A. Deuteration and Hydrogen Exchange Reactions

Hoffmann and Conradi (49) studied the deuteration of 4-ethylphenol in

supercritical D2 O at 460◦ C and 250 bar using high-pressure NMR. The methyl

protons were found to be stable under these conditions. The temperature was

raised to 500◦ C, and the deuteration of the methyl protons in conjunction with

decomposition reactions was monitored. From this investigation, the selective

deuteration of the different protons in 4-ethylphenol in supercritical D2 O could

be demonstrated.

Another investigation of the deuteration of resorcinol in supercritical D2 O

used a high-pressure NMR capillary cell as an in situ flow reactor (50). The

temperatures covered in these measurements ranged from 200◦ C to 450◦ C at a

pressure of about 400 bar. The deuterium exchange in resorcinol under these

conditions was observed using both proton and deuterium NMR as a function of

the resorcinol residence time in the capillary tubular reactor. The NMR results

indicate that H/D exchange in resorcinol for the ring protons was observed at

temperatures as low as 200◦ C. The activation energy of the H/D exchange of the

ortho/para ring protons on resorcinol was reported. The microvolume and low

thermal impedance of the capillary tubing contributes to the rapid temperature

equilibration in the flow-through reactor region in the NMR probe.

If the hydrogen exchange rate 1/τlife is comparable to the chemical shift

frequency difference, ωshift , of the spin exchanging sites, then lifetime broadening effects are visible in the NMR spectrum. Specifically, if hydrogen exchange

1, then one observes one sharp resonance. A

is fast, such that ωshift τlife

gradual slowing of the chemical exchange rate, to the regime of ωshift τlife ≈ 1,

results in resonance broadening. This eventually leads to the emergence of two

broad lines, each representing one of the two hydrogens. Finally, when hydrogen exchange is fast, such that ωshift τlife

1, two sharp lines are present in

the NMR spectrum. This was observed for a supercritical aqueous solution of

methanol when the density at a constant temperature of 400◦ C was gradually

decreased (49). Methanol in comparison with aliphatic or aromatic hydrocarbons

is a much stronger acid. At high densities and 400◦ C, hydrogen exchange is fast,

and one resonance line for the hydroxyl and water protons is observed. However,

with decreasing density the solvation characteristics of supercritical water and

methanol change. Hence, polar intermediates during hydrogen exchange, such

as H3 O+ , are less stabilized, which in turn slows the hydrogen exchange rate.

As a result, the hydrogen exchange rate at low, gas-like densities shows two distinct resonances for the hydroxyl and water protons. This example demonstrates

one of the major promises of supercritical fluids: reaction rates can be smoothly

altered at a fixed temperature by pressure-tuning (density-tuning) the solvation

characteristics of the supercritical fluid solvent.

Similar to lifetime effects based on chemical shift differences, the J coupling can be exploited to study changes in reaction rates as well (49). Using this

approach, the collapse of the J-coupling multiplets in ethanol (from the hydroxyl

proton coupling with the CH2 protons) was monitored as a function of pressure



Copyright 2002 by Marcel Dekker. All Rights Reserved.



at several constant temperatures. Interestingly, the J-coupling multiplet collapse

was observed in gaseous ethanol, indicating that even at low, gas-like densities

intermolecular hydrogen exchange is important. With the J-coupling constant

being 5 Hz, the exchange rate is 2π × 5 ≈ 30 sec−1 at these conditions.

B. Keto-enol Equilibrium

The keto-enol tautomeric equilibrium of acetylacetone is an intramolecular hydrogen exchange process. High-pressure NMR was used to study changes in this

equilibrium over a pressure range to 2.5 kbar and temperatures to 145◦ C (51).

With an increase in temperature at constant pressure, the equilibrium distribution shifted to the keto tautomer. An increase in pressure did not change the

keto-enol distribution at any temperature. From the high-pressure experiments

as a function of temperature the reaction enthalpy, H , and entropy, S, were

determined to be 2.80 ± 0.02 kcal/mol and 7.2 ± 0.3 cal/K mol, respectively.

A subsequent study investigated the effect of fluorine substitution on the

tautomeric equilibrium of acetylacetonate β-diketones (acetylacetone, trifluoroacetylacetone, and hexafluoroacetylacetone) (52). The equilibrium between

the keto and enol tautomers was studied as a function of pressure and temperature for both the pure compounds and those dissolved in supercritical CO2 .

Similarly, no pressure dependence was observed on the tautomeric equilibrium.

