CC5B Isomers - OCHEM Ch 2

2.1 Structural Isomers aka constitutional isomers

Also called constitutional isomers. => They are the least similar of all isomers. => The only thing structural isomers have in common are their molecular formula so their molecular weights must be the same. => Aside from this similarity, structural isomers have different chemical and physical properties.

Stereoisomers: CONFORMATIONAL isomers vs CONFIGURATIONAL isomers

Conformational isomers differ in rotation around single (σ) bongs Configurational isomers can be interconverted only by breaking bonds.

Isomers

Isomers have the same molecular formula, but different structures.

2.3 Relative and Absolute Configurations

Relative configuration of a chiral molecule is its configuration in relation to another chiral molecule and this is what is used to determine whether the molecules are enantiomers, diastereomers, or the same molecule Absolute configuration of a chiral molecule describes the exact spatial arrangement of the atoms or groups in the molecule and it is independent of other molecules => Cis-Trans determination => E/Z determination => R and S determination **Cahn-Ingold-Prelog priority rules are used for determining both E/Z forms and R/S forms

Configurational Isomers

Requires bond breaking to be superimposable

Do not confuse optical activity labels with absolute configurations. The direction of rotation of plane polarized light can ONLY be determine experimentally.

(+) and (d-) refer to clockwise rotation of plane polarized light while (-) and (l-) refer to counterclockwise rotation of plane polarized light. Do not confuse this with absolute configuration labels like (D-) and (L-) used with carbohydrates and amino acids (which are based on the absolute configuration of glyceraldehyde) or (R) and (S) labels. ****Optical activity does not consistently align with the other systems.

(R) and (S) Forms

(R) and (S) nomenclature is used for chiral (stereogenic) centers in the molecules. (R) for clockwise (S) for counterclockwise **Shortcut when the lowest priority group is not in the back: "anytime two groups are switched on a chiral carbon, the stereochemistry is inverted".

Potential Energy vs Degree of Rotation about the C2 to C3 bond in Butane

**Notice to convert from anti to gauche conformation, the molecule has to pass an eclipsed conformation, in which the two methyl groups are 120° apart and overlap with H atoms. **Every molecule wants the lowest energy state possible. The higher the energy, the less time the molecule will spend in that energetically unfavorable state.

Conformational Isomers

**Of all the isomers, conformational isomers are most similar. They are the same molecule except they differ at some points in their rotation around single (σ) bonds. **Conformational isomers arise from the fact that varying degrees of rotation around single bonds can create different levels of strain.

How can we seperate a racemic mixture?

1) Can run a racemic mixture through a chiral molecule (i.e. run it through a bacteria that will digest one of the enantiomer and secret the other enantiomer) 2) Add a stereocenter by a chemical reaction. This will produce the diastereomer, which will have different chemical and physical properties than the original enantiomer. Separate the two molecules. Then reconvert the diastereomer back into the original enantiomer.

Enantiomers: levorotatory isomer (l-) vs dextrorotatory isomer (d-)

A chiral compound and its mirror image are enantiomers Enantiomers differ only in their optical activity (i.e. in the direction in which they rotate PLANE-POLARIZED light [the randomly oriented light is first plane polarized then goes through the chiral sample and is rotated]) => Other than optical activity, enantiomers have the same physical properties **If an enantiomer rotates plane-polarized light to the right (clockwise), it is said to be (+) or "d-" (dextrorotatory isomer) **If an enantiomer rotates plane-polarized light to the left (counterclockwise), it is said to be (-) or "l-" (levorotatory isomer).

What makes a molecule chiral?

A chirality center is a tetrahedral (sp3 hybridized) carbon with 4 different groups. An object is considered chiral if its mirror image cannot be superimposed on the original object. This is because the molecule lacks an internal plane of symmetry. Alternatively, a carbon atome with only three different substituents is ACHIRAL because they do have an internal plane of symmetry and therefore, its mirror image is superimposable on the original object (i.e. fork)

Enantiomers vs Diastereomers

BOTH enantiomers and diastereomers are nonsuperimposable stereoisomers. Enantiomers => stereoisomers that are nonsuperimposable MIRROR images => no internal plane of symmetry => opposite configurations at ALL chirality centers **enantiomers are mirror images of each other because they have opposite configurations at all of their multiple chiral centers => Enantiomers will have the same chemical and physical properties except for the way they rotate light will be in opposite directions => Their chemical reactivity will be the same if they are reacting with another molecule that is not chiral (achiral). BUT if the molecule reacting with the enantiomer is chiral, then the reactivity of that molecule with either of the enantiomers will be different. Diastereomers => stereoisomers that are nonsuperimposable NON-MIRROR images => opposite configurations at SOME chirality centers **diastereomers are not mirror images of each other because they differ at some (but not all) of their multiple chiral centers => Diastereomers have different chemical and physical properties ***Diastereomers occur when a molecule has two or more stereogenic centers and differs at some, but not all, of these centers.

Why is the EZ system more inclusive than the cis/trans system?

Because the E-Z system is more inclusive. Unlike the cis/trans system, with the E-Z system you are comparing the two highest priority groups on each carbon so it doesn't necessarily have to be two identical groups that are being compared (as is the case with cis/trans system). Entegegen (E) means "opposite" => If the two higher priority groups are on opposite sides across the plane running through the double bond Zusammen (Z) means "together" => If the two higher priority groups are on the same side across the plane running through the double bond

Racemic Mixture

Enantiomeric excess (ee) is a measurement of the degree of purity of any chiral sample. It reflects the degree to which a sample contains one enantiomer in EXCESS over the other. A racemic mixture has an enantiomeric excess (ee) of 0% (both enantiomers are present in a 1:1 ratio) In contrast, a completely pure enantiomer has an EE of 100%. Ex: a mixture that contains 70% R isomer and 30% S isomer has an EE of 40%. A racemic mixture, the two enantiomers will cancel each other's rotation of plane-polarized light.

