Organic Chemistry By Dr. Mehnaz Kamal Assistant Professor, Pharmaceutical Chemistry Prince Sattam Bin Abdulaziz University

1-Defintion of Isomers. 2-How they could be Classified? 3- Naming of different isomers. 4-Some of their physical and chemical properties.

Stereochemistry It is that part of the science which deals with structure in three dimensions Study of the arrangement of atoms in space (three-dimensional shape “3D”) or molecules and how this affects their chemical and physical properties Z Y 2D vs 3D Y X X

Lecture Contents Isomerism Structural Isomerism Stereoisomerism 1. Chain isomerism 2. Position isomerism 3. Functional isomerism Stereoisomerism Optical active isomers. Geometrical isomers. Conformational isomers.

Isomerism Isomerism A phenomenon resulting from moleculs having the same molecular formula but different arrangement In space. When two or more organic compounds have the same molecular formula but differ in their physical or chemical properties they are called Isomers and the phenomenon called isomerism.

Type of Isomerism….cont 1-Structural isomerism /Constitutional isomers. They are different molecules. They have the same formula, but they are connected together differently You cannot convert one to the other without taking it apart and rebuilding it ( i.e., without breaking and remaking bonds). All the physical properties of constitutional isomers are different different melting points and boiling points, different solubility and densities, etc. Thy include: A) Chain Isomerism (Or Skeletal Isomerism) B) Positional Isomerism. C) Functional Isomerism

Type of Isomerism….cont 1-Structural isomerism /Constitutional isomers..cont Constitutional isomers include: A. Chain isomers C5H12 B. Position isomers C3H7Br C. Functional isomers C2H6O

Type of Isomerism….cont 1-Structural isomerism /Constitutional isomers..cont

Type of Isomerism….cont 1-Structural isomerism /Constitutional isomers..cont Examples Write all of the constitutional isomers having the molecular formula C3H6O2 C4H10 CH3CH2CH2CH3 C3H8O CH3CH2CH2CH2CH3 (CH3)4C C6H6O2

Type of Isomerism….cont 2-Stereoisomerism Greek, Stereos=occupying space). The stereoisomers have the same structural formulas but differ in their arrangement of atoms in space but have the same bonding pattern. In other words, stereoisomerism is exhibited by such compounds which have identical molecular structure but different configurations. Stereoisomers are the same constitutional isomer, but have a difference in the way they are arranged in three-dimensional space at one or more of their atoms.

Type of Isomerism There are two main classes of isomers: Isomers Structural isomerism (Constitutional isomers) Position of function groups Skeleton or chain of carbon Functional group Stereoisomerism Optical isomers (Diastereomers (Enantiomers Geometrical Cis & trans There are two main classes of isomers: Configurational Conformational

Type of Isomerism….cont 2-Stereoisomerism Conformational isomers The atoms at either end of a single bond can rotate relative to one another. compare Free rotation of carbon- carbon single bonds 

Type of Isomerism….cont. 2-Stereoisomerism…cont. Configuration Isomers Differ only in arrangement of their atoms in space (3D geometry) I-Diastereomers (Geometric isomerism) Compounds which have the same molecular formula but differ in arrangement of atoms or groups in space different configuration Diastereoisomers have different physical and chemical properties, as solubility and boiling points thus: - if liquids……. Fractional distillation - if solids …….. Fractional crystallization

Type of Isomerism….cont. 2-Stereoisomerism…cont. I-Diastereomers (Geometric isomerism) An isomerism resulting from rigidity in molecules and occurs only in two class of compounds alkenes and cyclic compounds Rigidity ≠ Flexibility σ – bond free rotation ( flexibility )  - bond C = C no free rotation ( rigidity ) σ – bond restricted rotation ( semi-flexible)

Type of Isomerism….cont. 2-Stereoisomerism…cont. I-Geometric isomerism…cont Restricted rotation of carbon-carbon double bonds 

Type of Isomerism….cont. 2-Stereoisomerism…cont. I-Geometric isomerism…cont i- Geometric isomerism in alkenes The requirement for this type of isomerism is that each carbon atom involved in the double bond has different substitution D ≠ E A ≠ B On same side cis On different sides trans

Geometrical Isomerism cis/trans isomers If a ≠ c and b ≠ d then there are 2 diastereomeric forms: cis, Latin on this side trans, Latin across cis-1,2-Dichloroethene trans-1,2-Dichloroethene

COMPARE cis / trans ISOMERS IN RING COMPOUNDS In alkenes cis / trans isomers used to be called geometric isomers, a term generally not used for cyclic systems (rings). You may find the term geometric isomers used in older books or papers.

