Lithium aluminum hydride alcohol synthesis from acid chlorides

Numerous methods for the synthesis of salicyl alcohol exist. These involve the reduction of salicylaldehyde or of salicylic acid and its derivatives. The alcohol can be prepared in almost theoretical yield by the reduction of salicylaldehyde with sodium amalgam, sodium borohydride, or lithium aluminum hydride by catalytic hydrogenation over platinum black or Raney nickel or by hydrogenation over platinum and ferrous chloride in alcohol. The electrolytic reduction of salicylaldehyde in sodium bicarbonate solution at a mercury cathode with carbon dioxide passed into the mixture also yields saligenin. It is formed by the electrolytic reduction at lead electrodes of salicylic acids in aqueous alcoholic solution or sodium salicylate in the presence of boric acid and sodium sulfate. Salicylamide in aqueous alcohol solution acidified with acetic acid is reduced to salicyl alcohol by sodium amalgam in 63% yield. Salicyl alcohol forms along with -hydroxybenzyl alcohol by the action of formaldehyde on phenol in the presence of sodium hydroxide or calcium oxide. High yields of salicyl alcohol from phenol and formaldehyde in the presence of a molar equivalent of ether additives have been reported (60). Phenyl metaborate prepared from phenol and boric acid yields salicyl alcohol after treatment with formaldehyde and hydrolysis (61). 

A slight modification of Corey synthesis (see Scheme 3.16) affords an estrane that bears a hydroxyl at C14. The 14-dehydroestrone intermediate from that synthesis is first reduced to give the corresponding 17[3-hydroxy analogue. This, in turn, is converted to its tert-butyldimethylsilyl ether (TBDMS) (32-1) by reaction with the silyl chloride (Scheme 3.32). Oxidation by means of w-chloroperbenzoic acid (mCPBA) affords the 14—15 epoxide 32-2 as a 3 1 mixture of a- and p-epimers. Treatment of the former with lithium aluminum hydride leads to the alcohol... 

Apart from syntheses aimed at producing substances for biological evaluation, which will be discussed later, most work in this area has employed aldehydes rather than ketones. Acidic conditions must be avoided during the isolation of the alcohols, since ethers are readily formed.47,76 In the great majority of cases the alcohol has been successfully reduced by the lithium aluminum hydride-aluminum chloride method to which we have already referred. Halogen substituents on the thiophene ring (even iodine) survive this procedure. The methods of synthesis discussed in the preceding sections are not suitable for the preparation of unsymmetric dithienylmeth-anes with free thiophene a-positions, and it is for these substances that the... 

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