PolytheneSam (Master Searcher)
03-12-02 16:05
No 281536
      Transamination idea     

Can Ni be used to cause transamination of tryptamine with dimethylamine to N,N-dimethyltryptamine?
See Post 43613 (CHEM_GUY: "Text implies Possible isomerization of l-meth", Chemistry Discourse) Post 75995 (PolytheneSam: "Re: Text implies Possible isomerization of l-meth", Chemistry Discourse)

../rhodium/chemistry /tryptophol.html


This is the article from J Org Chem USSR, 5, 2158 (1969) mentioned above

General procedure for the preparation of dialkyltryptamines:

Into a flask fitted with a Dean-Stark recieving trap were placed 0.1 moles of tryptophol [2-(3-indolyl)-ethanol], 0.1 moles of a secondary amine [dimethylamine for DMT], 4ml of skeletal nickel [Raney Ni] suspension in water and 100ml of benzene or xylene [I assume toluene is good too]. The reaction mixture was refluxed, and the condensed water collected for four hours, the hot solution filtered and the catalyst washed repeatedly with benzene or xylene [or toluene] and the mother liquor concentrated under vacuum. The product was either distilled in vacuo or isolated as the hydrochloride by acidifying with an equivalent of hydrogen chloride solution [they are probably referring to a non-aqueous HCl solution here]. The yields were in the 82-98% range.



J. Am. Chem. Soc. 61,3499 1939 gives the mechanism: the alcohol is catalytically dehydrogenated to the aldehyde, which reacts with the amine to an imine, which is subsequently hydrogenated to the amine. Usually this gives moderate yields and needs high temperatures (very uncool for the low-boiling dimethylamine).


04-20-02 14:21
No 299590

I've seen this, and I like it. My problem with this reaction has been with the proceedures for the production of tryptophol. However, with the tremendous Percent yields these guys are reporting, and simplicity of the proceedures, maybe I should look closer. If indoleacetic acid was like 12 bucks a kilo(wishful thinking), and the reduction ran nicely with Na in Ethanol, it would be pretty hard to resist. You are a busy man, Sam......Regards zed

Of course, we could produce our tryptophol from our theoretical Indoleacetaldehyde, that we haven't figured out how to aminate yet. Of course, that would be bass ackwards. And, the idea of reducing an Aldehyde to an Alcohol, so it can be oxidized, aminated, and reduced in another reaction.... Gives me horrors.....It just seems so, dirty, so wrong!

There does have to a reduction someplace, it just seems like too long a reaction sequence. Yields usually suffer.

So, do you think it could be done with the old Meerwein- Ponndorf-Verley? Probably not, but it is a charming Idea: Another trans-hydrogenation.
(Hive Bee)
05-17-02 15:14
No 310093
      Stealing from the Past!     

Sam, Tryptophol might be a little easier to come by than I imagined.

I found a two year old entry in the Archives wherein it is produced fairly reasonably via Ethylene Glycol (Antifreeze) and Indole.

The posters did not seem to make a connection between the tryptophol synthesis, and the clever transamination you are proposing.

Here it is:

Mastermind (Hive Bee) 07-29-00 21:07 No 34654 Re: DMAE of any use for DMT synth ?? (Rated as: excellent) Reply

Examples 1 and 2 copied from US patent 3,197,479 show a similar type of reaction.

EXAMPLE 1 3-(2-hydroxyethyl)indole

A 3-liter, stainless steel, rocker autoclave was charged with 117 grams of indole, 100 ml. of ethylene glycol, and 7.0 grams of potassium hydroxide. The autoclave was sealed and heated at 250 degrees C. for 19 hours while agitating the reaction mixture by rocking. The autoclave was then cooled, opened, and the contents were filtered to remove solids. The filtrate was evaporated under vacuum to a volume of about 400 ml. and then admixed with 1 liter of water. The aqueous mixture was extracted with ether. On vacuum distillation of the ether extract there were recovered 21 grams of 3-(2-hydroxyethyl)indole as a fraction boiling at 150-186 degrees C. at 1.0 mm Hg. A sample of the 3-(2-hydroxyethyl)indole, after recrystallization from toluene melted at 56-57 degrees C. [The melting point of 3-(2-hydroxyethyl)indole was reported by Oddo and Camberi, Gazz. Chem. Ital., 69, 19 (1939) to be 57-58 degrees C.]

