Epoxides, preparation from halohydrins

Epoxides can also be prepared from halohydrins, themselves produced by electrophilic addition of ffO X to alkenes (Section 8.3). When a halohydrin is treated with base, ffX is eliminated and an epoxide is produced by an intramolecular Williamson ether synthesis. That is, the nucleophilic alkoxide ion and the electrophilic alkyl halide are in the same molecule. 

The following section describes the preparation of epoxides by the base-promoted ring closure of vicinal halohydrins. Because vicinal halohydrins are customarily prepared from alkenes (Section 6.17), both methods—epoxidation using peroxy acids and ring closure of halohydrins—are based on alkenes as the starting materials for preparing epoxides. 

Enantioselective reductions. The neat reagent (1), prepared from ( + )-< -pinene, reduces aryl a-halomethyl ketones slowly but in high chemical yield to (R)-halohydrins in 90-96% ee, but optical induction is mediocre in the case of aliphatic a-halo ketones (35-66% ee). The chiral halohydrins are useful precursors to chiral epoxides. 

When an organic compound contains both a hydroxy group and a halogen atom on adjacent carbon atoms, an intramolecular version of this reaction forms an epoxide. The starting material for this two-step sequence, a halohydrin, is prepared from an alkene, as we will leam in Chapter 10. 

Since halohydrins are nearly always prepared from alkencs by addition of halogen and water to the carbon-carbon double bond (Sec. 6.14), this method amounts to the conversion of an alkenc into an epoxide. 

The epoxides were prepared from the corresponding olefins either by oxidation with various peracids such as peracetic acid or m-chloroper-benzoic acid or in a two-step procedure via the halohydrin (SCHEME IV). The direct epoxidation procedure is preferred due to the generally low yields of halohydrins obtained in the second method. The halohydrins are active herbicides and will be discussed in a future publication (9). 

As anticipated by the formation of oxiranes (oxacyclopropanes, epoxides) from halohydrins, the four-membered oxygen-containing ring, oxetane (oxacyclobutane), can be prepared by heating 3-chloropropanol (HOCH2CH2CH2CI) with potassium hydroxide (KOH) (Equation 8.51). 

They served for the preparation of halohydrins (after reductive cleavage from the auxiliary) and epoxides but were also used as intermediates en route to a-amino acids via azide substitution of the halide, saponification, and hydrogenolysis of the azide. 

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. 

Since esmolol is marketed as its racemic mixture, there were no stereochemical issues associated with the Payne-like [21] formation of the intermediate aryloxyep-oxide, particularly when the coupling reaction was carried out under the K2C03/ acetone conditions conducive to the formation of epoxides from alpha-halohydrins (see discussion in Chapter II-8). Likewise, even though over-alkylation had been a major problem when preparing the N-extemal ester targets because the N-alkyl-... 

Synthetic reactions that result in the bromohydroxylation of the monoester of 1-propenylphos-phonate with NBA in H2O at 15°C and in the chloro- or bromohydroxylation of the diacid with NCS or NBS were particularly useful in providing, in good conditions, the two isomeric threo-halohydrins, which can be separated before epoxidation. For example, crystallization from acetone of the mixture of diastereomeric bromohydrins prepared by bromohydroxylation of the monoester of propenylphosphonate provided the preferred t/ireo-bromohydrin in diastereomerically pure form. ... 

The lack of success in the preparation of 2,3-epoxy derivatives from 2-phospholenes has been obviated by the use of the halohydrin procedure. Thus, the treatment of the 2-phospholene 351 (R = Et, R = Me) with nba yields a stereoisomeric mixture of the halohydrins 366 which, when treated with KOAc in acetone, in turn, yields a mixture of two stereoisomers of the epoxide 367. The product from the same reaction with the corresponding 3-phospholene is identical with that obtained by the direct oxidation of the phospholene, and is therefore thought to have structure 368. ... 

One method for the preparation of epoxides from alkenes involves (1) treating the alkene with chlorine or bromine in water to form a chlorohydrin (or bromohydrin) followed by (2) treating the halohydrin with a base to bring about intramolecular displacement of Cl . These steps convert propene first to l-chloro-2-propanol and then to methyloxirane (propylene oxide). 

Oxirans. - The synthesis of l,2-anhydro-3,4-di-0-benzyl-6-deoxy-a-D-glucopyranose and its conformational analysis have been reported. A range of epoxides have been prepared by base treatment of bromohydrins, which were made by reaction of hydrogen bromide with aldonolactones. A one-pot conversion of vicinal diols into epoxides employs halohydrin ester intermediates generated from cyclic orthoacetates and either acetyl bromide or trimethylsilyl chloride. Levoglucosenone has been transformed into l,6 3,4-dianhydro-p-D-talopyranose by way of a trn/w-iodo-acetoxylation of the alkene moiety... 

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