However, the degree of fluorination was found to have a dramatic stabilizing

effect on the enol tautomer. This is because the electron-withdrawing fluorine

further stabilizes the enol form through enhanced electron delocalization in the

intramolecular resonance-assisted hydrogen bond. The stability of the enol tautomer in hexafluoroacetylacetone to temperature also points to the magnitude

of this enol stabilization. The H values indicate that the enol tautomer is enthalpically favored in both acetylacetone and trifluoroacetylacetone. The small

experimental difference seen in the value of S for acetylacetone and trifluoroacetylacetone can be rationalized on the basis of the differing hydrogen bond

strength in the enol form of the two compounds with trifluoroacetylacetone having a stronger intramolecular hydrogen bond. These findings imply that changes

in temperature should have dramatic consequences on supercritical fluid extraction involving β-diketones, whereas pressure should play a minor role. In

contrast to the increase in the intermolecular hydrogen bond strength of simple

alcohols with pressure, it is interesting to note that increasing pressure either

weakens or does not affect the intramolecular hydrogen bond strength for the

three molecules investigated.

C. Photolysis Reactions

An advantage of using the high-pressure capillary NMR cell is the ease of

access to optical light of the supercritical fluid solution. Therefore, the range



Copyright 2002 by Marcel Dekker. All Rights Reserved.



of chemical reactions in supercritical fluids that can be studied in situ by highpressure NMR can be broadened to include photolysis reactions. The benchmark

experiment that demonstrated the capability of this new technique was an investigation of the photoreversible fulgide, Aberchrome-540, as a function of

pressure and temperature to 2.0 kbar and 120◦ C (53). The interconversion of

the two Aberchrome-540 species (ring open and ring closed) was monitored

during continuous photolysis. One could readily determine the decrease in the

initial structure (ring open) and a concomitant increase in the ring-closed structure with time. For the ring-closed molecule, the equatorial methyl group in the

fulgide is deshielded by the carbonyl on the anhydride group as compared to

the axial methyl group. Thus, during photoconversion the largest chemical shift

occurs on ring closure for the methyl 1 H resonances due to the change in conjugation of the fulgide structure upon ring closure. The temperature dependence

of fulgide photoconversion was investigated at 25, 60, and 120◦ C at a constant pressure of 2.0 kbar. Interestingly, at 120◦ C there was no photoconversion

observed at 2.0 kbar. It was hypothesized that during photolysis at higher temperatures the back reaction of the photocyclization (ring closed to ring open) was

promoted.

For organometallic chemistry in supercritical fluids, high-pressure NMR

has the advantage of describing the physicochemical environment and molecular

structure of the ligand and complex directly coupled with the investigation of the

central metal atom (dependent on the spin of the nuclei under investigation). The

in situ photolytic substitution of ethylene and hydrogen for carbon monoxide on

cymantrene [CpMn(CO)3 ] and methylcymantrene [MeCpMn(CO)3 ] dissolved

in subcritical and supercritical solvents (CO2 and ethylene) was investigated by

high-pressure NMR over the temperature range −40◦ C to 100◦ C and the pressure

range 35 to 2000 bar (54). These in situ photolysis investigations of organometallic species involved the direct detection of reaction products and the observation

of the substituted ligand attached to the metal center. Photolytic substitution

of ethylene for CO proceeded to completion under all conditions investigated,

but only one ethylene was observed to add to the manganese complexes even

in neat ethylene under extreme conditions of pressure and temperature. Small

amounts of dihydrogen were observed to substitute for CO at 35◦ C in a binary

mixture of CO2 /H2 . Hydrogen is a very poor solvent for these organometallic complexes, and small amounts in either CO2 or ethylene can precipitate

the metal complex from solution or cause phase separation. The photolysis of

pentamethylcyclopentadienyl rhenium tricarbonyl [Cp∗ Re(CO)3 ], in H2 /CO2 at

35◦ C and 490 bar was observed in which the hydride was formed on displacement of one of the carbonyl ligands (51). Similarly, the photolysis reaction

chemistry of Cp∗ Re(CO)3 at 26.5◦ C and 540 bar in ethylene was investigated in

which the mechanism involves the formation of a diethylene-substituted complex Cp∗ Re(CO)(η2 -C2 H4 )2 (51). The diethylene-substituted rhenium complex



Copyright 2002 by Marcel Dekker. All Rights Reserved.



was studied using time-dependent high-pressure NMR, to investigate the slow,

thermal loss of ethylene for CO. This reaction sequence is

Cp∗ Re(CO)(η2 -C2 H4 )2 + CO



Cp∗ Re(CO)2 (η2 -C2 H4 ) + CO

Cp∗ Re(CO)3



(10)



From a kinetic fit to the time-resolved data shown in Figure 5, the rate constant for the two thermal loss reactions could be determined. Since the overall

reaction is first order in Cp∗ Re(CO)(η2 -C2 H4 )2 with no observed dependence

upon Cp∗ Re(CO)3 , the source of the CO appears to be the free CO in the supercritical ethylene solution liberated during the initial photolysis of Cp∗ Re(CO)3 .

