X-ray Crystal Studies of Musk Compounds

Summary

In order to have a better understanding of the mechanism of odour perception, the musk compounds have always been of particular interest. Consequently a number of structure-activity relationship studies have been advanced to correlate muskiness with the molecular properties. Since the geometry seems to playa dominant role among the characteristics used, the aim of the investigations described in this thesis was to try to obtain more direct and more reliable information on the geometry of the molecules in question by means of X-ray diffraction.
In Chapter 2 a brief survey is given of the literature of olfaction in general and musk compounds in particular.
In Chapter 3 the crystal structures of eight (nitro)benzene compounds are described. It is observed that nitro groups flanked by one or two substituents in ortho position are not coplanar with the phenyl ring. The substituent effect of a tert-butyl group on the endocyclic angles of the benzene ring is derived.
The following two chapters describe the crystal structures of bicyclic compounds: thirteen indan-related (Chapter 4) and seven tetralin-related (Chapter 5) structures. The disorder that can occur in the non-aromatic ring and/or in the nitro and acyl groups is discussed. In all compounds having a methyl group at the C(2), this group is invariably found in the equatorial position. The angle the acyl group is making with the plane of the phenyl ring varies 2-25°, even in the absence of neighbouring substituents. This is explained by the packing effects in the crystal. The acetyl group at the β-position of the aromatic ring is invariably facing the methyl group (if present) at the neighbouring β-position.
In Chapter 6 the crystal structure of a tricyclic structure is described. Its acetyl group is found to have the same behaviour as in the bicyclic compounds.
The attempts to solve the crystal structures of two macrocyclic compounds are described in Chanter 7.
The geometries of the musk and related compounds are examined in Chapter 8. The crystal structures dealt with in this thesis show that in general the orientation of the active group (nitro or acyl) is neither fixed at all, nor coplanar with the phenyl ring. The orientation of an active group is more or less fixed only when it is locked up between two bulky neighbouring groups. In that case the active group is (nearly) perpendicular to the phenyl ring. Therefore, the necessity of coplanarity as a decisive factor for muskiness can not be held.
The results of this thesis are discussed with respect to some of the existing correlation theories; in particular the one by Bersuker et al. since it is sufficiently detailed. Among the structures determined in this thesis, examples have been found in which the two fragments as defined by these authors are not observed in the crystalline state, whereas the compound shows muskiness. Also compounds have been found in which the molecular structure in the crystal is in agreement w1th Bersuker's fragments, although no odour is observed.

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