1 © David Gallagher 2002 Mount St. Helens, WA, USA, May 18, 1980 David Gallagher * Modeling...

1© David Gallagher 2002Mount St. Helens, WA, USA, May 18, 1980

David Gallagher *

Modeling Chemical Reactivity Visualization of chemical reactivity Kinetic & thermodynamics

2© David Gallagher 2002

Visualization of Reactivity

Susceptibility to electrophilic attack? (phenol)

* K. Fukui et al, J. Chem. Phys., 11. 1433-1442 (1953)** Also, nucleophilic, radical, electrostatic potential, superdelocalizability, etc.

HOMO onelectron

iso-densitysurface

HOMO

Largest HOMO density on para & ortho positions

Partial charges

Largest negative charge on para & ortho positions

••+-

Fukui’s Frontier Density*

Electrophilic susceptibility**

Highest frontier density on para & ortho positions


Susceptibility to Attack

*Fukui’s frontier density on electron isodensity surface

Electrophilic(occupied obitals)

Nucleophilic(unoccupied orbitals)

Radical(all valence orbitals)


Polyester Weatherability*

• New methyl propane diol based Polyester introduced

• Competitor claims “Norrish type II” degradation mechanisms

mean rapid degradation of diols with beta hydrogens under UV

radiation, unlike competitor’s neopentyl based polyester

H

methyl propane diol neopentyl diol


• Experimental accelerated test results inconsistent with “Norrish”

• “Radical susceptibilty” surfaces similar for both polyesters

* Published in Journal of Coatings Technology Vol. 67, No. 847, August ‘95

by Carl J. Sullivan & Charles F. Cooper, ARCO Chemical Company

CAChe & Tests Disprove Claims*

methyl propane polyester neopentyl polyester

H


Conrotatory sterically hindered

Insights into Catalysis

A. R. Pinhas, B. K. Carpenter, J.C.S. Chem. Comm., 1980, 15.

tricyclo-octadiene bicyclo-octatriene

X

Why does iron tricarbonyl apparently catalyse this reaction?

Fe(CO)3

Disrotatory ?


Frontier MO Control of Stereochemistry

• Thermal reaction: most reactive electrons in HOMO

Conrotatory

Sterically hindered

CAChe MOPAC AM1-d

Disrotatory

Sterically allowed

Fe

• Iron carbonyl changes symmetry of frontier orbital (HOMO)


Improve Yield, Minimize Byproducts

83% syn

17% anti

methylnitrone

monofluoroallene

+ ?

• Thermodynamic control? Isomers have same Hf, - No!

• Kinetic control? syn-product T-state is lower energy, - Yes!

• Why is syn lower? Visualize energy terms of T-state*

*Purvis III, G. D., J. Computer Aided Molecular Design, 5 (1991) 55-80

-ON+

CF

N

O

F

N

O

F


Sterics of the Transition-state

• Sterics, Frontier orbitals & Electrostatics all influence transition state

• Sterics slightly favor anti-product: but inconsistent with experiment (17%)

anti-addition (17%) syn-addition (83%)

methylnitrone

MFA

sterichindrance?


Orbitals of the Transition-state

• Closest energy frontier orbitals are nitrone HOMO & MFA LUMO

• Frontier orbital overlap suggest both transition states equally allowed


nitroneHOMO

MFALUMO

+

+

+

+

+

+

+

+


Electrostatic Control of Yield

• Anti-addition shows +/+ repulsion, syn seems energetically favored

• Product ratios are consistent with electrostatic control (strongest long-range)

• Thus, changing solvent (dielectric) or substituents could control product yield


nitrone

MFA

red: +ve

blue: -ve

Electrostatic isopotential surfaces: proton repelled by 20 kcals on red surface.

