Solid-state 13C NMR investigations of monosubstituted cyclohexanes in thiourea inclusion compounds

MACjhI.TIC RTSONANCE I N C’HfMISTKY, VOL 31, 113- 123 (1095I -~

Solid-state 13C NMR Investigations of Monosubstituted Cyclohexanes in Thiourea Inclusion compounds

Klaus Miiller Institut fur Ph)slkdllsche Cheniie der Univertitat Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany

Thiourea inclusinn compounds with substituted cyclohexanes bearing polar or non-polar substituents were studied by dynamic I3C magic angle spinning NMR spectroscopy. Variable-temperature experiments were performed to evaluate the specific features of the guest molecules comprising both the kinetic and the thermodynamic aspects. Further information was also obtained about potential guest-host interactions which might have a bearing on the molecular behaviour of the guest species. Quantitative analysis in these experiments revealed that within the temperature range cnvered, the relaxation behaviour is dominated by ring interconversions of the guest molecules. In addition, reorientational motions of the guest molecules exist on a very fast time-scale which are responsible for the observed significant reduction in the anisotropic magnetic interactions. The most prominent results are the evaluated unusual conformational equilibria. It is shown that the thiourea host lattice obviously stabilizes the axial conformational state. This is true for all systems with polar substituents whereas for those with non-polar substituents the conformational equilibria are not affected. These findings are related to specific guest-host interactions, probably of a polar nature.

KEY WOKIX NMR I3C NMR MAS Inclusion compounds Monosubstituted cyclohexanes

INTRODUCTION

Inclusion compounds are still the subject of a variet)? of research activities.lP5 On the one hand, this interest originates from the numerous applications of such compounds comprising topics such as the separation of isomers, inclusion polymerization or non-linear optics. On the other hand, inclusion compounds represent suitable model systems for the study of molecular guest- host interactions. In this connection, they can provide important information about non-covalent intermolecu- lar forces which are of particular importance in the field of topochemistry and for the understanding of the func- tional behaviour of enzymes.’-’

Generally, inclusion compounds consist of a host component which builds up a lattice with some hollow space. In the presence of suitable guest specics the empty sites are populated by the guest molecules without any covalent bond formation. Depcnding on both the host and the guest species, various types of lattice structures can be formed. Among the channel- forming system^.^,^ urea6 and thiourea7 inclusion compounds have been investigated in great detail. X-ray diffraction studies have shown that both compounds build up hexagonal channel structures which are stabil- ized by hydrogen bonds and which are mainly distinguished by their cross-sectional area6-’ At the same time, the size of the host matrix channel can be re- garded also as a discriminator of the guest molecules which are included. While the smaller urea channel is

appropriate for storing linear and branched hydrocarbon chains.‘ the thiourea channel is large enough to accommodate bulkier molecules such as mono- and disubstituted cyclic hydrocarbons’ or even metal- locenes. ’’ ’

Several studies have been published primarily dealing with the evaluation of the structural and dynamic features of the guest molecules within the host channels. In this contribution, we shall focus on inclusion compounds with thiourea where for the complexes with cyclohexane and ferrocene detailed studies employing x-ray diffraction, differential scanning calorimetry and nuclear magnetic resonance (NMR) techniques have been A further active field which has attracted interest more recently is the study of substituted cyclohexanes. Here, Raman,23 IR24- 26 and NMR27 studies have indicated that the guest molecules exist in uncharacteristic conformations. Primarily, this is manifested in a strong preference for the axial conformational state as found for chloro-, brorno- and iodo- substituted cycl~hexanes.~’ It should be emphasized that these findings are in contrast to the observations in the liquid or vapour phase where usually the equatorial conformer is dominant.

In a preliminary study,” we have shown by variable- temperature I3C magic angle spinning (MAS) NMR experiments on some selected monosubstituted cyclohexanes in thiourea that the guest molecules do not exist in a single stable conformation but undergo a chemical exchange process, i.e. ring interconversion (see Scheme 1) between the axial and equatorial conformers.

CCC 0749- 1 58 1/95/0201 13- 1 1 0 1995 by John Wiley & Sons, Ltd

Receiued I9 M a y 1994 Accepted (revised) 9 September 1994

114 K. MULLER

ax Scheme 1

Further, it has been demonstrated that only cyclohexanes with polar substituents exhibit the unusual conformational behaviour in thiourea while non-polar substituted cyclohexanes, as in solution, still prefer the equatorial conformational state. To put these results on a broader basis we have performed a comprehensive variable-temperature I3C MAS NMR s t ~ d y ’ ~ . ~ ’ on a complete series of monosubstituted cyclohexanes in thiourea (see Fig. 1). The primary goals of this work are: (i) the determination of the various guest conformers and (ii) the evaluation of their conformational dynamics.

