MAGNETIC RESONANCE IN CHEMISTRY, VOL. 30, 228-234 (1992)

13C Magic Angle Spinning NMR Investigations of Thiourea Inclusion Compounds

Klaus Miiller lnstitut fur Physikalische Chemie, Pfaffenwaldring 55, 7000 Stuttgart 80, Germany

Thiourea inclusion compounds of three monosubstituted cyclohexanes were studied by "C magic angle spinning NMR spectroscopy. Variable-temperature experiments were performed to evaluate the conformational and motional features of the various guest molecules. From a quantitative line-shape analysis it is found that the halocyclohexanes with chloro and bromo substituents exist predominantly in the axial conformation whereas methylcyclohexane, as in solution, prefers the equatorial position. Generally, it could be shown that within the temperature range investigated the cyclohexane guest molecules undergo ring inversion processes with kinetic parameters almost unaffected by the host lattice.

KEY WORDS 13C MAS NMR Thiourea inclusion compounds

INTRODUCTION

It is well known that thiourea forms inclusion com- pounds with a variety of organic species.' X-ray diffrac- tion studieszp5 have shown that the thiourea molecules build up a channel structure similar to that discussed for urea inclusion compounds.h37 Since the cross- sectional area is larger, the thiourea channels can accommodate even bulky guest molecules, such as cyclic hydrocarbons. Detailed studies applying various experimental techniques have been performed in order to evaluate the conformational and dynamic character- istics of the guest molecules trapped in the thiourea

IR and 13C magic angle spinning (MAS) NMR investigations, for example, have shown that monosubstituted cyclohexanes with bulky polar substit- uents such as chlorine, bromine or iodine prefer the axial conformation at room ternperat~re.~. ' ' Whether this is due to a single stable conformer or to a distribu- tion of fast-exchanging equatorial and axial conformers, however, is unknown.' '

Very recently, 2H NMR studies have proved that in the case of the cyclohexane thiourea inclusion com- pound the guest molecules undergo ring inversion on a similar time scale with that reported from kinetic studies in solution."

The intention of this work was to establish whether such ring inversions are a general phenomenon of thio- urea inclusion compounds. For this purpose, thiourea inclusion compounds with three different mono-

Ring inversion

substituted cyclohexanes (X = CI, Br, CH,) were studied by means of variable-temperature ' ,C MAS NMR. Inspection of the I3C NMR line shapes clearly indicates the existence of ring inversion processes in all systems investigated. From a detailed line-shape analysis, both the relative populations of the conformers and the kinetic parameters of the ring inversion process could be evaluated.

EXPERIMENTAL

Samples of thiourea inclusion compounds were pre- pared from a methanolic solution of thiourea and the: desired guest molecules as described elsewhere. All compounds were commercially available and used a!; received.

13C MAS spectra were recorded on a Bruker MSL. 300 spectrometer at a frequency of 75.4 MHz for 13C. All spectra were obtained by 90" excitation of the carbons followed by high-power proton decoupling with recycle delays between 12 and 15 s. Typically, 50-150 transients were accumulated. The samples were spun at frequencies between 2.5 and 3.5 kHz using a 7 mm Bruker MAS probe. The chemical shifts were xefer- enced to polydiethylsiloxane and corrected to TMS.13

The sample temperature was measured with two ther-- mocouples which monitor the inlet and outlet bearing gas temperature close to the MAS stator. They were externally calibrated under non-spinning conditions; with a third thermocouple placed in the rotor. In addi-. tion, a phase transition, observed for the bromo- cyclohexane thiourea inclusion compound, could be used as a reference point. The temperature stability was generally within k 1 K.

' 3C NMR line-shape simulations were performed using a computer program which accounts for two-site exchange between sites of different chemical shifts. Descriptions of such line-shape simulations are given, for example, in Refs 14-16.

0749- 1581/92/030228-07 $05.00 1992 by John Wiley & Sons, Ltd.

Receitwd 23 Ju ly 1991 Accepted (revised) 5 November 1991

I3C MAGIC ANGLE SPINNING NMR INVESTIGATIONS OF THIOUREA INCLUSION COMPOUNDS 229

RESULTS AND DISCUSSION

Experimental temperature-dependent I3C MAS spectra of thiourea inclusion compounds with chloro-, bromo- and methyl-cyclohexane are presented in Figs 1 , 2 and 3, respectively. The observed chemical shift values of these spectra are given in Table 1. It should be noted that the high overall motional mobility of the guest molecules' already results in a substantial reduction of

the anisotropic chemical shift tensor. Consequently, cross-polarization between protons and carbons is very inef f~ ien t . '~ Much better signal-to-noise ratios could be achieved by simple 90" excitation of the carbons. Like- wise, even slow MAS at frequencies of about 1 kHz was sufficient to spin out the whole MAS sideband pattern.'

Inspection of Figs. 1-3 reveals significant spectral changes with temperature, such as line broadening effects and changes in the chemical shift values." In the

L 246

-

ch

0

213

4a

b --

3.5 . lo3

I

3a 5a

1 I I I I I I I 1

70 50 30 10 70 50 30 10

6 ( P P n - 4 6 ( P P m ) Figure 1. Experimental and simulated 13C MAS spectra of the chlorocyclohexane thiourea inclusion compound. Assignments of the NMR signals are given in the experimental low- and high-temperature spectra (a =axial, e =equatorial).

