Ketal formation, mechanism

The mechanism of this hydrolysis reaction has been studied in great detail. Tb mechanism is the reverse of that for acetal or ketal formation. 

In a similar fashion to the formation of hydrate with water, aldehyde and ketone react with alcohol to form acetal and ketal, respectively. In the formation of an acetal, two molecules of alcohol add to the aldehyde, and one mole of water is eliminated. An alcohol, like water, is a poor nucleophile. Therefore, the acetal formation only occurs in the presence of anhydrous acid catalyst. Acetal or ketal formation is a reversible reaction, and the formation follows the same mechanism. The equilibrium lies towards the formation of acetal when an excess of alcohol is used. In hot aqueous acidic solution, acetals or ketals are hydrolysed back to the carbonyl compounds and alcohols. 

The formation of random copolymer, even when the starting materials are preformed homopolymer blocks, as was observed with DMP and MPP, is reasonably explained by the monomer-polymer and polymer-polymer redistribution reactions of Reaction 3 and 9. Block copolymers are accounted for most easily by polymer-polymer coupling via the ketal arrangement mechanism (see Reaction 15, p. 256). 

The reaction mechanism is the same for both aldehydes and ketones. If acetone (6) reacts with ethanol in the presence of a catalytic amount of j5-tol-uenesulfonic acid, 53 is formed but not isolated. This compound is formally analogous to the hemiacetal derived from an aldehyde, but it is derived from a ketone. Therefore, it is called a hemiketal. The isolated product is 54 (2,2-diethoxypropane)—again, analogous to the acetal however, the starting material is a ketone rather than an aldehyde, so the final product is called a ketal. A ketal is a compound derived from a ketone that contains two OR groups connected to the same carbon. The mechanism for ketal formation from ketones is identical to that for acetal formation, and every step in this sequence is reversible. The same methods used to remove water from the reaction that was used to drive the equilibrium toward the acetal in that reaction (see Section 18.6.3) can be used here for conversion of the ketone to the ketal. 

The key to the reaction of alcohols with aldehydes or ketones is to understand the equilibrium. If it is necessary to generate an equilibrium that favors the acetal or ketal, add a large excess of alcohol and remove the water. If it is necessary to generate an equilibrium that favors the aldehyde or ketone, add a large excess of water. The mechanism is the exact reverse of acetal or ketal formation, except that an excess of water is used and the alcohol is the leaving group. 

The sequence of chapters and topics in Organic Chemistry do not differ markedly from that of other organic chemistry textbooks. Indeed, the topics are presented in the traditional order, based on functional groups (alkenes, alkynes, alcohols, ethers, aldehydes and ketones, carboxylic acid derivatives, etc.). Despite this traditional order, a strong emphasis is placed on mechanisms, with a focus on pattern recognition to illustrate the similarities between reactions that would otherwise appear unrelated (for example, ketal formation and enamine formation, which are mechanistically quite similar). No shortcuts were taken in any of the mechanisms, and all steps are clearly illustrated, including all proton transfer steps. 

The mechanism of acid-catalyzed esterification involves two stages. The first is formation of a tetrahedral intermediate by nucleophilic addition of the alcohol to the carbonyl group and is analogous to acid-catalyzed acetal and ketal formation of aldehydes and ketones. The second is dehydration of the tetrahedral intermediate. 

The mechanism presumably involves partial opening of the ketal to permit enol formation, followed by bromination and reclosing of the ketal ... 

Similar results were encountered by Bianchetti et al. (i52), who found that e ketal derivatives of //-alkyl methyl ketones with morpholine led to the enamines of the condensation products of these ketones. The authors have Suggested the following probable mechanism for the dienamine formation. 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

There is no reason to doubt that the sequence of steps in the mechanism of hydrolysis of the ring compounds is the same as in the hydrolyses of dialkyl acetals and ketals. However, it must be expected that carbonium ion formation in the second step is reversible for the reactions of the ring compounds because the intramolecular return step (ring-closure) can successfully compete with the attack of water in the third step, i.e. 

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