Hemiacetals esterification

SAMPLE SOLUTION (a) The reaction given is the acid-catalyzed esterification of methanol by benzoic anhydride. The tetrahedral intermediate is formed by addition of a molecule of methanol to one of the carbonyl groups of the anhydride. This reaction is analogous to the acid-catalyzed formation of a hemiacetal by reaction of methanol with an aldehyde or ketone. 

Formation of hemiacetals and acetals, as well as of hemiketals and ketals, is reversible under acidic conditions, as we already have noted for acid-catalyzed esterification. The reverse reaction is hydrolysis and the equilibrium for this reaction can be made favorable by having an excess of water present ... 

The Mitsunobu protocol has also been investigated in the stereocontrolled synthesis of glycosyl esters (O Scheme 78g) [431]. Complete stereochemical inversion at C-1 of the starting sugar is observed when the esterification is conducted with anomerically pure glycosyl hemiacetals. By corollary, complementary ratios of inverted products are formed when an anomeric mixture of sugars is esterifled. The stereochemical outcome of the esterification is not affected... 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

The polymerization of aldehydes to give polyacetal is readily undertaken anionically in the presence of base, due to the susceptibility of formaldehyde to nucleophilic attack (Odian, 1991) as shown in Scheme 1.25. It should be noted that the resulting polymer is thermally unstable and stabilization is achieved by an esterification reaction of the unstable hemiacetal end groups after polymerization. 

Esterification of starch dialdehyde with chlorosulfonic acid in formamide gave a sulfate ester that could be transformed into an amide and methyl ester.532-536 The classical method of sulfonation, namely, by the action of sulfur trioxide in pyridine, is also applicable.537,538 Hemiacetals of starch dialdehyde result upon treatment with suitable alcohols in the presence of an acidic catalyst. In acetic media amides condensed with the carbonyl groups. Acetylation of starch dialdehyde with acetic anhydride is an obvious reaction. Esters with hexanedioic (adipic) acid were also prepared.537 Starch dialdehyde undergoes etherification with monochloroacetic acid in an alkaline medium.538... 

The oxidation of aldehydes to carboxylic acids has been most extensively investigated with horse liver alcohol dehydrogenases (65-67, 69, 73). There are two distinct reactions the direct oxidation of aldehydes as their hydrated gem-diol form [reaction (9)] and the oxidation of hemiacetals to esters [oxidative esterification, reaction (10)]. 

The reaction mechanism that proceeds via the hemiacetal is considered less likely since the Pd-Pb-catalyzed oxidative esterification proceeds in neutral to basic conditions rather than in acidic conditions, and an alkali is also integrated as the third component of the catalyst thus, a mechanism involving an acyl palladium intermediate is favored. The reaction mechanism in Figure 13.3 rationalizes the observation that the presence of aldehydes suppresses the production of MF. It is presumed that alkali is effective in increasing the adsorption equilibrium of the alcohol. 

Primary alcohols are more reluctant to undergo oxidation to aldehydes under solventless conditions. Typically, esters with small quantities of carboxyhc acids are observed under these conditions. It has been proposed that esters derive from the oxidation of the corresponding hemiacetal, rather than from the esterification of the carboxylic acid (Scheme 12.9). This proposal is based on the observation... 

Acetalization and ketalization, like esterification, are also important candidate reactions for RD. It is a reversible reaction between aldehyde/ketone and alcohol that generates one molecule of water with one molecule of acetal/ketal. Various acetals, such as methylal and dioxalane, are useful solvents in the chemical industry. Ma-samuto and Matsuzaki (1994) first prepared methylal from formaldehyde and methanol in the presence of cation-exchange resins using a laboratory scale RD column conveniently packed in the form of tea-bag structures [31]. Kolah et al. studied this reaction in both batch and continuous RD column, as shown in Fig. 1.6, with a theoretical analysis of multiple reactions in the RD column [32]. Along with the acetal, formation of dimers and hemiacetals also takes place with substantial con-... 

The species connecting the two stages is called a tetrahedral intermediate because the hybridization at carbon has changed from sp in the carboxylic acid to sp in the intermediate before returning to sp in the ester product. The tetrahedral intermediate is formed by nucleophilic addition of an alcohol to a carboxylic acid and is analogous to a hemiacetal formed by nucleophilic addition of an alcohol to an aldehyde or a ketone. The three steps that lead to the tetrahedral intermediate in the first stage of esterification... 

Bafilomycin Al can be modified to bafilomycin C-1 by esterification with a fumaryl group at the hydroxyl moiety in the hemiacetal ring (Figure 6.30). For the incorporation of the fumaryl moiety, it was assumed that fumaric acid is first... 

The second and third steps in Fischer esterification are also completely analogous to parts of aldehyde or ketone chemistry. A molecule of alcohol acts as a nucleophile and adds to the carbonyl carbon of the protonated carbonyl group (Fig. 17.21). For a ketone, this addition is followed by deprotonation, and gives the hemiacetal for the acid, a somewhat more complicated intermediate with one more hydroxyl group is formed. In both reactions, however, a planar, hybridized carbon has been converted into an intermediate with a tetrahedral carbon, called the tetrahedral intermediate. 

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