unit one part 8: stereochemistry - massey universitygjrowlan/chem101/lct8.pdfunit one part 8:...
TRANSCRIPT
Unit One Part 8: stereochemistrygjr-–-
• Describe the difference between stereoisomers & structural isomers• Nomenclature used for double bonds (cis-trans or E-Z)• Predict conformations of cyclohexanes• Define chirality and recognise stereocentres• Understand enantiomers and diastereoisomers
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dr gareth rowlands; [email protected]; science tower a4.12http://www.massey.ac.nz/~gjrowlan
Isomerismgjr-–-
OH
cyclopentanolC5H10O
OH
(E)-pent-3-en-1-olC5H10O
O4-methoxybut-1-ene
C5H10O
O
3-methylbutan-2-oneC5H10O
HO H
(S)-pent-1-en-3-olC5H10O
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structural isomers
enantiomers
diastereomers
different bond pattern
samebond pattern
non-superimposable mirror images
stereoisomers
ISOMERS
Structural isomers
Configurational isomerism or stereoisomerism gjr-–-
• The spatial arrangement of atoms in a molecule is its configuration • Configurational isomers have the same bonds• Configurational isomers can only be interconverted by breaking a bond• Easiest compounds to see this in are the alkenes...
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H
R H
R
Z or cisE or trans
H
R R
Hless stable
steric crowding
B
A C
D≠ A
B C
D
Atom connectivity identicalBut different configurationsKnown as diastereoisomers
They are different compounds
CO2Me
MeO2C
H
H
dimethyl fumaratetrans (E)mp 103°Cbp 193°C
H
MeO2C
H
CO2Me
dimethyl maleatecis (Z)
mp –19°Cbp 202°C
E and Z nomenclaturegjr-–-
• E-alkenes have the highest priority groups on the opposite sides• Z-alkenes have the highest priority groups on the same side
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H2C
CH3 > >CH3O
CH3 OH
C N ≡ CN
NNC
C
atom = Br>Cl>O>N>C>HAtomic number = 35, 17, 8, 7, 6 & 1
Priority rules1. Rank atoms attached to alkene in order of decreasing atomic number
2. If atoms are the same, move along substituent until a difference is found
.3. Multiple bonds are assumed to count as the same number of single bonds
C CCl
H3C CH3
CH2CH3
C CC
Br CH2CH3
CH2OHN
C CH3C C6H5
CH3H3CO
C CHO2C
Ph CH2OH
CHO
(Z)-3-hydroxymethyl-4-oxo-2-phenylbut-2-enoic acid
(E)-2-bromo-3-(hydroxymethyl)pent-2-enenitrile
(E)-3-methyl-4-phenylpent-3-en-2-one
(Z)-2-chloro-3-methylpent-2-ene
1 1
1
1 1
1
1 1
2 2
2
2 2
2
2 2
Cis–trans isomerism in cyclohexanesgjr-–-
HtBu
Me
HtBu
H
H
Me
bulky group equatorial favoured
tert-butyl group rarely is axial
• If two groups on a ring we must specify relative stereochemistry • Cis - both groups are on the same face• Trans - groups are on opposite faces
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Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cltrans-1,2-
dichlorocylohexane(anti)
cis-1,2-dichlorocylohexane
(syn)cis-1,2-
dichlorocylohexane(syn)
trans-1,2-dichlorocylohexane
(anti)
H
2Cl
H
1Cl
2Cl
H
H
1Cl
one conformation is disfavoured as it has two axial groups so maximum 1,3-diaxial interactions
H
1Cl
2Cl
H
1Cl
H
2Cl
H
both conformations have one axial substituent & are identical
X
Decalinsgjr-–-
• Another example of stereoisomers comes from fused bicyclic molecules• Like a double bond the substituents could be cis or trans • Like a double bond these two are not interconvertible unless a bond broken
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H
H
H
Htrans-decalin equatorial, equatorial
ring fusion
H
H
H
H
cis-decalin equatorial, axial ring fusion
Chiralitygjr-–-
• The most confusing form of stereochemistry• A chiral structure is one that is non-superimposble on its mirror image• Occurs in nature (snails, honeysuckle etc), man-made objects (propellers,
corkscrews etc) and in molecules...
