pHarmacist
(Hive Addict)
02-28-03 14:42
No 412547
      Synthesis of LSD from Lysergic Acid
(Rated as: excellent)
    

A mixture of 10.0 g (0.037 mol) of d-lysergic acid in 500 ml of dry dimethyl formamide (DMF), under argon, was treated with 9.0 g of carbonyl diimidazole and stirred at room temperature for 1 hour. The reaction was then treated with 38 ml of diethylamine and stirred at room temperature overnight. The reaction was concentrated under reduced pressure. The residue was taken up in 500 ml of methylene chloride and washed with 500 ml of water. Insoluble material was removed by filtration and the layers were separated. The organic portion was washed with 250 ml of saturated brine solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on 800 g of silica gel using 3% methanol in methylene chloride to yield 9.0 g (75%) of d-lysergic acid diethylamide (LSD) as a light brown amorphous solid after evaporation of the solvents.

Patent US2003013131

Accept No Imitations, There Can Only Bee One; www.the-hive.ws
 
 
 
 
    sean1234
(Newbee)
03-02-03 23:21
No 413169
      I wonder, would it be thier resposibility to...     

I wonder, would it be thier resposibility to include details on the lighting situation during synthesis in this sort of writeup? Are labs now ignoring the stifled lighting that was thought to be so essential in the past.
 
 
 
 
    darius
(Newbee)
03-03-03 21:47
No 413399
      of course not     

no but it's sort of commmon knowledge, along with other assumptions that would be made to someone with a degree of experience to perform the synth.  others are, regards to temp., inertness of the atmosphere, keeping everything anhydrous etc.

lata
D

the suttleties create the fine line between genius and insanity, between me and you.
 
 
 
 
    pHarmacist
(Hive Addict)
03-03-03 22:13
No 413407
      Audience     

The audience are not kids that want to make some acid in the kitchen when mom is not at home, but rather academic society, and it's quite known even to those chem-wannabe rave-kids that the process is rather sensitive even to the light.

Accept No Imitations, There Can Only Bee One; www.the-hive.ws
 
 
 
 
    Lilienthal
(Moderator)
03-04-03 00:30
No 413457
      You do not have to care about light while...     

You do not have to care about light while working with ergolines, that's something like an urban myth. Even academics believe in it and switch off the light while handling such substances. But there are a few papers which show that degradation by light doesn't play a role under handling conditions. There are scientific papers on that, UTFSE.
 
 
 
 
    pHarmacist
(Hive Addict)
03-04-03 00:38
No 413459
      Lili, are you sure?     

When it comes to LSD the light (especially sunlight) will indeed give lumi-LSD upon exposure, lumi-LSD is inactive...

Accept No Imitations, There Can Only Bee One; www.the-hive.ws
 
 
 
 
    Rhodium
(Chief Bee)
03-04-03 01:31
No 413468
      I think this is the first time TFSE has failed me     

So - how true is each statement by Shulgin here: Post 322099 (Rhodium: "lumi/iso-LSD", Tryptamine Chemistry)

Running your name through TFSE, restricted to posts between 04/2000 and 02/20021, using either "light", "sensitive", "uv", "lsd", "lysergic", or even "http" (if you had posted a link) as keywords gave no results... Could you help out?

[1] In April 2000, you "thought" that light sensitivity was overrated - Post 127086 (Lilienthal: "Re: LSA and heat", Tryptamine Chemistry) - and in February 2002 you knew it for a fact - Post 273556 (Lilienthal: "Re: trouble getting yields for LSD", Tryptamine Chemistry) - so you must have posted the refs inbetween...
 
 
 
 
    cattleprodder
(Newbee)
03-06-03 14:52
No 414288
      hv & LSD     

Ultraviolet light (hv) causes a Hoffman degradation on lsd meaning that you lose the C=O bond of the amide and end up with the N(Et)2 group where the C=O was.  Sunlight does in fact rapidly degrade lsd.

But, to simplify matters even more, to make lsd from lsa all you really have to do is to reflux the lsa in pyridine and diethylamine for a long time and then, using a sep funnel, do an acid/base extraction, followed by crystallization if you want. 

Since the hydroxide ion is a poor leaving group, your yields should suck, but you will conceivably have more lsd than you would personally want to consume by yourself.

Also, bear in mind that lsd-025 is/was one of the dirtiest drugs that people would repeatedly pay for IMO.  ETH-LAD (N-ethyl lysergic acid diethylamide), on the other hand, I would gladly ingest again in all likelihood if given the chance.

