formula54 (Hive Bee)
11-26-01 09:38
No 240809
      lysergic  Bookmark   

i was using the fse and found many pathways to lsd... swim wants to experiment, but is overwhelmed by the amount of information on this topic.
so: to begin with i thought itd be good to start a new discussion on shuglins synth, and start from there. while im sure that many are well versed, i also know that many still want to learn about the ins and outs of this delicate procedure...so i figure we can learn together.

http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml
ok- he starts with a lsa extraction from ergotamine tartrate. all chemicals here seem generally accessible: potassium hydroxide,sulfuric acid,ethanol,ammonia.

projected yeild is 3.5g d-lysergic acid hydrate from 10 grams et.   anyone have anything interesting to add to this?


(i hope that this thread will evolve into something great: a long discourse on various lsd methods for us youngins...even though i know im probly dreaming...seems like this might turn into lighter fluid for a utfse flame war)
54
 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 09:58
No 240826
      Re: lysergic  Bookmark   

Problem- ergotamine tartrate is highly watched and controled

You must get around this before dreaming this route, however the first step is fairly simple.  One thing I can say is that you should use photographic red lights whenever working with these compounds.  Or definately very low light, NOT a drop of sun or UV.

Do Your Part To Win The War
 
 
 
 
    hest
(Hive Bee)
11-26-01 10:00
No 240830
      Re: lysergic  Bookmark   

It is not the synthesis of LSD there is hard to doo.
The best one is the synthesis in thikal.

But the main problem is to obtain some lysergic acid, it is almost imposible to by and hardt to synthesis.
When you first get a way to make the acid/amin/ect. you are home.
I guess that the biosynt with Claviseps pupura is the best way to doo it, it is easye to obtain and grows fast on annye agar. But I have no ekspirience with bulk growing in fermentations tank. Acramon ect. did obtain app. 2g/l in their fermentation, im stil dreaming.
 
 
 
 
    formula54
(Hive Bee)
11-26-01 10:07
No 240834
      Re: lysergic  Bookmark   

cmon foxy, gimmie more credit than that.
i figured there was enough claviceps cult. discussion already...and of course cafergot pills, if you can getem. lets skip to the synthesis.

ok- next step uses diethylamine...heres a post on this. Post 71976 (halfapint: "Re: got dimethylamine?", Chemicals & Equipment)
 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 10:12
No 240837
      Re: lysergic  Bookmark   

Well Shulgin ain't working with crude cell culture extracts, so lets discuss or post how we will get this ergotamine feedstock.  Lay out your plans, best to start now, if your lucky you can still find some grain with ergot this fall.

So the first step is all set and worked out.  Ergotamine, oh yea I forgot No Problem

If I was serious I would bee trying to grow it now.

Do Your Part To Win The War
 
 
 
 
    formula54
(Hive Bee)
11-26-01 10:22
No 240842
      Re: lysergic  Bookmark   

ok, since egot cult does have some gray areas i guess we can start there. foxy: claviceps can be ordered...but if you really want natural cultures then its probly too late in the season.
heres some ergot refs ../rhodium/chemistry /references.txt

there seems to be only one net recipe that i can find on mass ergot cult. Ingredients:

6.5 g Potato Dextrose Agar
5.0 g Bacto Agar
500 ml distilled water
15 mg Rifampicin in 10 ml Methanol
15 mg Penicillin G in 10 ml 70% Ethanol

Mix the first 3 ingredients, autoclave for 20 min. and cool to room temperature. Add the antibiotics and pour into sterile petri dishes.

Plate out the fungi using a 10-4 dilution starting with 5 g dry weight of compost in 45 ml of the autoclaved phosphate buffer. Put this first dilution in a blender at high speed for 40 sec.

Perform serials dilutions to 10-4 and add 0.l ml of the final dilution to each plate.

Incubate the plates at 28C for 3 days.

Take counts and samples of fungal colonies at 3 days.


 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 10:37
No 240848
      Re: lysergic  Bookmark   

Bee careful acquiring, I thought they were gone but they are not. 

Ok those are colonies, not mass culture! T hat doesn't give you ergotamine.  A few plates won't add up to anything.  You need submerged cultures, do you have the procedure for those?

Do Your Part To Win The War
 
 
 
 
    formula54
(Hive Bee)
11-26-01 10:41
No 240853
      Re: lysergic  Bookmark   

oops..copied the wrong one..bee right back.ok:
Post 18071 (zephler: "Re: Ergot", Tryptamine Chemistry)
of course, ergot is poisonous, be careful, bla bla bla, no this thread is not for the eyes of idiots, bla bla, no  disclaimers for st anthonys fire ok? (saw this one coming.)
 
 
 
 
    hest
(Hive Bee)
11-26-01 11:30
No 240866
      Re: lysergic  Bookmark   

Wath is then the quistion ? All the chemicals in shuglins synthesis is easye to obtain, you can maybee tune the chromatograpic ting a bit, use the dry collum teqnice instead of flash collum (ore atlest use toluene insted off benzene) but that is abouth it.
 
 
 
 
    Antoncho
(Official Hive Translator)
11-26-01 11:37
No 240869
      Re: lysergic  Bookmark   

Dear Formula54, may i ask you a question, politely?

Have you (or SWINyou) ever tried to actually synthesize a synthetic drug from smth. other than ephedrine or essential oils?

