BS

Chapter 5: Stereoisomerism

  • Overview of Isomerism

    • isomers are compounds made of the same atoms with certain differences.

    • stereoisomers and constitutional isomers are both examples (differing in configuration or connectivity respectively)

    • examples of stereoisomerism can be cis-trans in which substituents exist on the same or opposite face of a double bond

    • cis-trans doesn’t apply to disubstituted alkenes

  • Introduction to Stereoisomerism

    • chirality

      • objects can have a mirror image. Some objects and their mirror image are identical to each other and are said to be superimposable

      • for others, the two aren’t identical and are therefore nonsuperimposable. For example, your left and right hands

      • objects that are nonsuperimposable to their mirror image are therefore also called chiral objects.

    • molecular chirality

      • molecular chirality is more common in sp³/tetrahedral carbon atoms with four different groups connected to it. In these cases, there are two ways that the groups can be arranged around the central carbon, which are nonsuperimposable mirror images of each other

      • by IUPAC rules, a tetrahedral carbon with four different groups is called a chirality center. More common names include chiral center, stereocenter, stereogenic center, or asymmetric center.

    • enantiomers

      • the nonsuperimposable mirror image of a chiral compound is called its enantiomer. The two are called a pair of enantiomers

      • enantiomer is used similarly to the word ‘twin’

  • Designating Configuration Using the Cahn-Ingold-Prelog System

    • Steps of classifying and naming enantiomers;

      • after the chiral center/s have been identified, the groups are named with 1 being the highest priority and 4 being the lowest. The largest atomic number receives the highest priority and the smallest receives the lowest.

      • Then, move or reconsider the molecule so that the lowest priority group is facing away from you (on the dashed bond)

      • Then the 1-2-3 sequence is read to see its direction upon which point the classification R (clockwise) and S (counterclockwise) is assigned

      • If the lowest priority is facing forward (on the wedged bond) simple reverse the observed direction (R→S, and S→R)

      • then, R or S is placed in front of the IUPAC name in parenthesis with the number corresponding to it’s position

    • assigning priorities to all four groups

      • sometimes groups and the atoms directly bonded to a chiral center are the same or very similar while the groups remain different; i.e. when there are 2 or more unique R groups

      • Then, list the atoms that are directly connected to the equivalent ones (excluding the chiral center itself), and evaluate those. If these are equivalent, move back one more on the C-chain until there is a deviation.

      • Double bonded atoms are counted twice, same for triple bonds

    • rotating the molecule

      • an easy trick for rotating a molecule is to just switch any two adjacent groups which inverts the molecule

      • for example: switching the dashed and wedged bonds can put the lowest priority in the correct position

    • designating configuration in IUPAC Nomenclature

      • enantiomer configuration is indicated by putting R or S in parenthesis and italicized in front of the regular IUPAC name and separating by a hyphen.

      • Multiple chiral centers must be indicated by corresponding number to their positions.

  • Optical Activity

    • enantiomers have identical physical properties such as the same boiling point since they have the same connectivity and relative stability

    • plane-polarized light

      • light is made of oscillating electric and magnetic fields in space. Each field is on a plane which are perpendicular to each other. the orientation of each field is called polarization of the light wave

      • when light passes through a polarizing filter, only particularly polarized photons are allowed through which creates plane-polarized light

      • plane polarized can only pass through a second filter if it is correctly oriented to do so

    • polarimetry

      • optically active compounds are certain organic compounds that can rotate the plane of plane-polarized light

      • those that can’t are optically inactive

      • this rotation is measured using a polarimeter.

        • The light source is typically a sodium lamp that emits a specific wavelength called the D line of sodium

        • the light passes through a polarizing filter and the resulting plane-polarized light continues through a tube with an optically active compound in solution, which rotates the plane

        • polarization of the resulting light can be determined by rotating a second filter and observing which orientation allows light through.

    • source of optical activity

      • optical activity is directly related to chirality.

      • chiral compounds are optically active and achiral aren’t

      • enantiomers will rotate the plane of light equally but in different directions

    • specific rotation

      • the observed rotation of a chiral compound depends on the number of molecules encountered as the light passes through the solution. As concentration increases, so does observed rotation

      • this is also true for pathlength or the distance the light travels to through the solution

      • a set of standard conditions was set to compare compounds (standard concentration is 1g/ml and standard pathlength is 1dm) and find the specific rotation (the observed rotation under these conditions)

      • specific rotation = [alpha]= alpha/c*l where [a] is specific rotation, a is observed rotation, c is concentration, and l is the pathlength

      • specific rotation is also sensitive to temperature and wavelength but these conditions can’t be considered in the equation since it isn’t linear relationship thus they are reported in junction with the specific rotation

      • rotation of enantiomers

        • enantiomers are equal in magnitude but have an opposite direction

        • those with a positive rotation are dextrorotatory

        • those with a negative rotation are levorotatory

    • enantiomeric excess

      • solutions with a single enantiomer are optically/enantiomerically pure in that the other enantiomer is completely absent

      • a racemic mixture contains equal amounts of both enantiomers and is optically inactive due to the conflicting optical nature of each enantiomer

      • solutions that have both in unequal amounts are optically active and is defined as having a percentage of enantiomeric excess calculated by subtracting the smaller percentage from the larger one

      • also calculated as the specific rotation of the mixture over the specific rotation of the pure enantiomer and multiplied by 100

  • Stereoisomeric Relationships: Enantiomers and Diastereomers

    • stereoisomers can be divided into two categories: enantiomers (which are nonsuperimposable mirror images) and diastereomers (which are nonsuperimposable but NOT mirror images)

    • the definition of diastereomer explains why cis-trans isomers are that and not enantiomers

    • this is an important consideration when looking at molecules with multiple chiral centers

    • a pair of cis-trans isomers of a molecule with two chiral centers will further have two sets of enantiomers each. The cis conformations are enantiomers, and the trans conformations are enantiomers to each other, but a cis enantiomer will be a diastereomer to a trans enantiomer

    • For three chiral centers, there are four possible sets of enantiomers that will be diastereomers to each other

    • therefore, the maximum amount of stereoisomers is 2^n where n is the number of chiral centers

  • Symmetry and Chirality

    • rotational symmetry verses reflectional symmetry

      • compounds that contain only one chiral center will be chiral, but compounds that contain two or more might not be

      • there are two types of symmetry

        • rotational symmetry involves an axis of symmetry

        • reflectional symmetry involves a plane or a point of symmetry

      • If a compound exhibits neither type of symmetry, than it is chiral

    • meso compounds

      • compounds that exhibit symmetry despite having chiral centers are meso compounds

      • a family of stereoisomers containing a meso compound will have less than the calculated 2^n stereoisomers since some of the pairs might be the same compound as they do not exhibit enantiomers

  • Fischer Projections

    • Portrays compounds with many chiral centers

    • chiral centers are represented by horizontal lines (coming out of the page) and vertical lines (behind the page)

    • used mostly for analyzing sugars, but also helpful for comparing stereoisomers

  • Conformationally Mobile Systems

    • the conformations of butane undergo constant rotation around the single bonds

    • chiral centers don’t invert configuration in the same way

    • similarly, substituted cyclohexanes also undergo rotation around single bonds which renders a lot of them achiral and optically inactive

    • evaluating chirality is a simple process to determine the optical activity of cyclic compounds.