Heterocyclic compounds Nomenclature of Heterocyclic compounds

HETEROCYCLIC COMPOUNDS Cyclic compounds with at least two different atoms in the ring are known as heterocyclic compounds. The ring itself is called a heterocycle A hetero atom is an atom other than carbon. The name comes from the Greek word heteros, which means "different." The N-atom is the most common heteroatom. Next in the importance are O- and S-atoms. Heterocycles with Se-, Te-, P-, As-, Sb-, Bi-, Si-, Ge-, Sn-, Pb- or B-atoms are less common.

It has been found that the introduction of hetero-atom in carbocyclic molecules makes predictable changes in their physical and chemical characteristics. These changes are not only in the behavior of the parent ring but also in the chemical behavior of the functional groups attached to these rings

NOMENCLATURE OF HETEROCYCLIC COMPOUNDS There are several methods to nominate heterocycles which can be summarized as follow: Trivial names These names are given to heterocycles and usually arising from the origin of compounds or of their utility and they are approved by the IUPAC

Five membered rings containing one heteroatom

Five membered rings containing two heteroatoms

Six membered rings

Hantzsch-widman system The basis for this system were introduced independently by A. Hantzsch and O. Widman. This system was suggested at the beginning for six and five membered rings and then was extended to include rings from 3 to 10 atoms. The names of the rings is derived by combining a prefix and a suffix ( i.e Name = prefix + suffix ) According to this system a prefix is used to indicate the nature of heteroatom in the ring (O, N, S, P,……) a suffix is used to indicate the size and the degree of saturation in the ring.

Prefix: is used to indicate the nature of heteroatom in the ring (O, N, S, P,……) When different heteroatom is present the highest priority will be as follow: Prefix Valence Elements oxa 2 5) Oxygen (O) thia 6) Sulphur (S) aza 3 9) Nitrogen (N)

O > S > N For a ring has O + N ► Oxaza The Latin numbers (di, tri, tetra,….) are used to indicate the number of heteroatoms. Ex: Tetra + aza ► tetraza When different heteroatom is present the highst periority will be as follow: O > S > N For a ring has O + N ► Oxaza For a ring has S + N ► thiaza For a ring has O + S ► oxathia

Suffix is used to indicate the size and the degree of saturation in the ring Suffix = Stem + end Stem Ring size ir 3 et 4 ol 5 in 6* ep 7 The end refers to the degree of unsaturation in the ring ( as shown in the next table)

2: System for Hantzsch-Widman names Rings containing no Nitrogen Rings containing Nitrogen Ring size Saturated Unsaturated Irane Irene iridine irine 3 etane ete etidine 4 olane ole olidine 5 ane*** ine ane** 6* epane epine **** 7 ocane ocine 8 onane onine onin 9 ecane ecine ecin 10

Irane Irene Iridine Irine etane Ete etidine ete Rings containing no Nitrogen Unsaturated Saturated Rings containing Nitrogen Ring size Irane Irene Iridine Irine 3 oxirane thiirane Oxirene thiirene Aziridine azirine etane Ete etidine ete 4 Thietane oxitane Thiete oxete Azetidine Azete

Olane Ole Olidine 5 Oxolane thiolane oxole thiole ane*** ine ane** 6* Oxane thiane Oxine thiine

The rings that have one heteroatom, the rings are numbered so that the heteroatom is given number 1. When different heteroatom is present the highest priority will be O > S > N and move in the direction that gives the other heteroatoms the nearest possible numbers.

For partially saturated 5-membered rings containing Nitrogen For partially saturated rings we must designate the location of the nearest unsaturated atom by Δn (where n = the number of the first unsaturated atom).

For full unsaturated rings which contain extra hydrogens, the positions of extra hydrogens are indicated as nH in the prefix

When a heterocycle contains two similar atoms, the one carrying the heavier substituent is numbered first. When a heterocycle contains two or more N atoms, we begin numbering from SP3 nitrogen without deviation from the priority

(iii) Replacement Nomenclature Heterocyclic systems are named by considering them to be derived from cyclic hydrocarbons by replacing a carbon corner by heteroatom. The heteroatoms are indicated by the same prefixes used in the Hantzsch-Widman nomenclature. When more than one heteroatom is present citation numbers are used (O>S>N).

