Hemiacetals base-catalyzed formation

A MECHANISM FOR THE REACTION ] Base-Catalyzed Hemiacetal Formation 736 [ A MECHANISM FOR THE REACTION ] Hydrate Formation 737... 

Grunwald also studied the mechanism of the base-catalyzed formation of the hemiacetal, and found it to be the same as that of base-catalyzed hydration (6-1, mechanism a) Grunwald J. Am. Chem. Soc. 1985,107, 4710. Sec also S0rensen Pedersen Pedersen Kanagasabapathy McClelland J. Am. Chem. Soc. 1988,110, 5118 Leussing J. Org. Chem. 1990, 55. 666. 

Exercise 15-16 Hemiacetal formation is catalyzed by both acids and bases, but acetal formation is catalyzed only by acids. Write the steps involved in the formation of 1-methoxyethanol from ethanal in methanol containing sodium methoxide ... 

Exercise 16-9 Write equations to show the steps involved in the following carbonyl-addition reactions (a) base-catalyzed addition of ethanol to ethanal to form the corresponding hemiacetal, 1-ethoxyethanol (b) formation of 1-ethoxyethanol from ethanol and ethanal, but under conditions of acid catalysis (c) formation of 1,1-diethoxyethane from 1-ethoxyethanol and ethanol with an acid catalyst and (d) formation of diethyl carbonate (CH3CH20)2C—0 from ethanol and carbonyl dichloride. 

We already have discussed additions of alcohols and, by analogy, thiols (RSH) to carbonyl compounds (see Section 15-4E). We will not repeat this discussion here except to point out that addition of water to the carbonyl group of an aldehyde is analogous to hemiacetal formation (Section 15-4E) and is catalyzed both by acids and bases ... 

Fig. 9.2. Base-catalyzed (top) and acid-catalyzed (bottom) hemiacetal formation from carbonyl compounds and alcohols.

All of these reactions are acid/base catalyzed enolizations or hemiacetal openings/formations. 

Upon treatment of the 7-hydroxyketone 2 with MsCl and 4-dimethylaminopyridine (DMAP), however, hemiacetal formation did not lead to a lactol, but the ansa-furan 3 was formed instead (Equation 4). Formation of this unexpected product is presumably initiated by a base-catalyzed retro-aldol reaction <2004TL6753>. 

Hemiacetal formation is catalyzed by both acid and base. The acid-catalyzed mechanism is identical to Mechanism 21.9, except that the reaction occurs in an intramolecular fashion, as shown for the acid-catalyzed cyclization of 5-hydroxypentanal to form a six-membered cyclic hemiacetal in Mechanism 21.11. 

In the proton-transfer mechanism, the alcohol is presumed to form a hemiacetal at the C(5) carbonyl group. Then an acid-base pair in the active site performs an elimination reaction, producing the aldehyde product and the reduced cofactor, PQQH2. The hydride-transfer mechanism envisions the approximation of the scis-sile C-H bond of the alcohol to C(5) of the cofactor, followed by an acid-base catalyzed delivery of hydride ion to C(5), resulting in formation of the aldehyde product and the ketol form of PQQH2, which can readily rearrange to the enediol form. 

Hemiacetal formation is catalyzed by acid or base, but acetal formation is possible only with an acid. Explain why with suitable examples. 

Hemiacetal formation can be catalyzed by either acid or base. 

Figure 16.37 contrasts the base-catalyzed reaction of a carbonyl compound in water to give a hydrate with the related formation of a hemiacetal in an alcohol. The hemiacetal is similar to a gem- o, except that the central carbon has an OH and an OR group rather than two OH groups. 

Imine Formation from an Aldehyde or Ketone 798 Enamine Formation from an Aldehyde or Ketone 800 Base-Catalyzed Addition of H2O to a Carbonyl Group 803 Acid-Catalyzed Addition of H2O to a Carbonyl Group 803 Acetal Formation—Part [1] Formation of a Hemiacetal 806 Acetol Formation—P ferma n of the Acetal 806... 

Formulate detailed mechanisms for (a) the formation of the hemiacetal of acetaldehyde and methanol under both acid- and base-catalyzed conditions and (b) the formation of the intramolecular hemiacetal of 5-hydroxypentanal (Section 17-7), again under both acid- and base-catalyzed conditions. 

FIGURE 14.17 Acid- and base-catalyzed formation of hemiacetals. 

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