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Mirror image Left & right hands Non-superimposable
Enantiomers
Mirror plane
Chiral
gjr-–-
• This form of stereoisomerism arises from a lack of symmetry• The molecule & its mirror image are different• The molecule & its mirror image are known as enantiomers
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rotate
Mirror plane
Achiral
For those of a sick & twisted disposition more info on chirality & stereochemistry can be found at my website: http://www.massey.ac.nz/~gjrowlan/teaching.html
X
rotate
X
Enantiomers IIgjr-–-
• Most common form of chirality has a carbon atom with 4 different groups attached & is called central chirality
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NH
O O
HN
O
O
(R)-thalidomide(morning sickness)
Me2NMe
Ph O
EtO
darvonpainkiller
NHMeN
nicotinetoxin / stimulant
Me CO2H
NH2
L-alaninemammalian amino acid
• Many other forms of chirality including helical, axial & planar
PPh2PPh2
(R)-(+)-BINAP(R)-2-(diphenylphosphino)-1-(2-(diphenylphosphino)naphthalen-1-yl)naphthalene
M-[8]helicene
FePh2PPh
(R)-2-phenyl-1-(diphenylphosphanyl)
ferrocene
Physical properties of enantiomersgjr-–-
• Enantiomers have identical physical properties such as mp, bp etc• They only differ in their interactions with other chiral entities
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α
light source
polariser plane polarised light
samplecell length l (dm)
readinglight (λ)
Ph CO2H
OHH
(R)-(-)-mandelic acid131-133°C[α]23 –153D
Ph CO2H
HHO
(S)-(+)-mandelic acid131-134°C[α]20 +154D
• Chiral compounds rotate the plane of polarised light (hence optical isomers)• As most biological systems are chiral, enantiomers can have different effects
O
H
(R)-carvonespearmint
O
H
(S)-carvonecaraway
H
(S)-limonenelemons
H
(R)-limoneneoranges
Two chiral centres (diastereoisomers)gjr-–-
enantiomerscis
epoxidemp = 98°C
• A molecule with 1 stereogenic centre exists as 2 enantiomers• Enantiomers have identical physical properties in an achiral environment
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NH2HN
N
O
OHNH2 NH
N
O
HOS R
Mirror
Two enantiomersdiffer by absolute configuration
O
CO2Me
O2N
O
CO2Me
O2N
enantiomerstrans
epoxidemp = 141°C
O
CO2Me
O2N
O
CO2Me
O2N
diastereoisomers
different mp
• A molecule with 2 stereogenic centres can exist as 4 stereoisomers• Enantiomers (mirror images) still have identical physical properties • Diastereoisomers (non-mirror images) have different properties
Chirality in our bodiesgjr-–-
• Common amino acids are all have the same stereochemistry (L or S)• Aspartame (sweetener) is a dipeptide (two amino acids) - two stereocentres• Potentially 4 compounds (n stereocentres can give 2n diastereoisomers)
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HO2C Me
NH2
HO2C
NH2
HO2C
NH2 N
HN
alanine phenylalanine histidine
H2N NH
CO2CH3
O
HO2C
• Insulin is made of 2 peptide chains - 1x30 amino acids & 1x21 amino acids• Potentially 2.25 x 1015 diastereoisomers• A relatively small protein is ribonuclease at 124 amino acids or• Potentially 2.13 x 1037 diastereoisomers
Chiral drugsgjr-–- 13
NH
HN
OH
Et OH
Et
Ethambutoltuberculostatic (anti-TB)
NH
HN
OH
EtOH
Et
(R,R)-enantiomercauses blindness
OHNH
Me Me
(–)-propanololβ-blocker for heart disease
(+)-propanololcontraceptive
OHHN
MeMe
NNS
N O NH
O
OH
(S)-timololhigh blood pressure
N NS
NONH
O
OH
(R)-timololglaucoma
Overviewgjr-–-
What have we learnt?• Molecules are three dimensional...and it makes a difference• The arrangement of atoms in space can form new isomers• Such isomers can only be interconverted by breaking bonds• Mirror images can have very different properties• Synthesis of single enantiomers is very important
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What's next?• A brief look at spectroscopy in many of its glorious forms• Starting with NMR or nuclear magnetic resonance spectroscopy• An idea of what information this tells us about protons in a molecule
dr gareth rowlands; [email protected]; science tower a4.12http://www.massey.ac.nz/~gjrowlan