A versatile but unexpected new clathrate inclusion host Results and discussion Vi T. Nguyen, Roger Bishop,* Donald C. Craig and Marcia L. Scudder School of Chemistry, The University of New South Wales, Sydney 2052, Australia. E-mail: R.Bishop@unsw.edu.au Received 15th December 1999, Accepted 2nd March 2000, Published 8th March 2000 Racemic endo-4,endo-8-dimethylbicyclo[3.3.1]nonane-endo-2,endo-6-diol 1 forms clathrate inclusion compounds when crystallised from many common solvents. From diethyl ether solution crystals of (1)3·(C4H10O) are produced in the cubic space group Ia3. Here the diol hosts assemble by means of hydrogen bonded (O–H)6 cycles into a network structure. The guests are enclosed in cages with only dispersion forces operating between the two molecular components.Crystals of solvent-free 1, produced by sublimation of (1)3·(C4H10O) under reduced pressure, occupy the monoclinic space group P21/c. Here the diols are linked by means of hydrogen bonded (O–H)4 cycles producing layers. This structure provides no indication of packing difficulties which might have allowed the versatile inclusion behaviour of 1 to be predicted. Table 1 Numerical details of the solution and refinement of the structures (1)3·(diethyl ether) and solvent-free 1a Formula Formula mass Space group a/Å b/Å c/Å b/° V/Å3 T/°C ZDcalc/g cm–3 1.11 m/cm–1 5.5 2 qmax/° 120 No. of intensity measurements 994 1629 No. of reflections (m) and 498 1146 Variables (n) in final refinement 64 119 R = åm|DF|/åm|Fo| 0.054 0.043 Rw = [åmw|DF|2/åmw|Fo|2]1/2 0.077 0.061 s = [åmw|DF|2/(m-n)]1/2 1.64 2.08 Crystal decay 1 to 0.85 1 to 0.74 a Details of structure solution, interatomic distances, interatomic angles, and thermal parameters for both X-ray structures have been deposited at the Cambridge Crystallographic Data Centre.Click here for full crystallographic data (CCDC no 1350/13). The ability of hydroxy groups to associate as hydrogen bonded cyclic hexamers has been known for many years. This (O–H)6 supramolecular synthon is of historical significance since it helps create the host lattices of the two classical clathrate hosts hydroquinone 4 and Dianin's compound 5.7 Introduction The majority of inclusion compounds result from association of guest species with a preformed host receptor.Cyclodextrins, calixarenes, crown ethers, cryptands, and their many analogues, are familiar examples of such host systems. Alternatively, self-assembly of many hosts and guests into a closely-packed inclusion lattice can yield a clathrate compound.1 While crystal engineering methods and analogies with known behaviour can help towards rational design of new clathrate hosts,2 the role of serendipity remains important. Following the latter timehonoured method3 we report that the alicyclic dialcohol 1 is a potent new clathrate host. Crystallisation of racemic diol 1 from many common solvents results in formation of crystalline inclusion compounds. Indeed, good quality crystals of pure 1 have not yet been obtained by crystallisation from any solvent tried.This behaviour was completely unexpected despite the considerable amount of previous work on dihydroxy host molecules carried out by ourselves4 and others.5–8 For example, closely related structures such as 2 and 3 display no inclusion properties whatsoever. Diol 1 was prepared by hydrogenation of 4,8-dimethyl bicyclo[3.3.1]nona-3,7-diene-2,6-dione9 using Adams’ catalyst. From diethyl ether solution, crystals of (1)3·(C4H10O) were produced. Numerical details of the solution and refinement of this X-ray crystal structure are presented in Table 1. Six neighbouring host molecules each contribute one hydroxy group to form a cyclic hydrogen bonded hexamer (O–H)6. Each remaining diol hydroxy group participates in a further identical (O–H)6 cycle, leading to a hydrogen bonded network structure in the cubic space group Ia3.CrystEngComm, 2000, 7 (C11H20O2)3.