5.1 Overview of Isomerism and Stereoisomers

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Constitutional Isomers and Stereoisomers

constitutional isomers and stereoisomers

Constitutional Isomers (a.k.a. Structural Isomers)

Constitutional isomers, also known as structural isomers, have the same molecular formula (i.e. are isomers) but have a different 'bond connectivity.'  Below are a couple of examples.

Constititutional Isomers Example 1
Constititutional Isomers Example 2

Stereoisomers

Stereoisomers have the same 'bond connectivity' but a different 3D spatial arrangement of the atoms.  There are two types of stereoisomers, enantiomers and diastereomers.  Stereoisomers that are mirror images are termed enantiomers (often technically defined as nonsuperimposable mirror images).  Stereoisomers that are not mirror images are termed diastereomers (often technically defined as nonsuperimposable non-mirror images).

 

Enantiomers, being reflections of each other, have the same physical characteristics: same melting point, same boiling point, same dipole moment etc.  This can make them difficult to separate.  Most separation techniques are based upon some difference in these physical characteristics between the compounds being separated.  Distillation works due to a difference in boiling point, and column chromatography works due to a difference in polarity, and neither can be used to separate a pair of enantiomers.  Diastereomers on the other hand usually have different physical characteristics and can often be separated by conventional means. 

 

Stereoisomers are generally possible with two main molecular features:

 

1. Cis/Trans isomers - These are possible for many alkenes and cycloalkanes.  Cis/Trans isomers are never mirror images and are therefore diastereomers.

 

2. Stereoisomers having chiral centers - Most stereoisomers discussed in this chapter will fall into this category.

 

Chiral centers are tetrahedral atoms (sp3 hybridized) that are bonded to 4 different groups.  In organic chemistry most chiral centers will be carbon atoms, but chiral centers could technically be any tetrahedral atom.  Chiral centers go by many names: chirality centers, stereogenic centers, asymmetric centers, and they are the most common example (but not the only example) of stereocenters.

 

Stereoisomers having chiral centers may either be enantiomers or diastereomers depending upon the comparison.  Below are a couple of examples of stereoisomers.  You should notice that they all have the same bond connectivity and that this is also evident in their names; the only differences in the names of stereoisomers are stereochemical designations at the beginning of the names (cis vs trans and R vs S).  We'll learn how to assign R and S later in this chapter (5.3 Absolute Configurations: Assigning R and S) and a new designation for alkenes, E and Z, in a later lesson on naming alkenes (7.5 Nomenclature of Alkenes).

Cis/Trans Isomers

diastereomers 1
diastereomers 2

Isomers Having Chiral Centers

enantiomers
diastereomers 3

Chiral vs Achiral

Chiral molecules are those that have nonsuperimposable (non-identical) mirror images (i.e. enantiomers), whereas achiral molecules are those that are identical (superimposable) to their mirror images.  To rephrase this:

 

The mirror image of a chiral molecule is its enantiomer.

 

The mirror image of an achiral molecule is identical to the original molecule (achiral molecules do NOT have enantiomers).

 

An example of a chiral and an achiral molecule are shown below:

Chiral

chiral molecule

Achiral

achiral molecule

Both examples above are shown alongside their reflection across a mirror plane.  The chiral molecule is nonsuperimposable (non-identical) with its reflection which is its enantiomer.  Whereas the achiral molecule is superimposable (identical) with its reflection in every respect.

The vast majority of chiral compounds have chiral centers, and therefore when trying to identify a molecule as chiral one should look for the presence of chiral centers.  Though rare, we will learn in a future lesson (5.7 Amine Inversion and Chiral Molecules without Chiral Centers) that there are a couple of molecules that are chiral even though they don't have chiral centers.  This is a relatively minor occurrence and many undergraduates are never even presented with these examples.

More importantly, there are many compounds that have chiral centers and are still achiral.  I like to think of them as exceptions, and they get a special name: meso compounds.  We'll learn more about them later in this chapter (5.4 Molecules with Multiple Chiral Centers), but for now the definition will suffice: meso compounds are achiral compounds that have chiral centers.

So when trying to identify a molecule as chiral, start by looking for chiral centers.  But it turns out there is a trick for identifying achiral molecules as well: any molecule with an internal mirror plane of symmetry (often termed a sigma plane) will be identical to its reflection and is achiral.  There are no exceptions either.  If a molecule has a sigma plane, it is achiral.  If we revisit methylcyclohexane which was identified as achiral above we can readily identify a sigma plane.

achiral sigma plane

However, a molecule only needs to have a sigma plane in any one of its rotational conformations to be achiral, and such a sigma plane may not be obvious.  In examining the molecule below on the left it may be difficult to recognize that it has a sigma plane.  Rotation around one of the C-C bonds makes it much easier to see. 

achiral sigma plane 2

The moral of the story is that it is not always straightforward to identify sigma planes.  Just because you can't find one don't immediately assume the molecule is chiral (though this is often true).  But if you do find a sigma plane the molecule is for sure achiral.  The example above is a meso compound fyi; it is achiral even though it has two chiral centers.

Optical Activity

There is another major difference between chiral and achiral molecules:  optical acitivity.  It turns out that chiral molecules rotate plane-polarized light and are termed optically active, whereas achiral molecules do not.

 

Light, with its wavelike characteristics can have its 'wave' oriented in any plane.  This is exactly the case with unpolarized light which has light in all possible orientations.  But when it is passed through a polarizing filter all orientations except for largely one are blocked.  The light that passes through is largely of a single orientation (plus or minus a few degrees) and is said to be plane-polarized.  If plane-polarized light passes through a solution of an achiral compound it will leave the solution with the same orientation with which it entered.  But when plane-polarized light passes through a solution of a chiral compound it will leave the solution rotated relative to the orientation with which it entered.  The degree of rotation will be dependent upon the identity and concentration of the compound and upon the path length of the solution, but the direction it is rotated is intrinsic to the particular enantiomer.  We'll get more into the numbers regarding this later in the chapter (5.8 Optical Activity).

 

Enantiomers always rotate plane-polarized light by the same degree (assuming equal concentrations and path lengths) but in opposite directions, and this can be used as an identifying characteristic for the two enantiomers.  The direction and degree of rotation is measured by a polarimeter.  The enantiomer that results in rotation to the right (clockwise) is termed the '+' or 'd' isomer (d is short for dextrarotatory).  The enantiomer that results in rotation to the left (counterclockwise) is termed the '-' or 'l' isomer (l is short for levorotatory).

dextrorotatory and levorotatory

+/- and d/l are referred to as relative configurations.  Whether we use the +/- or d/l convention it is worth noting that these configurations must be determined using a polarimeter; it is not possible to predict the direction of rotation by a simple inspection of the structure of the particular enantiomer.  But once you've identified the direction of rotation in one enantiomer, you know it will be the opposite direction for the other enantiomer.  In the next lesson we'll learn about the absolute configurations R and S (5.3 Absolute Configurations: Assigning R and S) which can be determined by a simple inspection of the structure of the particular enantiomer.

We'll end this discussion with the introduction of one more term: a racemic mixture.  A racemic mixture is a 50/50 mixture of enantiomers.  As half the molecules in the mixture will rotate plane-polarized light in one direction and half in the opposite direction, plane-polarized light is not rotated on average, and therefore a racemic mixture is optically inactive.

To summarize:

  • Chiral compounds are optically active.
  • Achiral compounds are optically inactive.
  • Racemic mixtures are optically inactive.