Meso Compounds

For a molecule to have optical activity, it must not only have chiral centers within it, but must also lack a plane of symmetry. Meso compounds have a plane of symmetry (either between chiral centers or through chiral centers) and therefore, do not have optical activity.

Cis-Trans Isomers (Geometric Isomers)

For cis/trans isomerism, you have to be comparing two identical groups on adjacent carbons across a double bond. Don't be tricked by two identical groups bonded on the same carbon.

When cyclohexanes undergo a Chair Flip

In a chair flip, all axial become equatorial and vice-a-versa. However, all dashes remain dashes and all wedges remain wedges. This interconversion can be slowed if a bulky group is attached to the ring. Ex: tert-butyl is a common example of this on the MCAT. For substituted rings, the bulkiest group will favor the equatorial position to avoid nonbonded strain (flagpole interactions) with axial groups. => so in these scenario's the interconversion will favor the conformation with the bulkier group in equatorial position (see image) **in rings with more than one substituent, the preferred chair conformation is one which places the bulkier group in equatorial position. **if both groups are located on same side of the ring, then molecule is cis. If opposite side, then it's trans.

§ Stereochemistry of covalently bonded molecules (OC) > Isomers . Structural isomers . Stereoisomers (e.g., diastereomers, enantiomers, cis/trans isomers) . Conformational isomers > Polarization of light, specific rotation

OCHEM CH 2: Isomers

Cyclic Conformations

Stability of cycloalkanes depends on ring strain. Ring strain arises from three factors: 1) angle strain - when bond angles deviate their ideal values 2) torsional strain - is the resistance to bond twisting when cyclic molecules must assume eclipse or gauche conformations 3) nonbonded strain (van der Waals repulsion) - when nonadjacent atoms compete for space [steric interaction]

2.2 Stereoisomers

Stereoisomers share the same atomic connectivity but different arrangements in space (i.e. their wedge-and-dash pattern). All isomers that DO NOT share the same connectivity are structural isomers (constitutional isomers). The rest fall into this category. Within stereoisomers, the isomers can either fall into conformational isomers or configurational isomers.

Observed Rotation vs Specific Rotation

The observed rotation depends on the number of molecules that hit the polarized light. So increasing the concentration or increasing the length of the polarimeter tube, will increase the observed rotation. **if you double the concentration or double the path length, you double the observed rotation (alpha) Specific rotation is a constant and is unique for each enantiomer. Specific Rotation = alpha / (C * l) alpha is observed rotation in (°) C is concentration in (M) l is length of path link in (dm) **Enantiomers have specific rotations that are equal in magnitudes but opposite in sign. Louis Pasteur was the first one to recognize this relationship.

Possibilities for achirality

There are two possibilities here for achirality. The first case is that there are no stereocenters on a particular molecule, and the second case is when a compound has a stereocenter, it can be achiral only when it is a meso compound.

The different conformational isomers again from most stable to least

These angles are called "dihedral angles" also called "torsional angles" 180° Staggered (anti) 60° Gauche 120° Eclipse 0° Total Eclipse **Staggered conformations have groups 60° apart and in the anti staggered conformation, the two largest groups are 180° apart. In gauche staggered molecules, the two largest groups are 60° apart.

Conformational Interconversion Barriers

These conformational interconversion barriers are small. It only takes about 19 kcal/mol to convert from anti staggered conformation to totally eclipsed conformation which are easily overcome room temperature. However, at lower temperatures, conformational interconversions will dramatically slow.

Physical vs Chemical properties

This is prime MCAT material that is often tested in context of isomerism. Physical properties = characteristics of processes that don't change the composition of matter. Examples include melting point, boiling point, solubility, odor, color, and density. Chemical properties = have to do with reactivity of the molecule with other molecules and results in changes in chemical composition. **chemical properties are determined by functional groups in the molecule

Diastereomers

Unlike enantiomers, the specific rotation of one diastereomer does not give any indication to the specific rotation of the other molecule in the diastereomeric pair. This is in stark contrast with enantiomers that will always have equal-magnitude rotations but in opposite directions.

Fischer Projections

Up/down means dashes: into the plane of the page ("straight up into the page") Side means wedges: out of the plane of the page For each of the Fischer projection manipulation: => switching a pair of substituents: inverts the stereochemistry => switching two pairs of substituents: retains the stereochemistry => rotating the molecule 90°: inverts the stereochemistry => rotating the molecule 180°: retains the stereochemistry ***trick when the lowest-priority group is pointing to the side (out of the page): whatever R/S configuration is determined, the true designation will be its opposite.

Newman Projection

Viewing the molecule with your eye facing the front of the carbon backbone. With butane, it is the eyeball facing the front of C2 and C3 hidden from sight by C2. With larger molecules, the conformations are determined by the relative positions of the two largest substituents about a carbon-carbon bond.

Cyclohexane nonplanar conformations

from order least stable to most: Twist-boat (or "skew-boat") Boat Chair *Chair is most stable of the conformations => axial - perpendicular to the plane of the ring (sticking up/down) => equatorial - parallel to plane of ring (sticking our) **Axial-equatorial orientations alternate around the ring (i.e. if the wedge on C1 is an axial group, the dash in C2 will also be axial, and the wedge on C3 will be axial)