Here, the use of I3C MAS NMR techniques31 appeared to be particularly suitable since previous studies have shown that highly resolved I3C NMR spectra are very sensitive to the actual conformational state and to the specific molecular mobility of substituted cyclohexane~.~’-~~ In fact, quantitative lineshape analysis allows a reliable determination of the conformational equilibria and the kinetic parameters of the ring interconversion process. These results are discussed with consideration of the known kinetic data from solution NMR studies and are examined with respect to non-bonded interactions which might be of importance for the molecular understanding of such systems

D N H .:

= /c=s NH*

thiourea

b)

4 6

X = H OH

F SH

CI NC

Br NO,

I CH,

Figure 1. (a) Schematic representation of the channel structure in thiourea inclusion compounds. The crystallographic 32- positions are the expected locations of the guest molecules. (b) Chemical structures of the guest species used.

EXPERIMENTAL

All compounds used for these studies were com- mercially available and used as received. Inclusion compounds were prepared from a methanolic solution of thiourea and the respective guest compound as described el~ewhere.~ The compositions of the complexes were determined by ‘H NMR spectroscopy yielding thiourea-to-guest ratios in agreement with previous findings.’ Calorimetric studies of the various samples were performed using a Perkin-Elmer DSC 7 differential scanning calorimeter. The phase transitions which were observed within the relevant temperature range of the present NMR investigations are summarized in Table 1.

I3C MAS NMR experiments were performed on a Bruker MSL 300 spectrometer at a frequency of 75.4 MHz. All spectra were obtained by single pulse excitation of the carbons followed by high-power proton decoupling (decoupling power o,/2n = 62 kHz). Typi- cally 50-300 transients were accumulated at recycle delays between 12 and 15 s. Two dimensional exchange spectra were recorded with the (n/2)-t -( n/2)-~,-( n/2)-t2 sequence employing appropriate phase cycling schemes. In the t , domain 128 increments were used with a time increment of 100 ps. In all experiments the samples were spun at frequencies between about 2.5 and 3.5 kHz using a 7 mm Bruker MAS probe. The chemical shifts were referenced to poly(diethylsi1oxane) and corrected to TMS.36

The sample temperature during the MAS experiments was measured with two thermocouples which moni- tored the inlet and the outlet bearing gas temperature close to the MAS stator. They were externally cali- brated under non-spinning conditions with a third ther- mocouple placed in the rotor. The actual sample temperature under MAS conditions was justified by the phase transitions given in Table 1 and was checked with samarium acetate t e t r a h ~ d r a t e . ~ ~ At the low spinning frequencies used, heating effects due to sample rotation were not observed. Generally the temperature stability was found to be within f 1 K.

I3C NMR lineshape simulations were performed using a Fortran program which accounts for two-site exchange between sites of different chemical shifts. Descriptions of the formalism for such lineshape, simulations, including analytical expressions, can be found elsewhere. 1 , 3 8 , 3 9

Table 1. Phase transition temperatures for thiourea inclusion compounds I from differential scanning calorimetry (DSC)]

Transition Transition temperature (K) enthalpy (J g - ‘ ) Compound

C,H, ,CI-thiourea 200 2.6 C,H, , Br-thiourea 237 2.5

237 4.8 C,H, , NC-thiourea C,H,,NO,-thiourea 228 1.6

C,H, ,I-thiourea 283 1 .o

115 "C NMR INVESTIGATIONS OF INCLUSION COMPOUNDS

RESULTS

Preliminary studies on thiourea inclusion compounds have shown a pronounced temperature dependence of the 13C MAS NMR spectra of monosubstituted cyclohexane guest molecules.28 As a result, a systematic varieble-temperature I3C MAS NMR study covering a temperature range between 210 and 320 K was per- f ~ r m e d . ' ~ . ~ ~

Figure 2 illustrates a general feature encountered with the 13C NMR spectra of all the compounds studied. The I3C NMR spectra given for chlorocyclohexane in thiourea refer to experiments with and without magic angle sample spinning. The spectra clearly prove that even for the static (non-spinning) sample the linewidths and thus the chemical shift anisotropies are substan- tially smaller than those usually encountered for a complete rigid system. This observation can be attributed to the presence of fast inherent molecular motions of the guest molecules leading to a reduction of all anisotropic magnetic interactions. Such a conclusion is in line with a recent ,H NMR study of the cyclohexane-thiourea inclusion compound where the motions occurring were analysed in great detail.,, Owing to these reduced linewidths, magic angle sample spinning at moderate spinning frequencies between 500 and 1500 Hz is sufficient to obtain high resolved spectra without any spinning sidebands. Thus, all 1D and 2D NMR experiments in this study performed under MAS conditions can be dealt with like those in solution.

