Student (Stranger)
03-18-02 15:58
No 284325
      Spearmint Oil Catalyzed Tryptophan Decarboxylation  Bookmark   


My recent post Post 276680 (Student: "Re: Decarboxylating Tryptophan", Tryptamine Chemistry) outlines a way to convert tryptophan to tryptamine using spearmint oil and xylene or turpentine. The procedure was optimized for simplicity and ease, and the equipment and ingredients were optimized for availability. Two areas needing further study were the suitability of turpentine as a solvent and a procedure for scaling the reaction up from the original small (500 mg) scale.

The advantage of turpentine is that the reaction takes hours instead of days. The downside is that there is significant non-volatile residue, at least in the can of turpentine studied.

A scaled up reaction using xylene began as follows: 50 mL of xylene (straight from the can), 4.78 g of L-tryptophan and 10 drops (about 0.2 mL) of spearmint oil were placed in a 250 mL Erlenmeyer flask and a cork with a four inch piece of glass tubing in it was placed in the top. No boiling stone was added since the decarboxylation was expected to provide bubbles to smooth the boiling, and magnetic stirring was not provided to simplify the equipment needed. The mixture was boiled at a sufficient rate to bring the refluxing vapor to the 150 mL mark but there was significant bumping because the solid settled and allowed overheating. After about 12 hours the cork had popped out of the flask, 10 mL of solvent had evaporated, and the mixture had begun to darken due to air exposure.

To rescue the $2 worth of tryptophan, the lost solvent and catalyst (assumed evaporated) were replaced and the cork was replaced with a rubber stopper holding a water cooled reflux condenser and the heat was turned up enough so that there was a fast return of solvent from the condenser. Rather than making the bumping worse, the bumping disappeared entirely because the rapid boiling kept the solid suspended. There was no further darkening and the reaction is still in progress.
 
 
 
 
    Student
(Stranger)
03-22-02 15:32
No 286406
      Conclusion of Initial Scale-Up  Bookmark   

The reaction took about three days to become clear, but it was about the color of coffee and there was a little dark solid deposited on the side above the liquid. The dark color may be due to the air exposure early in the reaction, and the destructive effect of the hot xylene vapor on the black rubber stopper. The stopper was actually elongated by the end of the reaction and the bottom felt spongy. A cork which seals well might work better. Of course, ground glass would be ideal but one goal of this work is to keep the equipment more common.

The heat was turned off. After partial cooling a seed crystal  (from a previous batch) was added to the flask and the setup was left overnight (about as cold as a refrigerator). In the morning the brown liquid was decanted from the brown crystals and the flask was left to drain. Later a stream of air from an aquarium pump was passed through the flask to dry the product. About two days later the crystals were scraped from the flask. They are the color of light brown sugar, and sparkely, and they weigh 2.49 g (66% yield). There is also some solidified oil in the flask which was not scraped out.

Obviously this procedure still needs improvement, but it looks like the way to go for someone without ready access to non-OTC materials. A convenient purification is also needed.
 
 
 
 
    Student
(Stranger)
04-02-02 17:12
No 291464
      Faster Reaction and Improved Purification  Bookmark   

Initial research for the purification was done on the solidified oil from the last batch. Recrystallization from water was attempted but no crystals formed, so 20 mL of 5% sulfuric acid was added and swirled to dissolve as much of the oil as possible. The aqueous solution was then used to extract the xylene mother liquor from the last reaction. The separated aqueous layer was filtered through a plug of cotton and strongly basified with strong sodium hydroxide solution, but an emulsion formed, so it was acidified again with sulfuric acid and then carefully brought to pH 7 with sodium hydroxide and the resulting white emulsion was extracted with 10 mL chloroform. The hazy aqueous layer was again filtered through a plug of cotton, which removed both solid and suspended solvent, and the filtrate was strongly basified with sodium hydroxide, producing an emulsion which changed to a suspension of white solid after a few seconds. After several hours the flask contained copious large, colorless, shiny flakes. These were gravity filtered, filling the funnel about half way. The solid was rinsed with about 25 mL of water to remove sodium hydroxide, but the solid seemed to shrivel away, down to about one quarter of the funnel! The aqueous solubility of tryptamine referenced on ChemFinder.com (34 g/L) had seemed dubious, but given that the chloroform leaves the tryptamine in the neutral water layer, the solubility of tryptamine in neutral water must be considerable. The filter paper was pressed between paper towels to remove all possible water and the air dried solid weighed 0.65 grams. The solid melted at 117-118.5C (Merck 118C) and had one tan spot (Rf ~ 0.1 - 0.2) on silica TLC, eluting with methanol containing ~50 mg of ammonium carbonate.

