[nj_bartel]

I'm trying to sythesize this

http://img15.imageshack.us/my.php?image=randomp.png

using anisole as my only organic carbon source.

So far, I cleaved anisole to give phenol, nitrated that to give para-nitrophenol, then reduced to give para-aminophenol.  I then set this product aside for later.

Then, I cleaved another anisole to give phenol, treated with PBr₃ to give bromobenzene, treated with Mg to form a grignard, reacted with CO₂ followed by acid to give benzoic acid, then treated with SOCl₂ to give the acyl chloride of benzoic acid.  I then reacted this with the product I had set aside.

Unfortunately, that gives the product pictured, except without the methoxy substituent in the bottom left-hand corner, and I'm drawing blanks on where I can work it in.

Thanks for any help.

[frenchy]

I'm not sure where this would react on your molecule but could you try trichloroacetyl chloride in a first reaction then in a second time react what you have with sodium methoxide.

[nj_bartel]

Unless you have a way of synthesizing the trichloroacetyl chloride, I wouldn't be allowed to use that due to it being an organic molecule that's adding carbons.  Thanks though.

[nj_bartel]

Got it, nvm 

[macman104]

Share share!

[nj_bartel]

Went about the second part in the wrong way.

It's still anisole -> p-aminophenol as stated above

Then anisole is brominated, and the para product is isolated to give p-bromoanisole, which is used to form a grignard, which reacts with CO₂ followed by acid to give p-methoxybenzoic acid, which is treated with thionyl chloride to give the acyl chloride, followed by p-aminophenol to product

[aldoxime_amine]

Can we use protecting groups? Even then I think the last step is doubtful, giving us a mixture of amides...

[sjb]

What do you mean by a mixture, I think the Beckmann is fairly stereospecific (I think that's the right word) -  what I mean is that if you follow the mechanism as at



if R = Et, and R' = Me (i.e. the oxime from butanone), then you get the major product as N-ethylacetamide, rather than N-methylpropionamide. Forming the required oxime isomer selectively may be a different problem, though

S

[aldoxime_amine]

Forming the required oxime isomer selectively may be a different problem, though

That was exactly my concern...the second to last step will give us a pair of diastereomers (in my scheme..) and hence we will get a mixture in the final step.

[sjb]

That was exactly my concern...the second to last step will give us a pair of diastereomers (in my scheme..) and hence we will get a mixture in the final step.

OK just checking, I read your initial post as suggesting that you get the (E)-oxime exclusively, then the scrambling occurs with the Beckmann. I suppose that if you're allowing separation of protected 4-hydroxy-4'-methoxybenzophenone and protected 4-hydroxy-2'-methoxybenzophenone then this may be OK.

Presumably we have a workable route from anisole to benzenesulfonyl chloride?

[aldoxime_amine]

then this may be OK.

But won't we have to separate the 2 amides after the last step? I used PhSO₂Cl as it did not add carbons, as it is only performing the work of an assistant.