Representative variable-temperature 3C MAS NMR spectra of cyclohexanethiol in thiourea are depicted in Fig. 3. It should be noted that only the aliphatic chemi-

6 ( P P ~

Figure 2. Experimental 13C NMR spectra of chlorocyclohexane in thiourea under (a) magic angle spinning and ( b ) static (non-spinning) conditions ( T = 293 K).

cal shift range is displayed, which is of importance for the hydrocarbon guests. In addition, the typical spectra show a further resonance at about 160 ppm due to the thiocarbonyl carbons, which, however, is broadened by a strong dipolar coupling between the 13C and the 14N n ~ c l e i . ~ ' - ~ ~

Inspection of Fig. 3 reveals significant spectral changes with temperature, such as line broadening effects and changes in the chemical shift values, which reflect the presence of a thermally activated exchange p r ~ i c e s s . ~ ~ . ~ ~ Thus, as outlined previously,28 the signals observed in the low-temperature spectrum at 231 K should arise from the two coexisting axial and equatorial conformers. At higher temperatures, the observed spectral changes are typical of the ring interconversion process, a simple two-site exchange process between the two conformational states. Hence, the increase in linewidths of the various signals up to about 246 K corre- sponds to the 'slow-exchange' region, which is characterized by rate constants smaller than the chemical shift differences of the exchanging species. Above this temperature the lines merge together and become narrow, which is in line with the 'intermediate-' and 'fast-exchange' region. The isotropic chemical shift values detected in the 'fast-exchange' limit are the weighted averages of the chemical shift values of the axial and equatorial species known from the low- temperature spectra ((S,,,) = p , &,, a + p , &,, e , where pi is the population of conformer i, Siso, is the chemical shift value of conformer i , e means equatorial and a means axial).

From a complete lineshape analysis, taking into account the assignments from the solution NMR studies of the neat guest compounds, usually the kinetic and thermodynamic parameters of the ring interconversion process can be obtained.,' However, for the present case of cyclohexanethiol in thiourea, the analysis is more complex, since from the corresponding solution NMR studies only the equatorial conformer is k n ~ w n . ~ ~ . ~ ' Here, the assignment of the signals can be obtained on the basis of 2D NMR exchange experi- m e n t ~ . ~ ~ Figure 4 depicts a contour plot of a representative 2D 13C NMR exchange spectrum for cyclohexanethiol in thiourea at 231 K. Provided that the mixing time 5, in this experiment is chosen to be long enough that a transition between the two conforms can take place, then the observed cross peaks directly assign those signals which are connected by the chemical exchange process. Together with the known chemical shift values for the equatorial conformer,45 the assignment of the various 13C NMR signals for this sample is also possible. The temperature-dependent 1 D MAS NMR spectra (Fig. 3) can then be analysed in terms of a ring interconversion process between the axial and equatorial conformers.

Similar 13C NMR lineshape changes reflecting the ring interconversion process of the guest molecules have been found for all systems investigated except for the derivatives with X = I, NO, and NC (see Table 2). Obviously, for the latter two compounds only a single conformer, assigned to be the axial one, is present throughout the temperature range covered here. The same is true for iodocyclohexane, although the situation appears to be more complex. Here, below 260 K the

1 I6 K . MULLER

1 / T ( s e c - ' )

5.7 x 10'

246

238

I I I r I 1 50 30 10 50 30 10

6 (ppm) 6 (ppm) Figure 3. Experimental and simulated 13C MAS NMR spectra of cyclohexanethiol in thiourea. Assignments of the NMR signals are given in the experiment low- and high-temperature spectra. The parameters used for the simulations are summarized in Table 3. The rate constants are shown on the right.

observed isotropic chemical shifts correspond exactly to the values known for the axial conformer in solution, while at higher temperatures considerable changes in the chemical shift values are observed with only minor

effects on the linewidths. Since these spectral effects exhibit a hysteresis behaviour they are related to a phase transition also observed during our DSC mea- surements (see Table l).29 At present, no further infor-

Table 2. Experimental chemical shift values of monosubstituted cyclohexanes in thiourea which do not show dynamic lineshape effects

Guest compound c-1

C,Hl,I 38.0

C,HllNCb 51.6

C,H, 1 NO, 82.9

(36.8a. 29.7e)

(51 .Oa, 52.5e)

(84.6e)

Isotropic chemical shift (ppm)" C-2.6 c-3.5 c-4 Temperature ( K )

37.4 23.4 27.6 256

31.9 21.2 26.6 246

30.5 23.6 26.2 256

(36.8a, 41.4e) (23.la. 29.7e) (26.4a. 25.6e)

(31.2a, 34.3e) (20.8a. 30.3e) (25.8a, 25.8e)

(31.4e) (24.7e) (25.5e)

"The values given in parentheses refer to the solution NMR data for the axial (a) and equatorial (e) conformers taken from Refs 34 and 45. bNC: 158.1 ppm (155.3a. 153.8e).

1 I7 I3C N M R INVESTIGATIONS OF INCLUSION COMPOUNDS

!

?-------*

I 1 I I l l 1 1 I I I 1400 1200 1000 800 600 A00 ZOO 0 -?OO -400 -600

% / 2 r (Hz) Figure 4. Experimental 2D 13C N M R exchange spectrum (contour plot representation, magnitude spectrum) of cyclohexanethiol in thiourea under M A S conditions (T=231 K, mixing time T,,, = 50 ms).

mation about the nature of this phase transition is available.

