Organic Chemistry 101: Acid Derivatives and Esters

This is an organic molecule. It consists of an alkane chain with a chlorine atom bound to a terminal carbonyl carbon.

To name an acyl chloride, remove the “-e” from the end of the name of the parent alkane and replace it with “-oyl chloride.” Since an acyl chloride is a terminal group, it is unnecessary to write “1-propanoyl chloride.”

butanoyl chloride, an acyl chloride.

To name an acyl chloride, remove the “-e” from the end of the name of the parent alkane and replace it with “-oyl chloride.”

This is an organic molecule containing two carbonyl groups connected by an oxygen atom.

Symmetric anhydrides, in which identical groups are bonded to the two carbonyls, are named by removing the “-e” from the parent alkane and replacing it with “-oic anhydride.” Asymmetrical anhydrides are named by alphabetically arranging the two parent alkanes, replacing the “-e” with “-oic” in both, and ending with the word “anhydride.”

ethanoic propanoic anhydride

Asymmetrical anhydrides are named by alphabetically arranging the names of the two parent alkanes, replacing the “-e” with “-oic” in both, and ending with the word “anhydride.”

This is an organic molecule. It consists of an alkane chain with a carbonyl carbon bound to a nitrogen atom.

Amides are named by removing the “-e” from the parent alkane and replacing it with “-amide.” Additional carbon chains bound to the nitrogen should be listed in front of the alkanamide name without spaces.

methylethanamide

To name an amide, remove the “-e” from the parent alkane and replace it with “-amide.” Additional carbon chains bound to the nitrogen should be listed in front of the alkanamide name without spaces, as “methyl” is here.

It is an organic molecule. It consists of an alkane chain with a carbonyl carbon bound to an -OR group.

Esters are named by removing the “-e” from the parent alkane chain and replacing it with “-oate,” then adding the name of the R group from the -OR moiety as a prefix.

propyl butanoate

To name an ester, first name the R group that is bound directly to the oxygen atom. After a space, add the name of the parent alkane, replacing the “-e” with “-oate.”

All acid derivatives have dipole-dipole interactions due to the polar carbonyl bond.

Additionally, derivatives can be involved in hydrogen bonding, but to varying degrees. For example, carboxylic acids themselves can both donate and accept hydrogen bonds, while esters are only weak H-bond acceptors.

Acid derivatives have higher boiling points than alkanes.

Due to its carbonyl group, an acid derivative is able to exert dipole-dipole interactions. These intermolecular forces are stronger than those present on alkanes, which are relatively nonpolar. Stronger intermolecular forces lead to higher boiling points.

Acyl chlorides, the most reactive of the derivatives, are often used in synthesis reactions. They can be converted into anhydrides, esters, and amides.

The chlorine atom on an acyl chloride is a good leaving group, and thus can be easily replaced via nucleophilic attack. Reacting with a carboxylic acid creates an anhydride, reacting with an alcohol creates an ester, and reacting with an amine creates an amide.

Acid derivatives undergo nucleophilic substitution reactions at their carbonyl carbons.

The carbonyl carbon is fairly electropositive. For this reason, a nucleophile can easily attack and replace the characteristic group bonded to that carbon. For example, a nucleophilic attack on an acyl chloride will replace the chlorine atom with the nucleophile.

A primary amine is created from the rearrangement and decarboxylation of a primary amide.

This reaction ocurrs in basic conditions and proceeds through an isocyanate (O=C=N-R) intermediate. Overall, the R group attached to the carbonyl bonds to the amide nitrogen, and the carbonyl group is lost as carbon dioxide gas.

This will produce 1-aminopropane. Carbon dioxide gas will also form as a side product.

This reaction is a Hofmann rearrangement. The R group bonds to the nitrogen atom, and the carbonyl group is lost as carbon dioxide gas.

The -OR group of an ester is replaced by a different -OR’ group. In other words, one ester is converted into another.

This reactants involved are the original ester and an alcohol in acidic conditions.

1. An alcohol (containing the new -OR’ group) is added to the original ester (containing the old -OR group) in acidic conditions.

2. The alcohol oxygen acts as a nucleophile, attacking the carbonyl carbon and replacing the ester -OR with the alcohol -OR’.

3. The original -OR group is protonated and leaves as an alcohol.

saponification

A triglyceride contains a glycerol backbone bound to three fatty acids through ester linkages.

