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In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of (). A specific example of an acyl chloride is acetyl chloride, . Acyl chlorides are the most important subset of .
Acyl chlorides of dicarboxylic acids, called diacyl chlorides (sometimes diacid chlorides or dioyl chlorides), follow similar rules, retaining either their common name or a multiplicative prefix before -yl and chloride.
When other functional groups take priority, acyl chlorides are considered prefixes — chlorocarbonyl-:
The simplest stable acyl chloride is acetyl chloride; formyl chloride is not stable at room temperature, although it can be prepared at –60 °C or below.
Acyl chlorides hydrolyze (react with water) to form the corresponding carboxylic acid and hydrochloric acid:
Propionyl chloride is produced by chlorination of propionic acid with phosgene:
Benzoyl chloride is produced by the partial hydrolysis of benzotrichloride:
Similarly, benzotrichlorides react with carboxylic acids to the acid chloride. This conversion is practiced for the reaction of 1,4-bis(trichloromethyl)benzene to give terephthaloyl chloride:
Thionyl chlorideJ. S. Pizey, Synthetic Reagents, Vol. 1, Halsted Press, New York, 1974. is a well-suited reagent as the by-products (HCl, ) are gases and residual thionyl chloride can be easily removed as a result of its low boiling point (76 °C).
Other methods that do not form HCl include the Appel reaction:" Triphenylphosphine-carbon tetrachloride Taschner, Michael J. e-EROS: Encyclopedia of Reagents for Organic Synthesis, 2001
Acyl chlorides hydrolyze, yielding the carboxylic acid:
Acid halides are the most reactive acyl derivatives, and can easily be converted into any of the others. Acid halides will react with carboxylic acids to form anhydrides. If the structure of the acid and the acid chloride are different, the product is a mixed anhydride. First, the carboxylic acid attacks the acid chloride ( 1) to give tetrahedral intermediate 2. The tetrahedral intermediate collapses, ejecting chloride ion as the leaving group and forming oxonium ion species 3. Deprotonation gives the mixed anhydride, 4, and an equivalent of HCl.
Alcohols and react with acid halides to produce and , respectively, in a reaction formally known as the Schotten-Baumann reaction. Acid halides hydrolyze in the presence of water to produce carboxylic acids, but this type of reaction is rarely useful, since carboxylic acids are typically used to synthesize acid halides. Most reactions with acid halides are carried out in the presence of a non-nucleophilic base, such as pyridine, to neutralize the hydrohalic acid that is formed as a byproduct.
Bases, such as pyridine or N,N-dimethylformamide, catalyze . These reagents activate the acyl chloride via a nucleophilic catalysis mechanism. The amine attacks the carbonyl bond and presumably first forms a transient tetrahedral intermediate, then forms a quaternary acylammonium salt by the displacement of the leaving group. This quaternary acylammonium salt is more susceptible to attack by alcohols or other nucleophiles.
The use of two phases (aqueous for amine, organic for acyl chloride) is called the Schotten-Baumann reaction. This approach is used in the preparation of nylon via the so-called nylon rope trick.
Unlike most other carbon nucleophiles, lithium dialkylcuprates – often called – can add to acid halides just once to give ketones. The reaction between an acid halide and a Gilman reagent is not a nucleophilic acyl substitution reaction, however, and is thought to proceed via a radical pathway. The Weinreb ketone synthesis can also be used to convert acid halides to ketones. In this reaction, the acid halide is first converted to an N–methoxy–N–methylamide, known as a Weinreb amide. When a carbon nucleophile – such as a Grignard or organolithium reagent – adds to a Weinreb amide, the metal is Chelation by the carbonyl and N–methoxy oxygens, preventing further nucleophilic additions.Kürti and Czakó 2005, p. 478.
Carbon nucleophiles such as , convert acyl chlorides to , which in turn are susceptible to the attack by second equivalent to yield the tertiary alcohol. The reaction of acyl halides with certain organocadmium reagents stops at the ketone stage. The reaction with also afford ketones, reflecting the low nucleophilicity of these lithium diorganocopper compounds.
Reduction
Acyl chlorides are reduced by lithium aluminium hydride and diisobutylaluminium hydride to give primary alcohols. Lithium tri-tert-butoxyaluminium hydride, a bulky hydride donor, reduces acyl chlorides to aldehydes, as does the Rosenmund reduction using hydrogen gas over a poisoned palladium catalyst.
Acylation of arenes
In the Friedel–Crafts acylation, acid halides act as electrophiles for electrophilic aromatic substitution. A Lewis acid – such as zinc chloride (ZnCl2), iron(III) chloride (FeCl3), or aluminum chloride (AlCl3) – coordinates to the halogen on the acid halide, activating the compound towards nucleophilic attack by an activated aromatic ring. For especially electron-rich aromatic rings, the reaction will proceed without a Lewis acid.Kürti and Czakó 2005, p. 176.
Because of the harsh conditions and the reactivity of the intermediates, this otherwise quite useful reaction tends to be messy, as well as environmentally unfriendly.
Oxidative addition
Acyl chlorides react with low-valent metal centers to give transition metal acyl complexes. Illustrative is the oxidative addition of acetyl chloride to Vaska's complex, converting square planar Ir(I) to octahedral Ir(III):
Hazards
Low molecular weight acyl chlorides are often , and they react violently with water, alcohols, and amines.
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