
In
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...
, an acyl chloride (or acid chloride) is an
organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
with the
functional group
In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...
. Their formula is usually written , where R is a
side chain
In organic chemistry and biochemistry, a side chain is a substituent, chemical group that is attached to a core part of the molecule called the "main chain" or backbone chain, backbone. The side chain is a hydrocarbon branching element of a mo ...
. They are reactive derivatives of
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
s (). A specific example of an acyl chloride is
acetyl chloride
Acetyl chloride () is an acyl chloride derived from acetic acid (). It belongs to the class of organic compounds called acid halides. It is a colorless, corrosive, volatile liquid. Its formula is commonly abbreviated to AcCl.
Synthesis
On an ...
, . Acyl chlorides are the most important subset of
acyl halides.
Nomenclature
Where the acyl chloride
moiety takes priority, acyl chlorides are named by taking the name of the parent carboxylic acid, and substituting ''-yl chloride'' for ''-ic acid''. Thus:
:
:
:
butyr''ic acid'' (C
3H
7COOH) →
butyr''yl chloride'' (C3H7COCl)
(Idiosyncratically, for some trivial names, ''-oyl chloride'' substitutes ''-ic acid''. For example, pival''ic acid'' becomes pival''oyl chloride'' and acryl''ic acid'' becomes acryl''oyl chloride.'' The names pivalyl chloride and acrylyl chloride are less commonly used, although they are arguably more logical.)
When other functional groups take priority, acyl chlorides are considered prefixes — ''chlorocarbonyl-'':
:
Properties
Lacking the ability to form
hydrogen bond
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
s, acyl chlorides have lower boiling and melting points than similar
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
s. For example, acetic acid boils at 118 °C, whereas acetyl chloride boils at 51 °C. Like most
carbonyl compound
In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such as aldehydes, ...
s,
infrared spectroscopy
Infrared spectroscopy (IR spectroscopy or vibrational spectroscopy) is the measurement of the interaction of infrared radiation with matter by absorption, emission, or reflection. It is used to study and identify chemical substances or functio ...
reveals a band near 1750 cm
−1.
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
Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
:
:
RCOCl + H2O -> RCOOH + HCl
Synthesis
Industrial routes
The industrial route to acetyl chloride involves the reaction of
acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the chemical formula, formula . Commonly abbreviated , it is one the simplest organic acid anhydride, anhydrides of a carboxylic acid and is widely used in the production of c ...
with
hydrogen chloride
The Chemical compound, compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hyd ...
:
:
(CH3CO)2O + HCl -> CH3COCl + CH3CO2H
Propionyl chloride
Propionyl chloride (also propanoyl chloride) is the organic compound with the formula CH3CH2C(O)Cl. It is the acyl chloride derivative of propionic acid. It undergoes the characteristic reactions of acyl chlorides. It is a colorless, corrosive, v ...
is produced by chlorination of
propionic acid
Propionic acid (, from the Greek language, Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula . It is a ...
with
phosgene
Phosgene is an organic chemical compound with the formula . It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. It can be thought of chemically as the double acyl chloride analog of ...
:
:
CH3CH2CO2H + COCl2 -> CH3CH2COCl + HCl + CO2
Benzoyl chloride is produced by the partial hydrolysis of
benzotrichloride
Benzotrichloride (BTC), also known as α,α,α-trichlorotoluene, phenyl chloroform or (trichloromethyl)benzene, is an organic compound with the formula C6H5CCl3. Benzotrichloride is an unstable, colorless or somewhat yellowish, viscous, chlorinat ...
:
:
C6H5CCl3 + H2O -> C6H5C(O)Cl + 2 HCl
Similarly, benzotrichlorides react with carboxylic acids to the acid chloride. This conversion is practiced for the reaction of
1,4-bis(trichloromethyl)benzene
1,4-Bis(trichloromethyl)benzene is an organic compound with the formula C6H4(CCl3)2. A white solid, it is prepared industrially by chlorination of para-xylene. It reacts with terephthalic acid to give terephthaloyl chloride, a precursor to Kevl ...
to give
terephthaloyl chloride
Terephthaloyl chloride (TCL, 1,4-benzenedicarbonyl chloride) is the acyl chloride of terephthalic acid. It is a white solid at room temperature. It is one of two precursors used to make Kevlar, the other being ''p''-phenylenediamine. TCL is us ...