All i know is that making LSD from pure alkaloids is considered to bee very complicated and only for the tough guys w/proper equipment.

If you're one of those then please forgive my sarcasm but i bet you aren't.

It's been SWIM's impression that synthing even the simple things may bee very hard for an amateur.

Antoncho

P.S. Foxy, you must bee laughin' now reading thiswink
 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 12:25
No 240877
      Re: lysergic
(Rated as: excellent)
 Bookmark   

Lol, well lets say I wish him luck and no Saint Anthony's Fire!!!
smile

Here are some articles

Production of peptide ergot alkaloids in submerged culture by three isolates of Claviceps purpurea.
Amici et al. 1969-464   Amici, A. M.; Minghetti, A.; Scotti, T.; Spalla, C.; Tognoli, L. (1969)
Appl Microbiol 18(3):464-468

On an alkaloid from ergot.
Anonymous (1935)
Science 82(2114):16

A note on the variability of alkaloid content of domestic ergot.
Atal, C. K.; Schwarting, A. E. (1957) 
J Am Pharmaceut Assoc Sci Ed 46:451
 
The new ergot alkaloid.
Dale, H. H. (1935) Science 82(2118):99-101

Effect of autoclaving and conventional and microwave baking on the ergot alkaloid and chlorogenic acid contents of morning glory (Ipomoea tricolor Cav. cv.) heavenly blue seeds
Friedman, M.; Dao, L. (1990)  J Agr Food Chem 38(3):805-808

Ergot alkaloid and chlorogenic acid content in different varieties of morning glory Ipomoea-spp seeds.
Friedman, M.; Dao, L.; Gumbmann, M. R. (1989) J Agr Food Chem 37:708-712

Recent advances in ergot pharmacology. Phillipson
JD & Zenk MH (ed) Indole & biogenetically related alkaloids.
Academic Press, London :285-291
Fluckiger, E. (1980)

Studies on cultural requirements of Claviceps purpurea and inactivation of ergotamine.
Michener, H. D.; Snell, N. (1950)
Am J Bot 37(Jan):52-59

Title: Biosynthesis of Ergot Alkaloids by Immobilized Mycelium of Claviceps paspali

Authors: Matošić, Srećko; Mehak, Milena; Ercegović, Lidija; Okwor, James
Journal: Prehrambeno-tehnol. biotehnol. rev
Number: 2
ISSN: 0352-9193
Volume:30, pgs83-88 (1992)
Language: hrvatski
Summary: The effect of the selected parameters on the biosynthesis ofergot alkaloids during semicontinuous cultivation of immobilizedmycelium of Claviceps paspali F-2057 was investigated. Comparingthe effect of various substrate mass in the me of biosynthesis ofergot alkaloids medium, it was established that the mediumcontaining 6% mannitol and 5% ammonium succinate yields moreergot alkaloids. For the biosynthesis of ergot alkaloids, 4.25g/L 6 days old mycelial inoculum appeared to be most favorable.Investigation of the effect of alginic acid concentration usedfor the immobilization, showed 4% alginic acid concentration tobe the mest favorable for alkaloid biosynthesis. Insemicontinuous process, the immobilized Claviceps paspalimycelium produced alkaloids over a period of 60 days (6reincubations). Productivity of the process in each of thereincubations with immobilized cells is 75 to 120 % higher thanin corresponding free cell cultivations and the totalproductivity with immobilized cells is two times higher than thatof free cells. The results obtained here show that immobilizationof mycelia forming microorganisms, might be effective inbiotechnological production of complex metabolites, such as ergotalkaloids.

Title: Effect of antifoams on the biosinthesis of ergot alkaloids by high-productive strain of Claviceps paspali F-2057
Authors: Matošić, Srećko; Mehak, Milena; Šušković, Jagoda; Golob, Zoran
Journal: Acta Bot. Croat.
ISSN: 0365-0588; Volume:53, pgs.39-47 (1994)
Language: engleski
Summary: The effect of several surfactants i.e. commercial antifoams on biosynthesis of ergot alkaloids was studied. Addition of some surfactants of polyglycole structure and Tweens to submerged cultures of high-productive strain of C. paspali F-2057 caused a change in alkaloid synthesis intesity. Pluronik (polyetoxypolypropoxy polymer) added in the range of 0.25 to 0.75 % markedly stimulated the production of ergot alkaloids. The Pluronik-supplemented culture reached maximal alkaloid yields one or two days erlier than the control. Production of alkaloids increased twice. The maximal yield achieved was 5.35 g/L with the process productivity amounting to 17.2 mg/L h.

Title: Physiological diferentiation of alkaloid producing strains of Claviceps purpurea (Fr.) TUL.

Authors: Matošić, Srećko; Mehak, Milena; Šušković, Jagoda
Journal: Acta Bot. Croat.
ISSN: 0365-0588
53, pgs.21-30 (1994)
Summary: Four different strains of Claviceps purpurea IC/39/20-B, G, R and W have been selected and isolated using common selection method. The relationship between intensity of pigmentation of the culture and the accumulation of ergot alkaloids have been noticed. Maximal alkaloid yields have been obtained with more pigmented strains R and W in the sucrose-asparagine medium (1.30 and 1.50 g/L respectively) and with less pigmented strains B and G in the sucrose-peptone medium (0.30 and 0.80 g/L).

