Mannitol 2.5- 0-methylene acetal

The readily available [77, 78] l,6-di-0-benzoyl-3,4-0-benzylidene-2,5-0-methy-lene-D-mannitol has been converted [79] into the benzyl ether (60), which on periodate oxidation and borohydride reduction gives the methylene acetal (61) which readily gives 1 -O-benzyl-L-glycerol for use in lipid synthesis. The acyl derivative (62) has been used [80] in glycolipid synthesis by glycosidation of the hydroxyl group. 

They found that these rules complied with the structures that were then known for the methylene acetals of sorbitol, mannitol, dulcitol, iditol, 6-desoxy-sorbitol, xylitol and ribitol. From the rules they predicted structures for methylene acetals of allitol and talitol, and several of these predicted acetals have been discovered in later researches. Among the... 

Six-membered acetal rings fused to seven-membered rings are found in acetals formed directly from mannitol and certain of its derivatives. The 1,3 2,5 4,6-structure has been proved for the tri-O-methylene " and tri-0-ethylidene " derivatives of mannitol, and the 1,3 2,5-structure for the di-O-methylene derivative of 6-deoxy-L-mannitol. " These acetals are markedly more stable than the 2,4 3,5-diacetals discussed above. Their stability has been related to the probable mechanism of formation,"" but is also understandable on conformational grounds. " The ring junctions are trans, and the triacetals LXI have the trans-anti-trans configuration, which... 

Mannitol has been converted to a mixture of 2-C-hydroxymethyl-DL-ribose and -xylose derivatives by periodate oxidation of its 2,5-0-methylene acetal followed by an intramolecular aldol condensation of the resulting dialdehyde the ribose enantiomers (18) predominate. ... 

As the acetal group in 2,5-O-methylene-D-mannitol is relatively resistant to hydrolysis, S. B. Baker" studied the stabilities of 1,4 3,6-dianhydro-2,5-0-methylene-D-mannitol and -D-iditol relative to that of the D-mannitol acetal. He synthesized l,4 3,6-dianhydro-2,5-0-methylene-D-mannitol by cyclizing 2,5-0-methylene-l,6-di-0-p-tolyl-sulfonyl-D-mannitol or by methylenation of l,4 3,6-dianhydro-D-man-nitol. The D-iditol isomer was prepared by cyclizing 1,6-di-O-benzoyl-... 

The dependence of the acid-lability of trialkylsilyl and related ethers on the type of substitution at silicon is illustrated by the formation302 of l-0-(tert-butyldiphenylsilyl)-2,3 4,5-di-0-methylene-D-mannitol (47) in 96% yield on treatment of 6-0-(terf-butyldimethylsilyl)-l-0-(fert-butyldiphenylsilyl)-2,3 4,5-di-O-methylene-D-manni-tol (48) with 80% acetic acid. 

The behavior towards potassium thiolacetate of a few alditols bearing acetal rings has been studied. On refluxing in acetone for 6 hours, 2,3,4,5-di-0-methylene-l,6-di-0-tosyl-D-mannitol gave36 an 89% yield of the... 

When the methylenation of D-mannitol is carried out at a higher temperature and for a shorter time, there is produced a dimethylene-D-mannitol (m. p. 204-208°), in addition to the triacetal previously mentioned.68 The dimethylene compound is not oxidized by periodic acid and its ditosyl ester does not exchange with sodium iodide, even in acetic anhydride at 140°.62 Consequently it must be either 1,2,4,6- or 1,3,4,6-dimethylene-D-mannitol (the 1,2,4,6- and 1,3,5,6-structures are identical) the 1,3 4,6-structure was favored by Ness, Hann and Hudson40 in view of the rapidity of its conversion into 1,3 2,5 4,6-trimethylene-D-mannitol. 

