Silk Road forums
Discussion => Off topic => Topic started by: 34trimethoxy on April 04, 2013, 05:18 pm
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Why I hate the question:
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“Is it hard to synthesize X”
Which I see on these boards all too often. Or "Is acid harder to synth then an NBOMe?".
LSD is magnitudes upon magnitudes immensely more challenging to produce then NBOMe’s (N-Benzyl-OrthoMethoxy), or phenethylamine based molecules in general.
Just compare the structures - one is a (relatively) simple phenethylamine skeleton, and the other a highly complex, chiral indole based molecule with amines, amides, Diels-Alder addition rings (which get messy fast), amongst many other accomplishments of chemical synthesis.
Even looking at them both from a retro-synthesis standpoint, if you've taken some years of organic, LSD will still give you a headache and a sense of "where the fuck do I begin?!" compared to its phenethylamine cousins.
The phenethylamines are silly easy to create in comparison. Precursors are of much less concern, and if they do come up as an issue they can be synthesized themselves quite easily.
Most LSD routes us E.T. or another ergotamine derivative, of which one-shoting in a flask is considered impossible, and itself very hard to acquire - and dangerous to work with (in that respect, most of the chemicals chemists work with are, like PCC). LSD also requires an inert atmosphere (usually Nitrogen).
It's not a dump and stir reaction like changing and alcohol to a ketone or even something like a palladium/H2 reduction from a nitro to an amine. The amide itself has to be formed from a multistep synthesis, either by reaction of a ketone or aldehyde with (most aryl ketones) with an amine to get an imine intermediate, and rearrangement to the subsequent amide there from acylation.
I really dislike when people ask questions like this - people think of chemistry as just adding two things into a beaker and demanding "cook!” It's not that simple at all. You have to recognize what you are doing in the lab, which takes practice - experience.
You need to know all of you reactions. You need to know that your retro won't work if you're trying to get that carboxcylic acid on a benzene ring via a Fridel-Crafts acylation (as I learned on an exam a long time ago - thinking I was all smart and had the answer down :D - how far I've come) - sure you can use an alkylation and get a methyl on first and then oxidize that to the acid, but this brings the inherent problems of over-adding the methyl group (the reaction over running).
I'm just trying to give an idea to the non-chemist the challenges of doing chemical synthesis retro-ly, working backwards, and the challenges that arise from them. You need to keep in mind what's going to direct Meta, what's ortho/para directing. What should be added to the ring first?
A lot of people like to add a nitro group and then reduce that to an amine. This is more difficult with an amide. You need a ketone to begin with just to get to the enamine and then reduce to the amide.
There's so much to this question. I hope I brought some clarity.
It’s also very important to know how to test your product – melting points, IR data (although we don’t really fuck with that much anymore), HNMR, CNMR, and mass spec in general. You don’t need LC/MS at all if you are a skilled chemist. All the tools are there for one to work with and get results if he is skilled.
I’ll answer any questions you may have, feel free.
In short - yes. 8) Chemical synthesis is not easy. ;)
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I know what mean, I get idiot questions, and I'm a non-expert, but a decent researcher. I had a friend ask me if his buddy could make LSD from HBWR seeds, after all, he could get concentrated LSA in the quarter/half gram range per 20ccs, how difficult would it actually be to isolate LSA and hydrolize it into almost-dry LAH? Would there be any problems assuming that very pure Diethyamine, DCM, PyBOP reagent, and POCl3 could be obtained, along with a chromatography column? it seems like an acid/base wash along with an alkaline lysis should be all you would need to get LAH. I know this method sounds improbable because of all the potential contaminants. Assuming one had an unlimited supply of LSA, would it be possible for people who have the resources, are experienced with extractions, but are not trained chemists? I get the feeling there are more than enough experienced chemists, and that the connections to get the lab-pure precursors and reagents are the real kicker here. Does anyone really grow their own Ergot? I've seen it for sale. I told my friend to tell his friend to give it up until he has a better handle on what he's doing, or can get someone with real experience to help.