MDA synth using formamide

[r2e3]

This post refers to the synthesis of MDA which can be found on page 79 of Psychedelic Chemistry, which was first published in Chemical Abstracts 52, 11965c (1958). 
Now I have a clear understanding the steps and factors that need to be considered upto the formation of MDP-2P - top marks for the forum and Rhodium.ws
I have a few concerns that I would like to clarify before I put valuable resources to work
This is an extract that I will ask a few questions in relation to and would be most grateful if the more experienced bees could give me a few tips or advice:

Add 23g 3,4-methylenedioxyphenylacetone to 65g HCONH2 (formamide)and heat at 190 deg for five hours.

Fine.

Cool, add 100ml H20, extract with C6H6 (benzene) and evaporate in vacuum the extract. 

H20 to remove excess formamide I'm assuming - is it not better to use 3x50ml? - it is after all quite nasty stuff.
Do I use separatory funnel - rid the mixture of the bulk of the water/formamide and then extact the free base intermediate with benzene/toluene and evap under vacuum to separate the FB and solvent?

Add 8ml MeOH (methyl alcohol -- methanol) and 75ml 15% HCl to residue, heat on water bath two hours and extract in vacuum (or basify with KOH and extract the oil with benzene and dry, evaporate in vacuum) to get 11.7 g 3,4-methylenedioxyamphetamine (MDA).

So on the water bath do I heat to 100C and then strip the excess water/MeOH in the vacuum to leave the FB - or strip the water and then distill the FB?

Then finally, does the reaction with the HCL and MeOH - form hydrochloride salt or is it an intermediate to the FB? Will I need to gas in other words?

Help would be appreciated.

I have looked at thoroughly and could not find a cleaner presentation of the mechanism/reaction.

A step by step account would go along way

cheers  

[Antibody2]

that is a very old proceedure and not at all as easy as it might appear.

there have been some modifications since; like doing the acid hydrolysis step without isolating the formyl intermediate, 190C is exessive temperature 165C will do, and at the end you will need to do an acid base extraction so yes you will need to gas.

If you are in earnest about this reaction search the hive using keyword "Leukart". But a word to the wise, this reaction is very difficult to get a respectable yeild from, not where a newbee wants to go 1st time out for sure.

forming an oxime from your phenylacetone with hydroxylamine then reducing it with Al/Hg will produce much better results and you stand a chance of succeeding the 1st time.

[r2e3]

Thanks Ab - i'm not too worried about the yield - im expecting maybe 40-50%, that's ok as I will be able to recover any unused precursors. this is mainly to cut my teeth. synthing MeNH2 seems like far more of a challenge at the mo. 1 step at a time.

I think i know what you are trying to say in your statements - maybe you are not sure. sounds like you know what you are talking about so in the mean time i will take on board what you have said and use my best judgement- in for a penny...

i looked for leukart here but had little in the way of joy. i will trawl other sources - i'm sure they are there - i have seen them but if memory serves they are the Al/Hg pathway. i only want +/- 100g (50g will do) of mda at the top end and have ~ 400g mdp-2p to play with but i have the reagents i need now and changing path is almost point-less and risky.

wasting my time?

[hypo]

> i looked for leukart here but had little in the way of joy.

yeah, because the good man's name was leuckart.

it's a tarry clusterfuck.  
but if done right, it works.

[Capt_Stubing]

The first time I saw product was from a NH4CH3Coo/ NaCNBH3 detail. So what if the yeilds are around 20%.... Your Guarented to see the goods if ya do the work up correct. The Luchy is great for MDA when ya get your shit straight but untill then take my advice if ya can. MDA kicks MDMA in the ass any day off the week. Trust me when I say that it's not only what ya want but what ya need..... Cut to the chase and let us know how it ends.

P.S.  DON'T try to get cute and ask " why not use methylated formamide". Look at those scheduled chems and see why I'm telling ya this.

[grellobanans]

The Leuckart isn't that hard to mess up for first time. Swim's only complaint is the low yield. But, if you have all the precursors already and don't have any hydrides, sodium, etc. lying around and such...

