Ritter reaction to MDA?

[Gbo]

A guy SWIG knows is thinking of doing this synth as it seems relatively easy.  He is going to use acetonitrile instead of sodium cyanide.  Even though the yields are crap (30%), he doesn't mind wasting safrole instead of using expensive PdCl2/benzo in a wacker.

Acetonitrile can be used in place of sodium cyanide to form the acetamide. The acetamide would need to be hydrolyzed with hydrochloric acid though.

Not being a chemist, can someone please explain this procedure to SWIG? 

Does anyone have the reference, SWIG got all this from rhodiums site, but does not have access to a library at the moment:

Ritter. J. J. and Kalish, J., "A New Reaction of Nitriles: II. Synthesis of t-Carbinamines," Journal of the American Chemical Society, Vol. 70, Dec. 1948, pp. 4048-4050.

Any help greatly appreciated.

For every action, there is an equal and opposite criticism

[psyloxy]

In TSII Strike sez (citing Ritter) that the Ritter rxn doesn't work on Safrol for many reasons, where did you read about 30% yields ??

--psyloxy--

[Osmium]

The Ritter reaction doesn't work for safrole.
I did that reaction once many years ago hoping it would work. I used 1 mol of safrole and ended up with about a gram of brown sticky crystals. They indeed produced some funny feelings and eye dilation, but definitely weren't the real thing. The reaction is incredibly exothermic, once the temp starts to rise above 40°C you have about two seconds to get away because it will boil over extremely violently. What a mess.
If you can get your hands on some allylbenzene you can try it out (small scale with lots of ice water), otherwise just forget about it.

[Gbo]

Bugger!  Read it in Chapter 7 of the complete exstacy book on Rhodiums site, and also An Evaluation of the Potential for Clandestine Manufacture of 3,4 Methylenedioxyamphetamine (MDA) Analogs and Homologs

"Reported yields for amphetamine using the Ritter reaction [45] (Scheme 7, Fig. 2) were less than 30%. As in Schemes 5 and 6, a two-step synthesis is involved. Safrole is first converted to the immediate precursor N-acetyl MDA. This compound must then be either hydrolyzed or reduced to yield the desired product."

Would the isosafrole formic acid/H2O2 method be the next best non wacker route to MDP2P?

SWIGs friend is thinking of future synths to MDP2P as he is about to finish school and will have limited access to purchasing chems.

He has some MDP2P good to go now, what is the easiest way to get to MDA? (has MDMA, but wants to try something else).  Would it be Al/HG amalgam with Ammonium chloride? or the Leuckhart with formic/methylamine

For every action, there is an equal and opposite criticism

[spric]

Amalgation with NH4Cl, do tell me more. 

Fuck the crank, smoke the dank

[Gbo]

Its in chapter 7 as well.  Oh fuck it, here it is:

Aluminum Amalgam Reduction[43]
72.5g of aluminum foil is cut into one inch squares and placed into a 3000ml erlenmeyer flask or other suitable glass container. A solution of 1.8 grams of mercuric chloride (HgCl2) in 2530 ml water is added, and the mixture is stirred occasionally over 30 minutes to amalgamate the aluminum. The solution is poured off and the foil is washed with four one-liter portions of water.

To the amalgam is added, in sequence, 80g of ammonium chloride in 101ml of water, 302ml of isopropyl alcohol (100%), 244ml of 25% NaOH solution, 89g (0.5 moles) of piperonylacetone, and then 588ml of isopropyl alcohol. The mixture is swirled occasionally for two hours, and kept below 60°C by cooling with an ice bath as necessary.

The mixture is then filtered through Celite (a diatomaceous silicate powder which is placed in a layer over the filter paper before filtering, it is sold by chemical companies as Celite), and the filter cake is washed thoroughly with methanol. Combine the liquid filtrates and distill off the methanol (65°C), isopropyl alcohol (82°C) and the water (100°C).

Dissolve the oil in 200ml of ether, and extract the MDA into two 500 ml portions of 3N HCl. The acid solution is washed with three portions of methylene chloride equal in volume to the acid solution (you will probably have to wash portions of the solution at a time unless you have a huge separatory funnel). The acid solution is basified with excess 25% sodium hydroxide solution (red litmus turns blue) and the liberated oil is extracted into three 500ml portions of methylene chloride.
The methylene chloride solution is dried with magnesium sulfate. The drying agent is filtered out and the methylene chloride distilled out. The residual oil is distilled under reduced pressure and the distilled oil then dissolved in ether
(or toluene or methylene chloride). HCl gas is bubbled through the solution until no more precipitate is formed. The precipitate is filtered off and allowed to dry (~70% yield can be expected).

Nichols et al, J. Med. Chem., 29, 2009-2015 (1986).

Obviously don't need that much HgCl2 but.



For every action, there is an equal and opposite criticism

[Osmium]

Al/Hg with NH3 doesn't work. Very low yields.

[Gbo]

Double bugger!  I just read the eleusis/UF piefight again and see that it is indeed bollocks. 

So N-methyl formamide is used to get MDMA and formamide to get MDA?  The former is made with formic acid and methylamine.hcl, can the latter be made as well?  Can you use formic and NH3?


For every action, there is an equal and opposite criticism

[sunlight]

Yes, NH3 doesn't work no matter what the article says. And Leuckart works, but may be yields are around 50-60 %.

[Sonson]

The easiest way to make MDA from MDP2P is via the oxime. Very, very easy and as a bonus high-yielding too. See my earlier post for details.

[Antibody2]

Formamide is easily made from formic acid and ammonium hydroxide. There is a thread detailing it in the Chemistry discourse.

Jimi loves ya

[Gbo]

Excellent, cheers Antibody, exactly what was wanted!

Very keen on Sonsons as well.  May try both.

For every action, there is an equal and opposite criticism

[fuckface]

thanx sounds good illcheck your post

[Vibrating_Lights]

Would the yeilds of the Al/Hg still be low if the ketone was refluxed for a couple of HrS In a Methanol saturated with Nh3 prior to the addition of the AL Agm.

Sonson posted about the ketone being converted to the oxamine by reflux with Hexamine then further reduced the oximine to the amine with Sodium Metal.  Can the oximine be reduced  to the amine with Al Instead.

[Osmium]

> Would the yeilds of the Al/Hg still be low if the ketone
> was refluxed for a couple of HrS In a Methanol saturated
> with Nh3 prior to the addition of the AL Agm.

Yes.

> Sonson posted about the ketone being converted to the
> oxamine by reflux with Hexamine



> then further reduced the oximine to the amine with Sodium
> Metal. 

I think you are talking about the oxime? It is prepared with hydroxylamine (not hexamine), and the oxime can be reduced to the amine with Na/EtOH.

> Can the oximine be reduced  to the amine with Al Instead.

The oxime can be reduced to the amine (or to the N-hydroxy-amine, which is just as active but more heat sensitive), and Al/Hg should work fine for this one.