Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts. New vocabulary and concepts Handedness Chirality Fischer Projections Depicting Asymmetric Carbons (R) and (S) Nomenclature Enantiomers Diastereomers Optical Activity Stereochemistry
Isomers: Different compounds that have the same molecular formula (composition) but different connectivity. Two classes:
- Structural (constitutional) isomers: same molecular formula but different bonding sequence
- Stereoisomers: same molecular formula, same bonding sequence, but different arrangement in space. Handedness…..Chirality
Handedness” right glove doesn’t fit the left hand. Superimposable: A term that describes the ability to precisely overlap one object over another. Only identical objects are superposable, everything else is non-superposable
superimposable nonsuperimposable Chiral molecules & Chirality Center
Chemical substances can be handed, and they are called chiral. Chiral Molecules: are molecules that are nonsuperimposable on their mirror image. A carbon atom that is bonded to four chiral carbon atom different groups is called chairal carbon atom or stereocenter (asymmetric carbon atom). It is sp3 carbon and labeled with a strict. Achiral: A molecule is achiral if it is superimposable on its mirror image
H H
Cl Cl Practices on Asymmetric Carbons
Example: Identify all asymmetric carbons present in the following compounds. Br Br
H OH H H CH2CH3 H C *C C C H Br CH3 * H H H H H H H H H3C Br CH3 * *
OH * CH CHCOOH* 3 * * * Fischer Projections:
➢ It is a two-dimensional representation of a three-dimensional organic molecule by projection. ✓Carbon chain is on the vertical line. ✓Horizontal bonds pointing out of the plane of the paper. ✓Vertical bonds pointing into the plane of the paper. Ex. Draw Lactic acid using Fischer projection
** In the original structure, wedge bonded group should be left and the dashed bonded group should be right. Fischer Projections:
Ex. Draw D-Threose using Fischer projection
O OH OH * CH-*CH-CHCH2OH * * Internal Plane of Symmetry
❖ Cis-1,2-dichlorocyclopentane contains two asymmetric carbons but is achiral because it contains an internal mirror plane of symmetry H H ❖ Any molecule that has an internal mirror plane of symmetry is achiral even if it contains asymmetric carbon atoms. It is called “meso” Cl Cl
❖Meso compound: an achiral compound that contains chiral centers often contains an internal mirror plane of symmetry
❖ Tartaric acid is also Meso compound because it contains 2 stereocenters and a plane of symmetry Practice on Internal Plane of Symmetry
Example: Which of the following compounds contain an internal mirror plane of symmetry?
Br HO2C CO2H H CH2CH3 H CH3 C C C C HO OH H H C H H H H3CH2C Br 3
H HO2C CO2H O C C F C OHF C HO H Cl H OH HO C H F H H C OH C OH O
C Chiral vs. Achiral
To determine if a compound is chiral: 0 asymmetric carbons: Usually achiral 1 asymmetric carbon: Always chiral 2 asymmetric carbons: Chiral or achiral: ❖Does the compound have an internal plane of symmetry? – Yes: achiral (meso) – No: chiral H Br Chiral vs. Achiral Br H Practice: Identify the following molecules as chiral or achiral. CH3
Cl CH3 CH3CH2 H CH3 C CH2CH3 Br CH CCH CH C C CH3CHCH2CH2CH3 3 2 3 H Cl Cl Br CH2CH3
H Br Br Br
Br H H H cis-1,2-dibromocyclobutane CH3trans-1,2-dibromocyclobutane
CH3 C CH2CH3 Cl
Br Br
H H Types of Stereoisomers
CO H Two types of stereoisomers: 2 CO2H Enantiomers: Two compounds that C C H H are nonsuperposable mirror images of CH3 H N H3C NH each other {(R), (S) isomers} 2 2
Diastereomers:Two stereoisomers that are not mirror images of each other.
Geometric isomers (cis-trans isomers) are one type of diastereomer.
H H H CH3 C C C C H3C CH3 H3C H cis-2-butene trans-2-butene Enantiomers and (R) & (S) Nomenclature
Assign a numerical priority to each group bonded to the asymmetric carbon: group 1 = highest priority (higher atomic numbers) group 4 = lowest priority (lower atomic numbers) priorities: I > Br > Cl > S > F > O > N > 12C > 1H
CH(CH3)2 > CH2CH2Br > CH3CH2
1 3 Cl CH 3 2 CH2CH2Br 3 C C 4 2 H C H3C H 4 OCH CH F NH2 3CHCH 2 3 1 3 2 H 2 CH(CH3)2 4 1 Remember the periodic table of elements Enantiomers and (R) & (S) Nomenclature
After assigning a numerical priority to each group bonded to the asymmetric carbon, Use a 3-D drawing or model, put the 4th priority group in back. Draw an arrow from the 1st priority group to the 2nd group to the 3rd group. Clockwise arrow (R) configuration Counterclockwise arrow (S) configuration If the 4th priority group is in the front, reverse the name Example: Name the following compounds.
1 1
4 4
3 3 2 2 (S)-lactic acid (R)-lactic acid
2 Although we have clockwise arrow, (we suppose to CH2CH3 name it (R), but because the H is in front, so we 1 C reverse the name to (S). Br 3 CH3 H 4 (S)-2-bromobutane Enantiomers and (R) & (S) Nomenclature
When naming compounds containing multiple chiral atoms, you must give the configuration around each chiral atom: position number and configuration of each chiral atom in numerical order, separated by commas, all in ( ) at the start of the compound name
Br H Note: in carbon #3 we see the configuration H clockwise , i.e. R, but we reverse it to S because Cl the H atom is in the front.