Just my 6th cents.
 
 
 
 
    Lilienthal
(Moderator)
03-06-03 14:59
No 414290
      Bullshit! Back it up with data!     

Bullshit! Back it up with data!
 
 
 
 
    pHarmacist
(Hive Addict)
03-06-03 15:28
No 414296
      >Also, bear in mind that lsd-025 is/was one     

>Also, bear in mind that lsd-025 is/was one of the dirtiest >drugs that people would repeatedly pay for IMO.

WHAT!? Get out of here! laugh

Accept No Imitations, There Can Only Bee One; www.the-hive.ws
 
 
 
 
    moo
(Hive Bee)
03-06-03 15:47
No 414300
      But hey!     

A great opportunity to brag about having tried ETH-LAD is not to be missed. And this is not even the only thread where I have seen this recently. How can you be certain it was ETH-LAD?

Like, the double-dipped blotters of mescaline and lsd were the shit, dude!

EDIT: I would also like to know that what has hydroxide ion as a leaving group got to do with your proposed synthesis?
 
 
 
 
    cattleprodder
(Newbee)
03-07-03 21:41
No 414656
      Ok.     

"Experiment 19:  Amides"

"Introduction.  Another important derivative of carboxylic acids is the amide group, formally a condensation product of a carboxylic acid and an amine.

"Because amides are the most stable and least reactive of the family of carboxylic acid derivatives, they can be produced by the reaction of amines with any of the more reactive relatives:  (a) acid chlorides (b) anhydrides, or (c) esters, OR [emphasis added] EVEN (D) FROM THE CARBOXYLIC ACID ITSELF, USING HIGHER TEMPERATURES [greater than 200 degrees Centigrade].  This chapter will present examples of several of these methods.

"(a) R-CO-Cl + R'-NH2 --> R-CO-NH-R' + HCl
(b) R-CO-O-CO-R + R'-NH2 --> R-CO-NH-R' + R-COOH
(c) R-CO-O-R + R'-NH2 --> R-CO-NH-R' + R-OH
(d) R-CO-OH + R-NH2 --> R-CO-NH-R' + H2O"

If you had ever had both METH-LAD and ETH-LAD, then I think that you would also probably be able to tell the difference.

As for acid being a "dirty" drug, well everyman is entitled to his opinion, and different drugs affect different people's bodies in different ways.  See also set and setting.

The fact that the hydroxide ion is a poor leaving group is the reason that higher temperatures must be used in example (d) from above, and it is also the reason that yields suffer when compared with method (a) from above.  Consult some organic chemistry textbooks and/or lab manuals if you are still confused.

Oh yeah, I've tried 2-MeO-3,4-MDA as well while on acid, and it was a nightmare.  How do I know for sure what they were?  I don't, but good luck convincing me otherwise.

Just my 888 cents.
 
 
 
 
    blasephilomath
(Stranger)
03-07-03 22:35
No 414663
      $'s & scents/cents/since/sense.     

According to _Pharmaceutical Substances_ by A. Kleemann and J. Engel on page 1441, POCl3 will help in the case of (d).  The compound under discussion there is 3-(N,N-diethylamido)pyridine.

Although no mention is made of solvent, I would think that it would have to be pyridine, as pyridine scavenges out trace moisture and POCl3 is, I believe, quite moisture sensitive. 

Triethylamine or another free base tertiary amine can also be used in the place of pyridine as a chloride ion scavenger when doing the amide from the acyl chloride reaction.
 
 
 
 
    yellium
(I'm Yust a Typo)
03-08-03 20:57
No 414859
      >Consult some organic chemistry textbooks...     

>Consult some organic chemistry textbooks and/or lab manuals >if you are still confused.

Nice variation on 'argueing by authority'. 'I'm right because mr. so-and-so says so, and I'm too lazy to look it up.'

On ETH-LAD vs LSD vs METH-LAD: I wonder if you could distinguish those blind from each other. See also the whole 'purple blotter is better than red/brown blotter' discussions popping up every so often. Include dosage/set/setting as variables and things get next to impossible.
 
 
 
 
    sean1234
(Newbee)
03-09-03 02:42
No 414918
      Re: LSD is an unusually fragile molecule and...     


LSD is an unusually fragile molecule and some comments are in order as to its stability and storage. As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely. There are two sensitive aspects of its structure




I was under the impression that the light warnings on some clandestine writeups were later written off here in the forums as referring to relatively small amounts, or degradation over a fairly long period of time.

