I. Modeling the Reaction I. Modeling the Reaction between Vinylamine and Singlet between Vinylamine and Singlet Oxygen Oxygen A Semi-Empirical Molecular Orbital Computational Study
Feb 04, 2016
I. Modeling the Reaction between I. Modeling the Reaction between Vinylamine and Singlet OxygenVinylamine and Singlet Oxygen
A Semi-Empirical Molecular Orbital Computational Study
Singlet OxygenSinglet Oxygen
Singlet oxygen (1O2) is an electronically excited form of molecular oxygen.
It is short-lived (~10-5 s), but very reactive.
Usually generated by dye-sensitization:
1Dye ____h____> 1Dye* 1Dye* ____(isc)____> 3Dye*
3Dye* + 3O2 __________> 1O2 + 1Dye
Electron Configuration of Electron Configuration of Singlet Oxygen (HOMO)Singlet Oxygen (HOMO)
3g 1g 1g
(ground state) 22 kcal/mol 37.5 kcal/mol
Triplet Singlet
Typical Modes of Reaction of Typical Modes of Reaction of Singlet OxygenSinglet Oxygen
1O2O
O+
1O2+O OH
X 1O2+
X
OO dioxetane
ene type product
endoperoxide
Reaction of Reaction of 11OO22 with Enamines with Enamines
NH2 1O2+
NH
CCH O
H
+ H2O
Based on product studies in more complex enamines (vinylamine is unstable and very difficult to prepare; it is modeled because it is small, and amenable to rapid calculation):
Modeling Singlet OxygenModeling Singlet Oxygen
Calculated Hf in kcal/mol
Structure MNDO AM1 MINDO/3
singlet O2 12.2 0.7 22.8
(Experimental value is 22.5 kcal/mol)
Intermediates Proposed for Intermediates Proposed for Reaction of Singlet Oxygen Reaction of Singlet Oxygen with Enamineswith Enamines
O
O NH2
O ONH2
OO
NH
OHO
NH2
OO
NH2
O
O
NH2
BackgroundBackground
We had strong kinetic (substituent effect) evidence that favored rate-limiting formation of a charge-transfer complex in the photo-oxygenation (reaction with singlet oxygen) of 1-benzyl-3,4-dihydroisoquinolines, which are in equilibrium with an enamine tautomer.
We decided to model a similar mechanism for vinylamine, the simplest enamine.
Modeling an InteractionModeling an Interaction
An AMPAC input file was created by merging two independently optimized structures: vinylamine and singlet oxygen
Various orientations were tried When one geometry showed
attractive interaction, it was examined more closely.
NCH2C
HH
H
O O
Optimizing the GeometryOptimizing the Geometry
The N-O ‘bond’ length was varied The N-O-O bond angle was varied The C-N-O-O dihedral angle was varied After optimizing one variable,
it was fixed to optimize another; then two were fixed to optimize the third.
Finally the structure was allowed to optimize starting with the best values of the three variables.
NCH2C
HH
H
O O
Attraction between Singlet Attraction between Singlet Oxygen and VinylamineOxygen and Vinylamine
Proposed Orbital InteractionProposed Orbital Interaction
N
O O (LUMO)
2p (HOMO)
Optimized Geometry of the Optimized Geometry of the Charge-Transfer ComplexCharge-Transfer Complex
NCH2C
HH
H
O O
An energy minimum was found at an N-O “bond” length of 1.55 Ao
The lowest energy complex was found to have an N-O-O “bond” angle of 111o
The lowest energy complex was found to have a C-N-O-O dihedral angle of 139o
Reaction Pathway Calculation:Reaction Pathway Calculation:Input File to Vary Bond LengthInput File to Vary Bond Length
t=5000 MINDO3
vinylamine
7 0.00000 0 0.0000 0 0.0000 0 0 0 0
6 1.38210 1 0.0000 0 0.0000 0 1 0 0
1 1.09000 1 113.9000 1 0.0000 1 2 1 0
6 1.34000 1 124.8000 1 179.9000 1 2 1 3
1 0.99900 1 122.4000 0 179.9000 1 1 2 3
1 0.99900 1 120.8000 1 0.0000 1 1 2 3
1 1.08000 1 124.7000 1 0.0000 1 4 2 1
1 1.08000 1 121.3000 1 179.9000 1 4 2 1
8 1.55000 -1 111.4000 1 137.1000 1 1 2 4
8 1.13000 1 111.1000 1 138.9000 1 9 1 2
0 0.00000 0 0.0000 0 0.0000 0 0 0 0
1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 2, 2.2, 2.4, 2.6, 3, 4, 6, 8, 10
Locating the Transition Locating the Transition StructureStructure
The keywords SADDLE, POWELL, and SIGMA were employed sequentially with the geometry of the reactant, a “guess” at the T.S. geometry, and the product geometry.
A FORCE calculation was done on the T.S. geometry provided by this method.
This yielded only 1 imaginary (negative) frequency, confirming the saddle point.
Reaction Energy Profiles: Reaction Energy Profiles: Zwitterionic Peroxide (a) and CT Complex Zwitterionic Peroxide (a) and CT Complex followed by Zwitterionic Peroxide (b)followed by Zwitterionic Peroxide (b)
ConclusionConclusion
A charge-transfer complex may be competitive with direct zwitterionic peroxide formation in the reaction of singlet oxygen with enamines, particularly in those cases where more complex structures may stabilize the intermediate complex or facilitate its rearrangement.
