Knowledge Based Reactions
Outside of quantum mechanical modeling, typical method is to explicitly specify the participating reactant atoms and how bonds are rearranged as a reaction profile
R1
O
OH
NH2-R2
H+
Sample Reaction Profile
R1
O
+ H2O
NH2-R2
Knowledge Based Limitations
Requires manual pre-specification of many different known reaction profiles to achieve any degree of generalization
+ +
+ +
+
Knowledge Based Limitations
A very generic reaction profile can cover everything from previous slide and indeed about 50% of all known organic reactions
Still, a screening or ranking method is needed to filter many unrealistic reactions proposed above
Many reactions with more sophisticated profiles are not covered without manually specifying more knowledge based profiles Diels-Alder Azide + Alkyne aromatic cyclization
A B
C D
A B
C D
Reaction Favorability Scoring
Simple scoring method to suggest predicted reaction feasibility and favorability based on a simplification of Hess’ lawHreaction = (BDEbroken) – (BDEformed)
Estimate change in enthalpy by looking up bond-dissociation energies (BDE)
Apply additional bonuses and penalties for aromaticity and ring strain
Pseudo-Mechanistic Reactions
First step towards more generalized, pseudo-mechanistic reaction modeling is the introduction of “intermediates”
Model breaking a bond in each reactant by separating charge, representative of the bond electrons moving to one atom
Closing the intermediates is then just a matter of matching + and - charges
A B
C D
A+ B-
C- D+
A B
C D
Pseudo-Mechanistic Reactions
Applying general electron-shifting rules on the intermediates before closing them into products provides a lot of power and chemically intuitive results
O- H+O H O
-
H+
O
Azide + Alkyne Example
R1 N N+ N-
R2 C CR3
R1 N+ N N-
R2 C- C+
R3
R1 NN N
C CR2
R3
Diels-Alder Example
C CC C
+
C C
C- CC+ C
+
C- C+
C CC+ C-
+
C- C+
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