[ctobin]

Hi,  I am curious if nitrous acid reacts with secondary aryl amides, like acetanilide?  Or to phrase it differently, is acetyl a good amine protecting group in the presence of nitrous acid?

I know nitrous acid and aniline will form a diazo group which is unstable at room temperature and will leave as N₂, leaving behind a radical.  Additionally, I know nitrous acid will also react with all amnies, primary through tertiary.  But I haven't been able to find much information on secondary amides, or more specifically aryl secondary amides.  Any insight would be much appreciated.

The reason I ask is because I am trying to graft aniline to a carbon electrode leaving the amine intact, as shown below.



Traditionally, to graft things to carbon electrodes you would use an amine which reacts with nitrous acid to form a diazo which then leaves as N₂ gas.  A radical is left behind which can form a bond with the electrode (I *think* with carboxyl groups on the surface).  But I need to preserve the amine.  I imagine starting with 1,4-phenylenediamine will not work because both amines will react with the nitrous acid.

I was thinking that I could protect one of the amines with acetyl.  Start with 4-aminoacetanilide and graft that to the electrode with nitrous acid (produced by HCl and NaNO₂). Then wash the electrode in water.  Then use heat and NaOH to hydrolyze the amide, forming aniline and acetic acid, as shown below.



But I am not sure the secondary amide will survive the first step.

[orgopete]

I believe an amide will react with nitrous acid, but it  should not react as rapidly. You should be able to do a selective diazotization. The hydrolysis could be done with acid or base.

[ctobin]

Thanks for the info!

One follow up question:  I found an old (1991) masters thesis on copper(II) catalyzed amide hydrolysis, http://digitool.library.mcgill.ca/R/?func=dbin-jump-full&object_id=60516&local_base=GEN01-MCG02  I was wondering if there have been any improvements to this catalyst since then, or if that is still the state of the art, aside from acid/base catalyzed hydrolysis?

I'm still going to try base catalyzed hydrolysis with refluxing KOH, but I'm always looking for better ways of doing things

[discodermolide]

I found this reference:

http://books.google.ch/books?id=oAlxIVRzrN8C&pg=PA1308&lpg=PA1308&dq=reaction+of+nitrous+acid+with+amides&source=bl&ots=P_I49HhpJe&sig=v6iGz83Kc5zDsODM2h5GrHoQEz8&hl=en&sa=X&ei=xueVUK-HJ4iWswbmzoCYBA&ved=0CGAQ6AEwCTgK#v=onepage&q=reaction%20of%20nitrous%20acid%20with%20amides&f=false

Reaction 5 says that they react to give carboxylic acids  nitrogen and water. But it does not say if they are aromatic or aliphatic amides. But it it something to be aware of.
Sorry for the long link.