Ritter
(Newbee)
11-22-00 14:21
No 70378
      Bromosaf to MDA: One Pot Shot
(Rated as: excellent)
 Bookmark   

The following is adapted from  J. Org. Chem., 47, 4327

A mixture of 2-bromosafrole (24.1g, .1mol), hexadecyltributylphosphonium bromide(5.1g, .01mol), sodium azide (16.2g, .25mol), and water (50ml) is magnetically stirred at 80'C for 24 hours.  Flask is cooled and phases are separated in sep funnel.  The dark reddish organic layer is diluted with toluene (20ml) and poured back into flask and stirring is restarted.  A solution of sodium borohydride (11.7g, .3mol) in water (30ml) is carefully added through an addition funnel over 30 minutes as temp is raised to 80'C and held there for 16h.  Contents of flask are cooled and poured into a sep funnel.   Aqueous layer is sepped off and organics are washed w/ 50ml dH20.  Three 40ml portions of 4M HCl (approx 10%) are used to extract MDA base from organic layer.  Combine all acid extracts and neutralize with 50% NaOH soln.  Golden beads of MDA base will fall out of soln.  Use two portions of 50ml toluene to isolate base.  At this point one of two things can be done.  If you are a greedy shoddy chemist you will dry the toluene extracts with anhydrous MgSO4 then bubble with HCl gas to isolate a relatively pure white MDA hydrochloride (8-12g) OR if you have any pride in your chemistry skills and product, toluene will be evaporated down to a orange oil and vacuum distilled using standard methods to yield 6.5-11.0g of water white pristine MDA base.  Distilled base is most easily crystallized by adding about 6 times volume of dry IPA and neutralizing w/ conc. HCl.  Place this in the freezer over night to find glorious white crystals of the hydrochloride.  At this point not all of the salt has precipitated and it won't  no matter how long you leave it in the freezer, so add the same volume of dry acetone to ppt. entire yield (6-12g). 

Notes:
1)     2-Bromosafrole was prepared using process developed by Fester.  HCl(g) is bubbled into a  soln of 48%(aq)HBr, HOAc and PURE DISTILLED safrole.  The procedure is archived on rRhodiums site and runs exactly as Fester claims, believe it or not!

2)     Yield of product is totally dependant on reaction time/temp of first step.  If literature citing is examined yields above 85% are reported for all primary alkyl bromides.  Problem with lower yield here is the fact that we are dealing with a secondary bromide. This introduces the possibility of occurrence of two yield killing side reactions.  Elemination of -Br resulting in isosafrole then elemination of azide may occur resulting in more isosafrole.  Perhaps reducing the temp and extending rxn time will slow rate of elemination resulting in higher yield of alkylazide.  Someone willing to try?

3)    Hexadecyltributylphosphonium bromide is very expensive.  Refs stating Aliquat 336 is a cheaper alternative PTC are on the Hive.

 
 
 
 
    improv_chem
(Hive Bee)
11-22-00 17:36
No 70408
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

Thanks for posting this article.
I was very interested in it before from PK's post, but now that we all have the full article Bees can have sweet dreams about this process....
...It might come in very useful someday if SWIM finds a PTC and some NaBH4.



laughsmile


If it doesn't work, smash it and start over
 
 
 
 
    jim
(Stranger)
11-27-00 11:07
No 71255
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

THis is CHEM_GUY, hello Ritter...


There was a post a long time ago in the serious chemists for about bromosafrole and it had an academic reference stating that the methylenedioxy bridge was unstable in HBr and acetic acid.  Use the search engine and check it out. 

The un-adapted version was probably without the methylenedioxy bridge...
 
 
 
 
    Ritter
(Newbee)
11-30-00 21:54
No 71765
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

Chem Guy: FANTASTIC TO HEAR FROM YOU!!!!!!  You're greatly missed around here by many!!!!

Well anyway, here's the skinny.  It doesn't matter what the refs say because I have done this reaction about 10 times and it works exactly as stated in my syth.  None of the post is bullshit. Period.  The final product was ABSOLUTELY ACTIVE MDA!!!!! 

Perhaps the researchers in the ref were using anhydrous conditions with lots of heat or something to that effect.  Those conditions would surely blow the methylene bridge to hell for sure but the procedure used in my above synth works fine. 

What SWIM did was use Festers preparation of bromosafrole than use that product as feed stock for the reaction detailed in the journal citing I provided in the post.

PM me for more details.
 
 
 
 
    jim
(Stranger)
12-01-00 09:04
No 71779
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

I can't recall if it was anhydrous conditions, but you are probably right Ritter.  ( as you usually are.)

The details look fine.
 
 
 
 
    foxy2
(Hive Addict)
12-02-00 13:56
No 71974
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

What intermediate is fotmed after addition of the Na-Azide??
Is it an Imine?
 
 
 
 
    Osmium
(Stonium's / Changer)
12-02-00 14:17
No 71982
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

No, it's an organic azide (R-N3) tongue
 
 
 
 
    foxy2
(Hive Addict)
12-02-00 23:12
No 72120
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

Hmmm
Says here that primary amines result from the hydrogenation of azides at room temperature and 3-4 atmospheres over platinum oxide or palladium catalysts.  The addition of acid is sometimes beneficial.