As far as these patent writeups simply assuming that light degradation of lsd is COMMON KNOWLEDGE, I dont buy that one. It may not be thier responsibility to include substance properties charts if the degradation is not as quick as was previously thought before, but if indeed the degradation is so fast that it seriously effects yields and fucks the entire goal of the patent up, it would be common sense that they would include at least some words on epimerization/light deg.

 


Also, bear in mind that lsd-025 is/was one of the dirtiest drugs that people would repeatedly pay for IMO. 



dude no offense, but thats the kind of comment that belongs on the couch...i dare you to make that implication that lsd is "dirty" hold as much water as a paper towel. its fine if you dont like the high but saing that its "dirty" implies that theres physiological side effects or, even worse, leftover contaminants from synthesis (thats completely rediculous, lest your nieghborhood dealer cut it post synthesis).

 
 
 
 
    bbell
(Stranger)
03-10-03 00:05
No 415168
      dirty lsd     

200 micrograms is about the same size as a grain of sugar.Ya cant put much filler in a micro dot, window pain,or blotter. lsd causes ataxia of the diaphram, a twitch, people getting high atribute this to strycnine. false you are high and are open to believe anything. ya can't put a hell of alot of poison in a blotter. 
 
 
 
 
    Lilienthal
(Moderator)
03-11-03 10:20
No 415643
      LSD is not that light sensitive as you might think
(Rated as: excellent)
    

J Anal Toxicol 1998 Oct;22(6):520-5  (Medline (PMID=9788528))

Stability study of LSD under various storage conditions.

Li Z, McNally AJ, Wang H, Salamone SJ.

A controlled study was undertaken to determine the stability of LSD in pooled urine samples. The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. LSD concentrations were measured quantitatively by the Abuscreen RIA and by HPLC using a fluorescence detection method. Good correlation was observed between the immunoassay and the fluorescent integrity of the LSD molecule. Thermostability studies were conducted in the dark with various containers. These studies demonstrated no significant loss in LSD concentration at 25 degrees C for up to 4 weeks. After 4 weeks of incubation, a 30% loss in LSD concentration at 37 degrees C and up to a 40% at 45 degrees C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. We also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA. This study demonstrates the importance of proper storage conditions of LSD in urine in order to insure proper analytical testing results over time.

"Table II illustrates that fluorescent light can cause decommposition of LSD in transparent containers when they are placed in close proximity [15 cm] to the light source. Under these conditions, the half-life of LSD was approximately 4 weeks. As the distance between the source of fluorescent light and the samples increased, the percent of LSD decomposition decreased. The results demonstrate that LSD can withstand normal room light conditions at a constant temperature of 25C for 1 week without noticeable structural change."


 
 
 
 
    Bubbleplate
(Hive Bee)
03-13-03 16:01
No 416563
      Trace Metal Ions     

F. Arcamone, the Italian scientist who was the first to successfully grow Claviceps paspali in large scale submerged culture, (1961) found, while extracting Lysergic Acid derivatives, that, quote:
"The crude mixture of (Lysergic)bases or Maleates, was freed from solvent on a Buchner funnel, care being taken to exclude daylight as much as possible during all operations. The products were stored in a desiccator covered with black paper. On exposure to light they darkened and gradually became transformed into intractable dark-brown resins. This transformation occured much more rapidly if the addition of Versene was omitted from the procedure, indicating that it was catalyzed by TRACES OF METALS."
Since he was using jacketed stainless steel pipes as fermenter vessels, there surely were trace metal ions in the culture medium.
Versene is the trade name for Sodium Edetate. It will react with most divalent and trivalent metallic ions to form soluable metal chealates.
Reference: Proc. Royal Soc. London, 155: 26-54
 
 
 
 
    Bubbleplate
(Hive Bee)
03-14-03 14:58
No 416978
      Anything Vessel That Can Be Steam     

sterlized at least once would be OK to use. One could even chemically sterilize (Bleach; H2O2, etc.) a large container like say a 5 gallon plastic Water Cooler jug, then add nutrient medium that has been steam sterilized.
Also certain Stainless Steel types, like 316L, are very inert and resistant to attack. They are "approved" by industry and are suitable to use in fermentation setups for things like headplates, air spargers, stirrer blades & impellers, electrodes, etc. and anything that will come into contact with the media and culture organisms.
However, the prefered vessels are good old glass. It has also been proven that cultures grown in glass actually get some needed Trace metals from the glass, since it is not totally inert. The organic acids and enzymes from the micro organisms will leach out the metal ions.
 
