5.2 Chiral Centers and Chirality

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Chirality

A chiral molecule is one that is not identical to its mirror image, but it is often technically defined has having a nonsuperimposable mirror image which we identified in the last lesson as its enantiomer.  And molecules don't have the monopoly on chirality as many objects from our every day experience are chiral, most notably our hands.

chiral hands

Our hands are reflections of each other but are not identical.  That's why both right-handers and left-handers baseball gloves are produced.  They are made unique to the hand they'll be worn on depending upon whether the player is right-handed or left-handed.  In fact we often loosely distinguish between a pair of enantiomers by referring to one as the right-handed enantiomer and the other as the left-handed.

But enantiomers are difficult to distinguish from one another as all of their physical properties (melting point, boiling point, dipole moment, etc.) are identical.  In fact it takes a chiral environment to distinguish between the right-handed and left-handed versions of a chiral compound.  (As baseball gloves are made specific to the right hand or left hand, they too are chiral.)  A great many drugs are chiral and often it is only one of the enantiomers that possesses the desired activity.

The most infamous example of a chiral drug is thalidomide, a sedative that was often also prescribed to pregnant women in the 1950s to treat morning sickness.  It turns out it was the R-isomer that was responsible for these effects.  However, the drug was sold as a racemic mixture, and unfortunately the S-isomer acts as a teratogen causing birth defects.  What you should take away from this is that proteins themselves are chiral and are often found to bind one enantiomer more strongly than another as is the case with thalidomide.  Quite a bit of research regarding thalidomide has been performed and those interested can read more in a great article in Nature.

Chiral Centers

Now that we have a little idea as to the significance of chirality, the question becomes how do we recognize when a molecule is chiral?  The greatest indication of whether or not a molecule will be chiral is the presence of chiral centers.  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.  While not all molecules having chiral centers will be chiral (i.e. meso compounds), the majority will, and there are very few examples of molecules that are chiral without having chiral centers.

 

Let's start by looking at a molecule having just a single chiral center.  A molecule having just one chiral center is chiral, period.  It is only possible to have chiral centers and be achiral (i.e. to be a meso compound) for molecules that have more than one chiral center.

chiral molecule

The compound and its mirror image are not identical (i.e. are nonsuperimposable).  If we take and rotate the molecule on the right 180o out of the plane of the page you can see that the Cl and H are not in the same position.

chiral molecule 2

After rotating the second enantiomer we can see that the ethyl group (green) and methyl group (black) line up and are superimposable.  But the Cl and H are not superimposable.  The only difference between the molecule on the upper left and the molecule on the lower left is that the atoms bonded with the wedged and dashed bonds are switched.  In fact this is at the very heart of the term stereocenter.  A stereocenter is an atom where switching two groups results in a different stereoisomer.  And it is not limited to switching the wedged and dashed bond (though this is the most common); switching any two groups on a chiral center will get you the other version.

This now gives us two ways to recognize when we have the reflected version of a chiral center:

1. When it is simply drawn as a reflection.

nonsuperimposable mirror images

2. When two groups have traded places on a chiral center (groups attached with wedged and dashed bonds switched here)

enantiomers stereocenter

Both of these will be important in learning how to recognize the exact relationship between two molecules which we'll be addressing in a lesson later in this chapter (5.6 Determining the Relationship Between a Pair of Molecules).

How to Identify Chiral Centers

A common question on this exam for undergraduates is to indicate the number of chiral centers in a molecule (often a multiple choice question) or to identify all the chiral centers in a molecule (often by circling them).  Identifying chiral centers seems straightforward enough; just identify the tetrahedral atoms that are bonded to four different groups, right.  It really is that straightforward, but that doesn't mean it's always easy.  For larger molecules I recommend you take a systematic approach.  Let's identify all the chiral centers in the following molecule:

how to identify chiral centers 1

1. Chiral centers must be tetrahedral atoms (sp3 hybridized), so eliminate all atoms that are sp or sp2 hybridized from consideration.  There are 8 sp2 hybridized carbon atoms in this molecule and I've crossed them out below.

how to identify chiral centers 2

2. Chiral centers must be bonded to 4 different groups.  Any carbon bonded to two or more hydrogen atoms won't be bonded to four different groups and can be eliminated from consideration.  There are 6 such atoms crossed out below.

