Acetals, acid catalyzed from ortho esters

Thus, two types of active esters are of interest those formed from an acid and a substituted phenol (12-15) and those formed from an acid and a substituted hydroxylamine (16-19). Both types are reactive by virtue of the electron-withdrawing properties of the OR moiety in 2. The level of activation of the substituted phenyl esters varies directly with the electronic effect going from 4-nitrophenyl to 2,4,5-trichlorophenyl, pentachlorophenyl, and pentafluorophenyl, which corresponds with the increasing acidity of the phenols. A diminution in the rate of aminolysis is caused by the presence of a substituent in the ortho position of the ring.f l An additional phenomenon contributes to the reactivity of the esters formed from substituted hydroxylamines, namely anchimeric assistance. Since the anoinolysis of active esters is a bimolecular reaction, it is dependent on concentration and can be forced to completion by an excess of one of the reactants. Aminolysis is also characterized by a pronounced dependence on the polarity of the solvent in particular for the esters formed from substituted phenols, the half-life of a 2,4,5-trichlorophenyl ester in the presence of benzylamine being one hundred times less in dimethylformamide than in benzene. Furthermore, aminolysis is catalyzed by mild acid such as acetic acid. The rate of anoinolysis is slowed if the side chain of the active ester contains a P-methyl substituent. 

Dialkyl acetals and ketals can easily be formed from carbonyl compounds with alcohols under acidic conditions. Some representative examples for the great variety of methods available for this transformation are given in Scheme 77. As is demonstrated, both simple alcohols themselves or formic acid ortho esters can be used for acetal formation in the presence of hydrochloric acid, toluenesulfonic acid °° or activated alumina (Montmorrilonite clay K-10). ° Owing to different carbonyl reactivities, regio- and chemo-selective differentiation is often realizable, as has been shown, for example, on androstane-3,17-dione (78). Acid-catalyzed acetalization selectively delivers the 3-ketal, whereas the sterically hindered 17-carbonyl function remains unaffected. Under neutral conditions the reactions are promoted by cata-... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

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