Gas Phase Applications of NMR Spectroscopy

660 GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY

Gas Phase Applications of NMR Spectroscopy Nancy S True, University of California, Davis, CA, USA

MAGNETIC RESONANCE Applications

Copyright © 1999 Academic Press

NMR spectroscopy has been used to study many aspects of the physics and chemistry of molecules in the gas phase for more than 50 years. The third report of the observation of the magnetic resonance phenomenon, which was published in 1946, described a study of H2 gas. The signal/noise ratio obtained from a 10 atm H2 sample (line width 600 ppm at 0.68 T) was ∼15/1 in that study. Nuclei in larger molecules have longer relaxation times and in many cases produce NMR spectra with natural line widths of less than 1 Hz. Currently, it is possible to obtain 1H and 19 F spectra with good signal/noise ratios from gases present at partial pressures of less than 1 torr. With this sensitivity, NMR spectroscopy can be used to address many questions about molecular interactions and dynamics in the gas phase. Experimentally measured chemical shifts and spin–spin coupling constants of gas-phase molecules are a benchmark for theoretical calculations of NMR parameters. Temperature- and pressure-dependent relaxation rate constants, T1, T2, and T1ρ, have been measured for several different nuclei in diatomic and small polyatomic molecules in the gas phase. These data provide information about relaxation mechanisms, rotationally inelastic collision cross sections, coupling constants and intermolecular forces. NMR spectroscopy is an important tool for studying hydrogen bonding in the gas phase. Thermodynamic parameters for keto–enol tautomeric equilibria and conformational equilibria of gases have been determined from measurements of temperature-dependent relative intensity ratios. Temperature- and pressure-dependent rate constants for low-energy intramolecular chemical exchange processes of gases including conformational interconversion, ring inversion and Berry pseudorotation have been measured using NMR spectroscopy. The motion of xenon atoms diffusing in zeolite matrices and the motion of gas-phase molecules in protein cavities can be studied using NMR spectroscopy. Gas-phase NMR spectroscopy can be used to study chemical reactions involving volatile species. Densitydependent chemical shielding and gas-phase spin– lattice relaxation were reviewed a few years ago. The application of gas-phase NMR spectroscopy to chemical exchange processes was reviewed more recently.

Principles Gas-phase chemical shifts and coupling constants

The general features of high-resolution NMR spectra of gases resemble those of liquids, but the actual resonance frequencies in the gas phase and in solution are different owing to differences in the local environment. A gas sample has a smaller bulk magnetic susceptibility and weaker intermolecular interactions than a liquid. The bulk magnetic susceptibility difference causes the entire gas-phase NMR spectrum to be offset a few ppm from that of the corresponding liquid. The direction and magnitude of the offset depend on the magnetic field strength, the shape of the sample, its orientation in the magnetic field and its chemical composition. The magnetic field experienced by the sample, B0(s), is B0(s) = B0[1+(4π/3 – α)κs], where B0 is the permanent magnetic field, κs is the volume susceptibility, a negative quantity which is much smaller for a gas than for a liquid owing to density differences, and α is a shape factor that is zero for a cylinder aligned along the magnetic field axis and 2π for a cylinder aligned perpendicular to the field axis. For the parallel arrangement of a cylindrical sample in a 7.2 T superconducting magnet, the gas-phase spectrum is shifted a few ppm to higher frequency from the spectrum of the corresponding liquid. In the gas phase, intramolecular factors primarily determine the relative resonance frequencies of the nuclei in a molecule. In a liquid, intermolecular interactions are also an important factor and the relative resonance frequencies of nuclei located at different sites within a molecule can be phase dependent. The largest phase-dependent shifts in relative resonance frequencies occur for nuclei in positions near the molecule’s exterior and for nuclei capable of strong intermolecular interactions such as hydrogen bonding. Figure 1 shows gas-phase NMR spectra of a series of alcohols obtained at 421 K. The major difference between these spectra and those of the corresponding liquid alcohols is the position of the hydroxyl proton resonance which, in each case, is near 0 ppm relative to gaseous TMS. The hydroxyl proton resonances of the corresponding alcohols in

GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY 661

Figure 1 1H NMR spectra of gaseous t-butanol (A), isopropanol (B), ethanol (C), and methanol (D) at their respective vapour pressures at 421.8 K. Reprinted from Chauvel JP Jr and True NS (1985) Gas-phase NMR studies of alcohols. Intrinsic acidities. Chemical Physics 95: 435–441, © 1985, with permission from Elsevier Science.

the liquid phase are several ppm lower than that of liquid TMS owing to participation in intermolecular hydrogen bonding. In contrast, the position of the resonances of the protons attached to the carbon atoms relative to TMS is similar for both gas-phase and liquid alcohols. For cases where intermolecular interactions are weaker, gas and solution spectra are more similar, but small relative changes are often observed. For example, the limiting 1H methyl chemical shift differences for dimethylacetamide and dimethylformamide are slightly smaller in the gas phase than in solution. The temperature and density dependences of the chemical shifts of nuclei of gas-phase molecules have received significant theoretical and experimental

attention. The chemical shifts of most nuclei at a constant temperature exhibit a linear density dependence for moderate densities up to ∼50 atm. Intermolecular effects are deshielding for almost all gas-phase molecules, except for molecules with π* electronically excited states. The temperature dependence of the chemical shift of nuclei of gas-phase molecules at constant gas density can be used to probe the effects of ro-vibrational shielding. Deshielding occurs with increasing temperature as the population of rotationally and vibrationally excited states increases and the average internuclear distances in the molecule increase. The phase dependence of spin–spin coupling constants is usually small since spin–spin coupling mechanisms are primarily intramolecular in nature. However, changes in conformational equilibria and molecular geometry can result from intermolecular interactions and can affect the magnitude of spin– spin coupling constants. For example, the magnitude of the spin–spin coupling between two nuclei separated by three bonds is dependent on the effective torsional angle and will be phase dependent if the conformational equilibrium established in the gas phase differs from that in solution. For substituted ethanes such as dimethoxyethane, the average 3JHH coupling constants in the gas phase have been measured as a function of temperature and used to determine conformational equilibria and barriers to internal rotation using models based on the Karplus equation. Solvent effects are determined by comparison with results of similar experiments performed on condensed-phase samples. Small phase-dependent differences in the 1JNH and 2JNH coupling constants of formamide have been observed and can be attributed to changes in bond lengths that occur upon solvation. For molecules that do not exhibit conformational isomerism or form strong intermolecular interactions, gas-phase and solution-phase spin–spin coupling constants are very similar. Relaxation

Nuclear spin–lattice relaxation of gas-phase molecules occurs primarily via the spin–rotation (SR) mechanism. The magnitude of the magnetic field generated by the rotational motion of the molecule changes at a rate that is dependent on the rotationally inelastic collision frequency. Scalar coupling of the nuclear spin angular momentum to this timedependent field provides an efficient relaxation pathway that is generally not available in condensed phases where rotational motion is hindered. For medium-sized molecules, 1H and 13C T1 values are typically on the order of a few hundred milliseconds

662 GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY

Figure 2 The density dependence of the proton T1 of ammonia gas at 300 K. The density of an ideal gas at STP is defined as 1 amagat. The solid line is the best fit of a theoretical model that allowed for multiple relaxation times to the data. Reproduced with permission of the American Physical Society from Lemaire C and Armstrong RL (1984) Proton spin longitudinal relaxation time in gaseous ammonia and hydrogen chloride. Journal of Chemical Physics 81: 1626–1631.

and 19F T1 values are typically on the order of 10 to 100 ms at a gas pressure of 1 atm. Figure 2 shows the characteristic nonlinear density dependence of T1 in the gas phase. Most NMR relaxation studies of gases report gas densities in units of amagats where 1 amagat is the density of an ideal gas at 1 atm and 273 K, i.e. 2.687 × 1019 molecules cm–3, or 44.612 moles m–3. At the T1 minimum, the collision frequency is approximately equal to the Larmor precession frequency of the nucleus. The T1 minimum can be used to determine the rotationally inelastic cross section, σNMR, and the average spin–rotation (SR) coupling constant. The density-dependent T1 data for the 1H resonance of NH3, shown in Figure 2, is consistent with a σNMR of 105(8) Å2. This value is almost twice as large as the geometric cross section of the molecule, 60 Å2, indicating that long-range interactions are important in the relaxation process. The effective 1H SR coupling constant of NH3 is 20.3(0.1) kHz, considerably larger than the 1H–1H dipole–dipole coupling constant in this molecule. Relaxation via dipole–dipole interactions and quadrupolar interactions has also been observed for

