University of Nizwa Oman Dr. Ghulam Abbas Assistant Professor University of Nizwa

Stereochemistry Stereochemistry is the study of molecules in three dimensions (3D). To study how the shape of a molecule affects its chemistry. 1.Chain isomerism 2. Functional group Isomerism Position Isomerism 4. Metamerism 5. Tautomerism

Stereochemistry

Definitions Stereoisomers – compounds with the same connectivity, different arrangement in space. Enantiomers – stereoisomers that are non superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation. Diastereomers – stereoisomers that are not mirror images; they are different compounds with different physical properties.

Asymmetric center – sp3 carbon with 4 different groups attached. Conti…… Asymmetric center – sp3 carbon with 4 different groups attached. Optical activity – the ability to rotate the plane of plane –polarized light. Chiral compound – a compound that is optically active (achiral compound will not rotate light). Polarimeter – device that measures the optical rotation of the chiral compound.

Isomers Compounds having same chemical formula but different structures are called isomers. There are two classes of isomers 1. Constitutional or Structural Isomerism Stereo Isomerism.

Constitutional or Structural Isomerism Constitutional Isomers will have the same number and types of atoms, but they are connected differently sequentially (they have a different Constitution). A simple example of Constitutional Isomers are ethanol and dimethyl ether. Ethanol Dimethyl ether Types of Constitutional Isomers. 1. Chain isomerism 2. Functional group Isomerism 3. Position Isomerism 4. Metamerism 5. Tautomerism

Chain Isomerism Compounds having same molecular formula but different carbon chain or skeleton are called chain isomers and this phenomenon is called Chain isomerism. Molecular Formula C5H12 Molecular Formula C4H10O

Functional group Isomers Compounds having same molecular formula but different functional functional groups are called chain isomers. H 3 C 2 O P r o p a n l e . 6 h s g t w F i m A c d M y f 4

Position isomerism Compounds having same molecular formula but different position of Functional group or double bond or triple bond are called position isomers and this phenomenon is called Position isomerism.

CH3-CH2-NH-CH2-CH3 and CH3-NH-CH2-CH2-CH3 Metamerism Compounds having same molecular formula same functional group but having different alkyl groups attach to same multivalent element like oxygen, Nitrogen, sulpher etc are called metamers and this phenomenon is called metamerism. Amine CH3-CH2-NH-CH2-CH3 and CH3-NH-CH2-CH2-CH3 Tautomerism Keto enol form of a compound is called Tautomerism.

Chirality The word chirality refers to the property of “handnesss” Your right and left hands are very similar, yet they are not identical. They are related to each other as mirror images and as such they can’t be superimposed on top of each other . Molecule can also be chiral if they contain one or more chiral centers.

Chiral Centre (stereogenic Centre) The carbon atom having four different atoms and can not be subdivided in to two equal halves.

Chirality Center Carbon has four different groups attached

Asymmetric (chiral) carbon Some molecules are chiral: Asymmetric (chiral) carbon

Prochiral A molecule is said to be prochiral if it can be converted from achiral to chiral in a single chemical step. For instance, an unsymmetrical ketone like 2-butanone is prochiral because it can be converted to the chiral alcohol 2-butanol by addition of hydrogen. + H2

ENANTIOMERS CONFIGURATIONAL isomers Are composed of ENANTIOMERS and DIASTERIOISOMER. ENANTIOMERS: The non-super imposable mirror images of a compounds is called enantiomers (d or l rotatory) they are are optically active because they cane rotate the plane of polarized either to right or to left. Example: 2, 3 Dibromobutane.

ENANTIOMERS 2, 3 Dibromobutane Lactic Acid

Cahn-Ingold-Prelog System

Cahn-Ingold-Prelog System

R and S Configuration Examples S = = S c) R

Tartaric Acid: Used by Pasteur Examples Meso Compound

R and S Configurations

MESO COMPOUND A compound whose molecules are superimposable on their mirror images, even though they contain chiral centers. It is optically inactive. (They have plane of symmetry).

