good decarboxylation results in DMF

[Lilienthal]

You can't use or buy p-amino-benzaldehyde because it's not stable.

[hypo]

the decarboxylation procedure sounds very cool, but a friend of mine simply has no luck with trp decarboxylation  

2g trp were refluxed in 30ml DMF with vivid bubling of H2 (from Al suspended in water + NaOH(aq)). the mixture never became clear and bright yellow, but clear and red. after about 45min the reaction was cooled in a water bath and once cool the H2 bubbling removed. the DMF was removed under aspirator vacuum leaving a dark red oil, on the edge of crystalizing (it didn't even after 30min in the freezer). so DCM was added, and first it looked like the oil would dissolve, but suddenly the little pieces floating arround clumped together forming an totally ugly chewing gum like sticky mass. the mess was tried to be partitioned between DCM and water with the result of red tar sticking all over the wall of the separatory funnel. the DCM extracts were washed three times with water giving an orange organic phase, which was dried over MgSO4. out of frustration, they were ignored for one week when the chemist noticed crystals on the bottom of the DCM layer. happily he filtered the brown crystals of, dried them and did an mp -> result: they did not melt even though the chemist went up to 200°C. the chemist is short of kicking his trp out of the window    i will report back when the DCM is evaporated - but am not very confident.

[Sunlight]

Why the hell did you bubble H2 ? H2 is not argon, and you have not to bubble, just if you can, make the rxn in an inert atmosphere, not bubble any gas in it.

[hypo]

well, the idea was that oxygen is bad, so replace it with something different. argon was not available, so H2 was the next candidate.

as for bubbling it, this was probably stupid. but it shouldnt have interfered, should it?

did you get the clear yellow solution? were you using an inert gas? would CO2 be suitable as inert gas?

[foxy2]

Hypo
Is it possible you had a tryptamine salt?

I wonder if the addition of a tiny amount of acid or base would dramatically affect the decarboxylation?  CO2 is slightly acidic, could a tiny amount of base help push the decarboxylation?  Just an idea.

Another idea is to add a little copper(II) salt to catalyze the reaction.  You could choose the salt based on its solubility in DMF.
Foxy
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[cilliersb]

Just use the Decarboxylation in Tatralin with Ketone Catalyst.

Swim did this (with Acetone as catalyst).

10g Tryptophan, 45ml Tetralin (this is one of the small tweaks) and 0.5ml Acetone.

Refluxed at 162C - 168C for 6 1/2 Hours with very good stirring. Added .5ml more Acetone at the 3 hour mark. When the reaction contents (Dark yellow/Orange/reddish liquid) was still hot (125C - 140C) I poured it in to a beaker and sealed the beaker with cling wrap. This was put in the fridge at 5-8C over night and in the morning the beaker had a yellow crystalline solid in the bottom of the beaker. The tetralin (now almost colorless with a slight hint of yellow) was decanted from the crystals.

I got 8.5g of pure Tryptamine after A/B with MP of 113C.

This is by far the simplest way to obtain your TRP.  

Swim is now Considering the following:
 A suspension of 1.0 g tryptamine in 50 mL ethyl formate was held at reflux for 15 h during which time the mixture became homogeneous. The volatiles were removed under vacuum, yielding an oily residue of the formamide. This may be purified by distillation but this unpurified product can serve satisfactorily in the following reaction. This residue was dissolved in 50 mL anhydrous THF and added, dropwise, to a solution of 1.0 M LAH in THF (40 mL, 40 mmole) which had been diluted with another 50 mL THF. After the addition was complete the reaction mixture was heated under reflux for 15 hours. Reflux was continued as a solution of 40 mL 1.0 M freshly distilled ethyl formate in THF was added dropwise over the course of 2 h. Heating was discontinued and the reaction mixture was quenched by the addition of excess solid sodium sulfate decahydrate at room temperature. The reaction mixture was filtered and the filtrate was concentrated under vacuum to yield 1.15 g pure N,N-dimethyltryptamine as an oil which solidified upon storage in the freezer. The material can be recrystallized from hexane to give white crystals with a mp 67 °C.

Rhodium, any thoughts on this procedure..... Does it even work?

[foxy2]

cilliersb
Tryptophan to tryptamine.
That post is either total bullshit or your tryptamine is very very very dirty.  Either way those decarboxylation results are no good as is.

You are saying you got a 108% yeild.
Thats impossible  

[Lilienthal]

Reduction of formyltryptamine with LiAlH₄ has been reported to give shitty yields. But maybe you have luck and get comparable yields to your decarboxylation reaction (108%).

