ISOMERISMSTEREOISOMER &

STEREOCHEMISTRY

Prepared by KH. Sadique FaisalASST.LECTURER

DEPARTMENT OF PHARMACY, NUB

Isomers are classified into two main classes-◦ Constitutional isomers

Chain isomers Positional isomers Functional group isomers Metamerism & Tautomerism

◦ Conformational isomers / Stereoisomers Geometrical isomers or cis-trans isomers & Optical isomers

Classification of Isomers

More appropriate way of classification

Connectivity of the atoms remain same unlike the constitutional isomers

But the orientation of atoms in space or spatial arrangement are different.

Stereoisomers have their atoms connected in the same sequence (the same constitution), but they differ in the arrangement of their atoms in space.

The consideration of such spatial aspects of molecular structure is called stereochemistry.

Stereoisomer

Changing configuration means bonds are broken

A different configuration is different molecule

Changing conformation of a molecule means rotating about bonds, but not breaking them

Conformation of a molecule are readily interconvertible, are all the same molecule

Configuration & conformation

Mirror images & superimposability

Enantiomers are non supersimposable mirror images of each other

Whereas diasteriomers are not mirror images of each other

Enantiomer & diastereomer

Contains chiral molecule Isomers are non superimposable mirror images of

each other Chiral molecule is not identical with its mirror

images Relationship is enatiomeric

Cis trans isomers or conformational isomers Not mirror images of each other Because of restricted rotation of groups joined by a

double bond

Enatiomer

Diastereomer

Chirality Or it is called handedness. (from Greek Cheir- Hand)

We can tell if an object has chirality by examining the object and its mirror image.

Every object has a mirror image. Many objects are achiral. By this we mean that the object and its mirror image are identical, that is, the object and its mirror image are superposable one on the other.

A chiral object is one that cannot be superposed on its mirror image.

Chirality

A tetrahedral atom with four different groups is an asymmetric carbon

◦ A stereocenter is defined as an atom bearing groups of such nature that an interchange of any two groups will produce a stereoisomer.

◦ The interconversion does not occur spontaneously as it requires breaking covalent bonds

Chiral center / stereogenic center

Which atoms in each of the following molecules are chirality centers?

Chiral center / stereogenic center

1. Chirality is a phenomenon that pervades the university.

1. The human body is structurally chiral. 2. Helical seashells are chiral, and most spiral like a

right-handed screw. 3. Many plants show chirality in the way they wind

around supporting structures.

2. Most of the molecules that make up plants and animals are chiral, and usually only one form of the chiral molecule occurs in a given species.

1. All but one of the 20 amino acids that make up naturally occurring proteins are chiral, and all of them are classified as being left handed (S configuration).

2. The molecules of natural sugars are almost all classified as being right handed (R configuration), including the sugar that occurs in DNA.

THE BIOLOGICAL IMPORTANCE OF CHIRALITY

3. DNA has a helical structure, and all naturally occurring DNA turns to the right.

3. Chirality and biological activity: 1. Limonene: S-limonene is responsible for the odor

of lemon, and the R-limonene for the odor of orange.

THE BIOLOGICAL IMPORTANCE OF CHIRALITY

2. Carvone: S-carvone is responsible for the odor of spearmint , and the R-carvone for the odor of caraway seed.

3. Thalidomide: used to alleviate the symptoms of morning sickness in pregnant women before 1963.

1. The S-enantiomer causes birth defect. 2. Under physiological conditions, the two

enantiomers are interconverted. 3. Thalidomide is approved under highly strict

regulations for treatment of a serious complication associated with leprosy

THE BIOLOGICAL IMPORTANCE OF CHIRALITY

Thalidomide’s potential for use against other conditions including AIDS, brain cancer, rheumatoid arthritis is under investigation.

The origin of biological properties relating to chirality: ◦ The fact that the enantiomers of a compound do not

smell the same suggests that the receptor sites in the nose for these compounds are chiral, and only the correct enantiomer will fit its particular site (just as a hand requires a glove of the ocrrect chirality for a proper fit).

◦ The binding specificity for a chiral molecule (like a hand) at a chiral receptor site is only favorable in one way. If either the molecule or the biological receptor site had the

wrong handedness, the natural physiological response (e.g. neural impulse, reaction catalyst) will not occur.

◦ Because of the tetrahedral stereocenter of the amino acid, three-point binding can occur with proper alignment for only one of the two enantiomers.

THE BIOLOGICAL IMPORTANCE OF CHIRALITY

◦ Superposibility of the models of a molecule and its mirage: If the models are superposable, the molecule that they represent

is achiral. If the models are nonsuperposable, the molecules that they

represent are chiral.

◦ The presence of a single tetrahedral stereocenter ⇒ chiral molecule.

◦ The presence of a plane of symmetry ⇒ achiral molecule A plane of symmetry (also called a mirror plane) is an imaginary

plane that bisects a molecule in such a way that the two halves of the molecule are mirror images of each other.

The plane may pass through atoms, between atoms, or both.

TESTS FOR CHIRALITY: PLANES OF SYMMETRY

The achiral hydroxyacetic acid molecule versus the chiral lactic acid molecule: ◦ Hydroxyacetic acid has a plane of symmetry that makes

one side of the molecule a mirror image of the other side.◦ Lactic acid, however, has no such symmetry plane.

TESTS FOR CHIRALITY: PLANES OF SYMMETRY

DESIGNATION OF STEREOCENTER

◦ R. S. Cahn (England), C. K. Ingold (England), and V. Prelog (Switzerland) devised the (R–S) system (Sequence rule) for designating the configuration of chiral carbon atoms.

◦ (R) and (S) are from the Latin words rectus and sinister: R configuration: clockwise (rectus, “right”) S configuration: counterclockwise (sinister, “left”)

◦ Configuration: the absolute stereochemistry of a stereocenter.

NOMENCLATURE OF ENANTIOMERS: THE (R-S) SYSTEM

1. Each of the four groups attached to the stereocenter is assigned a priority.

1. Priority is first assigned on the basis of the atomic number of the atom that is directly attached to the stereocenter.

2. The group with the lowest atomic number is given the lowest priority, 4; the group with next higher atomic number is given the next higher priority, 3; and so on.

3. In the case of isotopes, the isotope of greatest atomic mass has highest priority.

2. Assign a priority at the first point of difference. 1. When a priority cannot be assigned on the basis of

the atomic number of the atoms that are diredtly attached to the stereocenter, then the next set of atoms in the unassigned groups are examined.

THE (R-S) SYSTEM: (CAHN-INGOLD-PRELOG SYSTEM)

3. View the molecule with the group of lowest priority pointing away from us.

1. If the direction from highest priority (4) to the next highest (3) to the next (2) is clockwise, the enantiomer is designated R.

2. If the direction is counterclockwise, the enantiomer is designated S.

THE (R-S) SYSTEM: (CAHN-INGOLD-PRELOG SYSTEM)

THE (R-S) SYSTEM: (CAHN-INGOLD-PRELOG SYSTEM)

4. The sign of optical rotation is not related to the R,S designation.

5. Absolute configuration: 1. Groups containing double or triple bonds are

assigned priority as if both atoms were duplicated or triplicated.

THE (R-S) SYSTEM: (CAHN-INGOLD-PRELOG SYSTEM)

THE (R-S) SYSTEM: (CAHN-INGOLD-PRELOG SYSTEM)