Acetals by transacetalization

When an acetal is heated with an excess of an alcohol containing an acid catalyst, transacetalization occurs to some extent  

This process can be used for preparation of either symmetrical or mixed acetals.926 927 The equilibrium can be shifted in the direction of the new alcohol by using a large excess of the alcohol or by distilling off a lower-boiling alcohol or a lower-boiling acetal if such is formed.928 929 

Mixed alcohols can be prepared if an excess of the acetal is used. When an ester group is present in the molecule as well as an acetal group, transacetalization can be achieved without transesterification if precise reaction conditions are observed.930 Secondary alcohols can also beusedintransacetalizations.927 

Transacetalization is particularly suitable for the synthesis of cyclic acetals.931 932 It is sometimes an advantage first to prepare the starting acetal and then to perform the transacetalization operation in that reaction mixture.926 927 933 934 

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Diethylacetal 1 has been used to obtain various other acetals by transacetalization,6 14c such as the dimethyl, the ethyleneglycol, and the neopentylglycol acetal (2,2-dimethyl-1,3-propylidene acetal). 

Acetals of A. A -dimethyl hydrazones 4, derived from glyoxal (1) and various enantiomerically pure diols (c.g., 3a-f)24, are readily prepared by transacetalization of 2. Addition of methyl-or butyllithium to 4 provides the corresponding hydrazines in good yield (70-88%) and moderate to excellent diastereoselectivity (see Table 3)4,5. 

Support-bound alcohols and thiols can be used to immobilize aldehydes and ketones as acetals. Mixed acetals of carbonyl compounds with support-bound alcohols can be prepared by transacetalization of a symmetric acetal under acidic conditions [719]. The formation of mixed acetals on solid phase is, however, not always easy to perform and control, and so prior preparation of a mixed acetal in solution followed by loading onto a support is often the preferred protocol [626,637]. Carbohydrates can be linked to resin-bound alcohols or thiols as glycosides (Table 3.40). 

Preparation.l Dialkyl acetals of DMF are generally prepared by transacetal-ization of the dimethyl or diethyl acetal, but this reaction is not useful in the case of the di-r-butyl acetal. Replacement of one methoxy group of DMF dimethyl acetal occurs on refluxing in f-butyl alcohol conversion to the dw-butyl acetal is effected in the presence of 2,4,6-tri-f-butylphenol (equation I). 

Synthesis of acetonides can also be performed using 2-methoxypropene instead of 2,2-dimethoxypropane <20050L5011> however, 4,5-dihydro-l,3-dioxepins, such as 216 (Scheme 61), can only be obtained by direct acetalization or transacetalization with special substrates. 

Acetal formation is regularly achieved by transacetalization. not only in trans-... 

Table 2. Metal mediated deprotection of 0,0-acetals by hydrolysis or transacetalization.

In a study related to the conformational properties of the cyclohexane-fused six-membered heterocycles, new bicyclic dithiolanes, 285-/ra r (Scheme 52) and 285-crr (not shown), were prepared along the reaction pathway, as precursors used further for the syntheses of 2-methyl substituted and unsubstituted /ra r-fused 4a,5,6,7,8,8a-hexahydro-2//,4//-1,3-benzodithiines, exemplified by structure 288-/ra ir (R=R = H) <2002JOC1910>. Thus, ditosylation of cis-Z-hydroxymethyl cyclohexanol 284, and subsequent reaction with sodium sulfide and sulfur, provided a mixture of new bicyclic products 285 and 286, albeit in very low yields, with configurational inversion at C-1. These were reduced by LiAlH4 to provide /ra r-2-mercaptomethyl cyclohexanethiol 2 l-trans. Upon acetalization or transacetalization, the desired 2SS-trans derivative was obtained. The same methodology with the precursor 2E4-trans was extended to the preparation of the r-fused bicyclic compounds 285-288. 

Prepared from dimethylformamide diethyl ketal by transacetalization with ethylene glycol. In the presence of a catalytic amount of acetic acid, the reagent reacts selectively with saturated 3-ketosteroids to give the 3-ethyleneketal in the presence of other saturated or unsaturated keto functions. Under the mild conditions cited, A -3-ketosteroids and 12- and 20-ketosteroids do not react. 

The acetal is readily formed from an aldehyde upon treatment with pinacol and PTSA in toluene (95% yield). This group was used to protect an aldehyde during metalation and horonic acid formation when the dithiane group proved unsuccessful. It was removed by transacetalization with 1,3-propanedithiol and BF3-Et20 to give the dithiane (95% yield). ... 

