Host compound

Fig. 26. Clathrate receptor chemistry (a) a chiroselective crystalline host compound (clathrand) (b) a typical guest molecule to be included in the specified configuration and (c) the crystal stmcture of the respective clathrate (A and B denote host and C the guest species) (169).

There is, however, another possible explanation. For relatively weak complexes, as in these cases, a complex other than one of the insertion type may form in solution, for example a charge-transfer complex. An early observation which may indicate the formation of other types of complexes was reported by Bartsch and Juri (1980), but not interpreted the dediazoniation rate for 4-tert-butylbenzenediazonium tetra-fluoroborate in 1,2-dichloroethane decreases by 12% in the presence of one equivalent of 15-crown-5, a host compound which does not form insertion complexes. Kuokkanen and Virtanen (1979) also observed some stabilization towards dediazoniation of 2-toluenediazonium ion by 18-crown-6, even though, for steric reasons, an insertion-type complex is hardly possible in this case. 

Kuokkanen (1986, 1987 a, 1991) supported the proposal of Nakazumi et al. (1983) based on kinetic and spectrophotometric comparisons of arenediazonium salt solutions in the presence of 18-crown-6 and pentaglyme. He also extended the systematic work on complex formation of benzenediazonium salts, substituted in the 2-position, and in the presence of 15-crown-5 (Kuokkanen, 1990 Kuokkanen et al, 1991). He discovered a useful way to differentiate between the two types of complexes in Scheme 11-2. Increasing the relative concentration of the host compound shifts the ultraviolet absorption band of both types of complex hypsochromically, whereas the NN stretching frequencies are significantly increased only in the case of insertion complexes. ... 

Other molecules include cryptophanes (e.g., 23), ° hemispherands (an example is 24 ° ), andpodands The lastnamed are host compounds in which two or more arms come out of a central structure. Examples are 2S °° and 26. ° Compound 26,... 

Enantioselective bromination of cyclohexene (11) in an inclusion complex with the optically active host compound, (i, i )-(-)-trans-4,5-bis(hydroxy-diphenylmethyl)-2,2-dimethyl-l,3-dioxacyclopentane (10a) was accomplished. 

An enantioselective Michael addition reaction was also accomplished in an inclusion complex with a chiral host compound. Treatment of a 1 1 complex of 10c and 66b with 2-mercaptopyridine (137) in the solid state gave (+)-138 of 80% ee in 51% yield. By a similar method, 3-methyl-3-buten-2-one (139) gave (+)-140 of 49% ee in 76% yield [30]. 

It is not easy to control the steric course of photoreactions in solution. Since molelcules are ordered regularly in a crystal, it is rather easy to control the reaction by carrying out the photoreaction in a crystal. However, molecules are not always arranged at an appropriate position for efficient and stereoselective reaction in their crystals. In these cases inclusion chemistry is a useful technique, as it can be employed to position molecules appropriately in the host-guest structure. Chiral host compounds are especially useful in placing prochiral and achiral molecules in suitable positions to yield the desired product upon photoirradiation. Some controls of the steric course of intramolecular and intermolelcular photoreactions in inclusion complexes with a host compound are described. 

Furthermore, it is often possible to extract from the structural analysis of solid solvates a significant information on solvation patterns and their relation to induced structural polymorphism. An interesting illustration has been provided by crystal structure determinations of solvated 2,4-dichloro-5-carboxy-benzsulfonimide (5)35). This compound contains a large number of polar functions and potential donors and acceptors of hydrogen bonds and appears to have only a few conformational degrees of freedom associated with soft modes of torsional isomerism. It co-crystallizes with a variety of solvents in different structural forms. The observed modes of crystallization and molecular conformation of the host compound were found to be primarily dependent on the nature of the solvent environment. Thus, from protic media such as water and wet acetic acid layered structures were formed which resemble intercalation type compounds. 

