Stereochemistry The arrangement of atoms in space By: Dr. Manal F. Abou Taleb Organic Chemistry, 5 th Edition L. G. Wade, Jr. chapter 5

Isomerism Isomers are different compounds that have the same molecular formula. Constitutional isomers are isomers that differ because their atoms are connected in a different order.

Cahn-Ingold-Prelog Rules Assign a priority number to each group attached to the chiral carbon. Atom with highest atomic number assigned the highest priority #1. In case of ties, look at the next atoms along the chain. Double and triple bonds are treated like bonds to duplicate atoms. => 4

Geometric Isomers 5 cis-trans isomers

Geometric isomers: 6 cis or trans? E and Z Based on Priority: Cahn- Ingold-Prelongo: 1. Atomic Number 2. Atomic weight 3. Atomic number of the next atom Higher priority at the opposite side of pi bond (E) Higher priority at the same side of pi bond (Z) (E) ? ethene (E)-1-bromo-2-chloro- 2-fluoro-1-iodoethene

7 cis or trans? E and Z Based on Priority: (E) ? pentyne (E)-3-ethyl-2-pentene-4-yne

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Stereoisomers can be either enantiomers or diasteriomers A) Enanatiomers are stereoisomers whose molecules are nonsuperimposable mirror images of each other (different molecules). cis-1,2-dichlorocyclopentanetrans -1,2-dichlorocyclopentane

These two structures are enantiomers. Nonsuperimposable mirror images are called enantiomers, they occur in pairs. Enantiomers

B) Diastereomers (Geometric) are stereoisomers whose molecules are not mirror images of each other.

Enanatiomers “Optical isomer”  Same carbon  Same connection  Are mirror image  Nonsuperimposable  All configurations are opposite Diastereomers  Same carbon  Same connection  Are Not mirror image  Nonsuperimposable  Not All configurations are opposite

Chirality “Handedness”: right glove doesn’t fit the left hand. Mirror-image object is different from the original object. => 13 Molecule may be chiral or achiral

14 Stereoisomerisms Chiral: An object that cannot be superposed متطابقon its mirror image Chiral Carbon atom Chiral center Chiral molecules does Not contain a plane of symmatry

Chiral Carbons Tetrahedral carbons with 4 different attached groups are chiral. A tetrahedral carbon atom with four different groups attached to it is an asymmetric carbon. enantiomerIts mirror image will be a different compound (enantiomer). => 15

Br Cl H F Bromochlorofluoromethane is chiral It is not superimposable point for point on its mirror image. Note the four different attachments on C.

Br Cl H F Bromochlorofluoromethane is chiral H Cl Br F To demonstrate nonsuperimposability, rotate this model 180° around a vertical axis.

Br Cl H F Bromochlorofluoromethane is chiral H Cl Br F The structure on the right has been rotated.

Example: 2-butanol  I and II are mirror images of each other (figures a and b)  I and II are not superposable and so are enantiomers (figure c)  2-butanol is chiral molecule 19

Chlorodifluoromethane is achiral

The two structures at the top are mirror images, but because they can be superimposed on each other they are identical and are not enantiomers.

Mirror Planes of Symmetry achiral  If two groups are the same, carbon is achiral. (animation)  A molecule with an internal mirror plane cannot be chiral.* 22 Notes ! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed. =>  Chiral molecules does Not contain a plane of symmatry σ

Symmetry tests for achiral structures  Any molecule with a plane of symmetryor a center of symmetry must be achiral. Achiral center: a C atom is attached by 2 or more same groups Chiral  Non-superimposable with its mirror image  asymmetric carbon  4 different attached groups  Enanatiomers achiral  Superimposable with its mirror image  plane of symmetry  2 or more same attach groups.  not enantiomers

25 Clasiffy each of the following pairs as chiral or achiral. a) b) c) achiral chiral

26 Label the stereogenic centers in each molecule and decide if it is chiral. a) CH 3 CH 2 CH(Cl)CH 2 CH 3 achiral b) CH 3 CH(OH)CH=CH 2 chiral c) (CH 3 ) 2 CHCH 2 CH 2 CH(CH 3 )CH 2 CH 3 chiral

A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane has a plane of symmetry. 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. Plane of symmetry

29 These mirror images are not the same, even after rotation! These are two distinct 3-methylhexane enantiomers

(a) 2-Propanol and its mirror image, (b) When either one is rotated, the two structures are superposable and so do not represent enantiomers. They represent two molecules of the same compound. 2- Propanol does not have a stereocenter.

How is each pair of the following structures is related: (i) The Same(ii) Geometric isomers (iii) Structural isomers(iv) Not related at all

Which one of the following compounds can exist as a pair of geometric isomers? Which compound of the following cannot exhibit cis / trans isomerism (i) 1,4-Dibromocyclohexane (ii) 1,2-Dibromocyclohexane (iii) 1,1-Dibromocyclohexane (iv)1,3-Dibromocyclohexane

Which of the following molecules is trans-1, 2- dimethylcyclohexane? (i) (ii) (iii) (iv)

Absolute Conformation Assign (R) or (S) Working in 3D, rotate molecule so that lowest priority group is in back. Draw an arrow from highest to lowest priority group. Clockwise = (R), Counterclockwise = (S) => 36

37 Since enantiomers are two different compounds, they need to be distinguished by name. This is done by adding the prefix R or S to the IUPAC name of the enantiomer. Naming enantiomers with the prefixes R or S is called the Cahn-Ingold-Prelog system. To designate enantiomers as R or S, priorities must be assigned to each group bonded to the stereogenic center, in order of decreasing atomic number.  The atom of highest atomic number gets the highest priority (1). Labeling Stereogenic Centers with R or S

38  If two atoms on a stereogenic center are the same, assign priority based on the atomic number of the atoms bonded to these atoms. One atom of higher atomic number determines the higher priority.

39  If two isotopes are bonded to the stereogenic center, assign priorities in order of decreasing mass number. Thus, in comparing the three isotopes of hydrogen, the order of priorities is:

40  To assign a priority to an atom that is part of a multiple bond, treat a multiply bonded atom as an equivalent number of singly bonded atoms. For example, the C of a C=O is considered to be bonded to two O atoms.  Other common multiple bonds are drawn below:

41 Figure 5.6 Examples of assigning priorities to stereogenic centers

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43 Labeling Stereogenic Centers with R or S

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45 Figure 5.7 Examples: Orienting the lowest priority group in back

46 Label each compound as R or S. a) S b) R