Mechanisms acyl halide hydrolysis

Acid-catalyzed hydrolysis of Reissert compounds results in an aldehyde, a formal reduction product of the acyl halide utilized in the Reissert compound formation (11). The mechanism of the reaction according to McEwen and Cobb (3), is shown in Scheme 2. 

Anhydrides are somewhat more difficult to hydrolyze than acyl halides, but here too water is usually a strong enough nucleophile. The mechanism is usually tetrahedral. Only under acid catalysis does the SnI mechanism occur and seldom even then.s06 Anhydride hydrolysis can also be catalyzed by bases. Of course, OH- attacks more readily than water, but other bases can also catalyze the reaction. This phenomenon, called nucleophilic catalysis (p. 334). is actually the result of two successive tetrahedral mechanisms. For example, pyridine catalyzes the hydrolysis of acetic anhydride in this manner.507... 

The existence of acylium ions in the reactions of acyl halides with Lewis acids has been amply demonstrated88,89, but they have not so far been directly observed in hydrolysis reactions. To achieve direct observation of an acylium ion, it must, at best, be generated into a non-reactive environment if its rate of formation is slow, or be detectable in small concentrations if it is destroyed rapidly. The limiting factors are, therefore, the rate and mechanism of heterolysis and the stability and concentration of the acylium ion formed. In this... 

Investigations into the mechanism of hydrolysis and alcoholysis of acyl halides have been largely concerned with acyl chlorides and in particular with benzoyl chloride and the related aromatic acid chlorides. This was a result of the relatively slow rate of hydrolysis of benzoyl chloride compared with acetyl chloride (although their alcoholysis rates are easily measurable) and it is only comparatively recently90 that stop-flow techniques have been used to measure the faster rate of hydrolysis. However, in spite of this limitation, considerable progress has been made towards elucidation of the mechanism or mechanisms of hydrolysis and alcoholysis of these halides. 

Although, so far in this section, we have discussed the kinetic evidence in terms of the A-l and A-2 mechanisms favoured by Bunton et al. (p. 224), the same points which give rise to differences in detailed interpretation of mechanism for hydrolysis of acyl halides apply with equal weight to the hydrolysis of anhydrides. Butler and Gold67,68,298,299 have studied the spontaneous hydrolysis of acetic anhydride and presented the following scheme. 

Acyl halides are so reactive that hydrolysis is easily carried out. ° In fact, most simple acyl halides must be stored under anhydrous conditions lest they react with water in the air. Consequently, water is usually a strong enough nucleophile for the reaction, though in difficult cases hydroxide ion may be required. The reaction is seldom synthetically useful, because acyl halides are normally prepared from acids. The reactivity order is F < Cl < Br < If a carboxylic acid is used as the nucleophile, an exchange may take place (see 16-79). The mechanism ° of hydrolysis can be either SnI or tetrahedral, the former occurring in highly polar solvents... 

Acylation of amines by anhydrides has not been subjected to extensive mechanistic investigation but it seems highly probable that the mechanism is similar to that of anhydride hydrolysis, which brings the reaction in line with the mechanism of amine acylation by other reagents. Since acyl halides hydrolyse by an Sff2 mechanism, acyl acetate (acetic anhydride) should be more inclined to react in this way. Thus acetic anhydride would be expected to react with amines, stronger nucleophiles than water, via an Sjf2 reaction also. More direct evidence in support ofan S 2 mechanism comes from the work... 

By analogy with acyl halides, the SnI mechanism (Equation 8) should be possible for arylsulfonyl halides, provided they contain sufficiently electron-donating substitutents as in the hydrolysis of 2,4,6-trimethylbenzenesulfonyl chloride. However, this evidence has been disputed by the work of Rogne in Norway in a series of papers thus in the reaction of imidazole with substituted... 

Another FGI that gives carboxylic acid products is the hydrolysis of carboxylic acid derivatives, such as esters and nitriles. Such hydrolysis reactions can either be acid catalyzed (H3O+) or base promoted (1. NaOH, H2O 2. H3O ) and involve an acyl substitution mechanism (addition-elimination) that replaces any acyl leaving group with a hydroxyl group. The synthesis of carboxylic acids via nitriles is especially noteworthy since the introduction of the cyano group via Sn2 with CN involves the formation of a new C-C bond (adds one new carbon to the alkyl halide carbon chain). 

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