Anyway, swim's advice is what was already said before, 190 C is way too high. For the hydrolysis step, keep in mind that if you use base, you get freebase and if you use acid, you get the salt and then workup accordingly. Also, check for the bubbling in solution (the CO2 being evolved from rxn) and that is a good sign. Swim thinks past yield has suffered because the reaction was stopped while bubbling was still vigorous, so perhaps keeping the heat until bubbling slows is a better indicator of a finished reaction than the time that the writeups state. And instead of benzene/toluene, good old DCM can be used. Also, DCM is the best solvent for gassing MDA. Swim used a DCM/Acetone mixture.

[r2e3]

thanks for your replies everyone. i am going to do things over the next couple days and with a little patience and luck get some results.

i have had a look around and can see where you are coming from on the ideas/methods.

thanks again

[r2e3]

Hi all - well i found a much better version on the Leuckart reaction and feel more confident with the next step.

i have just done the MDP-2P synth work up. things went quite well but i had somewhat of a mysterious outcome. i have a 2 phase distillation product.

1 is what you may expect, the very light yellowish/greenish MDP-2P that came over at 134C (10mmHg) and the second water clear - i think (havent seperated) which came over at 138C.

now the vacuum was quite constant but the temp does tend to vary and keeping it stable is more of a challenge, hence i kept going when the temp spiked.

now the iso came over at about 118-120C

there are 2 isomers that distill at slightly diff temp accounting for the variation mentioned.

i am now just wondering if any one has ideas what i have made. the yellow liquid appears to less dense than the clear liquid.

this is probably a shot in the dark but are there 2 isomeric form of MDP-2P that would account for this?

any input appreciated

[Antibody2]

test each fraction with a saturated sodium bisulfite solution (sorry you will have to UTFSE) to see which if either is ketone

[r2e3]

swim was at work thinking - shit my peroxide must have gone off....
so he came home today and decided to face the music and separate and see if he had the 40g of mdp to do his reaction.

but to his pleasant surprise he finds that in fact it must have been some refraction quirk in the rbf that gave him this impression. i mean he followed the buffered performic to the letter - so wtf? peroxide....?
he he - 162g yield - that makes the reaction 70.34% effiecient (68% - no better!)

i'm dreaming of a white christmas.... - he he


swim says thanks Antibody - he has a brewer just down the road and he will be merrily trotting down there tomorrow morning.

peace

[flipper]

he he - 162g yield - that makes the reaction 70.34% effiecient (68% - no better!)

No No No. I don't believe that. With that old style Leuckart method?. I would believe it when you used this Leuckart version

Post 61613

(psyloxy: "Re: Leukard scaleable ?", Methods Discourse) but with that old method.... I don't know.
Serious is that yield 68%???

[r2e3]

when swim was looking for leuckart, he was planing ahead - for the next step. he had the info but has only digested it (doh!)(austran/logical ) free brain space after off-loading steps 1,2 and 3 he thinks....

in the previous post he was refering to my mdp yield. 70% in practise and 68 - 76% on paper - so he was happy, slap bam in the middle.

anyways - he said will report back tomorrow - if the gods are shining on him that is - otherwise he will have to go and sulk  


he has 8hrs and is counting..........

oh yea - yield is meant to be 70% - he wonders...

[r2e3]

when swim was looking for leuckart, he was planing ahead - for the next step. he had the info but has only digested it (doh!)(austran/logical ) free brain space after off-loading steps 1,2 and 3 he thinks....

in the previous post he was refering to my mdp yield. 70% in practise and 68 - 76% on paper - so he was happy, slap bam in the middle.

anyways - he said will report back tomorrow - if the gods are shining on him that is - otherwise he will have to go and sulk  


he has 8hrs and is counting..........

oh yea - yield is meant to be 70% for leukart (austran) - he wonders... 40 will do

[r2e3]

will know by the end of this evening what the outcome will be and also learnt - set out the projected time and then add another 25% if you want to do things straight down the line (aah no pun intended!)

later

[r2e3]

Well swim tried doing the Leuckart and it didn't work. Evolution of CO2 was painfully slow and swim also noticed that ammonia was generated - weird and quiet unpleasant extracting the stuff. Is this to be expected as a by-product?? Nothing was mentioned in the literature.

Swim did raise the temperature to over the 160C as swim had seen 4 different temperatures suggested (150, 160, 165, 190) so swim figured it wouldn't hurt and it just appeared speed up the reaction - CO2 coming off real quick. Solution progressed to a dark red/crimson colour after five hours at 180C.

Will not try this reaction pathway again. Due primarily to ammonia formation and formamide toxicity and extraction.