Chemistry 125: Lecture 29 November 13, 2009 “Absolute” Configuration X-ray and CIP Nomenclature...
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Chemistry 125: Lecture 29November 13, 2009
“Absolute” ConfigurationX-ray and CIP Nomenclature
Preparing Single Enantiomers Determination of the actual atomic arrangement in tartaric acid in 1949 motivated a
change in stereochemical nomenclature from Fischer’s 1891 genealogical convention (D,L)
to the CIP scheme (R,S) based on conventional group priorities. Methods of resolution are
described. 3D visualization of omeprazole. The chemical mode of action of omeprazole is
expected to be insensitive to its stereochemistry, making clinical trials of the proposed
virtues of a chiral switch crucial.
For copyright notice see final page of this filePRELIMINARY
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d-(+) l-(-)
How does Optical Activity work?
COOH
COOH
H
OH
HO
H
COOH
COOH
OH
H
H
HO
COOH
COOH
H
OH
HO
H
COOH
COOH
OH
H
H
HO ?
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Chirality and Circularly Polarized Light
In order to detect molecular chirality, some sort of chiral probe must be used.
Right- and left-circularly polarized light beams are mirror-image chiral systems and so can act as chiral probes:
Chiral molecules respond slightly differently to right- and left-circularly polarized light. A difference in absorption corresponds to circular dichroism; a difference in refractive index leads to optical rotation.
The instantaneous electric field vectors of right- and left-circularly polarized light beams propagating along z.
right
left
z
z
Changing Time
at Fixed Position
counter-clockwise
Fixed Time
clockwise
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Circular Differential Refraction
Linearly polarized light can be described as a coherent superposition of right- and left-circularly polarized waves of equal amplitude.
From P.W. Atkins, Physical Chemistry (OUP)
θΔ A difference in refractive index for the right- and left-circularly polarized beams means a difference in velocity. So the phase relation between the two contrarotating electric vectors will change, resulting in a rotation of the plane of polarization.
Go to Google Images for animations (Google ‘circularly polarized light’ and open the www.enzim.hu site).
)( RL nnl
−=λπθΔ
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A Scattering Picture of Optical Rotation
A circularly polarized light wave ‘bouncing’ from one group to the other as it scatters from a simple two-group chiral molecular structure will sample the chirality. The scattered intensity of right- and left-circularly polarized waves will be slightly different for a given handedness of the chiral structure.
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The Rotational Strength
The optical rotation angle is given by
Using quantum-mechanical perturbation theory this becomes
The molecular quantity responsible for optical rotation (and circular dichroism) is the rotational strength:
and m are electric and magnetic dipole moment operators, respectively, so the optical activity ultimately originates in interference between electric and magnetic dipole transitions during the light scattering process!€
R j ← n( ) = Im n μ j • j m n( ) .
)( RL nnl
−=λπθΔ
€
Δθ =2μolN
3h
ω2
ω jn2 −ω2
Im n μ j • j m n( )j≠n
∑ πc/λ
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The Carbonyl Chromophore
The carbonyl chromophore is an important source of optical activity in many organic compounds. The carbonyl group itself has a plane of symmetry so is not chiral/optically active. Optical activity is induced in its electronic transitions via perturbations from the chiral environment provided by the rest of the molecule.
n←∗π transition at ~ 290 nm
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linear displacement of charge(electric)
helical motionof charge
(both)
n
π*
n
π* n transition is magnetic dipole-allowed, electric dipole-forbidden. Electric dipole character is induced by mixing of the oxygen dYZ orbital into
the π orbital:
€
R π ∗+ λ dYZ( ) ← n( ) = Im n μZ π ∗+ λ dYZ( ) π ∗+ λ dYZ( ) mZ n( )
This generates a ZmZ component (from .m) of the rotational strength:
C O
C O
C O
C O
C OC O
rotation of charge(magnetic)
π* n dXZ n π + dXZ) n
x
z
y
mix
mixed by environment asymmetry
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Quantum-Chemical Calculations
€
Δθ =2μolN
3h
ω2
ω jn2 −ω2
Im n μ j • j m n( )j≠n
∑
The optical rotation can be calculated using ab initio quantum-chemical programs (Gaussian, Dalton). Often sufficiently good to determine absolute configuration from the sign and magnitude.
