MCAT Content / Covalent Bonds / Stereochemistry Of Covalently Bonded Molecules 2

Stereochemistry of Covalently Bonded Molecules

Topic: Covalent Bonds

Isomers are molecules that have the same molecular formula but have a different arrangement of the atoms in space.

A structural isomer, also known as a constitutional isomer, is one in which two or more organic compounds have the same molecular formulas but different structures. The two molecules below have the same chemical formula, but are different molecules because they differ in the location of the methyl group.

Conformational isomers exist when there is rotation about the carbon-carbon single bond. This allows for many different arrangements of the atoms, each corresponding to different degrees of rotation. Differences in three-dimensional structure resulting from rotation about a σ bond are called differences in conformation, and each different arrangement is called a conformational isomer.

Stereoisomers have the same connectivity in their atoms but a different arrangement in three-dimensional space. The molecules will have the same molecular formula and the same bonding arrangement, but a different arrangement of atoms in space.

Stereoisomers are isomers that differ in the spatial arrangement of atoms, rather than the order of atomic connectivity. One of the most interesting types of isomer is mirror-image stereoisomers, a non-superimposable set of two molecules that are mirror images of one another. The existence of these molecules is determined by concept known as chirality. The word “chiral” was derived from the Greek word for hand, because our hands are good example of chirality since they are non-superimposable mirror images of each other. The term chiral, from the Greek work for ‘hand’,  refers to anything which cannot be superimposed on its own mirror image. Your hands, of course, are chiral – you cannot superimpose your left hand on your right, and you cannot fit your left hand into a right-handed glove (which is also a chiral object). Another way of saying this is that your hands do not have a mirror plane of symmetry: you cannot find any plane which bisects your hand in such a way that one side of the plane is a mirror image of the other side. Chiral objects do not have a plane of symmetry.

Your face, on the other hand is achiral – lacking chirality – because, some small deviations notwithstanding, you could superimpose your face onto its mirror image.  If someone were to show you a mirror image photograph of your face, you could line the image up, point-for-point, with your actual face. Your face has a plane of symmetry because the left side is the mirror image of the right side.

What Pasteur, Biot, and their contemporaries did not yet fully understand when Pasteur made his discovery of molecular chirality was the source of chirality at the molecular level.  It stood to reason that a chiral molecule is one that does not contain a plane of symmetry, and thus cannot be superimposed on its mirror image.  We now know that chiral molecules contain one or more chiral centers, which are almost always tetrahedral (sp3-hybridized) carbons with four different substituents.

There are different classifications of stereoisomers depending on how the arrangements differ from one another including cis/trans isomers, enantiomers, and diastereomers.

  • Cis-Trans isomers: These exist where there is no free rotation around a double bond, the order of atom bonding is the same but the arrangement of atoms in space is different. For example, there are two different ways to construct the molecule 2-butene.

  • Enantiomers: These are non-superimposable mirror images. A common example of a pair of enantiomers is your hands. Your hands are mirror images of one another but no matter how you turn, twist, or rotate your hands, they are not superimposable. Objects that have non-superimposable mirror images are called chiral. When examining a molecule, carbon atoms with four unique groups attached are considered chiral.

  • Diastereomers: These are stereoisomers which are not mirror images of each other. Optical isomers differ in the placement of substituted groups around one or more atoms of the molecule. They were given their name because of their interactions with plane-polarized light. Optical isomers are labeled enantiomers or diastereomers.

Another type of optical isomer comprises those diastereomers which are not geometric (cis-trans) isomers). These are achiral (non-mirror image) optical isomers. Diastereomers have a different arrangement around one or more atoms while some of the atoms have the same arrangement. When drawing these molecules different shaped bonds are used. The solid wedge indicates a group coming out of the page/screen towards you and the dashed line indicates that a group is going away from you “behind” the page.

Compounds that rotate the plane of polarized light are termed optically active. Each enantiomer of a stereoisomeric pair is optically active and has an equal but opposite-in-sign specific rotation. Specific rotations are useful in that they are experimentally determined constants that characterize and identify pure enantiomers.

Identifying and distinguishing enantiomers is inherently difficult since their physical and chemical properties are largely identical. Enantiomers are optically active compounds, the right- and left-handed enantiomers of a chiral compound perturb plane-polarized light in opposite ways, either right R or left S. This perturbation is unique to chiral molecules and has been termed optical activity. Plane-polarized light is created by passing ordinary light through a polarizing device. Such devices transmit selectively only that component of a light beam having electrical and magnetic field vectors oscillating in a single plane. The plane of polarization can be determined by an instrument called a polarimeter.