 
 
 
    sYnThOmAtIc
(Hive Addict)
07-29-03 02:16
No 450479
      Plastics don't matter in the issue of ...     

Plastics don't matter in the issue of fermenting claviceps. Then only properties that plastic containers should idealy hold is ability to undergoe autoclave conditions repeatedly or at least once.

 So polypropylene would be best bet here. Preferably four neck reaction flasks, 3neck distilling flasks or bio reactors being the 600 dollar alternative to a 65 dollar flask 3neck flask.

Though I will tell you one thing if you can't afford the simplest of lab equipment to do culturing you will fail miserably at culturing claviceps.

Look around you can get several 500ml erlynmeyer flasks for around fourty bucks and the bugstopper .2micron hydrophobic silicone stopper for the flasks for ten bucks each making 2.5l of feremnting equipment under 100bucks. Then you need autoclave, culture dishes and tubes, preferably a small clean room helps efforts and such a million fold and a bunch of other shit I cold make a list that you SHOULD HAVE. Although if you have experience in aseptic cell culture you may be able to culture this efectively in ghetto style but don't expect high yield for long. I have noticed that upon infection with bacteria yields suffered drastically and required serial dillution and subsequent culture of dillutions to isolate the pure cells again to reachieve the high yields. You will also need a freeze drying setup to store conidia for later reuse when your strain begins to degrade and give poor yields. Although you can get by with isolation an storage in a refridgerator they will not keep as long and are at risk of contamination in a household refridgerator even a clean one with no food. You need a modified fridge with a ULPA filtering system and each batch of tubes of condidia must be sealed at cap rims and in a air tight plexi glass box in the fridge. I could go on forever but the point is much success if any will not be achieved with a poor budget in claviceps culturing. But anyway none of teh chemicals used in the proces will react with the plastic but some plastics may cause the cells to adhere possibly not sure though. For the most part thay shoudl jsut be autoclavable.

Yes, That pic really is me!
 
 
 
 
    flipper
(Hive Bee)
07-29-03 15:03
No 450545
      I don't understand this.     

I don't understand this. If I look to this:

Svensk Farmaceutisk Tidskrift, Vol.75, 933-40 (1971).
A suspension of 1.34g (5mmol) anhydrous D-Lysergic Acid in 80ml DMF was mixed at 20C with a solution of 0.89g (5.5mmol) N,N'-Carbonyldiimidazole in 25ml DMF and the reaction mixture was then stirred for 30 min at 20C in the dark. The clear solution was then mixed with a solution of 0.40g (5.5mmol) Diethylamine in 5ml DMF, and the mixture allowed to stand for 2h at 20C followed by 20h at 5C. The resulting amber solution was freed from DMF by evaporation at 50-60C under aspirator vacuum, the residue dissolved in 250mL 2% aqueous tartaric acid and the solution washed with diethyl ether. To the aqueous phase was added a small amount of Ostacol (activated carbon), the solution filtered with suction and basified to pH 8 with aqueous ammonium hydroxide. The liberated freebase was extracted with a 9:1 ether/ethanol mixture, and after separation and drying of the organic phase, the solvent was evaporated in vacuo to give 2.3g of crude product, which consisted of 57 weight% of the diethylamides of D-Lysergic acid (I) and D-Isolysergic acid (II) (81% yield calculated on the starting acid) and the rest being chiefly Imidazole. According to qualitative TLC analysis the crude product contained only the amides (I) and (II) as well as traces of D-Lysergic acid and a decomposition product.

The yields are It's 57% D-LSD and 24% D-isoLSD
But in this example of patent US2003013131

US2003013131
A mixture of 10.0 g (0.037 mol) of d-lysergic acid in 500 ml of dry dimethyl formamide (DMF), under argon, was treated with 9.0 g of carbonyl diimidazole and stirred at room temperature for 1 hour. The reaction was then treated with 38 ml of diethylamine and stirred at room temperature overnight. The reaction was concentrated under reduced pressure. The residue was taken up in 500 ml of methylene chloride and washed with 500 ml of water. Insoluble material was removed by filtration and the layers were separated. The organic portion was washed with 250 ml of saturated brine solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on 800 g of silica gel using 3% methanol in methylene chloride to yield 9.0 g (75%) of d-lysergic acid diethylamide (LSD) as a light brown amorphous solid after evaporation of the solvents.

It only gives 75% of D-LSD. Where is the D-isoLSD?!?! What is done differently in this synth that it does not give much isoLSD????
 