Cyclic hemiacelals and acetals are readily formed from y-hydroxyaldehydes,44s 45° ketones,451 or acetals.452 455 Either the carbonyl compound or the alcohol451 is deblocked before sponlaneous cyclization occurs. Aldehydes are regularly synthesized from alkenes via ozonolysis450 or periodate cleavage.449 Acetal 7. a starting material for nucleoside analogs, is prepared directly by transacetalization of alcohol 6 with 1 % ethanol/hydrogen chloride.452... 

The second general route to 1,3-dioxepanes (1) involves acid-catalyzed alcohol exchange of an acyclic acetal (6) with a 1,4-diol (transacetalization) <8iJOC298i>, as demonstrated by the synthesis of (12 X = C1, Br) by reaction of 2-halo-1,1-dialkoxyethane with 1,4-butanediol <79MI 911-01, 95JOC5729) or the preparation of (13) from benzil dimethyl acetal <90UKZlll6>. Transacetalization is preferred for the synthesis of 1,3-dioxepanes derived from ketones <61JOC4762> and the stereo-... 

Transacetalization, usually starting from the dimethyl acetal, is an important method for the preparation of amide acetals (465 Scheme 86) with long chain or secondary alkyl groups7 4 83t3235 Recently a method was described which allows the preparation of even the di-r-butyl acetal of DMF by transace-talization. To achieve good yields it is necessary to drive the equilibrium reaction to completion by distilling off the alcohol formed. Cyclic acetals (467) or dithioacetals (466) can be more easily synthesized by transacetalization. 24 28-3i-32,35... 

Another important optimization factor is the development of selective catalysts for the glycosidation process so that for example the formation of polydextrose and etherification reactions can be suppressed. As already mentioned, acetalization or transacetalization in the Fischer synthesis is catalyzed by acids. In principle, any acids with sufficient strength are suitable for this purpose, such as sulfuric acid, paratoluene- and alkylbenzene sulfonic acid, and sulfosuccinic acid. The reaction rate depends on the acidity and the concentration of the acid in the alcohol. 

The effect of propagation-depropagation equilibrium on the copolymer composition is important in some cases. In extreme cases, depolymerization and equilibration of the heterochain copolymers become so important that the copolymer composition is no longer determined by the propagation reactions. Transacetalization, for example, cannot be neglected in the later stages of trioxane and DOL copolymerization111, 173. This reaction is used in the commercial production of polyacetal in which redistribution of acetal sequences increases the thermal stability of the copolymers. 

The reaction of aldehydes with alcohols to form acetals is rapid and reversible, and both the rate and the position of acetal-aldehyde equilibria can be affected by the pH of the reactant solution [30-32], Thus far, however, relatively few studies have made use of transacetalization as... 

Resin-bound aldehydes and ketones have been used as linkers for 1,2- and 1,3-diols (Entries 4-6, Table 3.33). Cleavage of acetal-based linkers is usually effected by acid-catalyzed transacetalization or by hydrolysis. 

Acetals are usually easy to cleave by acid-catalyzed transacetalization or hydrolysis (Table 3.40). Dithioacetals, on the other hand, tend to be more resistant to hydrolysis, but cleavage can be achieved by treatment with mercury(II) salts or by oxidation with either [bis(trifluoroacetoxy)iodo]benzene [723] or periodic acid [724]. Use of the latter reagent can, however, also lead to the conversion of methyl ketones into iodo-methyl ketones [721],... 

Conducting the first two steps as a one-pit reaction10 was first suggested by Sharp less. Transacetalization of trimethyl orthoacetate with 10 under weakly acidic catalysis leads to the 2-methoxy-l,3-dioxolane 34. Addition of TMSC1 or acetyl chloride generates the 1,3-dioxolanylium cation 35, which is opened nucleophilically and regioselectively at the sterically least hindered position to chloro-acetate 36... 

An unsuccessful attempt was next made to simplify the problem of purifying the product by using dioxane as the extracting solvent with only enough benzaldehyde for solvolysis. Finally, on the assumption that an acetal should be as effective in transacetalization as an aldehyde or ketone, the benzaldehyde was replaced by 2,2-dimethoxypropane. In several experiments the hydrogen chloride was replaced by -toluenesulfonic acid also, dimethyl sulfoxide was tried instead of dioxane. All these experiments are summarized in Table I, and they lead to the following conclusions ... 

Possibilities include (a) the hydrolysis of the lignin-carbohydrate bond by small amounts of water present in the wood despite all precautions to make the system anhydrous, (b) the dehydration of carbohydrates under these conditions to produce water and hence hydrolytic conditions, (c) transacetalization of the extracting acetal with carbohydrates to liberate alcohol and create conditions of alcoholysis, and (d) transacetalization of the extracting acetal with free or bound keto groups in the wood to liberate acetone and create conditions of acetonolysis. 

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