chemotype (Stranger)
05-30-03 19:45
No 436693
      hmmm... 250 mg of ergotamine tartrate     

A butterfly happened to land upon a sunflower and found 250 mg of ET.  Is this even thepretically usable or is this a test of micromolar rxn skilz?  So much weight is lost after hydrolizing to the acid.  And then after several crystallizations. 

Now that we're on the subject... has anyone heard of a purification of LSD base on a regular silica column except for the the 5% MeOH/DCM/NH3 in a centrifugal column performed by Nichols?  I'm thinking the same conditions would be true for a straight column although certain tryptamines (5-meo-DMT) require a higher MeOH ratio like 15-25%. 

respect...
 
 
 
 
    Lego
(Newbee)
05-31-03 03:16
No 436757
      TIHKAL     

Ever thought about reading TIHKAL?

Shulgin describes a method for purifying the LSD derived from lysergic acid, POCl3 and diethylamine. This step is done with alumina and chloroform/benzene mixture.


Such nano reactions are usually more easy to perform than hundred-gram reactions because heating & cooling is much easier but you should have at least some experience in performing such reactions (e.g. working with syringes) because working with normal glassware is not appropriate for such small small amounts of solvents and reagents. Loosing a bit of product by carelessness will dramatically lower yield, loosing one drop of your product solution on a 1 M scale is not so dramatic.


Good luck..........

The candle that burns twice as bright burns half as long
 
 
 
 
    chemotype
(Stranger)
05-31-03 07:55
No 436783
      yes, have read many times... thank you     

What I'm saying is that after all the 15% NH/EtOH washes to remove lysergic acid plus precipitating w/ 2.5 N H2SO4 will yield very little lysergic acid hydrate.  I would recommend a more modern peptide coupling agent like pyBOP rather than the POCL3 method. 

Benzene/chloroform columns are a thing of the past.  Everyone used to run their columns with benzene until they realized that it was nasty shit.

can one bubble anh. NH3 through absolute EtOH to create the 15% soln?  They don't sell it in that concentration.

only one way to find out...
 
 
 
 
    VinnyC
(One Man Show)
05-31-03 12:32
No 436836
      Re: can one bubble anh.     


can one bubble anh. NH3 through absolute EtOH to create the 15% soln?




Yes... measure the weight before and after. Specifically, the starting weight should be ~78.9g and the final weight should be ~92.8g.

Edit: Substitute toluene for benzene by the way...


"...somebody is feeding these damn animals booze." Fear & Loathing
 
 
 
 
    chemotype
(Stranger)
05-31-03 15:02
No 436854
      Why is alumina preferred over silica?     

Why is alumina preferred over silica?  SWINM has never even seen a run on an alumina column before.  Silica is much more available. 

respect
 
 
 
 
    VinnyC
(One Man Show)
05-31-03 15:32
No 436862
      Silica gel-60 is just fine...     

Silica gel-60 is just fine...

"...somebody is feeding these damn animals booze." Fear & Loathing
 
 
 
 
    chemotype
(Stranger)
06-01-03 09:01
No 436992
      silica vs. alumina...     

I thought alumina was a basic packing medium whereas silica is acidic.  Wouldn't they have different RF values for each medium?
 
 
 
 
    hest
(Hive Adickt)
06-01-03 09:21
No 437000
      Collum     

Yes, dif. Rf's. These dayes you would run a dry collum.
(Vogel's 5'th p. 220). Im sure that a heptan/EtOAc/MeOH system will work.
 
 
 
 
    chemotype
(Newbee)
06-02-03 20:43
No 437383
      Isn't there and established procedure for...     

Isn't there and established procedure for flashing this stuff through a silica loaded column?  How polar is this molecule?
 
 
 
 
    hest
(Hive Adickt)
06-04-03 03:26
No 437753
      Flash     

Don't think so, but your TLC result's will give a good hint. Usual the product will emerge from the collum in that mixture with give an Rf on 0,5
 
 
 
 
    Lilienthal
(Moderator)
06-04-03 04:57
No 437758
      Yes, use the solvent system which gives an Rf...     

