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ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
CONCEPT: TYPES OF ISOMERS
Isomers are used to describe relationships between similar molecules.
□ We can order these relationships in order of increasing similarity
● _________________________________
● _________________________________
● _________________________________
● _________________________________
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: CHIRALITY
A molecule is chiral when, if placed against a mirror, a different (non-superimposable) image is obtained.
□ The mirror image of any chiral molecule is called an _________________________________
□ If a molecule has an internal line of symmetry, it will have the same mirror image (achiral)
EXAMPLE: Draw the mirror images of the following molecules. Determine if the mirror image is the same or different. If there is an internal line of symmetry, use a dotted line to indicate it on the original molecule.
a.
b.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: CHIRALITY TEST 1 – INTERNAL LINE OF SYMMETRY
As previously stated, if a molecule has an internal line of symmetry, it is ___________________
□ This test is the most useful for _________________
EXAMPLE: Are the following molecules chiral or not?
a.
b.
c.
d.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: CHIRALITY TEST 2 – STEREOCENTERS
Any atom that creates a stereoisomer after swapping groups is called a ______________________________
□ The gold standard chirality test for almost all molecules
EXAMPLE: Which of the following molecules contain a stereogenic center? Of these, how many are chiral?
a b c.
d. e f.
Stereogenic Center (Stereocenter)
● Any atom that creates stereoisomers after swapping groups
Chiral Center
● An atom with 4 different substituents. Chiral
Trigonal Center
● Any double bond capable of forming an E or Z isomer. Achiral
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: CAHN-INGOLD-PRELOG NOMENCLATURE
According to IUPAC protocol, each molecule must have a unique, unambiguous name – even stereoisomers.
Step 1. Assign priorities to the four atoms on the chiral center according to their atomic mass on the periodic table.
Step 2. When there is a tie between atomic weights, compare the next set of adjacent atoms (playoffs!).
Step 3. Double bonds count twice. Triple bonds count three times.
EXAMPLE: Determine priorities for the following chiral center:
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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EXAMPLE: Determine priorities for the following chiral center:
Step 4. IF the last priority group is in the back, then trace a path from _________ to _________ priority.
- Clockwise = _____, Counterclockwise = _____ □ Always Ignore group 4
Step 5. If the last priority group is NOT in the back, ________ that group with the group that is on the dash.
- Trace path as always, but this time _______ the sign since you ___________ groups.
● ___ ___
● ___ ___
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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PRACTICE: Provide the full name for the following molecules, taking stereochemistry into account.
a.
b.
c.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: TYPES OF STEREOISOMERS
□ Compounds with no chiral centers are usually achiral
□ Compounds with exactly one chiral center are always _____________, and they can form ___________________
□ Compounds with two or more chiral centers are usually chiral, and can form _____________________
● Follow the 2n (n = stereocenters) rule to predict total number of possible stereoisomers.
EXAMPLE: Draw all the stereoisomers for 2-bromocyclohexan-1-ol, and determine their relationships to each other.
EXAMPLE: Determine the total number of stereoisomers for the following molecule
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: ATROPISOMERS
Molecules that contain NO chiral centers yet are chiral due to their inability to freely ______________
1. Allenes
Use TEST 2 to identify trigonal centers (a type of stereocenter):
□ Visualize the allene as a big double bond. If it is able to form ____ or ____ isomers, it is ____________
□ Remember we stated that trigonal centers are achiral if they pass this test. Allenes are different.
EXAMPLE: Which of the following allenes is chiral?
a. b. c.
2. Substituted Biphenyls
These are chiral if all substituents are in the ortho- position, and if none of the rings have two of the same group on them.
EXAMPLE: Which of the following biphenyls is chiral?
a. b. c.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: MESO COMPOUNDS Meso compounds are created when two symmetrical chiral centers cancel out, yielding 2 _______________ enantiomers
□ Meso compounds have an internal line of symmetry (TEST 1), meaning they are actually _____________
□ Meso compounds follow the ____________ rule for total stereoisomers!
