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General
Organic ChemistryTwo credits
Second Semester 2009
King Saud bin Abdulaziz University for Health Science
Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. CareyThird Edition
Instructor: Rabih O. Al-Kaysi, PhD.
Chapter 7Chapter 7
Stereochemistry Stereochemistry
Lecture 13
7-3Dr. Wolf's CHM 201 & 202
Fischer ProjectionsFischer Projections
• Purpose of Fischer projections is to show Purpose of Fischer projections is to show configuration at chirality center without configuration at chirality center without necessity of drawing wedges and dashes or necessity of drawing wedges and dashes or using models. using models.
7-4Dr. Wolf's CHM 201 & 202
Rules for Fischer projectionsRules for Fischer projectionsRules for Fischer projectionsRules for Fischer projections
Arrange the molecule so that horizontal Arrange the molecule so that horizontal bonds at chirality center point toward you bonds at chirality center point toward you and vertical bonds point away from you.and vertical bonds point away from you.
Br Cl
F
H
7-5Dr. Wolf's CHM 201 & 202
Rules for Fischer projectionsRules for Fischer projectionsRules for Fischer projectionsRules for Fischer projections
Projection of molecule on page is a cross. When Projection of molecule on page is a cross. When represented this way it is understood that represented this way it is understood that horizontal bonds project outward, vertical bonds horizontal bonds project outward, vertical bonds are back.are back.
Br Cl
F
H
7-6Dr. Wolf's CHM 201 & 202
Rules for Fischer projectionsRules for Fischer projectionsRules for Fischer projectionsRules for Fischer projections
Projection of molecule on page is a cross. When Projection of molecule on page is a cross. When represented this way it is understood that represented this way it is understood that horizontal bonds project outward, vertical bonds horizontal bonds project outward, vertical bonds are back.are back.
BrBr ClCl
FF
HH
7-7Dr. Wolf's CHM 201 & 202
Physical Properties of Physical Properties of EnantiomersEnantiomers
7-8Dr. Wolf's CHM 201 & 202
Same:Same: melting point, boiling point, density, spectroscopy, etc..melting point, boiling point, density, spectroscopy, etc..
Different: Different: properties that depend on shape of molecule properties that depend on shape of molecule
(biological-physiological properties) can be(biological-physiological properties) can bedifferent different
Physical properties of enantiomersPhysical properties of enantiomersPhysical properties of enantiomersPhysical properties of enantiomers
7-9Dr. Wolf's CHM 201 & 202
OO OO
CHCH33 CHCH33
HH33CC HH33CCCHCH22 CHCH22
OdorOdorOdorOdor (–)-Carvone(–)-Carvonespearmint oilspearmint oil
(+)-Carvone(+)-Carvonecaraway seed oilcaraway seed oil
S- configuration R- configuration
7-10Dr. Wolf's CHM 201 & 202
IbuprofenIbuprofen is chiral, but normally sold as is chiral, but normally sold asa racemic mixture. The a racemic mixture. The SS enantiomer enantiomer is the one responsible for its analgesic is the one responsible for its analgesic and antiinflammatory properties. and antiinflammatory properties.
Chiral drugsChiral drugsChiral drugsChiral drugs
CHCH22CH(CHCH(CH33))22
HHHH33CC
CC
OO
CC
HOHO
7-11Dr. Wolf's CHM 201 & 202
Reactions That Create A Reactions That Create A
Chiral CenterChiral Center
Many reactions convert achiral Many reactions convert achiral reactants to chiral products.reactants to chiral products.
Many reactions convert achiral Many reactions convert achiral reactants to chiral products.reactants to chiral products.
It is important to recognize, however, that if all of the It is important to recognize, however, that if all of the components of the starting state (reactants, catalysts, components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture.formed as a racemic mixture.
This generalization can be more simply stated as This generalization can be more simply stated as "Optically inactive starting materials can't give "Optically inactive starting materials can't give optically active products."optically active products." (Remember: In order for a (Remember: In order for a substance to be optically active, it must be chiral and one substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the enantiomer must be present in greater amounts than the other.other.
ExampleExampleExampleExample
CHCH33CHCH CHCH22
CHCH33COOHCOOH
OO
HH33CC
OO
CHCH22CC
HH
Chiral, but racemicChiral, but racemicAchiralAchiral
50%50%
50%50%
epoxidation from this direction epoxidation from this direction
gives gives RR epoxide epoxide
epoxidation from this direction epoxidation from this direction
gives gives SS epoxide epoxide
RR
SS
ExampleExampleExampleExample
CHCH33CHCH CHCH22
Chiral, but racemicChiral, but racemic
BrBr22, H, H22OO
CHCH33CHCHCHCH22BrBr
OHOH
AchiralAchiral
ExampleExampleExampleExample
CHCH33CHCH CHCHCHCH33
Chiral, but racemicChiral, but racemic
HBrHBrCHCH33CHCHCHCH22CHCH33
BrBr
AchiralAchiral
7-17Dr. Wolf's CHM 201 & 202
Chiral MoleculesChiral Moleculeswithwith
Two Chirality CentersTwo Chirality Centers
How many stereoisomers when How many stereoisomers when a particular molecule contains a particular molecule contains two chiral centers?two chiral centers?
