Pharmaceutical Organic Chemistry PC305: Heterocycles 1

Pharmaceutical Organic Chemistry - PC305 Level Two, Part I: Heterocyclic Chemistry, Lec. 1

• Heterocyclic compounds are cyclic molecules containing at least one atom other than carbon in the ring structure.
• Common heteroatoms include nitrogen (N), oxygen (O), and sulfur (S). Other heteroatoms such as selenium (Se), phosphorus (P), silicon (Si), and boron (B) can also be incorporated.
• Heterocyclic compounds can have one or more heteroatoms, which can be similar or different.
• Heterocycles can be isolated or fused.
• Heterocycles are a significant class of organic compounds, comprising over half of all known organic compounds.
• Many drugs, vitamins, and natural products are heterocyclic.

Nomenclature of Heterocyclic Compounds

• Nomenclature is based on trivial (common) names and systematic names (IUPAC/Hantzsch-Widman).
• Trivial names often derive from the compound's properties or discovery.
• Systematic names use prefixes specifying the heteroatom type, ring size, and degree of saturation.

Heterocyclic Compounds Containing One Heteroatom

• Unsaturated heterocycles: Numbering starts at the heteroatom. Aromatic and non-aromatic types are distinguished.
• Saturated heterocycles: Naming follows similar principles using prefixes like pyrrolidine.

Heterocyclic Compounds Containing Two or More Heteroatoms

• Numbering starts with the prioritized heteroatom (O, S, then N) in a direction promoting the lowest possible numbers for substituents.

• If multiple heteroatoms of the same type are present, numbering starts from saturated one.

• If substituents are present, assign numbers to atoms bearing them and alphabetize.

Naming Heterocyclic Compounds With Saturation

• Use prefixes like dihydro, trihydro, or tetrahydro to indicate the number of saturated atoms. These prefixes precede the saturated structural name

Fused Heterocyclic Compounds

• Numbering starts at the nearest atom to the junction and prioritizes the heteroatom for the lowest numbers.
• No numbering for contact point unless it is carbon.

Coumarin-type Compounds

• Includes coumarin-2-one, chromene-4-one, and flavone.

N.B. Fused Heterocyclic compounds

• Xanthine, purine, carbazole, and acridine are examples
• The numbering differs from regular principles

Systematic Names (Monocyclic Systems)

• The heteroatom is positioned at position 1.
• Heteroatom type prefixes include oxa-, thia-, selena-, aza-, phospha-, sila-, and bora- for oxygen, sulfur, selenium, nitrogen, phosphorous, silicon, and boron, respectively.
• Prefix multiplications signal two or more of the same heteroatom (e.g., dioxa, dithia, diaza).
• Priority order (O > S > N) applies when multiple different heteroatoms are present.

Rule 2: Prefix and Suffix

• Ring size prefixes (e.g., irine, ete, ole, etc) are followed by respective suffixes indicating saturation level (e.g., saturated or unsaturated). Perhydro is applied when fully saturated.

Example: Aziridine

• 3-membered ring containing nitrogen.
• Combining prefix and suffix correctly eliminates vowels on the end.

Example: Oxadiazole

• 5-membered ring containing oxygen (O) and nitrogen(N).
• Using priority of oxygen- first, locants assigned to nitrogen.

Other Heterocyclic Nomenclature (oxirane, thi-irane, azetidine, etc) and examples listed in tables.

Rule 3 - State of Hydrogenation

• Use the suffix or prefixes (dihydro, tetrahydro, etc.) to indicate the degree of hydrogenation from the unsaturated parent or using ‘H’ symbol preceding numbers.

Rule 4 - Numbering Rules

• Start the numbering from the heteroatom and proceed around the ring to provide the lowest possible numbers for substituents.
• Oxygen (O) takes priority over sulfur (S) and sulfur (S) over nitrogen (N) for the first position.
• In cases with multiple different heteroatoms, number from the heteroatom that yields the lowest numbers overall.
• Arrange the lowest locant set according to the priority rule.

Examples of named compounds (including 3-methylfuran, 1,3-oxazole, 4-amino-1,3-diazine, etc.) and the correct naming procedures highlighted.

• Provide naming guidelines for fused polycyclic ring systems with examples (benzo[d]thiazole, benzo[b]pyridine)

This quiz covers the fundamentals of heterocyclic chemistry as part of Pharmaceutical Organic Chemistry - PC305 Level Two. Explore the structure, nomenclature, and significance of heterocyclic compounds, which play a crucial role in the pharmaceutical industry. Understand the various heteroatoms involved and their contribution to the properties of these organic molecules.