nuclear spins of molecular gases. Dipole–dipole relaxation is competitive with spin–rotation relaxation of H2 in the gas phase. For H2, the SR coupling constant is ∼110 kHz and the dipole–dipole coupling constant is 143 kHz. This mechanism has not been found to contribute significantly to spin– lattice relaxation of larger molecules, where dipole– dipole distances are greater. The lack of observable nuclear Overhauser enhancement (NOE) in gaseous benzene indicated that relaxation via dipole–dipole interactions is not significant at densities between 7 and 81 mol m–3 at 381 K. For 14N in nitrogen gas, the dominant relaxation mechanism is through intramolecular quadrupolar interactions. Experiments on ClF established that there is a significant contribution to T1ρF from modulation through quadrupolar relaxation of 35Cl and 37Cl of J(35Cl–F) and J(37Cl–F). The dependence of T1ρF on the spin-lock field strength allowed values of these two spin–spin couplings to be obtained. Dipole–dipole interactions occurring during collisions provide a relaxation mechanism for atoms in the gas phase. Xenon-129 atoms in the gas phase have spin–lattice relaxation times on the order of minutes which are dependent on gas density, temperature and the amount of other gases in the sample. For xenon-129 adsorbed in cavities inside zeolite matrices relaxation occurs via dipole–dipole interactions with hydrogen atoms that are bound to the sides of the cavities.

Methods Sample preparation

For many applications, gas-phase samples can be prepared using a routine vacuum line consisting of mechanical and diffusion pumps, a cold trap, thermocouple and capacitance manometer gauges and a manifold with attachments for sample tubes and gas inlets. NMR sample tubes are either sealed with a glass torch or constructed with self-sealing top assemblies. Preparation of samples at elevated pressures requires quantitative transfer operations. With few exceptions, gas-phase NMR samples used to study conformational processes contained a volatile bath gas in addition to the sample molecule, which usually has a low vapour pressure. Molecules with low vapour pressures tend to behave nonideally even at very low pressures and this factor must be taken into consideration when converting measured gas pressures into densities. Sample diffusion and convection are significant problems in temperature-dependent studies and in relaxation experiments using gases. In most NMR

GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY 663

probes the heater is positioned below the bottom of the sample and the top of the sample protrudes above the spinner. With this arrangement a significant temperature gradient occurs along the length of a standard NMR tube when working at elevated temperatures. This causes convection in the sample and makes it impossible to establish, maintain and measure the temperature. Diffusion can cause significant line broadening at low pressures and can result in large systematic errors in relaxation measurements. To minimize these problems, short NMR tubes are frequently used for gas-phase studies. They provide better temperature control and minimize diffusion of magnetized molecules from the active volume region of the receiver during monitoring of the free induction decay. For relaxation studies of gases, the sample must be confined to the active volume of the receiver for accurate measurements of relaxation times and the tube length cannot exceed the receiver coil dimensions. Short tubes can be placed directly inside a standard size coaxial outer tubing to facilitate sample spinning or they can be attached to a spinner via a stem. For samples containing total gas pressures of 3 atm and below, sample cells constructed from standard thickness 12, 10, or 5 mm o.d. NMR-quality glass tubing have been employed. Sample cells constructed from heavy-wall NMR-quality glass tubing, single-crystal sapphire and vespel can be used for studies of gases at pressures above 1 atm. Special precautions are necessary at all stages of assembling, testing and using any kind of high-pressure NMR apparatus because of the hazards involved. Samples in the 5–50 atm range can be prepared in small-diameter tubes with 2 mm thick walls that can withstand pressures of 50 atm. The maximum pressure is limited by the ratio of the outer diameter to the inner diameter of the tube. Pyrex and borosilicate glasses have been used. Xenon gas has been studied at pressures up to 200 atm in borosilicate glass (3.9 mm o.d./1.2 mm i.d.) Methane and ethane have been studied at pressures up to 300 atm in Pyrex tubes (5 mm o.d./0.5 mm i.d.) Sample cells constructed from single-crystal sapphire epoxied to titanium flanges that attach to vacuum lines have been used to prepare samples containing gases at pressures up to about 130 atm. A newer design allows use with 5 or 10 mm tubes, is light enough to allow spinning in most spectrometers and allows attainment of proton line widths of 0.5 Hz in 300 MHz spectrometers. Heavy-walled Vespel tubes have been used to study reactive systems at elevated pressures. This polyimide material is resistant to chemical attack but heavy walls are required and after several pressurizations the tubes tend to deform.

