Isomers

Structural Isomers

• The least similar of all isomers since they only share the same molecular formula, which means that their molecular weights must be the same
• Also known as constitutional isomers
• Physical Properties: characteristics of processes that don’t change the composition of matter. Things such as melting/boiling point, solubility, odor, colour and density.
• Chemical Properties: reactivity of the molecule with other molecules and therefore alters the chemical composition.
  • Usually dictated by the functional groups in the molecule.

Stereoisomers

• Have the same chemical formula and share the same atomic connectivity (have the same structural backbone)
• Differ in how their atoms are arranged in space.

Conformational Isomers

• The most similar isomers since they are the same molecule, just at different points in their natural rotation around a single (s) bond.
• Arise from the fact that varying degrees of rotation around single bonds can create different levels of strain
  • Only single bonds allow for rotation, while double bonds stay rigid.
• Depict these molecules as a Newman projection: molecule is visualized along a line extending through a carbon-carbon axis

Straight-Chain Conformations

• Staggered Conformation: no overlap of atoms along the line of sight
  • anti-conformation: the two largest groups are antiperiplanar
  • gauche: two largest groups are 60 degrees apart.
• In order to go from anti to gauche conformation, the molecule must pass through an eclipsed conformation (two methyl groups are 120 degrees apart). Higher E than gauche
  • Totally Eclipsed: Two methyl groups are directly over-top one another, 0-degree separation. This is the highest energy state and is thus the least favorable.  
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• For compounds larger than butane, the name of the conformation is decided by the relative position of the two largest substituents about a given C-C bond.

Cyclic Conformation

• Ring Strain: determines whether a cycloalkane will be stable or not
  • Angle Strain: bond angles deviate from their ideal angle by being stretched or compressed
  • Torsional Strain: cyclic molecules must assume conformation that have eclipsed or gauche interactions
  • Non-bonded Strain: nonadjacent atoms or groups compete for the same space
    • Dominant source of strain in the flagpole interactions of the cyclohexane boat conformation.
• Stress is alleviated by cycloalkanes adopting various nonplanar conformations:
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• Cyclohexane will be the one most seen on the MCAT, the most stable conformation is the chair conformation.
• Hydrogen atoms that are perpendicular to the plane of the ring (stick up or down) are called axial and those that are parallel (sticking out) are called equatorial.
• Cyclohexane can undergo a chair flip in which one chair form is converted to the other.
  • During this process, the cyclohexane passes through a fourth conformation called the half-chair.
  • After the flip all axial groups become equatorial and vice vera.
  • Interconversion is slowed if bulky group is present (tert-butyl are the most common).
    • Bulky groups will favor the equatorial position to reduce non-bonded strain.
• In rings with more than one substituent, the preferred chair form is determined by the larger group, which will prefer the equatorial position.
• If both groups located on same side of the ring, it is called For opposite sides of the ring: trans.

Configurational Isomers

• Only change from one form to another by breaking and reforming covalent bonds.
• Two categories are enantiomers and diastereomers which can be considered optical isomers since the different spatial arrangement of groups affects the rotation of plane polarized light.

Chirality

• Is considered chiral if the mirror image of an object cannot be superimposed on the original object. Means that the object has no internal plane of symmetry. (think of your hands)
• Achiral: objects that have mirrors which can be superimposed.
• Carbons with four different substituents is always chiral and the central carbon is known as the chiral center. Chiral center is a central carbon with asymmetrical substituents.
• Carbon with only three different substituents has a plane of symmetry and is therefore achiral.

Enantiomers

• Non-superimposable mirror images that have the same connectivity but opposite configurations at every chiral center of the molecule.
• Have identical physical and chemical properties except for optical activity and reactions in chiral environments.
• A compound is optically active if it has the ability to rotate plane-polarized light
• Optical Activity: the rotation of plane-polarized light by a chiral molecule. One enantiomers will rotate the light in the opposite direction but with the same magnitude.
  • Plane of polarized light to the right: dextrorotatory (d-) and is labeled with a (+)
  • Plane of polarized light to the left: levorotatory (l-) and is labeled with a (-)
  • Direction of rotation is not related to configuration of molecule and must be determined experimentally.
• Amount of rotation depends on the number of molecules the light encountered which further depends on the concentration of optically active compound and the length of the tube which light passes through
  • Standard values: 1 g/ml conc & 1 dm for length
  • Rotation at different concentration & tube lengths can be converted using:
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• Racemix mixture: both (+) & (-) enantiomers are present in equal concentrations and no optical activity is observed.

