dormouse (Member)
04-20-00 23:44
No 108398
      an alternative catalyst to NaBH3CN -weaponx  Bookmark   


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Author  Topic:   an alternative catalyst to NaBH3CN 
weaponx
unregistered   posted 06-19-98 04:19 PM           
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This has already been briefly discussed elsewhere on this board but I'm looking for some more information from all you chem gods so that this can become a full blown recipe. The substitute chemical is sodium triacetoxyborohydride, and before you go freaking out and saying that sounds even worse than sodium cyanoborohydride let me state a few of the facts about why NaBH(OAc)3 is better. It is easily made from NaBH4 and acetic acid (no HCN to deal with), 2-3 times cheaper, probably completely unwatched, no hazard charges for shipping (send that bad boy over night air if you want), safer to deal with, and it is available from Spectrum, Lancaster, etc... The journal article I read (I'm terribly sorry but I forgot my notes, but the ref is somewhere around on the hive already, I'll post it later) states NaBH(OAc)3 in 1,2 dichloroethane gives better yields, faster, and with less side products than NaBH3CN in methanol. The DCE can be substitud with THF but it will slow the reaction down a little bit. One could also add some Acetic Acid to the reaction (with either solvent) and speed the whole thing up a bit. It also stated that the amine source can be reduced 10 fold from the cyano method, but this is where the problem comes in. Ammonium Acetate is not soluble enough in DCE or THF for the reaction to run properly, so another amine source must be found. I am unfortunately an uneducated chem wannabee and my theory is very lacking (I'm working on that though). I'm asking your help in finding a replacement for the ammonium acetate that is soluble in DCE or THF and will beget a primary amine. The journal article listed such things as cyclohexylamine, pyridine, aniline, etc... Oh, and just for your knowledge methanol is a no-no, as is any aqueous solution, it degrades the catalyst. Oh noble warriors my cry goes out to thee. The War Is Over.


weaponx
unregistered   posted 06-19-98 04:33 PM           
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Ahh, those refs I spoke of are in Acquisition Discourse under NaBH4 vs. NaBH3CN, availability, yields, etc.. (or something along those lines).
 
ReFlux
Member   posted 06-19-98 04:45 PM          
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weaponx- First off, neither NaBH3CN or NaBH(OAc)3 are catalysts; they are reducing agents. I'm trying to nit-pick, there is a huge difference between these two kinds of reagents.

As for a source for primary amines that is soluble in DCE, orginal authors of this research found that Ammonium Trifluoroacetate worked well. Although the minimum amount of amine source req'd is 1:1 ratio w/ ketone, they do recommend at least a 20% excess, ie 1.2:1. This is still better than the five fold excess needed for cyanoborohydride reductions, but is by no means 1/10th the amount.
Why the primary amine source? Why not hypothetically use a secondary amine (i,e : MeNH2) to create a methyl-aminated product. MeNH2 is soluble in DCE and THF, if I'm not mistaken.

The other huge advantage to the NaBH(OAc)3 method is that it is not pH sensitive like the cyanoborohydride reductions, so no squirrly monitoring/adjusting of pH levels within a tight bandwidth.

The most recent journal ref to this work is J Org Chem 61, 3849-3862 (1996).


ReFlux
Member   posted 06-19-98 04:47 PM          
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whoops! That should read: I'm NOT trying to nit-pick! :-)
-ReFlux


quirks
Member   posted 06-19-98 04:54 PM          
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I have the paper here so if you have any specific questions ask away... It's a big fucker so I won't be scannign it for a while. but...
procedure: (direct reductive animation)

(a) the amine and carbonyl compounds are mixed with 1,2DCE (or DCM/THF/CH3CN) and treated with NaBH(OAc)3

(b) acetic acid helps but not nessacary

(c) amine salt can be used (freebase prefered)

molar ratio:

ketone:amine:NaBH(OAc)3:AcOH = 10:10:14:10

typical procedure:

1g hexamethylenemine(sp) + .84g cylclohexanone + 3g NaBH(OAc)3 in 35ml DCE and .6g AcOH were stirred under N2 for 24 hours at rt to give a 96% yeild

rxn quenched with addition of dilute NaOH or NaHCO3

(so, yea, it's cheaper but you need more...)

The ammonium acetate would would dissolve with the addition of more AcOH no?? It's not nessacary for the rxn, just helps drive it...


 
ReFlux
Member   posted 06-19-98 05:08 PM          
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Quirks-the problem is that the primary amine created is far more soluble than the ammonium acetate and as a result dialkylate amines are then produced instead. No, ammonium acetate is a not usable in this system.
 
xstatic
unregistered   posted 06-19-98 05:13 PM           
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Wow, this sounds pretty cool. Does anybody know if maybe Ammonium Chloride might be soluble in either solvent?
 
weaponx
unregistered   posted 06-19-98 05:28 PM           
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Whoops, sorry for the errors.
ReFlux: As I said I'm uneducated (I know what I'm looking for normally, but most of the time I don't know what its called). As I said I didn't have my notes handy as well, maybe that explains the 1/10 thing. Also, thanks for putting that info. about the 20% molar excess in there, I had forgot about that. As for using the MeNH2 I'm keeping that as something to fall back on, as secondary amines are not my primary goal, and MeNH2 is difficult to come by. I had read your previous post about the ammonium trifluoroacetate, but can't find this for sale anywhere. So thats been my limiting factor there. I was just looking for something along those same lines that was a bit easier to find. And don't worry about being to nitpicky, the more you pick the more I can learn.
Quirks: See above as for my mistakes. Sorry I forgot to look up M.W.'s before figuring out prices, thanks for setting me straight. I still find it much more preferable. I didn't see the part about DCM being acceptable. Did it say if that was slower than the DCE?
Thank you to both of you for your help.
 
