Solid state inclusion compounds

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]. 

The phenomenon of pseudopolymorphism is also observed, i.e., compounds can crystallize with one or more molecules of solvent in the crystal lattice. Conversion from solvated to nonsolvated, or hydrate to anhydrous, and vice versa, can lead to changes in solid-state properties. For example, a moisture-mediated phase transformation of carbamazepine to the dihydrate has been reported to be responsible for whisker growth on the surface of tablets. The effect can be retarded by the inclusion of Polyoxamer 184 in the tablet formulation [61]. 

The freeze of equilibrium by the complexation method is also applicable to some other compounds. 2-Mercapto substituted tropone 32 has been reported to exist as an equilibrium mixture of 2-mercaptotropone (32 a) and 2-hydroxytropothione (32 b), and the latter is predominant both in solution 17) and in the solid state 18). The equilibrium is frozen and the former was isolated by inclusion complexation with 1. When a solution of 1 and 32 in petrol ether was kept, a 1 1 complex 33 composed of 1 and 32a was obtained in 90% yield as orange prisms of mp 101 to 103 °C19). The structure of 32a in 33 was elucidated by IR spectroscopy which showed vSH at 2482 cm-1 33 gave also absorptions of a strongly hydrogen-bonded hydroxyl group at 3270 cm 1. 

An enantioselective photoreaction of a guest compound is expected when an inclusion complex of the guest with an optically active host compound is irradiated in the solid state. 

Inclusion complexation of racemic 63 with the meso isomer of 2 was also examined. The host compound included racemic 63 as did 2a, and photoreaction of the complex in the solid state gave racemic 65 again 23). 

Toda and Akai49 reported that compound 48 reacted with the stable solid state inclusion compound of chiral host 46 and meso-ketone 47, providing alkene 49 in 57% ee. 

Braun T, Buvari-Barcza A, Barcza L, Konkoly-Thege I, Fodor M, Migali B (1994) Mechanochemistry a novel approach to the synthesis of fullerene compounds. Water soluble Buckminster fullerene - gamma- cyclodextrin inclusion complexes via solid-solid reaction. Solid State Chem. 74 47-51. 

An important advantage of the inclusion complexes of the cyclodextrins over those of other host compounds, particularly in regard to their use as models of enzyme-substrate complexes, is their ability to be formed in aqueous solution. In the case of clathrates, gas hydrates, and the inclusion complexes of such hosts as urea and deoxycholic acid, the cavity in which the guest molecule is situated is formed by the crystal lattice of the host. Thus, these inclusion complexes disintegrate when the crystal is dissolved. The cavity of the cyclodextrins, however, is a property of the size and shape of the molecule and hence it persists in solution. In fact, there is evidence that suggests that the ability of the cyclodextrins to form inclusion complexes is dependent on the presence of water. Once an inclusion complex has formed in solution, it can be crystallized however, in the solid state, additional cavities appear in the lattice, as in the case of the hosts previously mentioned, which enable the inclusion of further guest molecules. ... 

Solvent-drop grinding was next applied as an eco-friendly modification to a previously described preparation of a crystalline organic inclusion compound. Initial work had demonstrated solution-mediated supramolecular organisation and solid-state topochemically controlled reactivity in a system involving l,2-bis(4-pyridyl)ethylene (bpe) 32 and 1,2,4,5-benzenetetracar-boxylic acid (bta) 33 [57]. A single crystal of a 2 1 bpe bta 32 33 cocrystal was... 

A Versatile Class of Macrocyclic Compounds, J. Vicens, V. Bohmer, Eds., Kluwer, Dordrecht, 1991, p. 65 G. D. Andreetti, F. Ugozzoli, Inclusion Properties and Host-Guest Interactions of Calixarenes in the Solid State, ibid., p. 87. 

Host and guest are terms covering all kinds of intermolecular associations from the well-defined supermolecules to loosely packed solid state inclusion compounds. 

A powdered 1 1 inclusion complex of (-)-l and 4-methoxy-l-methylpyridone 2c was irradiated by 100-W high-pressure Hg-lamp at room temperature in the solid state. The crude reaction product was chromatographed on silica gel using CHCI3 as a solvent to give a mixture of host compound and 3, from which 3 was isolated by distillation as an oil ([a]D-123° (c 0.026, CHC13), 100% ee). 

When a mixture of thiocoumarin 4 and optically active host compound (R,R)-(-)-l in butyl ether was kept at room temperature for 12 h, a 1 1 inclusion complex (mp 106-108 °C) was obtained as colorless needles. The 1 1 complex gave anti-head-to-head dimer (+)-5 (mp 254—255 °C) of 100% ee ([a]D+182 °, c 0.02 in CHC13) in 73% yield upon photoirradiation in the solid state. The optical purity of 5 was determined by HPLC on the chiral stational phase Chiralpak AS with using hexane-EtOH (95 5) as an eluent. 

Intramolecular [2 + 2] photocyclization reactions of 2- /V-(2-propcnyl)amino]cy-clohex-2-enones (67) are also controlled enantioselectively by carrying out irradiation in inclusion complex with a chiral host compound. When inclusion crystals of 67 with 12 are irradiated in the solid state, optically active 9-azatricyclo[5.2.1.0]-decan-2-ones (68) were obtained in the chemical and optical yields indicated in Table 3 [30],... 

Photoirradiation of inclusion crystals of the 4-(3-butenyl)cyclohexa-2,5-dien-l-ones (83) with the optically active host compounds (12c) in the solid state gave optically active l-carbomethoxytricyclo[4.3.1.0]dec-2-en-4-ones (84). For... 

Optically active oxazolidinones (91a-91d) of 95-100% ee were obtained by irradiation of the 1 1 inclusion complex crystals of nitrones (90a-90d) and optically active host compound 11 in the solid state in the chemical and optical yields indicated (Table 10) [48],... 

The enantioselective photodimerization of thiocoumarin (102) to optically pure (+)-a ft -head-to-head dimer (103) in the 1 1 inclusion complex of 102 with 12b was also found to proceed in a single-crystal to single-crystal manner. For example, when a mixture of thiocoumarin (102) and optically active host compound 12b in butyl ether was kept at room temperature for 12 hr, a 1 1 inclusion complex of 103 with 12b was obtained as colorless needles. Photoirradiation of a 1 1 inclusion complex in the solid state (400-W high-pressure Hg lamp, Pyrex filter, room temperature, 2 hr) gave a 2 1 complex of 12b with 103,... 

Enantioselective photoreactions in the solid state have many advantages as described in Section I. As reviewed in this chapter, highly enantioselective photoreactions can be accomplished in the solid state without using any chiral source. There are hopeful possibilities to find many other examples of similar absolute asymmetric photosynthesis in the solid state. Enantioselective photosynthesis in inclusion complex crystal with a chiral host compound will also be a new general method of asymmetric synthesis in future. By successful designing of many new chiral host compounds, the research field would also be developed widely. 

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