Prospective synthesis route to obtain [ LSD ] - Is it feasible?

[Acid Bath]

Let us discuss a possible synthesis pathway of L S D​

Dear design alchemists who practice the pursuit of knowledge,

I write to you today with almost feverish enthusiasm to share an idea that has been obsessively fermenting in my mind for weeks. I believe I have glimpsed a possible synthesis for obtaining the much famed lysergic acid diethylamide molecule.


I am urged to submit this theory to the scrutiny of sharp and inquisitive minds such as yours, who else than you to be able to chat about this so exhilarating subject? Only the frank exchange and serene discussion between like-minded minds can polish ideas and bring them closer and closer to the truth. I hope we can establish a dialogue as equals where honest curiosity and willingness to change perspective prevail.


I know that many of you devote sleepless hours to thoughts such as the one I now wish to expound. That is why I am so confident that you will be able to judge it fairly and refine it with your valuable observations. I beg you to help me refine this intuition that has me engrossed. I trust that this conversation will allow us all to advance in the understanding of complex subjects that excite our intellectual curiosity and to satiate our spirit of erudition.

I send you my warmest greetings and look forward to initiating a conversation with you that is as exciting as it is constructive. Research requires joint tenacity. Next we will see the reaction mechanism that yours truly developed with pen and paper
View attachment DgRb7meqh8.jpg

Here we describe the formation of the lysergic acid acetate ester. As we can see we are in the presence of an esterification reaction of the acetylation type that curiously in this reaction there are no alcohols. I did not take this proposal out of my pocket, this idea was designed and commented out loud by a Doctor in Organic Chemistry. "Having clarified this abyss, quite a question mark, let us continue." Next we will see the portrait of the reaction mechanism of nucleophilic substitution. The reaction between lysergic acid acetate ester and diethylamine to form LSD View attachment

View attachment yTOmtocFDl.jpg

In particular, it is a bimolecular nucleophilic substitution (SN2) that follows the following steps:

1. diethylamine acts as a nucleophile and donates a pair of electrons to form a covalent bond with the sp3 carbon atom of the acetate group.

2. This causes the simultaneous cleavage of the C-O bond of the acetate group.

3. The oxygen of the acetate leaving group leaves with the electron pair, forming acetate ion.

4. Meanwhile, the carbon remains attached to the diethylamino nucleophile by a new C-N bond.

5. The mechanism is concerted, i.e. it occurs in a single step and without formation of carbocationic intermediates.

Therefore, it is specifically a bimolecular nucleophilic substitution (SN2) where the diethylamine acts as a nucleophile substituting the acetate leaving group on the sp3 carbon of the ester, finally forming the LSD molecule.

I look forward to your comments. I do this in high spirits and looking forward to having more people to talk to about the fascinating organic chemistry.

I also took the trouble to make the synthesis of diethylamine and another one where I speculate the extraction of lysergic acid. Wait for the next post.​

 

[HerrHaber]

Not to sound rude or discouraging but on your second attachment and also in the text it's clear that you mean lysergic-acetic acid anhydride but in no case ester. This is such a different molecule in reactivity that I never heard anyone talking so elaborated science seriously (well I remember doing such a mistake while studying for my undergrad thesis). Better have this edited for your sake, I don't think anyone messing these two up should sound "to be taken seriously" advanced, with mechanistic details without any prior practical testing (not that it would work in my honest opinion). Now I'm no expert but as much as I try not to be inappropriate I just can't let this be as it is. Experts may leave a rather sourer comment. Even though the mechanism seems right I doubt it's actually applicable and I have no clue about the anhydride or so said "ester" method of synthesis.

 

[Acid Bath]

Hello HerrHaber, I have read your comment and appreciate you taking the time to review and analyze the post. I have been studying more deeply into some synthesis pathways and have realized how challenging it can be to extract lysergic acid, whether from morning glory seeds, ergot, or even obtaining LSA from Stipa robusta, as it is a very laborious process.

Once you have lysergic acid, adding diethylamine to obtain LSD seems relatively straightforward. I have discussed my proposal with chemistry doctors who assured me it could work. I proposed an LSD synthesis starting from lysergic acid, where first the acyl chloride is formed using PCl3, PCl5, or SOCl2, and then diethylamine is added for LSD formation. According to those I consulted, this synthesis seems correct, but they cautioned me about the difficulty of obtaining the precursors for acyl chloride formation, especially thionyl chloride, which seems hard to find in Latin America and is also risky due to its toxicity.

In response, I suggested synthesizing it independently, which elicited some laughter and warnings about the dangers involved. This prompted me to propose the synthesis I shared in this post, considering more accessible and cost-effective reagents. When I showed this new route, I received positive feedback and was told it could be a much more interesting and profitable option if pursued.

However, this remains a potential synthesis route, contingent upon the challenge of obtaining pure lysergic acid, which is a real hurdle based on my research.

Thank you for your attention, and I look forward to continuing this engaging discussion on the forum!

 

[HerrHaber]

Good intro though...

 

[Acid Bath]

Thanks friend

 

[HerrHaber]

Thionyl chloride is actually not over hand for us in EU from Poland... but you must find the right person to mask and successfully send it overseas in a well protected ampule, in fact POCl3 is what you ideally want, but acyl chlorides are the ingredients for the old-school method and I doubt your purpose is experimental archaeology. Just read about the PyBOP method, some genius applied the scientific advances of SPPS to LSD and all work is done with stirring like 5 minutes and half an hour without heating all doable in one day with what I could call high yield... it's also what I wish to do, after all I became a chemist because of my first acid trip. Cheers!