The coformational characteristics of the hydrocarbon guests in thiourea are obtained from a detailed lineshape analysis of the experimental 13C MAS NMR spectra. In Fig. 3 the experimental spectra are given together with their best-fit counterparts. The parameters used for the simulations are summarized in Table 3. It

should be noted that the final adjustement of the experimental spectra requires a slight temperature dependence of the chemical shifts of about 0.003 to 0.008 ppm K - *, in agreement with previous finding^.^' In fact, the chemical shift values used in the 'fast-exchange' region are extrapolated from the observed temperature dependence in the 'slow-exchange' regime. Generally, it is found that the chemical shift values of the cyclohexane derivatives in thiourea are fairly close to those reported for solution (see Table 3). The best-fit simulations yield the relative amounts of the conformers and the rate constants l / ~ (= k , + k , = k J p , = kelpa) of the ring interconversion process of the cyclohexane guests. Semi- logarithmic plots of the rate constants as function of the inverse temperature reveal a typical Arrhenius behaviour for all compounds studied. These kinetic data further can be analysed using the empirical Arrhenius equation :

k = Aexp( - Ea/RT)

and the Eyring equation of the absolute reaction theory :

k = K(kB T/h)exp( - AG$/RT)

= K(kB T/h)exp(AS$/R)exp( - AH$/RT) ( 2 )

where A, E , , k , and K are the frequency factor, the activation energy, the Boltzmann factor and the transmis- sion coefficient (taken as K = 0.5), respectively. The remaining quantities have their usual significance. The values of AH$ and AS$ were obtained via regression analysis and are summarized in Table 4. For comparison the published data from solution NMR studies are also given. Inspection of the derived activation parameters reveals very similar enthalpy values while the activation entropies in thiourea are a factor of two higher than those reported for solution.

The conformational equilibria which are summarized in Table 5 demonstrate large discrepancies between the thiourea inclusion compound and solution. For

Table 3. Simulation parameters used for I3C NMR lineshape calculations of monosubstituted cyclohexanes in thiourea

Guest Isotropic chemical shift (ppm)" Residual compound c-1 C-2.6 c-3.5 c-4 linewidth (ppm)

C,H,,F ax

C,H,,CI ax eq

C,H,, Br ax

C,H,,OH ax eq

C6H,,SH ax eq

C,H,,CH, axc eq

eq

eq

88.7b (88.8) 92.3b (92.2) 60.2 (60.0) 59.5 (60.0) 55.2 (55.2) 52.3 (52.2) 66.7 (65.5) 71.9 (70.2) 37.8 39.0 (38.5) 28.9 (27.5) 33.8 (33.5)

31.6 (30.8) 34.0 (33.2) 34.5 (34.4) 38.9 (38.2) 35.3 (34.9) 39.5 (38.9) 33.6 (32.5) 37.2 (35.6) 34.6 40.5 (38.5) 32.3 (32.0) 36.4 (35.8)

21.1 (20.5) 25.1 (24.3) 20.7 (20.6) 27.5 (27.1) 21.4 (21.2) 29.1 (28.0) 21 .o (20.2) 26.2 (25.0) 20.9 28.6 (26.8) 21.3 (20.7) 27.5 (27.0)

26.7 (25.6) 26.1 (25.1) 26.9 (26.2) 26.0 (25.5) 27.0 (26.1) 26.0 (25.2) 27.6 (26.3) 26.5 (25.6) 27.8 26.7 (25.9) 27.7 (27.2) 27.4 (26.9)

0.18-0.26 0.1 8-0.26 0.1 94.26 0.1 9-0.26

0.1 6 0.1 6

0.1 9-0.29 0.1 9-0.29 0.1 54.35 0.1 5-0.35 0.1 5-0.31 0.1 54.31

"The values given in parentheses refer to the solution N M R data taken from Refs 34, 45, 54 and 79. bJ,,,(ax) = 168 Hz, J,,,(eq) = 172 Hz. "CH,(ax), 17.9 ppm (17.3); CH,(eq), 23.9 ppm (23.4).

118 K. MULLER

Table 4. Evaluated kinetic parameters for the ring interconversion process of monosubstituted cyclohexanes in thiourea and solution

Thiourea Solution

Guest AH%" AsV Am As%

C6H11F 57.3 61.9 43.1 3" -0.33'

C6H1 lBr 39.3 -10.0 48.91 13.1 56.5 55.2

C6H,1SH 64.0 77.4 C6HllCH3 51.5 42.3

a i2.1 kJ mol-' . b*8.5 J mol-' K- ' . The error limits given are not statistical but refer to an estimation of errors from the scatter in the data.