Title(Thesis): Biosynthesis of Ergot Alkaloids by means of Immobiliyed mycelium of Claviceps paspali
Summary: Comparing the effect of various substrate concentration on thebiosynthesis of ergot alkaloid, it was obtained that a mediumcontaining 6% manitol and 5% ammonium succinate yields more ergotalkaloid. For the biosynthesis of ergot alkaloid, 4.25 g/L dayold mycelial inoculum appeared most favorable. Investigating theeffect of alginic acid concentration used for immobilization,obtained results showed 4% alginic acid to be most favorable foralkaloid biosynthesis. In semicontinuous process the immobilized,Clavicepd paspali mycelium produced alkaloids over a period of 60days (6 reincubations). Dilution of basic medium, or reducing thesubstrate concentration reduces alkaloid yields almost in aproportional manner. However, basic media diluted in the ratio of1:10 gave in a relative ratio higher alkaloid yield. Productivityof the process in each of the reincubations with immobilizedcells is 35% and 50% higher then in corresponding free cellcultivations in all tested substrate media, and totalproductivity with immobilized cells is three times higher than offree cells. Effect of surfactant-pluronik (0.25%) on ergotalkaloid biosynthesis in the medium diluted in the ratioo of 1:4was tested and obtained results showed that alkaloid yieldincreased by about 35%. The results obtained here show thatimmobilization technique, also of mycelia forming microorganisms,might be effecttive in biotechnological production of complexmetabilites such as ergot alkaloids.


Do Your Part To Win The War
 
 
 
 
    hest
(Hive Bee)
11-26-01 12:50
No 240887
      Re: lysergic  Bookmark   

And where do i find Acta Bot. Croat ??
smile
But the point with collor selektion sounds werrye promissing.
Acramon et.al. just selected the most pink one, after 3 generations (with 100 sampels in each) the strain yealded app. 2g/l that is enough for mee :-)
 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 13:34
No 240900
      Re: lysergic  Bookmark   

"And where do i find Acta Bot. Croat ??"

Why Croatia of course! :o)

The summaries give some valuable information in themselves.  Yes that pigment phenomenon could bee key, yeilding grams per liter makes things ALOT easier. smile

I am waiting for the picture of multi-grams of crystal LSD to bee posted to the Hive. laugh  Having that much acid would bee scary!!!  It would warrant some serious protective gear, unless you have time for an accidental long strange trip.cool

Do Your Part To Win The War
 
 
 
 
    hest
(Hive Bee)
11-26-01 13:43
No 240902
      Re: lysergic  Bookmark   

Yes i think the key is the collour thing. I have been growing claviceps on agar some time, and thinking abouth scaling up, but time you know :-)
quote tikhal
----------------------
A totally pure salt, when dry and when shaken in the dark, will emit small flashes of white light.
-----------------------

I want to see that cool
 
 
 
 
    formula54
(Hive Bee)
11-26-01 13:53
No 240907
      Re: lysergic  Bookmark   

dear antoncho,
             does it really matter? my discussion is valid. if you feel you are too intelligent, then why bother coddling us 'amatuers'.





-swi54
 
 
 
 
    foxy2
(Distinctive Doe)
11-26-01 14:14
No 240912
      Re: lysergic  Bookmark   

Formula54
Antoncho has a point.  I think you want at least a few hundred hours tinkering with chemicals in the lab before attempting LSD.  While you know what you want, I think that if you are truely interested in chemistry you will start out smaller.  Because if you don't then I can virtually guarantee you will get bored long before you make anything.  Hell if you don't want to take the risk then don't make drugs but play with chemicals some other way.

Chromatographic purification of DMT or Lysergic acid amides would bee great practice.  Any of the other commonly discussed stuff here is something to do and learn. 

Something to think about, but not to take away from this discussion, because this is a fun little chat.smile
Foxy

Do Your Part To Win The War
 
 
 
 
    Antoncho
(Official Hive Translator)
11-27-01 08:49
No 241273
      Re: lysergic  Bookmark   


dear antoncho, does it really matter? my discussion is valid. if you feel you are too intelligent, then why bother coddling us 'amatuers'.




Dear Formula54!

My reply wasn't meant to bee a flame or something - i swear, i never do that (xcept one time when someone prposed to make NH3 from N2 & H2 and vacuum - lol.
I was just trying to give you a truer picture of how it really is.

Beecause i remembered SWIMself, when his chemistry was purely theoretic he'd fancy he would do this and that and make all sorts of tryptamines - it all looked so fine in theory,
but now - AMOF, he just got his feet wet in this - compared to people like, say, SWIhest - and he just stopped to think of certain things for at least next 2 years or sosmilesmilesmile

See? All I said takes nothing from the validity (and usefulness as well) of this discussion. I just wanted to let you know, just in case.

BTW - people, this pink color thing ir REALLY cool, methinks.

Antoncho

 
 
 
 
    formula54
(Hive Bee)
11-27-01 13:50
No 241336
      Re: lysergic  Bookmark   

i understand the need for extensive lab experience, antoncho, and i understand where you are coming from, however lsd is a personal goal for swi54:basically this thread is   not   to see whether its too hard, but rather if the chemicals/equipment are at least reasonably available, to review the synthesis in depth, with attention also paid to the inherent danger in some of the components. btw..i dont consider ergot to be dangerous, since complete precautionary procedures would have to be assumed...like absolutely no physical contact with the substance.
ok ill continue step by step tomorrow.

