Once you understand the nature of the functional groups, you will be able to understand how to make them react chemically. And an important functional group in organic chemistry is the amine. There are so many molecules with amines that they are one of the most common substitution groups.
Amino groups are known to be basic substances and act as nucleophiles. Therefore, they are used in nucleophilic substitution reactions, but they can also be used as leaving groups. They can be used in special elimination reactions to synthesize alkenes.
Also, like amines, one important functional group in both nucleophilic substitution and elimination reactions is the thiol. Since the types of organic chemical reactions are similar, learning about them at the same time as amines will help you to understand the properties of thiols more efficiently.
Amines and thiols have fewer types of reactions. They are also easier to understand because they are not complex reaction mechanisms. We will explain how amines and thiols react with each other.
Table of Contents
- 1 Relationship Between Amine Properties and Amino Groups
- 2 Amino Groups Important as Nucleophiles
- 3 The Quaternary Ammonium Cation Acts as a Leaving Group
- 4 Learn the Properties of Amines and Thiols
Relationship Between Amine Properties and Amino Groups
First, what is an amine? An amine is ammonia (NH3) where the hydrogen atom is replaced by an alkyl chain. Understand that if the alkyl chain has a nitrogen atom attached to it, it is an amine.
Generally speaking, -NH2 is called an amino group. However, -NH2 is not the only amine. When more than one alkyl chain is attached to a nitrogen atom, it is also called an amine.
Also, since amines are generally basic, they produce a cation by pulling out the H+ (proton). These amines are basic when they are converted to ammonium cations.
Primary amines (amino groups), secondary amines (methylamino groups), and tertiary amines (dimethylamino groups) have almost the same basicity.
The exception to this is the amino group (such as aniline) attached to the benzene ring, which has significantly lower basicity than the amino group attached to the alkyl group. The reason for this is that the unshared electron pairs (lone pairs) of the amino group cause resonance.
For example, in aniline, the following resonance structures can be written.
Because the lone pair on the amino group moves to the benzene ring, the aniline is less likely to receive a proton. As a result, the amino group attached to the benzene ring becomes less basic.
Amino Groups Important as Nucleophiles
So what kind of synthetic reactions are amino groups used in? The most common organic synthesis of amines utilizes amino groups in nucleophilic substitution reactions.
Most compounds that are basic are nucleophilic. By attacking other molecules, they are able to create new bonds. This means that compounds with amino groups are often used as nucleophiles.
In addition to primary, secondary and tertiary amines, quaternary ammonium salts (quaternary ammonium cations) can also be synthesized by using amino groups as nucleophiles.
For example, the following quaternary ammonium salts can be synthesized using tertiary amines.
Quaternary ammonium salts are used in many situations such as disinfectants and anion exchange resins. They are one of the most widely used substituents in our lives.
Thiols (Mercapto Groups) and Sulfides Are Strong Nucleophiles
Thiols are also known as nucleophiles. Thiols have a mercapto group (-SH). The presence of mercapto groups is known to give off a foul odor.
Thiols show similar properties to alcohol (-OH), but are known to be very strong nucleophiles. It is also more acidic than alcohol. Therefore, unlike amines, thiols are weakly acidic in aqueous solutions. However, it is used as an excellent nucleophile.
Nucleophilic substitution reactions with thiols can create sulfide bonds (-S-). It is as follows.
When the molecule is connected to an oxygen atom, the functional group is called ether. On the other hand, when a carbon chain is connected to a sulfur atom, it is called a sulfide.
-Sulfides Have High Nucleophilic Properties and Create Ions
In addition, because thiols (mercapto groups) are highly nucleophilic, sulfides are also highly nucleophilic. Therefore, they can form ions by undergoing nucleophilic substitution reactions.
We explained that amines can make quaternary ammonium cations. In the same way, a sulfide can make anions by nucleophilic attack. For example, the following.