weaponx
unregistered   posted 06-19-98 05:47 PM           
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Oh, I forgot to ask. Does anybody have a synth or a ref. to point me in the right direction for ammonium trifluoroacetate. Thanks again.
 
quirks
Member   posted 06-20-98 09:18 AM          
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Yea, I read that after posting... BUT MeNH3 would work no??
weaponX: what do you mean secondary amines aren't your primary goal?? Should maybe it be weaponT?? (tryptamines)


weaponx
unregistered   posted 06-20-98 03:35 PM           
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I could be wrong and often am. Please correct me. I thought the primary amine in this case was MDA and the secondary amine would be MDMA. My goal is for a recipe using this reducing agent that would theoretically produce MDA using chemicals that are not too awfully difficult to get, I like the MeNH3 idea, but would still like to find a replacement for the ammonium triflouroacetate, although if anybody happens to know a company that sells this stuff my theorizing would be over. Again, thank you for your help, it is much appreciated.
 
007
unregistered   posted 06-20-98 04:38 PM           
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quirks: you say free base is prefered, so what is the best think to do with methylamine in this rxn? use a 40% aq. solution??
 
quirks
Member   posted 06-20-98 04:44 PM          
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a primary amine has one carbon attached to the carbon attached to the amine, a secondary has two carbons attached to the carbon attached to the amine, mdma and mda are both secondary amines.
If you want a quick and dirty mda route, why not go with pseudonitrosites?? Double reduction with activated alunimum, see sparky's tale... NaOH and CaO for otc isomerization, NaNO2 is a meat preservative. 66% clean sulphuric acid at battery supply houses.

Anybody know if activated aluimum will reduce n-formyl-mda to mdma?? or n-acetyl-mda to mde??


Rhodium
Administrator   posted 06-20-98 05:31 PM          
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Sorry quirks, the nomenclature is different with amines.
R-NH2 is a primary amine, R2NH a secondary and R3N a tertiary. It is not the same as with alcohols for example, the naming of them is just like you describe.


quirks
Member   posted 06-20-98 06:12 PM          
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opps... 
 
weaponx
unregistered   posted 06-22-98 10:45 AM           
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Don't use aq. methylamine. Aqueous solutions degrade the NaBH(OAc)3. As for the activated aluminum procedure, I prefer not to work with mercury compounds as they are bad for the environment.
OK, so Quirks, and Rhodium, I want to learn. Is MDA a secondary amine? And then would that make MDMA a secondary amine also? the difference being a methyl group? Thanks for the clarification on this.
 
Cherrie Baby
Member   posted 06-22-98 02:03 PM          
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MDA is a primary amine - becuase the nitrogen atom of the amine has two hyrogens but only one carbon attached. It's the one carbon that makes it primary.
MDMA is a secondary amine - nitrogen is bonded to only one hydrogen but to two carbon atoms.

Count the number of carbon atoms attached to the nitrogen to get the degree of the amine:
RNH2 primary
R1R2NH secondary
R1R2NR3 tertiary.

Remember R is an alkyl group which bonds to the nitrogen via a carbon.


 
weaponx
unregistered   posted 06-23-98 02:00 PM           
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Thank you Cherrie Baby, the cloud has lifted and I am enlightened. Now, does anybody know what amine sources could replace ammonium acetate in the above synthesis to create MDA? Whether or not they are soluble in said Solvents is not important, tests will be run. Even a good place to look for someone who is in the process of educating themselves would be greatly appreciated. Is this something that could be found in a basic O chem text? Just a shove in the right direction is all I ask. Thank you all for your help.
 
007
unregistered   posted 06-24-98 08:25 AM           
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weaponx: i just skimmed three articles on the subject of NaB(AcO) reductive animation and i believe i remeber reading that the best source for a primary amine product would be concetrated (28-30%) NH3.
I noticed there are differen procedure for amination if the amines are weakly or non-basic, in contrast to if they are strongly basic, so what i am wondering is what methylamine will do. it is a stronger base than ammonia, so will that work well enough fo consideration as a strong base? in merck pH of 1.0N aq solution is 11.6, so i would assume it is a strong enough base, but then since 40% aq. soln of methylamine is out of the question, how would the HCl salt interfere?
 
weaponx
unregistered   posted 06-24-98 11:05 AM           
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As usual I very well could be mistaken, but here goes.
007: According to what I've read on this aqueous solutions are out. The H2O degrades the reducing agent. So the conc. NH3 won't work (I think). I'm not sure about the MeNH2.HCl, I think it will work as long as it will dissolve in the DCE or THF. I don't believe this reaction is pH sensitive. ReFlux states that above and I seem to remember reading it as well. My current belief is that anhydrous ammonia gas will work, momomethylamine gas will work, and Methylamine HCl, and ammonium chloride should work. I'm thinking maybe I should just buy some DCE, and a bunch of different ammonium salts and check there solubility. The ammonia gas and methylamine gas don't sound like fun to work with or to acquire.
Anybody: Cyclohexylamine will dissolve in DCE. Will it form a primary amine, or something else?
Thanks for the help.
 
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