A-Halohydrins

Bromohydrin (Section 6.17) A halohydrin in which the halogen is bromine (see halohydrin). 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO-X to alkenes (Section 7.3). When a halohydrin is treated with base, HX is eliminated and an epoxide is produced. 

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. 

The final product is called a halohydrin (indicating that we have a halogen— Br— and an OH in the same compound). This reaction is commonly called halohydrin formation. 

When an alkene is reacted bromine in aqueous solution (rather than CCI4), the major product is a halohydrin (halo alcohol). 

Jones, A.R. Fakhouri, G. (1979) Epoxides as obhgatoiy intermediates in the metabolism of a-halohydrins. Xenobiotica, 9, 595-599... 

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. 

An illustrative example of oxirane formation by the action of alkali on a / -halohydrin is to be found in the reaction sequence involved in the Darzens glycidic ester synthesis (Section 5.7.6, p. 598). Three target molecules, namely 2-phenylaziridine (4), methyl (S)-thiiranecarboxylate (5) and cyclooctene sulphide (6), are selected here to exemplify this intramolecular cyclisation reaction type. 

When this reaction takes place with water, a halotn/rfriit is formed and Markovnikov s rule is followed where the electrophile adds to the least substituted carbon. Water acts as the nucleophile in the second step instead of the bromide ion. (A halohydrin is a hydroxyl group and a halogen attached to adjacent carbons.)... 

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). 

B-6. Which of the species shown is the most stable form of the intermediate in the electrophilic addition of Cl2 in water to cyclohexene to form a halohydrin Electron pairs have been omitted for convenience, and their absence should not be considered as part of the problem. 

The conversion of an alkene to a halohydrin can also be considered as an epoxidation because this can be achieved by a simple ring closure.184 Although no reagent is yet available to perform an asymmetric conversion of an isolated alkene to a halohydrin, the reaction can be controlled through diastereoselection. One such case is the halolactonization of y,8-unsaturated carboxylic acids, N,N-dialkylamides.185189... 

They can also be obtained from alkenes in a two-step process (Fig. A). The first step involves electrophilic addition of a halogen in aqueous solution to form a halohydrin. Treatment of the halohydrin with base then ionises the alcohol group, that can then act as a nucleophile. The oxygen uses a lone pair of electrons to form a bond to the neighbouring electrophilic carbon, thus displacing the halogen by an intramolecular SN2 reaction. 

The reaction of an alkene with a halogen like bromine and chlorine generally gives a vicinal dihalide. However, if the reaction is carried out in water as solvent, the product obtained is a halohydrin where the halogen adds to one end of the double bond and a hydroxyl group from water adds to the other. 

The product is called a halohydrin. Because the concentration of the water molecules is so much higher than the concentration of the halide anions (water is the solvent), water wins the competition to act as the nucleophile, and only the halohydrin is formed in significant amounts. 

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. 

A halohydrin is an alcohol with a halogen on the adjacent carbon atom. In the presence of water, halogens add to alkenes to form halohydrins. The electrophilic halogen adds to the alkene to give a halonium ion, which is also electrophilic. Water acts as a nucleophile to open the halonium ion and form the halohydrin. 

A second synthesis of epoxides and other cyclic ethers involves a variation of the Williamson ether synthesis. If an alkoxide ion and a halogen atom are located in the same molecule, the alkoxide may displace a halide ion and form a ring. Treatment of a halohydrin with base leads to an epoxide through this internal SN2 attack. 

Scheme 5.34 Application of a halohydrin dehalogenase for the synthesis of a carbon-carbon bond.

Acid-catalyzed ring opening with HX to yield a halohydrin (Sec. 18.6)... 

Halohydrins. The reaction of a slight excess of 1, Br, or Cl, and of P(C6H,)j in CH2CI2 with an epoxide results in a halohydrin in generally high yield. The orientation depends in part on the bulkiness of the halide ion, but the halogen ion generally attacks the less substituted carbon atom. 

Several related procedures for syn hydroxylation of alkenes involve a halohydrin ester (32) as the key intermediate. In Woodward s procedure an alkene in glacial acetic acid is treated with iodine and silver acetate. Acetyl hypoiodite, MeCOjI, formed by reaction of the latter two reagents attacks the alkene, R R 0=CR R in an electrophilic manner, from the less hindered side to give, by overall anti addition. 

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