Dope_Amine (Hive Bee)
10-18-01 06:56
No 226100
      Recrystalization of Cyano and Ammonium Acetate  Bookmark   

Hey I got a bit of old cyano around and come wet ammonium acetate.  I want to recrystalize and dry both of them. 

Merck says ammonium acetate is freely soluble in alcohol, but slightly soluble in acetone so I'm thinkin' recrystalize in freezer from minimum amount of boiling acetone? 

And for cyano, very soluble in MeOH, but slightly soluble in ethanol.  So, recrystalize from boiling ethanol?  Interestingly, it lists the solubility of cyano in water, says it is stable in acid to pH of 3 and then goes through rapid hydrolysis.  What the fuck!?! I thought water killed sodium cyanoborohydride!  I had always figured the reason everybody's yield were so low with cyano was b/c nobody treated it as an inorganic reagent, drying the imine solution and the ammonium acetate and keeping it under N2.  Now I'm very confuzudled....crazy

something for your mind.......
 
 
 
 
    Dope_Amine
(Hive Bee)
10-18-01 07:06
No 226103
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

Hmmm, for sodium borohydride, it says it is most stable in slightly basic water but then it says that it reduces Schiff bases in non-aqueous solutions so maybee that's the trick.  It won't bee destroyed, but can't bee reduced.  I wonder how much that effects the yield of the cyano IF the same is true for it?  IF the cyano is not destroyed by water, then is the yield reduced and in what amounts of water is it necessary to see a difference.  The first cyano I ever did was with very wet ammonium acetate and it still worked to at least 50%.  So would using MeOH or MeOH + EtOH bee enough to keep the water away from the reaction or am I wasting my time trying to purify these reagents?????crazycrazycrazy

something for your mind.......
 
 
 
 
    Rhodium
(Chief Bee)
10-18-01 07:06
No 226104
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

From "Purification of Laboratory Chemicals" 4th Ed.

Ammonium acetate:
Recrystallize twice from anhydrous acetic acid, and dry for 24h at 100C in a vacuum desiccator.

NaBH3CN:
Dissolve in 20% THF, filter and add a fourfold volume if DCM to the filtrate. Collect the solid by suction filtration and dry in a vacuum desiccator.


I believe the yield limit is from the inherent difficulty of the imine formation with NH3, and not so much on the purity of the reagents.
 
 
 
 
    mercvap01
(Stranger)
10-18-01 15:44
No 226240
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

First never use water with sodium cyano you will get disasterious results IE explosion or fire....  My friend used to to this reaction with MDP2P and almost always got 50% yield no matter what shape the ammonium acetate or sodium cyano was in.  I was always curious of why the yield could never go up higher than that.  One time he got 60% percent but was baffled.  He thought his lab skills just sucked or was using too much product.
 
 
 
 
    Dope_Amine
(Hive Bee)
10-18-01 19:39
No 226311
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

Oh Rhod you stud!  I have the fourth edition somewhere, but couldn't find it.  I looked in the third edition which is from 1988 and it SUCKED.  Thanks homie!  I wonder what might help the formation?  I understood that the reason for adding a 10 x excess of ammonium acetate was for this reason.  There has got to bee a better way to do it than that.  Yea, 50% yields are standard no matter what.  I was hoping that drying everything including the imine would help.  Don't ya think having some molecular seives in there to suck up water would drive it to the right (imine formation)?

An' I meant to say  earlier that the NaBH4 can't reduce not bee reduced.  And even earlier that should read "some wet ammonium acetate", not "come wet".  Duh!

something for your mind.......
 
 
 
 
    Dope_Amine
(Hive Bee)
10-19-01 01:17
No 226436
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

First of all, ya can't recrystalize ammonium acetate from acetone cuz of the imine formation.  Duh again!  I fully agree with the recrystalization from acetic acid though.  For the cyano, I think I'm gonna try ethanol instead and I'll either freeze it out or crash it out with DCM.  If it simply won't go into EtOH, then I'll disolve in MeOH and crash out with DCM.  How 'bout that?

Ok now on to our much more interesting topic of imine formation.  The removal of water would drive imine formation to the right IMO.  I think molecular sieves would be good, but if ya could somehow do a Dean Stark, that would bee a lot better.  The only problem is solubility, cuz I don't think it's gonna bee soluble in toluene at all and I'm not sure what alternative solvent would work better.  I wonder if there is any solvent it would go into that could then be dried with mag sulfate.  Time to brainstorm.  So far I think molecular sieves would bee the best with silica gel beads taking second place (just cuz they fuck with the pH a bit).  Dean Stark would bee first place if I knew of a way to get it to work.  'Till then I got my sieves in the oven drying.......tongue

something for your mind.......
 
 
 
 
    LaBTop
(Daddy)
10-28-01 18:46
No 229604
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

Dope Amine, try as your solvent a mix of dry 98% methanol (2 parts) and 98% toluene (3parts).
Solute first your ammonium acetate in boiling methanol, then add the toluene, which will bring the temp back to normal.
Use a combo of silicagel beads and MgSO4 (20% w/w each) to dry the imine forming step. Drip your ketone slowly in, to give the imine all the time needed to form slowly. Do not cool the imine step.
You will see an amazing improvement in imine yield. (silicagel is a weak Lewis acid)
Remove the silicagel/MgSO4 combo before the amination step. LT/

WISDOMwillWIN
 
 
 
 
    Dope_Amine
(Hive Bee)
10-29-01 22:30
No 230036
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

You like silica gel better than mol. sieves?  I've witnessed silica gel absorb honey so I'd assume it does tha same with 'tone.  Thanx for the tips. wink

something for your mind.......
 