 
 
 
    neohippy
(Newbee)
07-29-03 15:15
No 450547
      Where did the iso lsd come from?     

Looks like in the first synth they basified it.
May have given the epimerized iso LSD.
 
 
 
 
    bbell
(Newbee)
08-02-03 03:45
No 451158
      the iso-LSD?     

The iso-lsd will be the second band in the chromatographic column.(the slower band, blue florensent under black light)In the first synthesis Svensk Farm. Tidskrift by A.Hofmann you omited the chromatography on 50g. Al2O3 activity three-four.10mL benzene with 1% acetone, as elutant.
To many numbers in your U.S.patent number?
 
 
 
 
    Rhodium
(Chief Bee)
08-12-03 21:40
No 453154
      Stability study of LSD under various storage condi
(Rated as: excellent)
    

As mentioned in Post 415643 (Lilienthal: "LSD is not that light sensitive as you might think", Tryptamine Chemistry)
Scans made available by FreakyDMT, thanks!

Stability study of LSD under various storage conditions
Li Z, McNally AJ, Wang H, Salamone SJ.
J. Anal. Toxicol. 22(6), 520-5 (1998) (../rhodium/pdf /lsd.storage.stability.pdf)
 
 
 
 
    PapaSmerck
(Hive Bee)
09-10-03 21:27
No 458213
      flipper yield discrepancies     

flipper, some possibilities:

an excess of carbonyldiimidazole and DEA was used in the first reaction, and the resulting residue would hence contain LSD along with any remainders of the other two reagents. this residue was then dissolved in 250mL of 2% tartaric acid, enough water to be sure to react with residual carbonyldiimidazole, which decomposes to CO2 + imidazole. Under certain physical conditions, pockets of carbonic acid may drop in pH enough to influence yields. i also found a couple of papers that implied that imidazole group may bind with heavy metals, a la EDTA. the fact that imidazole accounted for the bulk of the 19% impurity in the raw  product indicates that virtually all of the catalyst was decomposed.

another possibility is that the activated charcoal in the first reaction contained trace amounts of heavy metals. a bit of both seems the most likely explanation for the large discrepancy, as the imidazole was still in solution when it was passed through the charcoal.

i notice that DMF is boiled off at 50-60degC under pressure in the first reaction. this seems an unusually high temperature to expose lsd to, so it may possibly explain the bizarre yield.

just a few educated guesses, please corrent me if i'm wrong smile
 
 
 
 
    flipper
(Hive Bee)
10-11-03 20:14
No 464032
      Solvents     

Can you use DCM, THF, acetonitrile or Chloroform instead of DMF in this synthesis?
Why do they prefer DMF?
In those other peptide synthesises they just say "In a suitable solvent". Why Don't that aply to this synthesis with the Carbonyldiimdazole?
 
 
 
 
    Bubbleplate
(Hive Bee)
10-12-03 17:30
No 464182
      DMF Is The Preferred Solvent For a Number of     

reasons. First, it is a good solvent for gasses and will tend to keep the diethylamine in solution. It also has a slow rate of evaporation. The reactants, lysergic acid, Carbonyldiimidazole also dissolve well in it. DMF also is alkaline, which I believe helps the reaction conditions.
DMF is known as a "universal solvent".
THF is an ether and would be hard to get/keep anhydrous.
 
 
 
 
    Lilienthal
(Moderator)
10-12-03 19:14
No 464194
      Wrong answer :-D . Polar solvents extremely...     

Wrong answer laugh. Polar solvents extremely enhance the reaction speed for nucleophilic substitutions.

Polar protic solvents promote the SN1 mechanism (by solvating and separating the ions) and polar aprotic solvents the SN2 mechanism (by stabilizing the transition state and by solvation of reactands and products).

You usually prefer solvents with a low boiling point (depending on the reaction temperature). DMF (which is not basic) could probably be substituted with acetonitrile which has a similarly high dielectricity constant.

(This should have been provided you with enough keywords...)
 
 
 
 
    Bubbleplate
(Hive Bee)
10-16-03 17:12
No 464985
      What Exactly Is the SN1 Mechanism     

then, in the particular reaction he referred to?
Feel free to use molecular diagrams, etc.
TIA.

"I'm just the cook!" - Steven Segall
 
 
 
 
    moo
(Hive Bee)
10-16-03 17:40
No 464989
      http://www.google.com/search?q=sn1+mechanism     

http://www.google.com/search?q=sn1+mechanism

fear fear hate hate