Acetalation methods

Acetale konnen durch elektrophile Hydride in den meisten Fallen reduziert werden, aus acyclischen Acetalen werden Ather und Alkohole, aus cyclischen tu-Hydroxy-ather erhalten. Der erste Schritt, der durch Lewis-Sauren katalysiert wird, ist auch hier die Bil-dung des entsprechenden Carbcnium-Ions (s.S. 409). Die Methode ermoglicht die einfa-che Herstellung von Athern aus Aldehyden und Ketonen. 

As these acetals could be converted into the 4,6-O-ethylidene derivatives on treatment with acid, it was reasoned that use of a cyclic vinyl ether, namely, 3,4-dihydro-2H-pyran, might prevent this second process, thus leading to a more useful method of selective acetalation.338 An equimolar reaction with methyl a-D-glu-copyranoside for 4 days in N,N-dimethylformamide led to utilization of 88% of the glycoside, and the 6-(tetrahydropyran-2-yl) ether constituted —85% of the crude reaction-product. In contrast to the steric control apparent in this instance, reaction of 3,4-dihydro-2H-pyran with the axial and equatorial hydroxyl groups in dl-1,4,5,6-tetra-O-acetyl-mi/o-inositol was completely unselective,339 a fact that has been rationalized310 in terms of the probable mechanism of these reactions. 

Acetals of o-GlcpNAc 28a (Z=NHAc) [99] and o-Glcp 28b [55] were prepared by condensation of the appropriate aldehyde or aldehyde dimethyl acetal with the unprotected carbohydrate. An improvement of the classical methods of acetalation (microwave irradiation of montmorillonite) made it possible to synthesize various 5,6-0- -alkylacetals of L-galactono-1,4-lactone [100]. 

A known method of acetalation by means of an enol acetate (2-acet-oxypropene),21 previously reported for some monosaccharides,22 has been reinvestigated.23 As it gave thermodynamically formed acetals in low to moderate yield (for instance, 30 and 54% yield, respectively, for the preparation of 2,3-O-isopropylidene-D-ribofuranose and 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose), it appears to have no special advantages over the methods already available. 

Several less general methods of acetalation are known [28], and a few of diem have found some application in carbohydrate chemistry. Because they can represent exceptional alternatives to classic procedures, they will be briefly presented here. 

Sulfonic esters are frequently prepared as intermediates in carbohydrate chemistry, and their widespread use in synthetic work may be attributed to several factors adequate methods are available for sulfonylation in good yield, and sulfonyloxy groups exhibit high stability under the conditions used for acetalation, glycosidation, esterification, etherification, and mercaptalation. In many cases, the substituents introduced by these reactions may also be removed with-... 

One method of synthesizing the aspirin substitute, acetaminophen, involves a three-step procedure as outlined in Fig. PI. 113. First, p-nitrophenol is catalytically hydrogenated in the presence of aqueous hydrochloric acid to the acid chloride salt of p-aminophenol with a 86.9% degree of completion. Next the salt is neutralized to obtain p-aminophenol with a 0.95 fractional conversion. Finally, the p-aminophe-nol is acetalated by reacting with acetic anhydryde, resulting in a yield of 3 kg mol of acetaminophen per 4 kg mol. What is the overall conversion fraction of p-nitro-phenol to acetaminophen ... 

There are two known methods of 3-fluorofurans synthesis from the fluorine-containing synthones. Hydrolysis of gew-difluorocyclopropenyl acetales under acidic conditions gives 1-aryl-2-fluorofurans 13. ... 

Methods for determining the anomeric configurations of ribonucleosides have been reviewed. The well known anomeric-proton rule for determining anomeric configuration from n.m.r. chemical shifts has been supplemented by the rule, which states that the heterocyclic proton on the carbon next to the glycosidically linked nitrogen is downfield in the isomer in which the base and the C-l hydroxy-group are trans to each other relative to the same proton in the cis isomer. The rule holds for unprotected and acetalated nucleosides, but not for acyl or benzyl derivatives. ... 

A very useful method for determining ring-size of cyclic isopropylidene acetals has been developed based on the chemical shift values of the acetalic carbon atom, and the difference in chemical shift for the two methyl groups. ... 

They also demonstrated that inexpensive molecular iodine can be used as a cheap, nontoxic, general, and fast catalyst for one-pot tandem acetalation-esteri-fication reactions of glycosides in good to excellent yields without the need of purification after every reaction step. Further, the addition of catalytic DMAP can be used to accelerate the esterification step and thus shorten the reaction times. The method is mild and compatible with different thioglycosides and 0-glycosides, applicable to the formation of 4,6-0-benzylidene and 4,6-0-p-methoxybenzylidene acetals in tandem reaction with either 2,3-0-di-acetate or 2,3-0-di-benzoate esters and also amenable to commonly used amino-protecting groups (e.g., phthalimides and 2,2,2-trichloroethoxycarbonyl chloride). 

Another common method for the synthesis of polyacetals involves trans-acetalation reactions of diols with acetylenic compounds [14] or vinyl ethers [15], The reaction of bis(chloromethyl) ether with diols in the presence of pyridine to give polyacetals is not recommended since bis(chloromethyl) ether is considered highly carcinogenic [16]. 

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