What works for salicylic acid wont necessarily work for other substrates

While acetylation is still esterfication, traditional esterfication and acetylation are almost two completely different things, especially when talking about large molecules like salvinorin B.

When using small alcohols like ethanol, methanol, and small carboxylic acids like phenols and acetic, esterfication is easy. Just heat it up with a bit of acid, h2so4, or boric in that case (still is fischer), and you can get a product that you can distill. But when your alcohol is salvinorin B, size and electronics of the molecule play a crucial role.

Also, you have to keep in mind for those acetylation reactions, they are use HUGE excess of alcohol or acid in order to push the reaction to completion. In the ethanol one you linked, they reflux for 6 hours IN ethanol, so that is at least 100-500x excess. The equivalent might be refluxing acetic acid in 100 fold excess of salvinorin a But the reverse is just as true, you can't reflux in excess acetic acid/acetate. Clandestine attempts to produce heroin from morphine without acetic anhydride have been attempted like this for years.

the alcohol is a beta-keto alcohol, which delocalizes the alcohol's electrons making it an even weaker nucleophile, additionally, the salvinorin molecule is so huge it can be difficult for the the other molecules to get to the active site for the reaction to take place. Which by traditional methods, would require stronger heating or a stronger acid catalyst, which of course catalyze destruction elsewhere in the molecule (there are other methyl esters and a lactone you need to worry about.) In practice, it just doesn't work.

acetylsalicyclic acid itself is actually a weak acetylating agent, that would be a place to start. But its hard for me to imagine for the same reasons i outlined


also


I don't know if I even believe this one either, by basic theory it doesn't. And my bet is also that it doesn't. It might work but there isn't any literature that i can find on it in a simple search, can't always trust those guys on researchgate if they don't back up with sources

Thanks mindlusion. I get your points and they are compelling, thanks for all the details. Time to move on then, looks like one really needs access to acetic anhydride to grow S. potentillifolia for practical Salvinorin b to a synthesis.

What about MaNoMaNom's question (see below) regarding the other salvinorin b analogs in the original post? Any hope for the kitchen alchemist? As you probably know already, there have been human tests with salvinorin b synthetic derivatives.

if i get the chance to grow some of the potentillifolia i will DEFINITELY give it a go, maybe some novel analogues

as for the other analogues, all are common chemicals, but difficult to find or make outside a lab. Methoxymethyl ether (MOM) and ethyoxymethyl ether are common protecting groups, can be made from chloromethylether or dimethoxymethane, both common industrial chemicals but again not easy for the kitchen chemist. Potentially one could make dimethoxymethane from methanol and formaldehyde, haven't looked into the details of that process myself.