Author Topic: Botched Foxy  (Read 2906 times)

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JedZed

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Botched Foxy
« on: May 15, 2000, 07:38:00 PM »
Hey, gang-
     I was talking on a cordless phone recently and happened to pick up snippets of the conversation of SWIM.  He said that he deacetylated some melatonin by refluxing in ethylene glycol with NaOH for an hour, cooled, & tried to extract with DCM.  On addition of salty water to break the accursed emulsion he got, he ended up with a pile of beige crystals, which he dried.
     These he then stirred with K2CO3 in acetonitrile (practically identical polarity with DMF) but accidentally added about a tenfold excess of iPrBr.  He let the pot stir for an hour and then attempted to crash out some product by adding water.  Nothing happened- no crystals, no oil, nothing.  Not even a little bit of the bromide in an organic layer.
      Knowing a little bit (a very little bit) about chemistry myself, I'm wondering if this poor guy got a quaternized salt, or could he have broken the methoxy ether in the amide hydrolysis?  Neither of these seems likely, as the first case would have to overcome a good bit of steric hindrance, and in the second case, he would've had a phenolic sodium salt at the end of the hydrolysis, which I think would've remained in solution.
       Any input for this guy, in case I ever pick up one of his conversations again & maybe can try to help him out?


CHEM_GUY

  • Guest
Re: Botched Foxy
« Reply #1 on: May 16, 2000, 06:52:00 PM »
Okay, it doesn't look like you added after the attempted alkylation.  My thought is that Foxy is dissolved in the MeCN and untill you add an acid it is going to stay there.  Try add HCl, the foxy will go to the water and then evaporate to leave the crystals. 

This post is for informational purposes only an is not intended to facilate illegal activity.

CHEM_GUY

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Re: Botched Foxy
« Reply #2 on: May 16, 2000, 06:53:00 PM »
FIRST LINE SHOULD READ:
 "It doesn't look like you added an acid after..."

This post is for informational purposes only an is not intended to facilate illegal activity.

JedZed

  • Guest
Re: Botched Foxy
« Reply #3 on: May 16, 2000, 07:16:00 PM »
No, this wasn't an attempt at a phase separation ('sthat what it's called?).  MeCN seems miscible with, or at least very soluble in water.
   It would seem that a free base 3* amine would not be soluble in <10%MeCN/H2O, but I could be wrong.  I'll try to communicate to that guy that he should just try an extraction to a nonpolar solvent.
For science's sake:  if that fails, then quaternization probably occured, and we'll all know that much more.  At least, the fortysix or however many of us who read this thread.


JedZed

  • Guest
No quat, after all
« Reply #4 on: May 18, 2000, 08:12:00 PM »
Thanks for the advice, Teo; I'd been wondering about the equation for that rxn.  You've posted it before, I think in the Breath of Hoax? thread.
     Anyhow, I saw that guy buying melatonin tabs and ethyl rubbing alcohol at the corner pharmacist's the other night.  He did a DCM extraction & the organic layer yellowed- signifying extraction, he was telling the clerk, but, he went on, then he went and spilled the MeCl2 and his product.  He felt very silly.
      I think it's very interesting that foxy freebase is so soluble in <10% (V/V) acetonitrile/water.  Let's all of us tryptophiles learn from this poor bee's educational screwups.


CHEM_GUY

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Re: No quat, after all
« Reply #5 on: May 18, 2000, 10:15:00 PM »
So it was dissolved in the water MeCN.  What kind of yield did you get...

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JedZed

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Yield, schmield
« Reply #6 on: May 18, 2000, 11:40:00 PM »
None to date.  There's been a pretty heavy BSSD (bureau of soporifics & safe drugs) presence in my neighborhood lately, so I assume that the dude is laying low with the smell-making solvents & all.  I'll keep you posted as I eavesdrop on the guy.


Teonanacatl

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Re: Yield, schmield
« Reply #7 on: May 19, 2000, 03:33:00 AM »
it's noted in Jerry March's "Advanced Organic Chemistry (4th ed.) p.415:
"Quaternary salts can be dealkylated with ethanolamine.
R4N+ + NH2CH2CH2OH --> R3N + R(NH2+)CH2CH2OH
In this reaction, methyl groups are cleaved in preference to other saturated alkyl groups."

also...Hunig; Baron Chem. Ber. 1957, 90, 395, 403.
...I've looked this one up before, but I'm not sure where's it at right now...

EC 2.1.1.XX
EC 1.14.XX.X

CHEM_GUY

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JedZed: Do a write up
« Reply #8 on: May 24, 2000, 09:04:00 PM »
Why not do a write up on the sucessful trials you've had.  You did suceed didn't you?

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JedZed

  • Guest
Write up, shmrite up
« Reply #9 on: May 27, 2000, 01:11:00 AM »
Not quite yet; I'm still working on it.  Busy, busy.
      I will say this:  MeCN may be selective for 5MeOT over melatonin.  When I dissolved the red oil left after extracting the Et glycol with dcm (& boiling off the solvent), I got a redorange solution & some white powder at the bottom.  Before I sin any more in formulating hypotheses without collecting all the data, I must get back to work.
      I'm sorry to keep you all in suspense- I'll try to finish quickly.  JZ


JedZed

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Reasonably quickly, that is
« Reply #10 on: May 28, 2000, 01:30:00 AM »
Sheeit.  When I finally give my yield, it'll be substantially reduced.  Fuckin'stupidass flammable ethyl acetate.  It seemed to give less of an emulsion than I've seen for with DCM for extracting out of acCN, though.
     I should have a crude yield really soon.  The crystals are enmeshed in a sort of tar, so I don't know what'll be lost to rextallization.  Back to work.
     By the way, Chem_trickster, way to trick me into saying that I'M the one doing all of this.  Cripes.