Specially designed NMR probes capable of withstanding high internal pressures have been described. Improved sensitivity and resolution have been obtained with toroidal probes. They consist of a toroidal-shaped RF detector inside a pressure vessel with RF and gas connectors mounted on the top and bottom, respectively, and are useful for studying pressurized reactor effluent. Spectral acquisition

Gas-phase NMR spectra can be acquired using procedures similar to those employed for liquid samples. Most gas-phase NMR spectra are obtained without use of a frequency lock. The field drift of most superconducting magnets is only a few hertz per day and does not contribute significantly to observed line widths of spectra acquired in a few hours or less. The absence of a lock necessitates that shimming must be done by observing the magnitude and shape of the free induction decay. Inclusion of several torr of TMS gas ensures a free induction decay of adequate magnitude for shimming. For very high-resolution work or long runs, a deuterated bath gas such as neopentane-d12 or isobutane-d10 can be used, but the low sensitivity in the lock channel on most spectrometers requires the presence of a partial pressure of at least 0.5 atm of these molecules to achieve a stable lock. Acquisition of gas-phase NMR spectra is facilitated by rapid spin–lattice relaxation. This is especially true for 13C studies of gases where T1 values can be hundreds of times shorter than in condensed phases and transients can be acquired much faster. However, relaxation times and mechanisms in the gas phase preclude many experiments involving intermolecular and intramolecular polarization transfer that are routinely performed on solution samples.

Applications Specific applications of gas-phase NMR spectroscopy to research in heterogeneous catalysis, conformational dynamics and absorption processes in zeolites are described below. The application of gas-phase NMR spectroscopy to many other research areas is described in the Further reading section at the end of this article. Heterogeneous catalysis

Gas-phase NMR can be used to study the kinetics of reactions that consume or generate volatile species. In a recent study, gas-phase NMR spectroscopy was used to follow the kinetics of the hydrogenation of cis/trans mixtures of perfluoro-2-butenes (R=CF3) and perfluoro-2-pentenes (R=C2F5) over palladium

664 GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY

supported on alumina (Eqns [1] and [2]).

Samples were prepared in 12 mm NMR tubes and contained a total gas pressure of ∼3.1 atm at 333 or 338 K. The time dependence of the composition of the sample was determined from 19F NMR spectra. Since the T1 values of all the 19F nuclei present are short, it was possible to obtain spectra, the result of 16 transients, with a signal/noise ratio of 1000 in 2.9 s. The data obtained in these experiments would be very labour intensive to obtain by conventional chemical techniques. Figure 3 shows typical data obtained in this experiment. The erythro/threo product ratio was the same as the starting cis/trans reactant ratio, indicating that the olefins did not isomerize during the reaction and hydrogenation of the cis olefins produces the corresponding erythro hydrofluorocarbons while hydrogenation of the trans olefins produces the corresponding threo hydrofluorocarbons. The rate of hydrogenation was faster for the trans isomer of both perfluoro-2butene and perfluoro-2-pentene, with the rate constant ratio, ktrans /kcis , ranging from 2 to 3.4. It was also found that the cis isomers are preferentially absorbed on the catalyst, a fact that may account for their lower relative reactivity.

