Chapter 5: Lecture PowerPoint Isomerism 2: Chirality, Enantiomers, and Diastereomers

5.1 Defining Configurational Isomers, Enantiomers, and Diastereomers Recall that conformational isomers are related solely by rotations about single bonds. Converting from one configurational isomer to another requires the breaking of a covalent bond

Flowchart for Determining the Type of Isomer

5.2 Enantiomers, Mirror Images, and Superimposability Enantiomers are nonsuperimposable mirror images. Molecules are nonsuperimposable if there is no orientation in which all atoms of both molecules can be superimposed. Please insert fig 5-2, pg 3 FIG05.02_Karty1_CH05 jmk: I italicized the first “nonsuperimposable” and bolded the second.

What does a Superimposable Image Look Like? Every molecule has a mirror image, but not every molecule has a nonsuperimposable mirror image. Superimposable mirror image compounds do not have enantiomers.

5.3 Strategies for Success: Drawing Mirror Images Drawing a molecule’s mirror image quickly and correctly is an essential skill.

Steps to Drawing a Mirror Imaged Compound

Steps to Drawing a Mirror Imaged Compound continued…

5.4 Chirality A molecule is chiral if it has an enantiomer. A molecule is achiral if it does not have an enantiomer. These objects are chiral:

Chirality and Conformational Isomers Rotation about single bonds can determine whether a molecule is chiral or achiral. If a molecule and its mirror image are rapidly interconverting conformational isomers, then the molecule is effectively achiral. The mirror image of 1,2-dibromoethane in one of its gauche conformations is its second gauche conformation.

Chirality and Conformational Isomers continued… These two gauche conformations are nonsuperimposable which suggests that 1,2-dibromoethane is chiral. Rapid interconversion between the gauche conformations causes the molecule to be achiral.

Haworth Projections Haworth projections are helpful in determining the chirality of all cyclics. Taking the chair conformation of cyclohexane to a flat hexagon allows us to quickly and accurately determine whether it is chiral or achiral.

The Plane of Symmetry Test for Chirality A molecule has a plane of symmetry if it can be bisected in such a way that one half of the molecule is the mirror image of the other half. A molecule that has a plane of symmetry must be achiral; an achiral molecule must not have a plane of symmetry.

Stereocenters and Stereochemical Configurations A tetrahedral atom bonded to four different groups is called a stereocenter. Tetrahedral stereocenters can be found in cyclics and acylic compounds.

Stereocenters and Stereochemical Configurations continued… Each tetrahedral stereocenter has two possible configurations. One configuration is the opposite (or inverse) of the other.

Stereocenters and Meso Compounds

Stereocenters Other than Carbon Nitrogen atoms can be sp3 hybridized, and can therefore have a tetrahedral electron geometry. A nitrogen atom bonded to four different substituents, such as in an ammonium ion, is a stereocenter.

Nitrogen Inversion The nitrogen atom in NRR’R”, such as methylethylamine, is potentially a stereocenter, so the molecule is potentially chiral.

Nitrogen Inversion continued… The two methylethylamine species rapidly interconvert and cannot be isolated, so methylethylamine is achiral and its nitrogen atom is not a stereocenter. The process by which NRR’R” species interconvert is called nitrogen inversion.

Diastereomers Diastereomers are stereoisomers that are not mirror images of each other. Cis-1,2-dichloroethene and trans-1,2-dichloroethene, are diastereomers. These have the same molecular formula and the same connectivity, but they are different molecules (chlorine atoms are on opposite sides. Also, they are not mirror images of each other.

Determining the Maximum Number of Stereoisomers Because a new configurational isomer can be obtained for each inversion of a tetrahedral stereocenter’s configuration, the number of configurational isomers that exist can double with the addition of each tetrahedral stereocenter. The maximum number of configurational isomers that can exist for a molecule with n tetrahedral stereocenters is 2n. Fewer than 2n configurational isomers exist when at least one of the isomers is a meso compound.

5.6 Fischer Projections and Stereochemistry The Fischer projection is a convenient way to depict complex molecules having more than one stereocenter. The intersection of a horizontal line and a vertical line indicates a carbon stereocenter. The substituents on the horizontal bonds are understood to point toward you (like a bowtie), whereas the substituents on the vertical bonds are understood to point away from you.

Manipulating a Fischer Projection

5.7 Strategies for Success: Converting Between Fischer Projections and Zigzag Conformations A molecule represented in a zigzag chain can still be converted to a Fischer projection. C1 is part of the CO2H group and C7 is part of the CH2OH group, so neither is a stereocenter. All that’s left to do is to place an H and an OH on each of the stereocenters.

Building a Complex Fischer Projection Which substituent should be placed on the left of each stereocenter and which should be placed on the right? This choice dictates each stereocenter’s specific configuration.

Converting the Zigzag Chain to a Fischer A molecular model is helpful when converting a zigzag structure to a Fischer projection. Steps For each stereocenter with the horizontal bonds pointing toward us, simply add the substituents on the left and right of the Fischer projection as they appear in the molecular model. Turn the molecule over so that the remaining stereocenters have their horizontal bonds pointing toward us, and repeat Step 1.

Converting the Zigzag Chain to a Fischer continued…

Converting the Fischer to a Zigzag Steps For each stereocenter in the model in which the horizontal bonds are pointing toward us, attach the substituents on the left and right as they appear in the Fischer projection. Turn the molecule over so that the remaining stereocenters have their horizontal bonds pointing toward us and repeat Step 1.

