ™PHIP, PHIP, hurray!∫ introduced to Prof.
Bargon×s group for successful PHIP measurements by Dr. Ste-
fan Klages is recognized. With this article, however, the slogan
may return to its original version ™HIP, HIP, hurray!∫ for the
term ™parahydrogen∫ or ™polarized∫ in the acronym PHIP
ted first and removed from the catalyst before the hydrogena-
tion of the designated reagent ethyl propiolate can occur.
Therefore, hydrogen was bubbled several times in 3 s intervals
into the reaction solution before PHIP signals of the desired
product were recorded. Sometimes, however, some ethyl acry-
late had already formed before COD was completely removed
from the catalyst precursor. If the amount of acrylate was sig-
nificant and seen in the NMR spectra even before a measure-
ment of PHIP hyperpolarization was conducted, we used the
difference between the integrated intensities of the acrylate×s
thermal signals before the reaction and after complete relaxa-
tion of the hyperpolarization to quantify the thermal signal in-
tensity of acrylate formed during the 3 s of hydrogen injection.
(
parahydrogen induced polarization or polarized hydrogen in-
ALTADENA Hydrogenation of Ethyl Propiolate with duced polarization) is no longer needed.
Rh(DPPB)(COD)]BF4
[
Similar to the PASADENA experiments, a reaction solution
was prepared by dissolving 3 mmol of [Rh(DPPB)(COD)]BF4
and, subsequently, 150 mmol of ethyl propiolate in 500 mL of
References and Notes
acetone-d . A 5-mm NMR tube with a septum screw cap was
6
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2
2645±2648.
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The H gas was either taken directly from an H gas bomb, from
[
[
2] C. R. Bowers, D. P. Weitekamp, J. Am. Chem. Soc. 1987,
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2
2
1
an electrolytic H generator, or after it had been enriched in
2
p-H to its thermal equilibrium at 77 K. The reaction was initi-
2
ated outside of the NMR magnet by intense shaking of the sam-
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4] C. R. Bowers, D. H. Jones, N. D. Kurur, J. A. Labinger,
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[7] J. Bargon, in: Applied Homogeneous Catalysis with Or-
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2
trogen temperature (77 K) was achieved by flowing H gas
2
[
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2
[
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Engl. 1990, 29, 58±59.
2
between o-H and p-H , which is otherwise forbidden. About
2
2
968
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 960±969

Hydrogen Induced Polarization±Nuclear-Spin Hyperpolarization
FULL PAPERS
th
[
[
[
[
[
[
11] J. Bargon, J. Kandels, K. Woelk, Z. Phys. Chem. 1993,
80, 65±93.
12] M. G. Pravica, D. P. Weitekamp, Chem. Phys. Lett. 1988,
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in P. W. Atkins, J. de Paula, Physical Chemistry, 7
1
edn., Oxford University Press, Oxford, 2002, pp. 662. It
appears that, in this common textbook, a rotational con-
±
1
±1
1
stant of B¼61m (instead of B¼61cm ) was mistak-
th
13] P. W. Atkins, J. de Paula, Physical Chemistry, 7 edn.,
Oxford University Press, Oxford, 2002, pp. 662±665.
enly used and leading to the very different result. For
±
1
the rotational constant B¼61cm , however, Atkins
th
14] P. W. Atkins, J. de Paula, Physical Chemistry, 7 edn.,
and Paula×s distribution represents the thermal equilibri-
Oxford University Press, Oxford, 2002, p. 1097.
15] K. H. Hellwege, Einf¸hrung in die Physik der Molekeln,
Springer, Berlin, 1974, pp. 188±190.
um at about 44000 K at which no H molecules exist.
2
[17] Tables and Other Useful Information, Bruker Almanac,
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[18] M. Haake, J. Barkemeyer, J. Bargon, J. Phys. Chem.
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16] The histograms in Figure 2 strongly deviate from the par-
tition-function histogram shown for H rotational states
2
Adv. Synth. Catal. 2004, 346, 960±969
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
969