[Urbanium]

We're investigating a series of reactions of thiols with alkynes. The reactions proceed via deprotonation of the thiol followed by a nucleophilic attack of the thiolate ion to the α-carbon atom of the triple bond. These reactions are performed in water and the pH is raised to 10 by addition of NaOH, since the pK_a of thiols is around 9,5. It's a methodology focused research, we are not doing total synthesis of any kind.

Could NaOH be substituted with some organic base which is stable in water in order to deprotonate the thiol? Maybe some non-nucleophilic base, so it does not react with the alkyne?

[OrganicDan96]

I have used triethylamine to deprotonate thiols before maybe that might work

[Babcock_Hall]

I have not used it in this regard, but triethanolamine might also work.

[Urbanium]

Thanks for suggestions. I also need an opinion on non-nucleophilic bases, e.g. DBU, DBN, DIPEA... might these deprotonate the thiol and are they stable in water?

[rolnor]

They are stable in water, I think you should try all of these.

[wildfyr]

These will react radically by thiol-ene/yne. I would not be surprised if you have a mix of mono and bis thiolated product. You should also try to run this experiment with no base. I would also try it in the dark and in lab light.



All those bases will deprotonate the thiol just fine I think. I just suspect that thiol-yne is a faster reaction and will be the real driving force. Do you have a citation showing this 2 electron mechanism of thiol substitution on alkynes?

[rolnor]

OK, I thought it was just Michael-type addition?

[Urbanium]

These will react radically by thiol-ene/yne. I would not be surprised if you have a mix of mono and bis thiolated product. You should also try to run this experiment with no base. I would also try it in the dark and in lab light.

Bis-thiolated product? That one might form when NaOH is used or when non-nucleophilic bases I suggested are used?

What I also noticed is when pH of the reaction mixture is ajdusted to 10, after 15 min of stirring at r.t. it drops down to approximately 7.5! What would be the reason for that behavior?

[wildfyr]

http://www.publish.csiro.au/temp/CH10214_S11.gif
This is the radical thiol yne reaction I would think about.


I dont know. Is your thiol highly water soluble? If not it may take a while for it to be deprotonated, and this consumes base.