EXAMPLE 2 3-(2-hydroxylethyl)indole

Employing apparatus and procedures similar to those described in example 1, an autoclave was charged with 234 grams of indole, 1146 grams of ethylene glycol, 126.2 grams of hydrated barium hydroxide (Ba(OH)2.8H2O) and 128 milliliters of water. The autoclave was flushed with hydrogen, sealed and heated at 250 degrees C. for 19.5 hours. There were produced 225 grams of 3-(2-hydroxyethyl)indole which were recovered as a fraction boiling at 160 to 174 degrees C. at 1.0 mm Hg.


Notice that example 2 includes the addition of water just as the Organic Synthesis article on indole-3-acetic acid. There's 18 examples in the patent using diols such as propylene glycol, butane diol, hexane diol, etc. Some include flushing with hydrogen. It says in the specification (column 4 lines 30-35) the following:

In addition, it has been found desirable, especially when a 3-(hydroxycarbyl)indole is the desired product, to conduct the reaction under a hydrogen atmosphere. The hydrogen pressure can vary from atmospheric pressure to 500 psig or more, with pressures of from 50 psig to 20 psig preferred. ----------------------------------------------------------

All things considered, this is probably do-able.........zed

225 g of Tryptophol seems like a useful amount.....yes?
(Master Searcher)
05-17-02 17:14
No 310151
      Trp decarboxylation     

You can make tryptamine by decarboxylating tryptophan, too.

The hardest thing to explain is the obvious
(Hive Bee)
05-18-02 04:11
No 310333
      True, but................     

True, but most of the methods used to transform tryptamine to DMT, have quite a few drawbacks.

The route Tryptophol+Dimethylamine.........to DMT appears to have a potential, the Tryptamine alkylations may not.

True, some heat and pressure are required to produce the tryptophol. But perhaps not an inordinate amount. The B.P. of Ethylene Glycol is ~200C, the reaction calls for ~250C. This is do-able. Especially, if one uses a bundle of smaller vessels, or "pipes" instead of a 3 liter one.

Alternately, commercial Tryptophol is available for ~50.00/Oz..

And, of course, testing the amination, via commercial product, prior to building a pressure apparatus, would be prudent.


Sometimes things that appear to be difficult, are easy!

Sometimes things that appear to be easy, are difficult!

(Master Searcher)
05-18-02 11:02
No 310411

In Patent US5679862 they discuss amination of alcohols with amines.  Note especially column 5.

The hardest thing to explain is the obvious
(Hive Bee)
05-20-02 05:25
No 311276
      DMT via Tryptophol.     

Yes, pretty much as I thought. All phases are reversable, and the reaction appears to be driven... by distilling off, and removing H2O as it is formed.

The problem being.... how to keep Dimethylamine in solution. Diethylamine has a higher B.P., so it would probably work fairly well.

The soluability of Dimethylamine in Benzene at B.P., can't be great. But, the problem might be overcome by running the reaction as a straight distillation. Just drip concentrated dimethylamine in benzene into the boiling reaction mixture while distilling. Trap excess dimethylamine gas as required. Repeat until no more water comes over in the distillate.

Alternately, it is conceivable that the reaction could be conducted under very different conditions. As the reaction appears to be driven by the removal of water, molecular sieves, chemical reaction, or some other means of water removal might work. Since distillation would not be required, lower temperatures and somewhat higher pressures might also be employed.

