Cyclophanes solvent effects

Ferguson, S. B., Sanford, E. M., Seward, E. M., Diederich, F., Cyclophane arene inclusion complexation in protic solvents - solvent effects versus electron-donor acceptor interactions. J. Am. Chem. Soc. 1991, 113, 5410-5419. 

A racemic mixture of three-layered [3.3]paracyclophane (45) was resolved into two enantiomers by chiral HPLC (on a Daicel OD column), and their absolute configuration was determined by a comparison of the experimental CD spectrum with the theoretical one at the TD-DFT-B3-LYP/TZVP level [55]. A simple model, composed of two p-xylenes and durene (the side chains were modeled again by methyl groups), was used to explain the origin of the chiroptical properties of the three-layered cyclophane system. Due to the flexibility of the [3.3]paracyclophanes, the solvent effects on the conformer distribution and thus on the chiroptical properties were significant (Fig. 10). 

This work on organic reaction mechanisms and our development of cyclophane chemistry were of great use to us in our later work. We did not shy away from tackling either multistep syntheses (up to 30 reactions) or highly asymmetric, designed systems needed in our studies of enzyme-mimicking systems. We needed both equilibria and kinetic techniques and an understanding of the importance of solvent effects in our more recent studies. 

Cyclophano-crown ether host (Scheme 8), possessing cyclic polyether and cyclophane moieties in a single molecule and ability to simultaneously bind a potassium cation and 6-methoxy-2-naphthonitrile in a water-methanol mixture, is of particular interest, since the contrasting solvent effects can be examined in the same host. Indeed, neutral 6-methoxy-2-naphthonitrile guest forms a 160-fold more stable complex with the cyclophane moiety in more hydrophilic 60 40 water-methanol solvent than in pnre methanol. In contrast, the affinity toward potassium ion is enhanced by a factor of 120 in pure methanol rather than in 60 40 water-methanol. Scheme 8... 

While the previous receptors are typically used in organic solvents, except for the cyclodextrins, there are special cases of cyclophane receptors supphed with peripheral charges (ammonium units) (107—12) or ionizable groups (carboxylate functions) (113,114) (Fig. 17) to allow substrate recognition, as in nature, in an aqueous medium, profiting from the solvophobic effects of water (115). 

A boxlike cyclophane receptor has been reported to complex p-nitrophenol with an association constant greater than 4 x 10 M in CDCI3 (Figure 82) [108], Large Ag values were observed in solvents such as chloroform and tetrachloroethane, whereas smaller solvent molecules such as CD2CI2 and 1,2-dichloroethane lowered the binding. A similar effect was earlier reported by Chapman and Still [109]. 

Fig. 4 Effect of solvent molecule size on complex stability between imidazole and cyclophane host. View thh art in color at WWW. dekker. com.)...

Currently, other catalytic systems have been developed, including N, M -disubstituted o-phenylenediamines, thiazolium cyclophane, ° and enzymes. The benzoin cndensa-tion is normally carried out in aqueous solution, and the addition of salt (LiCl, KCl) can increase the reaction rate however, the condensation can also be performed in organic solvent, such as anhydrous petroleum ether. In contrast to the salt effect in aqueous solution, the addition of salt (LiCl, LiClOa) into organic solvents (ethylene glycol, formamide, and DMSO) results in the decreasing of reaction rate. However, a few aldehydes were found not to form benzoin under the benzoin condensation condition instead ethylenediol and ethanediol were formed. This condensation when catalyzed by cyanide ion, is assumed... 

Hydrophobic effects arise from the exclusion of non-polar groups or molecules from aqueous solution. This situation is more energetically favourable because water molecules interact with themselves or with other polar groups or molecules preferentially. This phenomenon can be observed between dichloromethane and water which are immiscible. The organic solvent is forced away as the intersolvent interactions between the water molecules themselves are more favourable than the hole created by the dichloromethane. Hydrophobic interactions play an important role in some supramolecular chemistry, for example, the binding of organic molecules by cyclophanes and cyclodextrins in water (see Chapter 2, Sections 2.7.1 and 2.7.5, respectively). Hydrophobic effects can be split into two energetic components, namely an enthalpic hydrophobic effect and an entropic hydrophobic effect. 

In this context, it is intriguing to investigate the effects of the size and shape of solvent molecule on supramolecular association. For instance, the cyclophane host with functionalized tethers, illustrated in Scheme 9, can bind a small guest such as imidazole in ethers and chlorinated hydrocarbons. However, the binding constant for imidazole varies... 

The commercially available complex 2 shows higher activity and is metathesis active under mild conditions, typically ambient temperature up to 90 °C [3c, hj. RCAM reactions with 2 are often run at 80 °C in toluene or a related aromatic solvent However, rigorously inert (anhydrous and oxygen-free) conditions are required. The core structure is amenable to tuning by ligand modifications, reflected in a recent report which demonstrated that the effective RCAM of diyne 6 can be performed at room temperature to afford cyclic alkyne 8 in excellent yield when imidazolin-2-iminato tungsten alkylidyne catalyst 7 was employed (Scheme 7.5) [12], The same catalyst has also been employed in the preparation of cyclophanes [13]. 

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