[quantumnumber]

Hi everyone,

I wonder if this synthesis I attach could be acceptable. First, I'm not sure the step 1 could be possible, I mean, I'm not sure that the amine group wouldn't react with the SOCl₂ too.

If that step is correct and the product 2 is formed, then I thought that the amine could react with the acyl chloride formed to form an amide... but I hope that won't happen due to the steric hindrance of that possible product.

If that is correct, I think the synthesis may work...

Hope you can help me, thanks a lot!

[clarkstill]

Yeah I think you're going to have problems treating the 2-aminobenzoic acid with thionyl chloride.  Even if the SOCl2 didnt react directly with the aniline, it would probably form polymers by addition of the aniline to the acid chloride formed.

It seems like a shame not to exploit the hidden symmetry of the molecule... If you took your starting material and treated it with 2 equivalents of 2-chloroethanol, then used peptide coupling type reagents to close the ring, it should give the product you want.  The only issue might be getting clean double alkylation of the amine.

Anyone got a better way?

[discodermolide]

The standard method for making carbamates using chloroformates or indeed amides using acid chlorides is the Schotten-Baumann route. So your acid chloride, as has been stated, will react with the amino group.
You will probably get a mess with this first step.

[quantumnumber]

The standard method for making carbamates using chloroformates or indeed amides using acid chlorides is the Schotten-Baumann route. So your acid chloride, as has been stated, will react with the amino group.
You will probably get a mess with this first step.

Yeah, I guessed so. I just only thought that steric hindrance could avoid it in this case...

Yeah I think you're going to have problems treating the 2-aminobenzoic acid with thionyl chloride.  Even if the SOCl2 didnt react directly with the aniline, it would probably form polymers by addition of the aniline to the acid chloride formed.

It seems like a shame not to exploit the hidden symmetry of the molecule... If you took your starting material and treated it with 2 equivalents of 2-chloroethanol, then used peptide coupling type reagents to close the ring, it should give the product you want.  The only issue might be getting clean double alkylation of the amine.

Anyone got a better way?

I have another way in mind... I'll post it later! (I'm not at home now).

Thanks anyway!

[kriggy]

Yeah I think you're going to have problems treating the 2-aminobenzoic acid with thionyl chloride.  Even if the SOCl2 didnt react directly with the aniline, it would probably form polymers by addition of the aniline to the acid chloride formed.

It seems like a shame not to exploit the hidden symmetry of the molecule... If you took your starting material and treated it with 2 equivalents of 2-chloroethanol, then used peptide coupling type reagents to close the ring, it should give the product you want.  The only issue might be getting clean double alkylation of the amine.

Anyone got a better way?

You could protect the amine 1st, then make the ester, deprotect and alkylate. Two more steps but bulky protecting groups like tosyl helps with cyclization instead of some kind of polymer being formed

[quantumnumber]

Yeah I think you're going to have problems treating the 2-aminobenzoic acid with thionyl chloride.  Even if the SOCl2 didnt react directly with the aniline, it would probably form polymers by addition of the aniline to the acid chloride formed.

It seems like a shame not to exploit the hidden symmetry of the molecule... If you took your starting material and treated it with 2 equivalents of 2-chloroethanol, then used peptide coupling type reagents to close the ring, it should give the product you want.  The only issue might be getting clean double alkylation of the amine.

Anyone got a better way?

You could protect the amine 1st, then make the ester, deprotect and alkylate. Two more steps but bulky protecting groups like tosyl helps with cyclization instead of some kind of polymer being formed

If you protect the amine, then make the ester, might have problems when you want to deprotect the amine... cause using base or acid to do it you could destroy the ester too in the process.