Thanks for the Patent reference, I'll examine it more carefully.
(Hive Bee)
05-20-02 18:02
No 311589
      Synthesis of tryptophol     

I've been studying the synthesis of tryptophol for weeks now.  I've never run a rxn, beyond extractions, but I've put a lot of energy into studying this.  I hope to perform it in the near future (although I have yet to accuire anything beyong knowledge.) 

Tryptophol can be synthesized via an indole grignard.  Indole reacts with EtMgBr to form indole-n-MgBr, retaining the 2-3 double bond, and keeping the benzenoid ring intact.  This facillitates substitution in the 3 postion, rather than the 2. 

Indole n-mg br then reacts with ethylene oxide to form a  product (indole 3 et o mg br) that hydolysis under acidic contitions to tryptophol. 

It should all occur at room temp.  Stirring should initiate the rxn, and air is excluded by the column of ether rising up from the reflux, and, of course, the rxn should be set up for a reflux, with a water cooled condenser.

No barbed wire can cage a bee.
(Hive Bee)
05-21-02 11:42
No 312000
      Tryptophol Grignard     

A Grignard reaction was my first reaction. I had a pretty experienced chemist with me. It was demanding.

I can't suggest it for an unaccompanied first time chemist. Personally, I reserve such stuff for a well equipt Lab, with a good fume hood.

The Major concerns with this reaction, generally, are that diethylether the common Grignard solvent, both stinks and is wildly flammable, and that ethylene oxide shares the aforementioned qualities, additionally boiling at 10 Deg. C.. Even Ethyl Bromide can be a problem for the unwary.

The problems I see, are not in the reaction itself, but in safely handling the materials. Having run Grignards in non-ideal situations, I can tell you, even if all goes well, it is quite an experience. Arrrrggg Pheeewww.

Aside from personal toxicity, the concern is FLASHBACK. Meandering vapors, may be ignited by a distant source (pilot light, light switch, doorbell, cigarrette) and FLASHBACK to the reaction.......causing an explosion/fire. This is very bad, both legally and medically.

An experienced Bee, with preparation and good equiptment, in a well designed workspace, can handle such a reaction. It is a little complicated and hazardous for an unaccompanied first project.

If you have a Bee friend, or you can take a class, it will help you. As always, I recommend associating with that place....where they loan you millions of dollars worth of equiptment, pay for the reagents, and provide you quality personal instruction..........College.

Warmest Regards........................................zed

Of course, you may know all of this stuff already. If so, my apologies. Good luck in your endeavors.
(Hive Bee)
05-23-02 11:19
No 313225
      Thanks, zed     

I'm in college right now, althought I took the summer off from classes :). 

Your concerns are valid.  But I do intend to do it right.  Although i haven't had a chance to take organic yet, (it is offered in a sequence, and I finished Gen. Chem 2 in the wrong semester to continue immediately.)

I have spent a long time gathering information, though, and I just don't mean an understanding of the reactions.  I know a dozen places to get the reagents (of that purity), as well as the glass-ware, I also have a friend that has a workshop that specializes in manufacturing custom lab glass.  (Hell, I've been told twice this week that I could buy mason jars of ergot . . .)

Really, I have to reccomend not only college, but outdoor folk music lots, as a place  to find reagents :)  I saw some kids eating ground sassafras root, b/c they such things are flooded . . . they knew it was involved with drugs, but had no idea what to do with it.

Anyhoo, thaks zed, esp. for the comments about flashback.  I was planning on getting (maybe building) a fumehood, but I think an inert atmosphere might make my momma sleep a little better.  I was going to have a terrarrium built to test some theories about mushrooms growth;  a ladyfriend of mine's dad works in glass (sheeting).

What does the room think?  I'll be going out of state to do this (no idea where yet, mountains are nice, so are deserts), and I really intend to do this right, even if I do something else at first.

No barbed wire can cage a bee.
(Hive Bee)
05-23-02 22:38
No 313466
      Ethylene Oxide??     

