Halohydrins with base

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. 

One of the major uses of these halohydrins is for the preparation of epoxides. Treatment of the halohydrin with base, such as NaOH or KOH, results in deprotonation of the alcohol followed by an intramolecular nucleophilic substitution (see Section 10.3), as shown in the following example. Remember that the nucleophilic oxygen must displace the chlorine from the opposite side, resulting in inversion of configuration at that carbon. 

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. 

This formation of an epoxide by treatment of a halohydrin with base is just an intramolecular Williamson ether synthesis. The nucleophilic alkox-ide ion and the electrophilic alkyl halide are in the same molecule. 

This classical example of oxirane synthesis involves treatment of a halohydrin with base <84CHEC-1(7)115,85CHE1,85MI103-01). Kolb and Sharpless introduced a three-step protocol <92X10515,92TL2095) whereby chiral diols, available by Sharpless asymmetric dihydroxylation <92JOC2768>, are efficiently converted into chiral oxiranes (Scheme 55). 

Reaction with base brings the alcohol function of the halohydrin into equilibrium with Its corresponding alkoxide... 

Formation of oxiranes on the sterically more hindered side of the steroid ring system is usually carried out via /raw -halohydrins which afford oxiranes on treatment with base (c -Halohydrins yield ketones on exposure to base). Two general methods are available for the synthesis of tm s-halohydrins (1) the reduction of a-halo ketones and (2) the addition of a hypohalous acid to unsaturated steroids. 

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

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. 

Halohydrins, formed by electrophilic addition of HO—Cl(Br) to alkenes (Problem 6.33), are treated with base to give epoxides. 

PEG proves to be an efficient reaction medium for the reaction of vicinal halohydrin with carbon dioxide in the presence of a base to synthesize cyclic carbonates (Scheme 5.9) [42], Notably, PEG400 (MW = 400) as an environmentally friendly solvent exhibits a unique influence on reactivity compared with conventional organic solvents. Various cyclic carbonates can be prepared in high yield employing this protocol. The process presented here has potential applications in the industrial production of cyclic carbonates because of its simplicity, cost benefits, ready availability of starting materials, and mild reaction conditions. 

Sec. 7.8, 18.5) from alkenes by treatment with a peroxyacid (Sec. 18.5) from halohydrins by treatment with base... 

The mechanistic outline of carbenoid/carbonyl reactivity follows the paradigm illustrated at the outset of this chapter (Scheme 1 X = halogen). The nucleophilic lithium species adds to the carbonyl compound and suffers elimination to provide the epoxide. Competition from molecular rearrangements emanating from the intermediate halohydrin or the product epoxides is sometimes a problem, particularly with cyclic ketones. Also, the initial adduct frequently fails to cyclize when the reaction is quenched at low temperature, but it is usually a simple matter to effect ring closure by treatment of the halohydrin with mild base in a separate step. 

The reaction of chloro- or bromohydrins with bases provides an economical route for the preparation of epoxides. Halohydrins are readily accessible by treatment of an alkene with either hypochlorous acid (Clj -1- H2O —> HOCl), hypochlorite bleach solution (NaOCl), or hypobromous acid (NBS -1- HjO HOBr). These reactions involve the... 

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