[Lilienthal]

Oops, Foxy was a bit faster...    

The reported melting point is 114 - 119°C, so the tryptamine can't be very dirty (or a hydrochloride).

Anyway, the literature is full of statements that lithium aluminum hydride reduction of formyltryptamines or monomethyl-indolyl-glyoxylamides gives bad yields.

[cilliersb]

It appears that you're all right about my decarbox...

Swim was a little too when weighing goods. Forgot to Tare the @#$ scale.

I publically apologise for the misinformation. Upon weighing the TRP again I got only 5.7g

Why does The writeup in Phikal report 90%+ yeilds for this RXN if it is low yeilding, did the chemist make the same mistake I did or was he just being full of shit?

What literature are you referring to Lili?

[foxy2]

cill
Perhaps you should check lili's webpage, its chock full of references.
5.7g is not that bad of a yeild, its 73%, considering the small scale your working at there will probably bee considerable mechanical losses in the work-up/purification.  If I was you I would bee extremely happy considering the lack of success some have had. I'll bet that at the 100g scale the yeilds could climb considerably.
Foxy
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[cilliersb]

Thanks for the tips lili

It would seem that this procedure does indeed produce a very pure product.

Upon extracting the yellow crystals / red residue with Aq. HCL there was very little insoluble material left and washing this with Cloroform hardly introduced any impurities to the cloroform.

I'd say the Tetralin Decarb is a winner!! Swim will try it with one of the other ketones mentioned to see if that 2-pentanone 86.2% yield is reproducable like the Acetone one.

It is important for the beez to note that when using acetone it is essential to add more later in the reaction as quite a bit of it decomposes after some time at 165C. You'll see little pufs of smoke as the acetone hits the reaction during reflux.

Is KRZ's method with NaCNBH3 better than the LAH route?

[Sunlight]

May be smoke is the water released in the imine formation...

[cilliersb]

Sunlight, you may have a point there.

Judging by the smell and also the fact that it looks similar to Safrole decomposing when distilled without Vac, I say it's decomposing acetone. The pufs of smoke also don't get condensed by the condenser, they just waft slowly out of the flask. This is smoke, not H2O vapour(steam).

Prior runs where acetone was not replaced during the reaction resulted in a reaction time that was 10.5 hours instead of 6.5 hours (at 10g Levels). There was also quite a bit more of the impurities and a less pure post reaction product. This made the A/B difficult.

Lili. Did you ever try the NaBH4/Paraformaldehyde/ZnCl2 dimethylation of Tryptamine or any prim. amine for that matter. If so, what were the yeilds? You posted this procedure at some stage and it ended up @ Rhodium.

Here it is, so we're all on the same page:

These one-pot reactions utilize only cheap and (more or less) non-toxic chemicals (no carcinogenic and expensive methyl iodide!). Because of the aprotic, non acidic
reaction and work-up conditions no cyclization to beta-carbolines should occur. The yields after purification are good to excellent (phenylethylamine: 72%, diisopropylamine: 92%, holafébrine: 85%).

Synth. Comm. 25, 2061 1995. Sukanta Bhattacharyya

A mixture of prim. amine (5 mmol) or sec. amine (10 mmol), ZnCl2 (20 mmol) and paraformaldehyde (20 mmol) in 25 ml CH2Cl2 was stirred at RT for 1h under dry atmosphere. NaBH4 20 mmol was then added and the resulting mixture was stirred for 9 h (sec. amines) or 12h (prim. amines). The reaction mixture was then quenched by addition of aqueous ammonia (40 ml, 2 N), stirred for 10 min. and the organic layer was separated. The aqueous part was extracted with CH2Cl2 (1x25 ml) and the combined organic extracts were concentrated in vacuo after drying over anhydrous Na2CO3. Prim. amines were purified by distillation, crystallization or flash chromatography. The sec. amines afforded the pure tert amines without any chromatographic separation.

Hoping this will work as NaCNBH3 is 8X more expensive than NaBH4 in swim's country.

[Sunlight]

If it doesn't condense, it's not water.

[Lilienthal]

I currently believe that it is absolutely impossible to get reasonable yields (everything above 30%) with any procedure involving tryptamines and formaldehyde because of beta-carboline formation! This was the main product even in triethylamine as a solvent (in a reaction with triethylammonium formate, Pd/C, and formaline).

There were serious doubts about the yields for the NaCNBH3 route posted to the Hive...

Your smoke is probably acetone vapor - just compare the boiling points