When assigning R and S nomenclature where R means rectus (Latin for right) and S means sinister (Latin for left), it is good practice to prioritize the four groups attached to the chiral carbon by atomic mass. Rotate the molecule so the lowest priority group is facing away from the page. If the order of priority is clockwise the molecule is R, if the molecules priority is anti-clockwise the molecule is determined to be S. The R or S is then added as a prefix, in parenthesis, to the name of the enantiomer of interest.

When the chemical groups either side of a double bond are different. we can no longer use the Cis and Trans systems. We need to use E and Z isomerism nomenclature. E stands for entgegen which means opposite and Z which stands for zussamen which means together. These refer to the relative positions of atoms either side of the double bond. On either side of the double bond, we need to assign priority based on atomic mass. Using the priority we can then assign nomenclature, E if the highest priority groups are opposite and Z if the groups are on the same side of the axis.

Every chiral molecule has a characteristic specific rotation, which is recorded in the chemical literature as a physical property just like melting point or density.  Different enantiomers of a compound will always rotate plane-polarized light with an equal but opposite magnitude. (S)-ibuprofen, for example, has a specific rotation of +54.5o (dextrorotatory) in methanol, while (R)-ibuprofen has a specific rotation of -54.5o.  There is no relationship between chiral compound’s R/S designation and the direction of its specific rotation.   For example, the S enantiomer of ibuprofen is dextrorotatory, but the S enantiomer of glyceraldehyde is levorotatory.  A 50:50 mixture of two enantiomers (a racemic mixture)  will have no observable optical activity, because the two optical activities cancel each other out.

Chiral molecules are often labeled according to whether they are dextrorotatory or levorotatory (their effect on light) as well as by their R/S designation (their absolute structure in 3D).  For example, the pure enantiomers of ibuprofen are labeled (S)-(+)-ibuprofen and (R)-(-)-ibuprofen, while (±)-ibuprofen refers to the racemic mixture, which is the form in which the drug is sold to consumers.

It is very important to know that dl, (+), or () do not designate configurations. Thus, although ()-2-butanol actually has configuration  and (-)-2-butanol has configuration , there is no simple way to predict that a particular sign of rotation will be associated with a particular configuration.

 

Practice Questions

 

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MCAT Official Prep (AAMC)

Practice Exam 4 C/P Section Question 11


Key Points

• Isomers are molecules that have the same molecular formula but have a different arrangement of the atoms in space.

• Stereoisomers are isomers that differ in the spatial arrangement of atoms, rather than the order of atomic connectivity. There are different classifications of stereoisomers depending on how the arrangements differ from one another including cis/trans isomers, enantiomers, and diastereomers.

• Cis-Trans isomers: These exist where there is no free rotation around a double bond, the order of atom bonding is the same but the arrangement of atoms in space is different.

• Enantiomers: These are non-superimposable mirror images.

• Diastereomers: These are stereoisomers which are not mirror images of each other.

• Conformational isomers exist when there is rotation about the carbon-carbon single bond that can occur.

• Optical isomers differ in the placement of substituted groups around one or more atoms of the molecule and react differently to polarized light.

• Compounds that rotate the plane of polarized light are termed optically active.

• Every chiral molecule has a characteristic specific rotation.

• When assigning R and S nomenclature where R means rectus (Latin for right) and S means sinister (Latin for left), it is good practice to prioritize the four groups attached to the chiral carbon by atomic mass.

• When the chemical groups either side of a double bond are different, we use E and Z isomerism nomenclature. E stands for entgegen which means opposite and Z which stands for zussamen which means together. These refer to the relative positions of atoms either side of the double bond.


Key Terms

Isomer: Two or more compounds with the same formula but a different arrangement of atoms in the molecule and different properties.

Enantiomer: Each of a pair of molecules that are mirror images of each other.

Diastereomers: Stereoisomers that are not mirror images of one another and are non-superimposable on one another.

Optically active: Capable of rotating the plane of vibration of polarized light to the right or left.

Chiral: Mirror images that are not superimposable.

Chiral Center: Tetrahedral atoms (usually carbons) that have four different substituents; each chiral center in a molecule will be either R or S.

Achiral: Mirror images that are superimposable.

Polarized light: Light whose electric field oscillates in just one plane.

Specific rotation: A property of a chiral chemical compound. It is defined as the change in orientation of monochromatic plane-polarized light, per unit distance–concentration product, as the light passes through a sample of a compound in solution.

(E)-: The higher priority groups are on opposite sides of the double bond.

(Z)-: The higher priority groups are on the same side of the double bond.

(R)-: Rectus (Latin for right), used to name chirality centers.

(S)-: Sinister (Latin for left), used to name chirality centers.



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