Reaction control cyclodextrins

Water-soluble cyclodextrin complexes of water-insoluble monomers were achieved by stirring a slight excess of cyclodextrin derivatives, in most cases RAMEB, and different monomers in water. Several methods were applied to the characterizations of the host- fuest complexes. The most important behavior of the complexes is that the hydrophobic guest monomers become water-soluble by being included into cyclodextrin. Reaction control by thin-layer chromatography (TLC) with methanol as mobile phase, followed by UV detection and iodine development, shows complete conversion to the corresponding cyclodextrin complexes. The Rf values of the complexes are significantly different from the value of imcomplexed monomers and cyclodextrin (Table 1). 

Reduction via inclusion complexes has received considerable attention because it allows both the diastereo- and enantioselectivity of the reaction to be controlled. Cyclodextrins and water-soluble cyclophanes are the most frequently used hosts in aqueous medium. P-CD/ketone (1 1) complexes suspended in NaBH4 aqueous alkaline solution give the corresponding alcohols quantitatively but with modest ee [75]. An improvement is obtained by using crystalline a-, P- and y-CD inclusion complexes of achiral amine-boranes at 0°C in heterogeneous aqueous medium [76]. Under these conditions, 1-phenylethanone and 4-phenyl-2-butanone give the (5) and (R) alcohol with 91% and 89% ee, respectively. 

Several procedures are used to control the ratios of cyclodextrins produced. One is addition of a substance to the reaction mixture that can gready affect the formation of one specific cyclodextrin over another. For example, in the presence of 1-decanol and 1-nonanol, a-cyclodextrin is produced almost exclusively whereas hexane or toluene promote the production of P-cyclodextrin. Conversely both cyclodextrins are produced simultaneously in the presence of 1-heptanol (2,4). 

The use of cyclodextrins can allow stereo-, regio-, and optical selectivity, and thus molecular traffic control may be realized (Syamala et al. 1986). It has been claimed that the reaction of phenol with aqueous formaldehyde in the presence of cyclodextrins gives a 3 1 mixture of para to ortho at 38 % conversion in the absence of cyclodextrins, the ratio of para to ortho is around 2 3. 

The reaction was first conducted with success on sucrose [82], The degree of substitution (DS) obtained was controlled by the reaction time. Thus, under standard conditions (0.05% Pd(OAc)2/TPPTS, NaOH (1 M)/iPrOH (5/1), 50 °C) the DS was 0.5 and 5 after 14 and 64 h reaction time, respectively. The octadienyl chains were hydrogenated quantitatively in the presence of 0.8-wt.% [RhCl(TPPTS)3] catalyst in a HjO-EtOH (50/10) mixture, yielding a very good biodegradable surfactant (surface tension of 25 mN m-1 at 0.005% concentration in water) [84]. Telomerization reaction was also conducted with success on other soluble carbohydrates such as fructose, maltose, sorbitol and /i-cyclodextrin. 

The inclusion complexation of spiropyrans in cyclodextrins has also been explored as a means to control photochromic reactions.1591 Distinct differences in complexation of sulfonic acid-modified spiropyrans to various cyclodextrins were observed and the closed spiropyran form bound to (3-cyclodextrin was stable towards photochemical ring-opening. 

Alpha-cyclodextrin can also be produced using an organic precipitant.21,22 In the presence of decanol, the enzyme from B. macerans produces predominantly a-cyclodextrin. In the early stages of the reaction, a mixture of a- and (3-cyclodextrins are present, so the reaction must be allowed to proceed long enough for the (3-cyclodextrin to disappear. Choice of enzyme and precipitant is important. Some precipitants, such as cyclohexane, will produce a mixture of a- and (3-cyclodextrins by controlling the temperature, relative proportions of each can be controlled.32 As the temperature is increased, the relative amount of (3-cyclodextrin increases. 

Another aqueous heterogeneous polymerization was recently reported for the precipitation polymerization of MMA and styrene complexed with methylated /3-cyclodextrin.256 The polymerization was carried out in water with 1-21 (X = Br)/CuBr/L-4 to give polymers with controlled molecular weights and relatively narrow MWDs (MJMn = 1.3—1.8). Initially, the reaction mixture was homogeneous with the hydrophilic cyclodextrin-complexed MMA, but sooner or later it became heterogeneous due to the formation of water-insoluble polymers. 

Organized and constrained media may provide cavities and surfaces, sometimes called microreactors or nanoreactors,171 that can control the selectivity of photochemical reactions of reactants. There are many types of microreactors, for example, molecular aggregates of micelles or monolayers, macrocyclic host cavities of crown ethers or cyclodextrins and microporous solid cavities and/or surfaces of zeolites, silica or... 

Cyclodextrin has also been used to control the enantioselectivity of bioreductions1119-1211. When added to a reaction mixture, the substrate can reside in the cyclodextrin, which decreases the effective substrate concentration around the enzyme and results in the domination of reactions involving enzymes with low KM. The effect can be demonstrated by the reduction of ketopantoyl lactone by yeast. The enantioselectivity was improved from 73% to 93% by adding p-cyclodextrin to the reaction mixture. The improvement in enantioselectivity of the reduction in the presence of enzymes with different enantioselectivities and Km values by decreasing the substrate concentration was confirmed by the ineffectiveness of a-cyclodextrin which is too small to include the substrate. It was also confirmed by dilution of the reaction mixture, which improved the enantioselectivity in the absence of cyclodextrin. 

Cyclodextrins exhibit remarkable ortho-para selectivity in the chlorination of aromatic compounds by hypochlorous acid (HOCl) [22] (Scheme 5). Chlorination takes place via formation of a covalent intermediate, a hypochlorite ester of cyclodextrin. In the chlorination of anisole by hypochlorous acid, pura-chlorination occurs almost exclusively in the presence of sufficient cyclodextrin, although in control experiments maltose had no effect on the product ratio. For example, selectivity for para-chlorination in the presence of 9.4 X 10 M a-cyclodextrin is 96%, which is much larger than that in the absence of a-cyclodextrin (60%). In the proposed mechanism, one of the secondary hydroxyl groups reacts with HOCl to form a hypochlorite ester, which attacks the sterically favorable para position of the anisole molecule included in the cyclodextrin cavity in an intracomplex reaction. The participation of one of the secondary hydroxyl groups at the C-3 position in the catalysis was shown by the fact that dodecamethyl-a-cyclodextrin, in which all the primary hydroxyl groups and all the secondary hydroxyl groups at the C-2 positions are methylated, exhibited equal or larger ortho-para specificity than native a-cyclo-... 

In other work described in the same publication, a-cyclodextrin was converted to a solid polymer by reaction with epichlorohydrin, and this was used in a reactor to perform the flow reaction of anisole with HOCl. The product was completely pnra-chlorinated, and the reactor could be used repeatedly. Thus, the binding of substrate to an immobilized template has potential for practical synthesis with geometric control of selectivity. 

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