Halohydrins, epoxide formation

Bartnicki EW, CE Castro (1969) Biodehalogenation. The pathway for transhalogenation and the stereochemistry of epoxide formation from halohydrins. Biochemistry 8 4677-4680. 

Alkaline hydrogen peroxide epoxidation / 10 Conversion of an oxirane into its stereoisomer / 14 Epoxide formation via halohydrins / 15 Spectra / 18... 

Ketones from halohydrins. Palladium acetate complexed with a triarylphos-phine, particularly tri-o-tolylphosphine, converts halohydrins into ketones in the presence of K2C03. Yields are about 70-85% for substrates in which the halogen is secondary or tertiary, but less than 50% when the halogen is primary because of epoxide formation. The reaction is useful for conversion of alkenes to ketones in those instances in which halohydrins are formed regioselectively. 

As discussed in the epoxide formation section, the system CPO/F O chloride (or bromide) reacts with double bonds forming halohydrins [23, 98-100], The selectivity in the reaction has driven the reactivity of the hypohalide ion thus while a good regioselectivity is observed, the diastereoselectivity is almost negligible [23] (Fig. 6.8b). 

Generally, chemists prefer the peroxyacid method of epoxide formation to the halohydrin method. Reactions (a) and (b) show the peroxyacid method, but the halohydrin method could also be used. 

Epoxides can be synthesized by treating halohydrins with aqueous base. Propose a mecha- PRACTICE PROBLEM 11.13 nism for reactions (a) and (b), and explain why no epoxide formation is observed in (c). 

The mechanism of dehydrohalogenation under basic conditions of trons-fused bicyclo[4,n,0]alkane halohydrins (563)—(565) has been studied. Three reaction types are noted (i) epoxide formation, (ii) ketone formation, and (iii) ring contraction. trans-Diaxial chlorohydrins corresponding to (563)—(565) gave epoxides (566)—(568) with relative rates (derived from bimolecular rate constants) of 1 3 17. This rate sequence was rationalized in terms of deformation of the cyclohexane ring brought about by the nature of the fused ring. In particular, deformation is probably towards the half-chair conformation favoured by the cyclohexane epoxide which is formed in the slow step. trans-Diequatorial chlorohydrins represented by (563)—(565)... 

The most studied example of 0 -3 participation is probably the base-catalyzed hydrolysis of 2-chloroethanol to produce ethylene oxide. As mentioned above, the reaction is catalyzed by hydroxide but not by water. Studies of the solvent isotope effect along with spectroscopic and conductivity measurements have confirmed the postulated two-step process. The reaction is often used as a stereospecific route to the more hindered epoxide derived from an olefin (via initial halohydrin addition). The carbohydrate field serves as a rich field for the application of epoxide opening and closing reactions. In this respect, Cerny and co-workers have observed that (193), (194), and (195) undergo hydroxide-catalyzed epoxide formation with relative rates of 1 23.3 180, respectively. 

Halohydrins are useful intermediates especially in the synthesis of epoxides The main reaction is usually accompanied by the formation of a dihalide... 

The formation of vicinal halohydrins from alkenes was described in Section 6.17. Halohydrins are readily converted to epoxides on treatment with base ... 

The activities of both haloalkanol dehalogenase (halohydrin hydrogen lyase) that catalyzes the formation of epoxides from alkanes with vicinal hydroxyl and halogen groups, and epoxide hydrolase that brings about hydrolysis of epoxyalkanes to diols are involved in a number of degradations that involve their sequential operation. 

Formation of Halohydrins from Epoxides (3) OC-seco-Halo-de-alkoxylation... 

Halohydrins are useful intermediates especially in the synthesis of epoxides. The main reaction is usually accompanied by the formation of a dihalide. When the reactions are performed in the presence of acetic acid, then acetates of the hydrins can be the predominant products. With several exceptions, alkenes with a nonfluorinated C = C bond have been subjected to halohydrinations. Halogen cations usually undergo addition to the substituted carbon of the C = C bond in (fluoroalkyl)ethenes. 

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