Which of the following alkenes can exist as cis-trans isomers? 1,1,2-trichloroethene 1,1-dichloroethene cis-trans isomerism is not possible if one carbon atom of the double bond bears 2 identical groups. Which of the following alkenes can exist as cis-trans isomers? Draw their structures?

Summary Cis-trans isomers differ from one another in the way the atoms/ groups are positioned in space Cis –same, trans –across They have different physical and chemical properties They interact differently with enzymes/ receptor sites They cannot be interconverted by rotation around C-C bonds Rotation is restricted by double bond or cyclic structure

Type of Isomerism….cont. 2-Stereoisomerism…cont. I-Geometric isomerism…cont Diastereoisomers are designed cis or trans according to the priority order or sequence rule [ atomic number] 53I > 35Br > 17Cl > 16S > 9F > 8O > 7N > 6C > 1H

Type of Isomerism….cont. 2-Stereoisomerism…cont. I-Geometric isomerism…cont Sequence Rule or Priority Order 1- If the two atoms in question are different, the atom of highest atomic number receives the highest priority I > Br > Cl > …… trans cis cis

2-Stereoisomerism…cont. I-Geometric isomerism…cont Sequence Rule or Priority Order 2- If the two atoms are identical, the atomic numbers of next atoms are used, until the priority is determined at the first point of difference along the chain cis trans trans

2-Stereoisomerism…cont. I-Geometric isomerism…cont Sequence Rules or Priority Order 3- Atoms attached to double or triple bonds are given single-bond equivalencies, each doubly bonded atom is duplicated (or triplicated for triple bonds) > > > > > > RCH2OH RCN -CH=CR2

E / Z SYSTEM OF NOMENCLATURE

Diastereoisomers can also be designated by: 1- E instead of trans 2- Z instead of cis

1 1 cis or trans? 35 2 17 ---------------- 53 Cahn- Ingold-Prelog: E and Z Based on Priority: 35 2 17 1 ---------------- 53 Cahn- Ingold-Prelog: 1. Atomic Number 2. Atomic number of the next atom 1 9 2 (E)-1-bromo-2-chloro- 2-fluoro-1-iodoethene Higher priority at the opposite side of pi bond (E) Higher priority at the same side of pi bond (Z)

In this system the two groups attached to each carbon are assigned a priority ( 1 or 2 ). If priority 1 groups are both on same side of double bond: Z isomer = zusammen = together (in German) same side opposite sides Z E If priority 1 groups on opposite sides of double bond: E isomer = entgegen = opposite (in German)

ASSIGNING PRIORITIES 1. Look at the atoms attached to each carbon of the double bond. 2. The atom of higher atomic number has higher (1) priority. 1 1 example F > H I > Br 2 2 Since the 1’s are on the same side, this compound is Z (Z)-1-bromo-2-fluoro-1-iodoethene notice use of parentheses

On carbon c, the chloroethyl substituent is of higher priority than methyl On carbon d, the bromine substituent is of higher priority than chlorine IUPAC name is (Z)-1-bromo-1,4-dichloro-2-methylbut-1-ene

E Z

E Z

cis/trans Geometry of Alicyclic Compounds The cyclic systems use the traditional cis/trans nomenclature. trans-1,2-dimethylcyclobutane cis-1,2-dimethylcyclobutane trans-1,2-dimethylcyclohexane cis-1,2-dimethylcyclohexane

Sequence Rules or Priority Order Examples cis cis cis Cis Z Trans E

Useful resources http://www.chemeddl.org/resources/stereochem/definitions1.htm http://orgchem.chem.uconn.edu/courses/243f97-rs-practice.html