-swi54
 
 
 
 
    yellium
(Hive Bee)
11-27-01 14:15
No 241345
      Re: lysergic  Bookmark   

If you're going for self-sufficiency, you might as well try to get used to chemistry by synthing 2C-B or DOB first.

Note: don't sell DOB as `err, something like acid', because it isn't. Don't let people overdose themselves because they don't know (or are to impatient) to wait for three hours for full effects. frown
 
 
 
 
    Bozakium
(Hive Addict)
11-27-01 23:38
No 241529
      Re: lysergic  Bookmark   

  LSD is far, far, far more difficult to make than meth or MDMA, now that lysergic acid is very, very controlled..
 I have not found a single case of successful dish culture of the fungus, you must grow rye is the word.
  For a good starting point for the truly interested, try Fester's book: Practical LSD Manufacture, published by loompanics. Some may not be Fester fans, but it is the only reasonable book on the subject, easy to read and LOADED with references for the truly dedicated.
 
 
 
 
    bujinkan
(Stranger)
11-28-01 12:53
No 241726
      Re: lysergic  Bookmark   

BozAkium...why bother? Festers book is a cave drawing compared to the info here on the web.
I don't see why you're giving formula so much shit,and just when it was getting interesting too. then again formula, this post is probably redundant, and if you really want to learn you should access the serious chem forum. (it also means that you wont be able to spread more inane comments since they check your post before it gets put up.)
 
 
 
 
    paranoid
(Hive Bee)
11-28-01 19:51
No 241914
      Re: lysergic  Bookmark   

I don't think anyone was giving 54 a hard time, just some fair warning about the difficult journey of making LSD.
 
 
 
 
    slappy
(Hive Bee)
11-29-01 03:52
No 242024
      Re: lysergic  Bookmark   

The synthesis of LSD is not very hard, provided that you have a good organic chemistry background, and alot of first hand experience.

All of those old methods suck, big time. We have much better reagents nowadays. POCl3 dehydration? I don't think so. Thanks to the progress made in peptide synthesis over the last 20 years, we have a beautiful selection of amide coupling reagents available to us. And since this reaction is a simple amide coupling, we should use some of these gentle reagents. So all you need is your Lysergic Acid and your Diethylamine. From there I would go for the following routes:

PyBrOP coupling, catalysed by HOBt in DMF, Acetonitrile, or N-methyl-2-pyrrolidone. Used with a gentle base like TEA or DIPEA. Low temps, high yields.

You can also use a Carbodiimide coupling reagent, although the urea formed can cause problems with the workup. I would use the polymer bound ones, as the urea formed will remain bound to the solid phase, and can be removed by simple filtration.

Of course this would all be carried out at low temps, with the proper lighting precautions, etc.

As a general rule, this type of reaction can be carried out in just about any dry polar aprotic solvent, and with any coupling reagent. BOP, PyBOP, AOP, PyAOP, PyClOP, HBTU, TBTU, etc. would all work just fine.
 
 
 
 
    formula54
(Hive Bee)
11-29-01 07:39
No 242070
      Re: lysergic  Bookmark   

just an abstract i found: unrelated to the order.

FORMATION OF A LYSERGIC ACID DERIVATIVE DURING THE PARASITIC DEVELOPMENT OF A STRAIN OF CLAVICEPS PASPALI.
P. Bianchi, E.B.Chain
Infected florets were collected 5 weeks after innoculation. Infected tissue was seperated. The ground tissue was extd. with 2% tartaric acid in 70% Me2CO for 12 hrs. The suspension was filtered and the Me2CO was removed in Vacuo at 30deg. The turbid soln. was extd. with light petroleum ether to remove fats, the pH adjusted with NH4OH and the soln. reextd with CHCl3. The CHCl3 ext. was evaporated to dryness in vacuo at room temp., the dry ext. dissolved in .5 ml CHCl3 and chromatographed. (54 notes that this was performed using wild infected grain: earlier they appearantly tried infecting P.dilatatum with C. paspali (strain F550), but the infections were deemed 'abnormal'...which explains the next entry:
Reisolates of the fungus derived from the abnormal sclerotia derived from st. F550 produced the same alkaloid, but quant. yeilds varied widely.


-swis54
 
 
 
 
    formula54
(Hive Bee)
11-29-01 08:14
No 242078
      Re: lysergic  Bookmark   

ARTIFICIAL CULTIVATION OF ERGOT.
Jan Kybal, Jiri Protiva, Karin Strnadova
The cultivation was performed in 1000ml flasks filled with 600 ml. of medium composed of sucrose7.5, sorbitol 2.5, citric acid .05, NH3 0.54, Ca(NO3)2.4H2O 0.15, MgSO4 0.025, agar 0.05% and tap water.  The pH was adjusted to 6.0, the medium was sterilized at 1 atm. for 35 min., and innoculated with 20 ml innoculum of a 48 -hr. culture of claviceps purpurea isolated from the sclerotia paratizing on on rye and grown in 3deg Be.malt infusion on a rotary shaker at 25deg. The flasks were agitated and incubated at 25deg for 22 days. the mycelium was seperated, washed with H20 and dried in an air stream at room temp. it contained 14% ergotamine.