Calculated specific rotation of 2,3-hexadiene as a function of the number of excited states considered.
J. P
hys.
Che
m. A
, 200
8, 1
12, 2
415-
2422
Must sum >1500 excitations to get steady value!
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Absolute Configuration
J. M. Bijvoetvan't Hoff Laboratory, Univ. Utrecht
(1949-51)
Na Rb d-(L)-TartrateX-ray anomalous
dispersion
60 year old
Fischer Guessfor
(L)-Tartrate “The question of nomenclature is beyond the scope of our investigation... The problem of nomenclature now concerns given configurations, and requires a notation which denotes these configurations in an unambiguous and if possible self-explanatory way.” (Bijvoet, 1951)
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Naming Double Bond ConfigurationMalic Acid
(HO2C)CH(OH).CH2. (CO2H)Maleic & Fumaric Acids
(HO2C)HC=CH(CO2H)Δ
H
HOOC COOH
H H
HOOC
COOH
H
cis(on this side of)
trans(across)
H3C
H
CH3
COOH
cis or trans?
Absolute nomenclatureis hard to generalize
O OO
+ H2O
cistrans
(though relative is fine)
Δ
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Double Bond Configuration
H3C
H
CH3
COOH
H3C
H CH3
COOH
Assign groups at either end "priority"by atomic number (or weight for isotopes)
at first difference
H3C
H
C
C
HOO
O
HH
H
H3C
H
C
C
HH
H
HOO
OO
O
(E)ntgegen (Opposed) (Z)usammen (Together)The names trans and cis are "polluted" by previous usage.
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In Assigning PriorityProceed One "Shell" at a Time
(respecting previous decisions)
C
C
OO
O
HH
H
H
C
C
OO
O
CH
H
H
Cl
H3CCl
Tie
Win
Tie
Win
Cl is highin priority,
but irrelevant;the decision
is already made.
Cl
Cl
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Robinson: "Hello Katchalsky. What are you doing here in Zurich?"
from V. Prelog, My 132 semesters of chemistry studies (1981)
The 1950s "CIP" Priority Scheme is Conventional
R. S.Cahn
C. K.Ingold
V.Prelog
Robinson: "Well then, if it is not wrong, it is absolutely unnecessary."
Robinson: "You know, Prelog, your and Ingold's configurational notation is all wrong."
Prelog: "Excuse me, Sir Robert, I am only Prelog, and I live here."
Prelog: "Sir Robert, it can't be wrong. It is just a convention. You either accept it or not."
R. Robinson R. B.Woodward
by p
erm
issi
on J
. D. R
ober
ts
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Exercise for Monday:
Eadfrith’s Error
(Click here & create your very own chiral conventions)
http
://w
ww
.bl.u
k/on
line
gall
ery/
them
es/e
urom
anus
crip
ts/l
indi
sfar
ne.h
tml
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CIP (R/S) Nomenclaturefor Stereogenic Centers
(S)inister (left)
COOH
COOH
OH
H
H
HO4
3
2
1
1
3
4
2
(2R,3R)-2,3-dihydroxybutanedioic
acid
rightturn
H
(R)ectus (right)
H
HO D
CH3
H
leftturn
HO CH3
D
H
14
2
3
CH3 CH3
HO HODHHD
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Bloomer Gate
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Organic
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:B
Racemization
CH3
HO CO
OH
CH3
HO CO
OH
HOMO
π*LUMO
(R) (RS)
easy
harder(occasional)
CH3
HO CO
OH
dianionvery rare
planarachiral!
(R)-Lactic Acid
HCOOH
CH3
HO
(S)-Lactic Acid
COOHH
CH3
HO
H
HCOO
CH3
HO
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End of Lecture 29Nov. 13, 2009
Copyright © J. M. McBride 2009. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).
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The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0