:
:
C6H4(CCl3)2 + C6H4(CO2H)2 -> 2 C6H4(COCl)2 + 2 HCl
Laboratory methods
Thionyl chloride
In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with
thionyl chloride
Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately Volatility (chemistry), volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a Halogenation, chlorinating reagen ...
(). The reaction is catalyzed by
dimethylformamide
Dimethylformamide, DMF is an organic compound with the chemical formula . Its structure is . Commonly abbreviated as DMF (although this initialism is sometimes used for 2,5-dimethylfuran, dimethylfuran, or dimethyl fumarate), this colourless liqui ...
and other additives.

Thionyl chloride 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).
Phosphorus chlorides
Phosphorus trichloride
Phosphorus trichloride is an inorganic compound with the chemical formula PCl3. A colorless liquid when pure, it is an important industrial chemical, being used for the manufacture of phosphites and other organophosphorus compounds. It is toxic ...
() is popular,
although excess reagent is required.
[ Phosphorus pentachloride () is also effective,] but only one chloride is transferred:
:RCO2H + PCl5 -> RCOCl + POCl3 + HCl
Oxalyl chloride
Another method involves the use of oxalyl chloride:
:RCO2H + ClCOCOCl -> MF RCOCl + CO + CO2 + HCl
The reaction is catalysed by dimethylformamide
Dimethylformamide, DMF is an organic compound with the chemical formula . Its structure is . Commonly abbreviated as DMF (although this initialism is sometimes used for 2,5-dimethylfuran, dimethylfuran, or dimethyl fumarate), this colourless liqui ...
(DMF), which reacts with oxalyl chloride to give the Vilsmeier reagent, an iminium intermediate that which reacts with the carboxylic acid to form a mixed imino-anhydride. This structure undergoes an acyl substitution with the liberated chloride, forming the acid anhydride and releasing regenerated molecule of DMF.[ Relative to thionyl chloride, oxalyl chloride is more expensive but also a milder reagent and therefore more selective.
:]
Other laboratory methods
Acid chlorides can be used as a chloride source. Thus acetyl chloride can be distilled from a mixture of benzoyl chloride and acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...
:[
:CH3CO2H + C6H5COCl -> CH3COCl + C6H5CO2H
Other methods that do not form HCl include the Appel reaction:
:RCO2H + Ph3P + CCl4 -> RCOCl + Ph3PO + HCCl3
Another is the use of ]cyanuric chloride
Cyanuric chloride is an organic compound with the formula (NCCl)3. This white solid is the chlorinated derivative of 1,3,5-triazine. It is the trimer of cyanogen chloride. Cyanuric chloride is the main precursor to the popular but controversi ...
:
:RCO2H + C3N3Cl3 -> RCOCl + C3N3Cl2OH
Reactions
Acyl chloride are reactive, versatile reagents. Acyl chlorides have a greater reactivity than other carboxylic acid derivatives like acid anhydrides, ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
s or amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
s:
:::
Acyl chlorides hydrolyze, yielding the carboxylic acid:
:::
This hydrolysis is usually a nuisance rather than intentional.
Alcoholysis, aminolysis, and related reactions
Acid chlorides are useful for the preparation of amides, esters, anhydrides. These reactions generate chloride, which can be undesirable. Acyl chlorides are used to prepare acid anhydride
An acid anhydride is a type of chemical compound derived by the removal of water molecules from an acid.
In organic chemistry, organic acid anhydrides contain the functional group . Organic acid anhydrides often form when one equivalent of wa ...
s, amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
s and ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
s, by reacting acid chlorides with: a salt of a carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
, an amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
, or an alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, respectively.
:::
:::
:::
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 species 3. Deprotonation gives the mixed anhydride, 4, and an equivalent of HCl.
Alcohols and amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
s react with acid halides to produce ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
s and amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
s, 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
Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...
, to neutralize the hydrohalic acid that is formed as a byproduct.
Mechanism
The alcoholysis of acyl halides (the alkoxy-dehalogenation) is believed to proceed via an SN2 mechanism (Scheme 10). However, the mechanism can also be tetrahedral or SN1 in highly polar solvents (while the SN2 reaction involves a concerted reaction, the tetrahedral addition-elimination pathway involves a discernible intermediate).
Bases, such as pyridine
Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...
or ''N,N''-dimethylformamide, catalyze acylation
In chemistry, acylation is a broad class of chemical reactions in which an acyl group () is added to a substrate. The compound providing the acyl group is called the acylating agent. The substrate to be acylated and the product include the foll ...
s. 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''.
