Acetal hydrolyses

While the A1 mechanism shown above operates in most acetal hydrolyses, it has been shown that at least two other mechanisms can take place with suitable substrates. In one of these mechanisms the second and third of the above steps are concerted, so that the mechanism is Sn2cA (or A2). This has been shown, for example, in the hydrolysis of 1,1-diethoxyethane, by isotope effect studies ... 

In a moist air atmosphere, vinyl acetate polymerised spontaneously with extreme violence. The investigation led to the following interpretation. In the presence of moisture, the acetate hydrolysed forming acetaldehyde ... 

Characteristic markers of Venice turpentine are larixol and larixyl acetate, but in many cases they may remain undetected, as larixyl acetate hydrolyses and the methylation of hydroxyl groups is not as effective as for carboxylic acids. On-line derivatization with tetramethylammonium hydroxide (TMAH) is, for instance, scarcely effective on hydroxyl groups and involves a number of secondary reactions (isomerization, dehydration and cleavage of hydrolysable bonds) due to the strong alkalinity of the TMAH solution. When the experimental conditions are such that THM of labdanes occurs larixol and larixyl acetate are detected as a single peak since in the derivatization process larixyl acetate is hydrolysed to larixol [29]. 

The hydrolysis of substituted phenyl acetates has been studied in the presence of cyclodextrins (Van Etten et al, 1967a, b). No correlation was found between the rate constants for hydrolysis and a for the substituent group. Specificity was directed towards meta-substituents. m-t-Butylphenyl acetate hydrolyses 240 times faster in the presence of 0-01 M cyclohepta-amylose. Comparison of spectral shifts upon inclusion of p-t-butyl and m-t-butylphenol indicated that benzene rings of p-substituted phenols are included within the cavity of cyclodextrins [45], but that the benzene ring of the meta-isomer... 

Chiral N/O-acetals may racemize in the solid state when water of crystallization is present. Examples are the epimerizations of the oxazolidines 97 that contain water from their preparation by stereoselective condensation. Thus, the kinetically preferred products 97a,b (which are admixed to the thermodynamically more stable products 98a,b) epimerize within some weeks in the solid state to give enantiopure 98a,b [661 (Scheme 9). It appears that the N/O-acetal hydrolyses and recloses. Solid-state racemizations are quantitative if the 1 1 equilibrium between the enantiomers is obtained. Therefore they do not really fulfill the criterion of only one product. Numerous examples in the organo-metallic field are listed in [671 and [681. 

Heating the first-obtained product in a strong acid leads to the hydrolysis of the ester. The resulting (3-ketoacid loses carbon dioxide under reaction conditions the acetal hydrolyses also reveal the free aldehyde (106-6). Aldol condensation of this last intermediate in the presence of a base with readily available rhodanine (106-7) links the two fragments. The double bond in the first-formed product is then reduced catalytically to afford darglitazone (106-8) [117]. 

An intermediate in the synthesis of laulimalide by Davidson8 illustrates the differential protection of alcohols. The starting materials 56 and 57 already have an alcohol protected as a TBDMS silyl ether and a diol protected as an acetal. The alcohol in 58 is protected as a p-methoxybenzyl ether and the acetal hydrolysed by acetal exchange to give the free diol 60. Selective protection of the primary alcohol by a bulky acyl group (pivaloyl, i-BuCO ) 61 allows silylation of the secondary alcohol with a TIPS group 62. Finally the pivaloyl group is selectively removed by DIBAL reduction to release just one free alcohol 63. 

The available data on the effects of micellar systems on orthoester and acetal hydrolyses are summarized in Table 6. 

Acid-catalysed hydrolysis offers a cheap and obvious method for the cleavage of arylmethylene acetals but oftentimes the conditions required (or pH 1) can be quite harsh, e.g. dilute sulfuric acid at elevated temperature. The lability of arylmethylene acetals can be enhanced both electronically or sterically. For example, p-methoxybenzylidene acetals hydrolyse about 10 times faster than benzylidene acetals79 owing to participation of the p-methoxy substituent in resonance stabilisation of the oxonium intermediate as illustrated by the hydrolysis shown in Scheme 3.48.80 p-Methoxybenzylidene acetals can be hydrolysed in 80% aqueous acetic acid at room temperature. 

This question develops immediately from the last. The noncyclic acetal hydrolyses easily because the equilibrium favours the three molecules (one aldehyde and two alcohols). The two remaining acetals are a cyclic acetal or dioxolane and a cyclic dithioacetal or dithiane. The cyclic acetal jus needs more vigorous acidic conditions but the dithiane needs a Lewis acid that likes sulfur. Mercuri - Hg(II) - is a good example. The precise reagents and conditions are not important. 

Figure 3.19 Glycoside and acetal hydrolyses catalysed by electrophiles.

Acid catalysts 78 and 84 were both successfully used inacid-catalyzed acetal hydrolyses (Eqs. 33 and 34). However, the reactions did not always strictly turn on and off below and above the LOST of 78 and 84. For example, when 84 was usedin a biphasic toluene/water mixture at 1 °C, hydrolysis of the acetal of acetophenone was about four times slower than at 24 °C. At 48 °C (above 84 s LOST), the hydrolysis rate was ca. half the rate at 24 °C. In this case the reaction... 

Of course you want us to prove it. Well, in this example the starting material has three acetals an ordinary acetal formed from methanol (in black), a five-membered cyclic acetai, and a dithioacetal. Only the black acetal hydrolyses under these mild conditions. 

Sugar cyclopentylidene acetals hydrolyse slightly faster than the corresponding isopropylidene derivatives. l,2 3,5-Di-0-cyclopentylidene-a-D-xylose (11) was fully deprotected by use of strong acid resin and methanol, whereas use of methanolic HCl allowed the selective removal of the dioxane ring. This selectivity has been exploited, for... 

As acetic acid is produced on hydrolysis, the progress of the reaction is followed by withdrawing definite volumes of the reaction mixture at suitable time intervals and titrating against a standard alkali solution. The increase in the volume of alkali used is a measure of methyl acetate hydrolysed. If V,, and Too... 

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