The ether does not nucleophilic attack. On the other hand, sulfur atoms are highly nucleophilic and sulfide nucleophiles attack them, producing cations.
The Quaternary Ammonium Cation Acts as a Leaving Group
In general, their properties as nucleophiles, which we have discussed, are most important. However, in the case of amines, they can also be used as a leaving group. Quaternary ammonium cations, in particular, can be used as a leaving group.
Ordinary amines cannot be used as a leaving group. It is important to understand that the following amines will not cause an elimination reaction.
- Primary amines (amino groups)
- Secondary amines (methylamino groups)
- Tertiary amines (dimethylamino groups)
When a base is added, the hydrogen (proton) is withdrawn rather than undergoing an elimination reaction. This is why these substituents do not become leaving groups.
Amines are commonly known as basic substances. So even if you add a stronger base, the only thing that will happen is that the protons bound to the conjugated acid (in its positively charged state) will disappear. Also, amines have an extremely low ability to leave-out, so they are not leaving groups.
On the other hand, what about quaternary ammonium compounds? With quaternary ammonium cations, they are activated because they are positively charged. Furthermore, quaternary ammonium cations have no protons bound to them, so that when a strong base is added, the H+ is not pulled out.
Therefore, when quaternary ammonium salts are present in the molecule, the addition of a strong base causes elimination reactions. It is as follows.
Amines do not normally become leaving groups, but quaternary ammonium cations are exceptionally good leaving groups. When an amine is present in a molecule, it can cause elimination reactions after synthesizing a quaternary ammonium cation, to produce a compound with a double bond.
Quaternary Ammonium Cations Cause the Elimination Reactions by Hofmann elimination
Among the elimination reactions (E1 and E2 reactions), the Hofmann elimination occurs in the elimination reaction using quaternary ammonium cations. When a base pulls out a proton, there are two types of reaction mechanisms that can be used in the elimination reaction.
In general, the elimination reaction follows the Saytzeff rule. The base attacks the hydrogen atoms attached to the substituent-rich carbon atoms to produce polysubstituted alkenes.
However, in the case of molecules with quaternary ammonium cations, this does not follow the Saytzeff rule. When a double bond is formed in the elimination reaction, the proton attached to the carbon atom with fewer substituents is withdrawn. This is Hofmann elimination, and the reaction mechanism is as follows.
The reason it is a Hofmann elimination rather than the Saytzeff rule is that the quaternary ammonium salts are extremely bulky. Due to the steric hindrance, the base cannot get inside the molecule. Therefore, the hydrogen atoms on the outside of the molecule are pulled out, causing the elimination reaction.
Sulfide Becomes a Leaving Group in the SN2 Reaction
In the same way that amines act as a leaving group, sulfides can be a leaving group. As mentioned earlier, sulfides are highly nucleophilic and, like quaternary ammonium salts, can create ions by the nucleophilic attack.
If it is positively charged as an ion, it can become a leaving group. Since the functional group is activated, the addition of a base (nucleophilic agent) allows the synthetic reaction to proceed.
For sulfide, it is used as a leaving group in the SN2 reaction. The nucleophilic agent attacks it, causing the following reactions.
Unlike quaternary ammonium salts, sulfides are not suitable for elimination reactions (formation of alkenes). Therefore, they should be used when you want to synthesize by a nucleophilic substitution reaction instead of making a double bond.
Learn the Properties of Amines and Thiols
Amines and thiols are known to be functional groups that undergo nucleophilic substitution reactions and elimination reactions. In general, these functional groups are used as nucleophiles to initiate SN1 and SN2 reactions.
However, amines can make quaternary ammonium compounds. For sulfides, positively charged ions can also be synthesized. If they are activated by being positively charged, they can act as a leaving group.
For amines, double-bonded alkenes can be synthesized by Hofmann elimination. For sulfides, a nucleophilic substitution reaction can occur by the SN2 reaction.
Amines and thiols have these properties. They are not difficult properties, so make sure you understand how synthetic reactions occur.