Three Stereoisomers of 2,3-Butanediol MESO COMPOUNDS Three Stereoisomers of 2,3-Butanediol H OH CH3 HO CH3 OH H HO H CH3 OH 2R,3R 2S,3S 2R,3S chiral chiral achiral 6

Three Stereoisomers of 2,3-Butanediol MESO COMPOUND Three Stereoisomers of 2,3-Butanediol Meso forms have a plane of symmetry and/or a center of symmetry. Plane of symmetry is most common case. Top half of molecule is mirror image of bottom half. 2R,3S achiral 6

Meso Compounds Meso compounds have a plane of symmetry. If one image was rotated 180°, then it could be superimposed on the other image. Meso compounds are achiral even though they have chiral centers. 27 27

CHIRAL CENTERS OTHER THAN CARBON Silicon b b a a Si ---------------------------------------- d d Si c c Silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds have been resolved. 6

Nitrogen in Amines b b a very fast a N : : N c c Pyramidal geometry at nitrogen can produce a chiral structure, but enantiomers equilibrate too rapidly to be resolved. 6

Phosphorus in Phosphines b b a slow a P : : P c c Pyramidal geometry at phosphorus can produce a chiral structure; pyramidal inversion slower than for amines and compounds of the type shown have been resolved. 6

Sulfur in Sulfoxides b b a slow a + S : : S + O_ O_ Pyramidal geometry at sulfur can produce a chiral structure; pyramidal inversion is slow and compounds of the type shown have been resolved. 6

Symmetry in Achiral Structures Any molecule with a plane of symmetry or a center of symmetry must be achiral. Plane of symmetry Any molecule with a plane of symmetry or a center of symmetry must be achiral. A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane has a plane of symmetry. 21

Plane of symmetry A plane of symmetry bisects a molecule into two mirror image halves. 1-Bromo-1-chloro-2-fluoroethene has a plane of symmetry. 21

Center of symmetry A point in the center of the molecule is a center of symmetry if a line drawn from it to any element, when extended an equal distance in the opposite direction, encounters an identical element. 21

Properties of enantiomers a) Physical: Enantiomers have identical physical properties with the exception that they rotate the plane of polarized light in opposite directions although || is identical. b) Chemical: They have identical chemical properties except for their reaction with reagents which are, themselves, optically active. In this case, reaction rates differ and depend on which enantiomer of the reagent is used. (+)-Glucose is central to the fermentation process whereas (-)-glucose doesn’t react!

DIASTERIOISOMER Those stereo isomer which are not mirror images of one another are known as diasterioisomers. OR They are the stereoisomerisms which must have opposite (mirror image) configuration at one or more chiral centers but the same configurations at another chiral canters. DIASTERIOISOMER Diasterioisomers have different melting points, Boiling points and solubility reactivity and all other properties.

DIASTERIOISOMER Examples Vants Hoff Rule For a molecule with multiple chiral centers, the number of possible diastereoisomers is given by the equation X = 2n Where X is the number of possible isomers and n is the number of stereogenic centers.

Other Examples of Diastereoisomer is 2-chloro-2 Butanol

Diastereoisomer is 2-chloro-2 Butanol The relation between structure (i), (iii), (iv) is known as diastereoisomers, Structure (i), (ii) are enatiomers and they must have identical properties, the same true for structure (iii) and (iv). How ever the properties of Structure (i) and (ii) are not identical with those of structure (iii) and (iv). They have different melting points, Boiling points and solubility reactivity and all other properties.

Optical Isomerism The compounds having the same molecular formulas, structural formulas, physical and chemical properties but differing in their action on plane polarized light are called optical isomer and phenomenon is called optical isomerism. Optical activity The property of a compound to rotate the plane polarized light in either direction is called optical activity. OR The substance rotating the plane of polarized to the left or right is called optical active and this property of rotating planner polarized light is called optical activity.

Plane polarized light The light oscillating in single plane is called plane-polarized light. If we observed the beam of light of ordinary light from one end, we will find that oscillation of electric field and magnetic fields are occurring in all possible planes perpendicular to the directions of propagations. When ordinary light is passed through a polarizer, it loses its horizontal components. The resulting ray is oscillating in single plane.

Dextro rotatory ( or d form) Laevo Rotatory (or l form) The molecule rotating the plane of polarized light to the left is called Laevo rotatory or l form. Dextro rotatory ( or d form) The molecule rotating the plane of polarized light to the right is called dextro rotatory or d form.

