Halohydrin 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.

HC1, HBr, and HI add to alkenes by a two-step electrophilic addition mechanism. Initial reaction of the nucleophilic double bond with H+ gives a carbo-cation intermediate, which then reacts with halide ion. Bromine and chlorine add to alkenes via three-membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry. If water is present during the halogen addition reaction, a halohydrin is formed. 

Scheme 10.33 Schematic representation of the mechanism of SDRs (top) and the halohydrin dehalogenase HheC (bottom). Scheme adapted from Reference 129.

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 ... 

Problem 6.33 Alkenes react with aqueous Clj or Br to yield v/V-halohydrins, —CXCOH. Give a mechanism for this reaction that also explains how Br, and (CH,)jC=CH, give (CH,),C(OH)CH2Br. M... 

The mechanism and stereochemistry of halogenation, physical methods / 273 Dihalogenation / 276 The use of A-halo compounds / 280 The use of other reagents / 282 The oxidation of halohydrins / 283 Vinylogous a-halo ketones / 284... 

No attempt will be made here to cite every recorded instance of the preparation of a halohydrin from an olefin. It will be sufficient to consider (1) the various moans employed to generate hypohakuw acids (2) the mechanism of the reaction and (3) a few representative examples of its application. 

If. instead of CC14. water is used as the solvent in a halogen addition reaction, a halohydrin is formed. The student proposed that such a reaction would follow Mechanism A with water replacing bromine as the nucleophile. If this hypothesis is correct, which of the following is the most likely product for the addition of bromine to propene in water ... 

C is correct The key is that the secondary carbocation is more stable than the primary (and most likely to form). Yon don t need to know what a halohydrin is to answer this question Just look at Mechanism A, and substitute water for bromine as the nucleophile (the negatively charged species). 

Halohydrins are /J-halogenated alcohols. They can be obtained in H20-containing solvents from alkenes and reagents, which transfer Hal ions. N-Broniosuccinnuide (transfers Br Figures 3.43 and 3.44 as well as 3.47), chloramine-T (transfers Cl Figure 3.46), and elemental iodine (transfers I Figure 3.47) have this ability. Bromonium and chloronium ions react with H20 via an SN2 mechanism. This furnishes the protonated bromo- or chlorohydrins, which are subsequently deprotonated. 

The study of gas-phase acid-induced nucleophilic displacement on 2,3-dihalobutanes has provided stereochemical evidence for the occurrence of cyclic chloronium and bromo-nium ions (X = Cl, Br), but not fluoronium ions17. Protonation or methylation of the neutral 2,3-dihalobutane by a suitable acid GA+ produces a halonium intermediate 2, which in the presence of water ultimately leads to the corresponding halohydrin neutral product (Scheme 4). Analysis of these neutral products indicated that the reaction proceeds with retention of configuration when X = Cl, Br and with inversion of configuration when X = F. The results were rationalized by the mechanisms sketched in Scheme 4, namely direct bimolecular nucleophilic displacement by H20 on 2 when X= F and intramolecular nucleophilic displacement to convert 2 into the cyclic halonium ion 3 (with inversion of configuation) followed by bimolecular nucleophilic displacement on 3 (with inversion of configuration) when X = Cl and Br. 

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... 

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 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. 

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. 

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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