Halohydrins alkylation with

The 10l -acetoxy group can be red actively removed with zinc and acetic acid or chromous chloride to give I9-norsteroids in high yield. Thermal elimination (boiling tetralin) of acetic acid from the crude 10)5-acetoxy-A -3-ketone or treatment with methanolic alkali leads to aromatization of ring A. Estrone alkyl ethers are formed from 10)5-acetoxy-19-nor-A -androstene-3,17-dione by treatment with alcohols and perchloric acid. Similar aromatizations are observed with 5,10-oxido, 5,10-dihydroxy, 5,10-halohydrins or 5,10-dihalo-3-ketones. ... 

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 halohydrins are treated with base, HX 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. 

When gem-disubstituted epoxides (122) are treated with Grignard reagents (and sometimes other epoxides), the product may be 123, that is, the new alkyl group may appear on the same carbon as the OH. In such cases, the epoxide is isomerized to an aldehyde or a ketone before reacting with the Grignard reagent. Halohydrins are often side products. 

The first examples of the synthesis of CCs from halohydrins appeared during the early 1930s. In this case, vic-halohydrins were reacted with sodium hydrogen carbonate [190, 191] or sodium alkyl carbonates [192] to afford CCs in good yield (82%), especially when the reaction was carried out under high pressure and temperature. When tetramethylammonium hydrogen carbonate was used in acetonitrile (Equation 7.18) [193], the relevant carbonate could be prepared in high yields under mild conditions. 

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-... 

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. 

Oxirane formation by intramolecular displacement reactions of halohydrins (2-halo-1-ols) is a general and useful reaction, as discussed in Chapter 1.03.4.2. A unique example of an intramolecular substitution is observed during f-butyllithium addition to (156) the reaction involves 1,2-attack of the resulting alkoxide ion in (157) with concomitant 1,2-alkyl shift to give the protoadamantane derivative (158), reminiscent of a fragmentation reaction (Scheme 29) <91JOC1700>. 

This problem is similar to the one in part d) in that it requires the preparation of a halohydrin from an aUcyl halide. The strategy is the same. Convert the alkyl halide to an alkene, and then form the halohydrin by treatment with the appropriate halogen in aqueous solution. 

Dialkyl phthalates, in which the two alkyl grups may be the same or different, can be prepared by heating a sodium ihonoalkyl phthalate with an alkyl halide or a polymethylene halohydrin. ... 

Synthesis.—A new route to alkyl-substituted crown compounds involves" the reaction of polyethylene glycols with alkenes in the presence of a positive halogen source (Scheme 51), followed by base-catalysed cyclization of the halohydrins produced. One approach to aza-crown molecules relies on alkylation of toluene-p-sulphonamide anions, and a study of some methods for N-detosylation of the cyclic products has been published. 

It has to be added that 35 provides also halohydrins such as 39, which can react even with the sodium salt of adenine to generate a quantitative yield of a mixture of the Nj- (see 40) and N -alkylation products [11]. 

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