Friday, March 25, 2011

Detailed Synthesis of JWH-018!!

URGENT: ONLY YOU CAN STOP THE CRIMINALIZATION OF JWH AND OTHER RESEARCH CHEMICALS

Do so by clicking this link! http://pvox.co/8ZJafX
JWH Vendors, Free Sample Requesters, Makers, Lend me Your Ears 

Go to  http://pvox.co/8ZJafX and click the comment button and take the time to make your voice heard before your alternatives are TAKEN from you WITHOUT A VOTE. Otherwise you may need to stock up.   DON'T Just click oppose- COMMENT SO THAT YOUR CONGRESSMAN CAN GET THE MESSAGE... Let them know how RETARDED the bill is.
 Go to this post for more info: http://noidsandincense.blogspot.com/2011/05/you-can-stop-criminalization-of-jwh.html


Now back to our regularly scheduled post ;-)

Disclaimer: The Following is for educational purposes ONLY. It was posted on a well-known forum, and I cannot confirm or disprove that it is accurate, but it appears to be. I am not responsible for any foolhardy attempts to replicate this exercise. Any attempt to replicate this should be done only be qualified professionals in a licensed lab. I make no guarantees as to the accuracy of this experiment. For all we know, this may be the irresponsible recipe responsible for hospitalizations and making it illegal in various jurisdictions. 


Quote Originally Posted by pyramid
Here is an example of alkylation to JWH-018, 1-pentyl-3-(1-naphthoyl)indole, MW 341.4

To a 250ml 3 neck RBF fitted with thermometer, condenser and a stir bar there is added 3-(1-naphthoyl)indole (3g, 11mmol) followed by dry DMF 50ml. Potassium hydroxide flakes (1.5g, 27.5mmol 1.5eq.) were added in one portion and the setup purged with butane. The flask was heated to 60-70 degrees C on a water bath for 20 minutes with stirring. A green solution with ppt is obtained. After this time, 1-bromopentane (4.3g, 28.6mmol) was added in one portion via glass syringe. There is an immediate color change to red and the flask is heated at an internal temp of 60-65 C for 3 hours. KBr ppts in the first few minutes after addition of the alkyl halide. It is then cooled to RT and diluted with 150ml H2O, and extracted with DCM 3x 40ml. The organics are washed with water 3 times then the solvent is evaporated. There is excess bromopentane as noticed by the smell so it is removed under vacuum in a hot water bath. 3g of amber oil was obtained (8.8mmol, 80% yield) The amber oil that remains is the product. It is a pain to get it to crystallize. Only after 1 month in the refrigerator did crystals begin to form. By covering them with a small amount of IPA cleaned them up and caused all of the oil to crystallize. Once you have a seed crystal the oil can be directly crystallized after alkylation, but I have had no luck getting it to crystallize right after without the seed or with ethanol. The obtained material is completely melted by 61 C, lit Mp is 60-62 C.

The product is fucking active and is obtained as beige to yellow slightly gummy crystals. It would be best to straight chromotograph the oil but not everyone can do that. :P

Huffman JW, Mabon R, Wu MJ, Lu J, Hart R, Hurst DP, Reggio PH, Wiley JL, Martin BR.
“3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB(1) cannabinoid receptor”.
Bioorg Med Chem. 2003 Feb 22;11(4):539-49.
Quote Originally Posted by meme
Shouldn't alkylation be done first? If only to eliminate the (mildly) acid pyrrole nitrogen from the Grignard? While it is not needed (indole grignards are routine chemistry), is there any advantage to doing that step last?

Also, all of the JWH compounds that the DEA has issued intent to control contain the napthoyl moiety, perhaps that would be best to "leave off." The naphthoyl group can be replaced with a LARGE variety of functionals, much more than the 1-position of the indole can withstand and retain psycho-activity.
Quote Originally Posted by pyramid
I do not know how it would effect the reaction by alkylating first, but the main reason for making the naphthoyl indole first was it opens up a few compounds that can be made directly from it. Now of course if alkylation first resulted in the product we want then I'd probably want to do it first, and this would not make a difference in the order of alkylation. It is worth a shot though, however I won't be attempting that soon.

Yes indeed most of these compounds are scheduled or soon will be so analogs containing other groups would be an excellent thing to research. A wide variety of analogs can be made with alkoxy-naphthoyl chlorides and finding synthesis options for many of the starting acids would be useful. What ideas do you have for replacement of the naphthoyl? I'm not super knowledgable in pharmacology affecting groups so not sure what to start thinking of in that regard. Keep in mind, this is purely at home chemical curiosity for me and I do not have EXTENSIVE knowledge yet.
Quote Originally Posted by meme
2-substituted phenylacetic acid compounds seem quite worthwhile (i.e. JWH 250).

Anthracene is another homolog of naphthalene which fits into this discussion.
Quote Originally Posted by pyramid
250 is definitely on my to do list. I'M also thinking of 4-methoxybenzoyl chloride, which following the same steps would give RCS-4. Am I right in assuming 4-methoxybenzoic acid can be simply turned into the acid chloride with the usual method? Then the main issue is acquiring the acids, but its not too hard.
Quote Originally Posted by Intergalactic Captain
A thread was posted under my SN on SMDB a year or two ago regarding a couple of potential ideas - Which were, for the most part, seen as either unfeasible or stupidly circuitous. The concensus, IIRC, was that huffmann's original and later routes were the quickest, cleanest, and cheapest; alkylate indole, then react with the naphthoyl (or whatever) chloride; indole + acid chloride, then alkylate...

