In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group -COCl. Their formula is usually written RCOCl, where R is a side chain. They are reactive derivatives of carboxylic acids. A specific example of an acyl chloride is acetyl chloride, CH3COCl. Acyl chlorides are the most important subset of acyl halides.
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:
When other functional groups take priority, acyl chlorides are considered prefixes — chlorocarbonyl-:
- (chlorocarbonyl)acetic acid ClOCCH2COOH
Lacking the ability to form hydrogen bonds, acyl chlorides have lower boiling and melting points than similar carboxylic acids. 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 chloride hydrolyzes (reacts with water).
- (CH3CO)2O + HCl → CH3COCl + CH3CO2H
- CH3CH2CO2H + COCl2 → CH3CH2COCl + HCl + CO2
- C6H5CCl3 + H2O → C6H5C(O)Cl + 2 HCl
- C6H4(CCl3)2 + C6H4(CO2H)2 → 2 C6H4(COCl)2 + 2 HCl
Laboratory methods: thionyl chlorideEdit
Thionyl chloride is a well-suited reagent as the by-products (HCl, SO2) 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 chloridesEdit
Phosphorus trichloride (PCl3) is also popular, phosphorus pentachloride (PCl5). although excess reagent is required. Phosphorus pentachloride is also effective but only one chloride is transferred:
- RCO2H + PCl5 → RCOCl + POCl3 + HCl
Laboratory methods: oxalyl chlorideEdit
Another method involves the use of oxalyl chloride:
- RCO2H + ClCOCOCl → RCOCl + CO + CO2 + HCl
The reaction is catalysed by dimethylformamide (DMF), which reacts with oxalyl chloride in the first step to give an iminium intermediate, which reacts with the carboxylic acid, abstracting an oxide, and regenerating the DMF catalyst. Relative to thionyl chloride, oxalyl chloride is more expensive but also a milder reagent and therefore more selective.
Other laboratory methodsEdit
- CH3CO2H + C6H5COCl → CH3COCl + C6H5CO2H
- RCO2H + Ph3P + CCl4 → RCOCl + Ph3PO + HCCl3
- RCO2H + C3N3Cl3 → RCOCl + C3N3Cl2OH
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 anhydrides, amides and esters, by reacting acid chlorides with: a salt of a carboxylic acid, an amine, or an alcohol, respectively.
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).
Base, e.g. pyridine or N,N-dimethylformamide, catalyze acylations. These reagents activate the acyl chloride via an nucleophilic catalysis mechanism. The amine attacks the carbonyl bond and presumably forms first a transient tetrahedral intermediate and afterwards, by the displacement of the leaving group, a quaternary acylammonium salt. This quaternary acylammonium salt is more susceptible to attack by alcohols or other nucleophiles.
Conversion to ketonesEdit
Carbon nucleophiles such as Grignard reagents, convert acyl chlorides to ketones, 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.
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 arenesEdit
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.
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
Low molecular weight acyl chlorides are often lachrymators, and they react violently with water, alcohols, and amines.
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