Hydrolysis acyl chlorides

Hydrolysis (Section 20 4) Acyl chlorides react with water to yield carboxylic acids In base the acid is converted to its carbox ylate salt The reaction has little prepara tive value because the acyl chloride is nearly always prepared from the carboxyl ic acid rather than vice versa... 

FIGURE 20 2 Hydrolysis of an acyl chloride proceeds by way of a tetrahedral intermediate For mationofthe tetrahedral intermediate is rate determining... 

Acid anhydrides are more stable and less reactive than acyl chlorides Acetyl chlo ride for example undergoes hydrolysis about 100 000 times more rapidly than acetic anhydride at 25°C... 

Nucleophilic acyl substitutions at the ester carbonyl group are summarized m Table 20 5 on page 849 Esters are less reactive than acyl chlorides and acid anhydrides Nude ophilic acyl substitution m esters especially ester hydrolysis has been extensively mves tigated from a mechanistic perspective Indeed much of what we know concerning the general topic of nucleophilic acyl substitution comes from studies carried out on esters The following sections describe those mechanistic studies... 

Alcoholysis of 1 -chloro-2-acyl-1,1,2-trifluoroethane, available from trifluoro-ethylene, an acyl chloride, and aluminum chloride, leads to 1-fluoro- 1-acylacetates [/] (equation 1) It is surpnsing that the remaining carbon-tluorine bond resists hydrolysis. 

Carboxylic acid derivative (Section 20.1) Compound that yields a carboxylic acid on hydrolysis. Carboxylic acid derivatives include acyl chlorides, acid anhydrides, esters, and amides. 

Small amounts of water present will lead to partial hydrolysis of the acyl chloride to give the carboxylic acid 7, which then may further react with the acyl chloride to give a carboxylic anhydride 8 ... 

Reductive decarbonylation and decarboxylation can be carried out by (TMSlsSiH using acyl chlorides, phenylseleno esters, or N-hydroxypyridine-2-thione esters. Examples are shown in Reactions (17)-(19). Hydrolysis of the methyl ester followed by decarbonylation at the C2 position of hexahydropyrro-loindole (+)-17 afforded the desired tricycle (+)-18 in 84% yield and >99% ee. ... 

Xun et al. 1999 Ohtsubo et al. 1999). The degradation of 2-chlorohydroquinone, which is produced during the degradation of y-hexachlorocyclohexane, is carried out analogously by dioxygenation followed by hydrolysis of the acyl chloride to 3-hydroxymuconate, which is mediated by an unusual extradiol fission enzyme encoded by linE (Miyauchi et al. 1999 Endo et al. 2005). 

Because the reaction of an amine with an acyl chloride is much faster than the hydrolysis of the acyl chloride, the reaction can usually be carried out in an aqueous alkali solution. This is well known as the Schotten-Baumann procedure.6 For example, a number of N-acyl taxol analogs have been prepared under Schotten-Baumann conditions by the reaction of A-debenzoyltaxol with various acid chlorides (Eq. 9.4).7 Highly purified /V-long-chain-acyl neutral amino acids such as potassium AMauroyTy-aminobutyrate, useful as surfactants for detergent... 

Cleavage of the oxirane C-0 bond produces a zwitterionic intermediate (Fig. 10.22), which that can undergo chloride shift (Pathway a) to 2,2-dich-loroacetyl chloride (10.90) followed by hydrolysis to 2,2-dichloroacetic acid (10.91). Furthermore, the zwitterionic intermediate reacts with H20 or H30+ (Pathway b) by pH-independent or a H30+-dependent hydrolysis, respectively. The pH-independent pathway only is shown in Fig. 10.22, Pathway b, but the mechanism of the H30+-dependent hydrolysis is comparable. Hydration and loss of Cl, thus, leads to glyoxylyl chloride (10.92), a reactive acyl chloride that is detoxified by H20 to glyoxylic acid (10.93), breaks down to formic acid and carbon monoxide, or reacts with lysine residues to form adducts with proteins and cytochrome P450 [157], There is also evidence for reaction with phosphatidylethanolamine in the membrane. 

Acyl chlorides of the stronger acidic groups are formed by the reaction with thionyl chloride 35, 45). The amount of easily hydrolyzed chloride was equivalent to the NaHCOj neutralization or to the difference between NajCOj and NaHCOa neutralization. Both values were equal in most examples. About twice this amount of chlorine was bound at the same time in a form that was resistant to hydrolysis. The nature of the chlorine bonding is not yet known there was no sulfur in the samples. 

Ammonolysis. Reactions involving ammonia. Ammonolysis of esters, acyl chlorides, and anhydrides give amides aniline is produced by ammonolysis of chlorobenzene. The reaction is analogous to hydrolysis, with ammonia substituted for water. 

Ab initio SCRF/MO methods have been applied to the hydrolysis and methanol-ysis of methanesulfonyl chloride (334). ° The aminolysis by aromatic amines of sulfonyl and acyl chlorides has been examined in terms of solvent parameters, the former being the more solvent-dependent process.Solvent effects on the reactions of dansyl chloride (335) with substituted pyridines in MeOH-MeCN were studied using two parameters of Taft s solvatochromatic correlation and four parameters of the Kirkwood-Onsager, Parker, Marcus and Hildebrand equations. MeCN solvent molecules accelerate charge separation of the reactants and stabilize the transition... 

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

Even an oligopeptide has been attached to (Table 4.3, compound 130) [111]. This was achieved by a coupling reaction of the carboxylic group in the side chain of the cyclopropane ring as well. First, the tert-butylcarboxylate 129 was synthesized by the reaction of the corresponding diazomethylbenzoate with Cgg. After hydrolysis with trifluoromethanesulfonic acid, the acyl chloride was generated by treatment with oxalyl chloride. Finally, in a one-step procedure the fullerene peptide 130 was obtained by the reaction with the N-deprotected pentapeptide H-(L-Ala-Aib)2-L-Ala-OMe. 

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 effect of substitution in the benzene ring on reactivity of the acyl chloride group was investigated by a series of workers, using hydrolysis and alcoholysis. Data from these workers are compiled in Table 15 for mono-substituted benzoyl chlorides. 

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). 

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