Ah, MgSO4 could be used in the reaction to remove any water produced yes? None the less using paraformaldehyde would reduce the molar amount of water present significantly over formalin.

Im starting to become very skeptical as well, besides the erowid german patent reference, all other references with relation to producing secondary amines from primary amines generally involve the use of NaBH4, NaCNBH3 or catalytic hydrogenation...

Hmm, maybe I should investigate the other methods and not waste anymore amine on this. Would need to start procuring again though which is a pita.

Interesting, aminating acetone provides isopropylamine yes? With diisopropylamine being the equivalent secondary amine?

Or am I way off

excellent, thanks. I should get on to this once im happy with the hofmann.

methyl bromide, like all other methyl halides are nasty. the higher you go in the periodic table, the nastier due to increased volatility. i would not even contemplate using it outside the hood, and i would be very careful when working in the hood. you do not want something going wrong. you will become n-methyldingbow and so will your dna.

I'm thinking of giving this a go soon - imine formation with paraformaldehyde and reduction with zinc or calcium.

I want to try the imine reduction with zinc in basic aqueous conditions. I'm not too sure what the solubility and other chemical properties of the imine is like and how to extract it from the alcohol it was formed in. Do you think flushing it with water will force it to precipitate out?

Another question, should i be worried about diimine formation? Would these side-products be easy to remove?

look this pdf method II

For the zinc/water/NaOH reduction, looking at their table 1, the diamine formation seems to depend on there being a large substituent for r3. There is no entry for the percentage of diamine for the imine on row1h (which has the methyl group on r3). Does this mean they didn't detect any diamine?

"A  small ammount of diamines  3a-e was  formed as a by-product.  In the case of  imines  lf-g  and li-j,  the  formation  of diamine  tended  to be  increased. "

It doesn't mention row 1h so i'm hoping for no diamine... I guess a tlc would be a good idea if i go this route.

Alright so heres the deal with the latest runs I did with monomethylation. I ran Klutes method basically, to the tee (well sorta..). All the indicators were spot on and matched Klutes description, but when it came to gassing, it failed, twice.

-I successfully made methyl tosylate. A dense non-polar liquid was formed.
-The imine was formed with the aldehyde, indicated by clear solution becoming opaque with water.
-The water was driven off, indicated by a clear solution (dont have a dean stark unfortunately).
-The methylammonium tolsylate formed, indicated by a dark orange liquid which separated, which was then extracted with h20. This aqueous layer was then basified with KOH, which did indeed release an amine smell, slightly stronger and different to the primary amine smell im used to, very exciting.
-I know at this point, the amine is mixed in with the also liberated aldehyde used originally for the imine formation. Klute from memory says purification of amine can be done via distillation.
-I find this unsuitable due to working at 10 mmole scale, so instead I tried doing a mild A/B hoping it would leave behind the aldehyde and bring over the secondary amine. The indications looked good, upon basifying the acidic aqueous layer, much table salt (presumably) was visually seen and again the smell of an amine was present. A non polar extract yielded a slightly yellow solution.
-This was gassed, which yielded something like 150mg of the HCL salt, which is obviously terrible. Im not even sure if this is just primary amine that went through the whole procedure unreacted.

I ran this twice, with pretty much identical results and yield. Not sure if anyone has any experience or can help out with this one. I cant experiment for a while anyway, but thought the info might be useful to someone. Whilst the primary amine has been great, the elusive secondary amine has been a holy grail for me and it seems its still just out of reach!

...which yielded something like 150mg of the HCL salt, which is obviously terrible. Im not even sure if this is just primary amine that went through the whole procedure unreacted...

All right, its been a long time. But I can confirm that from the bioassay, it seems the producted yielded from this reaction did indeed give me a secondary amine. It was much more euphoric, empathic and way less of a stimulant effect then the primary amine. Great stuff!

Hopefully I can run this procedure again and get some decent yields, but at least it worked.