Author Topic: Copper Chelate Decarboxylation  (Read 162 times)

JustDreaming

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Copper Chelate Decarboxylation
« on: June 19, 2011, 12:47:49 AM »
Well considering no one else has reported success/failure retrying this method figured I'd give it a go.

Cu(C2H3O2)2 was prepared by double replacement reaction with Ca(C2H3O2)2 and Cu(SO4). 6.1g of tryptophan was dissolved in 600mL of warm water, to this a slight excess of the Cu(C2H3O2)2 was added. Immediately the solution turned purple and a precipitate rained down. After vacuum filtration and washing the compound was set aside.

75mL of DMSO was placed into a 250mL RBF. The chelate complex was there added. A liebig condenser was fitted onto the RBF and the solution was kept slightly under boiling temperature(with a little boiling in-between) for 12 minutes. The solution was allowed to cool and was filtered from elemental copper and some of the undissolved/unreacted complex.

The solution was diluted to 250mL in volume with D. H2O. An appropriate amount of NaOH solution was added to make the mixture basic. 35mL of toluene was stirred into the mixture 3 times and each time removed(not using a sep. funnel as there was a large amount of solid in the aq. layer *this is possibly a mistake, meaning the reaction may have been haulted early which is confusing because it was left hot and no more evolution of CO2 was noted for 2 minutes*).

The toluene had taken on an orange hue and was transferred to the sep. funnel where it was rinsed 3x with dilute HCl water. The toluene's color changed from orange to blue/yellow. A strange blue/black precipitate loomed between the organic and aq. layer, though the water was taken away with no visible contamination(slightly mint green tinge to the water). The pulls were basified with NaOH and again taken into Toluene which took on an orange hue.

Any suggestions on how to isolate the tryptamine specifically? I'm not afraid to run a column, just not sure what eluent to choose. Kind of wondering how much has possibly even been recovered. This route does not seem very appropriate compared to others around, it is being done simply out of inquiry and repeatability.
« Last Edit: June 19, 2011, 12:54:34 AM by JustDreaming »
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JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #1 on: June 19, 2011, 01:05:50 AM »
Ahh well shit balls, on a search to find tryptamine's solubility in toluene I found a snippit of text that says it is negligably soluble. Is this true? If so I have screwed the pooch.
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Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #2 on: June 19, 2011, 02:38:59 AM »
First, you need to post the original procedure.

hxxp://www.erowid.org/archive/rhodium/chemistry/tryptamine.kametani-2.html

Quote
The solution was allowed to cool and was filtered from elemental copper and some of the undissolved/unreacted complex.

Is tryptamine soluble in DMSO? I don't think so. So, you probably tossed out the goods in this step. Tryptamine is soluble in DMSO. Unfortunately, tryptamine base isn't soluble in toluene. Tryptamine is soluble in ethyl acetate and DCM (but apparently you have to use a whole lot of DCM and keep the extracts cool, otherwise the tryptamine will react with the DCM), as well as ethanol and acetone.

You will also need to break any kind of coordination complex formed by Cu2+ and the amine. I assume adding NaOH soln will do this, but I'm not sure.

« Last Edit: June 23, 2011, 10:49:09 PM by Enkidu »

JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #3 on: June 19, 2011, 04:26:51 AM »
phew good thing I kept all the filter papers from the day. Thanks for the advice I was having a hard-time finding solubilty data and assumed the goods were in the DMSO. Good thing I have little bottle of EtOAc handy. Thanks again. I'll repost with hopefully results tomorrow.
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Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #4 on: June 19, 2011, 04:37:46 AM »
Instead of worrying with organic solvents, try the following procedure with maybe a third of your filtrate.

Dry and crush filtrate, unless it is waxy, in which case divide it as finely as possible. Add water [to the filtrate] and then NaOH solution as indicated in the workup. The idea here is to get the unreacted acid in soln as the sodium salt. Also, I think this step is supposed to break any amine/Cu2+ complexes. Filter any remaining solids. Acidify slowly until most of the remaining precipitate is in soln. Now you have tryptamine.HCl in solution. Here you might want to extract with a nonpolar to get rid of some of the other decomposition products. Base, and filter your tryptamine.
« Last Edit: June 23, 2011, 10:51:08 PM by Enkidu »

JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #5 on: June 19, 2011, 04:50:29 PM »
Alright.

