Hydrolysis, of acyl chlorides

RCC1 + H20 RCOH Hydrolysis of acyl chlorides and anhydrides. These derivatives... 

The hydrolysis of acyl chlorides to a carboxylic acid and hydrogen chloride is rapid and violent in the lower aliphatic acyl chlorides. With increase in the complexity of the radical there is a corresponding increase in stability. Aryl acyl chlorides are only slowly hydrolyzed at low temperatures. In general, however, the halogen attached to the acyl group is very much more reactive than a halogen attached to other organic radicals. 

D) Hydrolysis of Acyl Chlorides. To a test tube containing 5 ml of water add a few drops of acetyl chloride. Observe the result immediately, and then again after shaking the tube. Repeat, using benzoyl chloride. If no reaction takes place, warm the tube. How can the products be identified ... 

FIGURE 20.3 Hydrolysis of acyl chloride proceeds by way of a tetrahedral intermediate. Formation of the tetrahedral intermediate is rate-determining. 

Our work evolved from early investigations into the mechanism of hydrolysis of acyl chlorides (9-11) and the reactivity of nucleophiles toward organophosphorus compounds (12). I was intrigued at that time by the fact that some nucleophiles rapidly dealkylated phosphate esters and hence were important in deprotection in nucleotide chemistry, and other nucleophiles were rapidly phosphorylated, and this finding is important in the search for antidotes for the nerve gases and also in predicting the reactivity of organophosphorus insecticides. 

Table 19.1 concludes with the hydrolysis of acyl chlorides. Because acyl chlorides are themselves prepared by the reaction of carboxylic acids with thionyl chloride (Section 12.7) ... 

Table 19.2 gives examples of two reactions of acetic anhydride. In the first, the anhydride carbonyl is converted to the more stabilized carbonyl group of an ester in the second, a more stabilized amide carbonyl results. Hydrolysis under neutral or acid-catalyzed conditions yields two moles of a carboxylic acid per mole of anhydride, but, like hydrolysis of acyl chlorides is of little preparative value and is not included in the table. Likewise, hydrolysis in aqueous base according to the following equation is omitted from the table. 

NMI can also be used in combination with TMEDA catalyt-ically in water using a pH buffer of 11.5 to prevent hydrolysis of acyl chlorides, creating a Schotten—Baumann-type method for esterification and amide formation (eq 49). ... 

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. 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

This mechanism explains much of the experimental evidence obtainedhfrom studies of the solvolysis of acyl chlorides, but it may not be in agreement (as was pointed out to Minato by a referee) with the linear relationship between electrophilic catalysis observed in the solvolysis of certain acid chlorides would possibly be explained by a simpler mechanism such as the SN1 or hydration-ionisation mechanism. However, it is of interest to see how the mechanism applies to acetyl, benzoyl and mesitoyl chlorides. For acetyl chloride, kY and k-Y would be very large and the rate would approximate to... 

Rate parameters for the hydrolyses of some alkyl and acyl chlorides are compared in Table 20. The value of AS for dimethylcarbamyl chloride is close to that observed for the hydrolysis of /-butyl chloride in 90% water/10% dioxan566 (+ 8 eu). 

ACTIVATION ENERGIES AND ENTROPIES FOR THE HYDROLYSIS OF ACYL AND ALKYL CHLORIDES... 

The mechanism for both of these reactions is very similar to the mechanism for the reduction of acyl chlorides by LATB—H. The first step is an acid-base reaction between an unshared electron pair on oxygen or nitrogen with the aluminum atom of the DIBAL—H. The second step is the transfer of a hydride ion from the DIBAL—H to the carbon atom of the carbonyl or nitrile group. The last step is the hydrolysis of the aluminum complex to form the aldehyde. 

Although hydrolysis of acyl halides and anhydrides is infrequently used in the preparation of acids, several important examples are noted. The acyl chlorides, ArjC = CHCOCl, from the action of oxalyl chloride on di-arylethylenes are hydrolyzed to yS,yS-diarylacrylic acids by stirring with ice-cold sodium carbonate solution. a-Halo acids prepared by the Hell-Volhard-Zelinsky reaction are obtained from the a-halo acid halide by stirring with cold water (method 67). 

By applying the theoretical consideration described elsewhere to the polymerization of styrene in the presence of TCAC, we can predict that about 90% of the PS molecules must have terminal acyl chloride groups. Therefore, the finding that the graft coupling efficiency is lower than 0.9 would be the result of the disappearance of acyl chloride groups by hydrolysis due to trace amounts of water in the coupling medium. 

Silyl alkyl ketene acetals, as ester enolate equivalents, are capable of regioselective acylation by acid chlorides. Rathke and Sullivan showed that a variety of acid chlorides reacted with the acetal (3) to give protected -keto esters (Scheme 11). Acid hydrolysis of the silylated products gave the free -keto ester. The reaction was successful with a variety of acyl chlorides, including acetic, butanoic, (2 )-buten-... 

The neutral and acid-catalysed hydrolysis of mesitoyl chloride in acetonitrile containing 1% 018-enriched water is not accompanied by O18 exchange (Bender and Chen, 1963). It is suggested that in both cases unimolecular heterolytic bond fission occurs with the formation of an acyl cation. In alkaline solution a tetracovalent intermediate is postulated on the basis of a comparison of the effect of substituents on the rate of hydrolysis of the corresponding benzoate esters. The exchange of O18 in alkaline solution was not determined experimentally. 

This reaction was first reported by Blomquist in 1947. It is the reaction to form intermediate to macrocyclic ketones via the process of intramolecular condensation of aliphatic diketenes at diluted concentration followed by hydrolysis and decarboxylation of cyclic ketene derivatives. The intermolecular condensation of diketenes will form even larger macrocyclic diketones, which can be converted into simple macrocyclic diketones." The ketene can be easily obtained by the treatment of acyl chloride of dicarboxylic acid with tertiary amines, of which triethylamine gives the best result. Although some polyketene products also form in this process, they can be easily removed. Other methods for preparing macrocyclic ketones include the Ziegler, Hunsdiecker, Ruzicka, and Glinski reactions. 

This reaction was initially reported by Grundmann in 1936. It is the conversion of acyl chloride into aldehyde with the exact same carbon skeleton via the following consecutive steps a) treatment of acyl chloride with diazomethane to form a ketone, (b) conversion of such a ketone into ketol acetate with acetic acid, (c) reduction of ketol acetate with aluminum isopropylate, and d) hydrolysis and oxidation with lead tetraacetate. This method is especially useful in the preparation of aliphatic aldehydes with methylene-interrupted double bond(s). Although polymers might form in the preparation of highly unsaturated aldehydes during the reduction with aluminum isopropylate, the reduction from lithium aluminum hydride can eliminate such drawbacks. ... 

Increasing the amounts of acyl chloride relative to sucrose to molar ratios of over 3 1 did not improve the ester yield but rather initiated the hydrolysis of sucrose. Hydrolysis was not found to occur at lower levels of acyl chloride. A ratio of sucrose to alkyl chloride of 1 1.5 was found to be preferable. A similar reagent threshold amount was found in the etherification of sucrose with alkyl halides. The use of 1.3 moles of e.g. methyl iodide per mole of sucrose chelate seemed preferable. Ratios over 3 moles of alkyl halide caused sucrose hydrolysis, as was observed with earlier attempts at sucrose esterification ( ). ... 

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