Ghost_Of_BT (Hive Bee)
08-30-01 22:28
No 208733
      Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I think I've located safe sources for all the chemicals for Krz's DMT synth exept for the damn NaCNBH3. Im wondering if there if a good substitute. Now in Tihkal #6, Shulgin uses ethyl formate and LAH to convert tryptamine to DMT. I don't know much chemistry, but I am assuing that this is the same sort of reaction that Krz does. So can LAH substitute NaCNBH3 in Krz synth? If so, what quantities should I use and what modifications should I make?

Visit www.the-hive.ws
 
 
 
 
    Lilienthal
(Moderator)
08-31-01 00:40
No 208786
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

These are different reactions and lithium aluminum hydride can't be used for one-pot reductive aminations (or should I write animations?). 
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
08-31-01 01:16
No 208794
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

OK, thanks.

please share chemical sources with me via p.m.
 
 
 
 
    terbium
(Hive Addict)
08-31-01 03:40
No 208830
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   


So can LAH substitute NaCNBH3 in Krz synth?



Does that mean you can get LiAlH4 easier than you can get NaCNBH3? If so, then perhaps a route starting with indoleacetic acid.

 
 
 
 
    Ghost_Of_BT
(Hive Bee)
08-31-01 05:55
No 208862
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Well I see an online chem site selling LiAlH4 and they seem friendly. I think you know the place I'm thinking of. I have read all the DMT synths on Rhodium's page and Tihkal and I thought Krz's was by far the simplest. Another possibility is the indole route but in that case the especially difficult chemical to obtain is dimethylamine (anahydrous in ether?). Perhaps I can synthesize it by refluxing DMF with HCl, like one of the proceedures says and mix dimethylamine HCl with NaOH and gass it through ether. Would that work? 

please share chemical sources with me via p.m.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
08-31-01 06:16
No 208868
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I found a relatively easy-looking proceedure for indole to DMT. It didn't say who wrote it. Here it is
-------------------------------
indole 25g
oxalylchloride 50g
dimethylamine 100g
lithium aluminium hydride 20g
tetrahydrofuran 1L
dry ethyl ether 1.5L
undried ethyl ether 1L
benzene 100ml
methanol 200ml
 
STAGE 1: Dissolve 25g indole in 1 litre dry ethyl ether and cool solution to 0oC - cool 50ml dry oxalylchloride to -5oC and add to indole solution (WARNING: this is a violent reaction avoid splattering - oxalylchloride will react with moisture to form hydrochloric acid - avoid breathing fumes, skin contact, eyes and humidity) allow solution to cool in ice bath while reaction subsides

STAGE 2: Cool 100ml dry ethyl ether to 0oC - cool dimethylamine (without opening bottle) to 0oC - carefully pour 100ml dimethylamine into ether.


STAGE 3: Slowly add solution from stage 2 to solution from stage 1 - remove solution from ice bath and stir vigorously until solution reaches room temperature - this should lead to formation of white precipitate (if precipitate has orange streaks continue stirring until it is as near to white as possible) Filter by suction - pour undried ether over precipitate and filter by suction - repeat washing with undried ether and wash twice with water then allow to dry on a non-metallic surface.


STAGE 4: Place solid from stage 3 in large beaker and cover with about 2cm methanol-benzene solvent (mix 100ml benzene with 100ml methanol) heat in water bath and more solvent if required - allow to cool until needle shaped crystals form - pour off solvent and dry crystals (this should produce approximately 25gms of crystals) dissolve crystals in tetrahydrofuran.


STAGE 5: Dissolve 20grams lithium aluminium hydride in 200ml tetrahydrofuran (WARNING: LiAlH4 ignites on contact with moisture take precautions as previously)


STAGE 6: Add solution from stage 5 to solution from stage 4 and heat in water bath for 3 hours stirring vigorously for 2 minutes every 15 minutes (when not stirring solution keep aspirator tube in place) - when complete allow to cool to room temperature then cool in ice bath to 0oC add chilled methanol while stirring gently until white precipitate forms - pour liquid through paper filter and collect filtered liquid in flask - pour about 100ml tetrahydrofuran through filter and collect liquid in same flask - heat liquid in water bath until tetrahydrofuran evaporates and thick paste remains - pour onto non metallic surface and allow to dry - this is slightly impure but good quality DMT


please share chemical sources with me via p.m.
 
 
 
 
    Rhodium
(Chief Bee)
08-31-01 10:19
No 208919
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

40% Aqueous dimethylamine can be used instead of anhydrous dimethylamine (added to the indoleglyoxyl chloride). The yield is more like 50% than the 80% gotten with anhydrous dimethylamine, but the procedure still works. The byproduct acid could isolated and rechlorinated for another run.