230

T(Er‘l

283

2.6

4

274

KLAUS MULLER

f / r ( s e c - ’ )

3.4 x 104 3.5

265

1

r 1 I I I 1 I 1 30 10 70 50 30 10 70 50

6 ( P P m ) 6 ( P P m ) Figure 2. Experimental and simulated 13C MAS spectra of the bromocyclohexane thiourea inclusion compound Assignments of the NMR signals are given in the experimental high-temperature spectrum.

case of the chlorocyclohexane inclusion compound, e.g. at 213 K (‘slow exchange limit’) two sets of I3C NMR signals show up which on the basis of solution NMR dataz0 couid be attributed to the chemical shifts of the corresponding axial and equatorial conformers (see Fig. 1). On heating, the rate constant of the ring inversion process increases, associated with line broadening and changes in the chemical shifts. At 283 K (‘fast exchange limit’) sharp NMR lines are again observed where the

chemical shifts are weighted averages of the values for the exchanging axial and equatorial conformers. ‘ 5 . 1 9

Similar features are visible in Figs 2 and 3 for the samples of bromo- and methyl-cyclohiexane, where gen- erally the overall line-shape effects are less pronounced than with chlorocyclohexane. However, as shown by the line-shape analysis, the spectral effects are sufficient to evaluate reliable rate constants and populations of the two conformers. Finally, it should be noted that for the

13C MAGIC ANGLE SPINNING NMR INVESTIGATIONS OF THIOUREA INCLUSION COMPOUNDS

2,6 I 1 1

1

23 1

3,4,5 I 213 5.1 x 10’

C H 3

1 , 5 . 2 ~ 104

i / r (sec-’)

bromocyclohexane thiourea inclusion compound a low- temperature ‘slow exchange’ spectrum could not be detected, since the system undergoes a phase transition associated with a complicated splitting of the NMR lines. Complementary ’H NMR and calorimetric studies are being performed to obtain further informa- tion about the molecular characteristics at this phase transition.

Line-shape simulations were performed using a two- site exchange mode1,14-16 which could be carried out

since no spinning sideband patterns were present. Otherwise, a complex computer analysis of the whole spinning sideband pattern would have been necessary.2 The simulation parameters are summarized in Table 2 and Fig. 4. The assignment of the chemical shifts for the exchanging sites is based on published data from solu- tion NMR studies on such monosubstituted cyclo- hexanes.*’ These values were adjusted to achieve a reasonable line-shape fit of the low-temperature spectra (see Table 2). The line-shape simulations of the other

232 KLAUS MULLER

Table 1. Experimental chemical shift values obtained for chloro-, bromo- and methyl-cyclohexane thiourea inclusion compounds

X Temperature ( K ) c - 1 C-2.6 c-3.5 c - 4 CH3

CI 21 3a 60.1 159.5 34.5138.9 20.6127.5 26.9126.1 231 60.2 34.7 20.6 27.0 246 60.4 35.2 21.1 27.1 265 60.4 35.5 21.7 27.1 283 60.5 35.5 21.9 27.2

Br 246 55.3 35.5 21.7 27 1 256 55.3 35.8 22.0 27.2 265 55.3 35.8 22.1 27.2 274 55.3 35.8 22.1 27.2 283 55.3 35.8 22.1 27.2

CH3 21 3 33.8 36.6 27.7 27.7 23.9 231 33.8 36.5 27.7 27.7 24.1 246 33.4 36.4 27.3 28.0 23.8 256 33.3 36.4 27.1 28.0 23.7 274 33.1 36.3 26.8 28.1 23.5

a Values refer to axial/equatorial conformers.

temperature points were then performed, accounting for a slight temperature dependence of the chemical shifts of 0.003-0.008 ppm Kp1.22

The relative populations from these line-shape simu- lations for the axial conformers are summarized in Fig. 4. In agreement with previous findings, the two halocy- clohexanes exist predominantly in the axial conforma- tion in thiourea inclusion compounds.' l Thus, the relative amount of the axial conformers is found to p,(X = CI) = 0.9 and p,(X = Br) = 0.95, respectively,

Table 2. Parameters used for the line-shape simulations of monosubstituted cyclohexanes in thiourea

Chemical shift values (pprn)

Conformer" X = C l X = Br X = C H ,

c-1 a e

C-2.6 a e

c-3.5 a e

c-4 a e

CH-3 a e

60.2 59.5 34.5 38.9 20.7 27.5 26.9 26.0

55.2 52.3 35.3 39.5 21.4 29.1 27.0 26.0

29.1 33.6 32.6 36.6 21.5 27.7 27.9 27.6 20.1 23.9

Residual line widths (pprn)

x :- CI X:Br X = C H ,

0.1 9-0.26 0.16 0.1 9-0.26

Rate constants 1 'T = k a + k e (s-l) Temperature (K) x - C I x = Br X = C H ,

21 3 221 231 246 256 265 274 283

5.0 x 10' 5.1 x 10' 1.9 x 102 2.0 x 1 o2 4.5 x lo2 8.3 x 10'

