[AhBeng]

Hi,

This query is regarding the synthesis of artificial sweetener 5-Nitro-2-propoxyaniline.


http://www.answers.com/%205-Nitro-2-propoxyaniline

According to the question (published in the Cambridge University 'A' level Exams 2008), 5-Nitro-2-propoxyaniline can supposedly be synthesized in just 2 simple steps, beginning with propoxybenzene.

While in theory it seems easy enough : add aqueous HNO3, then reduce one of the nitro groups to amine group (by using Sn and conc HCl).

But in practice, here are two serious problems :

1) When using the aqueous HNO3, how can the chemist ensure only di-nitration occurs, instead of mono or tri nitration? (the propoxy group directs the incoming nitro electrophile to the ortho and para positions).

2) When carrying out reduction, how can the chemist ensure only one of the two nitro groups (and furthemore, to be precise, the nitro group ortho to the ethoxy group)  gets reduced to amine?

I would think the yield would be too low for such a synthesis pathway to be viable. However, since this compound is a commercially synthesized artificial sweetener (albeit a toxic one), so I wonder if there is a better synthesis strategy for this compound, and also if the Cambridge exam question is a fair one (ie. it probably isn't a fair question if the only 2-step synthesis possible, gives too low a yield to be viable).


Any help is very much appreciated.

[AhBeng]

Oh, I almost forgot. I have a scanned image of the offending question here :

[Astrokel]

Hey Ahbeng!! this is exactly the question i posted on http://www.chemicalforums.com/index.php?topic=29447.0 2 days ago. I have got a response from a teacher and she said "don't question a question!" and that if cambridge wants it to be only disubstitued, you have to assume it. As for your 2nd question, she wasn't too sure about the answer why only 1 of the nitro group is reduced, she mentioned something about amine salt, i forgot about it. Anyway by any chance you doing H3 chem?

[macman104]

Each time you nitrate, the ring becomes more and more deactivated.  The ring is activated towards the addition the first time, due to the oxygen.  The second time, the ring is effectively neutral (it's got a deactivator and an activator). The third time, it will be the slowest addition.

This same thing happens on unsubstituted rings, or TNT (trinitrotoluene).  The first nitro addition is quick, the second slower (since the first nitro deactivates), and the third addition even slower.

I don't like the selective reduction.  The only thing I can think of is some sort of metal-assisted reduction, where the metal coordiantes to both the oxygen and the nitrogen.

[kiwi]

...
I don't like the selective reduction.  The only thing I can think of is some sort of metal-assisted reduction, where the metal coordiantes to both the oxygen and the nitrogen.

from memory sodium sulfide reduction of dinitroarenes stops at mononitroanilines, but i'm not sure whether you would be expected to know this for a-levels

[AhBeng]

Hi Kiwi,

from memory sodium sulfide reduction of dinitroarenes stops at mononitroanilines, but i'm not sure whether you would be expected to know this for a-levels

Thanks Kiwiw!!! That's what I was looking for! ( "It is also possible to form a nitroaniline by reduction of a dinitroarene using sodium sulfide" - http://en.wikipedia.org/wiki/Reduction_of_nitro_compounds )

I knew that since this commercial compound exists, there must be a better (ie. higher yield) pathway for its synthesis. Evidently, Cambridge University in setting the 2008 'A' level paper, thought it would make for an interesting question to use this compound and ask for an unrealisitc 2-step synthesis pathway, even if sodium sulfide reduction is not taught within it's syllabus and without such the selective reduction of only the ortho nitro group would result in a pitiably low yield.

That's all I needed to know. Thanks again, Kiwi.

And thanks for your helpful comments, macman104.

And Astrokel, Ho Sae Bo? So basically we've got our answer - this H2 SEAB-Cambridge Qn is flawed. Only possible answer within scope of syllabus will give a horribly low yield. And no, I don't do H3 (or even H2). I assume you do? If so, have fun hor! (and cross your fingers that SEAB doesn't come up with more of such 'fun' qns! heh!)
 
Once again, thanks ("snacks") to all 3 of you, Kiwi, macman104 and Astrokel.

[macman104]

Yea, I'm in my 4th semester of organic, and never once have I heard of that reduction (although, some sort of reduction by Na₂S does sound vaguely familiar from a lecture, but only briefly).  Apparently it is called the Zinin Reduction, and is pretty old chemistry (with the initial info published in those old German journals, ~1842).  I found an old text relating to it, I've uploaded the PDF for you to see.  At the end of the 3rd page, they mention the selective reduction of di or tri-nitro compounds.

I got the paper, here, but there was some security certificate stuff that you have to approve, so I thought I'd post it instead of requiring people to go download it.

https://sciencemadness.org/talk/viewthread.php?action=attachment&tid=433&pid=86632

[AhBeng]

Thanks a lot (for taking the time and effort to search and upload this), macman104! Much appreciated.

Yes, the Zinin Reduction is obscure, for sure. I couldn't find it in any of my (half-a-dozen) Organic Chem texts, and finally found a mention in pg 1817 of "March's Advanced Organic Chemistry, 6th Edition".

Online search reveals similar obscurity :
http://www.answers.com/Zinin%20Reduction

Well, point proven. SEAB-Cambridge must think it most amusing to annoy 'A' level (H2 level) students with this question (which is impossible to answer within the context of their limited syllabus).


Thanks again, Kiwi and MacMan.

Yea, I'm in my 4th semester of organic, and never once have I heard of that reduction (although, some sort of reduction by Na₂S does sound vaguely familiar from a lecture, but only briefly).  Apparently it is called the Zinin Reduction, and is pretty old chemistry (with the initial info published in those old German journals, ~1842).  I found an old text relating to it, I've uploaded the PDF for you to see.  At the end of the 3rd page, they mention the selective reduction of di or tri-nitro compounds.

I got the paper, here, but there was some security certificate stuff that you have to approve, so I thought I'd post it instead of requiring people to go download it.

https://sciencemadness.org/talk/viewthread.php?action=attachment&tid=433&pid=86632

[macman104]

Thanks a lot (for taking the time and effort to search and upload this), macman104! Much appreciated.

Yes, the Zinin Reduction is obscure, for sure. I couldn't find it in any of my (half-a-dozen) Organic Chem texts, and finally found a mention in pg 1817 of "March's Advanced Organic Chemistry, 6th Edition".

No problem.  And right, ONE part of a page in March.  Not really something you might just browse across (does anyone even "browse" March for fun? lol)...

Anyway, glad the question could be answered, but truly an unfair question I believe.

[Astrokel]

Nicely answered! Thanks all

or even H2).

I'm confused, what do you do? Unless you are a t..

[kiwi]

...
 
Once again, thanks ("snacks") to all 3 of you, Kiwi, macman104 and Astrokel.

No problem. March - is there anything it doesn't know?...