II. Modeling the Quenching of II. Modeling the Quenching of Singlet Oxygen by AminesSinglet Oxygen by Amines
A Semi-Empirical Molecular Orbital Computational Study
Singlet OxygenSinglet Oxygen
Singlet oxygen (1O2) is an electronically excited form of molecular oxygen.
It is short-lived (~10-6 s), but very reactive.
Usually generated by dye-sensitization:
1Dye ____h____> 1Dye* 1Dye* ____(isc)____> 3Dye*
3Dye* + 3O2 __________> 1O2 + 1Dye
Singlet Oxygen...Singlet Oxygen... It is quenched efficiently by tertiary amines, especially DABCO (diazabicyclooctane):
DABCO is sterically unhindered, unlike most tertiary amines, and has a low IP...therefore it
should be a good electron donor.NN
Quenching of Singlet Oxygen Quenching of Singlet Oxygen by Aminesby Amines
Ionization Energy vs Log Kq
5
5.5
6
6.5
7
7.5
8
7.5 8 8.5 9 9.5
Ionization Energy
Lo
g K
q
QuenchingQuenching
No chemical reaction involved...amines are unchanged
Physical quenching…rate related inversely to ionization potential of the amine
Very sensitive to steric effects in the vicinity of nitrogen
This data suggests a charge-transfer mechanism.
Proposed Orbital InteractionProposed Orbital Interaction (same as for C.T. complex formation)(same as for C.T. complex formation)
N
O O (LUMO)
2p (HOMO)
Our Approach:Our Approach:
Model various amines and singlet oxygen (optimized separately) in proximity to one another and look for an interaction (attraction); AMPAC/MINDO3 was used.
When an attraction is observed, examine the complex more closely to determine the optimum geometry.
Use knowledge gained from geometry of vinylamine-singlet oxygen complex.
Determining the Optimum Determining the Optimum N-O ‘Bond’ Distance N-O ‘Bond’ Distance
-0.5
0
0.5
1
1.5
2
2.5
3
1.45 1.5 1.55 1.6 1.65N-O DISTANCE
RE
LA
TIV
E E
NE
RG
Y
Determining the Optimum Determining the Optimum N-O-O ‘Bond’ Angle N-O-O ‘Bond’ Angle
-0.5
0
0.5
1
1.5
2
114 116 118 120 122
BOND ANGLE
RE
LA
TIV
E E
NE
RG
Y
Determining the Optimum Determining the Optimum N-O-O-O Dihedral Angle N-O-O-O Dihedral Angle
-0.5
0
0.5
1
1.5
2
2.5
3
160 170 180 190 200DIHEDRAL ANGLE
RE
LA
TIV
E E
NE
RG
Y
Typical Optimum Geometry of Typical Optimum Geometry of Amine-Amine-11OO22 Complexes Complexes
N-O ‘bond’ length of 1.55 Ao
N-O-O bond angle of 119o
C-N-O-O dihedral angle of 180o
Transfer of ~0.3 esu of charge from N to distal O is observed (more than in vinylamine).
Modeling Charge-Transfer Modeling Charge-Transfer Complexation of Amines Complexation of Amines with Singlet Oxygenwith Singlet Oxygen
N-O “bond” distance = 1.55 Ao
qN = +0.35esu qOdistal = -0.33 esu
Unexpected Results!Unexpected Results!
0
5
10
15
20
25
02468
N-O Separation, Angstroms
En
tha
lpy
of
Fo
rma
tio
n,
kc
al/
mo
l
Primary
Secondary
Tertiary
An Alternative Hypothesis:An Alternative Hypothesis:
Perhaps rate-limiting step is NOT formation of the
charge-transfer complex, but instead is intersystem
crossing (ISC) to the triplet complex:
[ 1O2 . . . 1NR3 ]
___ISC___> [ 3O2 . . . 3NR3 ]
This process can not be modeled, but can be
estimated by single point calculations.
Considering Triplet ComplexConsidering Triplet Complex
-24
-16
-8
0
8
16
24
32
40
48
-8 -6 -4 -2 0 2 4 6 8
N-O Separation, Angstroms
Rela
tive E
nth
alp
y o
f F
orm
ation,
kcal/m
ol
Triplet with
Singlet geometry
Singlet Triplet
Consistent with Slow ISC !Consistent with Slow ISC !
4.5
5
5.5
6
6.5
7
7.5
15 25 35 45
Enthalpy of Activation forIntersystem Crossing
Log
kq r = - 0.97
Acknowledgments: Financial Acknowledgments: Financial and Technical Supportand Technical Support
UNCW Office of Information Technology for use of the VAX computer
M.J.S. Dewar (now deceased) and Eamon F. Healy for providing a free copy of AMPAC
NSF for an ILI grant (1996) to Integrate Molecular Modeling into the Chemistry Curriculum (computers and software)
Acknowledgments: Acknowledgments: The WorkersThe Workers
Reaction of Singlet Oxygen with Vinylamine: David B. Allen and Kelly N. Taylor
Quenching of Singlet Oxygen by Amines: Charles K. Marschke, Jr., Chris A. Cottle and Noah W. Allen, III.