fentanyl analogs

[TYSON8888]

Hello, im new to this forum, and looking through the archives, i found a post referring to fentanyl analogs. The post was by drone and in the thread drone discussed posting an otc recipe, but  i asume it was never posted. Id greatly appreciate it if drone could post the recipe, or at least discuss it, all thoughts on this matter are very much welcomed.

[Rhodium]

The method was posted, and is archived at

https://www.thevespiary.org/rhodium/Rhodium/chemistry/dronefent.txt

There is no detailed step-by-step method posted though, and that is probably a good thing, as someone who is not able to synthesize the fentanyl analog from the directions given in that document is not an experienced chemist enough to handle a strong compound like that analog without risking poisoning/killing himself in the process.

[TYSON8888]

Well, considering you posted

Rhodium         [Image] posted 07-31-98 08:31 AM
   Administrator
                   [Click Here to See the Profile for Rhodium]
                   -------------------------------------------------------
                   When will we get a step-by-step "recipe" for the
                   production of OTC fentanyl analogs here? Such a text
                   would get a special place on my chemistry page. It is
                   always fun to change the world as we know it
I dont think it's an unreasonable question to ask, it would be very interesting, and i agree with you , it is very dangerous, more the reason to have a detailed method. Btw, if my post sounds snotty, I apologize, computers are very impersonal, it just comes out this way:)

[Rhodium]

Don't drag up things I wrote four years ago... I was almost fresh out of highscool back then, and the advice I give nowadays is somewhat wiser and more mature.

The main reason there is no step by step method written yet is that nobody has performed the particular synthesis yet. The activity of the compound was extrapolated from various SAR assays and its synthesis gleaned from at least a half-dozen different chemistry journals, and has not been put together to an optimized method yet.

[yellium]

Another problem with those super-active compounds is that it becomes a major pain in the ass to distribute, and that OD'ing is too fucking easy.

[Rhodium]

Distribute? Just make a millimole batch and make a solution of it to use for yourself (for the next few years or so).

Yes I know, anyone making the stuff would obviously distibute the stuff. I suggest the old idea of making a very dilute alcoholic solution of the fentanyl, and soak sugarcubes or blotter papers with it, if distribution is unavoidable...

[bicepules]

     Same advice swim gave the guy who wanted to transport his mdma crystals by dissolving in a solvent. Swim thinks the blotter and sugar cubes are played out.  Swim likes gingersnaps, more surface area and much more tasty than blotter.  Who doesn't like cookies?  
"No I'll tell you what insanity is, insanity is majority rules"

[Cyrax]

Since fentanyl is too potent for recreational use (ED50 = 0.0011 mg / kg), I suggest the synthesis of the open-chain analogue: 2,3"seco"fentanyl (ED50 = 0.35 mg / kg).  This minimizes the danger of ODing.

[Rhodium]

The Synthesis and Pharmacological Evaluation of 2,3 “Seco” Fentanyl

(https://www.thevespiary.org/rhodium/Rhodium/pdf/secofentanyl.pdf)

Abstract
A structurally novel, 2,3 “seco” analogue of fentanyl has been synthesized by a short and efficient procedure.
Central-analgesic activity was found to be ca. 30 times lower than fentanyl but still several times higher than morphine.

[LaBTop]

Where's that write-up from that guy who suddenly came out of the woodwork and declared he made a mole of some potent fentanyl derivative, and got quite pissed off when people started to doubt him?
He explained how he did it with all precautions in place, and succeeded.
That thread gone? LT/ (has it somewhere ona HD.)
WISDOMwillWIN

[Rhodium]

I think he said he used Siegfrieds writeup on my page.

[Cyrax]

I think that Siegfrieds procedure is a very elegant one.

One can easily modify it to get alpha-methyl fentanyl, 3-methyl fentanyl or sulfentanyl.  After some consideration, I think that is not very wise to produce the last two derivatives.

After the condensation of aniline with NPP you can also  use Zn / AcOH to reduce the imine (instead of NaBH4).  See procedure for 2,3 'seco' fentanyl.

I have a question.  What would happen if you used acetic acid anhydride to acylate the ANPP instead of propionic acid anhydride?  Would the product be active?

[Rhodium]

The N-acetyl analog is 14 times weaker than the N-propionyl (fentanyl), making it almost weak enough to handle without a glove-box.

[terbium]

The N-acetyl analog is 14 times weaker than the N-propionyl (fentanyl)
So, I would hazard a guess then that the amine intermediate prior to acylation is nearly inactive. If so, since acylation is the last step, purification should be done on the amine then the pure amine can be acylated in such a manner as to never require that the active, amide form be isolated from solution.

[Cyrax]

Terbium, you are right !!!

So, are the intermediates is the synthesis (NPP and ANPP) toxic?

[Rhodium]

Yes, definitely. I would expect no noticeable activity from the amine at all. The N-butyryl derivative is 1/10 the potency of fentanyl too, so propionyl is certainly the optimal chain length.

After the amine is acylated, it should be taken up in a non-polar solvent, and washed with base to remove propionic acid, the only materials left in solution should be Fentanyl and unreacted amine. They should be separable by column chromatography, by their varying polarity. The resulting fractions of fentanyl are then collected and quantitatively assayed.

But I guess nobody would bother with that separation, as I believe noone would have second thoughts about ingesting microgram quantities of a compound even if it would only be 75% pure.

[blondie]

i have seen a ref using Zn/AcOH  to reduce the n-subst-piperidone-aniline imine derivitive in place of NaBH4. is there any reason why Al/Hg cannot not be considered to reduce the imine?

[Rhodium]

Al/Hg is probably a viable alternative too.

[PrimoPyro]

Rhodium (or anyone who would like to comment) :

All active (read as potent) fentanyl analogs I've seen onlone and in The Designer Drugs Directory all have the propionamide function in the molecule. Coincidentally, this also happens to be pretty much the last step in the synthesis of these beauties (not counting salt formation).

I have been wondering, as it seems logical to me at least, if a synthesis of fentanyl or analogs is only dangerous in the final stages, where the propionyl group is added to the amine, and a salt is formed. What I mean is, the biological danger of fentanyl synthesis is not present until these stages where the active (potent) compound is brought into being.

This means that all the preceeding stages are normal lab procedure (although a few interesting chemicals are required, yes) and the final stages are the only ones where the extra extra extreme caution need be exercised, such as gloveboxes, etc.

I just wanted a 2nd and possibly 3rd opinion on this notion, if I could get one.

                                                  PrimoPyro
Vivent Longtemps La Ruche!

[Rhodium]

Yes, that's correct. The Fentanyl molecule without the propionamide function is completely inactive, so all the steps up to and including the anilinopiperidine are not dangerous, only during/after the acylation and the subsequent salt formation.