Hemiacetal hydrolysis

You learned in Section 17 8 of the relationship among hemiacetals ketones and alcohols the for mation of phenol and acetone is simply an example of hemiacetal hydrolysis The formation of the hemiacetal intermediate is a key step in the synthetic procedure it is the step in which the aryl—oxygen bond is generated Can you suggest a reasonable mechanism for this step" ... 

This would disperse the positive charge over several atoms and diminish the sensitivity of the reaction to substituent effects. The p values that are observed are consistent with this interpretation. Whereas p is —3.25 for acetal hydrolysis, it is only —1.9 for hemiacetal hydrolysis. ... 

Once the three-membered ring is opened, the rest of the reaction amounts to acid-catalysec hemiacetal hydrolysis. The alcohol is a hydroxylamine and the carbonyl compound benzaldehyde. An alternative mechanism, favoured by the original authors (J. H. Fendler ar.c group, /. Chem. Soc., Perkin Trans. 2, 1973, 1744), starts with protonation of the oxygen atom and ends up with the hydrolysis of an imine. Again, the second or the third step could be ratedetermining. 

Epithio sugars acylation, 7, 171 hemiacetals hydrolysis, 7, 170 Epitiostanol, 7, 182, 183 Epoxidations... 

The obvious place to start is cychzation of the phenol onto a ketone to form a six-membered ring. The product is a hemiacetal that will surely eliminate by a combination of hemiacetal hydrolysis and the ElcB mechanism. 

Once the three-membered ring is opened, the rest of the mechanism amounts to acid-catalysed hemiacetal hydrolysis. The original workers favoured an alternative mechanism that starts with protonation of the... 

Reactions of Vinyl Ethers. Vinyl ethers undergo the typical reactions of activated carbon—carbon double bonds. A key reaction of VEs is acid-catalyzed hydrolysis to the corresponding alcohol and acetaldehyde, ie, addition of water followed by decomposition of the hemiacetal. Eor example, for MVE, the reaction is... 

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

In contrast to acetals, which are base-stable, hemiacetals undergo base-catalyzed hydrolysis. In the alkaline pH range, the mechanism shifts toward a base-catalyzed elimination. 

Base-catalyzed fragmentation also occurs on treatment of 5,6j9-epoxy-19-aldehyde (hemiacetal, hemiacetal-acetate or 3)5,6/ -acetal) accessible from nitrous acid-acetic acid treatment of 5a-bromo-6jS-hydroxy-19-oximes followed by mild base hydrolysis (yield not reported)... 

These reactions liberate carbonyl fluonde and fluorotnmethylsilane and thus require no hydrolysis A fluorinated erythromycin derivative is obtained from fluorination of 3 O raycarosyl-8 9-anhydroerythronolideB 6,9 hemiacetal, an enol ether [iS] (equation 16)... 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

The lithium etiolate of acetaldehyde DMH has recently been utilized in the opening reaction of the ot-epoxide obtained by DM DO oxidation ofenol ether 142, to provide hemiacetal 143 after mild oxidative acid hydrolysis. The protected carbonyl functionality was subsequently used for the introduction of the trans enyne chain through a Wittig olefmation reaction to provide alcohol 144, which was then transformed into (+)-laurenyne (Scheme 8.37) [71]. 

A retroaldol fragmentation subsequent to the addition of p-TsOI I and a small amount of water to epoxide 206, obtained by oxidation of enol ether 205 with DMDO, resulted in the direct formation of dialdehyde hydrate 208, possessing the spirostructure necessary for the construction of the fused-rings core of ( )-ginkoli-de B. Apparently, hydrolysis of the epoxide produces the hemiacetal 207, which undergoes retroaldol fragmentation of the cydobutane to afford the dialdehyde, which forms the stable hydrate 208 (Scheme 8.52) [94]. 

The last step is hydrolysis of the unstable hemiacetal. Alkoxycarbocation intermediates (73, R=alkyl) have been isolated in superacid solution at low temperatures, and their structures proved by The protonated hydroperoxides... 

The metabolism of NPYR is summarized in Figure 1. a-Hy-droxylation (2 or 5.position) leads to the unstable intermediates and decomposition of gives 4-hydroxybutyraldehyde [ ]. The latter, which exists predominantly as the cyclic hemiacetal 1, has been detected as a hepatic microsomal metabolite in rats, hamsters, and humans and from lung microsomes in rats (9-13). The role of 1 and as intermediates in the formation of 6 and 7 is supported by studies of the hydrolysis of 2-acetoxyNPYR and 4-(N-carbethoxy-N-nitrosamino)butanal, which both gave high yields of 7 (9,14). In microsomal incubations, can be readily quantified as its 2,4-dinitrophenylhydrazone derivative (15). The latter has also been detected in the urine of rats treated with NPYR ( ). 

Periodate oxidation followed by reduction and acid hydrolysis gave rise to glycerol and Xyl in a molar ratio of 88 12. However, when the polyol was reoxidized with periodate and reduced, acid hydrolysis gave rise to glycerol and Xyl in a molar ratio of 94 6, as expected. Interunit hemiacetal formation must have taken place during the initial periodate treatment inhibiting further oxidation. 

O-acetylophiocarpine (381) with ethyl chloroformate afforded the C-8—N cleaved urethane 382 in quantitative yield. Sequential treatment of 382 with silver nitrate, PCC, sodium hydroxide, and p-toluenesulfonic acid in ethanol furnished acetal 384, which was reduced with lithium aluminum hydride followed by hydrolysis to afford the hemiacetal 385. Oxidation of 385 with PCC provided (+ )-a-hydrastine (369). Similar treatment of O-acetylepi-ophiocarpine (386) afforded ( )-/J-hydrastine (368) however, in this case, C—N bond cleavage of 386 with ethyl chloroformate proceeded without regioselectivity. 

The pyranocoumarin 105 can be prepared via a three-component Diels-Alder reaction between 4-hydroxycoumarin, ethyl vinyl ether and an a-dicarbonyl compound. Similarly to the above, upon treatment of 105 with sulfuric acid in THF, hydrolysis and rearrangement occur to give the furofurochromenone 106. The hemiacetal functionality in 106 may then be oxidized with pyridinium chlorochromate (PCC) to give the lactone 107 <2001EJ03711> (Scheme 28). 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

Pacsu4 5 has suggested a structure for starch involving a small number of non-cyclic hemiacetal linkages, the number being presumably sufficient to account for the number of endgroups determined by the methylation method. Halsall, Hirst and Jones6 have commented on this structure, however, and have shown it to be incompatible with the results of periodate-oxidation studies. In addition, these authors pointed out that it would be difficult to explain enzymic hydrolysis and dextrin formation on the basis of such a structure. 

In an extension beyond hetaryl onium salt promoted hemiacetal activation, Ishido and coworkers have reported the carbodiimide activation of hemiacetals [141]. In the method (Scheme 3.13), the hemiacetal donor 1 is treated with a carbodiimide electrophile 83 and copper(I) chloride to provide glycosyl isourea intermediate 85. Highly susceptible to hydrolysis, the isourea 85 was not isolated but could be detected by 13C NMR and IR spectroscopy [142,143], Accordingly, the reaction between intermediate 85 and the glycosyl acceptor (NuH) provides glycoside product 3, along with urea by-product 84. 

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