isomerism

isomerism

• isomers are molecules that have the same molecular formula, but have a different arrangement of the atoms in space

• 2 types: constitutional isomerism and stereoisomerism

constitutional isomerism

• same molecular formula

• different structural formula → different arrangement of atoms

• 3 types: chain isomerism, positional isomerism, and functional group isomerism

stereoisomerism

• same molecular formula

• same structural formula

• different spatial arrangement of atoms → different 3-d orientation of atoms in space

• 2 types: cis-trans isomerism and enantiomerism

chain isomerism → constitutional isomerism

• chain isomers differ only in the structure of their carbon skeleton

• have similar chemical properties but different physical properties

positional isomerism → constitutional isomerism

• positional isomers belong to the same homologous series with the same functional group at different positions of the same carbon skeleton

• have similar chemical properties but different physical properties

functional group isomerism → constitutional isomerism

• functional group isomers have different functional groups

• have different physical and chemical properties ⇒ different homologous series

stereoisomerism

stereoisomers have the same structure and functional groups but differ in the way their atoms are arrange in space → atoms or groups are orientated differently to each other

cis-trans isomerism

• for a molecule to exhibit cis-trans isomerism, the following 2 criteria must be met:

  1. there is restricted rotation about a carbon-carbon bond ⇒ double bond or ring

  2. two different groups (or substituents) bonded to each carbon with the restricted bond

cis-trans isomerism in alkenes

• there is restricted rotation about the C=C double bond in alkenes ⇒ due to presence of the π bonds in the C=C double bond

• cis-trans isomerism occurs only if there are two different substituents attached to each carbon atom of the double bond

• an alkene with cis-trans isomerism can exist as a pair of cis-trans isomers

1. cis-isomer has the two identical groups on the same side of the double bond

2. trans-isomer has the two identical groups on different sides of the double bond

• cis and trans isomers have different physical properties

  • cis-isomer:

    1. higher boiling point because of its higher polarity

    2. lower melting point because of its poorer packing in its solid state, giving rise to less extensive instantaneous dipole-induced dipole interactions between the molecules

• cis and trans isomers generally have similar chemical properties

  • certain cis and trans isomers can differ in their chemical reactivities due to difference in the proximity of the functional groups

cis-trans isomerism in cyclic compounds

• atoms joined in a ring are not free to rotate around the sigma bonds of the ring ⇒ ring takes the place of the rigid double bond

• two substituents on adjacent (side-by-side) carbon atoms of a cyclic compound ⇒ cis-trans isomerism

to identify if a compound can exhibit cis-trans isomerism

1. check that it has at least one double bond OR a ring

2. check that there are 2 different substituents bonded to each C where there is restricted rotation

• cycloalkenes with 8 carbon atoms in the ring or less do not exhibit cis-trans isomerism ⇒ those with 8 or more carbon atoms can exhibit cis-trans isomerism

chiral molecules, achiral molecules and chiral centres

• chiral: non-superimposable mirror images

• achiral (not chiral): superimposable mirror images

• enantiomers (chiral): non-superimposable mirror images of the molecule (itself and mirror image)

• a molecule is chiral if it

  1. has at least one chiral carbon atom

     • indicated by a *

     • bonded to 4 substituents/groups

  2. no plane of symmetry

  3. non-superimposable on its mirror image ⇒ definitive criterion for a molecule to be chiral

chiral centres

• presence or absence of chiral carbons or centres is a useful but not a sufficient condition for a molecule to be chiral or achiral

• a molecule can possess chiral centres and yet remains achiral

• a molecule without chiral centres can still be chiral

plane of symmetry

a molecule with a plane of symmetry must be achiral, while a molecule without a plane of symmetry is usually chiral but not always

wedge-dash notation

• the shape of the molecule is tetrahedral with respect to C atom → 109.5°

• when drawing a pair of enantiomers, the three-dimensional structure should be represented using the wedge-dash notation:

chemical properties of enantiomers

• enantiomers have identical chemical properties (dependent on functional group) except in their interactions with another chiral molecule

• enantiomers show different rates of reaction towards other chiral molecules and have different solubilities in solvents that are chiral

physical properties of enantiomers

enantiomers have identical physical properties (identical structure) except for the direction in which they rotate plane-polarised light

optical activity

the ability of a substance to rotate the plane of plane-polarised light passed through the substance

• polarised light is light that vibrates in only one plane, in contrast to ordinary light which vibrates in all planes

  • when polarised light is passed through certain substances, the plane of the vibration is rotated a certain angle, different for each substance

  • instrument: polarimeter

• a sample which can rotate the plane of polarised light: optically active and contains chiral molecules

• a sample containing only achiral molecules do not rotate the plane of polarised light and are optically inactive

• enantiomers rotate the plane of polarised light in equal amounts but in opposite directions (clockwise or anticlockwise)

  • a mixture which contains equal quantities of each enantiomer (50% (+) and 50% (-) forms) ⇒ racemic mixture/racemate and is indicated by (d,l) or (±) sign

    • since the rotating capacity of one enantiomer is cancelled out by that of the other, the racemic mixture is said to be optically inactive ⇒ does not rotate plane polarised light

enantiomerism in cyclic compounds

chiral centres in cyclic compounds

• to determine if a carbon atom in a ring is chiral, examine the connection of atoms in the ring from the carbon of interest

• the carbon atom is chiral if we do not encounter the same sequence and type of groups when we go in one direction as compared to the other direction on the ring

determining the number of stereoisomers

• in general, for compounds with chiral centres and/or double bonds:

maximum number of stereoisomers = 2^n+m

• n: number of chiral centres

• m: number of C=C double bonds which can exhibit cis-trans isomerism

biological properties of stereoisomers

• different stereoisomers exhibit different biological properties

• most drugs are chiral → usually only one mirror image form of the drug provides the desired effect, while the other mirror image form can be less active, inactive and even toxic

  • to exert its biological action, a chiral molecule must fit into a chiral receptor at some target site → only one of the mirror images forms can fit properly into the receptor, and the other form is thus inactive

• e.g.: thalidomide contains two enantiomers

  • (+)-isomer has the intended effect of curing morning sickness

  • (-)-isomer causes birth defects