Ethers with strong acid

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly to ethynodrel (39), an orally active progestin. This is the progestational component of the first oral contraceptive to be offered for sale. Treatment of the ethynyl enol ether with strong acid leads to yet another oral progestin employed as a contraceptive, norethindrone (40). ° In practice these and all other so-called combination contraceptives are mixtures of 1-2% mestranol... 

Alcohols can be dehydrated with strong acid catalysts and high reaction temperatures to produce ethers. This method is particularly useful for the preparation of symmetrical lower alkyl ethers, such as ethyl ether. 

The reacting species is a rather weak electrophile and, therefore, only particularly reactive aromatics are suitable substrates. Consequently, the reaction is restricted for polyhydric phenols and their ethers, and reactive heterocycles. With strong acidic systems, such as AICI3 in halogenated benzene solvents, alkylben-zenes can react at more elevated temperatures (>50°C). Trichloroacetonitrile works also well with nonactivated aromatics. The 12 chloroimine, the protonated nitrile (13), or the nitrile coordinated with the Lewis acid are possible involved electrophiles. 

The properties of the ethers may be summarized hy (ltvvilh the exception of dimethyl ether which is a gas. die ethers arc volatile, mobile, inflammable liquids that are lighter than H O 121 they are relatively inert chemically, not being acted on by alkali metals or alkalis and not reacting with dilute acids (31 they form substitution producls when reacted wiih chlorine and bromine and (4t they decompose when healed with strong acids, yielding esters. 

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