Bromination using cyclodextrins

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.

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. 

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-... 

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. ... 

The effect of racemization on this reaction was examined by using the optical active eryt/iro-dibromide ([a]g -27.2°, 40 % e.e. calculated from the value [a] -68.3° in literature22), as shown in Table IV. When the optical active dibromide included in 3-cyclodextrin was exposed to bromine at 25°C for 3 h, the e.e. of recovered erythro-dihro-mide, identified by NMR, decreased remarkably, its decrease corresponding to 78 % of racemization, and thoi the dibromide racemized perfectly after 10 h. In contrast, the optically active dibromide alone did not racemize even after 20 h of exposure to bromine. This result shows that the racemization was catalyzed by 3-cyclodextrin. 

ABSTRACT The gas-solid halogenation and hydrohalogenation using micro-crystalline cyclodextrin complexes are found to be efficient for production of the optical active halides of ethyl trans-cinnamate in moderate optical yields On exposure to HBr at 2QOC for 15-20 hr, the cinnamate in solid a- and S-cyclodextrin complexes yields ethyl R-(+)-3-bromo-3-phenylpropanoate in 46% e.e., and S-(-)-enantiomer in 31% e.e., respectively. No addition nor substitution products are obtained with HCl vapor at 0-50°C for 15-65 hr. Bromination of the B-cyclodextrin complex results in the formation of optical active ethyl erz/t/zrc>-2,3-dibromo-3-phenylpropanoate, while chlorination gives the optical active mixture of trans and cis addition products, ethyl erythro- and threo-2,3-di-chloro-3-phenylpropanoates in 60-80% yields. Mechanism of chiral induction in the present gas-solid reaction has been proposed on the basis of the crystal structure of the complex. 

Cyclodextrins can also be directly perhalogenated on the primary rim. Using triphenylphosphine and a halogen donor, such as iodine, bromine, or N-chlorosuccinimide (NCS), perhalogenated cyclodextrins 7a-e were obtained in good yields (Scheme 9.3) [15]. 

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