[itsintheworkup]

I'm trying to make a tetra-boc spermine-5-carboxylate compound (three steps from ornithine). The literature says to react ornithine with 2.5eq acrylonitrile in methanol at RT/ON. Ornithine HCl won't dissolve in methanol without 2 eq of tetramethylammonium hydroxide to neutralize. This reaction produces one major blue spot in the TLC stained with ninhydrin. It's pretty straight forward producing mostly just the dinitrile product.

The subsequent dinitrile reduction over Raney Nickel with H2(g) is supposed to be in 0.5M KOH in EtOH. This reaction is super sluggish and does not go to completion. If I omit the KOH or reduce in MeOH instead of EtOH I get a better reduction but there is this dark wine amber color which appears in the reaction after a day. I can only imagine this is leaching of either Ni or Al from the catalyst.  I also tried using recrystallized dinitrile product from the first step in the reduction but I get the same effects.  In the literature, the crude from this reaction should be solid white.  I'm get an amber semisolid after high vac.

The final published protection reaction is suppose to be with Boc-ON in THF. The reduction crude dissolves poorly in THF. I've found that reactions are actually better with Boc2O and a DMAP base in MeCN. However, the products I get from the reduction are never very pure (and impossible to purify).  Since the protection reaction isn't going to completion either, I'm left with a mess of isomers and partially reacted products in the crude which are also difficult to separate.

What is happening to my reduction? Has anyone else had similar problems with Raney Nickel and sluggish reactions or trouble with the slow appearance of an amber color?  I'm using a generic active catalyst in a water slurry from Sigma. 

[rolnor]

Raney-Ni reductions of nitriles are not straightforward, often people uses 2M NH3 in MeOH to suppress side reactions. You can try Alumina plates for TLC or use RP-plates, usually there is one method to purify that works, you can run RP-column or Alumina-column chromatography. You have amines and to add TEA to a silica-TLC system can also make separation better.

[itsintheworkup]

Ok.  So... You think the wine amber color material is actually byproducts and not nickel or aluminum ions?  I don't get any colored reaction forming if include KOH in the reduction solution.  I'll try ammonia in methanol and see if this helps.

[rolnor]

Very often small amounts of coloured material is formed, you need to get a good TLC so you can see what you have, or NMR. GC is not very useful perhaps, you have a high boiling point for the product