Another way would be to mix equimolar amounts of dimethylamine HCl with triethylamine in ether (to give a solution of dimethylamine freebase and Et3N*HCl), and then add the acid chloride to this solution. It would be equivalent to using straight etheral diethylamine freebase, and give the 80%-ish yields Shulgin describes in Tihkal.

Ghost: Where did you find that prodedure?
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
08-31-01 16:45
No 208968
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I dont remember exactly where I found it. I was just doing a search and I came acrose a web page giving that synth. There where no links or anything else on the page.

please share chemical sources with me via p.m.
 
 
 
 
    Osmium
(Stoni's sexual toy)
08-31-01 18:23
No 209017
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

> Well I see an online chem site selling LiAlH4 and they
> seem friendly. I think you know the place I'm thinking of.

It's not a question of friendliness. They have to play by the rules like everybody else, and they will NOT bend over for you. Nobody will, when the cops ask to have a look into their records they will give them what they want, because they have to.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
08-31-01 22:26
No 209103
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I know that they will cooperate with the police, what I mean by they seem friendly is that I dont think they'll ask what my intentions are. There are four routes that I am looking into. Each one has at least one problem for me. There's A)Krz method (requires NaCNBH3) B)indole route (requires dimethylamine and oxylyl chloride) C)Shulgin's ethyl formate route (ethyl fromate watched) D)IAA route (requires dimethylamine and the proceedure isn't perfectly clear to me). If NaCNBH3 cant be replaced and I can't find a source (p.m. me if you know of a friendly source), than that crosses off the option of Krz's method. Than there's the indole route. Do you think ordering dimethylamine is dangerous? What about oxylylchloride? The IAA routes that I've read seemed relatively difficult. If somone who suceeded with that route would do a detailed writeup, that would be great.

please share chemical sources with me via p.m.
 
 
 
 
    Lilienthal
(Moderator)
09-01-01 00:33
No 209140
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Look into these threads: Post 7781 (Lilienthal: "Re: maybe 4 steps from tryptophan to DMT/DET/DPT", Tryptamine Chemistry) and Post 197106 (Lilienthal: "Re: looked up some nice ref's", Tryptamine Chemistry), and Post 17677 (C_Nemo: "useful tryptamine methods", Tryptamine Chemistry).
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
09-01-01 07:03
No 209229
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Uh, yeah but --- are there any substitutes for sodium cyanoborohydride in the reductive formylation of tryptamine? Very seldom can a reduction be limited to only one possible reagent. I recall someone asking about, or rather mentioning, catalytic hydrogenation in this context, but not answered. The problem is cyclization, I believe, happening with overly vigorous reduction.

Lilienthal, your answers are always so authoritative they seem to still further discussion. Yet they are so terse, they leave me hungering for further details. Quite similar to your website! (particularly for someone without chem library access.) I would love to see you post some general overviews on tryptamine chemistry. These compounds are sly and tricky to an extraordinary degree, for they are exceptions to so many general principles of chemistry that they must bee ensorcerelled!

Reduction is the keystone. I am tired of hearing about lithium aluminum hydride, when you know we can't get any. I know there must be two-step reductions of an indole glyoxylamide to the amine, without LAH; what are they? Would lithium borohydride work for the one-step reduction as well as LiAlH4, as in smiley_boy's Post 196781 (smiley_boy: "Re: One more idea for LAHless nitrostyrene reductions", Novel Discourse)

  Re: One more idea for LAHless nitrostyrene reductions   
...under aprotic conditions you can combine NaBH4 and add a little LiCl (or better yet LiBr) to obtain LiBH4 in situ - a much, much more powerful reducing agent.

Here's a quick, overly-simplified lesson on the chemistry of borohydrides and aluminum hydrides and their activity. When the metals complex with BH4- or AlH4-, the relative size of the metal atoms has a huge effect. For example, with Li+, the overlap of electron orbitals around the Li is much too small to really overlap much with BH4-, plus lithium is not so free-and-easy with giving up its elecxtrons like a cation is supposed to (at least compared to other metals.) The result: the borohydride is very reactive. LiBH4- readily reacts with water or simple alcohols, just like LiAlH4. LiBH4 can reduce nitro groups to amino groups.



or his mention of borane-THF Post 196785 (smiley_boy: "Re: One more idea for LAHless nitrostyrene reductions", Novel Discourse)


Actually, speaking of borane, that seems like a topic that hasn't been as well addressed as I feel it should. Now, correct me if I'm wrong, but borane*THF can be produced from sodium borohydride by partial decomposition with sufuric acid in THF:

2 NaBH4 + H2SO4 + 2 THF -> 2 BH3*THF + Na2SO4 + 2 H2

So why isn't this taken advantage of? The reduction of nitrostyrenes using borane-ether complexes is a well-established procedure in the literature, providing good yields  and remarkable chemoselectivity; for some arylethylamines, its the only practical route. So why aren't people experimenting with this around here? Am I forgetting something?

