Reactions involving acyl-oxygen cleavage

The category BAC2 (ref. 1, p. 753) referred originally to alkaline hydrolysis, but included the then relatively small class of hydrolytic reactions proceeding in neutral solution. It is our picture of this class of reactions which has changed most dramatically in the past fifteen years, with the discovery of a multitude of catalytic processes which can assist hydrolysis in neutral solutions. Alkaline hydrolysis itself can be regarded as just one example, albeit a special case, of a large class of reactions which involve nucleophilic attack on esters 

Catalysis of hydrolysis is observed if the reaction with the nucleophile is faster than hydrolysis under the reaction conditions, as long as the initial product is also more reactive than the starting material, viz. 

The slow step of this process is often the initial nucleophilic displacement, and although the alkaline hydrolysis reaction (Y = HO ) is unique in that only a single displacement is involved, the step concerned is the same as the ratedetermining step for the reaction with many other nucleophiles. Kinetically, therefore, the reactions are comparable. A second important type of catalysis by nucleophilic reagents does not involve direct attack by the nucleophile on the ester. For example, the hydrolysis of ethyl dichloroacetate is catalyzed by aniline, and no anilide is produced in the reaction186, viz. 

Reactions of this sort usually involve the nucleophile as a general base. They are not immediately distinguishable from nucleophilic reactions, since both may be first-order in both ester and nucleophile. The mechanism of general 

This is a termolecular process and would be expected to be entropically highly unfavourable, as indeed reactions of this sort generally are. A considerable amount of data is now available, (some of it is given in the appropriate sections below) and intermolecular reactions thought for other reasons to involve general base catalysis commonly have entropies of activation in the region — 40 to —50 eu. 

---

All these reactions involve acyl-oxygen cleavage. This has been demon-... 

Dmgs that contain ester linkages include acetylsalicylic acid (aspirin), physostigmine, methyldopate, tetracaine and procaine. Ester hydrolysis is usually a bimolecular reaction involving acyl-oxygen cleavage. For example, the hydrolysis of procaine is shown in Scheme 4.2. 

The broad outline of the mechanism of catalysis of ester hydrolysis by hydroxide ion is not in doubt. The reaction is well known to involve acyl-oxygen cleavage, and seems invariably to be of the second order, being first order in both ester and hydroxide anion. General base catalysis in the usual sense is not a possibility, the partial removal of a proton from water cannot generate a species more reactive than hydroxide ion, so direct nucleophilic attack must be involved. (However, if it is accepted that the high ionic nobility of the hydroxide ion in water is explained by a Grotthus-type mechanism... 

Once it was established that hydroxide ion attacks the carbonyl group in basic ester hydrolysis, the next question to be addressed concerned whether the reaction is concerted or involves an intermediate. In a concerted reaction acyl-oxygen cleavage occurs at the same time that hydroxide ion attacks the carbonyl group. 

All these facts—the observation of second-order kinetics, acyl-oxygen cleavage, and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown in Figure 20.5. Like the acid-catalyzed mechanism, it has two distinct... 

The AacI (acid-catalyzed, unimolecular, acyl-oxygen cleavage) mechanism is shown in Figure 7.17. The reaction is unimolecular because the rate-limiting step involves dissociation of ROH from the protonated ester. This... 

The polymerization undergoes coordination-insertion mechanism. The initiation step involves nucleophilic attack of the active group, such as hydride, alkyl, amide, or alkoxide group, on the carbonyl carbon atom of a lactide or lactone to form a new lanthanide alkoxide species via acyl-oxygen cleavage. The continued monomer coordination and insertion into the active metal-alkoxo bond formed completes the propagation step as shown in Scheme 27. The reactions with stereoselectivity proceed by means of a chain-end control mechanism , which is the chirality of the propagating... 

The acid-catalysed esterification reaction usually proceeds via an acyl-oxygen fission process. This involves the cleavage of the bond between the original carbonyl-carbon atom and an oxygen of an hydroxyl group in the intermediate (6) arising from nucleophilic attack by an alcohol molecule on the pro-tonated carboxylic acid group (5). 

Next, hydroxide attacks at the carbonyl carbon and displaces alkoxide ion. That is to say, reaction involves cleavage of the bond between oxygen and the acyl... 

The mechanism of the Pummerer reaction can essentially be broken down into four steps (equations 21-24). "" The initial step involves acylation of the sulfoxide oxygen to form an acyloxysulfonium salt (83). In the following step, removal of a proton from the ot-carbon of (83) produces an acylsulfonium ylide (84). This ylide subsequently undergoes concurrent electron reorganization and S—O bond cleavage to give the ion pair (85). In the final step, condensation of acetate ion with the sulfur-stabilized car-bocation gives the a-acyloxy sulflde product (86). 

Amides having only one nitrogen substituent can react with carbonyl difluoride in three ways by iV-acylation, by cleavage, or by displacement of oxygen with fluorine [632], Reactions involving AT-acylation and oxygen displacement are illustrated by the examples given in Table 13.24. The three reaction types are all illustrated by the transformations of... 

ROP is carried out in solution, in the melt, in the bulk or in suspension. The involved mechanism can be ionic (anionic or cationic), coordination-insertion or free-radical polymerization [19].The cationic pol)rmerization is initiated by only two catalysts, trifluoromethane-sulphonic acid and its methyl ester [10, 15]. Initiators such as potassium methoxide, potassium benzoate, zinc stearate, n-, sec-, fer-butyl lithium or 18-crown-6-ether complexes are added for the anionic polymerization to induce a nucleophilic reaction on the carbonyl to lead to an acyl-oxygen link cleavage. According to Jedkinski et al. only the primary alkoxides, such as the first mentioned catalyst, can yield polymers with negligible racemization, transesterification and termination [10]. 

The proposed reaction mechanisms can be distinguished by two factors (i) whether ester cleavage occurs between the oxygen atom and the acyl carbon atom or between the oxygen atom and the alkyl carbon atom, and (ii) whether the reaction involves only a single step or involves an intermediate. ... 

The reactions of these ions with acids and esters were also examined. Reaction 79, a displacement involving cleavage of the acyl-oxygen bond and the formation of acyllum ion products ... 

---