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Topic: HCl Salt of an Acid Sensitive Compound  (Read 3025 times)

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Offline Silica

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HCl Salt of an Acid Sensitive Compound
« on: December 07, 2006, 10:49:23 AM »
Sounds like a bad idea, but sometimes you've just got to have a solid derivative, and sometimes bubbling that HCl gas into an ether solution just won't do.

I can't take for this credit other than I came up with this idea and later saw it in a patent (so don't go out and try to get rich with this):

You can form the HCl salt of an aliphatic amine by treating a solution of the amine with a solution of pyridine hydrochloride.  The aliphatic amine is so much stronger a base that the proton transfer is essentially quantitative, and you can use excess pyridine hydrochloride if you want.  The pyridine keeps you from destroying something you don't intend to.  There are lots of molecules I wouldn't expose to HCl/ether but wouldn't hesitate to toss into a solution where the strongest acid around is pyridinium ion.

Acetonitrile is a nice solvent, because pyridine hydrochloride is very soluble in it, whereas aliphatic amine hydrochlorides tend not to be.  A typical precipitation involves mixing a homogeneous solution of the amine in acetonitrile with a homogeneous solution of pyridine hydrochloride in acetonitrile.  The amine hydrochloride crashes out, and the pyridine and whatever excess of pyridine hydrochloride stay in the acetonitrile. 

If you don't have a jar of pyridine hydrochloride, you can add some HCl/ether to a slight excess of pyridine in acetonitrile.  For that matter, you can use HBr or camphorsulfonic acid or whatever. 

The amine doesn't even need to be acid sensitive.  It's a lot more pleasant to crack open a jar of pyridine hydrochloride than a cylinder of HCl gas.  Easier to weigh it out, too.


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