Diastereomers

• Non mirror image configurational isomers. Occur when a molecule has two or more stereogenic centers and differs some (not all) centers.
  • Requires diastereomers to have more than two chiral centers.
• For any molecule with n chiral centers, there are 2ⁿ possible stereoisomers
• Have different chemical properties and physical properties
• Will also rotate light but rotation is not related to any other diasteromers

Cis-Trans Isomers (geometric isomers)

• Subtype of diastereomers in which substituents differ in their position around an immovable bond (like a double bond, or around a ring structure)
• For simple compounds with only one substituent on either side of the bond, we use cis (same side) and trans (opposite sides).

Meso Compound

• A molecule with chiral centers that has an internal plane of symmetry
• Are not optically active even though they have chiral centers.
• Plane of symmetry can be between chiral centers or through chiral center.

Relative and Absolute Configurations

• Configuration refers to the spatial arrangement of the atoms or groups in a molecule.
• Relative configuration of a chiral molecule is its configuration relative to another chiral molecule.
  • Can be used to determine whether molecules are enantiomers, diasteromers or the same molecule
• Absolute configuration: describes the exact spatial arrangement of these atoms or groups.

E and Z Forms

• Used for compounds with poly-substituted double bonds (more complex version of cis/trans)
• Identify the highest priority substituent that is attached to each double-bonded carbon using the Cahn-Ingold-Prelog priority rules.
  • Priority is assigned based on the atom bonded to the double bonded carbons: the higher the atomic number, the higher the priority. If equal, look for the atoms with the next highest atomic number.
• Alkene is named (Z) if the two highest priority substituents on each carbon are on the same side of the double bond
• Alkene is named (E) if they are on opposite sides.

R and S Forms

• Used for chiral centers in molecules

Step 1: Assign Priority

• Use priority rules described above and assign priority to the four substituents.
• Highest priority given to atom attached to the chiral center with the highest atomic number. Only use other atoms in substituents if there is a tie.
• Ties are settled by working outwards from the stereo-center until the tie is broken.
• Double bonds count as two individual bonds

Step 2: (Classic Version) Arrange in Space

• Orient molecule so that the atom with the lowest priority is at the back of the molecule.
• Three other substituents should then radiate outwards from the central carbon.

Step 2: (Modified Version) Invert the Stereochemistry

• Any time two groups are switched on a chiral carbon, the stereochemistry is inverted.
• This can help in visualizing the rotation of three-dimensional structures
• Done so by simply switching the lowest priority group with the group at the back of the molecule.
• This process inverts the configuration (opposite), so then the final answer needs to be switched (from R to S or vice versa).

Step 3: Draw a Circle

• Draw a circle from priority 1-2-3. If circle is counterclockwise, then the atom is called (S). If the circle is clockwise, then the atom is called (R).
• Remember to switch orientation if modified version used

Step 4: Write the Name

• Write (R)/(S) separate from the rest of the name by brackets and a hyphen.
• If more than one chiral center, have a number precede each R/S designation

Fischer Projections

• Way to represent three-dimensional molecules.
• Horizontal lines indicate bonds that project out from the plane (wedges)
• Vertical Lines indicate bonds that project into the plane of the page (dashes)
• Intersection is the carbon atom
• Rotating a Fischer projection into the plane of the page by 90 degrees will invert the stereochemistry of the molecule.
  • Interchanging two pairs will then revert the compound back to its original stereochemistry.
• Rotating a Fischer projection in the plane of the page by 180 degrees retains the stereochemistry of the molecule.
• Have different tricks to make sure that the lowest priority substituent is pointing into the page.:

Option 1: Make 0 Switches

• Draw a circle from 1-2-3 and just skip over number 4. Then the true designation will be the opposite of the obtained designation

Option 2: Make 1 Switch

• Swap lowest priority group with one of the groups on the vertical axis. Obtain the (R)/(S) designation and the true designation will be the opposite of this

Option 3: Make 2 Switches

• Start with option 2, and then switch the other pair as well. Designation will then be the same as the initial molecule.