Halohydrin formation from mechanism

A MECHANISM FOR THE REACTION ] Halohydrin Formation from an Alkene 365... 

The mechanism for halohydrin formation is similar to the mechanism for halogenation addition of the electrophile X (from X2) to form a bridged halonium ion, followed by nucleophilic attack by H2O from the back side on the three-membered ring (Mechanism 10.4). Even though X is formed in Step [1] of the mechanism, its concentration is small compared to H2O (often the solvent), so H2O and not X" is the nucleophile. 

The mechanism for halohydrin formation involves the formation of a cyclic bromo-nium ion (or chloronium ion) in the first step of the reaction, because Br (or Cl ) is the only electrophile in the reaction mixture. In the second step, the bromonium ion rapidly reacts with whatever nucleophile it bumps into. In other words, the electrophile and nucleophile do not have to come from the same molecule. There are two nucleophiles present in solution H2O and Br . Because H2O is the solvent, its concentration far exceeds that of Br . Consequently, the bromonium ion is more likely to collide with a molecule of water than with Br . The protonated halohydrin that is formed is a strong acid (Section 1.19), so it loses a proton. 

Haloperoxidases have been shown to transform alkenes by a formal addition of hypohalous acid to produce halohydrins. The reaction mechanism of enzymatic halogenatitHi has been debated for some time and it is now accepted that it proceeds via a halonium intermediate [1770, 1771], similar to the chemical formation of halohydrins (Scheme 2.228). The former species is derived from hypohalous acid or molecular halogen, which is in turn produced by the enzyme via oxidation of halide [1772]. In support of this, a HOCl-adduct of Fe -protoporphyrin IX was identified as a direct enzyme-halogen intermediate involved in chloroperoxidase-catalyzed halogenaticHi [1773]. 

Figure 11.5 shows a mechanism that has been postulated for this reaction. First, an electrophilic mercury species adds to the double bond to form a cyclic mercurinium ion. Note how similar this mechanism is, including its stereochemistry and regiochemistry, to that shown in Figure 11.4 for the formation of a halohydrin. The initial product results from anti addition of Fig and OH to the double bond. In the second step, sodium borohydride replaces the mercury with a hydrogen with random stereochemistry. (The mechanism for this step is complex and not important to us at this time.) The overall result is the addition of H and OH with Markovnikov orientation. 

The formation of halohydrins can be promoted by peroxidase catalysts.465 Recently 466 it has been shown that photocatalysis reactions of hydrogen peroxide decomposition in the presence of titanium tetrachloride can produce halohydrins. The workers believe that titanium(IV) peroxide complexes are formed in situ, which act as the photocatalysts for hydrogen peroxide degradation and for the synthesis of the chlorohydrins from the olefins. The kinetics of chlorohydrin formation were studied, along with oxygen formation. The quantum yield was found to be dependent upon the olefin concentration. The mechanism is believed to involve short-lived di- or poly-meric titanium(IV) complexes. 

Oxiranes cannot be prepared directly from 1,2-diols by dehydration. Formation of the oxirane intermediate has been studied in connection with the mechanism of the pinacolic rearrangement. Oxiranes can be prepared stereoselectively from the acetals and ketals of 1,2-diols. D-(+)-2,3-epoxybutane has been obtained from an optically active diol via conversion of the ketal 64 to a halohydrin ester (Eq. 52). ... 

HCl in benzene gave (270) and the cis-halohydrin (271) in approximate ratio 2 9. Trichloroacetic acid converted (269) into (270) (63.5 %X and after hydrolysis into (272) (33.5%), and (273) (< 1%). The secondary trichloroacetate of (272) isolated from the reaction is probably a secondary product from the tertiary ester via an acyl shift. In aqueous sulphuric acid the product composition from (269) was (270) 17.5 %, (272) 35 %, and (273) 47.5 %. Analogously obtained product data from (268) and (274) are assembled in the Table these data indicate for (274) a high preference for syn-adducts (via an ion-pair intermediate consequent upon benzylic cation formation) and for (268) a high preference for anti-adducts. Epoxide (269) represents an intermediate situation the high syn-stereoselectivity in the reaction with trichloroacetic acid is, however, indicative of an ion-pair mechanism and also suggests that the conjugative electron release of methoxy is transmitted to the benzylic centre in spite of the built-in steric constraints. In aqueous acid the lack of stereoselectivity exhibited by (269) has been... 

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)... 

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