Acid Chlorides and Anhydrides

Acid Chlorides

There are a number of related compounds in which the –OH group in the carboxylic acid is replaced by
something else. Compounds like this are described as carboxylic acid derivatives.

Acid chlorides, also known as acyl chlorides, are one example of a carboxylic acid derivative. In this case,
the –OH group has been replaced by a chlorine atom.

Molecular and Structural Formula

RCOCl

Nomenclature

Acid chlorides are named by replacing the –ic acid ending with –yl chloride, or replacing the carboxylic
acid ending with –carbonyl chloride . The suffix –carbonyl chloride is used for attachments to rings other
than benzenes.

Preparations and Reactions

Replacing the –OH group using phosphorus(V) chloride, PCl5

Phosphorus(V) chloride is a solid which reacts with carboxylic acids in the cold to give steamy acidic
fumes of hydrogen chloride. It leaves a mixture of the acid chloride and a phosphorus compound,
phosphorus trichloride oxide (POCl3).

The acid chloride can be separated by fractional distillation.

Replacing the –OH group using phosphorus(III) chloride, PCl3

You end up with a mixture of the acid chloride and phosphoric(III) acid (old names: phosphorous acid or
orthophosphorous acid), H3PO3-.

Replacing the –OH group using sulphur dichloride oxide (thionyl chloride)

Sulphur dichloride oxide reacts with carboxylic acids to produce an acid chloride, and sulphur dioxide
and hydrogen chloride gases are given off.
Acid chlorides are the most reactive carboxylic acid derivatives, and easily converted to acid anhydrides,
esters and amides via nucleophilic acyl substitution. Acid chlorides are sufficiently reactive with H2O,
and quite readily hydrolysed to carboxylic acid.

Acid chlorides react with carboxylic acids to form anhydrides.

Acid chlorides react with water to form carboxylic acids.

Acid chlorides react with water to form alcohols to form esters.

Acid chlorides react with ammonia, primary and secondary amines to form amides.

Properties

Appearance

An acyl chloride like ethanoyl chloride is a colourless fuming liquid. The strong smell of ethanoyl chloride
is a mixture of the smell of vinegar (ethanoic acid) and the acrid smell of hydrogen chloride gas.

Solubility in water

Acyl chlorides can't be said to dissolve in water because they react (often violently) with it. The strong
reaction means that it is impossible to get a simple aqueous solution of an acyl chloride.

Boiling point

Taking ethanoyl chloride as typical: Ethanoyl chloride boils at 51°C. It is a polar molecule, and so has
dipole-dipole attractions between its molecules as well as van der Waals dispersion forces.
However, it doesn't form hydrogen bonds. Its boiling point is therefore higher than, say, an alkane of
similar size (which has no permanent dipoles), but not as high as a similarly sized alcohol (which forms
hydrogen bonds in addition to everything else.)

Uses

Acyl chlorides are used to synthesize with the carboxylic acid derivatives. They readily react with
alcohols or phenols to give esters; with ammonia or amines to give amides; with carboxylic acid salts to
give anhydrides; with sodium azide (NaN3) to give acyl azides; with aromatic rings in the presence of
aluminum chloride (AlCl3) to give ketones in a reaction known as Friedel-Crafts acylation; and with
lithium dialkylcopper reagents (R′2CuLi) to give ketones.

Anhydrides

Loss of water from two molecules of carboxylic acid results in an acid anhydride. “Anhydride” means
without water. An acid anhydride is an organic compound that has two acyl groups bound to the same
oxygen atom.

Molecular and Structural Formula

(RCO)2O

Nomenclature

Symmetrical anhydrides are named like carboxylic acids except the ending –acid is replaced with –
anhydride. This is true for both the IUPAC and common nomenclature.

Unsymmetrical anhydrides are named by first naming each component carboxylic acid alphabetically
arranged (without the word acid) followed by the word anhydride.

Preparations and Reactions

Acid anhydrides are the second most reactive of the carboxylic acid derivatives. They are fairly readily
converted to the other less reactive carboxylic acid derivatives, e.g. esters, carboxylic acids and amides.
Acid anhydrides undergo many reactions similar to those of acid chlorides, and they can often be used
interchangeably.

Anhydrides are commonly formed when a carboxylic acid

reacts with an acid chloride in the presence of a base.

Anhydrides give essentially the same reactions as the acyl chlorides, although they generally react more
slowly. This can be an advantage or a disadvantage. The reason that anhydrides are less frequently used
in these reactions is due more to availability considerations than to reactivity. In most cases, the acyl
chloride is easier or less expensive to obtain than the corresponding anhydride. Acid anhydrides are
most often used to prepare carboxylic esters and amides and in Friedel-Crafts acylations.

Properties

We will take ethanoic anhydride as typical.

Appearance

Ethanoic anhydride is a colorless liquid, smelling strongly of vinegar (ethanoic acid). The smell is because
ethanoic anhydride reacts with water vapor in the air (and moisture in your nose) to produce ethanoic
acid again.

Solubility in water

Ethanoic anhydride can't be said to dissolve in water because it reacts with it to give ethanoic acid.
There is no such thing as an aqueous solution of ethanoic anhydride.

Boiling point

Ethanoic anhydride boils at 140°C. This is because it is a fairly big polar molecule and so has both van der
Waals dispersion forces and dipole-dipole attractions. It does not, however, form hydrogen bonds. That
means that its boiling point isn't as high as a carboxylic acid of similar size. For example, pentanoic acid
(the most similarly sized acid) boils at 186°C.

Uses

• They are used in the manufacture of many things like pharmaceuticals industrial chemicals,
explosives and perfumes

• Synthesis of esters by acetylation of alcohols

• Synthesis of aspirin (Acetyl salicyclic acid)

References

• Chem.libretexts.org (2015)

• Chemistry for Pharmacy Students (2007) by Satyajit D. Sarker and Lutfun Nahar

• Organic Chemistry: A Brief Course (2002) by Robert C. Atkins and Francis A. Carey

• Carboxylic Acid (2018) by William H. Brown and Jerry March

• Organic Chemistry, Fifth Edition (2007) by Paula Yurkanis Bruice