[Will]

I have tried to search for an answer in google and on Chemical Forums so I apologise if it has already been answered!

I was wondering if it is possible to substitute the hydroxyl group with an amino group with sodium amide (NaNH₂) in NH_3(l). I know that it is done industrially with NH_3(g) at 300-400^oC with alumina (Al₂O₃) catalyst.

If it is possible to do it with sodium amide then what would be the conditions?

Thanks

Will

PS I don't intend to do this in the lab! Just wanted to know if it is possible.

[laotree]

No. Hydroxyl group is not a good leaving group under the condition you described. Hydroxyl group could become a good leaving group in Mitsnobu condition or acidic condition.

[Albert]

If I were you, will17, I'd use MeOSOCl in order to obtain an excellent leaving group in 'standard' conditions (I hope you to understand what I mean).

[Will]

Thanks for the helpful replies- I really enjoyed reading up about the Mitsunobu reaction which I have never heard of before. I am somewhat doubtful about acidic conditions helping since sodium amide is very reactive.

Sorry, but I have no idea about the CH₃OSOCl! I don't even know which of the two possible structures it is. Please could you explain this ?

Any more suggestions on whether it is possible to do this reaction with sodium amide under ANY conditions are welcome!

Hope everyone had a great Christmas/Hanukkah.

[Albert]

have no idea about the CH₃OSOCl! I don't even know which of the two possible structures it is. Please could you explain this ?

CH3SO2Cl is an extremely common reagent especially in the syntheses of drugs (to be frank with you, I'm almost fed up with it ): if you're curious, I can show an example.
It is used for providing an excellent leaving group (the red one) in SN2 reactions involving alcoholic functions.

[Albert]

Oh, and thanks to MeSO2Cl, I think you might use even NH3 as reactant.

[Will]

Thanks for explaining that! The A-level syllabus is really bad, not that this is at all relevant to it- I just like teaching my teachers  !

Would this have to be a two step process, since the HCl(g) produced would react with the ammonia? Also, what solvent would you use?

Thanks again for your help.

[Albert]

HCl is generally neutralized by adding a certain quantity of pyridine.

[Will]

Thanks! It makes sense, but could you use NaNH₂ after the CH₃SO₂Cl has done its bit, not NH₃?

[Albert]

Of course! In fact, NaNH2 is a stronger nuclephile if compared with NH3 (which is 'only' more common).
Moreover I was just wondering whether you could use NH3.

So, generally speaking, NaNH2 is better than NH3.

[HP]

I was wondering if possible the group R-OSO2CH3 to be transformed to R-COOH by reaction with HCOOH?

[Albert]

AH AH AH! lol

You're in love with HCOOH, aren't you?

No, I don't think so. Try CO2.

Following your pathway you could come across an ester(maybe with the help of NaH), I guess. By the way, I think formic acid to be a too weak nucleophile to react the way you think.

[ksr985]

there are quite a few reagents you can use to make -OH a good leaving group. aside from MeSO2Cl, you can use the tosylate or triflate groups, like in the modified beckmann rearrangements .. these reagents are also quite common.

[HP]

Hehe you right great in love with HCOOH
May be you right this reaction not possible as i think..By the way please tell me how CO2 could work with mesylate or tosylate derivative?
Now on the topic: Another god leaving group for OH- to NH2 transformation is p-nitrophenyl carbonate intermediat then NH3 autoclave or NaNH2 rt. Theres some procedure and with hydrazine...

[Albert]

Neither can CO2 serve as a source of COOH-groups (according to what I know), I was just kidding, sorry.

I was wondering if possible the group R-OSO2CH3 to be transformed to R-COOH by reaction with HCOOH?

However, here is a present for you (not too late for Christmas, I hope).
Ok, this is not the reaction you were thinking about, but is an uncommon, useful (epirubicine is an anti-tumoral, industrially synthesized from daunomycine) and quite unpredictable reaction involving a derivative of your beloved formic acid.