2) Heterocyclic with one heteroatom. Pyrrole, pyridine. Aromatic. Acid-baseproperties. Electronic structure of pyrrolic and pyridinic nitrogen atom.

Five membered heterocyclic with one heteroatom:

PyrroleTiophene Furan Pyridine

For example, pyridine:

However, unlike benzene and its derivatives, pyridine is more prone to nucleophilic substitution and metalation of the ring by strong organometallic bases. The reactivity of pyridine can be distinguished for three chemical groups. With electrophiles, electrophilic substitution takes place where pyridine expresses aromatic properties. With nucleophiles, pyridine reacts via its 2nd and 4th carbon atoms and thus behaves similar to imines and carbonyls.

Pyridines –Nucleophilic Reactions

Regiochemical Outcome of Nucleophilic Addition to Pyridines:

Pyridines – Directed Metallation

The reaction with many Lewis acids results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines. The ability of pyridine and its derivatives to oxidize, forming amine oxides (N-oxides), is also a feature of tertiary amines.

The nitrogen center of pyridine features a basic lone pair of electrons. Because this lone pair is not part of the aromatic ring, pyridine is a base, having chemical properties similar to those of tertiary amines.Pyridine can act as Lewis base, donating its pair of electron to a Lewis acid as in the sulfur trioxide pyridine complex. Pyridine itself is a relatively weak ligand in forming complexes with transition metal ions.

In pyridine the atom of nitrogen is in a condition sp² – hybridization and shows electron acceptor character. Atom of nitrogen more electronegative (3,0) than atoms of carbon in sp² – hybridization (2,80).

The free not divided properties pyridine as bases.

Atom of nitrogen with such by electronic structure are accepted to name pyridinic. A result structure are pyridinic atom of nitrogen decreases electron density on atom of carbon an aromatic ring. Nitrogen of pyridine experic electrons deficit.

The derivatives of parrot enter in the composition of B₁₂ vitamin.

The derivatives of furan are furfural is used for obtaining of medicines furacyline and furasolidine at treatment of inflammation processes.

furfurol furasyline furasolidine

Thiophenecontains in coal pitch. Its derivate biotin contain in H vitamins. Absence of H vitamin disturbs protein metabolism in an organism.

Biotin

3) Heterocyclicwithtwoheteroatoms. Pyrazole, imidazole, pyrimidine.Their derivatives.

Five membered heterecyclic with two heteroatoms:

Five membered heterecyclic with two heteroatoms from which one atom of nitrogen and another can be atom of nitrogen, sulfur and oxygen.

pyrazole imidazole tiazoloxazole

Pyrimidine

The derivative of imidazole is histidine:

Decarboxylation reaction of histidine in tissues is forms biogenic amine – histamine:

Histamine: 1. Decreases secretion of gastric juice.

2. Causes local expansion of vessels.

3. Decreases blood pressure.

Tiozol is included into structure of vitamin B₁₂ penicillin sulfanilamide preparations.

Penicillin

Imidazoles and pyrazoles– Reactivity :

Electrophilic substitution: via addition-elimination :

reactivity: reactive towards many electrophiles (E+); >benzene but <pyrrole, furan &thiophene

regioselectivity: substitution at electron rich carbons predominate (cf. electronic distribution):

imidazole: C4 >C5 (for NR systems; if NH then C4 and C5 are identical)

pyrazole: C4 – less reactive than imidazole

Metallation: (imidazole NH pKa = 14.5; pyrazole NH pKa = 14.2)

 deprotonation by strong bases more facile than for pyrrole (pKa = 17.5) or indole (pKa = 16.2):