M.C. Dart and H.B. Henbest, Nature, 183, 817 (1959).

M.C. Dart and H.B. Henbest, J. Chem. Soc., 3563 (1960).
 
 
 
 
    psychokitty
(Kitty-KrZ)
12-05-00 14:09
No 72742
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

Ritter, is there any danger in performing this reaction without a hood?  Does the elimination of HBr potentially reacting with sodium azide to possibly form hydrazoic acid present any problem whatsoever?  This is the only risk factor that I see.  Otherwise, the method is truly gold.

--PK
 
 
 
 
    Ritter
(Newbee)
12-07-00 20:28
No 73593
      Re: Bromosaf to MDA: One Pot Shot  Bookmark   

In all honesty, swinm was worried about the same thing in the beginning but never ran into any problems associated w/ hydrazoic acid.  In fact, it is still only conjecture on my part that the azide group could possibly be eliminated from the alkane resulting in hydrazoic acid and isosaf.  HBr is not a product of the PTC reaction.  The Br- anion reacts with the Na+ cation to form sodium bromide as a byproduct.   PSkitty, dont worry about it- much experience with this rxn proves it is safe.  Just go ahead w/ the procedure and you will be most pleased!
 
 
 
 
    endo1
(Stranger)
06-16-02 17:36
No 322253
      1 pot shot a shot  Bookmark   

SW has made way too much bromo (322022) and has wasted lots in "low yield" pipe bombs and wants to try something new. Ritter has not got around to that write up he promised us in article 294411 =) so he will give the ol one pot shot a shot!... oh yeah and he will go 10x the scale.

water, bromo, hex and azide added in that order with stirring. temp raised very slowly and held very close to 80 for 24 hours. SW has no external thermastat but SW checked before and after sleep time and was very close to 80. contents poured in to sep funnel and red-brown organic layer was retrieved and diluted with hardware store toluene (All other reagents were lab grade).  Some toluene was spilled in the process but I think I got it pretty close to 200 mls. The "pot" was not washed out! SW is confused at this point because the write up on rhodium shows in diagram that a PTC is also used in the reduction of the azide. Thinking that perhaps the traces of hex left in the pot will be important in the next stage, he does not wash it out. NaBH4 added to water and placed in drop funnel. slowly added while bringing temp up to 80... oops it got 86 quick! Toluene/water azeotrope is boiling, put the condenser on for reflux. OK temp bounced around a bit but when it seemed like it was holding close to 80 so he went to bed. SW wakes up to find a precipitate had formed a large solid mass and the stir bar was still going but the vortex could no longer reach the organic layer. the layers had seperated and the temp of the organic layer was only 60. temp get to low or high over night? dH20 added but SW ran out of room in the pot. Oh well, there was only 4 hours left to go, and Ritter says yield is mostly dependent on first stage which seemed to go well. He pours contents in to sep funnel and seps off aquatic layer. 500ml dH2o added  followed by vigorous shaking.... Hmm... the contents of the sep funnel formed a white "milk" after adding much toluene and water and waiting an hour a very thin organic layer was spotted at the top but it was crystal clear!? Hmmm SW thinks maybe there were traces of HCl in his graduated cylinder he used to measure the toluene. perhaps a little lye solution.... VOILA! The milk was gone and phases seperated clearly and the brown colour (yes SW is Canadian) came back to the top layer! Interesting. The rest of the a/b went as expected and golden beads DID fall out of solution. extracted with toluene and tried once more to wash with plane d water... bad move theres that "milk" again. Lye added again to fix the problem and aquois layer sepped. OK, ready for the vaac.... ARGH! Mom just called.. gotta go for fathers day dinner! I'll post the finall results later!
 
 
 
 
    endo1
(Stranger)
06-17-02 19:44
No 322613
      1 pot shot a shot  Bookmark   

84.5 g of the freebase. Not too great but I guess not too bad for the first time. SW will probabbly try aliquat 336 instead of hex next at same scale.
 
 
 
 
    psytech
(Stranger)
10-11-02 19:28
No 367482
      Hexadecyltributylphosphonium br vs aliquat 336  Bookmark   

Im have use any PTC before, but should i assume you would use a molar eq. if you sub aliquat 336 for Hexadecyltributylphosphonium bromide . I i assume yields would be about the same, 25-35%.
 
 
 
 
    Bwiti
(PVC-Analog Taste-Tester)
10-12-02 17:34
No 367779
      It's about time bees started talking about this ...  Bookmark   

  It's about time bees started talking about this route more, but all this 9/11 shit makes explosive compounds like azides harder to get.frown

Love my country, fear my government.
 
 
 
 
    Rhodium
(Chief Bee)
10-12-02 17:57
No 367785
      MDA PTC  Bookmark   

The method posted above (archived at ../rhodium/chemistry /mda.azide.html ) gives up to 56% molar yield according to the writeup, and that should be possible to attain. Yes, if substituting Aliquat 336, then use 3.36g of that instead (incidentally 336 is the molecular weight of that Aliquat).