STEREOISOMERS ARRANGEMENTS IN 3D- SPACE 1
Isomers 2
Physiological Proper@es of Stereoisomers (Enan@omers) Enan@omers can have very different physiological proper@es. 3
Oranges and Lemons found in oranges found in lemons 4
Chirality Handedness : Right glove doesn t fit the let hand. Mirror- image object is different from the original object. 5
Achiral Objects that can be superposed are achiral. 6
Stereoisomers Enan)omers: Nonsuperimposable mirror images, different molecules with different proper@es. 7
Chiral Molecules Chiral molecules have an asymmetric center. An asymmetric center is an atom that is a[ached to different groups. 8
Chiral Carbons Carbons with four different groups a[ached are chiral. It s mirror image will be a different compound (enan@omer). 9
Enan@omers Enan@omers are nonsuperimposable mirror images. 10
Enan@omers The two isomers are called enan@omers. Enan@omers are different compounds: they can be separated. Enan@omers have the same physical and chemical proper@es. 11
Achiral Compounds Take this mirror image and try to superimpose it on the one to the le4 matching all the atoms. Everything will match. 12
Planes of Symmetry A molecule that has a plane of symmetry is achiral. 13
Chiral and Achiral Molecules Chiral compounds have nonsuperimposable mirror images. Achiral compounds have superimposable mirror images (they are iden@cal molecules). 14
Asymmetric Center versus Stereocenter Asymmetric center: an atom a[ached to four different groups. Stereocenter: an atom at which the interchange of two groups produces a stereoisomer. 15
(R) and (S) Nomenclature Different molecules (enan@omers) must have different names. Usually only one enan@omer will be biologically ac@ve. Configura@on around the chiral carbon is specified with (R) and (S). 16
Rule 1: Cahn Ingold Prelog Rules Sequence Rules (IUPAC) Look at the four atoms directly a[ached to the chirality center, and rank them according to atomic number. With the lowest priority group poin@ng away, look at remaining 3 groups in a plane Clockwise is designated R (from La@n word for right ) Counterclockwise is designated S (from La@n word for let )
Sequence Rules (Con@nued) Rule 2: If a decision cannot be reached by ranking the first atoms in the subs@tuents, look at the second, third, or fourth atoms un@l difference is found 18
Sequence Rules (Con@nued) Rule 3: Mul@ple- bonded atoms are equivalent to the same number of single- bonded atoms
Assign (R) or (S) Working in 3- D, rotate the molecule so that the lowest priority group is in back. Draw an arrow from highest to lowest priority group. Clockwise = (R), Counterclockwise = (S) 20
Assign Priori@es Atomic number: F > N > C > H Once priori@es have been assigned, the lowest priority group (#4) should be moved to the back if necessary. 21
Assign Priori@es Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group 1. Ignore Group 4. Clockwise = (R) and Counterclockwise = (S) 22
Example When rota@ng to put the lowest priority group in the back, keep one group in place and rotate the other three. 23
Example (Con@nued) 24
Example Draw the enantiomers of 1,3-dibromobutane and label them as (R) and (S). (Making a model is particularly helpful for this type of problem.) Solu@on The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first priority, the ( CH 2 CH 2 Br) group second priority, the methyl group third, and the hydrogen fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign (R) or (S) as shown. 25
Proper@es of Enan@omers Same boiling point, mel@ng point, and density. Same refrac@ve index. Rotate the plane of polarized light in the same magnitude, but in opposite direc@ons. Different interac@on with other chiral molecules: Ac@ve site of enzymes is selec@ve for a specific enan@omer. Taste buds and scent receptors are also chiral. Enan@omers may have different smells. 26
Op@cal Ac@vity Enan@omers rotate the plane of polarized light in opposite direc@ons, but same number of degrees. 27
Polarimeter Not related to (R) and (S) 28
Specific Rota@on Observed rota@on depends on the length of the cell and concentra@on, as well as the strength of op@cal ac@vity, temperature, and wavelength of light. [α] = α (observed) c l Where α (observed) is the rota@on observed in the polarimeter, c is concentra@on in g/ml and l is length of sample cell in decimeters. 29
Example When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed rotation is 4.05 counterclockwise. The solution was made by diluting 6 g of 2-butanol to a total of 40 ml, and the solution was placed into a 200-mm polarimeter tube for the measurement. Determine the specific rotation for this enantiomer of 2-butanol. Solu@on Since it is levorotatory, this must be ( )-2-butanol The concentration is 6 g per 40 ml = 0.15 g/ml, and the path length is 200 mm = 2 dm. The specific rotation is 25 4.05 [α] D = (0.15)(2) = 13.5 30
Biological Discrimina@on 31
Racemic Mixtures Equal quan@@es of d- and l- enan@omers. Nota@on: (d,l) or (±) No op@cal ac@vity. The mixture may have different boiling point (b. p.) and mel@ng point (m. p.) from the enan@omers! 32
Racemic Products If op@cally inac@ve reagents combine to form a chiral molecule, a racemic mixture is formed. 33
Op@cal Purity Op@cal purity (o.p.) is some@mes called enan@omeric excess (e.e.). One enan@omer is present in greater amounts. o.p. = observed rota@on rota@on of pure enan@omer X 100 34