□ A compound will be meso if it meets the following 3 criteria:
1. It has ____ or more chiral centers
2. It is atomically ______________________
3. An even number of chiral centers are _________________ to each other
EXAMPLE: Which of the following molecules are meso, and therefore achiral? a. b.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: CHIRALITY TEST 3 - DISUBSTITUTED CYCLOALKANE SHORTCUTS
Some of the most commonly tested molecules fall in this category. Although TEST 1 and/or TEST 2 could be used to
determine chirality, it will be much faster for us to just memorize simple rules for them.
□ TEST 3 only applies when a ring has two identical substituents
● Always achiral ● Cis = Meso, Achiral ● Always achiral
● Trans = Chiral ● Only possible on even-#’d rings
● Except: 1,2-cyclohexane = Chiral
EXAMPLE: Using TEST 3, which of the following molecules is chiral?
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: ISOMETRIC RELATIONSHIPS
In a previous chapter, we used the following flowchart to identify constitutional isomers:
Step 1. (Are the atoms all the same?) Count non-_______________ atoms and IHD in both compounds
- If not exactly the same, they are ____________________________
- If the same, then go to step 2
Step 2. (Are the atoms all connected the same?) Look for a _____________ atom, then count bonds from there.
-If not exactly the same, they are _______________________________
-If the same, then _____________________________
Due to the possibility of stereoisomers, now we have to add one more step to the flowchart:
Step 3. Count the number/type of stereogenic centers on the molecule
- If _____ chiral/trigonal centers, the two molecules are ______________
- If _____ chiral center,
● Same: ________________
● Different: ___________________
- If _____ chiral centers,
● All same: ________________
● If one or more different: ___________________
● All different: ___________________
- If _____ chiral centers, symmetrical, opposite: __________________________
- If _____ trigonal center,
● Same: ________________
● Different: ___________________
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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PRACTICE: Identify the following compounds as identical, constitutional isomers, enantiomers or diastereomers
a.
b.
c.
d.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: FISCHER PROJECTIONS
□ Like Newman projections, there are several common projections used to visualize molecules in different perspectives.
● In all cases, we will often need to convert these structures into ____________________ before analyzing them.
Converting Fischer to Bondline:
□ Make a caterpillar, then rotate every ________ bond
EXAMPLE: Convert the following Fischer Projection into bondline structure.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: FISCHER CONFIGURATIONS
□ We use a slightly different method for determining R and S configurations in Fischer Projections.
● Determine location of lowest priority group:
- If _________________________, chirality is as it looks
- If _________________________, chirality is flipped.
EXAMPLE: Determine the absolute configurations for all chiral centers present.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: OPTICAL ACTIVITY—SPECIFIC AND OBSERVED ROTATION
One of the special features of chiral molecules is that they are able to __________ plane-polarized light.
● Clockwise rotation = dextrorotary (d) or ________ ● Counterclockwise rotation = levororatory (l) or _______
□ These random names have ____________ to do with the chirality of a molecule!
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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Enantiomeric Excess:
● Specific rotation [α] is the rotation that 100% pure enantiomers produce. Opposite enantiomer = _____________ rotation.
● A perfect 1:1 ratio of enantiomers is called _________________ ● Non-1:1 ratio is called _________________
The enantiomeric excess: Observed Rotation:
EXAMPLE: Calculate the ee and observed rotation for the following chiral mixtures where S-enantiomer
has [α] = +20.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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PRACTICE: OPTICAL ACTIVITY
a. When 0.200 g of lactose is dissolved in 10.0 ml of water and placed in a sample cell 10.0 cm in length, the observed rotation is +2 O. Calculate the specific rotation of lactose.
b. Calculate the observed rotation of a chiral mixture that contains 65% (S)-stereoisomer where the [α] of pure (S)-stereoisomer = -118
c. An optically pure (R)-stereoisomer of a molecule has a specific rotation of – 20O. What specific rotation would be observed for a mixture of the (R) and (S) stereoisomer where there is an enantiomeric excess equal to (S) 60%
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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CONCEPT: NON-CARBON CHIRAL CENTERS
Chirality may exist on atoms other than carbon. Common non-carbon chiral atoms are ( ), ( ), ( ), ( ).
□ The lone pair on a neutral nitrogen is able to _____________________ relatively easily, losing its chirality.
● Chirality is determined using the R/S naming system, where the _________ __________ is always group number _____.
ORGANIC - EGE 5E
CH. 6 - STEREOCHEMISTRY
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