-swis54
 
 
 
 
    slappy
(Hive Bee)
11-29-01 15:42
No 242274
      Re: lysergic  Bookmark   

Claviceps is toxic, and will eat away your skin if it gets on you. Ergot cultivation, like LSD synthesis, is easier said than done.
 
 
 
 
    hest
(Hive Bee)
11-29-01 17:09
No 242314
      Re: lysergic  Bookmark   

Slappy is it a joke ??
I'v been growing claviceps on agar a couple of times. Its much easyer to handel than psilocybe.
 
 
 
 
    terbium
(Old P2P Cook)
11-29-01 18:29
No 242343
      Re: lysergic  Bookmark   

Claviceps ... will eat away your skin if it gets on you.
??? Pre 1950s or so, ergot was commonly gathered by sending children out into the fields to pick the infected grain heads.
 
 
 
 
    formula54
(Hive Bee)
11-29-01 23:02
No 242428
      Re: lysergic  Bookmark   

intresting...ive always wondered what exactly st anthony's fire was... is it like gangrene? or does ergot release poisonous chemicals?
terbium, ive heard that too...maybe it isnt as poisonous as originally thought.


-swis54
 
 
 
 
    Rhodium
(Chief Bee)
11-30-01 06:09
No 242493
      Re: lysergic  Bookmark   

Ergotamine alkaloids causes constriction of the blood vessels in your extremities, causing gangrene. That is St Anthony's fire.
 
 
 
 
    flipper
(Newbee)
12-05-01 03:08
No 244432
      Re: lysergic  Bookmark   

Maybe a stupid question but how do I use these coupling reagents.


slappy(Hive Bee)11-29-01 12:52 No 242024 Re: lysergic

The synthesis of LSD is not very hard, provided that you have a good organic chemistry background, and alot of first hand experience.

All of those old methods suck, big time. We have much better reagents nowadays. POCl3 dehydration? I don't think so. Thanks to the progress made in peptide synthesis over the last 20 years, we have a beautiful selection of amide coupling reagents available to us. And since this reaction is a simple amide coupling, we should use some of these gentle reagents. So all you need is your Lysergic Acid and your Diethylamine. From there I would go for the following routes:

PyBrOP coupling, catalysed by HOBt in DMF, Acetonitrile, or N-methyl-2-pyrrolidone. Used with a gentle base like TEA or DIPEA. Low temps, high yields.

You can also use a Carbodiimide coupling reagent, although the urea formed can cause problems with the workup. I would use the polymer bound ones, as the urea formed will remain bound to the solid phase, and can be removed by simple filtration.

Of course this would all be carried out at low temps, with the proper lighting precautions, etc.

As a general rule, this type of reaction can be carried out in just about any dry polar aprotic solvent, and with any coupling reagent. BOP, PyBOP, AOP, PyAOP, PyClOP, HBTU, TBTU, etc. would all work just fine.




New routes from ET to LSD (../rhodium/chemistry /et2lsd.txt)

 
 
 
 
    formula54
(Hive Addict)
12-05-01 03:41
No 244439
      Re: lysergic  Bookmark   

didnt you just answer your own question?

-swis54
 
 
 
 
    flipper
(Newbee)
12-05-01 08:41
No 244493
      Re: lysergic  Bookmark   

No.
How do I know how much reagent I have to use.
 
 
 
 
    Rhodium
(Chief Bee)
12-05-01 10:23
No 244510
      Re: lysergic  Bookmark   

The document you linked does provide you with all the amounts... Foe example, with BOP:

Proposed LSD synthesis procedure:

1eq. LSA is dissolved in a suitable solvent(must be fairly dry) at RT, 1.05 eq BOP-reagent 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.
 
 
 
 
    flipper
(Newbee)
12-05-01 12:38
No 244548
      Re: lysergic  Bookmark   

But not with ByProP.
 
 
 
 
    Rhodium
(Chief Bee)
12-05-01 13:54
No 244576
      Re: lysergic  Bookmark   

Do you have any lysergic acid and all the needed equipment available, so that it any meaning with anyone of us figuring the exact reaction details out for you? I would guess that a slight molar excess of any peptide coupling reagent is always used to form amide bonds.
 
 
 
 
    formula54
(Hive Addict)
12-05-01 14:01
No 244580
      Re: lysergic  Bookmark   

Why are you so intent on using ByProP? this is lsd chemisty not meth...we cant afford to fuck around, its hard enough as it is! Use BOP.
!
 
 
 
 
    flipper
(Newbee)
12-06-01 01:56
No 244895
      Re: lysergic  Bookmark   

It's just a question. You guys have a lot of unreleased anger . Try some Yoga. Why Is it so difficult to answer a question. Damn. If it is so easy to do then why is it so difficult to do a little favor and answer this question instead of getting mad and frustrated. Are you quys on prozac or something.
I'm Just very interested and wan't to know everything. Is that a crime? 
 
 
 
 
    foxy2
(Distinctive Doe)
12-06-01 02:27
No 244902
      Re: lysergic  Bookmark   

"How do I know how much reagent I have to use."

No one really knows the answer.

You have to look for procedures using the respective coupleing agents to perform similar reactions and compare them.  This should give you some indication as to whether or not yours will work.  Don't expect people to start extrapolating in a very specialized segment of organic chemistry.