Figure 3 Time dependence of the concentrations of reactants and products of the Pd/Al2O3-catalysed hydrogenation of a 24.8/ 75.2% cis/trans mixture of perfluoro-2-pentene at 65°C obtained by 19F gas-phase NMR. Reprinted with permission from Kating PM, Krusic PJ, Roe DC and Smart BE (1996) Hydrogenation of fluoroolefins studied by gas phase NMR: a new technique for heterogeneous catalysis. Journal of the American Chemical Society 118: 10 000–10 001. © 1996 American Chemical Society.

and kinetic parameters can be compared with similarly obtained parameters in condensed phases to determine the direction and magnitude of solvent effects on these processes. Gas-phase results also provide a critical test for theoretical calculations. The pressure dependence of rate constants for chemical exchange processes in the gas phase provides information on the microscopic dynamics of these processes in isolated systems. Rate constants for the chemical exchange processes that occur in alkyl nitrites, cyclohexane, substituted cyclohexanes, sulfur tetrafluoride and formamide are pressure dependent. The mechanism for these thermally initiated, unimolecular gas-phase processes, reported by Lindemann in 1922, involves competition between the reaction and collisional deactivation of the critically energized molecule, A* (Eqn [3]).

Conformational kinetics

For many gas-phase molecular processes with activation energies in the 5–20 kcal mol–1 range, temperature- and pressure-dependent rate constants can be obtained from analysis of exchange-broadened NMR line shapes. Frequently, rate constants can be obtained with accuracy comparable to that obtained in the best liquid-phase studies. This technique can be applied successfully to gases that have at least 1 torr of vapour pressure at temperatures at which slow or intermediate exchange can be observed. Temperature-dependent gas-phase rate constants

where ka, kd and k(E) are the rate constants for activation, deactivation and reaction. The rate constant for reaction, k(E), is energy dependent. The solution of this mechanism yields the macroscopic

GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY 665

pseudounimolecular rate constant, kuni (Eqn [4]).

At large [M] the integrand reduces to k(E)ka/kd and kuni is a constant. At small [M] the integrand reduces to ka[M] and kuni is a linear function of the gas density. The zero of energy is taken at the energy at threshold. The details of the fall-off curve, i.e. the rate constant kuni as a function of gas density, provides information about intramolecular energy transfer in the critically energized molecule. If this is ergodic and rapid on a timescale that is short compared to the reaction rate constant, statistical theories such as RRKM theory can be used to calculate k(E). The molecular conditions that favour statistical behaviour are high densities of states in the reactant and efficient coupling mechanisms. Reactions of large molecules at high internal energies can generally be modelled adequately with statistical theories. The processes that can be studied by gas-phase NMR spectroscopy occur at much lower energies where state densities are sparse and coupling mechanisms are inefficient. The shape and location of the experimental fall-off curves of chemical exchange processes provide a test of the applicability of statistical kinetic theories to these low-energy processes. Figure 4 shows exchange-broadened gas-phase 1H NMR spectra of n-propyl nitrite obtained at 240.6 K as a function of CO2 bath gas pressures. Each sample contained 2 torr of n-propyl nitrite. Rate constants for the syn–anti conformational exchange process, obtained from the spectral simulations, range from 315 s–1 at 720 torr to 112 s–1 at 11.8 torr. The pressure dependence of these rate constants was compared with predictions using RRKM theory. The agreement obtained indicated that vibrational redistribution in n-propyl nitrite is statistical or nearly so at the average internal energy required for the syn– anti conformational interconversion process, which is ~12 kcal mol–1. The observed fall-off curve is dependent on the bath gas used in the study and relative collision efficiencies for activation of the conformational process can be obtained from studies that vary the bath gas. Smaller nitrites, SF4 and formamide have lower state densities and are currently the subjects of detailed analysis. Absorption processes in zeolites

Several factors make xenon a very useful probe nucleus for studying absorption processes in

Figure 4 Gas-phase 1H NMR spectra of n-propyl nitrite at 240.6 K. The spectral region shown corresponds to the methylene protons attached to the carbon bonded to the oxygen. Samples contained 2 torr of n-propyl nitrite and various pressures of CO2. Spectral labels refer to the total sample pressure in torr. In each plot the top trace is the simulated spectrum, the middle trace is the experimental spectrum and the lower trace is the difference between the two. Reprinted with permission from Moreno PO, True NS and LeMaster CB (1990) Pressuredependent gas-phase 1H NMR studies of conformational kinetics in a homologous series of alkyl nitrites. Journal of Physical Chemistry 94: 8780–8787. © 1990 American Chemical Society.

