I've spent a lot of time this past week researching synthetic cannabinoids, particularly JWH-018. Despite my efforts, I haven't been able to find much on its synthesis. The simplest I've got so far is the following:

From Huffman's 'Synthesis of Cannabimimetic Indoles':
"The synthetic sequence is three steps from indole and the appropriate arylacetic acid. The first steps are N-alkylation of the indole and conversion of the acid to the acid chloride. Modified Friedel Crafts acylation, followed by purification provides the target compounds"

The general outline is...
Indole ---> 1-pentyl-indole
1-napthoic acid ---> 1-napthoic acid chloride
Friedel-Crafts with those two and you have 1-pentyl-3-(1-napthoyl) indole.
Recrystallize using ethyl acetate and hexanes

Would someone please elaborate? I'm not as much of a chemistry buff as I'd like to be. The more this can be broken down, the better. Perhaps it would be good to start with a list of ingredients and equipment required?

3-Indolyl-1-naphthylmethanes: New Cannabimimetic Indoles
Provide Evidence for Aromatic StackingInteractions with the
CB1 Cannabinoid Receptor
John W. Huffman,a,* Ross Mabon,a Ming-Jung Wu,a Jianzhong Lu,a Richard Hart,b
Dow P. Hurst,b Patricia H. Reggio,b Jenny L. Wileyc and Billy R. Martinc

Bioorganic & MedicinalChemistr y 11 (2003) 539–549



http://science.kennesaw.edu/projects/cab/BioorgMedChem-Huffman%20et%20al.-2003.pdf

you are correct sir there is one xquisite fragrance from which one can extract indole and i think you'll just love it.
it's called eau de human feces have a fine time extracting indole from this, no shit! and sorry about the puns just could'nt help meself.

.......naphthoyl chloride would be the least of your worries, ever messed with ethyl aluminum dichloride?? naaaasty stuff if you don't know what you are doing.

wtf......aaaah i'm on fire......my lungs are burning.....


you need it in like 1% solution in DCM.....  and that being otc, or readily available, nah.

check out msds 


http://cameochemicals.noaa.gov/chris/EAD.pdf

I remember researching OTC FCs extensively and realized that in order to be able perform the reaction with the original acid you'd need a superacid like triflic/tosic* or a superacidic clay. Alternatively, I recall a green chemistry synthesis of one of the compounds in the series (I think it was the morpholino substituent?), one could use ionic liquids, which are DEFINITELY out of reach for the clandestine chemist.

Jon: Indole FC reactions are almost universally selective for the 3 position; you need something special to select for another position. The most applicable variation on the aromatic amine alkylation is both tested and discussed extensively on blacklight where it was found not to work. The method involved microwaving a base, alkyl halide, and indole. Though doing a quick google will tell you that there are other methods that are also pretty easy (note: this ionic liquid thing is getting to be quite the problem!) and (to my knowledge) haven't been tried since that blacklight thread.

* A ref to get you started: http://www.erowid.org/archive/rhodium/chemistry/fc.acylation.tsoh.html

Skatole (3-methyl indole) which can found in feces would be of little use in synthesizing this class of cannaboids

Man, that's a baaaaaad idea.

The common synthesis goes from indole, they turn it to N pentyl indole and they put a napthalene ring on it with proper conditions. This goes with "good" yields, but it is made from pure reagents and not reagents what are made from shit.

The Skatole can be converted to indole, by halogenization of the methyl group, than hydrolyze it with a base to get the corresponding alcohol and than oxidize it to carboxylic acid what could be decarboxylized to indole... Direct oxidation yields a black tar with no indole in it. Looks great? Yes, I also think that.

So, you get the skatole from feces with a really little yield, after it you can turn it into indole with a bad yield and than you can start the JWH synthesis what is also a messy thing. Doesn't seems so good.

There is an easier way also.... Turn the indole 2 carboxylic acid at first to N-pentyl indole 2 carboxylic acid and turn this to the corresponding acid chloride and make a friedel crafts reaction with the naphthalene. Woala, JWH formed. The only problem is, that the naphthalene ring is not so easily reacted with the acid chloride, it is too stable. So you will need a better lewis acid than AlCl3 to get "good" yields.

So, think it again.