(C4H10O) C11H20O2 627.0 184.3 Ia3 P21/c 19.966(1) 8.020(2) 19.966(1) 12.777(2) 19.966(1) 12.147(3) 90 117.61(1) 7959.3(4) 1103.0(5) 21(1) 21(1) 8 4 1.05 5.2 120Fig. 1 Part of the lattice structure of (1)3·(C4H10O) showing one complete, and several partial (O–H)6 cycles. Host oxygen atoms are red, the diethyl ether guest oxygens are dark blue and carbons light blue. Hydrogen bonds are shown as dashed lines. All hydrogen atoms are omitted for simplicity. Only one position is shown for each disordered guest. Click on the image or here to obtain a 3D view of the image, which shows the disorder.Fig. 2 Part of one layer of solid solvent-free 1 showing the arrangements of hydrogen bonded (O–H)4 cycles. Oxygen atoms are red, hydrogen bonds are dashed lines, and all hydrogen atoms are omitted for simplicity. Click on the image or here to obtain a 3D view of the image. In these structures six different host molecules each contribute one hydroxy group to the hexamer and these six contributing molecules are alternately positioned up–down– up etc. relative to the plane of the hydrogen bonded cycle. This is also the case in the structure (1)3·(C4H10O). Each (O–H)6 cycle is generated by 3 symmetry at its centre, and each disordered guest molecule also occupies a 3 symmetry site either above or below the cycle at a distance of approximately 8.6 Å from it (see Fig.1). The guests occupy cages with only dispersion forces between the two components. Sublimation of (1)3·(C4H10O) (110 °C, 2 mm Hg) gave crystals of solvent-free 1. Numerical details of the solution and refinement of this X-ray crystal structure are presented in Table 1. Four neighbouring host molecules each contribute one hydroxy group to form a cyclic hydrogen bonded tetramer (O–H)4. Each remaining diol hydroxy group participates in a further identical (O–H)4 cycle, leading to a hydrogen bonded layer structure in the monoclinic space group P21/c (Fig. 2). This (O–H)4 motif is commonly encountered amongst alicyclic diols. 10 One approach being used by synthetic chemists to obtain new lattice inclusion hosts is to design molecules which pack inefficiently by themselves.2 Normally molecules in the crystalline state are arranged to minimise intermolecular repulsions and pack as efficiently as possible, but if regular packing occupies less than about 60% of the crystal volume then an amorphous state is energetically more favourable.11–13 A greater packing coefficient then may be obtained through inclusion of guest molecules.The occupancy of pure 1 in its solid state structure is, however, a respectable 71%. Other possible signs of crystal packing difficulties can comprise incomplete hydrogen bonding, more than one crystallographically independent molecule, and disorder phenomena. In both structures here, each hydroxy group has one donor and one acceptor hydrogen bond, there is only one crystallographically unique molecule of 1, and there is no diol disorder.In short, there is nothing obvious about the structure of pure 1 which is a pointer to its strong preference towards forming lattice inclusion compounds when presented with the opportunity. This is a timely reminder that while such characteristics are useful in synthetic design, they are far from being the full story for the prediction of new hosts. Isostructural clathrate compounds are produced if 1 is recrystallised from other small organic solvents such as benzene, dioxane, or chloroform. These, and different inclusion structures of 1, are under further investigation.We gratefully acknowledge financial support from the Australian Research Council. References 1 Inclusion Compounds, ed. J. L. Atwood, J. E. D. Davies and D. D. MacNicol, Academic Press, London, 1984, vol. 1–3; Inclusion Compounds, ed. J. L. Atwood, J. E. D. Davies and D. D. MacNicol, Oxford University Press, London, 1991, vol. 4–5. 2 R. Bishop, Chem. Soc. Rev., 1996, 25, 311. 3 R. M. Roberts, Serendipity: Accidental Discoveries in Science, Wiley, New York, 1989. 4 R. Bishop, in Comprehensive Supramolecular Chemistry, ed. D. D. MacNicol, F. Toda and R. Bishop, Pergamon, Oxford, 1996, vol. 6, ch. 4, pp. 85–115. 5 E. Weber, in Inclusion Compounds, ed. J. L. Atwood, J. E. D. Davies and D. D. MacNicol, Oxford University Press, Oxford, 1991, vol. 4, ch. 5, pp. 188–262. 6 F. Toda, in Comprehensive Supramolecular Chemistry, ed. D. D. MacNicol, F. Toda and R. Bishop, Pergamon, Oxford, 1996, vol. 6, ch. 15, pp. 465–516.7 D. D. MacNicol, in Inclusion Compounds, ed. J. L. Atwood, J. E. D. Davies and D. D. MacNicol, Academic Press, London, 1984, vol. 2, ch. 1, pp. 1–45. 8 I. Goldberg, in Inclusion Compounds, ed. J. L. Atwood, J. E. D. Davies and D. D. MacNicol, Oxford University Press, Oxford, 1991, vol. 4, ch. 10, pp. 406–447. 9 P. A. Knott and J. M. Mellor, J. Chem. Soc. C, 1971, 670. 10 S. C. Hawkins, M. L. Scudder, D. C. Craig, A. D. Rae, R. B. Abdul Raof, R. Bishop and I. G. Dance, J. Chem. Soc., Perkin Trans. 1, 1990, 855. 11 A. I. Kitaigorodsky, Acta Crystallogr., 1965, 18, 585. 12 A. I. Kitaigorodsky, Molecular Crystals and Molecules, Academic Press, New York, 1973. 13 A. I. Kitaigorodsky, Mixed Crystals, Springer Verlag, Berlin, 1984. Paper a909836d CrystEngComm © The Royal Society of Chemistry 2000