lysergic

[flipper]

Thanx    I know I can be a pain in the ass. Sorry for that.  

[slappy]

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]

thanks for your practical and much needed info!
But what about HATU or hbtu as coupling reagents?

[flipper]

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]

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]

"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]

Thanks for your help foxy 2! And just when i was beginning to think there was some sort of "conspiracy".

[flipper]

Thanks anyway. I've learned alot in this topic and i'm gratefull for that. You can't have it all.

[flipper]

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]

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

(https://www.thevespiary.org/rhodium/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]

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]

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]

Is it possible?

TFSE gives no matches.

[lugh]

It's not listed as a peptide coupling reagent  

[goiterjoe]

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]

loompanics books are not to be trusted

[bbell]

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]

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]

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)

(https://www.thevespiary.org/rhodium/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 (missing)

(Aurelius: "Ref #2 J.Biol.Chem. 104, 547-551, (1934)", General Discourse)
And has been further HTMLized in

https://www.thevespiary.org/rhodium/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)

(https://www.thevespiary.org/rhodium/Rhodium/djvu/jacobs.djvu)

[bbell]

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.