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
What are all the possible What are all the possible RR and and SS combinations of combinations of the two chirality centers in this molecule?the two chirality centers in this molecule?
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
What are all the possible What are all the possible RR and and SS combinations of combinations of the two chirality centers in this molecule?the two chirality centers in this molecule?
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
4 Combinations = 4 Stereoisomers4 Combinations = 4 Stereoisomers
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
4 Combinations = 4 Stereoisomers4 Combinations = 4 Stereoisomers
What is the relationship between these stereoisomers?What is the relationship between these stereoisomers?
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS
enantiomers:enantiomers: 22RR,3,3RR and 2 and 2SS,3,3SS22RR,3,3SS and 2 and 2SS,3,3RR
2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid
OO
CHCH33CHCHCOHCHCHCOH
HOHO OHOH
2233
Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS
but not all relationships are enantiomericbut not all relationships are enantiomeric
stereoisomers that are not enantiomers are: stereoisomers that are not enantiomers are: diastereomers…….diastereomers…….
similar but not identical chemical and physical propertiessimilar but not identical chemical and physical properties
COCO22HH
CHCH33
Fischer ProjectionsFischer ProjectionsFischer ProjectionsFischer Projections
recall for Fischer recall for Fischer projection: horizontal projection: horizontal bonds point toward bonds point toward you; vertical bonds you; vertical bonds point away point away
staggered conformation staggered conformation does not have correct does not have correct orientation of bonds for orientation of bonds for Fischer projectionFischer projection
Fischer projections Fischer projections Fischer projections Fischer projections
transform transform molecule to molecule to eclipsed eclipsed conformation conformation in order to in order to construct construct Fischer Fischer projectionprojection
Fischer projections Fischer projections Fischer projections Fischer projections
COCO22HH
CHCH33
OHOH
OHOH
HH
HH
Erythro and ThreoErythro and ThreoErythro and ThreoErythro and Threo
stereochemical prefixes used to specify stereochemical prefixes used to specify relative relative configuration configuration in molecules with two chirality in molecules with two chirality centerscenters
easiest to apply using Fischer projectionseasiest to apply using Fischer projections
orientation: vertical carbon chainorientation: vertical carbon chain
when carbon chain is vertical, same (or when carbon chain is vertical, same (or analogous) substituents on analogous) substituents on same sidesame side of of Fischer projectionFischer projection
COCO22HH
CHCH33
OHOH
OHOH
HH
HH
––9.5°9.5° +9.5°+9.5°
COCO22HH
CHCH33
HH
HH
HOHO
HOHO
ErythroErythroErythroErythro
when carbon chain is vertical, same (or when carbon chain is vertical, same (or analogous) substituents on analogous) substituents on opposite sidesopposite sides of of Fischer projectionFischer projection
+17.8°+17.8° ––17.8°17.8°
OHOH
COCO22HH
CHCH33
HH
HH
HOHO
COCO22HH
CHCH33
OHOHHH
HHHOHO
ThreoThreoThreoThreo
7-30Dr. Wolf's CHM 201 & 202
Achiral MoleculesAchiral Moleculeswithwith
Two Chirality CentersTwo Chirality Centers
It is possible for a molecule to have It is possible for a molecule to have chirality centers yet be achiral.chirality centers yet be achiral.
2,3-Butanediol2,3-Butanediol2,3-Butanediol2,3-Butanediol
Consider a molecule with two equivalently substituted Consider a molecule with two equivalently substituted chirality centers such as 2,3 butanediol.chirality centers such as 2,3 butanediol.