Ref. 35. " Ref. 55.

compound (kJ mol-') (J mol-' K - ' ) (kJ mol-') (J mol-' K-')

C6H 1 1 51.9 48.1 51.21 " 22.0"

- -

- - C6H110H

- -

example, for chlorocyclohexane in solution the relative population of the axial conformer is given by 20% (pa = 0.2) in thiourea the corresponding value is found to be 90% (pa = 0.9). A similar dramatic increase in the population of the axial conformation in thiourea is registered for all cyclohexanes bearing polar substituents, while those with non-polar substituents such as methylcyclohexane show almost identical values for solution and the inclusion compound. Likewise, cyclohexanes with substituents such as isopropyl or tert- butyl (not shown here) exist exclusvely in the equatorial conformation for both the inclusion compound and solution.

Finally, it should be noted that the conformational equilibria for the polar substituted cyclohexanes are independent of temperature. In contrast, for methylcyclohexane a satisfactory fit of the experimental line- shapes (i.e. changes in chemical shifts and linewidths) can only be achieved by including a temperature dependence of the conformational equilibrium (T = 213 K,

pd = 0.96; T = 273 K, pe = 0.77).28 This temperature dependence further allows a determination of the difference in enthalpy between the axial and equatorial conformers of methylcyclohexane where a value of AH' = - 15.5 kJ mol-' has been derived.

DISCUSSION

Although inclusion compounds with thiourea have been known for years, only the complexes with cyclohexane and ferrocene have been characterized in great detail.' 2-22 This is surprising, since former investigations have indicated a variety of unusual molecular properties of the included hydrocarbon guests. For example, in the case of substituted cycloalkanes there was evidence of significantly altered conformational e q ~ i l i b r i a . ~ ~ ~ ~ ~ , ~ ~ Likewise, calorimetric20 and magnetic resonance" investigations on thiourea inclusion compounds with cycloalkanes of different size (C,H,,-C,H,,) suggested an unusually high mobility of the guest species. The latter findings were quantified recently by a comprehensive 2H NMR study of the cyclohexane-thiourea inclusion compound22 where two relevant relaxation mechanisms of the guest molecules could be evaluated; (i) at low temperatures fast reorientational motions around the C, symmetry axis of the molecules in the GHz region and (ii) at higher temperatures above 220 K ring interconversion processes of the cyclohexane molecules in the kHz to MHz region. In addition, a high degree of orientational disorder of the guest molecules has been detected, which resembles the observations in plastic crystals49 and liquid crys- t a l ~ . ~ ~ ~ ~ ~

A recent 13C and 'H NMR study on disubstituted cyclohexanes (with non-polar substituents) came to similar conclusion^.^^ In fact, it could be shown that even these bulky compounds are highly mobile and can undergo conformational and reorientational motions

Table 5. Populations and conformational equilibria of monosubstituted cyclohexanes in thiourea and solution

Population of Equilibrium Guest axial conformers pa constant. K =p,lp,

compound Thiourea Solution" Thiourea Solution

C6H11F

C6H11CI C6H1 lBr

C 6 H 1 1 1

CGHllOH C6HllSH C6H11NC

1

C6H11CH3

0.50 0.26 (1 83 K) ' 0.90 0.20 (193 K)b 0.95 0.18 (198 K)'

>0.99 0.18 (195 K)' 0.20 10.01 (180 K)" 0.65 0.04 (193 K)"

> 0.99 0.38 (183 K)' >0.99 0.05 (193 K)"

0.01-0.23 0.01 (163 K)'

1 .o 0.36' 9.0 0.25b

19.0 0.22b >99.0 0.22'

0.25 < 0.01 1.85 0.04d

> 99.0 0.61 >99.0 0.05"

0.01 -0.30 0.01 =

a Values refer to the temperatures given in parentheses; conformational equilibria of the thiourea inclusion compounds, except for C,HllCH3, are independent of temperature. ' Ref. 33.

Ref. 34. *Ref. 46.

Ref. 79.

1 I9 I3C NMR INVESTIGATIONS OF INCLUSION COMPOUNDS

within the thiourea channels. As discussed for non- substituted cyclohexane, again the guest molecules are orientationally disordered while the positional order is unaffected. ”

The primary motivation of the present I3C NMR investigations on thiourea inclusion compounds with monosubstituted cyclohexanes was to shed further light on the specific molecular features of the guest molecules. Here, the application of dynamic 3C NMR techniques yields valuable information about the molecular properties of the guest molecules including both thermodynamic and kinetic aspects. In the following these molecular quantities will be discussed separately in concert with the results from related studies. In addition, potential interactions between the various com- ponents will be taken into consideration in order to understand the derived molecular parameters for the hydrocarbon guests examined.

