[kd.gns]

I'm trying to figure out the mechanism for the substitution of a chloro group on a purine with a hydroxide. I've found many papers which uses 2-mercaptoethanol and sodium methoxide in methanol, at reflux as the reaction conditions for this substitution however I can't figure out how the mechanism works. I know that the first step should be the 2-mercaptoethanol replacing the Cl, and that the -OH on the 2-mercaptoethanol can H-bond with the sulfur to make it a good leaving group. The next step should be a hydroxide ion acting as a nucleophile to replace this leaving group, but I cant figure out where this hydroxide ion can come from, from the reactants given, wouldn't the sodium methoxide form a -OMe group instead of a hydroxide?

[Captain Sci]

I used 2-mercaptoethanol and sodium methoxide in methanol to synthesise DTT derivatives for field-effect transistors. The reaction was essentially a conjugate addition (that is, the Sulphur electrons attacking the back end of a C=C-C=O system), followed by in situ base-mediated cyclisation and dehydration to afford the fused thiophene system.

Why don't you post an image showing your starting materials and how you think the reaction starts off?

[kd.gns]

I'm not so sure how to post images here, so I drew it in chemdraw and pasted it into a paint file and saved as JPG. The mechanism I am thinking of is the substitution of the chloro group with 2-mercaptoethanol, the N is electron withdrawing so there is a partial postitive charge at the carbon for the OH ion to attack, the hydrogen bonding from the OH on the 2-mercaptoethanol makes the sulfur a good leaving group, resulting in the product. However, the problem with this mechanism is that given reaction conditions, I'm not sure what the source of the hydroxide ion is, its most likely from the sodium methoxide, but how?

[Captain Sci]

Interesting problem. I think the thiol would be deprotonated so you would actually get attack of S^-, not HS:

Also, I think displacement of Cl would not be concerted - an intermediate having a quaternary carbon atom, with both Cl and the thiol attached to it would exist, said internediate having the negative charge "parked" on the near-by nitrogen atom.

So, what happens next? I'll get my ChemDraw out and see if I can help.

[Captain Sci]

From the reaction conditions, it is not immediately obvious where the OH should come from. Could it be from the mercaptoethanol itself? I have attached a rather unlikely mechanism - don't open the champagne bottle just yet. I would need attack by MeO^- to finish it off, but I didn't bother to go that far since I am sceptical enough to this stage as it is.

[orgopete]

Without regard to the procedure, I surmise an OH must come from methanol. In order for that to occur, then logically the methoxide substitution should occur first. Then the mercaptoethanol can effect an SN2 substitution of the methyl ether to give the requisite OH and the methyl sulfide.

[kd.gns]

The mercaptoethanol attacks first, this is confirmed because there is an intermediate that can be seen which is the purine substituted with the mercaptoethanol, without a methyl ether attached.

[orgopete]

Well, in that case, I don't know where the OH comes from either. I thought the procedure might have been an initial reaction with methoxide and then a subsequent reaction with the mercaptoethanol.

Perhaps a variant of the scheme proposed by Athan might work. The S to O-migration would release the less basic sulfide. Now an intramolecular alkylation to give an episulfide and the requisite OH could occur?

[Dan]

Now an intramolecular alkylation to give an episulfide and the requisite OH could occur?

That's what I was thinking, the leaving group is a resonance stabilised anion so I'd say it's at least plausible.