Heterocyclic compounds are divided into two categories: aliphatic heterocycles and aromatic heterocycles. Heterocyclic rings in the molecular skeleton that cannot reflect aromatic properties are called aliphatic heterocyclic compounds; on the contrary, heterocyclic rings with properties similar to benzene are called aromatic heterocyclic compounds.

== Aliphatic heterocycle== 

The chemical properties of aliphatic heterocycles are similar to those of the corresponding chain compounds. Small-cycle aliphatic heterocycles are more active than corresponding chain compounds due to their greater tension and easy ring opening, while macrocyclic systems are relatively inert.

Oxygen heterocycle 

Compared with chain ethers, epoxy compounds generally have stronger nucleophilicity. This is because the alkyl group on the oxygen atom makes the bond angle smaller due to the role of the ring, which reduces the air resistance of the lone pair of electrons of the oxygen atom, making it easier for the lone pair of electrons to react with the electricity-deficient system. Therefore, the basic property of epoxy compounds is the ring-opening reaction, whose driving force lies in the release of ring tension. The interaction of lone pairs of electrons with Lewis acids can be used to make ethers more reactive. BF3 is often used to activate cyclic ethers facing nucleophilic attack.

Nitrogen heterocycle 

The basic reactions of nitrogen heterocycles are the same as those of chain amines. There are two main types of reactions: nucleophilic addition and nucleophilic substitution. The nucleophilicity of nitrogen atoms in cyclic amines is stronger than that of chain amines. The reason for this is the same as that of oxa. Same as ring. As the substituent at the α position of the nitrogen atom of the oxygen heterocyclic ring increases, the nucleophilicity of the nitrogen atom will gradually weaken. However, the cyclic structure does not have a significant effect on the basicity of the amine because the proton is small enough that its binding to the amine is not easily affected by steric hindrance.

Sulfur heterocycle 

Compared with oxygen and nitrogen atoms, the hydrogen atom on the α-position carbon atom connected to the sulfur atom is more acidic because the sulfur atom can stabilize the carbanion connected to it. Compared with the same oxygen heterocyclic ring, whether it is a five-membered or six-membered sulfur heterocyclic compound, it is easier to form negative ions and undergo nucleophilic reactions under the action of a base.

== Aromatic heterocycle ==

Electronic structure 

For five-membered heterocycles such as furan, thiophene, and pyrrole, the lone pair of electrons of the heteroatom participates in the conjugation of the entire ring system. The electron-donating conjugation effect is greater than the electron-withdrawing induction effect, and the heterocycle is electron-rich. For the six-membered ring pyridine, the lone pair of electrons on the nitrogen atom does not participate in conjugation, and the heterocyclic ring is electron deficient. The above four heterocycles all have 6π electrons and are aromatic. When the carbon atoms are further replaced with nitrogen atoms in the above-mentioned aromatic heterocycle, these new nitrogen atoms are all pyridinic nitrogen atoms, making the entire ring system more electron-deficient than the original one. 

Alkaline

 Compared with ordinary amines, the basicity of pyrrole is very weak due to the lone pair of electrons on the nitrogen atom participating in conjugation. The electron density of pyrrole is higher at the C2 position, and protonation mainly occurs at this position. The negative ion formed by the loss of a hydrogen atom from pyrrole is more delocalized and therefore somewhat acidic than a similar saturated amine. Compared with the nitrogen atom in pyrrole, the oxygen atom of furan has two lone pairs of electrons, one of which participates in conjugation and the other pair does not participate in conjugation. Therefore, furan can be protonated quickly under suitable conditions. , usually still occurs in the C2 position. Thiophene can be protonated either at the C2 position or on the sulfur atom.

Among the 1,3 azoles, oxazole is the least basic and imidazole is the strongest. This is because the oxygen atoms in the 1,3 oxazole ring have a strong electron-withdrawing induction effect, while in imidazole, the electron-donating conjugation effect of the pyrrole nitrogen atoms is strong. The connection of two heteroatoms will cause the basicity of the pyridine nitrogen atom to decrease, so 1,2 azole compounds are less basic than the corresponding 1,3 azole compounds. Since triazole compounds have more nitrogen atoms than pyridines, they are less basic and more acidic than imidazole. Compared with pyrrole, pyridine's lone pair of electrons does not participate in conjugation, making it more basic. However, because its nitrogen atom is sp2 hybridized, while the nitrogen atom in aliphatic amine is sp3 hybridized, pyridine is slightly less basic than ordinary aliphatic amines. There are two nitrogen atoms on the azine ring. Since both nitrogen atoms have an electron-absorbing effect, the basicity of diazine is weaker than that of pyridine.

Electrophilicity & Nucleophilicity 

Aromatic electrophilic substitution reactions of aromatic heterocycles containing pyrrole heteroatoms are easier to carry out, and nucleophilic substitution reactions generally do not occur, such as pyrrole, furan, and thiophene. However, aromatic electrophilic substitution reactions of aromatic heterocycles containing pyridine heteroatoms are difficult to carry out, and electron-deficient systems make it easier for nucleophilic substitution reactions to occur, such as pyridine. For pyridine, electrophilic substitution can only occur when there is an electron-donating activating group, and the nitrogen oxide of pyridine is active in the face of both electrophiles and nucleophiles. In addition, because of its acidity, pyrrole can be hydrogenated by a base to form a pyrrole anion, which can further react with an electrophile on the nitrogen atom. For example, pyrrole reacts with Boc anhydride to cause the nitrogen atom to be protected by Boc. Five-membered heterocycles can also act as dienes in the Diels–Alder reaction.

== Benzoheterocycle ==

The two rings of five-membered heterocyclic benzo systems such as benzopyrrole (indole), benzofuran, and benzothiophene are planar structures. The entire system has 10π electrons and is aromatic. The π electron cloud density on the five-membered heterocyclic ring is higher than that on the benzene ring, so the aromatic electrophilic substitution reaction occurs preferentially on the heterocyclic ring. Indole and benzothiophene tend to occur in the 3-position, and benzofuran occurs in the 2-position. The basic chemical properties of quinoline and isoquinoline are combinations of pyridine and benzene rings. Therefore, they are basic and can undergo electrophilic and nucleophilic substitution reactions. Electrophilic substitution occurs on the benzene ring, while nucleophilic substitution occurs on pyridine. The purine ring can be regarded as a parallel ring system formed by the combination of pyrimidine and imidazole, which plays an important role in our lives. 1-Hydroxybenzotriazole (HOBt) is an important condensing agent and is widely used in the synthesis of amides.

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