Chem 125 Lecture 10 9/26/07 Preliminary
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Transcript Chem 125 Lecture 10 9/26/07 Preliminary
Chemistry 125: Lecture 29
November 13, 2009
“Absolute” Configuration
X-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.
PRELIMINARY
For copyright
notice see final
page of this file
COOH
H
HO
OH
H
HO
H
H
OH
COOH
d-(+)
COOH
?
HO
H
H
OH
H
HO
OH
H
COOH
l-(-)
How does Optical Activity work?
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:
right
z
clockwise
Changing
Time
Fixed
atTime
Fixed
Position
The instantaneous electric field
vectors of right- and leftcircularly polarized light beams
propagating along z.
counterz clockwise
left
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.
Circular Differential Refraction
Linearly polarized light can be described as a coherent
superposition of right- and left-circularly polarized waves
of equal amplitude.
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.
l L
(n n R )
Go to Google Images for animations (Google
‘circularly polarized light’ and open the
www.enzim.hu site).
From P.W. Atkins, Physical Chemistry (OUP)
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.
The Rotational Strength
The optical rotation angle is given by
l L
(n n R )
Using quantum-mechanical perturbation theory this becomes
2mo lN
2
Im n m j
2
2
3
jn jn
j mn
2c/
The molecular quantity responsible for optical rotation (and circular
dichroism) is the rotational strength:
R j n Im n m j
j m n .
m 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!
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
transition at ~ 290 nm
* n transition is magnetic dipole-allowed, electric dipole-forbidden.
Electric dipole character is induced by mixing of the oxygen dYZ orbital into
the orbital:
C
O
C
O
C
O
*
C
O
C
O
C
O
x
z
mix
y
n
* n
n
dXZ n
linear displacement
of charge
(electric)
rotation of charge
(magnetic)
mixed by
environment
asymmetry
+ dXZ) n
helical motion
of charge
(both)
This generates a mZmZ component (from m.m) of the rotational strength:
R dYZ n Im n mZ dYZ dYZ mZ n
2mo lN
2
Im n m j
2
2
3
jn jn
j mn
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.
Must sum >1500 excitations to get steady value!
J. Phys. Chem. A, 2008, 112, 2415-2422
Quantum-Chemical Calculations
Calculated specific rotation of 2,3-hexadiene as a function of the number of excited states considered.
Absolute Configuration
J. M. Bijvoet
van't Hoff Laboratory, Univ. Utrecht
(1949-51)
Na Rb d-(L)-Tartrate
X-ray anomalous
dispersion
60 year old
Fischer Guess
for of our
“The question of nomenclature is beyond the scope
investigation... The problem of nomenclature (L)-Tartrate
now concerns
given configurations, and requires a notation which denotes
these configurations in an unambiguous and if possible selfexplanatory way.” (Bijvoet, 1951)
Naming Double Bond Configuration
Malic Acid
(HO2C)CH(OH).CH2. (CO2H)
(HO2C)HC=CH(CO2H)
Maleic & Fumaric Acids
Absolute nomenclature
is hard to generalize
(though relative is fine)
H3C
cis
CH3
H
H
COOH
cis or trans?
H
H
COOH
HOOC
O
+ H2O
O
cis
COOH
O
(on this side of)
HOOC
H
trans
(across)
Double Bond Configuration
Assign groups at either end "priority"
by atomic number (or weight for isotopes)
at first difference
H
H3 C
H
C
CH3
HO
H
O
C
COOH
O
H
HO
O
O
O
C
COOH
O
H3 C
H
H
H
C
CH3
H
The names
trans and cis are "polluted"
previous usage.
(E)ntgegen
(Opposed)
(Z)by
usammen
(Together)
In Assigning Priority
Proceed One "Shell" at a Time
(respecting previous decisions)
O
H
O
C
H
O
C Win
Tie
O
H
C
H
O Cl is high
in priority,
but irrelevant;
H the decision Cl
is already made.
H3 C
Win
O
Tie
H
C
C
H
Cl
R. S.
Cahn
V.
C. K.
Ingold Prelog
R. Robinson
by permission J. D. Roberts
The 1950s "CIP" Priority Scheme is Conventional
R. B.Woodward
Robinson: "Hello Katchalsky. What are you doing here in Zurich?"
Prelog: "Excuse me, Sir Robert, I am only Prelog, and I live here."
Robinson: "You know, Prelog, your and Ingold's configurational
notation is all wrong."
Prelog: "Sir Robert, it can't be wrong. It is just a convention.
You either accept it or not."
Robinson: "Well then, if it is not wrong, it is absolutely unnecessary."
from V. Prelog, My 132 semesters of chemistry studies (1981)
http://www.bl.uk/onlinegallery/themes/euromanuscripts/lindisfarne.html
Exercise for
Monday:
Eadfrith’s
Error
(Click here & create your
very own chiral conventions)
D
H
HO
left
turn
1
CIP (R/S) Nomenclature
CH3 for Stereogenic Centers HO
2
2
CH3
2
D3
HO
H4
(S)inister (left)
H
HO
OH
3
H
D
right
turn
CH3
COOH
4
CH3
1
H
1
HO
H4
D3
(R)ectus (right)
COOH
H
(2R,3R)2,3-dihydroxy
butanedioic
acid
H
Bloomer Gate
Organic
Racemization (R)
(RS)
CH3
O
HO
planar
achiral!
(R)-Lactic Acid
CH3
C
(S)-Lactic Acid
OH
CH3
CH3
HOMO
HO
HO
H
H :B
CH3
HO
O
COOH
COO
H
easy
C
H
HO
*
COOH
LUMO
OH
harder
(occasional)
CH3
O
HO
C
OH
dianion
very rare
End of Lecture 29
Nov. 13, 2009
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