CHCH33CHCHCHCHCHCH33
HOHO OHOH
3322
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3RR 22SS,3,3SS 22RR,3,3SS
chiralchiral chiralchiral achiralachiral
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3RR 22SS,3,3SS 22RR,3,3SS
chiralchiral chiralchiral achiralachiral
CHCH33
CHCH33
OHOHHH
HHHOHOHH OHOH
CHCH33
CHCH33
HHHOHO HH
CHCH33
CHCH33
OHOH
OHOHHH
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3RR 22SS,3,3SS
chiralchiral chiralchiral
these two arethese two areenantiomersenantiomers
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3RR 22SS,3,3SS
chiralchiral chiralchiral
CHCH33
CHCH33
OHOHHH
HHHOHOHH OHOH
CHCH33
CHCH33
HHHOHOthese two arethese two areenantiomersenantiomers
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3SS
achiralachiral
the third structure is the third structure is superposable on itssuperposable on itsmirror imagemirror image
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3SS
achiralachiral
therefore, this structure therefore, this structure and its mirror imageand its mirror imageare the same are the same
it is called a meso formit is called a meso form
a meso form is an achiral a meso form is an achiral molecule that has molecule that has chirality centerschirality centers
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3SS
achiralachiral
HH
CHCH33
CHCH33
OHOH
OHOHHHHHHOHO
CHCH33
CHCH33
HHHOHO
therefore, this structure therefore, this structure and its mirror image and its mirror image are the same are the same
it is called a meso formit is called a meso form
a meso form is an achiral a meso form is an achiral molecule that has molecule that has chirality centerschirality centers
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3SS
achiralachiral
meso forms have a plane of meso forms have a plane of symmetry and/or a center of symmetry and/or a center of symmetrysymmetry
plane of symmetry is most plane of symmetry is most common casecommon case
top half of molecule is mirror top half of molecule is mirror image of bottom halfimage of bottom half
Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol
22RR,3,3SS
achiralachiral
HH
CHCH33
CHCH33
OHOH
OHOHHHHHHOHO
CHCH33
CHCH33
HHHOHO
A line drawnA line drawnthe center ofthe center ofthe Fischer the Fischer projection of aprojection of ameso formmeso formbisects it intobisects it intotwo mirror-two mirror-image halves.image halves.
HOHO OHOH
HH
HH
HOHO
HH33CC
HH
HHCHCH22CHCH22COCO22HH
CHCH33
HH
CHCH33
11 chirality centers11 chirality centers
221111 = 2048 stereoisomers = 2048 stereoisomers
one is "natural" cholic acidone is "natural" cholic acid
a second is the enantiomer of a second is the enantiomer of natural cholic acidnatural cholic acid
2046 are diastereomers of cholic 2046 are diastereomers of cholic acidacid
Cholic acid Cholic acid Cholic acid Cholic acid
maximummaximum number of stereoisomers = 2 number of stereoisomers = 2nn
where where nn = number of structural units capable of = number of structural units capable of stereochemical variationstereochemical variation
structural units include chirality centers and cis structural units include chirality centers and cis and/or trans double bondsand/or trans double bonds
number is reduced to less than 2number is reduced to less than 2nn if meso forms if meso forms are possibleare possible
How many stereoisomers?How many stereoisomers?How many stereoisomers?How many stereoisomers?
3-Penten-2-ol3-Penten-2-ol
HOHO HH
EE RR
HH OHOH
EE SS
HHHOHO
ZZ RR
HH OHOH
SS
How many stereoisomers?How many stereoisomers?How many stereoisomers?How many stereoisomers? ZZ
A single starting material can give two or moreA single starting material can give two or morestereoisomeric products, but gives one of themstereoisomeric products, but gives one of themin greater amounts than any otherin greater amounts than any other
++
CHCH33
HH
CHCH33
HH
68%68% 32%32%
Stereoselective reactionStereoselective reactionStereoselective reactionStereoselective reaction
CHCH33
CHCH22
HH CHCH33
HH
CHCH33
HH
HH22
PtPt
Chirality CentersChirality CentersOther Than CarbonOther Than Carbon
SiliconSiliconSiliconSilicon
Silicon, like carbon, forms four bonds in its stable Silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds compounds and many chiral silicon compounds have been resolvedhave been resolved
SiSi SiSidd dd
aabb
cc
aabb
cc
Nitrogen in aminesNitrogen in aminesNitrogen in aminesNitrogen in amines
Pyramidal geometry at nitrogen can Pyramidal geometry at nitrogen can produce a chiral structure, but enantiomers produce a chiral structure, but enantiomers equilibrate too rapidly to be resolvedequilibrate too rapidly to be resolved
NN NN:: ::
aabb
cc
aabb
cc
very fastvery fast
Phosphorus in phosphinesPhosphorus in phosphinesPhosphorus in phosphinesPhosphorus in phosphines
Pyramidal geometry at phosphorus can produce a Pyramidal geometry at phosphorus can produce a chiral structure; pyramidal inversion slower than chiral structure; pyramidal inversion slower than for amines and compounds of the type shown have for amines and compounds of the type shown have been resolvedbeen resolved
PP PP:: ::
aabb
cc
aabb
cc
slowslow
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