高等有机化学--lecture 12
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energy
C-H TS ZPE
Scope of Lecture
Diels-Alder in water
kinetic isotope effects
measuring
KIEs at natural
explicit
abundance
solvation
computational
and FEP
chemistry II
(2) Make measurements on natural abundance material, which removes the need to synthesize carbon-13 labeled material.
I like to maintain a strict connection between theory and experiment, so let us start with the experimental details of how to measure an isotope effect. Under normal circumstances:
E. Kwan
Lecture 12: Computational Chemistry II
Chem 106
Applications of Computational Chemistry
Eugene E. Kwan September 28, 2011.
Key Questions
(1) How can carbon-13/carbon-12 kinetic isotope effects be measured at natural abundance? How can the results be interpreted?
experimental
implicit
transition states
solvation
Claisen rearrangement,
dihydroxylation
Key References
R
R0
1 F1
k2
1
k1
C-D TS ZPE
C-H ZPE
C-D ZPE
reaction coordinate (2) What is involve in solvation? How does it affect the
While the connection between KIEs and computations may not be immediately apparent, we will see here that they are a sensitive probe of transition state geometries. It is now possible to predict heavy atom KIEs for many reactions. In some cases, this has allowed mechanisms that are kinetically very similar to be distinguished by comparing the computed and observed KIEs for the different possibilities.
(3) Do not measure the rates at all; instead, perform competition experiments and infer the relative rates from isotopomer distributions.
kH
AH
kD
AD
P H fast P D slow
Assuming that the bond to the hydrogen or deuterium is broken magnitude is of no concern. You will soon see that these KIEs in the rate-determining step ("primary"), the KIE will generally be can be predicted with similar accuracy, allowing comparisons.
rates of Diels-Alder reactions?
1. Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics. 2nd ed. Lewars, E.G. Springer, 2011.
KIE = kH >1 kD
Generally, carbon-13 NMR is used, allowing KIEs to be measured with quantitative accuracy. These isotope effects are generally small (primary: 1.01-1.05), but since they can be measured with three decimal place precision, their small
Singleton has developed (Singleton JACS 1995 117 9357) an alternative strategy:
(1) Measure carbon 12/carbon 13 KIEs, which can be predicted with quantitative accuracy.
I think Professor Daniel A. Singleton (Texas A&M) for numerous discussions and advice.
E. Kwk.baidu.coman
Lecture 12: Computational Chemistry II
Chem 106
Kinetic Isotope Effects
2. Molecular Modeling Basics Jensen, J.H. CRC Press, 2009.
3. Computational Organic Chemistry Bachrach, S.M. Wiley, 2007.
O +
O
O O
4. Essentials of Computational Chemistry: Theories and Models (2nd ed.) Cramer, C.J. Wiley, 2004.
C-H TS ZPE
Scope of Lecture
Diels-Alder in water
kinetic isotope effects
measuring
KIEs at natural
explicit
abundance
solvation
computational
and FEP
chemistry II
(2) Make measurements on natural abundance material, which removes the need to synthesize carbon-13 labeled material.
I like to maintain a strict connection between theory and experiment, so let us start with the experimental details of how to measure an isotope effect. Under normal circumstances:
E. Kwan
Lecture 12: Computational Chemistry II
Chem 106
Applications of Computational Chemistry
Eugene E. Kwan September 28, 2011.
Key Questions
(1) How can carbon-13/carbon-12 kinetic isotope effects be measured at natural abundance? How can the results be interpreted?
experimental
implicit
transition states
solvation
Claisen rearrangement,
dihydroxylation
Key References
R
R0
1 F1
k2
1
k1
C-D TS ZPE
C-H ZPE
C-D ZPE
reaction coordinate (2) What is involve in solvation? How does it affect the
While the connection between KIEs and computations may not be immediately apparent, we will see here that they are a sensitive probe of transition state geometries. It is now possible to predict heavy atom KIEs for many reactions. In some cases, this has allowed mechanisms that are kinetically very similar to be distinguished by comparing the computed and observed KIEs for the different possibilities.
(3) Do not measure the rates at all; instead, perform competition experiments and infer the relative rates from isotopomer distributions.
kH
AH
kD
AD
P H fast P D slow
Assuming that the bond to the hydrogen or deuterium is broken magnitude is of no concern. You will soon see that these KIEs in the rate-determining step ("primary"), the KIE will generally be can be predicted with similar accuracy, allowing comparisons.
rates of Diels-Alder reactions?
1. Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics. 2nd ed. Lewars, E.G. Springer, 2011.
KIE = kH >1 kD
Generally, carbon-13 NMR is used, allowing KIEs to be measured with quantitative accuracy. These isotope effects are generally small (primary: 1.01-1.05), but since they can be measured with three decimal place precision, their small
Singleton has developed (Singleton JACS 1995 117 9357) an alternative strategy:
(1) Measure carbon 12/carbon 13 KIEs, which can be predicted with quantitative accuracy.
I think Professor Daniel A. Singleton (Texas A&M) for numerous discussions and advice.
E. Kwk.baidu.coman
Lecture 12: Computational Chemistry II
Chem 106
Kinetic Isotope Effects
2. Molecular Modeling Basics Jensen, J.H. CRC Press, 2009.
3. Computational Organic Chemistry Bachrach, S.M. Wiley, 2007.
O +
O
O O
4. Essentials of Computational Chemistry: Theories and Models (2nd ed.) Cramer, C.J. Wiley, 2004.