JedZed

  • Guest
Write-up
« Reply #11 on: May 29, 2000, 10:46:00 PM »
7.3g melatonin was refluxed in 100mL ethylene glycol (distilled from antifreeze) with a 1.25 molar equivalent of KOH (do the math; I can't recall the mass), for fortyfive minutes, by which time the solution was a very menstrual sort of red-orange.  The mixture was allowed to cool and then cut with water and extracted with DCM.  The extracts were pooled and solvent removed to yield a dark red, slightly fishysmelling oil.
     The oil was dissolved into ~100 mL acetonitrile, at which point chunks of white powder precipitated at the bottom of the vessel (unhydrolyzed melatonin?).  This liquid was poured into a 500mL flask and more solvent added to bring the total volume up to ~475 mL.  Isopropyl bromide and K2CO3 were added in a 5:2:4 molar ratio to the theoretical amount of mexamine.  At this point, the experimenter was disturbed to note that the carbonate salt really did not want to go into solution.  The mixture was stirred for four hours, after which time the carbonate still had not all gone into solution.  Hmmmm...
     This was not a problem the last time this procedure was attempted, but then, proportionately more solvent was used that time.  The mixture was allowed to stir for about twenty more hours at room temperature, at which point dissolving the entire amount of salt was given up as hopeless.  The experimenter hopes that he merely misweighed the amount of salt he added.
      As per drone's second breath of hope, the reaction mixture was poured over an equal amount of water and extracted with ethyl acetate, which did not emulse as much as DCM usually does (in the experimenter's experience) with aqueous tryptamine solutions.  The pooled EtOAc extracts were then greatly reduced in volume by a combination of evaporation, boilover, and combustion.  The former process is preferable to the latter two.
     The more-concentrated EtOAc sol'n was treated with a few drops of [HCl] in water, and the whole mess evaporated, giving an ichorous red tar of a product.  This tar was dried to give off-white crystals and chunks of darker tar, m = 3.3g.  Recrystallization from isopropanol gave red (?) crystals, m = 2.1g and a very red mother liquor.
      At this point, the yield is obviously terrible and a bioassay has not yet been conducted as the experimental animals are all on holiday.  The results will be submitted as soon as the data are gathered.
      Sorry I'm such a lousy chemist.


Rhodium

  • Guest
Re: Write-up
« Reply #12 on: May 29, 2000, 11:44:00 PM »

JedZed

  • Guest
Mexamine is
« Reply #13 on: May 30, 2000, 12:03:00 AM »
5-MeO tryptamine, also meksamine, according to Merck.
      I don't know what I was thinking, above- the final HCl crystals were not red but light grey-tan in color.


JedZed

  • Guest
Curses
« Reply #14 on: June 04, 2000, 12:58:00 AM »
The isolated hydrochloride is not active.
I haven't had yet the time to test its antiradiation properties & mp analysis is not presently possible, but my guessis that it's either unreacted (because of the base's poor dissolution) 5MeOT or possibly the mono-iPT.  Hmm, I should look that one up in the good book.  Wait a second here...
   Hm, no, not that.  About 0.25 mg/kg was insufflated, and with no effects other than what may have been slight periperal flickers, another 0.25 mg/kg was sucked up an hour later.  This had no effect other than an enduring fatigue which was probably unrelated.  The tiredness lasted ~36h; longlasting and pronounced but not exactly mindbending.
    Sheeit.  The doctor made one of the diPTs with a PTC and strong base in DCM; I don't see why this wouldn't work.  Probably, as is obvious, I just need shall we say a little work on my kitchen, er, lab technique.
    Why the fuck wouldn't the K2CO3 dissolve, though?  My only idea is that there was unreacted melatonin in the rxn mixture.  This would make the solution less polar, yes?  I wonder if there might be the opposite effect of salting out an emulsion here:  can you depolarize(?) out a salt?  The alkaloids werein solution before the salt was added.
     In the first attempt at this, the base went easily into solution... but the 5MeOT had been rextlzd from EtOH.  This is the biggest difference I can think of.  If anybody has any ideas, I'd love to learn from them, & I'm sure that many others would, too.


CHEM_GUY

  • Guest
Re: Curses
« Reply #15 on: June 04, 2000, 11:21:00 PM »
A PTC or a base is unnessary for a alkylation of tryptamines.  It helps speed up the process, but it can be done with just heat and patience. 

Try a 5 fold excess of isopropyl-X and add some heat and wait about 1 day...  Make sure that the tryptamine is a free base and dissolved well in the same medium as the isopropyl-X.

This post is for informational purposes only an is not intended to facilitate illegal activity.

foxy2

  • Guest
Re: Curses
« Reply #16 on: June 12, 2000, 11:54:00 PM »
If you still have the ACN/H2O shit you may be able to separate the phases.  Ive been working with these solvents, if the solution is saturated and i mean saturated with salt, we used sodium sulfate they will sep into 2 phases. One with the salty h2o and the other will be your nitrile.  You will probably need to reflux to get the salt in.  Make sure to use a higher salt than NaCl, im mean highr ionic strength, could make all the difference.