Nomenclature of Heterocyclic Compounds M.Sc. II S.M. Joshi College Prof. Pawar A.A.

What are heterocyclic compounds? These are considered to be derived from the carbocyclic compounds by the replacement of one or more carbon atoms by the heteroatom(s) such as N, O, S etc.

Introduction In earlier days of organic chemistry, names were given to compounds as a means of identifying them, usually before their structure were known. A systematic nomenclature is necessary so that the structure of the compound can be deduced from its name. Several different systems of nomenclature have been devised for heterocyclic compounds. The most systematic nomenclature so far devised is “Replacement Nomenclature” But, normally, particularly for aromatic heterocycles, a hybrid of trivial and Hantzch-Widman systems is used.

Trivial names of Common ring systems These were given before their structural identification. Trivial names of the heterocycles were given on the basis of their characteristic properties (or) on the sources from which they are obtained. Eg: Picoline, Furfurol, Pyrrole. Therefore the trivial names hardly provide any structural information. There are about 49 ‘recognized’ trivial names. Eg: Pyrole, Pyrazole, Pyran, Purine, Pyrimidine, Quinoline, Isoquinoline, Xanthene, Perimidine.

Why trivial names? The surviving trivial names are important because they are used as basis for constructing- more systematic, names for derivatives (or) for polycyclic systems.

Systematic (Hantzsch-Widman) nomenclature system. This is the most widely used systematic method and is used for naming three- to ten-membered heterocyclic systems with various degrees of unsaturation. This nomenclature specifies the ring size, nature, type and position(s) of the heteroatom(s). Trivial names eg: pyrrole, imidazole, pyridine must be preferred over the sytematic names. For partially saturated heteromonocycles, the prefixes ‘dihydro’, ‘tetrahydro’ etc should be used.

Combination of prefix(es) with stem The heteromonocyclic system is named by combining one or more ‘a’ prefixes for the heteroatom(s) with a stem indicating the size of the ring. If the stem begins with vowel, the terminal letter ‘a’ of the ‘a’ prefix is dropped. Prefixes: The prefixes indicate the heteroatoms present in the heterocyclic systems. The prefixes for different heteroatoms are presented in the table in the order of preference. Stems: The stems are used to indicate the size of the ring and the saturation/unsaturation in the heteromonocyclic systems.

When two or more heteroatoms of the same type are present, then the prefixes, di-, tri-, etc. are used and placed before the prefix used for the heteroatom. When two or more different heteroatoms are present in the same ring, the prefixes of heteroatoms are combined in the order of preference.

Numbering With two or more identical heteroatoms: The ring is numbered in such a way that the heteroatoms are assigned the lowest possible set of number of locants. With two or more different heteroatoms: The numbering starts from the heteroatom with the highest preference as in the table (O>S>N…). The remaining heteroatoms are given lowest number locants.

Presence of saturated atom (indicated hydrogen) When heterocyclic ring with maximum number of noncumulative double bonds contains a saturated atom, its position is given the lowest possible locant and is numerically indicated by an italic capital H before the name of heterocyclic ring system. However, the heterocyclic system in which a carbon atom of the ring is involved in the carbonyl group, the indicated hydrogen is normally cited as an italic capital H in parenthesis after the locant of the additional structural features.

Naming of fused ring systems The fused heterocyclic system is considered to be constructed by the combination of two or more cyclic structural units. The cyclic structural units contain maximum number of non-cumulative double bonds and are fused in such a way that each structural unit has one bond common with other.

Rules for naming fused heterocyclic rings: The fused heterocyclic system is dissected into its components in which one is base component and the other(s) is attached component(s). The components are given their recognized trivial names (if possible) else, systematic name is used. The base component should always be a heterocyclic system. If there is a choice, it is determined by order of preference.

Selection of base component: Nitrogen containing component: a nitrogen containing component is selected as base component. If nitrogen is absent, then ring with other heteroatom(s) is selected as base component (order of preference as in the table) Component with greatest number of rings is selected and named with recognized trivial name if possible.

