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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: caanmaro on November 22, 2015, 09:41:24 AM

Title: synthetic route
Post by: caanmaro on November 22, 2015, 09:41:24 AM

Good morning friends
I need to develop the following syntax, I can shed some light
Thank you

Title: Re: synthetic route
Post by: Shadow on November 22, 2015, 10:23:00 AM

The second step is Nef reaction.

Title: Re: synthetic route
Post by: beardy on November 24, 2015, 12:22:22 AM

1st part

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fi.imgur.com%2FKEUw36p.jpg&hash=691db49a40d0266012e373cf69ab6e0e30495b10)

beta addition with nitrile, nucleophilic acyl substitution to create an amide for hoffman rearrangement (lose a carbon, particularly the c=o), oxidize amine to nitro

Let me know of any mistakes or shorter routes.

Title: Re: synthetic route
Post by: Shadow on November 24, 2015, 07:00:56 AM

Good one.

Title: Re: synthetic route
Post by: sjb on November 24, 2015, 07:27:44 AM

I don't know if you can add the nitro group directly e.g. http://pubs.acs.org/doi/abs/10.1021/ol702545z ?

You may be able to hydrate the nitrile directly without isolation of the acid/acid chloride - http://chemwiki.ucdavis.edu/Organic_Chemistry/Nitriles/Reactivity_of_Nitriles/Conversion_of_nitriles_to_amides

Title: Re: synthetic route
Post by: Shadow on November 24, 2015, 07:51:07 AM

Quote from: sjb on November 24, 2015, 07:27:44 AM

I don't know if you can add the nitro group directly e.g. http://pubs.acs.org/doi/abs/10.1021/ol702545z ?

You may be able to hydrate the nitrile directly without isolation of the acid/acid chloride - http://chemwiki.ucdavis.edu/Organic_Chemistry/Nitriles/Reactivity_of_Nitriles/Conversion_of_nitriles_to_amides

That addition would introduce an extra C atom.
Yeah, milder conditions would afford the amide directly.

Title: Re: synthetic route
Post by: orgopete on November 24, 2015, 03:52:44 PM

How about adding hydroxylamine? Dehydration would give an imine, which on hydrolysis the ketone.

Title: Re: synthetic route
Post by: Shadow on November 24, 2015, 04:11:02 PM

How to dehydrate it?

Title: Re: synthetic route
Post by: beardy on November 24, 2015, 04:36:38 PM

Part 2

As Shadow said, Nef reaction.

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fi.imgur.com%2FHIieJzF.jpg&hash=dbc5b2e38d1483bc5d3c11b18f282823046f69d2)

Title: Re: synthetic route
Post by: orgopete on November 24, 2015, 05:33:11 PM

Quote from: Shadow on November 24, 2015, 04:11:02 PM

How to dehydrate it?

I don't "know" the answer. I would treat it with a mineral acid, like H2SO4 and see what happens. I was trying a shortcut to the obvious route of adding ammonia, oxidizing to nitro, and hydrolysis of the acinitro-form. There are other variations to an amine addition in which one could make an imine, proton transfer to isomeric imine, and hydrolysis. If I were doing this in the lab, I'd try one of these methods.

Title: Re: synthetic route
Post by: Shadow on November 25, 2015, 03:16:24 AM

I think Beckmann fragmenation/rearrangement will happen.

Title: Re: synthetic route
Post by: orgopete on November 25, 2015, 08:49:10 AM

Oximes react via a Beckman rearrangement, I don't think a hydroxylamine would. I'm expecting loss of a proton in analogy to alcohol-ketone oxidations. Protonation of the oxygen would pull electrons with it. Loss of a proton would balance the charge and give an imine. Compare this with an oxidation with NaOCl.

That is all speculation. Someone could just look this up and tell me it doesn't work, protonation occurs on nitrogen, etc. Anyway, if this is a student scheme, it might be better if the poster realized conjugate addition would be the easier way to add the amine.

Title: Re: synthetic route
Post by: clarkstill on November 25, 2015, 11:25:15 AM

I'd go 1,4 addition of azide (TMSN3, AcOH):

Org. Lett., 1999, 1 (7), pp 1107–1109

Then direct conversion of the azide to the nitro (HOF.MeCN):

JACS 2003, 125, 8118

Then Nef