In this investigation, advantage was taken of the fluid solution homogeneity to

investigate rates of reactions involving small molecules (CO and ethylene) that

are normally only obtainable in the gas phase. These in situ high-pressure NMR



Figure 5 The time-resolved high-pressure NMR spectra of the back reactions for

Cp∗ Re(CO)(η2 -C2 H4 )2 and CO at 345 bar and 30◦ C in supercritical ethylene; (A)

Cp∗ Re(CO)3 , (B) Cp∗ Re(CO)2 (η2 -C2 H4 ) and (C) Cp∗ Re(CO)(η2 -C2 H4 )2 . The spectra are spaced about 80 min apart from bottom to top.



Copyright 2002 by Marcel Dekker. All Rights Reserved.



studies have provided direct mechanistic insight into the photoinduced ligand

substitution reactions of these organometallic compounds in supercritical fluids.

D. Homogeneous Catalysis

CO2 (CO)8 -catalyzed hydroformylation of olefins is an important reaction in the

field of organometallics and is probably the first homogeneous catalysis reaction

that has been studied by in situ NMR using supercritical carbon dioxide as the

reaction solvent (55). The significantly reduced line width of the quadrupolar nuclei 59 Co in the supercritical fluid made it possible to resolve all of the catalytic

intermediate species [RC(O)Co(CO)4 , HCo(CO)4 , and Co2 (CO)8 ], and the high

solubility of hydrogen in supercritical CO2 resulted in a single-phase reaction

mixture, thus eliminating the need for agitation. Hence, the concentrations of all

the intermediate species were followed directly in real time with 59 Co NMR.

The olefin decline and aldehyde production were followed by 1 H NMR over the

course of the hydroformylation reaction at 80◦ C (88% product yield).

One important intermediate step in the catalytic reaction of Co2 (CO)8

involves the chemical equilibrium:

CO2 (CO)8 + H2



2HCO(CO)4



(11)



This equilibrium is established in supercritical CO2 at 80◦ C in less than 2 hr

for both the forward and reverse reactions (55). This equilibrium was subsequently studied as a function of temperature and the reaction enthalpy (4.7 ±

0.2 kcal/mol) and entropy [4.4 ± 0.5 cal/(mol K)] were determined (56).

Co2 (CO)10 was also observed to efficiently promote the hydrogenation of

Mn2 (CO)10 (57). Using in situ 55 Mn NMR, this finding was exploited to establish the reaction enthalpy (8.7 ± 0.3 kcal/mol) and entropy [8.5 ± cal/(K mol)]

for the hydrogenation of Mn2 (CO)10 .

A second concurrent reaction involving the catalytic activity of Co2 (CO)8

is the carbonyl exchange reaction of free and coordinated carbon monoxide.

An earlier investigation of temperatures up to 80◦ C used a magnetic transfer

technique for labeling the nuclear spins to track the chemical reaction (58). In

this technique, one selectively inverts the spin population of one NMR signal

and follows the transfer of the inverted population through the chemical reaction sequence with time. With knowledge of the individual T1 relaxation times,

one can separate out the relaxation contributions and obtain the reaction rates.

At temperatures exceeding 80◦ C, the CO exchange rate was too fast to use

the magnetization transfer technique. Another study was carried out at temperatures up to 180◦ C using lineshape analysis (44). It was observed that the 13 CO

chemical shift showed a large temperature dependence. This unusual chemical

shift dependence was interpreted as a contact shift from the interaction of the

paramagnetic radical metal center ·(CO)4 with the 13 CO ligand. The tempera-



Copyright 2002 by Marcel Dekker. All Rights Reserved.



ture dependence of the contact shift was used to estimate the homolytic bond

dissociation energy of Co2 (CO)2 (19 ± 2 kcal/mol). This value compared favorable with the experimental results from magnetic susceptibility and linewidth

measurements (44), as well as the value predicted from the Marcus theory. In

contrast to Co2 (CO)8 , the CO exchange rate in the corresponding manganese

carbonyl compounds was too small to be measured (44).

The temperature–pressure behavior, as well as the solvent dependence

of the equilibrium species of phosphine-substituted and unsubstituted cobalt

carbonyl oxo catalysts, was investigated using in situ NMR techniques (59).