With the aid of these rules, we have predicted the structures of the acetals which would be expected to result from the benzylidenation, ethylidenation and methylenation of all the tetritols, pentitols and hexi-tols. As will be seen from Table IV, the predicted structures agree very well with the accepted structures of the compounds. The rules explain, too, the syntheses of 3,5-benzylidene- and 3,5-methylene-gluco-[Pg.180]

Bicyclic trans diacetals with one axial residue will be considerably less stable than the acetals with equatorial residues this is shown by the absence of 3,5 4,6-diacetals of glucitol, 1,3 2,4-diacetals of mannitol and 2,4 3,5-diacetals of arabitol from the products of acetalation of the free glycitols. However, by suitable masking of hydroxyl groups, some trans diacetals with axial substituents should be obtainable. The most interesting will be 2,4 3,5-di-0-methylene-D-talitol (LIII), in which one terminal group is axial and the other equatorial (see p. 43). 

The conformational flexibility postulated for the 2,4 3,5-diacetals of mannitol would disappear in acetals prepared from higher aldehydes and therefore possessing substituents at the acetal carbon atoms, but the status of such acetals is at present obscure., Two isomers of l,6-dichloro-l,6-dideoxy-2,3,4,5-di-O-ethylidene-D-mannitol are known, but the structures have not been determined. Two stereoisomers with the 2,4 3,5-structure and related to the H-inside and 0-inside conformations LVI and LVII, respectively, are clearly possible, but the structures 2,3 4,5 and 2,5 3,4 must also be considered. There is considerable scope for more work on 2,3,4,5-diacetals of mannitol, and confirmation of the structure XLVII advanced by Ness, Hann and Hudson for their mono-O-benzylidene-mono-O-methylene derivative is a necessary step in the assessment of the relative stability of the different structural types. 

The two endo hydroxyl groups in LXIV are sufficiently close together to afford cyclic acetals, and 1,4 3,6-dianhydro-2,5-0-methylene-D-mannitol is readily obtainable. The formation of cyclic acetals from LXV and LXVI appears to be impossible because of the wide separation of the hydroxyl groups, and the substance reported as 1,4 3,6-dianhydro-2,5-0-methylene-L-iditol must have some other structure. 

Tri-O-methylene-D-mannitol (1 mole), on treatment with the 10 1 mixture, that is, acetic acid (45 moles) and trifiuoroacetic anhydride (4.5 moles), showed a similar differentiation in reactivity of the acetal rings. The only product recoverable in the early stages of the reaction at 50° was (30), with the further product (31) appearing much later. Higher temperatures were... 

Ring Scission of Cyclic Acetals. Part III, Reaction of Acetyl Trifluoroacetate with l,3 2,5 4,6-Tri-0-methylene-D-mannitol, T. G. Bonner, E. J. Bourne, and D. Lewis, J. Chem. Soc., C, 2321-2336 (1967). 

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. 

Cyclitols, Alditols, and otho Acyclic Derivatives.—epi-Inositol.SrClj/ dl-mannitol, ° l,3,4,6-tetra-0-acetyl-2,5-0-methylene-D-mannitol/ o-mannitol l,2 3,4 5,6-tris(phenylboronate)/ l-(l-S-ethyl-l-thio-D-arabinitol-l-yl)-5-fluorouracil and its 2, 3, 4, 5 -tetra-acetate/ 4,5,6-tri-0-benzoyl-2,3-di S-ethyl-... 

Two epimeric dideoxyinositols were obtained from qninic acid by way of the corresponding trihydroxycyclohexanone (6 ) (Fig. 2). Micheel cyclized the 1,6-diiodohydrin of di-O-methylene-D-mannitol by heating it with molecular silver in toluene or xylene at 165-170 to obtain a dimethylene derivative of a dideoxyinositol (63), Removal of the acetal groups gave... 

The presence of the hydrofuran ring also may alter drastically the stability of acetal substituents. For example, the benzylidene acetal moiety, normally stable to alkali, is removed from 3,5-0-benzylidene-6-chloro-6-deoxy-l,4-anhydro-D-glucitol when the compound is heated in alkaline or neutral solution (75). Similarly, l,4 3,6-dianhydro-2,5-0-methylene-D-mannitol loses its methylene group upon heating in aqueous solution (76). 

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