Methylene acetals, acetolysis

By acetolysis of a- or /3-methylene acetals of polyols with trifluoroacetic anhydride-carboxylic acid mixtures, derivatives may be prepared71 that are O-acylated at the primary hydroxyl group, and that have free hydroxyl groups at certain secondary positions. 

In general, only methylene acetals have been selectively depro-tected in this way on acetolysis, benzylidene and isopropylidene acetals are readily converted into the corresponding peracetates of the... 

Much work was conducted by Hudson and his school on the acetolysis of methylene acetals of alditols. Their principal finding was that a methylene acetal that links primary and secondary positions is cleaved readily, and preferentially, at the primary position to give the primary acetate and the acetoxymethyl ether of the secondary hydroxyl group (Scheme 1). The reagent... 

Only two comparisons of acetolysis of secondary-secondary methylene acetals were made 1,6-di- O-benzoyl-2,4 3,5-di-O-methylene-D-glucitol... 

Prolonged treatment of 1,3-erythro methylene acetals of alditols does, however, cause their acetolysis. ... 

Trifluoroacetic anhydride-acetic acid, when used for the acetolysis of methylene acetals of alditols, shows the same specificity as acetic anhydride-sulfuric acid. - However, the products formed can be converted, by very mild hydrolysis, into the acetate-hydroxy derivative (6), because of facile cleavage of the (trifluoroacetoxy) methyl ether linkage (5). 

Methylene acetals may be cleaved by acidic hydrolysis [136], by acetolysis [137], and by treatment with BCI3 [138]. The use of the methylene protecting group is somewhat limited by its comparative resistance to acidic hydrolysis. Thus 1,3 4,6-dimethylenedulcitol (65) remained unchanged after it had been treated with boiling 0.1 AT-hydrochloric acid for 1 hr however, it was hydrolyzed by AT-acid under the same conditions [139]. 

Notable progress in the structural analysis of methylene derivatives of the polyhydric alcohols resulted from the investigations of Hann, Hudson and their co-workers26 80,40-4 into the behavior of these compounds during acetolysis. It was found that a mixture of acetic anhydride, acetic acid and 1-2% sulfuric acid ruptures preferentially any methylene bridge which spans a primary and a secondary position, giving the acetate ester of the primary hydroxyl and the acetoxymethyl ether of the secondary hydroxyl subsequent treatment with sodium methoxide removes each of these substituents. Under similar conditions, the acetolysis of a benzylidene compound results in the replacement of the arylidene residue, wherever it is located in the molecule, by two acetyl groups.16 29 47 48... 

One acetal group of the trimethylene derivative was shown to span positions 2 and 4 by the demonstration that the compound afforded 2,4-methylene-D-talitol when subjected to acetolysis and then to treatment with sodium methoxide.46 The two labile groups may have been of the 1,3 5,6-, 1,5 3,6- or 1,6 3,5-type, of which the first was highly probable accordingly the triacetal was named l,3 2,4 5,6-trimethylene-D-talitol (XXXII).46... 

Benzylidene acetals are much less resistant to acetolysis than are their methylene analogues, and all rings are readily ruptured, even those engaged at secondary positions (see Table VI). 

Limited Acetolysis and Saponification of Methylene and Benzylidene Acetals... 

Following the observation that benzyl ethers are cleaved by acetic anhydride in the presence of sulfuric acid or perchloric acid, Allerton and Fletcher S extended the work to carbohydrate systems. 2,5-Di-O-benzyl-l,3 4,6-di-0-methylene-D-mannitol (12) gave 1,3,4,6-tetra-0-acetyl-2, 5-di-O-benzyl-D-mannitol in the presence of 0.09% of sulfuric acid, but, with 2.4% of the acid, the hexaacetate was formed. With 1,6-di-O-benzyl-2,4 3,5-di-0-methylene-L-iditol (13), brief acetolysis gave the di-0-acetyl-di-O-methylene derivative longer treatment gave the hexaacetate. 

As seen from Table 11, the kinetically controlled products of the reaction between the methyl-substituted cations 545 and 547 are mainly tertiary, rather than secondary, acetates but in every case the products have only a cis-configuration. Upon acetolysis of 6,6-dideuterated monomethyl-substituted cis-tosylate 544 the tertiary acetate contains, judging by the PMR spectra, two H atoms in the methylene group of the cyclopropane ring, and the secondary — one H atom on the average, in full conformity with the structure of the intermediate ion 545. On the other hand, the secondary acetate formed on solvolysis of the trans-epimer contains two D atoms in the cyclopropane group. Thus in this case, either, no conversion is observed of a classical ion into a nonclassical one in the trans-epimer solvolysis. 

Acetolysis of the 6a,7a-methylene-4/3-mesyIoxycholestane (136) gave the 7a-acetoxymethyl compound (137) as the sole product.The ring expansion of steroidal halogenocyclopropyl acetates derived from enol acetates and haloge-nated carbenes has been studied in further detail.The base-catalysed reactions... 

In a less complex rearrangement, Coates and Chen (66) found that acetolysis of longicamphenilyl tosylate (104) affords, in addition to nor-longicyclene (105) and acetate products, the novel tricyclic olefins (106) and (107). The rearrangement pathway from (104) to (106) is pictured as a C-3 to C-4 hydride shift, followed by methylene migration and then proton elimination. In formic acid, (106) goes over to (107). 

The structures of many methylene sugar derivatives have not been determined, but those of many of the alditol derivatives are known. The greater ease of acetolysis of methylene groups attached to primary hydroxyls over those attached to secondary hydroxyls, has been of considerable value in the elucidation of the structures of these compounds by Hudson and co-workers (96), Thus the linkages at carbons 1 and 6 of 1,3 2,4 5,6-tri-O-methylene-D-glucitol are cleaved with sulfuric acid in acetic anhydride and acetic acid as shown in the formulas. The structure of the mono-0-methylene-D-glucitol is demonstrated by its oxidation with periodic acid... 

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