Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Will on December 16, 2005, 04:00:37 PM
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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 NH3(l). I know that it is done industrially with NH3(g) at 300-400oC 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.
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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.
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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).
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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.
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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 :D): 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.
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Oh, and thanks to MeSO2Cl, I think you might use even NH3 as reactant.
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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 ;D!
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. ;)
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HCl is generally neutralized by adding a certain quantity of pyridine.
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Thanks! It makes sense, but could you use NaNH2 after the CH3SO2Cl has done its bit, not NH3?
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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. :D
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I was wondering if possible the group R-OSO2CH3 to be transformed to R-COOH by reaction with HCOOH?
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AH AH AH! ;D 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.
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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.
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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...
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Neither can CO2 serve as a source of COOH-groups (according to what I know), I was just kidding, sorry. ;D
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.
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Nice present thank you :) Actinomicine group antibiotics are really interesting but and quite a toxic one.. anyway this synthetic example much excited me. Mechanism is some unclear but it seems i should learn much about my beloved ;)
CO2 may be used for very efficient conversion Grignards to COOH as follows:
R-X + Mg---> R-MgX
R-MgX + CO2dry---> RCOOMgX
RCOOMgX + HCl---> R-COOH
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CO2 may be used for very efficient conversion Grignards to COOH as follows:
R-X + Mg---> R-MgX
R-MgX + CO2dry---> RCOOMgX
RCOOMgX + HCl---> R-COOH
Yes, I know. But YOU wondered about ROSO2Cl. However, I think this doesn't have anything to do with this topic.
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Here what i found for conversion OH to NH2 by variant of Staudinger reaction:
"Treatment of alcohols with NaN3 and two equivalents of PPh3 in CCl4-DMF(1:4) at 90°C afforded amines in an excellent yields (85-95%). Formation of amines may be visualized as the initial azide formed would react with second equivalent of Ph3P giving the iminophosphorane which in turn converted to the amine upon treatment with water."
Here used Na-azide do you think using NaNH2/PPh3 may lead to direct substitution OH ???
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Thanks for suggesting that- it would be great to hear from someone if they think that might work. I finally found out, from a decent source, about the Mitsunobu reaction, which laotree suggested. This uses Ph3P and DEAD, but suggests the nucleophile should be HNu, do you think NaNu ie. NaNH2 would work?
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do you think using NaNH2/PPh3 may lead to direct substitution OH ???
I don't think so.
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He he NH3 gas i see, but may be in pressure conditions at closed system;)
I am not very fammiliar with nucleophility NaN3 in comparison NaNH2 but is stupid to write:
R-OH + NaN3-->reverse R-O:-Na+ HN3
HN3--> how decompose: hope no "bum!" :)
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Make significant supplimentment:
Reaction ROH with NaN3/PPh3 in and with CBr4 as sourse of Br for first conversion R-OH to R-Br and after that R-Br + NaN3 and so on and so on...
You should agree R-Br may react with NaNH2 pretty nice :P
Nice discussion friends!
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Ok, if you don't want to use MeSO2Cl, use HBr (Br2 in conc. AcOH).
Then add NaN3 to your R-Br: it's an SN2 reaction.
Final step consists in a catalytic hydrogenation with H2/Pd.
It's always my pleasure.
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He he NH3 gas i see, but may be in pressure conditions at closed system;)
I am not very fammiliar with nucleophility NaN3 in comparison NaNH2 but is stupid to write:
R-OH + NaN3-->reverse R-O:-Na+ HN3
HN3--> how decompose: hope no "bum!" :)
HN3 is a NASTY little compound that I believe outranks HCN in terms of its ability to kill you. It's fairly unstable too, as are all azides, and will tend to decompose into hydrogen gas and nitrogen gas. As long as you have good ventillation, I don't think enough of it will build up to cause an explosion hazard, but it also doesn't take very much to kill you if you breathe it in.
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HN3 very toxic and hazardous compound i agree. Please everyone be very carefull in working with it. I know many methal azides are high explosive such as Ag and Pb-azides used to initiate explosion of Nobel's dinamite.