The fact that you ask that question in the way you did indicates that you are not even close to being prepared to attempt this synth.  Go to the library and find at least 5 references where they use ByProP to produce amides, preferably dialkylamides.  Get familiar with these and then come up with your own procedure!!


Do Your Part To Win The War
 
 
 
 
    Rhodium
(Chief Bee)
12-06-01 02:27
No 244903
      Re: lysergic  Bookmark   

We don't know everything off the top of our heads, but we can find out with a literature search, but before we go through that trouble we would pretty much like to know of it is of any use that we do that job, or if the information will just lie around unused.

I always answer the questions that I already know the answer to, but I only do literature searches for people when I feel that the result is actually going to be used.
 
 
 
 
    flipper
(Newbee)
12-06-01 04:18
No 244931
      Re: lysergic  Bookmark   

laughThanx smile I know I can be a pain in the ass. Sorry for that. cool
 
 
 
 
    slappy
(Hive Bee)
12-07-01 01:33
No 245241
      Re: lysergic  Bookmark   



Poster: formula54
Subject: Re: lysergic

Why are you so intent on using ByProP? this is lsd chemisty not meth...we cant afford to fuck around, its hard enough as it is! Use BOP.
!




I think perhaps you need to question your own knowlage before making a comment such as this.

Generally, it has been found that AOP reagents are better than BOP. But, when you use BOP or AOP, HMPA is produced as a breakdown product of the BOP. HMPA is a rarely used polar aprotic solvent which is also know as "liquid cancer" because it is a fluorine away from sarin. Seeing as though you probably wouldn't want this in your product, you would want to use PyBOP, which has pyrrolidino groups instead of dimethylamino, and does not produce HMPA.

PyBrOP is a supirior reagent for coupling of N-methyl Amino Acids with low enantiomerization. The coupline of N-methyl amino acids is difficult, and usually only gives low to moderate yields of products which are often contaminated with unwanted diasteromers. Many coupling reagents are ineffective or not practical to use:  BOP and HOBt are often useless; BOP-Cl, pivaloyl chloride, and Dpp-Cl require long reaction times and activate at 0°C. For some hard substrates, PyBrOP is used with dimethylaminopyridine (DMAP). Since Diethylamine is a secondary amine, like N-methyl Amino Acids, BOP might be next to useless. That is why I recommended PyBrOP.

 
 
 
 
    formula54
(Hive Addict)
12-07-01 02:50
No 245257
      Re: lysergic  Bookmark   

thanks for your practical and much needed info!
But what about HATU or hbtu as coupling reagents?
 
 
 
 
    flipper
(Newbee)
12-08-01 05:29
No 245595
      Re: lysergic  Bookmark   

I'm trying to find some literature about ByPrOP but till now I haven't found anything. Slappy where did you have your info from??? It could be a smal step for you but it could also be a huge step for humankind and the psychonauts.
 
 
 
 
    formula54
(Hive Addict)
12-08-01 09:15
No 245628
      Re: lysergic  Bookmark   

Its understandable that they dont want to give out too much detailed info on LSD...this is the most powerful substance int he world...the nitroglycerin of psychoactives. With it comes much responsibility, spiritual, and other, since you are infact taking the higher development of human beings in your hands. With that in mind, you have to acnknowledge that LSD can be used to harm people...especially with the pure crystals that we wouldn't be producing.
Flipper, in one of my other posts here in tryptamine chem i have a link to a paper on coupling reagents.
 
 
 
 
    foxy2
(Distinctive Doe)
12-08-01 10:39
No 245646
      Re: lysergic  Bookmark   

"Its understandable that they dont want to give out too much detailed info on LSD"

Yes its a big conspiracy to hold you down.

Do Your Part To Win The War
 
 
 
 
    formula54
(Hive Addict)
12-08-01 10:43
No 245647
      Re: lysergic  Bookmark   

Thanks for your help foxy 2! And just when i was beginning to think there was some sort of "conspiracy".
 
 
 
 
    flipper
(Newbee)
12-09-01 04:05
No 245815
      Re: lysergic  Bookmark   

Thanks anyway. I've learned alot in this topic and i'm gratefull for that. You can't have it all.
 
 
 
 
    flipper
(Newbee)
12-12-01 09:18
No 246819
      Re: lysergic  Bookmark   

I found this link on the net. Is it of any use? I don't understand the most of the text. It's like Russian for me.

http://www.oup.co.uk/pdf/0-19-963754-7.pdf
 
 
 
 
    flipper
(Hive Bee)
01-23-02 05:30
No 259844
      Re: lysergic  Bookmark   


All of those old methods suck, big time. We have much better reagents nowadays. POCl3 dehydration? I don't think so. Thanks to the progress made in peptide synthesis over the last 20 years, we have a beautiful selection of amide coupling reagents available to us. And since this reaction is a simple amide coupling, we should use some of these gentle reagents. So all you need is your Lysergic Acid and your Diethylamine. From there I would go for the following routes:

PyBrOP coupling, catalysed by HOBt in DMF, Acetonitrile, or N-methyl-2-pyrrolidone. Used with a gentle base like TEA or DIPEA. Low temps, high yields.

You can also use a Carbodiimide coupling reagent, although the urea formed can cause problems with the workup. I would use the polymer bound ones, as the urea formed will remain bound to the solid phase, and can be removed by simple filtration.