 
 
 
    LaBTop
(Daddy)
10-30-01 11:58
No 230450
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

Next test you would do will be a comparison between the above and one addition:
saturate your MeOH/Toluene/AA mixture with NH3 gas(cylinder or generator), and keep slowly bubbling in NH3 gas while adding the ketone then slowly like above.
 
Adding the ketone starts the imine forming, and doing it slowly gives you certainty that the solution has always an excess of NH4+ and NH3 gas in it, to force the imine forming and not the propanol endreaction step, if excess AA and NH3 is not present. Propanol forming seems to be the bottleneck when too much water (even minimal amounts) is present.

In the MDMA boro procedure, even with water present while imine is forming, that is no obstacle, here it certainly is.

The whole difference with the other ketone/boro procedures is the fact that NH4+ or NH3 forms the imine so difficult and slowly, and is prolly touchy to form at a certain pH, around 5 (refs).
The cyanoboro procedure with AA depends on a pH of 7.3 at imine forming, so some differentiation from known refs about the pH 5 in NH3 procedures with NaBH4 amination should be tried perhaps, to find the optimum.

The amount of AA is also important, ratio's of 1:3 gmole to methanol seem good to me, but others came up with 1:10 even, which seems a bit overdone to me.

Water in the imine forming must be removed by any means possible, or propanol is formed instead of imine. I even thought about boiling the mix (if 100C can be reached without boiling) while adding ketone, to steam out all water formed by the imine reaction.
When your 2-3 hour addition of ketone is ready, your solution should have changed from light yellow to dark yellow.

(Toluene seems to have an important influence here, which I can not explain, it doesn't mix with water, but prolly does with methanol, and thus perhaps blocking water uptake by the MeOH/Toluene/AA mixture).

Then you cool the imine mixture down to +4 to +7 Celsius, and begin slowly adding NaBH4, waiting every time till the foaming stops and the temp is back to 4-7C. And let it stirr for in total 36 hours, to get max yield. Then flood with 8x the volume water, and let mix 30 min, then stop mixer and wait 30 min to let the MDA raw oil separate to the bottom, and tap off.
Then do a quick A/B wash, and collect the now nearly pure MDA base oil again and gas with HCl gas or just add 33% HCl until pH 5 and then boil off all water from the 33% HCl added, untill you have a dry crystall mass, wash with acetone to obtain white crystals and dry. LT/

PS: silicagel and MgSO4 mini-rocks can easily be washed with some methanol afterwards, and added to the motherliquid to collect all traces of imine attached to them. The Lewis acid nature of silicagel plays also an important role, never explained totally by researchers.


WISDOMwillWIN
 
 
 
 
    LaBTop
(Daddy)
11-02-01 16:25
No 232132
      Re: Recrystalization of Cyano and Ammonium Acetate  Bookmark   

I got another idea after re-reading Post 208935 (sunlight: "MDA with NaBH4 and am acetate review.", Methods Discourse), the whole thread.
As stated there somewhere by me, most imines are reduced in situ.
So why not add the 10-12% NaBH4 already to the Toluene/MeOH/AA mix?
Or if that doesn't work, use a Toluene/MeOH/sat.NH3gas solution, pH buffered by AA to get to pH 5.
Then the slowly dripped in ketone will form imine, and that imine will directly be reduced by the excess NaBH4 present, giving no way to the imine to proceed further to the propanol.
The ketone must be dripped in faster, because the NaBH4 will degrade slowly in the MeOH part.
Someone attended me on the fact that the MeOH:Toluene ratio should be different, because in practice it was noted that only a big amount of MeOH would totally dilute in a smaller amount of Toluene, if the other way round, 2 layers formed.
So it seems better to have the following ratio's:

I.   100 MDP2P, 600 MeOH, 200 Toluene, 300 AA, 12 NaBH4. Slow ketone dripping.
or
II.  100 MDP2P, 1200 MeOH, 400 Toluene, 400 AA, 12 NaBH4. Faster ketone dripping.
or
III. 100 MDP2P, 1000 MeOH, 333 Toluene, saturate with NH3gas, 300 AA, 12 NaBH4 (eventually add more boro, if bubbling of H2 gas decreases). Fast ketone streaming in.

There is a member who knows the data to do this reaction perfectly, so he told me, but he probably  has personal reasons to keep it to himself, which I do understand, but do not totally agree with.
He claimed to had a yield of 89%, and thought that yield could be even more when the procedure will be fine-tuned.
It would be a nice gesture if he would come out of the woodwork, and help us out.
He could PM me, and I could tell him some facts why it is redundant now to keep to his principles, situations have changed to the positive for him.
I can't for some reason open my hushmails, the connection here is seemingly so slow, that I constantly get a "30 second delay caused hush to stop access to the server" message. So who knows his last mails are waiting for me, but I can't access them.

Any other members who promissed to test it out at small scale: it is obvious, that the solution to the NH3 boro one pot will open a lot of other improvements for other procedures where NH3 is involved.
So do your part of the war, get started. LT/

WISDOMwillWIN