8.8 x lo3 5.0 x lo3 1.2 x lo4 3.5 x 103 2.0 x 103 4.8 x 103

2.3 x 104 9.2 x 103 2.5 x 104 6.0 x 104 2.0 x lo4 5.2 x 104 1.3 x lo5 3.4 x lo4

a = Axial, e = equatorial Residual line width of methyl group up to 0.63 ppm

and is within the sensitivity of the I3C NMR spectra, independent of the particular temperature This should be compared with the much lower values from solution NMR studies, where populations of pa(:'< = CI) = 0.2 and p,(X = Br) = 0.18 have been reported.'' At first sight it appears that spatial constraints of the thiourea host lattice are responsible for the observed strong pref- erence for the axial conformer. However, since the van der Waals radii of the chlorine and bromine substit- uents are smaller than that of a methyl group, other interactions, such as polar guest-host effects, should be taken into consideration. Here, the evaluation of the actual orientation of such guest molecules within the thiourea channels might be very helpful for the under- standing of these results. Finally, it should be noted that

t 1

d R 0.51

t + +

4 + 0.oc + +

Figure 4. Amount of axial conformers, p a , in thiourea inclusion compounds with monosubstituted cyclohexanes Substituent @, CI, m, Br. *. CH,

"C MAGIC ANGLE SPINNING NMR INVESTIGATIONS OF THIOUREA INCLUSION COMPOUNDS 233

Table 3. Activation energies evaluated for the ring inversion process of cyclohexane derivatives in thio- urea inclusion compounds and solution

Activation enthalpy. AM (kJ rnol-') X Inclusion cornpound Solution

CI 51.8 2.8 51.21 * 0.6324 Br 39.1 i 2.7 48.91 0.6324

H 43.9'2 48.2 i 1 .224 51.4 * 3.1 - CH,

c

1 0 3 / ~ ( K - ' ) Figure 5. Arrhenius representation of the rate constants, 1/r, evaluated for the ring inversion process of ( 0 ) chloro- and (m) brorno-cyclohexane in thiourea inclusion compounds.

a stabilization of the axial conformers has also been reported for other trans-1,2- and trans-l,4-disubstituted cyclohexanes in thiourea.'

A different situation is encountered for the methyl- cyclohexane thiourea inclusion compound. In this case the equatorial conformation is preferred, in agreement with previous solution NMR studies.23 As can be seen from Fig. 4, the actual population, however, is strongly temperature dependent. At low temperatures only the equatorial conformer is detected, whereas at room tem- perature the amount of the axial conformer has increased to pa = 0.26. This behaviour might originate from an increasing spatial requirement of the guest mol- ecules due to thermally activated overall motions." On the other hand, as mentioned previously, the conforma- tional ratios of the halocyclohexanes are temperature independent, within experimental error (see Fig. 4). At present no simple explanation for this phenomenon is available.

Representative Arrhenius plots of the ring inversion rate constants l / z ( l / ~ = k , + k , = ka/p,, where p e is the relative amount of equatorial c ~ n f o r m e r ' ~ ) are given in Fig. 5. The data for methylcyclohexane are not shown since they overlap to a large extent with those of chlo- rocyclohexane. The activation enthalpies were derived from the slopes of these curves, and are summarized in Table 3 together with literature values from kinetic studies in solution24 and those obtained for unsubstituted cyclohexane. Inspection of these data

reveals almost identical ring inversion parameters for the monosubstituted cyclohexanes independent of the particular host matrix, i.e. inclusion compound or solu- tion. Similar conclusions have also recently been drawn from 'H NMR investigations on the cyclohexane thio- urea inclusion compound.' 2*2 This result is surprising, since the above conformational analysis has shown a strong influence of the host lattice on the guest confor- mational state. In a similar way, an effect was expected from the thiourea channels on the activation parameters of the ring inversion process. The reason why this is not observed is not yet understood. Further investigations on related systems with bulkier substituents, also using disubstituted compounds, are in progress.

In conclusion, we have demonstrated that the ring inversion process of the guest molecules presents a major relaxation mechanism for thiourea inclusion compounds with monosubstituted cyclohexanes. From a comparison with previous kinetic studies in solution, it was concluded that this motional mechanism remains almost unaffected by the thiourea host lattice. This is contrary to the particular conformational state where the actual population of the axial and equatorial con- formers is strongly altered by the thiourea channels. As a result, cyclohexane derivatives with bulky polar sub- stituents such as chlorine and bromine preferably adopt the axial conformation.

The results presented here illustrate the potential of variable 13C MAS NMR experiments to evaluate the conformational features of guest molecules confined in thiourea inclusion compounds. Further investigations along these lines on compounds such as disubstituted cyclohexanes are in progress.

Acknowledgements

We thank Mrs Omiecienski for technical assistance during this work. Valuable discussions and the comments of Professor G. Kothe and Professor Z. Luz are gratefully acknowledged.

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