capitulo 9

9. StereochemistryBased on McMurrys Organic Chemistry, 7th edition

McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

StereochemistrySome objects are not the same as their mirror images (technically, they have no plane of symmetry)A right-hand glove is different than a left-hand glove. The property is commonly called handednessOrganic molecules (including many drugs) have handedness that results from substitution patterns on sp3 hybridized carbon


Why this Chapter?Handedness is important in organic and biochemistry

Other types of stereoisomers besides cis/trans

Molecular handedness makes possible specific interactions between enzymes and substrateseffecting metabolism and pharmaceuticals


Examples of EnantiomersMolecules that have one carbon with 4 different substituents have a non-superimposable mirror image Enantiomers = non-superimposable mirror image stereoisomersEnantiomers have identical physical properties (except for one)Build molecular models to see this


ChiralityIf an object has a plane of symmetry its the same as its mirror imageA plane of symmetry divides an entire molecule into two pieces that are exact mirror images Achiral means that the object has a plane of symmetry

Molecules that are not superimposable with their mirror images are chiral (have handedness)Hands, gloves are prime examples of chiral objectThey have a left and a right versionOrganic molecules can be Chiral or Achiral


Chiral CentersA point in a molecule where four different groups (or atoms) are attached to carbon is called a chiral centerThere are two nonsuperimposable ways that 4 different different groups (or atoms) can be attached to one carbon atomIf two groups are the same, then there is only one wayA chiral molecule usually has at least one chiral center


Chiral Centers in Chiral MoleculesGroups are considered different if there is any structural variation (if the groups could not be superimposed if detached, they are different)In cyclic molecules, we compare by following in each direction in a ring


9.3 Optical ActivityLight restricted to pass through a plane is plane-polarizedA polarimeter measures the rotation of plane-polarized light that has passed through a solutionRotation, in degrees, is []Clockwise (+) = dextrorotatory; Anti-clockwise (-) = levorotatory

Plane-polarized light that passes through solutions of achiral compounds remains in that plane ([a] = 0, optically inactive)Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active


Measurement of Optical RotationThe more molecules of a chiral sample are present the greater the rotation of the light = concentration dependentTo have a basis for comparison, define specific rotation, []D for an optically active compoundSpecific rotation is that observed for 1 g/mL in solution in a cell with a 10 cm path using light from sodium metal vapor (589 nm)

The specific rotation of the enantiomer is equal in magnitude but opposite in sign (+)-lactic acid = +3.82; (-)-lactic acid = -3.82


9.4 Pasteurs Discovery of EnantiomersLouis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right handed and left handed formsThe solutions contain mirror image isomers, called enantiomers and they crystallized in distinctly different shapes such an event is rareA (50:50) racemic mixture of both crystal types dissolved together was not optically activeThe optical rotations of equal concentrations of these forms have opposite optical rotations


Sequence Rules for Specification of ConfigurationA general method applies to determining the configuration at each chiral center (instead of to the whole molecule)The configuration is specified by the relative positions of all the groups with respect to each other at the chiral centerThe groups are ranked in an established priority sequence and compareduse the same priority ranking as we did for E/Z namesThe relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule

Method Assign each group priority 1-4 according to Cahn-Ingold-Prelog Rotate the assigned molecule until the lowest priority group (4) is in the back, look at remaining 3 groups in a plane Clockwise 1-2-3 movement is designated R (from Latin for right) Counterclockwise is designated S (from Latin word for left)


Priority (Cahn-Ingold-Prelog) Rules [REVIEW CH. 6]

Rule 1:Look at the atoms directly attached to the chiral carbon and assign priority based on highest atomic number (O > N > C > H)Rule 2:If decision cant be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until difference is foundRule 3:Multiple-bonded atoms are equivalent to the same number of single-bonded atoms


9.6 DiastereomersMolecules with more than one chiral center have mirror image stereoisomers that are enantiomersIn addition they can have stereoisomeric forms that are not mirror images, called diastereomers


DiastereomersDiastereomers are similar, but they arent mirror images Enantiomers have opposite configurations at all chiral centers; Diastereomers are opposite at some, but not all chiral centersDiastereomers have different physical properties

Epimers are diastereomers different at only 1 chiral center


9.7 Meso CompoundsTartaric acid has two chiral centers and two diastereomeric formsOne form is chiral and one is achiral, but both have two chiral centersAn achiral compound with chiral centers is called a meso compound it has a plane of symmetryThe two structures on the right in the figure are identical so the compound (2R, 3S) is achiral Identical substitution on both chiral centers


9.8 Racemic Mixtures and The Resolution of EnantiomersA 50:50 mixture of two chiral compounds that are mirror images does not rotate light called a racemic mixture (named for racemic acid that was the double salt of (+) and (-) tartaric acidThe pure compounds need to be separated or resolved from the mixture (called a racemate)To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent)This gives diastereomers that are separated by their differing solubilityThe resolving agent is then removed


Using an Achiral amine doesnt change the relationship of the productsStill cant separate the Enantiomeric Salts


Using a Chiral amine changes the relationship of the productsNow we can separate the Diastereomeric Salts


9.9 A Review of IsomerismThe flowchart summarizes the types of isomers we have seen


Constitutional IsomersDifferent order of connections gives different carbon backbone and/or different functional groups


StereoisomersSame connections, different spatial arrangement of atomsEnantiomers (nonsuperimposable mirror images)Diastereomers (all other stereoisomers)Includes cis, trans and configurational


9.10 Stereochemistry of Reactions: Addition of H2O to AlkenesMany reactions can produce new chiral centers from compounds without themWhat is the stereochemistry of the chiral product?What relative amounts of stereoisomers form?Example addition of H2O to 1-butene


Achiral Intermediate Gives Racemic ProductAddition via carbocationTop and bottom are equally accessibleAchiral reactant + Achiral reactant = Optically Inactive ProductOptical Activity doesnt come from nowhere


Addition of H2O to a Chiral AlkeneWhat is the sterochemical result of the addition of H2O to a chiral alkene R-4-methyl-1-hexeneProduct has 2 chiral centers

Chiral + Achiral = Optically Active

-Chiral Intermediate has different topand bottom sides

-Amounts of the two products will bedifferent

-Product will have optical activity


9.12 Chirality at Nitrogen, Phosphorus, and SulfurN, P, S commonly found in organic compounds, and can have chiral centersTrivalent nitrogen is tetrahedralDoes not form a chiral center since it rapidly flipsIndividual enantiomers cannot be isolated = Achiral


Also applies to phosphorus but it flips more slowlyCan isolate individual enantiomers = Chiral

Trivalent Sulfur Cations are also Chiral


9.13 ProchiralityA molecule that is achiral but that can become chiral by a single alteration is a prochiral molecule

Re and Si are used to describe the faces of the prochiral sp2 reactant


Prochiral distinctions, paired atoms or groupsAn sp3 carbon with two groups the same is also a prochiral center

The two identical groups are distinguished by considering either and seeing if it was increased in priority in comparison with the other

If the center becomes R the group is pro-R and pro-S if the center becomes S


Prochiral Distinctions in Nature Biological reactions often involve making distinctions between prochiral faces or or groupsChiral entities (such as enzymes) can always make such a distinctionExample: addition of water to fumarate


Chirality in Nature and Chiral EnvironmentsEnantiomers have same physical properties, different biological onesStereoisomers are readily distinguished by chiral receptors in nature

Properties of drugs depend on stereochemistryThink of biological recognition as equivalent to 3-point interactionEnzymes can make only one enantiomer from an achiral reactantIn the chiral environment, pro-R and pro-S are chemically different


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