Objectives

After completing this section, you should be able to

1. use molecular models to show that only a tetrahedral carbon atom satisfactorily accounts for the lack of isomerism in molecules of the type CH₂XY, and for the existence of optical isomerism in molecules of the type CHXYZ.
2. determine whether two differently oriented wedge-and-broken-line structures are identical or represent a pair of enantiomers.

Chiral Molecules

The term chiral, from the Greek work for ‘hand’, refers to anything which cannot be superimposed on its own mirror image. Certain organic molecules are chiral meaning that they are not superimposable on their mirror image. Chiral molecules contain one or more chiral centers, which are almost always tetrahedral (sp³-hybridized) carbons with four different substituents. Consider the molecule A below: a tetrahedral carbon, with four different substituents denoted by balls of four different colors.

The mirror image of A, which we will call B, is drawn on the right side of the figure, and an imaginary mirror is in the middle. Notice that every point on A lines up through the mirror with the same point on B: in other words, if A looked in the mirror, it would see B looking back.

Now, if we flip compound A over and try to superimpose it point for point on compound B, we find that we cannot do it: if we superimpose any two colored balls, then the other two are misaligned.

A is not superimposable on its mirror image (B), thus by definition A is a chiral molecule. It follows that B also is not superimposable on its mirror image (A), and thus it is also a chiral molecule.

A and B are called stereoisomers or optical isomers: molecules with the same molecular formula and the same bonding arrangement, but a different arrangement of atoms in space. Enantiomers are pairs of stereoisomers which are mirror images of each other: thus, A and B are enantiomers. It should be self-evident that a chiral molecule will always have one (and only one) enantiomer: enantiomers come in pairs. Enantiomers have identical physical properties (melting point, boiling point, density, and so on). However, enantiomers do differ in how they interact with polarized light (we will learn more about this soon) and they may also interact in very different ways with other chiral molecules – proteins, for example. We will begin to explore this last idea in later in this chapter, and see many examples throughout the remainder of our study of biological organic chemistry.

Let’s apply our chirality discussion to real molecules.

Consider 2-butanol, drawn in two dimensions below.

Carbon #2 is a chiral center: it is sp³-hybridized and tetrahedral (even though it is not drawn that way above), and the four substituents attached to is are different: a hydrogen (H) , a methyl (-CH₃) group, an ethyl (-CH₂CH₃) group, and a hydroxyl (OH) group. If the bonding at C₂ of 2-butanol is drawn in three dimensions and this structure called A. Then the mirror image of A can be drawn to form structure B.

When we try to superimpose A onto B, we find that we cannot do it. Because structure A and B are not superimposable on their mirror image they are both chiral molecules. Because A and B are different due only to the arrangement of atoms in space they are stereoisomers. Because A and B are mirror images of each other they are also enantiomers. When looking at simplified line structures is clear that there are two distinct ways of drawing 2-butanol which only differ in their spatial arrangement around a chiral carbon.

The 3D Structures of the Two Enantiomers of 2-Butanol

For comparison, 2-propanol, is an achiral molecule because is lacks a chiral carbon. Carbon #2 is bonded to two identical substituents (methyl groups), and so it is not a chiral carbon. Being achiral means that 2-propanol should be superimposable on its mirror image which is shown in the figure below. A more detailed explaination on why 2-propanol is achiral will be given in the next section.

2-propanol is achiral:

Stereoisomers

Stereoisomers have been defined as molecules with the same connectivity but different arrangements of the atoms in space. It is important to note that there are two types of stereoisomers: geometric and optical.

Optical isomers are molecules whose structures are mirror images but cannot be superimposed on one another in any orientation. Optical isomers have identical physical properties, although their chemical properties may differ in asymmetric environments. Molecules that are nonsuperimposable mirror images of each other are said to be chiral. Optical activity will be discussed in more detail in Section 8.3.

Geometric isomers differ in the relative position(s) of substituents in a rigid molecule. Simple rotation about a C–C σ bond in an alkene, for example, cannot occur because of the presence of the π bond. The substituents are therefore rigidly locked into a particular spatial arrangement. Thus a carbon–carbon multiple bond, or in some cases a ring, prevents one geometric isomer from being readily converted to the other. The members of an isomeric pair are identified as either cis or trans, and interconversion between the two forms requires breaking and reforming one or more bonds. Because their structural difference causes them to have different physical and chemical properties, cis and trans isomers are actually two distinct chemical compounds.mers have the same connectivity, but different arrangements of atoms in space. Geometric isomers will be discussed in more detain in Sections 8.5.

Symmetry and Chirality

Molecules that are nonsuperimposable mirror images of each other are said to be chiral (pronounced “ky-ral,” from the Greek cheir, meaning “hand”). Examples of some familiar chiral objects are your hands. Your left and right hands are nonsuperimposable mirror images. (Try putting your right shoe on your left foot—it just doesn’t work.) An achiral object is one that can be superimposed on its mirror image, as shown by the superimposed flasks 25.7.1b in the figure below. 25.7.1b.

An an important questions is why is one chiral and the other not? The answer is that the flask has a plane of symmetry and your hand does not. A plane of symmetry is a plane or a line through an object which divides the object into two halves that are mirror images of each other. When looking at the flask, a line can be drawn down the middle which separates it into two mirror image halves. However, a similar line down the middle of a hand separates it into two non-mirror image halves. This idea can be used to predict chirality. If an object or molecule has a plane of symmetry it is achiral. If if lacks a plane of symmetry it is chiral.