+/+


Visualization of Reactivity

* K. Fukui et al, J. Chem. Phys., 11, 1433-1442 (1953)

Electrostatics (AM1)

partial charges (menu)

electrostatics on surface

electrostatic isopotential

Frontier orbitalsHOMO, LUMO, etc.

susceptibility*, (substrate only)

superdelocalizability*, (both reactants)

Stericsspace-filling

VdW (electron isodensity)

MM conformation search


Thermodynamics & Kinetics

1. Thermodynamics (heat of reaction) Eproducts – Ereactants

Heats of Formation are calculated by MOPAC PM3http://www.shodor.org/UNChem/advanced/kin/arrhenius.html

Reactant Er

Energy of reaction = Ep – Er

Product Ep

Activation energy Ea = Et – Er

T-state Et

2. Kinetics (activation energy) Etransition-state - Ereactants

k = A*exp(-Ea/R*T)


Substitution Position by Kinetics

Lowest energy* transition state = fastest reaction = main product

2) Ortho: 171 Kcals1) Para: 167 Kcals 3) Meta: 183 Kcals

Br

Br

Br

Transition states for electrophilic attack by Br+ on phenol


Urethane Polymerization Reaction

• Lower temperature would reduce costs and thermal decomposition

R-N=C=O + CH3OH = RNHCOOCH3

R

Catalyst

*Malwitz, N., Reaction Kinetic Modeling from PM3 Transition State Calculations, J. Phys. Chem., Vol 99, No. 15, 1995 p. 5291

R Catalyst Solvent Activation Emethyl 43.7 kcalphenyl 41.3 kcalmethyl N(CH3)3 32.0 kcalphenyl N(CH3)3 26.9 kcalphenyl N(CH3)3 CH3OH 16.7 kcal

• Model transition states, then calculate catalyst & solvent effects

• To save time & money, CAChe used to explore reaction conditions

Project successful, saving many months& cost of chemicals for pilot scale


Unexpected Insights

R

Catalyst


• Literature states lone-pair of trimethylamine ‘attacks’ + of carbonyl ‘C’

• Modeling does NOT support this (lone pair of catalyst attaches to proton)

• New insight reveals alternative (or true?) mechanism


Polyurethane: “Summary”

“... capable of offering insight useful toward

• minimizing unwanted side reactions

• optimizing yields

• suggesting reaction conditions

• and determining polymer composition...”



CPD Dimerization & Temperature

* G = H - T S

* * *

Exo

ther

mic

En

do

ther

mic

low temp

high temp


Hf RMS errors (kcal.mol-1) compared to experiment

*Comparison of the accuracy of semiempirical and some DFT methods for predicting heats of formation, James J. P. Stewart, J Mol Model (2004) 10:6-12

MOPAC & DFT Accuracy

Errors in Heats of Formation (kcal/mol)*No. in set RMS error Max. error

MNDO 1,238 29.69 178.8AM1 1,238 13.80 86.1PM3 1,238 7.82 38.1PM5 1,238 6.65 33.8DFT B88-LYP (DZ) 1,238 8.50 40.3DFT B88-PW91 (DZ) 1,238 8.51 39.8


Strategies for locating T-States

1. Sketch a ‘guess’

2. Modify similar TS

3. Map reaction

4. Search for saddle


Map the Reaction

Screen capture with “SNAP32”, AVI movie made with “GIF Movie Gear”

Diels Alder

MOPAC PM3 Optimized Grid


Reactant Product

2. Copy & name it “Product”

Search for Saddle (keto-enol)

1. Sketch “Reactant” with atom #s

T-state

4. Copy “Reactant”, name “T-state”

3. Edit to “Product” structure

5. Experiment: Search for Saddle


Verifying the T-State

1. Refine

2. Verify (IR spectrum)


Verify Transition State

3. Do calculated bond-orders seem reasonable?

“View | Pt. Chg. & Calc. Bond Order”

2. Do atom-distances seem reasonable?

“Adjust | Define geometry label”

1. Single negative

vibration?

“Verify T-state”


Intermediates?

? ?

Intrinsic Reaction Coordinate (IRC)


Reaction Path (IRC)

Intrinsic Reaction Coordinate (IRC)

Water-catalyzed keto-enol tautomerization, reaction path


Solvents & Radicals


Summary for locating T-States

1. Create an approximate T-state

2. Refine (consider solvents & radicals)

3. Verify (neg. vibration, bonds)

4. Check reaction path for intermediates


Safe Laboratory Practice

“The purpose of computing

is insight, not numbers”

Amdahl

“Calibrate before use!”

(experiment or ab initio)

Old Chemists never die… they simply fail to react

1 © David Gallagher 2002 Mount St. Helens, WA, USA, May 18, 1980 David Gallagher * Modeling...

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Transcript of 1 © David Gallagher 2002 Mount St. Helens, WA, USA, May 18, 1980 David Gallagher * Modeling...