Nevertheless, as in many previous observations, the clathrate formation by dipolar host compounds could not have been predicted in advance. In fact, there are no channels in the crystal structures of hydrated moxnidazole hydrochloride (closely related species to furaltadone hydrochloride) and of hydrated furaltadone base (Fig. 13)37). Rather, the latter two structures are best described as solvates with the H20 molecules contained in local voids between adjacent moieties of the host. 

The question that emerges at the climax of this survey relates to the possibility of using crystalline inclusion phenomena for optical resolutions of molecular species. Can this be done effectively with suitably designed host compounds The definitely positive answer to this question has elegantly been demonstrated by Toda 20) as well as by other investigators (see Ch. 2 of Vol. 140). An optically active host compound will always form a chiral lattice. Therefore, when an inclusion type structure is induced, one enantiomer of the guest moiety should be included selectively within the asymmetric environment. 

Accordingly the most important feature of a host compound designed for coordina-toclathrate formation 2) is a bisection in the molecule, as schematically shown in Fig. 7, providing ... 

Table 4. Selective guest inclusion of host compound 13...

A careful examination of the results given in Tables 7 and 8 reveal that with the exception of 2,3-dimethyl-2-butene (in the case of 47) only cyclic guest molecules are taken up into the lattices of the host compounds 46-48, but not the respective open-chain analogues. Saturated 2,3-dimethylbutane, as a compound for comparison, is not accommodated either, either by 46 or by 47. Moreover, only cycles with distinct ring sizes (five- to eight-membered rings) are effective, indicating the presence... 

Comparison (Tables 7-9) shows that 47 and 48 are similar in their host properties, but they are not equivalent in hehavior. Thus, host compound 48 is more qualified to select according to spatial aspects (see benzene derivatives) and, as a rule, it also forms the thermally more stable inclusions. This may be attributed to the rigid molecular geometry of the spirane 48, whereas the biaryl 47 allows sterical adaptation to different guests via the flexible hinge to a certain degree. 

Fig. 16. Stereo drawing of the packing in the crystal structure of free host compound 4874) (H atoms are shown as sticks only)...

Shape and Symmetry Considerations Dihedral Angles of Host Compounds... 

When guest molecules are arranged together in the channel of a host-guest inclusion complex, intermolecular reactions of the guest compound may proceed stereoselec-tively and efficiently. An enantioselective reaction is expected when optically active host compounds are used. 

All host compounds except 8-10 have been described in vol. 140 of this series, Molecular Inclusion and Molecular Recognition-Clathrates I . The new host compound (—)-8a was prepared by reaction of PhMgBr and (—)-trans-4,5-bis(ethoxycarbonyl)-... 

Host compound Guest compound Reaction time (h) Inclusion complex ... 

Furthermore, irradiation of a 1 4 mixture of 1 and 11a under the same conditions as above for 72 h gave 13a in 87 % yield. This result shows that the host compound 1 was used almost twice like a catalyst. This is illustrated in Scheme 2. By mixing 1 and 11a, the 1 2 inclusion complex is formed, and irradiation of the complex gives 1 and 13 a. Further mixing of the recovered 1 and 11a forms a new complex which upon irradiation gives 13a again. 

Heating of a mixture of pinaeol 41 and 33% sulfuric acid under reflux for 2 h gave two pinacolones 42 and 43 in 80 and 20 % yields, respectively. However, when hydrogen chloride gas was passed at room temperature over finely powdered 41 for 3 h, 42 was obtained selectively in 90% yield. The treatment of 44 with sulfuric acid as above gave a complex mixture of reaction products, 45, 46, and 47 in 48,29, and 5 % yields, respectively 27). The oily pinaeol 44 formed a 1 2 complex (48) with the host compound 4 as colorless crystals. The treatment of finely powdered 48 with hydrogen chloride gas under the same conditions as above gave 45 selectively in 44% yield 27>. 

When an optically active host compound is used instead of 4, formation of an optically active pinacolone is expected by an enantioselective pinaeol rearrangement in the solid state. 

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