Symmetry can be used to explain why a carbon bonded to four different substituents is chiral. When a carbon is bonded to fewer than four different substituents it will have a plane of symmetry making it achiral. A carbon atom that is bonded to four different substituents loses all symmetry, and is often referred to as an asymmetric carbon. The lack of a plane of symmetry makes the carbon chiral. The presence of a single chiral carbon atom sufficient to render the molecule chiral, and modern terminology refers to such groupings as chiral centers or stereo centers.

An example is shown in the bromochlorofluoromethane molecule shown in part (a) of the figure below. This carbon, is attached to four different substituents making it chiral. which is often designated by an asterisk in structural drawings. If the bromine atom is replaced by another chlorine to make dichlorofluoromethane, as shown in part (b) below, the molecule and its mirror image can now be superimposed by simple rotation. Thus the carbon is no longer a chiral center. Upon comparison, bromochlorofluoromethane lacks a plane of symmetry while dichlorofluoromethane has a plane of symmetry.

Identifying Chiral carbons

Identifying chiral carbons in a molecule is an important skill for organic chemists. The presence of a chiral carbon presents the possibility of a molecule having multiple stereoisomers. Most of the chiral centers we shall discuss in this chapter are asymmetric carbon atoms, but it should be recognized that other tetrahedral or pyramidal atoms may become chiral centers if appropriately substituted. Also, when more than one chiral center is present in a molecular structure, care must be taken to analyze their relationship before concluding that a specific molecular configuration is chiral or achiral. This aspect of stereoisomerism will be treated later. Because an carbon requires four different substituents to become asymmertric, it can be said, with few exceptions, that sp² and sp hybridized carbons involved in multiple bonds are achiral. Also, any carbon with more than one hydrogen, such as a -CH₃ or -CH₂– group, are also achiral.

Looking for planes of symmetry in a molecule is useful, but often difficult in practice. It is difficult to illustrate on the two dimensional page, but you will see if you build models of these achiral molecules that, in each case, there is at least one plane of symmetry, where one side of the plane is the mirror image of the other. In most cases, the easiest way to decide whether a molecule is chiral or achiral is to look for one or more stereocenters – with a few rare exceptions, the general rule is that molecules with at least one stereocenter are chiral, and molecules with no stereocenters are achiral.

Determining if a carbon is bonded to four distinctly different substituents can often be difficult to ascertain. Remember even the slightest difference makes a substituent unique. Often these difference can be distant from the chiral carbon itself. Careful consideration and often the building of molecular models may be required. A good example is shown below. It may appear that the molecule is achiral, however, when looking at the groups directly attached to the possible chiral carbon, it is clear that they all different. The two alkyl groups are differ by a single -CH₂– group which is enough to consider them different.

Here are some more examples of chiral molecules that exist as pairs of enantiomers. In each of these examples, there is a single stereocenter, indicated with an arrow. (Many molecules have more than one stereocenter, but we will get to that that a little later!)

Here are some examples of molecules that are achiral (not chiral). Notice that none of these molecules has a stereocenter.

It is difficult to illustrate on the two dimensional page, but you will see if you build models of these achiral molecules that, in each case, there is at least one plane of symmetry, where one side of the plane is the mirror image of the other. Chirality is tied conceptually to the idea of asymmetry, and any molecule that has a plane of symmetry cannot be chiral. When looking for a plane of symmetry, however, we must consider all possible conformations that a molecule could adopt. Even a very simple molecule like ethane, for example, is asymmetric in many of its countless potential conformations – but it has obvious symmetry in both the eclipsed and staggered conformations, and for this reason it is achiral.

Looking for planes of symmetry in a molecule is useful, but often difficult in practice. In most cases, the easiest way to decide whether a molecule is chiral or achiral is to look for one or more stereocenters – with a few rare exceptions (see section 3.7B), the general rule is that molecules with at least one stereocenter are chiral, and molecules with no stereocenters are achiral. Carbon stereocenters are also referred to quite frequently as chiral carbons.

When evaluating a molecule for chirality, it is important to recognize that the question of whether or not the dashed/solid wedge drawing convention is used is irrelevant. Chiral molecules are sometimes drawn without using wedges (although obviously this means that stereochemical information is being omitted). Conversely, wedges may be used on carbons that are not stereocenters – look, for example, at the drawings of glycine and citrate in the figure above. Just because you see dashed and solid wedges in a structure, do not automatically assume that you are looking at a stereocenter.

Other elements in addition to carbon can be stereocenters. The phosphorus center of phosphate ion and organic phosphate esters, for example, is tetrahedral, and thus is potentially a stereocenter.

We will see in chapter 10 how researchers, in order to investigate the stereochemistry of reactions at the phosphate center, incorporated sulfur and/or ¹⁷O and ¹⁸O isotopes of oxygen (the ‘normal’ isotope is ¹⁶O) to create chiral phosphate groups. Phosphate triesters are chiral if the three substituent groups are different.

Asymmetric quaternary ammonium groups are also chiral. Amines, however, are not chiral, because they rapidly invert, or turn ‘inside out’, at room temperature.