Conformational equilibria

From earlier IR, Raman and NMR studies it is known that the conformational ratios of substituted cyclohexanes in thiourea are significantly altered.23-26* 48

Until recently, absolute numbers for the conformational equilibria of these systems were available only from IR i n v e ~ t i g a t i o n . ~ ~ * ~ * In contrast, I3C NMR studies performed at room temperature only allowed estima- t i o n ~ . ~ ’ Explicitly, it was unknown whether the observed NMR signals arise from two conformers undergoing fast chemical exchange or whether they stem from a single stable isomer. This latter problem could be solved easily by performing variable- temperature NMR experiments as presented in a previous preliminary communication on the cyclohexanes with X = C1, Br, CH,.’* The quantitative lineshape analysis then allowed a complete assignment of the existing conformers and their relative populations.

The conformational equilibria obtained from our present lineshape study are summarized in Table 5. The most prominent feature of this data collection refers to the unusual stabilization of the axial conformational state in the case of polar substituted cyclohexanes. Sur- prisingly, in some cases, i.e. cyclohexanol and cyclohexanethiol, the axial conformers could be established for the first time during these investigations of the thiourea inclusion compounds whereas in solution NMR studies so far only the equatorial conformers could be detected.

Generally, it should be noted that the majority of the guest molecules examined here display a finite population of both conformational states. These conformers are by no means static species. As in solution they undergo mutual exchange via the ring interconversion process. The present dynamic NMR methods can then be used to follow and characterize this process at about 100 K (see below).

The observed experimental NMR spectra suggest that three cyclohexane derivatives (X = I, NO, and NC) possess only a single stable conformer in thiourea. On the basis of the chemical shift values from solution NMR studies they have been assigned to have the axial one. Here, only the spectral assignment for nitro-

cyclohexane was not unambiguous owing to the minor differences in the chemical shift values found in the thiourea complex relative to those reported from solution, where practically only the equatorial conformational state is populated.45946 However, the present assignment is supported by an independent IR investigation which showed that nitrocyclohexane is characterized by a high population of the axial conformational state.53

In distinct contrast to the findings for the polar substituted cyclohexanes, the conformational equilibria of the cyclohexanes with non-polar substituents are not affected by the thiourea host lattice. That is, methylcyclohexane exhibits the same preference for the equatorial conformer as reported for the corresponding solution NMR studies. The same is true for isopropyl and tert-butylcyclohexane, which exist exclusively as equatorial conformer^.^^

Comparable data on the conformational equilibria of substituted cyclohexanes in thiourea are rare. Until recently such data were only available from IR s t ~ d i e s , ~ ~ , ~ ’ where also the entire halogen group has been investigated. Although those investigations already indicated the general tendency for stabilization of the axial conformers in thiourea, direct comparison with our present data displays large deviations for the absolute numbers of the equilibrium constants. For example, the IR studies on chloro- and bromocyclohexane yield equilibrium constants of 2.22 and 3.47 while our analysis of the 13C NMR spectra gives values of 9.0 and 19.0, respectively (see Table 5). These deviations probably stem from the analysis of the IR experiments, where usually identical absorption coefficients of both conformers are assumed. However, for solids such an assumption might result in an incorrect data analysis since different molecular electronic environments might affect the main direction of the polarization vector and thus the absorption coefficients. In dynamic NMR spectroscopy such limitations do not exist. At low temperatures (‘slow-exchange’ case) the equilibrium constants can be taken directly from the relative signal intensities of the two conformers. Likewise, at higher temperatures (‘intermediate-’ and ‘fast-exchange’ cases) lineshape simulations can be used to determine the relevant molecular quantities.

During the preparation of this paper we became aware of a further independent I3C NMR study on similar thiourea inclusion compounds with monosubstituted cyclohexanes (X = C1, Br, I, NH,, OH, CH3).54 Generally, the values for the equilibrium constants reported in that study are very close to those given here. However, for some compounds deviations exist which might stem from the fact that the populations given in that paper were derived from the low- temperature spectra. Here, phase transitions already might have taken place (see previous discussion and Table l), giving rise to a discontinuous change in the molecular characteristics of the guest molecules. In fact, such phase transition effects can be seen by a further splitting of the 13C NMR signals which are not due to dynamic effects but arise from the existence of species in different crystallographic environment^.^*-^^

What are the stabilizing forces for the axial conformers in thiourea? Contributions have to be considered from (i) the energy difference between the

120 K. MULLER

isolated axial and equatorial conformers (intramolecular contribution), (ii) interaction between different guest molecules and (iii) interactions between guest molecules and host matrix. In addition, both steric and polar interactions have to be taken into account. While the intramolecular conformational energy difference is usually known from either experimental or theoretical work, knowledge about the guest-guest and the guest- host interactions in these systems is limited. From the present experimental results it is obvious that in the case of the polar substituted cyclohexanes the guest- guest and the guest-host interactions must compensate the energy difference between the axial and (energetically more favourable) equatorial conformational state, which typically is of the order of a few kJ for isolated molecules.55956.