HCl water was added to the precipitate which was filtered away from the decarboxylation reaction mixture and stirred. 20 mL of toluene was placed on top, where it took on an orange tone. This was discarded and the aq. layer kept.

Enough NaOH was added until a precipitate was visible in the solution. 3x 25mL EtOAc extractions were performed. The Ethyl Acetate took on a dark purple hue and on the third pull had all of the solids migrate into it's layer. The solvent pulls were combined and filtered through a cotton ball leaving behind a purple solid.

The Ethyl acetate now dark brown/black was washed with 35mL of dilute HCl water several times. The H+ water took on a yellow/light green hue.


*edit* 5mL was basified with NaOH and a green precipitate was visible as well as a faint sparkling white one. To this 6mL of acetone was added in hopes of the product crashing out.
« Last Edit: June 19, 2011, 08:35:50 PM by JustDreaming »
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Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #6 on: June 19, 2011, 11:01:04 PM »
After you added the NaOH the first time, you should have tested the precipitate's MP.

At the end you add base and then acetone. Why? Tryptamine is soluble in acetone...

JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #7 on: June 20, 2011, 12:46:03 AM »
Yea I found this out pretty quickly... I'm finding all mixed up information about solubility its rather aggravating. For example in this procedure it says to extract with chloroform, yet on several websites it says it is insoluble in chloroform.

When I added base the first time there was what I assume to be copper hydroxide floating around, no point in M.P. testing that. That was done just as a test, I was told similar aryl amines have crashed out in similar ratios of water to acetone, so I figured if there was a chance I'd have to at least try it. Still have plenty of solution to work with, not going for a total yield or anything at this point  :'(. Trying to salvage anything usable.

Figure tomorrow I'll work up some chloroform, and hope I can reasonably make enough to dissolve the solid(hopefully 10mL will dissolve a half gram or so) after distilling out the ethyl acetate fraction remaining in the current solution. Do you know where I can find reliable information about tryptamine solubility, this is starting to get annoying...
« Last Edit: June 20, 2011, 12:49:38 AM by JustDreaming »
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Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #8 on: June 20, 2011, 02:09:37 AM »
If you add your tryptamine/acetone soln to a significantly larger volume of water, the tryptamine will crash out..

Solubility data from merck.


JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #9 on: June 20, 2011, 06:03:57 PM »
Alright so on the final basification a dark green frail precipitate formed. It does smell somewhat of new shoes but that could mean anything, and is probably 0.1g in mass(hasn't dried yet nor fully precipitated). Unless tryptamine freebase is an oil hanging out in the solution of course.

I realized a lot of mistakes I made.

First of all
Quote
The liquid produced after filtering a suspension of a solid in a liquid is called filtrate, while the solid remaining in the filter is called retentate
So I wasn't supposed to use the precipitate, I was supposed to use the reaction liquid as I thought originally.

Secondly, I shouldn't have refluxed I should have open boiled, to allow CO2 that was generated to boil off and allow the equilibrium to sway towards products.

Thirdly I shouldn't have used as much of the copper complex in the initial boil. Clearly all of it hadn't reacted, because on  basification of the reaction mixture a lot of what appeared to be Cu(OH)2 or another unhappy copper solid had formed.

See I would assume the chloroform is used then as a wash to remove impurities from the reaction. However, it appears they are extracting the goods with it. Which does not coincide with the given solubility data(Merck). Unless they are distilling the DMSO out of the final reaction mixture, in-which case the water it was diluted with would come over first, leaving tryptamine(+ NaOH + byproducts) and tryptamine to be heated way to hot. Unless they are implying under vacuum. Ripping DMSO under vacuum seems like a stinky chore I'd rather not do.
« Last Edit: June 20, 2011, 06:07:31 PM by JustDreaming »
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Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #10 on: June 21, 2011, 12:16:51 AM »
First of all, "The liquid produced after filtering a suspension of a solid in a liquid is called filtrate, while the solid remaining in the filter is called retentate."

Damn! That's right. I've always called the filtered precipitate the filtrate and the liquid the mother liquor. :-[


Quote
Secondly, I shouldn't have refluxed I should have open boiled, to allow CO2 that was generated to boil off and allow the equilibrium to sway towards products.