Another large scale reaction was run using 75 mL of turpentine, 7.14 grams of L-tryptophan, and 15 drops (0.25 grams) of spearmint oil in a 250 mL Erlenmeyer flask with a water cooled reflux condenser attached by a rubber stopper, boiling fast enough so that there was at least a drop/second coming out of the condenser. The mixture became clear in four hours and heating was turned off after another 30 minutes. There was a little yellow solid on the side of the flask above the liquid. After sitting overnight there was a clump of yellow crystals in the corner of the flask and solidified dark oil across the bottom. The flask was refrigerated for the day and the orangish mother liquor was decanted.
To the flask were added 150 mL of 5% distilled vinegar along with 5 mL of chloroform and the flask was briskly swirled until all solid was gone and there was only a little dark brown oil not dissolved in the yellow suspension. The hazy yellow liquid (pH 5-6) was filtered through a plug of cotton and the dark brown organic layer was extracted with another 10 mL of vinegar. To the combined filtrates were added 5 mL of chloroform and enough sodium bicarbonate (10.58 g) in portions so that further addition caused very little foaming. The flask was swirled thoroughly and the hazy yellow aqueous layer was filtered through a fresh plug of cotton. The filtrate was cooled in the freezer for 15 minutes, basified with 12 mL of 25% sodium hydroxide solution, and set back in the freezer for 30 minutes. The solid was dislodged from the sides with a metal scoop and the mixture was filtered through filter paper. The flask and crystals were rinsed with 100 mL of ice cold household ammonia in portions. The filter paper was pressed between paper towels until damp and set aside to dry. The light yellow crystals weigh 3.64 grams (65% yield).
The turpentine mother liquor from the last reaction, still containing spearmint oil and some tryptamine, was used directly to decarboxylate 7.23 grams of L-tryptophan. This time the reaction took seven hours, so apparently some of the catalyst was removed during the first reaction. This time both the turpentine and the solid product were extracted with vinegar as above, and brought through the same process, to give 5.21 grams (92% yield) of light yellow crystals. The combined yield for the last two reactions is 79%.

Note that the use of a water cooled condenser in this process is unnecessary - a foot or two of wide glass tubing would suffice.
 
 
 
 
    urushibara
(Hive Bee)
04-08-02 01:34
No 293879
      A/B?  Bookmark   

Wouldn't an a/b get rid of any turps crud? The tryptamine should crystallise if you stick it in the freezer (along with some water and stuff, then A/B that, after filtering off the non frozen part. Then make slightly more acidic, collect the garbage with an np (naptha, warm), then basify, NP extract and - well freebase is perfectly fine in most reactions to go further from there.

I know naaaathing.
 
 
 
 
    Student
(Stranger)
04-08-02 15:59
No 294206
      Tryptamine Purification  Bookmark   

Yes, the acid/base extraction in this process is removing turpentine and other non-amine impurities. The process was modeled after the tryptamine purification outlined in the Tryptophan and Tryptamine FAQ (../rhodium/chemistry /tryptophan.html. The main improvement I found for the procedure was to rinse with aqueous ammonia to minimize loss of the product, whereas the FAQ leaves the wash solvent unspecified.
It sounded like the change you were suggesting was to replace chloroform with naphtha. This may be a good alternative, but chloroform is a good solvent for the dark impurities and I doubt that naptha would be. It would certainly get rid of turpentine though. Although chloroform is not easily obtained OTC, there is what sounds like an excellent procedure for its preparation from bleach and acetone at ../rhodium/chemistry /chloroform.html.
 
 
 
 
    element109
(Hive Bee)
05-06-02 22:48
No 305525
      Good stirring is necessary !  Bookmark   

SWIM tried Student's procedure with 7.14 gr L-tryptophan and 75 ml turpentine a couple of days ago. He used 20 drops of oil of dill seed (50% carvone) as the ketone catalyst. Without stirring the TRP does not dissolve and lays on the bottom, when the temp reaches 170C it begins to cause 'eruptions' in the flask. It stayed at this temp for 8 hours.

He only got asub gram amount at the end and was left with most of his starting amount of TRP, coloured brown by now. If you try this make sure you have good stirring. Pure carvone would probably be nicer, too.


But there's also some good news: you can exhangethe chloroform in the washings for cheap trichloroethylene with excellent results. On small scale that is, of course.




e109
 
 
 
 
    Student
(Stranger)
05-31-02 05:17
No 316162
      Carvone enantiomers  Bookmark   

Well, stirring sure doesn't hurt if it's available. I was able to get away without it. My theory is that the tiny bubbles produced during decarboxylation served as nuclei the way the bubbles in boiling stones do. As I remember, I got severe bumping unless I heated the flask strongly enough to keep the solid suspended. Sitting on the bottom allows superheating of the liquid trapped between the glass and solid. I know it seems counterintuitive to add more heat when a mixture is already bumping!
My other thought was that the dill oil shouldn't be expected to provide the same catalysis as spearmint oil because dill oil contains d-carvone while spearmint oil contains l-carvone. l-Tryptophan is chiral, so its interaction with either enantiomer will not be identical. In preliminary tests I was able to get complete dissolution using an extract of caraway seeds (containing d-carvone) in xylene, but I didn't isolate much product. I didn't use the current work-up though.
Thank you for trying this new method. I hope you'll give it another chance, with adjustments.