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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 materials, i.e., matter in its various forms that contain carbon atoms.Clay ...
, an acyl chloride (or acid chloride) is an
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
with the
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the res ...
. Their formula is usually written , where R is a side chain. 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 R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
s (). A specific example of an acyl chloride is acetyl chloride, . Acyl chlorides are the most important subset of acyl halides.


Nomenclature

Where the acyl chloride
moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...
takes priority, acyl chlorides are named by taking the name of the parent carboxylic acid, and substituting ''-yl chloride'' for ''-ic acid''. Thus: : : 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 (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing ...
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 R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
s. For example, acetic acid boils at 118 °C, whereas acetyl chloride boils at 51 °C. Like most carbonyl compounds, infrared spectroscopy 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: :RCOCl + H2O -> RCOOH + HCl


Synthesis


Industrial routes

The industrial route to acetyl chloride involves the reaction of acetic anhydride with hydrogen chloride: :(CH3CO)2O + HCl -> CH3COCl + CH3CO2H Propionyl chloride is produced by chlorination of propionic acid with
phosgene Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, es ...
: :CH3CH2CO2H + COCl2 -> CH3CH2COCl + HCl + CO2 Benzoyl chloride is produced by the partial hydrolysis of benzotrichloride: :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 Kevla ...
to give
terephthaloyl chloride Terephthaloyl chloride (TCL, 1,4-benzenedicarbonyl chloride) is the acyl chloride of terephthalic acid. It is a white solid. It is one of two precursors used to make Kevlar(R), the other being ''p''-phenylenediamine. TCL is used as a key compone ...
: :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 (). The reaction is catalyzed by dimethylformamide 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). The reaction with thionyl chloride is catalyzed by dimethylformamide.


Laboratory methods: phosphorus chlorides

Phosphorus trichloride () is also popular, phosphorus pentachloride (). although excess reagent is required. Phosphorus pentachloride is also effective but only one chloride is transferred: :RCO2H + PCl5 -> RCOCl + POCl3 + HCl


Laboratory methods: oxalyl chloride

Another method involves the use of oxalyl chloride: :RCO2H + ClCOCOCl -> MF RCOCl + CO + CO2 + HCl The reaction is catalysed by dimethylformamide (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 In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...
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 Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula . It is a colourless, fuming liquid with an irritating odour, and consists of a benzene ring () with an acyl chloride () substituent. It i ...
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 componen ...
: :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: :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 oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
s or
amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s: :::


Nucleophilic reactions

Acid chlorides are useful for the preparation of amides, esters, anhydrides. These reactions generate chloride, which can be undesirable. Acyl chlorides hydrolyze, yielding the carboxylic acid: ::: This hydrolysis is usually a nuisance rather than intentional. 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 R(CO)O(CO)R'. Organic acid anhydrides often form when one equiva ...
s,
amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s and
ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
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 R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
, an
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
, or an alcohol, respectively. ::: ::: :::


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, weakl ...
or ''N,N''-dimethylformamide, catalyze acylations. 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''.⁠


Conversion to ketones

Carbon nucleophiles such as Grignard reagents, convert acyl chlorides to
ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...
s, 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 Gilman reagents 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 Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
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

With
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 sp ...
catalysts like ferric chloride or aluminium chloride, acyl chlorides participate in Friedel-Crafts acylations, to give aryl ketones: : 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): :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

{{Authority control Functional groups