Yes, use the solvent system which gives an Rf of 0.5 - 0.75 on TLC plates. An Rf closer to 0.75 would be better for columns, otherwise you would waste solvents and time.
 
 
 
 
    Bubbleplate
(Hive Bee)
06-04-03 14:28
No 437820
      pyBOP ?     

Could you elaborate a bit about pyBOP coupling agent, and why it'd be preferable over the POCl3 method? (and pyBOP is ???)
Seems to me that the POCl3 method is straight forward, simple,and easy to set up and run.
Is pyBOP similar to the old N,N Carbonyl Diimidazole method/reagent?
 
 
 
 
    Rhodium
(Chief Bee)
06-04-03 15:20
No 437827
      PyBOP     



PyBOP; Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

Molecular Weight: 520.40
Appearance: White crystalline powder
CAS #: 128625-52-5

Use: http://www2.vuw.ac.nz/staff/paul_teesdale-spittle/peptide-synthesis/pep-syn-files/activation-coupling.htm
 
 
 
 
    flipper
(Hive Bee)
06-04-03 15:42
No 437832
      but     

those peptide coupling agents. Don't they make an awful lot of iso-lsd? Converting it to lsd is also 30% loss of yield.
If you do a peptide coupling reaction and it yields 80% of 50% iso-lsd and 50% lsd and you convert the iso-lsd to lsd your yield of lsd will be between the 60 and 70%.
Same with POCl3 only POCl3 reaction only takes 5 minutes.
Peptide coupling agents are exotic chemicals (i think) and usually they use more then one agent.
And to prevent isomerization they use HOBt or HOSu. That's alot of difficult and expensive to aquire chemicals.
Isn't the POCl3 method not much more better fot the average home chemist?

By the way. When is somebody improving the hydrolysis method of Ergot Alkalo´ds to LSA monohydrate?

crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy crazy
 
 
 
 
    Rhodium
(Chief Bee)
06-04-03 16:02
No 437834
      Dave Nichols reccommend PyBOP for LSD     

Dave Nichols used PyBOP in his latest paper on LSD analogs (70-85% yield of pure tartrate salts, no mention of iso-byproducts): Post 353379 (Rhodium: "New LSD analogs from the Nichols Lab", Tryptamine Chemistry)


PyBOP: A new peptide coupling reagent devoid of toxic byproducts
Tetrahedron Lett. 31, 205-208 (1990)
DOI:10.1016/S0040-4039(00)94371-5

Abstract

PyBOP« (benzotriazolyloxy-tris[pyrrolidino]-phosphonium hexafluorophosphate), an analog of BOP where dimethylamino groups are replaced with pyrrolidino, is the only analog exhibiting equivalent properties in peptide bond formation. It can be used instead of BOP for the sake of safety.
 
 
 
 
    chemotype
(Newbee)
06-04-03 19:22
No 437877
      EDC and HOBt might work fine also...     

Using, EDC (can't remember chemical name too damn long) and HOBt to slow things up might work.  I don't think any epimerization would occur with most of the new coupling reagents.  EDC is cheaper than pyBOP but if these things are available, use them.  The workup is so damn easy!!

On the notion of using a silica loaded column, I'm presuming the LSD molecule is polar because of the acidic hydrogen hanging of that indole nitrogen.  Other tryptamines required some sort of base (such as NH4OH) along with a polar eluent (such as DCM/MeOH).  The base is there to keep it from streaking down the column.  I think the LSD molecule might be a more neutral than simple substituted tryptamines. 

Only one way to find out.  15% NH3 in abs EtOH is a stinky bitch of a mess. 

respect...
 
 
 
 
    Lilienthal
(Moderator)
06-05-03 01:51
No 437929
      Usually 1% aqueous ammonia would be enough to...     

