Acyl chlorides with water

An acyl chloride, for example, generally reacts by losing a chloride ion—z. very weak base and thus a very good leaving group. The reaction of an acyl chloride with water is an example. 

There is no ambiguity in the halogenation of acids as they can of course enolise on one side only. Reliable methods are bromination with PCI3 and bromine or red phosphorus and bromine. The acid is converted into the acyl chloride with PCI3 or the acid bromide by PBr3, formed in the reaction mixture from red phosphorus and bromine. Bromohexanoic acid 34 can be made in good yield if the reaction mixture is worked up with water.7... 

Any carboxylic acid derivative can be converted to any other using one or more of the reactions discussed in the previous sections. If the conversion requires going from a less reactive derivative to a more reactive one, then an indirect route may be necessary. Remember that any derivative can be hydrolyzed to a carboxylic acid using water and acid or base. Also remember that the carboxylic acid can be converted to the acyl chloride with thionyl chloride, providing access to the other derivatives. 

The mesoporous aluminosilicate AlMCM-41-type material, prepared from BEA zeolite seeds, can be utilized as catalyst in the acylation of anisole with acyl chloride with the aim of improving the transport of the reactants, especially for the relatively hindered molecules such as octanoyl chloride. The catalyst shows good activity, being para-octanoyl anisole obtained in 90% yield after 1 h. As commonly observed, the use of carboxylic acid as acylating agent results in a slower process (-20% yield after 26 h) due to its lower electrophilicity and the production of water that inhibits the active sites of the zeolite, as previously observed by Beers et al. ... 

The preparation of amides by reaction of an amine, an acyl chloride, or an acid anhydride in the presence of aqueous alkali is the well-known Schotten-Baumann reaction. Since the rate of reaction of the acyl chloride with amines is greater than the rate of hydrolysis of the acyl chloride, amide formation is favored. In some cases, the stability of acyl chlorides to aqueous caustic solution is surprising. For example, benzoyl chloride may be kept in contact with sodium hydroxide solutions for long periods of time. We presume that a thin layer of sodium benzoate forms rapidly and that this acts as a protective coating unless the benzoyl chloride is stirred or shaken to disturb the protective layer. As a matter of fact, the Schotten-Baumann reaction (and the analogous Hinsberg reaction with aromatic sulfonyl chlorides) appears to be most satisfactory when acyl chlorides are used which are relatively insoluble in water. Many years ago, we noted that the addition of a small percentage of a surfactant (e.g., sodium lauryl sulfate as well as cationic surfactants) assisted in the dispersion of the acyl chloride with an increase in reaction rate. These may have been early examples of phase-transfer reactions. 

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... 

The reaction of 1,2,4-triazine 4-oxides 55 with water in the presence of benzoyl chloride affords 3-hydroxy-1,2,4-triazines 78. The mechanism suggested for this reaction includes acylation of the substrate at the oxygen of the iV-oxide group, followed by the addition of water to the 1,2,4-tiiazinium cation and the autoaromatization of the (T -adducts with the elimination of benzoic acid. 

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 ... 

Methyl pyrazine-2-carboxylic acid is refluxed with thionyl chloride in anhydrous benzene for approximately 12 hours. Benzene and thionyl chloride excess is removed by distillation. Then some anhydrous dioxane is added and this acid chloride solution is allowed to drop into p-(/3-aminoethyl)-benzenesulfonamide suspension in dioxane and anhydrous pyridine. The resulting mixture is then refluxed for 3 hours. Dioxane is removed by distillation and then the residue is washed with water and acetic acid. The raw acylated sulfonamide is then filtered and crystallized from 95% ethanol, thus obtaining a product of MP 200 to 203 C. 

Conversion of Acid Halides into Acids Hydrolysis Acid chlorides react with water to yield carboxylic acids. This hydrolysis reaction is a typical nucleophilic acyl substitution process and is initiated by attack of water on the acid chloride carbonyl group. The tetrahedral intermediate undergoes elimination of Cl and loss of H+ fo give the product carboxylic acid plus HC1. 

Silylcuprates have been reported to undergo reactions with a number of miscellaneous Michael acceptors [65]. Conjugate addition to 3-carbomethoxy acyl pyri-dinium salts [65a] affords 4-silyl-l,4-dihydropyridines. Oxidation with p-chlorand generates a 4-acyl pyridinium salt that gives the 4-silylnicotinate upon quenching with water, and methyl 4-silyl-2-substituted dihydronicotinates upon quenching with nucleophiles (nucleophilic addition at the 6-position). The stabilized anion formed by conjugate addition to an a, j8-unsaturated sulfone could be trapped intramolecularly by an alkyl chloride [65b]. 

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. 

Quantitative stoichiometric gas-solid or solid-solid (these at 0 °C) acylations of amines with acid chlorides are varied (Scheme 32). However, for a clean reaction the liberated hydrochloric acid has to be neutralized by an additional gaseous or solid base that may also be a second mole of the amine. The reactions are performed in an evacuated flask or in a ball-mill, respectively. There are only minimal losses of the amides or sulfonamides upon removal of the stoichiometric coproduct with water [91]. The solid-solid reactions can be turned into sustainable 100% yield processes with optimal atom efficiency by milling stoichiometric 1 1 1 mixtures of acid chloride, aniline derivative, and K2CO3... 

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. 

The aerobic pathway of metabolism (pathway 1) (Fig. 7.77) produces trifluoroacetyl chloride, a highly reactive acyl chloride, which can react with nucleophiles such as amino groups similar to those on proteins. Alternatively, reaction with water yields trifluoroacetic acid. Trifluoroacetylchloride is the probable reactive metabolite that trifluoroacylates protein, most probably at lysine residues (Fig. 7.77). Removal of the trifluoroacyl moiety from the... 

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