Cyclodextrin bromination

Scheme 9. Bromination of a,/l-unsaturated carboxylate ligands in 97 and 99 (256). The bowl-shaped representation of the ligand (L19)2-should not be confused with the one used for the cyclodextrins.

Table A4.2 cyclodextrin.fl Catalysis of bromine attack on phenols and phenoxides by a-...

Attempted asymmetric halogenation of fraws-2-butenoic acid in a crystalline a-cyclodextrin using gaseous Br2 or CI2 at 45-50 °C was unsuccessful, giving very poor enantioselectivity162. Exposure of chiral crystals of dibenzobarrelene (90) to bromine vapour results in formation of the rearranged addition product 91 in up to 8% e.e.163. 

The effect of cyclodextrin complexation on the bromination of styrene, methyl cinnamate, phenylacetylene, and allylbenzene has been studied.27 The corresponding bromohydrin was obtained as a major product along with dibromide in the bromination... 

Microsolvent effects in the cyclodextrin cavity have also been observed in hypochlorite chlorination of acetophenone1029. Higher para selectivity has been observed in the bromination of acetanilide and benzanilide in presence of cyclodextrins or amylose1030 and in the anodic chlorination of anisole with cyclodextrin-modified electrode1031. 

Of particular interest are the gas-solid bromination, chlorination and hydrobromina-tion of unsaturated acids complexed with cyclodextrins, which proceed with a high degree of chiral induction. For example, in the gas/solid chlorination of methacrylic acid complexed with a-cyclodextrin1032, (-)-2,3-dichloro-2-methylpropanoic acid is obtained in a 100% optical yield. 

Cyclodextrins can be used as reaction vessels. Chlorination, bromination,229 carboxylation,230 azo coupling, and others, favor the para-isomers over the meta- and ortho-isomers, when the compound being treated is inside a cy-... 

The effect of the cyclodextrins on the regioselectivity of bromination of anisole is similar to that seen with acetanilide (Figure 3.2b). With systems more activated to electrophilic substitution, such as 3-methylacetaiulide and 3-methylanisole, the cyclodextrins... 

Figure 3.2 Effect of cyclodextrins on the pyridinium dichlorobromate bromination of a) acetanilide, b) anisole, ° c) 3-methylanisole ° and d) 3-phenylpropanoic acid, and e) the orientation of 3-phenylpropanoic acid in an amino cyclodextrin to shield the ortho-positions from reaction and leave the para-position exposed...

P G. Dumanski, C. J. Easton, S. F. Lincoln, J. S. Simpson, Effect of cyclodextrins on electrophilic aromatic bromination in aqueous solution, Aust. J. Chem., 2003, 56, 1107-1111. 

Oxidation and Bromination of Other Functional Groups. Selective oxidation of alcohols may be achieved using a 1 1 complex of NBS and tetrabutylammonium iodide, whereas 1,2-diols are converted into 1,2-diketones using iV-bromosuccini-mide. An efficient and mild procedure has been reported for the preparation of benzoic acids via oxidation of aromatic carbonyl compounds by employing NBS and mercuric acetate. Selective and efficient oxidation of sulfides to sulfoxides has been achieved with NBS in the presence of /3-cyclodextrin in water. Epoxides and aziridines are conveniently oxidized to the corresponding a-hydroxy or Q -amino ketones using cerium(IV) ammonium nitrate and NBS. ... 

It was demonstrated that a complexation of trans-stilbene with cyclodextrin led to a decrease in stereoselectivity of additive bromination and to a significant yield of DL-stilbene dibromide in contrast to the formation of meso-stilbene dibromide in nonpolar solvents [98]. The authors suggested that this reversal of stereoselectivity was attributed to the polar environment provided by the secondary hydroxyl groups of... 

As one of the enzymic reactions, asymmetric synthesis catalyzed by cyclodextrins has been studied in the past, but gave all the products in a low optical yield. We have already found a strong chiral induction for the chlorination of methacrylic acid in the crystalline cyclodextrin complexes. 100 % enantiomeric excess (e.e.) of (-)-2,3-dichloro-2-methyl-propionic acid and 88 % e.e. of its enantiomer were isolated in a- and 3-cyclodextrins, respectively. This paper describes asymmetric addition of gaseous halogens and hydrogen halides in the crystalline complexes comprising trans-cinnamic acid as a reactant and a- or 3-cyclodextrin as chiral matrix. Asymmetric bromination of menthyl cinnamate and of salts from the acid and several chiral amines have been reported, but gave low chiral inductions up to 2 16 % e.e.. 

The solution reactions were carried out with or without cyclodextrins in (CH3)2S0, (CH3)2SO-d0 or carbon tetrachloride. The typical experimental procedure was as follows. tra/7S-Cinnamic acid (11 mg, 0.08 mmol), powdered cx-cyclodextrin complex (162 mg, contained 0.08 mmol of the acid), and 3-cyclodextrin complex (100 mg, contained 0.08 mmol of the acid) were dissolved in 0.4 ml of (CH3)2S0-d6, to which 0.1 ml of the same solvent containing bromine (0.08 mmol) was added at 25°C. At 2 h intervals, the conversion of the acid was determined by NMR spectra. Then the reaction mixtures were poured into 20 ml of 15 wt % aqueous sodium chloride soluticn, followed by extraction with diethyl ether. The products were obtained as white solid by evaporation of the ether layer and their optical rotations were measured in ethanol on a polarimeter. 

As seen from Table I, molecular size of attacking reagent affected this gas-solid reaction, trans-Cinnamic acid in the cavity of o-cyclodextrin reacted with smaller hydrogen bromide molecule but did not with bromine and chlorine with larger molecular sizes. 

In addition, bromination of the organic acid with or without cyclodex-trins was carried out in (CH3)2SO-d0 solution at 25°C for 65 h. The acid with or without g-cyclodextrin reacted with bromine to give eiytAro-di-... 

In fact, at the end of the reaction of trans-cinnamic acid with chlorine under air, the sticky solid product was obtained, but with bromine no change of the solid was observed. However, when the addition of these reagents to the acid proceeded in the microcrystalline cyclodextrin matrix, there was no visual evidence of liquid phase on the crystal even in chlorination of it under microscope. 

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