Recap
In the previous article, we have explained much of basic stereochemistry. Stereoisomers refer to molecules that are different only regarding their spatial arrangements (i.e. these molecules are exactly the same except for how they look in a three-dimensional space). One specific class of stereoisomers is enantiomers, which refer to compounds which rotate plane-polarized light in opposite directions. Only chiral molecules are able to display stereoisomerism, and the presence of chirality is determined by whether plane-polarized light is rotated, not whether the molecule possesses a chiral atom. Molecules which contain an uneven number of chiral atoms are usually chiral themselves; however, molecules which have both a plane of symmetry and chiral atoms are not chiral. They are instead meso compounds, which are unable to rotate plane-polarized light. Finally, equimolar amounts of a pair of enantiomers results in a racemic mixture, where the effects of the enantiomers cancel out and plane-polarized light is not rotated.
Stereocenters (Continued)
We ended off the first part of this article by listing down a few different cases of compounds which are chiral. Such cases include compounds with chiral atoms, of which there are compounds with one chiral carbon or other similar quadrivalent atom, or compounds with a tervalent chiral atom. Recall that for the atom to be chiral, all substituents it is bonded to must be chemically different (therefore, CH3 and CH3CH3 are considered chemically different substituents), not simply the atom. In this next part we will be considering more of such chiral compounds. Firstly, there are what is known as perpendicular dissymmetric planes. Although the name may sound relatively complex, they simply refer to molecules with two planes that are perpendicular with respect to each other. The biphenyl in Fig. 1 is a demonstration of such a molecule. The presence of the large iodine atoms prevents the molecule from being planar, because planarity would lead to destabilizing steric interactions and is therefore not energetically favorable.
Fig. 1: Structure of a chiral biphenyl.
The biphenyls above are also known generally as atropisomers; the term refers to two isomers that are different because of the lack of rotation about a single bond. In the biphenyl, there is also a lack of rotation about the carbon-carbon single bond. Why are biphenyls chiral? As we may notice, there are six chiral atoms in the molecule; the four bonded to the bromine and iodine atoms, as well as the two ‘bridging’ carbon atoms. This would normally cause the molecule to possess a plane of symmetry, however the molecule appears to lack this plane since there cannot be rotation about the single bond, preventing the plane of symmetry from occurring. In other cases of atropisomers, bond rotation may occur after a period of time, giving them a half-life.
Another molecule that displays interesting chemistry is hexahelicene. Hexahelicene, along with meso compounds, are all good reasons why the presence or absence of a stereocenter does not determine whether a molecule is chiral or achiral (not chiral), respectively. In the figure of hexahelicene below, we note that there is a lack of chiral atoms. Despite this, it has been found to rotate plane-polarized light, suggesting that the molecule itself is chiral. For this molecule, as well as the above molecule (the biphenyl atropisomer), another type of chirality, known as axial chirality, is demonstrated. This is a case where one part of a molecule is oriented differently to another part, such that the mirror image of this molecule would not be superimposable onto itself, making it chiral. In such cases, the chirality cannot be pinpointed onto a single atom, but rather on the whole molecule as a whole. The enantiomers of hexahelicene are shown in Fig. 3.
Fig. 2: Structure of hexahelicene.
Fig. 3: Enantiomers of hexahelicene.
Speaking of axial chirality, we will note several other types of molecules where such chirality occurs. This is the case as well in a class of molecules known as cyclophanes (Fig. 4). In such molecules, there are bonds formed between two aromatic rings, creating a cyclic structure. Rotation about the single bond in cyclophanes is not possible since there is considerable ring strain due to the large size of the molecule, and because of this, the mirror image of the cyclophane is not superimposable on it, making it chiral. Furthermore, another cyclic molecule, specifically perchlorotriphenylamine (Fig. 5), is unable to assume planarity due to the large steric hindrance caused by the presence of the moderately-sized chlorine atoms, allowing for axial chirality to occur as well.
Fig. 4: Structure of a cyclophane.
Fig. 5: Structure of perchlorotriphenylamine.
Fischer Projections
It is not always a simple task to depict the stereochemistry of a molecule, especially when the molecule is large and bonds overlap (when the structure is drawn). Another way of representing the structure of three-dimensional molecules, known as the Fischer projection, provides a convenient way for the structure of molecules to be displayed. Normally, the stereochemistry of a molecule is drawn with a ‘dash’ bond signifying the bond facing toward the reader and a ‘wedge bond’ signifying the bond facing away from the reader. In the Fischer projection, horizontal bonds face towards the reader while vertical bonds face away from the reader. This is shown in Fig. 6. Note that only full rotations of the Fischer projection are allowed, as half rotations make the diagram misleading. When two groups on a chiral atom in the diagram are exchanged, the corresponding enantiomer is formed.
Fig. 6: Example of a Fischer projection.
The Fischer projection, however, is only generally used for molecules like sugars, where there are multiple chiral centers (for example, in the sugar depicted above, all four carbons are chiral), because only in the case of chiral atoms can the Fischer projection’s horizontal and vertical bonds be used. When depicting an achiral atom, the ‘normal’ way of drawing bonds has to be applied. This makes the drawing of the Fischer projection more inconvenient the smaller and simpler the molecule, and in those cases the conventional way of drawing structures is typically used instead.
Cahn-Ingold-Prelog System
Lastly for this article, we will be explaining a system on how to distinguish enantiomers. The nomenclature for enantiomers was problematic because the (+) and (-) nomenclature system, used since the 19th century, was inconvenient; x-ray crystallography had to be applied to determine whether the molecule was (+) or (-). A new system, the Cahn-Ingold-Prelog (CIP) system, was later developed to replace this inconvenient system. Instead of using the (+) and (-) signs, the R (rectus) and S (sinister) letters are used for each chiral atom in a molecule; the assignment of R and S is determined by a few rules that are discussed below.
Fig. 7: Structure of 2-chloro-3-methylbutane.
Firstly, the substituents are listed in the order of decreasing atomic number: for example, refer to the figure above (Fig. 7) for the structure of 2-chloro-3-methylbutane. In its case, there is only one chiral atom, the atom bonded to the chlorine. As such, we list the substituents in the order: Cl, C, C, H. We notice that the chiral carbon is bonded to two similar atoms, and as such, we have to apply the next rule: for any two atoms with the same atomic number, we rely on the atomic number of the next atom bonded to these two atoms. The next atom bonded to the 1-carbon is hydrogen (H), while the next atom bonded to the 3-carbon is carbon (C) as well. The same order of precedence is applied as above, making the substituents’ order as such: Cl, C(C), C(H), H. At this point, we have ordered the substituents, so we can stop here.
However, there is still some trouble when we consider divalent or trivalent atoms (nitrogen and oxygen); in such cases, we assume that these atoms are bonded to more phantom atoms, which possess a atomic number of zero, preventing them from being the highest substituent in the list. For isotopes, the higher ones take precedence over the lower ones; lastly, double and triple bonds are ‘broken down’ into two and three single bonds, respectively. This means that an alkyne carbon would be assumed to have three single bonds to three other carbon atoms. After we determine the order, we then ‘rotate’ the molecule (in our heads), such that the lowest priority atom is in a dash bond. The remaining three atoms will then be arranged clockwise or anticlockwise from a higher to lower atomic number (Fig. 8). Clockwise orientations lead to the R configuration, while anticlockwise orientations lead to the S configuration.
Fig. 8: Determination of R or S configuration.
In the next article, we will proceed to consider other types of stereoisomers (other than enantiomers), as well as alternative nomenclature for certain molecules. Part 1 of this article is here, while Part 3 is here.
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