Optical Isomerism 

Specific rotation The observed angle of optical rotation α when plane-polarized light is passed through a sample with a path length of 1 decimeter and a sample concentration of 1 gram per 1 milliliter. It is the main property used to quantify the chirality of a substance. []t =  l x c  - angle of rotation measured in degrees t - temperature  - wavelength of light l - length of sample cell c - concentration in grams of substance contained in 1 mL of solution

The Chirality Axis Some molecules are chiral but do not contain a chirality center. Some of these contain a chirality axis, an axis about which groups are arranged so that the spatial arrangement is not superimposable on its mirror image. Examples include substituted biphenyls and allenes: 2

Atropisomerism In the appropriately substituted biphenyls, rotation around the bond joining the rings is restricted and the enantiomers can be isolated: Conformational isomers that are stable, isolable compounds are called atropisomers.

Atropisomerism Substituted 1,1’-binaphthyl derivatives exhibit atropisomerism due to hindered rotation about the single bond that connects the two naphthalene rings. An example is (S)-(-)-BINAP shown below.

Nonmobile Conformers The planar conformation of the biphenyl derivative is too sterically crowded. The compound has no rotation around the central C—C bond and thus it is conformationally locked. The staggered conformations are chiral: They are nonsuperimposable mirror images. 48 48

Allenes Some allenes are chiral even though they do not have a chiral carbon. Central carbon is sp hybridized. To be chiral, the groups at the end carbons must have different groups. 49 49

Penta-2,3-diene Is Chiral 50 50

STEREO ISOMERS ARE OF TWO TYPES. Configurational Isomerism Conformational Isomerism Configurational Isomerism The isomerism in which two compounds are inter converted only by the breaking and making of bonds such compounds are called Configurational Isomerism.

Conformational Isomers The different arrangements of atoms that result from bond rotation are called conformations, and molecules that have different arrangements are called conformational isomers, or conformers. Different conformers often can not be isolated because they interconvert very rapidly. Rotation is possible around carbon–carbon bonds in open-chain molecules. In ethane, for instance, rotation around the C - C bond occurs freely, constantly changing the spatial relationships between the hydrogens on one carbon and those on the other.

Example: Conformational isomers are represented in two ways; Sawhorse representation: It shows molecules at an angle, showing a molecular model. C-C bonds are at an angle to the edge of the page.

Conformational Isomers Newman projections: Bonds to front carbon are lines going to the center while bonds to back/rear carbon are lines going to the edge of the circle. There is a small (12 kJ/mol or 2.9 kcal/mol) barrier to rotation and some conformations are more stable than others.

Newman Projection The lowest energy, most stable conformation is the one in which all six C - H bonds are as far away from one another as possible called staggered conformation. The highest-energy, least stable conformation is the one in which the six C -H bonds are as close as possible called eclipsed Newman projection.

Newman Projection In butane, the lowest-energy arrangement, called the anti conformation, is the one in which the two methyl groups are as far apart as possible—180° away from each other. Butane- Anti conformation Butane-eclipsed conformation (0 kJ/mol) (16 kJ/mol)

Beyer Strain Theory (Angle strain) According to this theory (Adolf von Baeyer in 1885), any deviation from the normal bond angle cause strain, called angle strain in the molecule, and greater the deviation form the normal angle, the greater the strain and the less stability. In cycloalkanes, since each carbon atom is sp3 hybridization, the C-C-C bond Angle should be tetrahedral (109.5o).

Strain Theory • Angle strain— the strain due to expansion or compression of bond angles. • Torsional strain —the strain due to eclipsing of bonds on neighboring atoms. • Steric strain —the strain due to repulsive interactions when atoms approach each other too closely.

Conformations of Cyclohexane 23KJ/mol higher Energy than Chair.

Cyclic Alkanes

Geometrical Isomerism Compounds in which carbon to carbon free rotation is restricted may exhibit geometrical isomerism. These compounds don’t rotate the plane of polarized light and properties of isomer are not identical. They are also called as cis-trans isomer

Geometrical Isomerism

Geometric isomers In a diasteromeric cyclic compound the substituents can give the appearance of being either cis or trans to each other and these are referred to as geometric isomers. An example is the two geometric isomers of 1-hydroxy-2-methyl-cyclobutane (form 1 and form 2).

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