666 GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY

microporous materials such as zeolites. It is chemically inert, monatomic and of a convenient size, and its chemical shift is very sensitive to environmental factors and is amenable to theoretical modelling. Two of the stable isotopic species of xenon, 131Xe and 129 Xe have magnetic moments. 129Xe, which has a spin of , a natural abundance of 26.44%, a receptivity 31.8 times greater than 13C and T1 values on the order of seconds, is the most extensively used. The effects of environmental interactions on the chemical shift of xenon have been modelled using grand canonical Monte Carlo simulations, allowing the determination of the cluster size of xenon in cavities in a zeolite from chemical shift measurements. A recent study of xenon adsorbed in AgA zeolite, which is a system of silicoaluminate cages containing charged Ag clusters separated by 8-membered Si–O–Si rings,

demonstrated that up to 10 different cluster sizes could be distinguished by their differences in chemical shifts. Figure 5 shows static NMR spectra of 129Xe in AgA zeolite. Spectral labels refer to the zeolite composition, dehydration temperature, and average number of xenon atoms per cage. Chemical shifts are referenced to xenon gas present in spaces between the crystallites. Exchange between cages is slow and the 129 Xe NMR spectrum consists of a series of lines corresponding to cages with different numbers of xenon atoms. The 129Xe resonances from high field to low have chemical shifts that range over 200 ppm and are assigned to cages containing from 2 to 8 xenon atoms. Xenon intercage exchange dynamics can be studied using 2D-EXSY experiments. If chemical exchange occurs on the order of the mixing time, off-diagonal cross peaks appear in the 2D spectrum between the

Figure 5 NMR spectra of xenon in AgA zeolite. The axis in each spectrum is labelled in ppm with 0.00 ppm corresponding to the chemical shift of xenon gas in the space between the crystallites in the sample. Spectral labels refer to the zeolite composition, sample preparation temperature, and the average number of xenon atoms per α cage. The progression of lines to lower field corresponds to resonances from 1 xenon atom per α cage to 8 xenon atoms per α cage, respectively. Reprinted with permission from Moudrakovski IL, Ratcliffe CI and Ripmeester JA (1998) 129Xe NMR study of adsorption and dynamics of xenon in AgA zeolite. Journal of the American Chemical Society 120: 3123–3132. © 1998 American Chemical Society.

GAS PHASE APPLICATIONS OF NMR SPECTROSCOPY 667

sites involved in the exchange. The cross peaks provide information about the exchange pathways and their intensities are a function of the exchange rate constant. Rate constants for exchange between cages indicate that sorption energies decrease at higher loading.

List of symbols B0(s) = magnetic field experienced by sample; ka, kd, k(E) = rate constants for activation, deactivation, reaction; kuni = macroscopic pseudo-unimolecular rate constant; α = shape factor; κs = (sample) volume susceptibility; σNMR = rotationally inelastic cross section.

See also: High Resolution IR Spectroscopy (Gas Phase) Applications; High Resolution IR Spectroscopy (Gas Phase) Instrumentation; NMR Relaxation

Rates; Parameters in NMR Spectroscopy, Theory of; Xenon NMR Spectroscopy.

Further reading Armstrong RL (1987) Nuclear magnetic relaxation effects in polyatomic gases. Magnetic Resonance Review 12: 91–135. Dybowski C and Bansal N (1991) NMR spectroscopy of xenon in confined spaces: clathrates, intercalates, and zeolites. Annual Reviews of Physical Chemistry 42: 433–464. Jameson CJ (1991) Gas-phase NMR spectroscopy. Chemical Reviews 91: 1375–1395. True NS (1996) Gas phase studies of chemical exchange processes. In: Grant DM and Harris RK (eds) Encyclopedia of NMR, pp 2173–2178. New York: Wiley. True NS and Suarez C (1995) Gas-phase NMR studies of conformational processes. In: Hargittai M and Hargittai I (eds) Advances in Molecular Structure Research, Vol 1, pp 115–155. Stanford, CT: JAI Press.

GC–IR Applications See Chromatography-IR, Applications.

GC–MS Methods See Chromatography-MS, Methods; Hyphenated Techniques, Applications of in Mass Spectrometry.