Pharmaceutical Chemistry II: Heterocyclic Chemistry

Study Notes

UPC 213 (Pharmaceutical Chemistry II)
Heterocyclic Chemistry is the main topic
Topics include Introduction, Nomenclature, Structure, Reactions, and Synthesis of aromatic heterocyclic compounds
Aliphatic heterocycles, including oxirane, tetrahydrofuran, tetrahydropyran, aziridine, azetidine, pyrrolidine, piperidine, and morpholine are examples
Aromatic heterocycles, including pyrrole, furan, thiophene, pyridine, quinoline, isoquinoline, and indole are examples

The course will study the nomenclature, structure, reactions, and synthesis of aromatic heterocyclic compounds
Also covers aliphatic heterocycles

Heterocyclic compounds contain rings with at least one atom other than carbon.
These molecules show special chemical properties due to the presence of heteroatoms ( like O, N, S, etc) in the ring
A recent Chemical Abstracts analysis from June 2007 illustrated that approximately two-thirds of organic compounds contain heterocycles.
Many pharmaceuticals depend on heterocyclic structures.

The IUPAC rules define three heterocycle nomenclature systems (Hantzsch-Widman, Common names, and Replacement)
The Hantzsch-Widman system depends on the ring size, the type of heteroatom, and the presence of unsaturation in the ring
The common names are widely recognized and used for some compounds (e.g., furan, pyrrole, and pyridine)
The Replacement nomenclature system is based on naming the carbocyclic analogue with prefixes for the heteroatoms

Heteroatoms are indicated with prefixes in the naming of heterocyclic compounds.
Ex: O, N and S have the prefixes 'Oxa', 'Aza', and 'Thia' respectively.

The Hantzsch-Widman nomenclature adds suffixes to the prefix based on ring size and saturation
Ring sizes 3-10 are commonly used.
Table I and Table II in the notes define prefixes and suffixes, respectively, for ring sizes and saturation levels
The presence of unsaturation is also determined by the number of non-cumulated double bonds.

When heterocycles contain less than the maximum possible number of double bonds, prefixes like "dihydro"or "tetrahydro" are added
The system prioritizes saturated atoms over unsaturated ones while numbering within the ring.

The classification of aromatic heterocycles is based on their π-excess or π-deficiency, which are dependent on resonance stabilization.

Heterocycles with π-deficiency (e.g., pyridine) react slower with electrophiles than benzene
Nitration of pyridine, for example, proceeds significantly less quickly than nitration of benzene

Heterocycles with π-excess (e.g., furan) react faster with electrophiles than benzene
Halogenation and acylation of furans proceed at the α-position
Metalation with n-butyllithium occurs primarily at position 2 on furan

Nucleophilic reactions on heterocycles, such as pyrrole reacting with sodium hydride, often result in salt-like compounds

Various reactions, such as addition reactions and ring-opening reactions, are common and important in the chemistry of heterocyclic compounds
Vilsmeier-Haack reaction

Many chemical structures are given as examples in the document. They illustrate specific heterocycles and their nomenclature characteristics
These examples provide further understanding of the various types of heterocyclic structures

This is a drug used for the treatment of anxiety disorders, tremors, delirium, seizures, or hallucinations caused by alcohol withdrawal
It is used to relieve muscle spasms associated with certain neurological diseases.
Diazepam is often synthesized through multi-step reactions