To make myself more clear, this is what I'm proposing: you can replace the LiAlH4 in your average nitrostyrene reduction procedure with NaBH4 and H2SO4! Safe, cheap, available. How's that for practical? Hopefully this generates some interest...



Likewise, in this reductive formylation of tryptamine, what is the key to making this feasible for more beez? Converting sodium borohydride to cyanoborohydride is not totally beyond reach, but no one likes working with cyanide at all, at all. I hate having this feeling that you know these secrets, but are just too haughty to tell us. If you were just more verbose in your posts, filling us in with greater detail, your work could serve more as a catalyst for cooperative discoveries rather than so many discouragements.

Excuse the critical tone. I know you like to maintain only the highest caliber of technical excellence in every statement you make. But I wish you could unbend a little, and try to help us out here. What about an informal review of reducing agents used in making tryptamines? We want to find a way through this maze: a way we can make tryptamines, without owning stock in a chemical distributor.




turning science fact into <<science fiction>>
 
 
 
 
    Lilienthal
(Moderator)
09-01-01 21:05
No 209318
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

The problem is that there are many questions and speculations but very few people to answer them. All I can do is to share my thoughts and my literature work and sometimes may practical experiences (even if these may sound a bit vague from time to time...).

OK, a few remarks (most of it already posted):

Alanate reduction of N-formyl-tryptamines to secondary tryptamines is a mess with yields below 30%, several statements from my literature agree with that.

But alkyloxycarbonyl-tryptamine reductions with alanate should work fine.

Reductive aminations of tryptamines are always sensitive to beta-carboline formation (Pictet-Spengler reaction). I think there should be reaction conditions to minimize this sidereaction, KrZ's yields are encouraging. But this still has to be worked out.

NaBH4 will not reduce indolyl-glyoxylamides in one step. Any NaBH4 'enhancers' like AcOH, Ni salts, copper salts, or zink salts are bearing the risk of reducing the indole to a 2,3-dihydroindole (indoline).

When I tried it a while ago with the above reagents the Ehrlich's color reaction of the product spots after TLC was bright yellow, typical for indolines (indoles usually have violet to blue colors).

The most simple and established ways to substituted tryptamines are the tryptophol / indolyl-ethyl-bromide route and the hydrazine / amino-butyraldehyde condensation. Search my literature and the Hive for extremely simple precursor syntheses and remarks.

BTW, I think that 'someone without chem library access' should not try even these simple syntheses, to say nothing of experimental or more complex reaction sequences. You need to have a good background knowledge (about chemistry, the reagents, the mechanisms, similar reactions, alternative reactions...). A simple recipe cannot provide you with that. You have to do your own (library) work.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-05-01 16:51
No 210367
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

This is a rough-draft of a detailed proceedure for going from IAA to DMT via tryptophol that I put together from the bits and pieces of information that I've read. Tell me if you think it will work and the possible problems.
1)Dissolve IAA (free acid crystals) in THF and add an equal-molar amount of LAH in THF dropwise with stiring. Let react at RT for a couple days. When complete, add an access of sodium sulfate decahydrate and filter. Evaporate solution on an evaporation dish with a fan.
2)Dissolve residue in THF and add 1/3 as many moles as residue (3-(2-hydroxyethyl)-indole) of PBr3. Let react at RT for a couple days. When completed, add water and extract with DCM. Add MgSO4, filter and evaporate on a dish with a fan.
4)Add residue to an acess of an aquious dimethylamine solution and let react at RT for a couple of days (if I'm wrong and this rxn must by anahydrous, than use dimethylamine in ether or THF). Extract with DCM, dry with MgSO4 and evaporate to get DMT.
Side steps:
Make PBr3 by adding RP to bromine water and boiling away the mixture to leave dry crystals.
Make dimethylamin solution by mixing equal-molar amounts of dimethylamineHCl with NaOH in water.
Make the methyl ester of IAA, wich should increase yields, by refluxing an acess of MeOH with IAA, than dry solution with MgSO4 and evaporate. Ok, I've probably got a million things wrong with this whole proceedure, but help me out.

please share chemical sources with me via p.m.
 
 
 
 
    Rhodium
(Chief Bee)
09-05-01 17:15
No 210374
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Your outline sounds all right (looks like the one in ../rhodium/chemistry /tryptophol.txt, but my own preferred choice would be to make the IAA ester, and use this procedure: ../rhodium/chemistry /indoleaceticacid.txt
 
 
 
 
    Lilienthal
(Moderator)
09-05-01 19:42
No 210399
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

1) The reaction should be done in under one hour with some heating. LiAlH4 generates a lot of heat while dissolving, be careful! Adding solvent to LiAlH4 in the flask may often be safer.