Since this is an irreversible rxn, you don't have to worry about that. Even if you had a balloon on top, the worst that could happen is that the tryptamine carbonate would be formed if water is available (i.e., the DMSO wasn't dry).

Quote
See I would assume the chloroform is used then as a wash to remove impurities from the reaction. However, it appears they are extracting the goods with it. Which does not coincide with the given solubility data(Merck). Unless they are distilling the DMSO out of the final reaction mixture, in-which case the water it was diluted with would come over first, leaving tryptamine(+ NaOH + byproducts) and tryptamine to be heated way to hot. Unless they are implying under vacuum. Ripping DMSO under vacuum seems like a stinky chore I'd rather not do.

Yes, their work up is very confusing. They say, "the filtrate was added to a suitable amount of water." DMSO and water are miscible, so if the DMSO soln contains the tryptamine, the addition of water would "crash out" the tryptamine if enough were added.

JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #11 on: June 21, 2011, 12:46:35 AM »
Hey no worries buddy. This is science, exploring things, trying, failing, retrying, working together, etc.

Well there was a black swampy goop that crashed out of the reaction(after basing). So this must have been where the goods as well as a bunch of undesirable compounds loomed. The DMSO is not dry but it's reasonably close compared to refluxing with CaH2 and distilling under vacuum hehehe.

anyhow I found an interesting clip yet another referance going against Merck's solubility information:
Quote
By making the mixture definitely alkaline, O.5N in respect to sodium hydroxide and extracting with chloroform, tryptophane was found quantitatively in the aqueous layer while tryptamine, indole, and skatol went into the chloroform.
from - "Abstracts of papers - American Chemical Society: Volume 112 American Chemical Society. Meeting, American Chemical Society - 1947"

So here we go, it is soluble in chloroform, now if only I could find out how soluble it was. Merck seems to be wrong on quite a lot of things, I wonder if they fudge numbers just to fill pages or something. If the chloroform fails I will try adding a metric ass-load of water(real scientific vernacular :P).

Good news on the reflux being okay, because that will help control the stink factor. Well I will have another go at this in a few days or so, now that everything is making a bit more sense hehehehe.
« Last Edit: June 21, 2011, 12:50:06 AM by JustDreaming »
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antibody2

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Re: Copper Chelate Decarboxylation
« Reply #12 on: June 23, 2011, 08:34:00 PM »
Yes the merck is odd! They say recrystallize from pet ether? You would need an awful lot of boiling pet ether to dissolve a very minute amount of tryptamine, although the resulting crystals are snow white. I triied, the volumes involved get ridiculous. Instead I use pet ether to crash tryptamine out of solution.

I don't usually extract the tryptamine. It usually drops out as a solid upon addition of aq. NaOH and refrigeration. I recystallize from there. When cleaning up tryptamine, I recrystallize by dissolving it in the smallest amount of EtAcO that will dissolve it and then slowly crash it out with pet ether. The first batch of xtals (80%) are usually pretty clean, the subsequent batchs after refrigeration (20%) need to be recrystallized again.


Enkidu

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Re: Copper Chelate Decarboxylation
« Reply #13 on: June 23, 2011, 10:46:55 PM »
I don't usually extract the tryptamine. It usually drops out as a solid upon addition of aq. NaOH and refrigeration.

Are you referencing this procedure specifically, i.e., the tryptamine is dissolved in DMSO, and then when the aq. NaOH is added, it crashes out? How much water should be added?

antibody2

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Re: Copper Chelate Decarboxylation
« Reply #14 on: June 23, 2011, 11:55:33 PM »
No sorry, didn't mean to mislead. I use acetophenone to decarboxylate, then mix with dilute HOAc, save the aqueous phase, then basify.
« Last Edit: June 24, 2011, 12:09:31 AM by antibody2 »

JustDreaming

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Re: Copper Chelate Decarboxylation
« Reply #15 on: June 25, 2011, 07:45:06 AM »
Excellent suggestions, sorry for the hang time. Not all is lost on this one, I have a flask with that fresh smell, which pleasantly over-rides that of the remnants of decanted oxidized DMSO. Which saves some time because if this can be salvaged then there's no need to restart the experiment :).

Ought to get my hands on some acetophenone though, this is quite silly.
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