(iv) Naming substituted monocyclic compounds In case of heterocycles with one heteroatom the hetero atom is given No. 1. Numbers are then given in the way that gives substituents least possible numbers. (When more than one heteroatom is present the heteroatom of highest priority is numbered 1. Numbering is then made in the way that gives other heteroatoms least possible numbers. This means least difference between the first two atoms and not least algebraic sum of numbers. According to IUPAC rules the organic compounds are arranged in order of decreasing priority as follow:

a. Cation and anions b. Acids: Carboxylic, peroxycarboxylic, thiocarboxylic, sulfonic, sulfinic,… Etc. c.Derivatives of acids: anhydrides, esters, acyl halides, amides, hydrazides, imides, amidines, …… etc. d. Nitriles: cyanides, isocyanides. e. Aldehydes, thioaldehydes and their derivatives f.Ketones, thioketones and their derivatives. g. Alcohols, phenols, thioles, and their esters derivatives with inorganic acids. h. hydroperoxides. i. Amines, imines and hydrazines. j. Ethers, thioethers. k. Peroxides. All other functional groups, which are included in one of these classes, are then written as prefixes in form of the name in alphabetic order.

B) Polycycles (A) Trivial names Trivial names approved to be utilized are given below. These were drawn from the IUPAC (Blue Book).

Fusion names When a heterocyclic ring is fused to a carbocyclic ring, the hetero ring is chosen as the parent or base component. Then the systematic name is formulated from the prefix benzo- and the trivial name of the heterocyclic component as follows: The bonds between the ring atoms are denoted according to the successive numbers of the ring atoms by the letters a, b, c, etc. The letter must be as early as possible and hence benzo[d]thiophene is incorrect.

•Polycyclic systems with two or more heterocycles The base component is chosen as that in the Hantzsch-Widman nomenclature except that of nitrogen is given the highest priority. Prefixes are formed by changing the terminal (e) of the trivial or the Hantzsch-Widman names of the components into (o) Chose of the base component. i- Is there only one component which contains nitrogen? No Yes: choose this as base component

ii- Is nitrogen absent from all the rings? NO Yes: choose the ring containing a heteroatom Which occurs highest?

iii- Are there more than two rings presents? No Yes: choose the component containing the greater number of rings

iv- Are the two rings of different size? No Yes: choose the larger one

V- Do the rings contain different numbers oh heteroatoms? No Yes: chose the one with the greater number

Vi- Are there differences between the numbers of each kind of heteroatom in the two rings? No Yes: choose the ring with the greater number of atoms listed first

Vii- In case of the two rings are of the same size and contains the same heteroatoms, how to select the base component? Rule is to select the base ring to be the one in which heteroatoms has less separation between the heteroatoms. Thus:

Viii- The ring containing the greatest Varity of heteroatom arranged according to their order priority

How to Choose of the base component (Summary) 1- When a heterocyclic ring is fused to a carbocyclic ring (choose the hetero ring as the parent or base component 2- One ring only contains N (choose the ring containing N) 3- No, Nitrogen ( choose according to the priority O ˃ S )

4- One consists of two or more rings (Choose one with the greater number of rings) 5- Two rings of different size (choose the larger) 6- Choose the one with more heteroatoms

7- Same number of heteroatoms (choose O > S > N) 8- Same type and number of heteroatoms, and same ring size (choose lower separation between atoms) 9- Choose the ring containing the greatest Varity of heteroatom.

Bridge Specification Acenaphthylene Acenaphtho Naphthalene Naphtho Adding prefixes to the name of a base component The base component is chosen as before Prefixes are formed by changing the terminal e of the trivial name into <O> (e.g. pyrazole is converted to pyrazolo) Some prefixes are formed as in the following table Acenaphthylene Acenaphtho Naphthalene Naphtho Anthracene Anthra Perylene Perylo Benzene Benzo Pyridine Pyrido Furan Furo Pyrimidine Pyrimido Imidazole Imidazo Quinoline Quino Isoquinoline Isoquino Thiophene Thieno

Name = prefix[number, letter]base The position of fusion between the prefix and the base is indicated by inserting (in square brackets) number for the prefix and italic letter for the base component. Name = prefix[number, letter]base

If a position of fusion is occupied by a heteroatom, the names of the two component rings are chosen in a way that both contain this heteroatom.

Symmetric and Asymmetric Heterocycle

Other examples for Bridge Specification

a)- Give low numbers to the heteroatoms

b) Give low number to heteroatoms in the order O> S> N

c) Give hydrogen atom the lowest numbers

A carbon atom common to two or more rings is given a lower case letter after the numeral of the atom immediately proceeding. A heteroatom common to two or more rings receives an individual locant.