5.8 Physical and Chemical Properties of Isomers Constitutional Isomers Due to different connectivities, these isomers must have different physical and chemical properties. Enantiomers Have the same connectivities and precisely the same polarities.

Physical and Chemical Properties of Isomers continued… Diastereomers Just as with enantiomers, diastereomers have the same connectivity. They are not mirror images of each other, however, so they must behave differently (chemically). Diastereomers must have different physical and chemical properties.

5.9 Stability of Double Bonds and Chemical Properties of Isomers Alkyl substitution is the number of alkyl groups bonded to the alkene carbon atoms. The greater the degree of alkyl substitution the more stable the alkene. The stability of the alkene is observed in its heat of combustion (DHc).

Heats of Combustion of the Isomeric Alkenes of C6H12 Double bond stability increases as the amount of alkyl substitution increases. Trans-alkenes are more stable than cis-alkenes due to having less steric repulsion.

5.10 Separating Configurational Isomers Since diastereomers have different physical properties they can often be separated by common laboratory techniques such as fractional distillation, crystallization, and simple chromatography. Enantiomers cannot be separated by these methods in an achiral environment.

Louis Pasteur Louis Pasteur was the first to isolate a pair of enantiomers from each other. Pasteur noted that the crystals appeared to grow in one of two varieties—left-handed crystals and right-handed crystals—that are mirror images of each other Pasteur physically separated the two types of crystals using tweezers.

Separating Enantiomers Separating enantiomers the way that Pasteur did is not feasible in most situations. A different way to separate enantiomers takes advantage of diastereomers having different physical properties. Option for Separating Enantiomers Temporarily convert the enantiomers into a pair of diastereomers (will now have different physical properties). Separate those diastereomers from each other by exploiting their different physical and chemical properties. Regenerate the enantiomers from the separated diastereomers.

5.11 Optical Activity Chiral molecules interact with plane-polarized light. When all photons from a light source have their electric fields oscillating in the same plane, then the light is plane polarized.

The Polarizer Most light sources emit light that is unpolarized. A polarizer generates plane-polarized light by filtering out light whose electric field oscillates in any other plane. If plane-polarized light passes through a sample of a compound, the plane in which the light is polarized can change, depending upon whether the compound is chiral or achiral.

Enantiomers can Plane Polarized Light One enantiomer rotates polarized light in one direction while the other enantiomer rotates it in the opposite direction. Enantiomers have identical physical and chemical properties except the direction at which they rotate polarized light.

Optical Activity The angle a chiral compound rotates plane-polarized light, called the measured angle of rotation ([a]), can be obtained using an analyzer. Light enters the analyzer after it exits the sample. Chiral compounds that rotate light clockwise (in the + direction) are called dextrorotatory, and those that rotate light counterclockwise (in the - direction) are called levorotatory. The direction of rotation generally is unknown without performing the experiment.

Factors That Govern the Angle of Rotation As the concentration (c) of a chiral compound increases, so does the angle of rotation. As the length of the sample (l) increases, so does the angle of rotation. The specific rotation, [a]lT, is a constant that is characteristic of a chiral compound’s propensity to rotated plane-polarized light. By convention, c is in units of g/mL and l is in units of decimeters (dm) (1 dm = 1/10 meter). Enantiomers have equal but opposite [a]lT.

Racemic Mixture and Enantiomeric Excess A racemic mixture contains equal amounts of the (+) and (-) enantiomers of a chiral molecule. Light traveling through a racemic mixture encounters an equal number of molecules of each enantiomer. A racemic mixture of enantiomers is optically inactive, despite being made up of chiral molecules. If a mixture of enantiomers is not racemic, then it will be optically active. The excess percentage that favors one enantiomer is the enantiomeric excess (ee), which is viewed as being composed of one of the pure enantiomers.

5.13 The Chirality of Biomolecules Thalidomide is teratogenic (causes birth defects). It is estimated that more than 10,000 children worldwide were born with deformed or missing limbs. Thalidomide is chiral and was sold as a racemic mixture of its two enantiomers. The enantiomer on the left is primarily responsible for reducing nausea, whereas the one on the right is responsible for the teratogenic properties.

5.14 The D/L System for Classifying Monosaccharides and Amino Acids Each chiral amino acid and monosaccharide has two enantiomers, specified using the D/L system. The basis of the D/L system is the optical rotation of glyceraldehyde. In the Fischer projection of any D sugar, the OH group of the highest numbered stereocenter is on the right.

5.15 The D Family of Aldoses

Summary and Conclusions A variety of isomers types were examined in this chapter. A molecule is chiral if it has an enantiomers. If it does not, it is achiral. Enantiomers and diastereomers are types of configurational isomers. Enantiomers are mirror images of each other, while diastereomers are not. A tetrahedral atom bonded to four different substituents is called a stereocenter. Meso compounds, although having tetrahedral stereocenters, are overall achiral as a result of an internal plane of symmetry.

Summary and Conclusions continued… Fischer projections are convenient ways of depicting complicated molecules that have more than one stereocenter. Alkyl substitution affects the stability of alkenes (can be observed experimentally by their heats of combustion). Chiral compounds can be detected and their concentrations measured by using plane-polarized light. Enantiomers have equal but opposite specific rotations. In Chapter 8 (and will apply throughout the rest of the book), when a reaction produces a mixture of configurational isomers, we will be able to determine whether they will be produced in equal or unequal amounts.