how to identify chiral centers 3

3. Chiral centers must be bonded to 4 different groups.  Any atom very obviously bonded to two (or more) identical groups won't be bonded to four different groups and can be eliminated from consideration.  There is 1 such atom crossed out below.  It is bonded to two methyl groups.

how to identify chiral centers 4

4. Examine the remaining atoms to see if they are indeed bonded to 4 different things.  At this point there are only three carbon atoms remaining to examine (the oxygen atom is sp3 hybridized but 2 of its 4 electron domains are lone pairs of electrons and it won't therefore have 4 different groups).

how to identify chiral centers 5

We'll examine the remaining atoms one at a time.

how to identify chiral centers 6

The carbon circled in blue in the above image is bonded to 3 carbon atoms and a hydrogen atom.  All three carbon atoms are unique (i.e. part of a distinct group) however, and the circled carbon atom is indeed a chiral center.  One of the carbon atoms it's bonded to is a methyl carbon and is easily seen as different than the other two carbon atoms.  The last two carbon atoms are both members of rings and are a little more difficult to distinguish.  Rather than worry about what they're attached to and following that until we find a difference, it's actually easier just to compare the entire side of the molecule each is on at once.  I've drawn a plane (blue dashed line) through the carbon under examination and between the two carbon atoms (in red) we're comparing.  The only way these two carbon atoms would be equivalent is if the entire part of the molecule left of the dashed line was exactly the same as the entire part of the molecule right of the dashed line, and it is easy to see that they are not.

how to identify chiral centers 7

The carbon circled in blue in the above image is bonded to 2 carbon atoms, an oxygen atom, and a hydrogen atom.  The two carbon atoms (in red) are unique, and the blue circled carbon atom is indeed a chiral center.  The two carbon atoms are easily identified as distinct as they differ in hybridization and one is part of a ring while the other isn't.  But once again I prefer to just compare the entire side of the molecule each is on at once.  I've drawn a plane (blue dashed line) through the carbon under examination and between the two carbon atoms (in red) we're comparing.  The parts of the molecules on either side of the dashed line are quite obviously different indicating again that these two carbon atoms are distinct.

how to identify chiral centers 9

The carbon circled in blue in the above image is bonded to 3 carbon atoms and a hydrogen atom.  All three carbon atoms are unique, and the circled carbon atom is indeed a chiral center.  One of the carbon atoms it's bonded to is a methyl carbon and is easily seen as different than the other two carbon atoms.  The remaining two carbon atoms it is bonded to can be distinguished as one is bonded to two hydrogen atoms and the other only one.  But once again I prefer to just compare the entire side of the molecule each is on at once.  I've drawn a plane (blue dashed line) through the carbon under examination and between the two carbon atoms (in red) we're comparing.  The parts of the molecules on either side of the dashed line are quite obviously different indicating again that these two carbon atoms are distinct.

And there you have it; this molecule has 3 chiral centers (circled in blue in the image below).

how to identify chiral centers ten

Chiral Centers Besides Carbon?

Chiral centers don't necessarily have to be carbon, but there are two reasons most of the examples you'll see in an organic chemistry course will be.

 

1. This is organic chemistry, the chemistry of carbon.

 

2. Carbon can make 4 bonds and most other atoms you're likely to find in organic molecules usually don't.  This limits the possible atoms that might be bonded to 4 different things.

 

But one of the 4 different things an atom is bonded to doesn't actually have to involve another atom or a bond; 1 of the 4 things can be a lone pair of electrons.  We'll see something unusual with nitrogen for many amines at the end of this chapter (5.7 Amine Inversion and Chiral Molecules without Chiral Centers) so I'll ignore nitrogen for now, but check out the following ion in which sulfur is a chiral center.  The sulfur atom is bonded to the carbon of a methyl group, the carbon of an ethyl group, the carbon of a propyl group, and has a lone pair of electrons.

sulfur chiral center

Now that we know what a chiral center is and how to identify them, we'll learn how to assign absolute configurations, R and S, in the next lesson (5.3 Absolute Configurations: Assigning R and S).