The attached component is added as a prefix to the name of the base component. The terminal ‘e’ is replaced by ‘o’. The bonds of the base component are alphabetalized with consecutive italic letters starting with ‘a’ for 1,2-bond….. The atoms are other component are numbered in the normal way 1,2,3….in the principle of lowest possible numbering.

The atoms common to both rings (side of fusion) are indicated by appropriate letters and numbers and are enclosed in a square bracket and placed immediately after the prefix of the attached component. The numbers (positions of attachment) of the second component are placed in the sequence in which they are attached to the base component. If a position of fusion is occupied by a heteroatom, both the components (ring systems) are considered to posses that heteroatom.

Numbering of fused systems: Fused heterocyclic system is numbered independently of combining components. The numbering is started from the atom adjacent to the bridgehead position with the lowest possible locant(s) to the heteroatom(s). If there is choice, priority is given according to the table. Carbon atom common to two rings is given the lowest possible position, both not numbered. However, the common heteroatom is numbered. The position of a saturated atom is indicated by an italic hydrogen and is given the lowest possible number locant.

Nomenclature of Benzofused systems: If a benzene is fused to the heterocyclic ring, the compound is named by placing number(s) indicating position(s) of the heteroatom(s) before the prefix benzo- (from benzene) followed by the name of the heterocyclic component. However, the heterocyclic system in which two benzene rings are orthofused to a six-membered 1,4-diheteromonocycle containing the same heteroatoms are named by adding the replacement prefix for the heteroatom to the term ‘-anthrene’ replacing ‘a’.

If two benzene rings are ortho-fused to a six membered 1,4-dihetero monocyclic ring containing different atoms, then it is named by adding the prefix ‘pheno-’ to the H-W name of heterocycle.

Replacement Nomenclature System This system is based on the fact that the heterocylic compounds are derivatives of carbocyclic compounds. Therefore the rules of nomenclature are similar to those applied for the carbocyclic compounds. It is used for the heterocycles containing unususal heteroatom(s), spiro- and bridged heterocyclic systems.

Monocyclic Heterocycles Fused Heterocycles Spiro Heterocycles Bridged Heterocycles Heterocyclic ring assemblies

Monocyclic Heterocycles: The ring obtained from the heterocyclic compound by replacing heteroatom(s) by CH2, CH or C according to the valence of heteroatom(s) is named by IUPAC rules. The type of heteroatom is indicated by the prefix (according to the table). Since all the prefixes end with the letter ‘a’ the replacement nomenclature is also known as ‘a’ nomenclature. The position and prefix for each heteroatom are placed before the name of the corresponding carbocyclic sytem. The replacement names derived from benzene are retained only if three double bonds are present, otherwise the names with –ene, - diene, etc as necessary are used.

The sequence and numbering of the heteroatoms follow the rules as in systematic nomenclature. However, the preferential order is: 1st preference : heteroatom appearing highest in table. 2nd : Other heteroatoms according to table. 3rd : Multiple bonds. 4th : substituents, if there is a choice, alphabetical order is followed.

Fused Heterocycles The position(s) and prefix(es) for the heteroatom(s) are written in front of the name of the corresponding carbocyclic ring. The numbering of the corresponding carbocyclic ring is retained irrespective of the position(s) of the heteroatom(s). However, the lowest possible number locants are assigned to the heteroatoms in the complete fused heterocyclic system. If there is a choice, Table 1 is followed. The heteroatom at the ring junction is assigned individually number in fusion nomenclature, where as in the replacement nomenclature system the heteroatom at the ring junction is given the same locant as an adjacent nonconjunction carbon atom but with suffix ‘a’ or ‘b’, etc.

6. The heterocyclic ring assemblies constructing of three or more identical heterocyclic systems are named as: The appropriate numerical prefix, ter-, quater-, etc., is placed before the name of the corresponding heterocyclic system. Unprimed numbers are assigned to the one of the terminal heterocyclic systems and others are assigned single, double, triple etc. primed numbers. The points of attachment are assigned as the lowest possible numbers.

Thank You !