ORGANIC - BROWN 8E CH.3 - STEREOISOMERISM AND CHIRALITY.

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2 CONCEPT: TYPES OF ISOMERS Isomers are used to describe relationships between similar molecules. We can order these relationships in order of increasing similarity Page 2

3 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. Page 3

4 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. Page 4

5 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 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 EXAMPLE: Which of the following molecules contain a stereogenic center? Of these, how many are chiral? a b c. d. e f. Page 5

6 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: Page 6

7 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. Page 7

8 PRACTICE: Provide the full name for the following molecules, taking stereochemistry into account. a. b. c. Page 8

9 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 2 n (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 Page 9

10 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. Page 10

11 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. Page 11

12 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? Page 12

13 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: Page 13

14 PRACTICE: Identify the following compounds as identical, constitutional isomers, enantiomers or diastereomers a. b. c. d. Page 14

15 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. Page 15

16 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. Page 16

17 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! Page 17

18 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. Page 18

19 PRACTICE: OPTICAL ACTIVITY a. When 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 20 O. 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% Page 19

20 CONCEPT: OPTICAL ACTIVITY ENANTIOMERIC PERCENTAGES When given the specific and observed rotations, we must use the following relationships to determine the mixture. EXAMPLE: The [α] of pure S-epinephrine is +50. Calculate the ee of a solution with the following observed value. Calculate percent of each enantiomer. Then sketch the approximate mixture in our sample polarimeter tube. a PRACTICE: The [α] of pure S-epinephrine is +50. Calculate the ee of a solution with the following observed value. Calculate percent of each enantiomer. Then sketch the approximate mixture in our sample polarimeter tube. b Page 20