Of course this would all be carried out at low temps, with the proper lighting precautions, etc.

As a general rule, this type of reaction can be carried out in just about any dry polar aprotic solvent, and with any coupling reagent. BOP, PyBOP, AOP, PyAOP, PyClOP, HBTU, TBTU, etc. would all work just fine.





Generally, it has been found that AOP reagents are better than BOP. But, when you use BOP or AOP, HMPA is produced as a breakdown product of the BOP. HMPA is a rarely used polar aprotic solvent which is also know as "liquid cancer" because it is a fluorine away from sarin. Seeing as though you probably wouldn't want this in your product, you would want to use PyBOP, which has pyrrolidino groups instead of dimethylamino, and does not produce HMPA.

PyBrOP is a supirior reagent for coupling of N-methyl Amino Acids with low enantiomerization. The coupline of N-methyl amino acids is difficult, and usually only gives low to moderate yields of products which are often contaminated with unwanted diasteromers. Many coupling reagents are ineffective or not practical to use:  BOP and HOBt are often useless; BOP-Cl, pivaloyl chloride, and Dpp-Cl require long reaction times and activate at 0°C. For some hard substrates, PyBrOP is used with dimethylaminopyridine (DMAP). Since Diethylamine is a secondary amine, like N-methyl Amino Acids, BOP might be next to useless. That is why I recommended PyBrOP.




Are the procedures the same as for a BOP-reagent or another proposed procedure on This Paper (../rhodium/chemistry /et2lsd.txt) or is the procedure totally different?
Is the TEA or DIPEA for separating the phases in replacement of NaHCO3 or is it just for catalyzing the reaction?

What is the mechanism in these reactions? There is alot of stuff on the net but I can't find that holy paper that just explains everything. How different can these procedures be?  

 
 
 
 
    Rhodium
(Chief Bee)
01-23-02 07:21
No 259866
      Re: lysergic  Bookmark   

Do a websearch on these reagents, and then come back and tell us why you don't think the explanations in the hundreds of PDF files available out there doesn't satisfy your explanatory needs. I don't believe there is a free "holy paper" that describes it all, you have to buy a book on peptide coupling to get something like that.
 
 
 
 
    bujinkan
(Hive Bee)
01-23-02 13:25
No 259996
      Re: lysergic  Bookmark   

in another one of these top lsd posts theres a link to info on coupling reagents...adobe acrobat.

http://www.hq.nasa.gov/office/pao/History/SP-4406/4406-028.jpg
 
 
 
 
    Narayana
(HyperLab Bee)
07-05-02 17:47
No 329177
      P2O5 instead of POCl3 as a coupling agent ?  Bookmark   

Is it possible?

TFSE gives no matches.
 
 
 
 
    lugh
(Moderator)
07-05-02 17:59
No 329179
      Coupling Reagents  Bookmark   

It's not listed as a peptide coupling reagent frown
 
 
 
 
    goiterjoe
(Title on BackOrder)
07-05-02 18:02
No 329180
      TIHKAL references  Bookmark   

Shulgin mentions under his extensions and commentary for LSD that thionyl chloride could be used as well, albeit with reduced yields I think.

All paths are the same: they lead nowhere
 
 
 
 
    bbell
(Stranger)
01-16-03 16:36
No 398873
      uncle festers full of crap  Bookmark   

loompanics books are not to be trusted
 
 
 
 
    bbell
(Newbee)
05-24-03 16:18
No 435267
      Shulgin wrong  Bookmark   

You have to remove the tartrate salt before starting this synthesis.This is done by the following from:W.A.Jacobs & L.C.Craig.J.Biol.Chem.page245-53(1936)p.249 Experimental Section. A solution of 0.6 g. ergotamine tartrate was treated with excess sodium carbonate solution, and extracted with warm chloroform.  After drying of the extract, the chloroform was removed in vacuo.  The residue was dissolved in methyl alcohol and the solution was again concentrated to remove any chloroform.  From here the article goes on to give the alkaline hydrolysis steps.
 
 
 
 
    Rhodium
(Chief Bee)
05-24-03 17:12
No 435281
      I don't think that shulgin is wrong here...  Bookmark   

I hardly believe that Shulgin is wrong on that matter, he merely offers an alternative method of doing it, see my comments in Post 435276 (Rhodium: "Why freebase and not the tartrate?", Tryptamine Chemistry).
 
 
 
 
    Rhodium
(Chief Bee)
05-29-03 19:49
No 436450
      Discovery of Lysergic Acid
(Rated as: excellent)
 Bookmark   

Here is another paper by Jacobs & Craig I had lying around in my collection:

The Ergot Alkaloids II - The Degradation of Ergotinine with Alkali. Lysergic Acid
Walter A. Jacobs & Lyman C. Craig
J. Biol. Chem. 104, 547-551 (1934) (../rhodium/pdf /ergotinine2lysergic.acid.pdf)

The historical quote from the paper reads as follows:

"However, a new substance was obtained in good yield on gentle acidification, which possessed both acid and basic properies and which we have named lysergic acid. This acid is optically active [...] and crystallizes in beautiful leaflets."