2) The reaction proceeds fast, one hour should be enough. A slight excess of reagent would be better.

3) You probably need a solvent to dissolve indolyl-ethyl-halogenides and at least a twofold excess amine. Methanol or THF work. Theoretically anhydrous acetonitrile or THF would give the fastest reaction.

PBr3 is a liquid which is extremely sensitive to humidity, it produces HBr gas on contact with (humid) air.

You don't have to make the methyl ester for the LiAlH4 in THF reaction.

It is HIGHLY recommended to use TLC to follow the reactions! It's cheap, simple, and fast. I posted a how-to a while ago. Without TLC a chemist is blind (like this guy: cool).
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-05-01 22:15
No 210442
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Thanks for the replies. Man, I feel like an idiot for refering to PBr3 as a solid and not realizing that it reacts with water. That means it can't be synthesized with home-made bromine (at least using the proceedure I've used to produce Br). 

please share chemical sources with me via p.m.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-06-01 16:15
No 210757
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Would aquious HBr work ok as a substitute for PBr3?

please share chemical sources with me via p.m.
 
 
 
 
    Rhodium
(Chief Bee)
09-06-01 21:40
No 210833
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Not as good at all, as it requires much more vigourous reaction conditions.
 
 
 
 
    terbium
(Hive Addict)
09-07-01 04:16
No 210944
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   


This is a rough-draft of a detailed proceedure for going from IAA to DMT via tryptophol that I put together
...
1)Dissolve IAA (free acid crystals) in THF and add an equal-molar amount of LAH



If you have LAH and THF why go through the tryptophol? If you prepared the N,N-dimethyl-indoleacetamide you should be able to reduce that directly to DMT with LAH in THF. This would obviate the need for PBr3.

I think that you could produce the amide by the action of dimethylamine on an IAA ester.

 
 
 
 
    Rhodium
(Chief Bee)
09-07-01 13:44
No 211058
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Yes, that's exactly what I said and referenced in my post with the links above.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-07-01 16:52
No 211091
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I'm considering doing that. In fact, I'll probably expirement with both ways. Given PBr3, the route via tryptophol seems easier and higher yeilding. I'm planning on generating anahydrous Br by passing Cl through dry NaBr and condensing the bromine in a dryice/acetone bath. Than I'll add an acess of RP and filter the clear PBr3. Man, I beter get alot of DMT at the end! I'm not one to give up easily, though.
 
 
 
 
    Rhodium
(Chief Bee)
09-07-01 16:58
No 211095
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

But, as I said in another thread, the dry ice will also condense the chlorine gas, which has a boiling point of -33C, and the dry ice holds a temperature of -78C.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-07-01 17:05
No 211097
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I understand, thank you for pointing that out to me. I would remove the container from the bath first and let it come to room temp than pour the Br into another container (to get it away from lingering Cl) and place it back into the bath. I'd be waring gogles and a mask, of course.
 
 
 
 
    foxy2
(Distinctive Doe)
09-07-01 19:16
No 211119
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Use Agent Smith's Br2 prep in the OTC MDMA thread in the chemistry forum, it is easier than what you are proposeing.
Post 189907 (Agent_Smith: "OTC MDMA is now easy and cheap!!", Chemistry Discourse)

Do Your Part To Win The War
 
 
 
 
    Rhodium
(Chief Bee)
09-07-01 19:49
No 211128
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

I don't know whit what kind of ease the compound BrCl forms when chlorine and bromine is mixed, perhaps someone out there knows? It could be another possible obstacle.
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-07-01 20:39
No 211141
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Foxy, I am familiar with that method, but the problem is that the bromine produed is cirtainly not anahydrous. That means HBr will be produced when mixed with phosphorus. The proceedure I sugessted seems easy enough. Rhodium, I didn't think about that. I didn't even know there is such a thing as BrCl. I'll look that up. What other compounds could be formed considering the enviorment?
 
 
 
 
    foxy2
(Distinctive Doe)
09-08-01 10:42
No 211314
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Well it shouldn't be that hard to dry.

Anhydrous magnesium sulfate(epsome salts) or sodium sulfate should work.  Just extract the aqueous Br2 with DCM and dry it then distill off the DCM.  Probably need a fractionateing column for a good separation.  Two relatively easy steps should allow synthesis of a sizable amout of bromine without doubts to its actual composition since you fractionally distill it.

Do Your Part To Win The War
 
 
 
 
    Ghost_Of_BT
(Hive Bee)
09-09-01 18:11
No 211604
      Re: Substitution for NaCNBH3 in Krz's DMT synth  Bookmark   

Another way could be to react PCl3 with NaBr. The problem with that is making pure PCl3.