   Happens to be the primary ingredient in the blu-52 fuel air explosive system, ( unless they gotten around to replacing it with the hmx/al slurry yet)...  I believe one of it's cute properties is that it will detonate at any mixture ratio from 7% on up... (might be off a few but not by much)..


Infinite Radiant Light - THKRA
(Master Searcher)
01-14-03 11:25
No 398166
      Here's another patent     

Patent US3366687

The hardest thing to explain is the obvious
(Hive Bee)
02-25-03 20:50
No 411792

If high temps are required to make indole and ethylene glycol into tryptophol, then maybe a distillation rig with the cooking flask inside the microwave would work?

I know naaaathing.
(Hive Bee)
07-16-03 17:17
No 447877
      what about using the HCl of the dialkylamine     

In the tryptophol + dimethylamine --Ni--> dmt reaction, what I am gathering is that if nickel catalyst is used that the water has to be distilled off, and the whole thing run hot. This is obviously a problem with dimethylamine being low boiling as it is, and so forth.

I have had two thoughts - what about doing the reaction under mild pressure, say 2atm or so. I know that would make the distillation rig a bit tricky since it's gotta remain sealed to hold in the pressure, and also that will raise the boiling point of the water too - which is desirable I would think?. the other thought - what if the dimethylamine was the HCl of dimethylamine?

we can't stop here, this is bat country
12-06-03 04:07
No 474996

personally i think its much easier to toss a handful of tryptophan into your brew to get tryptophol, not sure how you'd clean it out of all the other byproducts but i've heard its been done successfully and it's easy. can anyone say if DiMeAm.Hcl could be used in that reaction as you said U? Would that form dmt.hcl straight up from the rxn? i'm really keen on this method.
12-06-03 13:53
No 475073
      Theoretically this reaction would work: ...     

Theoretically this reaction would work:

tryptamine + HN(CH3)2 <--Ni--> DMT + NH3

Excess HN(CH3)2 would push the reaction to the right (LeChatlier's principle).  The above equation is an example of transamination.

If you look carefully at equation A.* (make R3 = H) here:
Post 75995 (PolytheneSam: "Re: Text implies Possible isomerization of l-meth", Chemistry Discourse)
and column 5 here:
Patent US5679862
you should see why.

Remember that this works even though dimethylamine is a secondary amine:

tryptophol + HN(CH3)2 <--Ni--> DMT + H20

*Equation A is at the bottom of column 3 here:
Patent US2608583
Also see
Patent US2797243
12-06-03 15:10
No 475083
      Possible one pot process?     

Possible one pot process?

tryptamine + H2O <--Ni--> tryptophol + NH3

tryptophol + dimethylamine <--Ni--> DMT + H20
(Hive Addict)
12-07-03 06:19
No 475210
      Mmmm dunno..     

tryptamine + H2O <--Ni--> tryptophol + NH3

Dunno about this step, somehow I doubt its efficiency but if you could provide me with a ref, I'd be very happy to be proven wrong. smile

Flight of the Bumble Bee (http://www.geocities.com/eric_vornoff/BumbleBee.mp3)
(Hive Addict)
12-07-03 06:38
No 475212
      Transamination: check this out..     

Found a great article! cool
Afsah, El-Sayed M.; Jackson, Anthony H.
J.Chem.Soc.Perkin Trans.1, 8 (1984), p.1929-1932


Synthesis and Reactions of N-Indol-3-ylmethylalkylamines and Related Compounds

A series of new N-indol-3-ylmethylalkylamines (1) have been synthesized in excellent yields via transamination between gramine and the appropriate primary alkylamine.The use of tryptamine and propane-1,3-diamine in the exchange reaction afforded N-indol-3-ylmethyltryptamine (2), and N,N'-bis(indol-3-ylmethyl)propane-1,3-diamine (3) respectively, where as the use of methylamine gave N,N-bis(indol-3-ylmethyl)methylamine (4).The exchange reaction has been extended by the use of amino acids to give N,N-bis(indol-3-ylmethyl)tryptophan (6) and N,N-bis-(indol-3-ylmethyl)glycine (8).The secondary amines (1), (2) and the previously known bis(indol-3-ylmethyl)amine proved to be valuable intermediates for the synthesis of some new compounds related to gramine as well as to other indole alkaloids.

