[brewmaster]

Hello,

First time poster to the forum!  Did a quick search and couldn't find an answer to my question.  Literature searches turned up nothing very helpful either.  Hopefully someone here can help me out.  Here's my problem that needs solved:

I am looking to use L-Arginine as an amine rich component for formation of urea in a synthesis process.  The  problem is, L-Arginine is a solid with an extremely high BP (>250C) and is soluble in water.  Water CANNOT be part of my synthesis process so I am looking for a substitute that is fairly inert in my chemistry as well as bio-compatible!  For example, DMSO. 

In short, what conditions, solvents, acid/base can L-Arginine be dissolved in?  I have had the best luck with Sulfuric Acid (H2SO4) + DMSO, but the acid concentration is almost 1:1 ratio with the L-Arginine and I'm afraid that's too high.  We've tried DMF with similar, if not worse results.  Ethanol and methanol are not options because of an undesired reaction with the hydroxl group.

As a secondary question, has anyone used L-Arginine in synthesis and if so, have you charged it as found in it's solid phase?  What happened?  What temperature and reaction conditions?

Thanks ahead.  Any feedback is appreciated!

[TheUnassuming]

Is the arginine the free amine or the HCl salt?  I've only ever used R in one protected form or another, so the solubility was different.

[brewmaster]

Thanks for the response Unassuming.  We are currently using the free amine form as the acid can greatly affect our kinetics and we are avoiding any other associated compounds such as the HCl salt.

[TheUnassuming]

In that case, if it's not going into DMSO/DMF well enough and you can't use protic solvents, you might need to rethink your experiment approach.

[brewmaster]

Yeah I think we've exhausted our solvents.  He had some luck with formic acid too, but I think I'm going to use a slightly acidic (~500 ppm H2SO4) with DMSO to create a slurry.  The reaction should be very fast and I don't anticipate residual L-Arg to be left behind (this is what I'm trying to avoid obviously).

I'll post back results next week.  Thanks again Unassuming.

[Babcock_Hall]

Have you tried HMPT?  What if you started with the free acid and added an equivalent of tetramethylammonium hydroxide?  I don't have personal experience with arginine, so these are just ideas.

[brewmaster]

Interesting idea.  I don't have experience with HMPT but I'll pitch the idea to my team.  It does have a relatively low BP though at about 50C, so it would just boil off in our reactor.

[brewmaster]

Oops just saw it's carcinogenic and mutagenic.  That's a big no-go in our product!

Germ cell mutagenicity
Hamster
Kidney
Morphological transformation

Carcinogenicity
IARC: 2B - Group 2B: Possibly carcinogenic to humans
NTP: Reasonably anticipated to be a human carcinogen

[Babcock_Hall]

The only other solvent I can think of is propylene carbonate.

[Dan]

I'd try tetraalkylammonium hydroxide as Babcock_Hall suggested.

[brewmaster]

UPDATE:

Firstly, thanks for everyone's contribution to my first thread.  Really appreciate it.

I went forward with my synthesis as a slurry, using a diluted L-Arg/DMSO charged to an isocyanate rich reactant.  To my surprise, NOTHING happened.  The theory is that the amine rich L-Arg will react with the isocyanates to create a urea.  I am very experienced with the isocyanate and create a lot of urethanes with this reactant (using polyols instead of polyamines).  The amine/isocyanate reaction is typically lightning fast when compared to alcohol/isocyanate.  Instead, my slurry remained a slurry and the solids did not decrease in size.  The analytics didn't show urea formation so I knew my reaction was stalled.   This was all done at 85C with excellent mixing.

There's not a lot of literature for L-arginine used as a polyamine so I'm wondering if my theory is just not feasible.  I'm disappointed but there's a few other things I'm going to try.  Might even explore lysine as another option.

Any thoughts on my observations (or lack thereof)?

[phth]

Try a glyme solvent e.g. tetraglyme triglyme...  They have a huge liquid range, they dissolve everything from water to non polar solvents.  DMPU, and PEG are other choices

[brewmaster]

Unfortunately I think the problem is now beyond the solvent.  I can't figure out why an amine rich L-arginine won't react with a diisocyanate?  That reaction should be lightning fast.

[DrCMS]

L-Arginine in an amino acid and acids inhibit isocyanate reactions. 

Less than 10ppm of phosphoric acid can more than half the rate of reaction between a polyol and IPDI.

[brewmaster]

L-Arginine in an amino acid and acids inhibit isocyanate reactions. 

Less than 10ppm of phosphoric acid can more than half the rate of reaction between a polyol and IPDI.

Yes, I agree acid is a very strong inhibitor for these reactions.  However, isn't arginine a basic amino acid?  pK = 12.5?  This is why I'm scratching my head.

http://www.thinkpeptides.com/aminoacidproperties.html