Halohydrin Formation Mechanism

Figure 7.3 Mechanism of the oxymercuration of an alkene to yield an alcohol. The reaction involves a mercurinium ion intermediate and proceeds by a mechanism similar to that of halohydrin formation. The product of the reaction is the more highly substituted alcohol, corresponding to Markovnikov regiochemistry.

The reagent may require acid activation depending on the type of transformation being attempted. The mechanism parallels that of halohydrin formation using an electrophilic source of halide in an aqueous medium ... 

Stereochemistry of Halohydrin Formation Because the mechanism involves a halonium ion, the stereochemistry of addition is anti, as in halogenation. For example, the addition of bromine water to cyclopentene gives fran.v-2-bromocyclopentanol, the product of anti addition across the double bond. 

The above mechanism is the same as that for halohydrin formation, shown in Section 7.3. In this case, the nucleophile is the hydroxyl group of 4-penten-l-ol. 

This reaction mechanism is similar to the mechanism of halohydrin formation. 

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. 

How can the orientation of the halogen and hydroxyl be explained in these reactions For example, in propylene chlorohydrin, the chlorine is attached to the terminal carbon, not the middle one. This orientation, and the others, can be accounted for by the mechanism of halohydrin formation. It involves intermediate carbonium ions. 

Halohydrin formation, as depicted in Mechanism 6.7, is mechanistically related to halogen addition to alkenes. A halonium ion intermediate is formed, which is attacked by water in aqueous solution. 

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

The first step is the same as that for halogen addition. In the second step, however, the two mechanisms differ. In halohydrin formation, water acts as the nucleophile and attacks one carbon atom of the halonium ion. The three-membered ring opens, and a protonated halohydrin is produced. Loss of a proton then leads to the formation of the halohydrin itself. 

The proposed mechanism for halohydrin formation can justify the observed regioselectivity. Recall that in the second step of the mechanism the bromonium ion is captured by a water molecule ... 

In other words, the transition state for this step will bear partial carbocationic character. This explains why the water molecule is observed to attack the more substituted carbon. The more substituted carbon is more capable of stabilizing the partial positive charge in the transition state. As a result, the transition state will be lower in energy when the attack takes place at the more substituted carbon atom. The proposed mechanism is therefore consistent with the observed regioselectivity of halohydrin formation. 

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. 

Mechanism 8-7 Addition of Halogens to Alkenes 350 8-9 Formation of Halohydrins 352... 

Mechanism 8-8 Formation of Halohydrins 352 8-10 Catalytic Hydrogenation of Alkenes 355 8-11 Addition of Carbenes to Alkenes 358 8-12 Epoxidation of Alkenes 360... 

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). ... 

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