Someone please dig this one up!

DOI:10.1039/P19840001929 (not available yet!)

With a little bit of luck.. maybe it works with secondary amines too.


2-indol-3-yl-ethylamine hydrochloride


Reagent: sodium carbonate
Other Conditions: 1.) aq. ethanol, 2.) reflux, 24 h
Yield given. Multistep reaction



Yield: 91 percent
Other Conditions: Heating

Flight of the Bumble Bee (http://www.geocities.com/eric_vornoff/BumbleBee.mp3)
(Chief Bee)
12-07-03 10:09
No 475226
      Tryptophol amination with Ni catalyst     

This article is of relevance here: Post 9737 (Rhodium: "Re: maybe 4 steps from tryptophan to DMT/DET/DPT", Tryptamine Chemistry)
12-07-03 19:21
No 475318
      Username: Vitus_Verdegast tryptamine + H2O...     

Username:  Vitus_Verdegast
tryptamine + H2O <--Ni--> tryptophol + NH3
Dunno about this step, somehow I doubt its efficiency but if you could provide me with a ref, I'd be very happy to be proven wrong.

Can anyone find a reference? If not i can see a possible synth.. tryptophan + sugar --yeast--> tryptophol + ethanol.
The problem is the dimethylamine has such a low bp. what about a stainless steel bomb w/ dimethylamine, tryptophol and raney nick. in the oven? would the raney react with the vessle? if not, would the pressure affect the reaction? either way that might be the way to get around the DiMeAm-reflux-low boiling point problem.
(Hive Bee)
12-15-03 20:01
No 477131
      Here's J.Chem.Soc.Perkin Trans.1, 8 (1984),...     

Here's J.Chem.Soc.Perkin Trans.1, 8 (1984), p.1929-1932 in DejaVu format:


N'ętre que de la drogue
(Hive Bee)
12-16-03 17:16
No 477287
      DejaVu files don't seem to download from ...     

DejaVu files don't seem to download from ripway.com.  Here's the article in pdf format.  Its over 900 KB so it might take a couple minutes to download.


N'ętre que de la drogue
(Hive Bee)
12-19-03 08:46
No 477854
      Look at example 5 in column 7 here: us 3450760     

Look at example 5 in column 7 here:
Patent US3450760
Only the worthy will understand its significance.

N'ętre que de la drogue
(Hive Addict)
12-19-03 10:22
No 477864
      Example 5     

Preparation of N,N-dimethylcyclohexylamine

N,N-dimethylcyclohexylamine was prepared using the apparatus of Example 1. Two parts of cyclohexylamine and 3 parts of dimethylamine were fed into the reactor tube along with 20 parts of hydrogen gas at a space velocity of 2000 and reacted at 200 p.s.i.g. at about 150-165°C. The crude product mixture contained 17.5% by weight of N,N-dimethylcyclohexylamine. Also present in the crude product mixture were 9.4% of N-methylcyclohexylamine and 16.3% of dicyclohexylamine. The remainder of the crude mixture was cyclohexylamine. The composition of the crude product mixture was determined by the vapor chromatography method.

Nice find, Sam!
Although the amount of pressure is not critical and it is only advantageous to increase the output of products and to facilitate fractional distillation of difficultly condensible components (page 4), what worries me a bit is the fact that these are vapor phase reactions, something which is not really practically feasible with tryptamine IMO. But this certainly doesn't mean that the idea of transamination is not viable.

The Other War (http://www.markfiore.com/animation/drugs.html)