Glycoluril moieties

The term Molecular Clip has been coined for molecules of type 2. That these molecules do indeed possess the geometric features of a clip is apparent from the X-ray structure of the tetramethoxy derivative 3a (Fig. 2) [lla,b]. The o-xylylene moieties of this molecule define a tapering cavity, the walls of which are at an angle of 39.5 with the centers of the benzene rings 6.67 A apart. The carbonyl groups of the glycoluril moiety, which are hydrogen-bond acceptor sites, are separated by 5.52 A. It was also possible to obtain a crystal structure of the chiral dibromo-derivative 4 of clip 3 (Fig. 3). This compound was separated into its enantiomers by HPLC on a chiral stationary phase [12]. 

Although there are many non-covalent systems already developed, and a great deal of scope for more, two systems have proved to be dominant in this area. These are systems containing glycoluril moieties (see next section) and those utilising urea as linking groups (see below). 

Rebek and co-workers have also produced self-assembling capsules where the monomer possesses C3 symmetry (as opposed to C2), by incorporating multiple glycoluril moieties into a flattened aromatic surface. For example, jelly donut dimer 50 forms in CDCI3 from monomer 49. This capsule features a flattened spherical interior cavity that can accommodate disk-shaped molecules like benzene and eyclohexane (Scheme 4-11) [43]. 

Another belt-shaped molecule is cucurbituril (53) which was presumably synthesized as early as 1905 by Behrend et al. [42]. The structural formula of 53 was resolved in 1981 by Freeman. Mock, and Shih [43] only when modern spectroscopic methods were available. Cucurbituril (53) is easily obtained from urea, glyoxal, and formaldehyde in an acid-catalyzed condensation reaction with glycoluril (52) as an intermediate. The initially formed polycondensation product, insoluble in all common solvents, is treated with hot concentrated sulfuric acid. After dilution with water and subsequent boiling a solid is obtained in a yield of 40-70%. The H-NMR spectrum shows only three signals of equal intensity and the infrared spectrum suggests retention of the glycoluril moieties. The compound is not suitable for usual mass spectrometry due to its low volatility. However, an X-ray crystal structure of the calcium complex obtained from sulfuric acid solution was undertaken. 

Cucurbituril (269) is a nonadecacyclic cage compound consisting of six tetrazocane units fusing six glycoluril moieties. It is readily synthesized from urea, glyoxal, and formaldehyde (see Section 9.26.9.1.1 for details on the synthesis of cucurbituril and derivatives, and Section 9.26.3.3 for details on structure). 

Figure 3.57 (a) The unsubstituted glycoluril moiety, (b) its incorporation in a self-assembling molecule (R = C02Et) gives rise to (c) a dimeric capsule (for clarity, ethyl ester groups have been omitted). 

Figure 3 Structural representation of partially substituted Q[n], 5 = substituted glycoluril moiety, u = regular glycoluril moiety, and n = s + u. The number of s units in a substituted Q[n] is...

A molecular capsule can be composed of more than two units also a sphere can be obtained assembling together a generic number n of slices. Rebek and collaborators, in their extensive exploration of the properties and features of self-assembled capsules [36], developed a L-shaped molecule characterized by the presence at one end of the glycoluril hydrogen bond system, and at the other end, separated by an aromatic ring, a sulfamide moiety (Fig. 14). 

To fully explore the seope and limitations of the dimerization reaction we needed to access a range of glycoluril derivatives bearing a variety of substituents on their convex face, on their aromatic rings, and containing either free ureidyl NH compounds or cyclic ether moieties. The following sections outline the synthesis of those compounds. 

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