Enan@omeric Excess Enan@omeric excess tells us how much of an excess of one enan@omer is in a mixture. 35
Calculate % Composi@on The specific rota@on of (S)- 2- iodobutane is +15.90. Determine the % composi@on of a mixture of (R)- and (S)- 2- iodobutane if the specific rota@on of the Mixture is - 3.18. Sign is from the enan6omer in excess: levorotatory. 3.18 o.p. = 15.90 X 100 = 20% l = 60% d = 40% 36
R and S Versus (+) and ( ) Some R enan@omers are (+) and some are ( ). Some S enan@omers are (+) and some are ( ). 37
If One Enan@omer Is (+), the Other Is ( ) 38
Chirality of Conformers If equilibrium exists between two chiral conformers, the molecule is not chiral. Judge chirality by looking at the most symmetrical conformer. Cyclohexane can be considered to be planar, on average. 39
Chirality of Conforma@onal Isomers The two chair conforma@ons of cis- 1,2- dibromocyclohexane are nonsuperimposable, but the interconversion is fast and the molecules are in equilibrium. Any sample would be racemic and, as such, op@cally inac@ve. 40
Nonmobile Conformers The planar conforma@on of the biphenyl deriva@ve is too sterically crowded. The compound has no rota@on around the central C C bond and thus it is conforma@onally locked. The staggered conforma@ons are chiral: They are nonsuperimposable mirror images. 41
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. 42
2,3- Pentadiene Is Chiral 43
Fischer Projec@ons Flat representa@on of a 3- D molecule. A chiral carbon is at the intersec@on of horizontal and ver@cal lines. Horizontal lines are forward, out- of- plane. Ver@cal lines are behind the plane. 44
Fischer Projec@ons (Con@nued) 45
Fischer Rules Carbon chain is on the ver@cal line. Highest oxidized carbon is at top. Rota@on of 180 in plane doesn t change molecule. Do not rotate 90! 46
180 Rota@on A rota@on of 180 is allowed because it will not change the configura@on. 47
90 Rota@on A 90 rota@on will change the orienta@on of the horizontal and ver@cal groups. Do not rotate a Fischer projec@on 90. 48
Fischer Mirror Images Fisher projec@ons are easy to draw and make it easier to find enan@omers and internal mirror planes when the molecule has 2 or more chiral centers. H C l C H 3 C l H C H 3 49
Fischer (R) and (S) Lowest priority (usually H) comes forward, so assignment rules are backwards! Clockwise 1-2- 3 is (S) and counterclockwise 1-2- 3 is (R). Example: C H 3 (S) H C l C l H (S) C H 3 50
Compounds with Two Asymmetric Centers Diastereomers 1 and 2 are enan@omers. 3 and 4 are enan@omers. Diastereomers are stereoisomers that are not enan@omers. 1 and 3 are diastereomers. 1 and 4 are diastereomers. 2 and 3 are diastereomers. 2 and 4 are diastereomers. Diastereomers have different physical and chemical proper@es. 51
Perspec@ve Formulas of the Four Stereoisomers 52
Diastereomers Molecules with two or more chiral carbons. Stereoisomers that are not mirror images. 53
A Meso Compound Has a Superimposable Mirror Image Meso compounds are op@cally inac@ve even though they have asymmetric centers. 54
Two Asymmetric Centers: Three Stereoisomers (a meso compound and a pair of enan@omers) 55
Number of Stereoisomers The 2 n rule will not apply to compounds that may have a plane of symmetry. 2,3- dibromobutane has only 3 stereoisomers: (±) enan6omer and the meso diastereomer. 56
A Meso Compound A compound with two asymmetric centers that have the same four groups bonded to each asymmetric center will have three stereoisomers: a meso compound and a pair of enan@omers. 57
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. 58
Two Asymmetric Centers, Four Stereoisomers The cis stereoisomers are a pair of enan@omers. The trans stereoisomers are a pair of enan@omers. 59
Iden@fying an Asymmetric Center An asymmetric center is a[ached to four different groups. two asymmetric centers, four stereoisomers 60
No Asymmetric Centers There are only two stereoisomers: cis and trans. 61
No Asymmetric Centers There are only two stereoisomers: cis and trans. 62
A Meso Compound For cyclic compounds with the same subs@tuent bonded to two asymmetric centers, cis = a meso compound and trans = a pair of enan@omers. 63
Two or More Chiral Carbons When compounds have two or more chiral centers they have enan@omers, diastereomers, or meso isomers. Enan@omers have opposite configura@ons at each corresponding chiral carbon. Diastereomers have some matching, some opposite configura@ons. Meso compounds have internal mirror planes. Maximum number of isomers is 2 n, where n = the number of chiral carbons. 64
Comparing Structures 65
Proper@es of Diastereomers Diastereomers have different physical proper@es, so they can be easily separated. Enan@omers differ only in reac@on with other chiral molecules and the direc@on in which polarized light is rotated. Enan@omers are difficult to separate. Convert enan@omers into diastereomers to be able to separate them. 66
Resolu@on of Enan@omers React the racemic mixture with a pure chiral compound, such as tartaric acid, to form diastereomers, then separate them. 67
Chromatographic Resolu@on of Enan@omers 68
Separa@ng Enan@omers separa@ng by hand separa@ng by chromatography 69
Physical Proper@es of Stereoisomers 70
Nitrogen and Phosphorus Can Be Asymmetric Centers 71