Usually 1% aqueous ammonia would be enough to prevent tailing effects of amines.
 
 
 
 
    doktor_alternate
(Stranger)
04-11-04 19:14
No 500290
      coupling reagent "better than PyBOPÖ"     

http://www.pepnet.com/hctureagent.html
http://www.pepnet.com/images/HCTU.jpg

inexpensive, little racemization, non-toxic, non-irritant, stable...


A key element for developing a new condensing agent is the resulting stereochemistry of the amino acid; it is critical to maintain chiral integrity during chain elongation. Incorporation of a better leaving group during amide bond formation can lead to racemization of the alpha-carbon due to its increased acidity which promotes enolization and oxazolone formation during the activation step (2). Recently at the European Peptide Symposium Di Fenza and Rovero reported reduced rates of racemization when HCTU was used as the coupling reagent as compared to BOP. Overall, HCTU is an excellent, new coupling reagent that offers high yields and low levels of racemization.

- - says the manufacturer - -

this would be good for our favorite lysergic conversion due to the chiral importance of that 8 position, no?

so, i cut this from
../rhodium/chemistry /lsd.coupling.agents.html

Proposed LSD synthesis procedure:

1eq. LSA is dissolved in a suitable solvent(must be fairly dry) at RT, 1.05 eq HBTU/HATU is added. 2eq. of diethylamine is added and the rxn is stirred at RT until it goes to completion (15min-2hr). The solvent is removed under vacuum and the residue partitioned between EtOAc (or other suitable solvent) and saturated NaHCO3 (or NH4OH). The layers were separated and the organics were washed with NaHCO3 (or NH4OH), H2O, saturated NaCl, dried over MgSO4, filtered and concentrated in vacuo to remove the solvent and excess diethylamine. The crude LSD, which should be fairly pure, is then further purified by chromatography and converted to the tartrate salt.

now, if i suppose correctly, hctu can be used in its place... does anyone see any problems there?

at $125usd/100g it is not so expensive...
oops, my brother wants his computer back so i have to leave this thought unfinished. i was in the middle of doing a weight-cost analysis for the chems involved in a hctu lsd synth from lsa...
 
 
 
 
    doktor_alternate
(Stranger)
04-12-04 19:59
No 500491
      water scavenger?     

to run an amide coupling reaction... buddy sais "must be fairly dry" is this like, dry solvent, N2 flushed atmosphere, water traps on all glass openings, vac. dessicated reagents, flame dried casks... or do you want to use a water scavenger in the mixx too? could you just do it in dry toluene, thereby doing it in a solvent that would be its own water scavenger by forming an azotrope? maybe just a dean-stark trap plus some non-amine scavengers and a lower-boiling solvent... anything else that i'm missing?

about the post on rhodium.ws titled:
../rhodium/chemistry /lsd-buzz.html
is it just me... or is this synth possessing of problems? like:
"Cool, acidify with dilute sulfuric acid, and shake in a separatory funnel with 1 1iter of dry ether."
- - why use dry ether if you're shaking over an aqueous sol'n? and

the procedure sais to convert all iso-LSA to LSA before converting to LSD, yet all syntheses produce some iso-LSD which must then be converted to LSD a la "Add 50 ml of ethanol and 5 ml of 4 N KOH per every gram of iso-LSD. Let this mixture stand for 2 hours at room temp. Evaporate in vacuo to get the LSD".... so why waste time and solvents doing the initial conversion? coupling reagents dont prefer an optical isomer over the other for the reaction. or is the iso- sometimes discarded?
 
 
 
 
    hest
(Hive Adickt)
04-13-04 13:05
No 500636
      Fairly     

Fairly dry means standing over molecularsieves ( alternative use and virgin bottle) for 48 hours befoer use, nothing more.
A common rule in chemistry is "Garbage in garbage out". It's just good practise to use as good starting material as posible, but ofcourse you can use a mixture of plain/iso-LSA to start with and then seperate them with chromatography.