In a recent paper, Schofield et aLS7 outlined that in the chlorocyclohexane-thiourea complex the axial conformational state is favoured owing to a more efficient packing of the guest molecules (steric interactions) and a more negative guest-host energy term (presumably including both steric and polar contributions). On the basis of our experimental data we further conclude that polar guest-host interactions provide a major contribution to the stabilization of the axial conformational state, i.e. in order to compensate the conformational energy difference between the two conformers. The extent to which polarization effects or direct dipole- dipole interactions are involved is unknown so far. At the same time, steric interactions alone would be unable to explain the fact that substituents such as F, C1, or Br with a small molecular volume possess a higher tendency than the large methyl group to adopt the axial conformation.

Consequently, the observation of temperature- independent conformational equilibria of the polar substituted cyclohexanes reflects the entropy factor of these systems. For the gas phase usually it is assumed that ASa is primarily determined by vibronic5' and rotational55 contributions. In thiourea inclusion compounds an additional contribution to ASo might be expected from the orientational disorder of the guest molecules, which, as mentioned previously, in fact is very characteristic for these systems. Hence, a different degree of orientational disorder of the two conformational states presumably explains the differences found for the equilibrium constants of the various polar substituted cyclohexanes. This conclusion, however, requires further evidence. In this context, information about the overall motional dynamics and thus the orientational order of the guest molecules is highly desirable.

At the same time, the conformational equilibrium of methylcyclohexane (non-polar substituent) displays a pronounced temperature dependence, which was used to calculate the enthalpy difference between the axial and equatorial conformational state. The value of A H o = - 15.5 kJ mol-' derived from our experimental data is very close to the theoretical value of - 14.06 kJ mol-' found by Cremer et aL5' via ab initio methods for the isolated molecules. Along with the observation that the conformational equilibrium is similar to that in solution, these findings support our assumption that polar guest-host interactions are responsible for the

compensation of the conformational energy difference of the guest molecules in the thiourea channels.

In this connection the question also might arise of whether the exchanging conformers exist in two non- equivalent locations within the thiourea lattice. This problem certainly cannot be solved by the present NMR investigation. However, from the available x-ray data on the thiourea inclusion compounds with cyclohexane and chlorocyclohexane8-' there is no evidence for the presence of non-equivalent locations of the guest species within the thiourea host matrix.

Finally, it should be mentioned that unusual conformational equilibria have also been detected for other host systems. Here again, IR investigations suggested a high proportion of axial conformers for tri-o-thymotide complexes with chloro- and bromocyclohexane.60*61 Future investigations using the NMR techniques presented here might provide further information about the origin of the molecular behaviour of the cyclohexane guests within this particular host lattice.

Conformational dynamics

A further common feature of the guest molecules in thiourea inclusion compounds is manifested in their expectedly high mobility, as already suggested from very early x-ray investigations. This mobility imme- diately explains the observed reduction in orientational order of the guest molecules discussed previously. Further detailed information about the nature and the time-scale of the molecular processes in such compounds can be obtained by dynamic NMR methods, which in the past have been applied successfully for a variety of different chemical ~ y ~ t e m ~ . ~ ~ . ~ ~ * ~ ~ - ' ~

The molecular mobility of the guest molecules is primarily reflected in the corresponding I3C NMR spectra by (i) a significant reduction of the linewidths even for the static sample (see Fig. 2) and (ii) characteristic lineshape changes in the MAS NMR spectra as a function of the sample temperature. The former observation is directly related to the overall motions of the guest molecules. As mentioned before, in case of the cyclohexane- thiourea inclusion compound,22 these motional processes have been assigned to a threefold jump around the molecular symmetry axis. In a similar way, monosubstituted cyclohexanes should undergo such overall reorientational motions. However, the corresponding motional mechanisms are certainly much more complex and cannot be evaluated on the basis of the present experimental data. 'H NMR investigations of selectively deuteriated guest molecules could provide further information about this topic.

As mentioned previously, owing to the motionally induced reduction in linewidths, even slow spinner frequencies are sufficient to achieve highly resolved MAS NMR spectra without spinning sidebands.' 1-74 Like- wise, the cross-polarization technique75 does not result in a significant improvement in the signal-to-noise ratio. The latter result is in agreement with studies on other mobile system^.'^ which have shown that the polarization transfer strongly depends on the type of molecular motion and its actual time-scale. Therefore, during the present work all experiments were performed using a

I3C NMR INVESTIGATIONS OF INCLUSION COMPOUNDS

a)

C

121

Figure 5. Space filling model of a single chlorocyclohexane molecule (axial conformer) in the thiourea channel: (a) view along the thiourea channel axis; (b) view perpendicular to the channel axis. The thiourea lattice data were taken from Ref. 8. Hydrogen atoms of the thiourea molecules are not shown.

single pulse excitation of the carbons. This also ensures that the experimental signal intensities are not altered by cross polarization effects.75

The I3C MAS NMR techniques used here are particularly suitable for studying the ring interconversion dynamics of substituted cyclohexanes. This has been exploited extensively during previous dynamic 3C NMR investigations in solution. These showed that the exchanging conformers are usually well distinguished by their isotropic chemical shift value^.^*-^^ Again, the 13C NMR lineshape changes observed during our studies above about 210 K are very characteristic of the presence of ring interconversions of the guest species. Obvi- ously, substituted cyclohexanes undergo such intramolecular motions even in the presence of the large spatial constraints imposed by the surrounding rigid host matrix.