Edit: The paper has been transcribed to ASCII in Post 454275 (Aurelius: "Ref #2 J.Biol.Chem. 104, 547-551, (1934)", General Discourse)
And has been further HTMLized in ../rhodium/chemistry /ergotinine2lysergic.html


...and the paper below is the one referenced by bbell a few posts up.

The Ergot Alkaloids XI - Isomeric Dihydrolysergic Acids and the Structure of Lysergic Acid
Walter A. Jacobs & Lyman C. Craig
J. Biol. Chem. 227-238 (1936) (../rhodium/djvu /jacobs.djvu)
 
 
 
 
    bbell
(Newbee)
06-01-03 17:11
No 437080
      sorry wrong journal  Bookmark   

Very sorry but the artical is 'Journal Organic Chemistry vol.1 pages245-53(1936)'.Most ergot alkaloids are insoluable in H2O, therefore methanol is used.
 
 
 
 
    Rhodium
(Chief Bee)
06-01-03 17:42
No 437085
      Okay then, here you go. Collect the whole series!
(Rated as: excellent)
 Bookmark   

The Ergot Alkaloids X - On Ergotamine and Ergoclavine
Walter A. Jacobs & Lyman C. Craig
J. Org. Chem. 245-253 (1936) (../rhodium/pdf /the.ergot.alkaloids.10.pdf)

The Hydrolysis of Ergotinine and Ergoclavine
Walter A. Jacobs & Lyman C. Craig
J. Am. Chem. Soc. 57, 960-961 (1935) (../rhodium/pdf /ergotinine.ergoclavine.hydrolysis.pdf)
 
 
 
 
    kreiselmeier
(Stranger)
06-07-03 05:21
No 438445
      Pixie got some Ergometrine Maleate  Bookmark   

My magic pixie just got some ergometrine maleate. Does the hydrolysis take longer than with ET? Thats what I read in Otto Snows Book, even it was pretty fuzzy. And if how much longer?

 What I hear now Et is pretty much available in A,dam now, people pay around 500 Euro / Gramm  , Ergometrin a bit more, like 800 / gramm,  but still not too bad he?

My pixi is in the factory, she gets it for free heheheheheh...just kidding, would be to good to be true. Sniff.

I will keep you posted

I'll do it!
 
 
 
 
    Rhodium
(Chief Bee)
06-16-03 02:45
No 440270
      Ergot & Urk  Bookmark   

Yes, in the unlikely event you had such an ergot solution, you would extract the acidified aqueous mixture with a non-polar solvent instead of a basified one. 

Regarding the Van Urk question of yours, I'm very sure you can find the answer in TFSE.
 
 
 
 
    Lilienthal
(Moderator)
06-16-03 03:49
No 440275
      Lysergic acid is zwitterionic and wouldn't...  Bookmark   

Lysergic acid is zwitterionic and wouldn't dissolve in non-polar solvents.
 
 
 
 
    Rhodium
(Chief Bee)
06-16-03 04:09
No 440278
      Hofmann Acidity Scale - revision in order? ;-)  Bookmark   

Oh, is that the case, I thought the acididity predominated. It's really confusing that 'acid' is actually a base.

We might have to revise this one: Post 204510 (Rhodium: "Hofmann Acidity Scale (Funny)", General Discourse) wink
 
 
 
 
    algebra
(Newbee)
06-16-03 04:45
No 440282
      funniest things i have every seen....  Bookmark   

i know this is way off topic - but i was looking for that post on the hofmann acidity index the other day. i remember when i first saw it - was giggling out loud for about 20mins. id stick it on my bedroom door if i thought anyone around here knew lsd nomenclature and would understand the joke.
 
 
 
 
    bbell
(Newbee)
07-16-03 19:21
No 447896
      problem with tihkal synthesis LSD  Bookmark   

On page 490 of 'Tihkal' a soln. of 6.7g. KOH in 100ml.,H2O, under inert atmosphere,magnetically stirred, was brought to 75 deg. and 10g. ergotamine tartrate added, reflux 1 hour.
Jacobs and Craig J.Org.Chem.vol.1,page245(1937)State The free base was separated from the salt and was then submitted to alkalie hydrolysis as described in the experimental section(page 249).
Use methanolic KOH not aqueous as Shulgin reports.I am Starting to look for other errors in my copy of Tihkal. Will keep ya posted.
 
 
 
 
    neohippy
(Stranger)
07-16-03 19:30
No 447897
      basic hydrolysis  Bookmark   

Journal of Biological Chemistry volume 104 page 547.

uses the freebase alkaloids, and the amides are dissolved in
methanol and KOH. Themethanol is then evaporated and water and KOH are added. Then heated for an hour. Cooled and precipitated with sulfuric acid at pH 3.
 
 
 
 
    bbell
(Newbee)
07-17-03 18:53
No 448152
      Shukgin's synthesis to LSD wrong.  Bookmark   

I think he is wrong on at least two steps. You must use the base of ergotamine tartrate to yield L.A. Next it must be refluxed in methanolic KOH.I am going to look up the potassium oxychloride route and see if there are any discrepancies.Keep ya posted.
 
 
 
 
    neohippy
(Stranger)
07-17-03 19:57
No 448158
      shulgin synth  Bookmark   

I am pretty sure that the basic hydrolysis is carried out
in water. However, shulgin does nothing to recover
the iso - lysergic acid in solution. Probably why he only got about a 70% yield.