I have successfully modelled the reaction pathway for the nucleophilic addition of an electronegative nitrogen attacking a slightly electropositive carbon. What was a double bond of an oxygen to this carbon then becomes a single bond and the oxygen atom becomes protonated. I now want to capture a transition state where a hydrogen belonging to the nitrogen transfers to the protonated oxygen. This should cause the oxygen to disassociate from the carbon and a double bond between carbon and nitrogen. But I see this as three steps happening simultaneously. The hydrogen transfers (1) to the oxygen from the nitrogen, the oxygen moves away from the carbon (disassociation of water) (2) and a double bond between the nitrogen and carbon forms (3). Does anyone have any experience of the best approach to try and model this particular TS? Will I see all three manouvers as a single vibration (the single imaginary vibration)?
Many thanks
Anthony
Hi Anthony,
There are loads of literature about this subject, depending on what is the actual reaction taking place. The key issue that comes to mind is the solvent/catalyst role. In aqueous solvent the surrounding water shell will be involved in abstracting the proton, having it transported and then adde to the oxygen. In non aqueous solvent you still probably will have some species acting as a general catalyst.
You mention that the oxygen is getting protonated in the first TS the carbonyl oxygen gets protonated. Where is this proton from? Do you mean that it ends up with a negative charge?
This whole issue is quite complex and requires quite a bit manual preparation of starting geometry to explore the different possibilities; direct trasnfer, solvent mediated ...
I have worked in modelling ester hydrolysis, you can sort of get a feel of what the whole water / catalyst issue is all about if your system is somewhat similar.
Mechanisms of lactone hydrolysis in neutral and alkaline conditions
R Gómez-Bombarelli, E Calle, J Casado
The Journal of organic chemistry 78 (14), 6868-6879
Mechanisms of lactone hydrolysis in acidic conditions
R Gómez-Bombarelli, E Calle, J Casado
The Journal of organic chemistry 78 (14), 6880-6889
All the best
Rafa
Hi Rafa,
Thanks for your reply. It is after the nucleophilic addition of lysine to linear D-glucose. I have successfully modeled the nucleophilic addition, where the nitrogen attacks the carbon to oxygen double bond of glucose. This then leaves the glucose oxygen to become protonated. The nitrogen atoms loses a proton and the oxygen gains a second proton. Hence a double bond is now formed between carbon and nitrogen, as the oxygen leaves as water. It is a Schiff base formation. After reading your post I don't think I am representing the proton transfer correctly. I think I shoud disassociate the proton off the nitrogen using the solvent, then disassociate the water by exchanging a proton from the solvent onto the oxygen.
Thanks
Anthony
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