Electrophilicity of Aldehydes and Ketones (Reactor context)

User 81a38f9467

23-11-2011 22:43:42

I am using Reactor 5.7.0.  I obtained unexpected results while using a Borch reductive amination reaction with this selectivity rule:  -electrophilicity(ratom(1));  -nucleophilicity(ratom(2))     and a tolerance of 0.01.  The reaction is defined as shown below. 

Aryl aldehydes are more electrophilic than aryl ketones, yet this is not what is observed.

CC(=O)C1=CC=CC(C=O)=C1.C1CCNCC1>>CC(=O)C1=CC=CC(CN2CCCCC2)=C1 |c:5,9,22,32,t:3,20|
CC(=O)C1=CC=CC(C=O)=C1.C1CCNCC1>>CC(=O)C1=CC=CC(CN2CCCCC2)=C1.CC(N1CCCCC1)C1=CC=CC(C=O)=C1 |c:5,9,22,32,45,49,t:3,20,43|

The Calculated result is clearly wrong.    I would like the electrophilicity calculation to be fixed so that it makes the correct predictions.

Interestingly, for a related example, the expected and calculated results were the same, namely:



ChemAxon d76e6e95eb

23-11-2011 22:57:06

I suppose, that currently only aromatic electropholicity is calculated on Huckel-basis, but my colleague will correct me if I am  wrong.
I would suggest to use something like this instead:


where the carbonyl carbon is mapped with number 1. Not too sophisticated, but it is fast and always prefers aldehydes to ketones.

User 851ac690a0

28-11-2011 14:05:00


Yes ,  the simple Huckel molecular orbital (SHMO) calculation can  not  make difference between the  "keto" and the "aldehyde" groups. Because only  delocalizable atoms are included in the scope of the SHMO calculation.The  "Methyl" side of the "keto" group and  the "H" atom of the "aldehyd" groups are ineffectives in the SHMO, this is why the calculated  electrophilicity of the two functional groups will be the same.

We are going to discuss inhouse,  what we can do  with this problem.