Reactions with carbanions
Acid halides react with carbon nucleophiles, such as Grignards and enolate
In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the Organic synthesis, synthesis of organic compounds.
Bonding and structure
Enolate ...
s, although mixtures of products can result. While a carbon nucleophile will react with the acid halide first to produce a ketone, the ketone is also susceptible to nucleophilic attack, and can be converted to a tertiary alcohol. For example, when benzoyl chloride (1) is treated with two equivalents of a Grignard reagent, such as methyl magnesium bromide (MeMgBr), 2-phenyl-2-propanol (3) is obtained in excellent yield. Although acetophenone
Acetophenone is the organic compound with the formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances.
Production
Acetophenone is formed as a byproduct of the cumene ...
(2) is an intermediate in this reaction, it is impossible to isolate because it reacts with a second equivalent of MeMgBr rapidly after being formed.
Unlike most other carbon nucleophiles, lithium dialkylcuprates – often called Gilman reagent
A Gilman reagent is a diorganocopper compound with the formula Li uR2 where R is an alkyl or aryl. They are colorless solids.
Use in organic chemistry
These reagents are useful because, unlike related Grignard reagents and organolithium reage ...
s – 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 chelated by the carbonyl and N–methoxy oxygens, preventing further nucleophilic additions.
Carbon nucleophiles such as Grignard reagent
Grignard reagents or Grignard compounds are chemical compounds with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromi ...
s, convert acyl chlorides to ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
s, which in turn are susceptible to the attack by second equivalent to yield the tertiary alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
. The reaction of acyl halides with certain organocadmium
Organocadmium chemistry describes the physical properties, synthesis, reactions, and use of organocadmium compounds, which are organometallic compounds containing a carbon to cadmium chemical bond. Cadmium shares Group 12 element, group 12 with zin ...
reagents stops at the ketone stage. The reaction with Gilman reagent
A Gilman reagent is a diorganocopper compound with the formula Li uR2 where R is an alkyl or aryl. They are colorless solids.
Use in organic chemistry
These reagents are useful because, unlike related Grignard reagents and organolithium reage ...
s also afford ketones, reflecting the low nucleophilicity of these lithium diorganocopper compounds.[
]
Reduction
Acyl chlorides are reduced by lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula or . It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthe ...
and diisobutylaluminium hydride
Diisobutylaluminium hydride (DIBALH, DIBAL, DIBAL-H or DIBAH) is a reducing agent with the chemical formula, formula (''i''-Bu2AlH)2, where ''i''-Bu represents isobutyl (-CH2CH(CH3)2). This organoaluminium chemistry, organoaluminium compound is a r ...
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
Hydrogen is a chemical element; it has symbol H and atomic number 1. It is the lightest and most abundant chemical element in the universe, constituting about 75% of all normal matter. Under standard conditions, hydrogen is a gas of diatomi ...
over a poisoned palladium catalyst.
Acylation of arenes
In the Friedel–Crafts acylation, acid halides act as electrophiles for electrophilic aromatic substitution
Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is attached to an aromatic ring, aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitut ...
. A Lewis acid
A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any ...
– such as zinc chloride
Zinc chloride is an Inorganic chemistry, inorganic chemical compound with the chemical formula, formula ZnCl2·''n''H2O, with ''n'' ranging from 0 to 4.5, forming water of hydration, hydrates. Zinc chloride, anhydrous and its hydrates, are colo ...
(ZnCl2), iron(III) chloride
Iron(III) chloride describes the inorganic compounds with the formula (H2O)x. Also called ferric chloride, these compounds are some of the most important and commonplace compounds of iron. They are available both in anhydrous and in hydrated f ...
(FeCl3), or aluminum chloride
Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms a hexahydrate with the formula , containing six water molecules of hydration. Both the anhydrous form and the hexahydrate are col ...
(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
Acetyl chloride () is an acyl chloride derived from acetic acid (). It belongs to the class of organic compounds called acid halides. It is a colorless, corrosive, volatile liquid. Its formula is commonly abbreviated to AcCl.
Synthesis
On an ...
to Vaska's complex, converting square planar Ir(I) to octahedral Ir(III):
:IrCl(CO)(PPh3)2 + CH3COCl -> CH3COIrCl2(CO)(PPh3)2
Hazards
Low molecular weight acyl chlorides are often lachrymators, and they react violently with water, alcohols, and amines.
References
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Functional groups