Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: 408 on June 14, 2010, 02:43:38 PM
-
Hi everyone.
I have had no luck finding a selective reducing agent in the literature. I have an aromatic azido group, and an amine N-oxide in the same molecule. I wish to reduce the azido group to an amine. Does anyone know a reducing agent that will leave the N-oxide intact?
Thanks,
408
-
As much as I hate doing this etiquette wise, *Ignore me, I am impatient*! Anyone?
Please note the title was meant to say azide reduction, not nitro reduction. I really doubt there is a method of reducing a nitro group in the presence of an N-oxide. :P
-
http://www.jstage.jst.go.jp/article/cl/29/7/29_816/_article may be of some interest - can't see the paper myself, but google abstract seems to include a tantalising "At the same time, azides are selectively reduced in the presence ... tively obtained without any further reduction of nitro group. (entry 4). ..." ?
-
Looks pretty good! I assume the similarity of a nitro group and a N-oxide means the latter will be left intact...I hope. I shall try this soon. Thank you.
I think I will just have to try things, due to the semi-rarity of N-oxides I do not think I will find a paper saying "the chemoselective reduction of azides in the presence of N-oxides "
-
Generally I don´t trust these Indian Papers. I have seen a lot of scientific fraud. I give that
Much better is it to use 1,3-propanedithiol. Tet. Lett. 1978, Volume 19, Issue 39, Pages 3633-3634.
It stinks but the reaction proceeds smoothly.
-
Caveat emptor, of course.
What else is in your molecule, could you afford to reduce it all, then reform the N-oxide?
S
-
Thanks OC, the sulfur route seems highly promising, and the solubility will likely work better for my compound.
sjb: As much as I would like to say my exact molecule, making assistance easier, unpublished work and all that... Suffice to say the N-oxide is not possible to form when the amine is present using the reaction conditions I have been.
-
Should the Staudinger reaction (http://www.organic-chemistry.org/namedreactions/staudinger-reaction.shtm) not work for this (Reduction with triphenylphosphine, room temperature)? I had a quick search for reactions between triphenylphosphine and amine oxides, and found this: http://pubs.acs.org/doi/abs/10.1021/ja01515a050 which says that you need a high temperature to get reaction, so I would guess that your amine oxide should be alright at room temperature?
-
The literature method for removal of an N-oxide (ex furoxans to furazans) often involves a PR3 or PX3 species, allowing easy oxide loss by forming the strong P-O bond. So I had immediately discounted the use of phosphorus agents... But if temperature control would work, that would be great! Due to the more difficult work up procedure, I may try this if the stinky method fails. The produced dithiolane should be easy to separate.
-
You definitely know more than me RE: N-oxides so go how you feel. I just found that paper with a quick search for triphenylphosphine and amine oxide. I do some work with azides, and I was just offering what I knew from that perspective.
-
This isn't based upon anything I know, but I am guessing that it would be easier to break an N-X>N-O>N-N>N-C bond. Hence, I am guessing this is going to be uphill. I would think you could do the reverse selectively, reduce the N-oxide in the presence of an azide.
-
impossible, I think.
N-oxide must be reduced firstly.
you can use different Protecting Groups, then detach them one by one.
-
Orgopete: But the mass spec of cpds containing both azide and N-oxide show an M-28 peak, and not an M-16 peak :) So perhaps the N-N bonding is not as strong as you feel :).
I finally got reagents in for the thiol reduction. So I will know within a week if this works.
tritiger: based on what? and what protecting groups would you suggest?
-
Ok, I am running this reaction. I presume N2 should be eliminated if there is azide reduction occurring. I have seen nothing yet.
Perhaps I make more azide oxide, and then also run the staudiger reaction cold if this fails....
-
Amine oxide exists in the mass spec. The azide oxide is gone. There may have been a small amount of oxide reduction, but that peak is not intense.
This really, really, stinks. I am attempting to work up the reaction, and all my extracts stink!
-
It doesn´t matter if it stinks. All the matter is if the reaction works ;D.
But I agree...organosulfur chemistry is a bit painful. I was running reactions with Lawesson´s reagent on a several hundred grams scale last week. My technician who had to conduct the experiments was a bit pissed... 8)
-
Use mild hydrogenation, azide to amine. Be aware the system you generate will be a redox system, that is the N-oxide can move between the two nitrogen atoms, so you will end up with a mixture of N-oxides
-
Another stinky reduction from tetrahedron:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6THR-4789VFT-S&_user=10&_coverDate=12%2F09%2F2002&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1530029010&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1bc9f6b4a27c3ef2a3b66fa38490b7ea&searchtype=a#toc5
I cannot view the article without going to the library, but the abstract looks promising.