H3C CH3 (2S, 3S)-2-bromo-3-chlorobutane Practices on (R) and (S) Nomenclature H Excercies: Identify theC asymmetric carbon(s) in CH(CH3)2 each of the followingCH compounds and determine whether it has the (R)3 orBr (S) configuration.
CO2H CO2H H CH3 (…)-alanine (…..)-alanine C C C C H CH CH CH(CH3)2 H CH 2 3 H3C 3 CH NH2 H2N OH 3 Br O OH C Br CH3 CH3 (…..)2-butanol C C C CH CO HC CH2CH3 3 2 CH CH H CH CH 2 3 OH 2 3 H H (…..)2-bromoprobionic acid OH O OH C C
CH2CH3 Depicting Structures with Asymmetric Carbons
Example: Draw a 3-dimensional formula for (R)-2-chloropentane. C1l Step 1: Identify the asymmetric carbon. Cl CH3 C CH2 CH CH Step 2: Assign priorities to each group 3 * 2 2 3 CH3 C CH2CH2CH3 attached to the asymmetric carbon. H H 4 Step 3: Draw a “skeleton” with the chiral atom in Cl the center and the lowest priority group attached CH3 C CH2CCH2CH3 to the “dashed” wedge (i.e. pointing away from you). H C Cl H Step 4: Place the highest priority group at the top. CH3 C CH2CH2CH3 Cl Step 5: For (R) configuration, place the 2nd andH 3rd priority C groups around the chiral atom in a clockwise direction. H Cl Step 6: Double-check your structure to make C sure that it has the right groups and the right H CH2CH2CH3 configuration. CH3 How many stereoisomers?
For 2,3 dichloropentane, how many stereoisomers ? ? ❖ Number of isomers = 2n Since “n” = the # of asymmetric centers here, we have 2 asymmetric centers, So we should have 4 isomers
❖ Some of these isomers are enantiomers and some of them are diastereomers. We may find some of them identical !!!!!
❖ Structures (1 ,2) and (3 ,4) are enantiomers (note each S became R and vice versa) ❖Structures ( 1, 3) ,( 1,4) ,(2,3) and (2,4) are diastereomers (note one S became R, and the other dose not change)
How many stereoisomers?
For 2,3 dichlorobutane, have 2 asymmetric centers, so we should have 4 isomers. But is this true?!!!!!
❖Structures (1,2) are identical (meso compound) because the molecule contains internal plane of symmetry. Thus we just have 3 isomers not four. ❖ Structures (3 ,4) are enantiomers. ❖Structures ( 1, 3) ,( 1,4) and (2,4) are diastereomers. How many stereoisomers?
For 2,3,4-trichlorohexane, we have 23 = 8 isomers ? ?
❖ (1 ,2) and (3 ,4), (5,6) , (7,8) are enantiomers ❖( 1, 3) ,( 1,4) ,(2,3) and (2,4) are diastereomers Flow chart summarizing the relationship between two molecules: Practices
Check the relation between each pair of the following molecules:
Ex 1 Ex3 Ex2
Ex4 Ex5 Ex5 Examples
COOH COOH H * OH HO * H HO * H H * OH COOH enantiomers COOH (2R,3R)-tartaric acid (2S,3S)-tartaric acid
COOH H * OH A meso compound, contains 2 or more H * OH COOH stereocenters and a (2R,3S)-tartaric acid plane of symmetry Importance of Stereochemistry
Stereochemistry plays an important role in determining the properties and reactions of organic compounds. HN The properties of manyH drugsN depends on their stereochemistry:
O O O O CH CH NHCH3 NH3NCHH3 3NH
Cl Cl Cl Cl
(S)-ketamine (R)-ketamine anesthetic hallucinogen Properties of Enantiomers
1. Same boiling point, melting point, density 2. Same refractive index 3. Different interaction with other chiral molecules e.g.Enzymes Enzymes are capable of distinguishing between stereoisomers:
4. Different direction of rotation in polarimeter
5. Enantiomers are difficult to separate Polarimetry
Polarimeter measures optical rotation of a compound
Use monochromatic light, usually sodium D Movable polarizing filter to measure angle Clockwise = dextrorotatory = d or (+) (R enantiomer) Counterclockwise = levorotatory = l or (-) (S enantiomer) Polarimetry
Plane-Polarized Light through an Achiral Compound
Plane-Polarized Light through a chiral Compound Specific Rotation, [α]
[α] = α / cl a = observed rotation, c = concentration in g/mL l = length of tube in dm Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counter clockwise rotation
Specific Rotations of some Common Organic Compounds:
Compound [a] # * centers Penicillin V +233.0 3 Sucrose +66.5 10 Camphor +44.3 2 MSG +25.5 1 Cholesterol -31.3 8 Morphine -132.0 5 Diastereomers
Stereoisomers that are not mirror images. Molecules with 2 or more chiral carbons. Geometric isomers (cis-trans), since H H H CH3 they are not mirror images. C C C C H3C CH3 H3C H cis-2-butene trans-2-butene Properties of Diastereomers:
Diastereomers have different physical properties: m.p., b.p. They can be separated easily.