1. A triglyceride and a base (generally NaOH) are combined.

2. One equivalent of OH- acts as a nucleophile, attacking the carbonyl carbon of one of the triglyceride’s ester linkages.

3. The bond between this ester and the glycerol backbone breaks, allowing part of the molecule to leave as a fatty acid salt.

4. The same process occurs with the remaining two ester linkages, requiring two additional equivalents of OH-. The final products are glycerol and three fatty acid salts, which can later be acidified to carboxylic acids.

• glycerol

• three fatty acid chains

This reaction is a saponification, also known as a hydrolysis of fats or triglycerides. Three hydroxide ions from the basic solution act as nucleophiles, attacking the carbonyl carbons and allowing the backbone to leave as an alcohol.

The leaving group is an amine. Overall, products of such a reaction include the amine and a carboxylic acid.

In amide hydrolysis, a hydroxide ion acts as a nucleophile and attacks the carbonyl carbon. This allows -OH to bind and replace the amine.

• propanoic acid

• aminomethane (methylamine)

From most to least reactive:

acyl chlorides > anhydrides > esters > amides

Acid derivatives with better leaving groups will be more reactive in a nucleophilic substitution. Halogens (like chlorine) are the best leaving groups, while deprotonated amines (like NH2-) are the worst.

ester

The ester’s OR- group is a better (more stable) leaving group than the amide’s amino group. This allows the ester to react more readily.

It decrease the overall reactivity.

Large substituents near the carbonyl carbon cause steric hindrance, blocking the nucleophile’s access to the electrophilic carbon.

These would not affect the reaction.

Since the tert-butyl groups are far from the carbonyl carbon, they will not cause steric hindrance that would hinder a nucleophilic attack.

Able to stabilize negative charge.

For example, the chloride anion is electronegative and fairly capable of holding a negative charge. Thus, acid chlorides react well in nucleophilic substitution reactions. In contrast, a deprotonated amine does not stabilize negative charge well, making it very reactive and a poor leaving group.

It stabilizes negative charge more effectively. Since it displays resonance between its two electronegative oxygen atoms, it is able to "spread out" the charge.

This makes the carboxylate anion a better leaving group, which is why anhydrides are more reactive than esters in nucleophilic substitution reactions.

It increases the reactivity of a cyclic acid derivative.

A ring-opening reaction (hydrolysis, for example) will be very energetically favorable as it eliminates this strain. Such reactions will generally be very exothermic.

This (such as ß-lactam) is much more reactive due to its significant ring strain that is relieved upon hydrolysis.

An amide's carbon-nitrogen bond has partial double bond character. This increases ring strain in cyclic amides because it limits the rings from bending.

• ketone

• carboxylic acid

Keto acids with the ketone group on the alpha carbon are called alpha keto acids, also known as 2-oxoacids. Beta keto acids, also known as 3-oxoacids, have the ketone group on the beta carbon.

ß-ketobutanoic acid

| 3-oxobutanoic acid

To name a keto acid, first identify the location of the ketone group relative to the carboxylic acid carbon (alpha, beta, gamma, etc.). Place this identifier in front of the carboxylic acid name.

Keto acids may also be named as oxoacids, with a number indicating the number of carbons from the carboxyl carbon to the ketone carbon. The name of the carboxylic acid follows that number and the prefix "oxo-."

ß-keto acids

The carboxylic acid group will be lost as carbon dioxide, and the resulting reaction intermediate is stabilized in the enol form.

• 2-butanone

• carbon dioxide gas

The ß-keto acid undergoes a decarboxylation, losing its carboxylic carbon in the form of CO2.

The alpha protons of a ß-keto ester are the most acidic. This is also true of other carbonyl-containing molecules.

When the alpha proton is deprotonated, the resulting molecule is stabilized by resonance. On a ß-keto ester, the electronic stabilization from the two carbonyl groups makes the alpha proton(s) even more acidic.

It is the interconversion of a molecule between a keto form (containing a carbonyl group) and an enol form (containing an alcohol).

This type of tautomerism includes the movement of an alpha hydrogen and the bonding electrons of a pi bond. Note that this is distinct from resonance, in which the atoms do not move.

The ester is in the keto form. The molecule shown here is the enol form of the same ester.

After decarboxylation of a ß-keto acid, the enol form stabilizes the reaction intermediate. The molecule then tautomerizes to form the keto final product.