The solvent polarity was found to have a dramatic effect on the equilibrium

concentrations of species present and a new, as yet unidentified species was

observed to be present preferentially in nonpolar solvents.

Another investigation describes a high-pressure NMR flow cell for the

in situ study of homogeneous catalysis (60). This flow cell was constructed

from a sapphire tube and reaction intermediates from a ruthenium-rhodium

organometallic complex with CO were detected for the first time.



IV. CONCLUSIONS AND FUTURE DIRECTIONS

NMR is a very useful and versatile technique for the investigation of supercritical

fluids, gases, and liquids under extreme conditions of pressure and temperature.

Some of the examples discussed in this chapter demonstrate the potential for

studying chemical reactions and solution dynamics in supercritical fluids as a

function of density using high-pressure NMR. With pressure as a variable one

gains an understanding of the solution process that is unobtainable through temperature variation alone. Spectroscopic studies of the physicochemical properties

of supercritical fluid solutions and reactions are still at an initial stage of growth.

There are areas of current application of NMR in the arena of materials and solution chemistry that a chapter of this nature allows one to explore for their

potential impact in the future on high-pressure, high-temperature NMR studies

in fluids and liquids. A synopsis of these areas is included in the following

discussion.

A notable recent impetus for the growing interest in using supercritical

fluids as a reaction medium has come from the efforts to explore chemical routes

using carbon dioxide as a carbon source for the synthesis of organic compounds.

The exploitation of CO2 as an inexpensive, nonhazardous C1 building block for

organic reactions has long been a research topic of wide interest. However, only

since the early 1990s has it been realized that the reactant may also be used as

the supercritical solvent with beneficial miscibility and transport properties for

these reactions (61,62). Researchers in this area have traditionally used NMR

not only to identify and structurally characterize the reaction products but also to



Copyright 2002 by Marcel Dekker. All Rights Reserved.



follow reaction kinetics. However, with the exception of one early investigation

(63), these studies were exclusively conducted with ex situ NMR methods. Only

recently have in situ NMR methods been adopted in this research field (64,65).

This research area will in particular benefit from in situ high-pressure NMR

techniques because, as pointed out by Burgemeister et al., “every step of the

catalytic cycle for the rhodium-catalyzed hydrogenation of CO2 to formic acid

can be monitored by 1 H-NMR spectroscopy” (66).

A new development in high-pressure NMR probe design is a multipurpose high-pressure autoclave made from the thermoplastic polyetheretherketone

(PEEK) (67). This NMR autoclave was used for in situ NMR imaging of a

compressed gas system, namely, the exchange of methanol for liquid CO2 in

nanoporous silica-alcogels, reported for the first time.

Magic-angle spinning (MAS) solid-state NMR spectroscopy has for a number of years provided a means to study heterogeneous catalysis reactions by

directly probing the chemical species present on the catalyst surface. Some of

these experiments have been conducted at temperatures in excess of 200◦ C

(68–71) and up to 400◦ C (72). By application of laser (73) or rf heating (74),

fast transient sample heating (temperature jump) can be achieved. However, the

most interesting development is the very recent construction of an isolated flow

MAS NMR probe (75). This development has brought solid-state NMR much

closer for studying heterogeneous catalysis in supercritical fluids.

Another area of potential impact on high-pressure NMR in the future

may come from recent advances in enhancing NMR sensitivity by use of laserpolarized noble gases. The pioneering theoretical and experimental work by

Happer (76) laid the foundation for understanding the physics involved. The major research efforts in this area have focused on (a) applying the laser-polarized

noble gases directly, as in magnetic resonance imaging, or (b) transferring the

129 Xe polarization to another nuclei. Recently, significant progress has been

made in transferring the polarization from laser-polarized 129 Xe to other nuclei.

Signal enhancements of 70-fold in 13 C NMR have been achieved by crossrelaxation from laser-polarized liquid xenon (77). A further breakthrough was

recently reported by the Pines et al. (78), who can routinely polarize supercritical

xenon to enhancements of about 1000 that last for hundreds of seconds. These

reports suggest numerous applications to supercritical fluids, i.e., the study of

the efficiency of cross-relaxation from polarized supercritical xenon to dissolved

solute molecules as a function of temperature and density (pressure). Second,

a spin-labeled reactive functional group may be useful for studying chemical

reactions in supercritical xenon (or eventually in other supercritical fluids).

These are a few of many potential areas were new techniques in combination with high-pressure NMR could make an important contribution to the

fundamental understanding of solution chemistry and physics in supercritical

and high-pressure liquid solvents.



Copyright 2002 by Marcel Dekker. All Rights Reserved.