Table 4 summarizes the kinetic parameters evaluated for the ring interconversions of monosubstituted cyclo-

hexanes in thiourea. The data reveal that the activation enthalpies of the ring interconversion process in thiourea are only slightly higher than those found earlier from solution NMR studies. At the same time, the enthalpy values for most of these compounds fall within a very limited range. We therefore conclude that steric interactions by the surrounding matrix which might have some impact on the energy of the transition states are of minor importance for such conformational changes. This result is in line with the observations of the conformational dynamics of non-substituted cyclohexane in a variety of different host matrices where also no significant deviations for the activation parameters have been derived.77

On the other hand, the activation entropies evaluated for the thiourea inclusion compounds are significantly larger than those found in solution. For the gas phase it is usually considered that AS$ is dominated by a pseudo-rotation of the cyclohexanes in the transition

~ t a t e . ~ ~ ” ~ A possible explanation of the deviations found for the inclusion compounds can be given by an additional contribution to AS$ due to a decrease in the molecular orientational order of the guest molecules in the transition state. That is, in the ground state the molecular diameter of the guest species is small enough that the molecules can be placed with their molecular C , symmetry axes (neglecting the substituent) parallel to the main chanel axis (see Fig. 5). In the transition state the spatial requirement due to the substituents is expected to be higher. Therefore, the molecules must undergo some kind of reorientational motion giving rise to a reduction of the orientational order along with an increase in AS$. The slight increase observed for the A H $ values would also be consistent with this model assumption.

The fact that the values for bromocyclohexane do not fall within the range of the other compounds investigated might stem from larger errors in the analysis.28 First, the chemical shift values of the isolated isomers could not be determined since at low temperatures, before reaching the slow exchanging limit, the compound undergoes a phase transition. For the lineshape analysis, therefore, the chemical shift values from solution NMR studies have been taken. Second, within the limited temperature range the observed lineshape effects for this compound turned out to be weak, which is a direct result of the strong preference for the axial conformer (pa = 0.95).28

Generally, we can conclude that the observed deviations of the activation parameters, i.e. the activation entropies, probably arise from steric reasons due to the particular orientations of the guest molecules within the host channels. Polar effects responsible for the unusual conformational equilibria obviously have no influence on conformational kinetics. A final proof for our model assumption, however, is not possible on the basis of the present experimental data. The determination of the absolute orientations of the guest molecules within the thiourea channels might be very helpful for a more detailed interpretation of the kinetic parameters.

122 K. MULLER

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CONCLUSION

This variable-temperature solid-state 3C NMR investigation allowed a reliable determination of the molecular features of monosubstituted cyclohexanes in thiourea. By performing a quantitative lineshape analysis it can be shown that between about 200 K and room tem-

perature the ring interconversion of the guest species is the dominant relaxation mechanism. Surprisingly, the activation enthalpies of this molecular process are almost unaffected by the thiourea host matrix. On the other hand, there is evidence that the deviations found for the activation entropies are related to the orientational disorder effects which are common in such systems. In addition, fast reorientational motions of the molecules must be present which cause the experimen- tally observed reduction of all anisotropic magnetic interactions. At present the nature of these latter processes is unknown. Future studies employing ’H NMR studies of selectively deuterated samples should yield further information on this topic.

The most prominent result, however, concerns the evaluated conformational equilibria. From our data it is obvious that the thiourea host lattice exerts a stabilizing effect on the axial conformational state. Generally, this holds for cyclohexane derivatives with polar substituents where a significant increase in the population of the axial conformers is registered, which, in addition, is independent of temperature. As a result, for some compounds for the first time the axial conformers can be detected in such inclusion compounds whereas in solution or in the gas phase such conformers usually are unstable. At the same time, it is found that for the cyclohexane derivatives bearing non-polar substituents the conformational equilibria are not altered. Therefore, we attribute this unusual phenomenon primarily to the presence of polar guest-host interactions.

MAS NMR spectroscopy is a suitable method for studying the molecular properties of hydrocarbon guests in thiourea inclusion compounds, which is of particular importance for the understanding of molecular interactions in such systems. We expect that these techniques can be successfully employed with related systems. In particular, a combination of the present dynamic NMR techniques with x-ray, calorimetric and molecular mechanics studies appears to be very promising and should allow further detailed information to be obtained about the inherent interactions present in inclusion compounds.

Summing up, we have shown that dynamic

Acknowledgements

We thank Mrs D. Miiller for technical assistance during this work. Financial support by the Fonds der Chemischen Industrie i s gratefully acknowledged.

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Documents

Solid-state 13C NMR investigations of monosubstituted cyclohexanes in thiourea inclusion compounds