Methylene acetal

Methylene acetals and diphenylmethylene acetals (see section 3.2.5) are the runts of the acetal family litter. They are not used often but they have properties that in special circumstances can be useful. The prime virtues of methylene acetals are their hydrolytic stability and negligible mass they can survive rather harsh reaction conditions unscathed. Likewise, the prime detraction of methylene acetals is their stability they require rather brutal conditions to remove them hence, they have limited utility. 

Selective hydrolysis of the highly labile trifluoroacetate ester was then easily achieved by adjusting the pH of the reaction mixture to 6.5 with aqueous sodium carbonate to give the diol monoacetate 92.6 in 87% yield. 

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Methylene acetals are the most stable acetals to acid hydrolysis. Difficulty in their removal is probably the reason that these compounds have not been used much. 

MeO)2CH2, LiBr, TsOH, CH2CI2, 23°, 83% yield. In this case a 1,3-methylene acetal is formed in preference to a 1,2-methylene acetal from a 1,2,3-triol. These conditions, also protect simple alcohols as their MOM derivatives. 

CH2(OMe)2, CH2CI2, TfOH, 4 h, 25°, 65% yield. This method is suitable for the formation of primary, secondary, allylic, and propargylic MOM ethers. Tertiary alcohols fail to give a complete reaction. 1,3-Diols give methylene acetals (89% yield). 

Cleavage of the POM group in the presence of neighboring hydroxyls can result in the formation of methylene acetals. ... 

Nal, SiCl4, rt, 20-60 min, 78% yield. Cleavage results in subsequent formation of a diiodide, but this is not a general process. For the most part, ketals are cleaved to give the ketone, while catechol methylene acetals return the catechol. ... 

Diol monoacetates are obtained from the diols via the intermediate formation of the bromomethyl acetals and their conversion into cyclic methylene acetals, which undergo acid-catalysed ring-opening to yield the acetate ester [31]. The ring-opening is regio-specific to form the ester at the least hindered hydroxyl group. 

The second dianhydro-xylitol was obtained23 by methylenation of 1,4-anhydro-DL-xylitol, with paraformaldehyde and concentrated hydrochloric acid, to give the 3,5-methylene acetal this was methylated to the 2-methyl ether, which was hydrolyzed, and the product mono-p-toluenesulfonylated to the 5-p-toluenesulfonic ester. On treatment with aqueous sodium hydroxide at 40-50°, the last gave syrupy l,4 3,5-dianhydro-2-0-methyl-DL-xylitol (17, D form). 

The crucial methylenation step in this synthesis undoubtedly gave the 3,5-methylene acetal, not the 2,3-acetal (or the highly improbable 2,5-methylene acetal), because, otherwise, a 6-0-methyl-2(or 3)-0-p-tolylsulfonyl compound would have been obtained which could only have formed an epoxide (oxirane). The oxirane ring might have been opened under the conditions of the saponification the product would not then have been a dianhydride. 

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... 

An interpretation of the oxidation of acetals by chromium trioxide is summarized in Scheme 1 the reagent could initially remove a proton from the acetalic carbon atom, to give a dioxolan-(or dioxan-)2-ylium ion, rapidly hydrolyzed to an ester (formyl, acetyl, or benzoyl) of an a-alcohol, which would be further oxidized to a ketone [see Scheme 1, path (a)] in the case of methylene acetals, in the presence of acetic anhydride (which acts as a water scavenger), the intermediate is further oxidized, probably through a chromic ester. 

Summarizing, it may be concluded that the ease of hydrogenolysis is (1) cyclic orthoester > isopropylidene acetal, cyclohexylidene acetal > benzylidene acetal > ethylidene acetal > methylene acetal, and (2) 5,6-O-linked and 3,5-O-linked > 1,2-0-linked acetals. 

Reaction of diethyl ethoxymethylenemalonate or ethyl cyanoethoxy-methylene acetate with l-phenyl-4-aminopyrazole gave esters 187a, which cyclized in boiling Dowtherm to the corresponding pyridones 188a.158 The... 

Methylene acetals.1 Carbohydrate methylene acetals are prepared conveniently liom 1,3-diols and cis- or iranv-1,2-diols by reaction with dibromomethane in dry I )MS<) in the presence of finely powdered potassium hydroxide. Yields are 35-90%. 

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. 

The phase-transfer technique is a simple and efficient tool for the benzylation of carbohydrates. With benzyltriethylammonium chloride or tetrabutylammonium bromide as a catalyst, a mixture of aqueous, 50 % sodium hydroxide and benzyl bromide or chloride in benzene or dichloromethane solution gives a good yield of the fully protected product [103, 104], such as methyl 2,3-di-0-benzyl-4,6-0-benzylidene c-D-glucopyranoside, when stirred at room temperature for several hours. The latter catalyst is slightly more efficient. Dichloromethane has been observed to produce methylene acetals from cis vicinal diols under comparable conditions [103]. 

HI - PRE6N-4-ENE-3>20-D10NE. 21-fUUORO-17-HYOROXY-6-METHYLENE-. ACETATE... 

Our interest in such methylene acetal derivatives is connected with the design of mimetics of Sialyl Lewis X (sLex) 1, a proposed native ligand for the selectin family of cell adhesion molecules. sLex-selectin interactions have been... 

The introduction of a methylene acetal tether needs some further discussion. The 2-propenyl ether is prepared by reaction of a C(2) acetyl group with Tebbe reagent, (C5H5)2TiMe2. Treatment of the resulting enol ether with p-toluenesulfonic acid results in the formation of an oxocarbenium ion, which upon reaction with an alcohol provides an acetal. As can be seen in the reaction scheme, the acid is regenerated, thus only a catalytic amount is required. 

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