3 reagents, 2 synthetic steps - How could it be easier? Well, try aquiring indole, napthoyl chloride, phenylacetyl chloride (substituted, etc), napthoylindole, etc... Or any common acid a-halogenation reagents for that matter, in quantities over 1-5 grams, as an individual... The quantity qualifier is important, as these reagents CAN be found, but at one hell of a "price of convenience" premium. Alkyl halides are a piece of cake, provided you can find the parent alcohol (and don't bother looking for n-pentanol or n-pentyl esters - Unless you get a COA, you've probably got iso or sec-amyl... I've found one source, expensive, but it's a cornucopia that doesn't operate on the quasi-legal side of the fence...Not gonna mass-publicize them)...

The goal here should be finding a way to AVOID huffman's routes - They're nothing special, nothing novel, just sophomore-level o-chem hoisted to infamy for the end result. Given an academic lab, anyone could do it - However, without that type of stockroom, where are we left?

...In summation, here's an idea, or a few that I've been tossing around... Phenylacetic halides are ripe for exploration and "relative" ease of preparation... Many substitution patterns are readily availabe as their benzaldehydes, acetophenones, and benzoic acids - These are all simple starting blocks for homologation to the phenylacetic acids and, (the caveat), the phenacyl halides... A few reactions to look up - Stephen reduction, and (Don't think there's a name for it, but it's patented) and one-pot from a benzoic acid to a benzonitrile via NaHSO4/Urea/Sulfamic Acid ... And the reaction of a benzyl halide with a cyanide... And probably countless others...

So, long story short, we should be focusing on the precursors (as it used to be?)... Short and sweet (minus the chromatographic separation), but that's only when one has the napthoyl or phenacyl halide - Perhaps those interested should be focusing instead on the preparation of acid-halide reagents, or a new route altogether (and forget grignards - I haven't explored EVERYTHING, but that nitrogen, alkylated or not, seems to fuck with just about any grignard or grignard-style organometalic couplings)...

New Legal DEA compliant Blends And how to synthesize JWH!

We have been seeing a number of blends and products touting 100% legal DEA compliance in recent days/weeks.

Most of these have a mix of any number of JWH 250 or JWH-081, JWH-210, AM2201, and even questionable ones like RCS4 and NRG1.

Look out for newer ones like JWH-307, others in the HU series that haven't been banned and others you have never heard of like JWH-011 and JWH-203. Look out for these new wonder JWH's and possible dangers/side effects- and feel free to report on them in the comments!

And for those of you wanting to synthesize JWH yourself there is a website I've found, run by some folks in China with their own private lab- with pictures of the lab and stages of production on their site. They claim that you can synthesize jwh "in house" and from the pictures on their site of the lab, it looks as though you can do so- albeit with questionable reliability/safety/accuracy

They also claim to sell:
"- The list of substances for production JWH (all) and MDPV (all substances aren’t prohibited by the law)
- A complete management to use + video
- As you will get constant support from our employees + a discount for ready substances
Cost: The price individual (write on an e-mail: support@fitaniumwf.com)

For production JWH (all) and MDPV we will give all necessary substances to you (All necessary documents and licenses will be applied (for customs)).
After purchasing of technology of synthesis you can make JWH (all) and MDPV in house conditions.
"

They take wire transfer as payment, of course. It appears to this blogger that they may actually be legit, although you may question their procedure/understanding of the products. The only way to find out is for some brave soul to contact them at the email above, and ask about synthesis (Try asking about 081, as it's universally accepted as relatively forgiving to researchers and probably one of the easier ones to synthesize). 

If you do get any satisfaction, answers, or responses, PLEASE post them here in the comments, so that we can list them as confirmed to be a legitimate supplier and lab for JWH, or a con.

If anyone brave decides to go for it, please let us know, 
A) How much do they charge for products and synthesis technology? Hundreds? Thousands?
B)  What do they send you exactly? Equipment, lists, (EASY) instructions?
C) If legit, how much skill/danger is involved? Safety/accuracy/reliability of instructions etc.
D) What impurities and problems are involved? What chemicals are required and how easy is it to produce/get them
E) How professional is their service? I.E. Is it some weak instructions; complicated details lost in translation, or sub standard anything?

F) How likely is it for the average joe to learn to make the stuff?


Tuesday, March 1, 2011

Well, the JWH Ban is Finally HERE...

But what of the other jwh varieties not specifically included in the DEA's temporary ban of jwh-018?

What of jwh-210, jwh-081 and jwh-203 and jwh-398 and all those other numbers that go in between 1 and like, what, 400?

Will the other jwh cannabinoids be considered analogs, and if so will that hold up in court?

What of AM-2201 and all the other various cannabinoids?

JWH is a powerful industry thanks to media hype, so will it stay? Perhaps. Let's hope that whatever happens it will be in favor of personal freedom and choice.