• N&PD Moderators: Skorpio | thegreenhand

Phenylpiperidine Opioids - how low can you go?

Is there any way to put that furanyl thing in the place of n-methyl in morphine? I think an n-phenethyl substituted version was 14x more active than morphine, so much the same SAR as with the piperidines.
 
Probably more healthy than krokodil...

YES.

I just cannot fathom why it's just F abalogues that are turning up. If U-47700 was sufficiently profitable then something with the reputation of being the most euphoric opioid on the planet would appear attractive. The methylfuryl moiety may confir too much sigma activity but the 2 N-ethylaniline analogue of ketobemidone hinted at in Opiates (Lenz et al) and detailed on the Eunoia Disc shows that in stage 1a trials at least, parenteral administration suggested that it was some x6.5 more potent and had the same set of side-effects. Given that 25mg of ketobemidone = 60mg of morphine (parenteral) suggests 15-16x M. Of course, it's synthesis is lower yielding but once again.... just what profit margins do these clandestine chemists want? Is 10000% still too small? I don't know.

The book by Lenz can be downloaded free by anyone. It only convers around 50% of the opioids on the Eunoia disc but it's still a MASSIVE storehouse of data.
 
'Healthier than krokodil'

And the award for understatement of the fucking year goes to..........=D

Although as far as I'm aware, desomorphine-D itself, isn't responsible for the horrific effects of that noxious shite, its all the corrosive byproducts and the poor workup of synth FAR too harsh for phenanthrene opioids (here I'm referring to the Nagai reduction, it's just too damn harsh.)

Been meaning to give it a go when I'm back on my feet properly (had a recent operation on one leg, still not up for too much walking), did get as far as alpha-chloromorphide, but that proved too interesting to test in its own right, so never got around to trying catalytic reduction with Pd/C in iPA to reduce the intermediate cleanly.
 
When a drug is more potent, less impurities can fit in a single dose... Much like how "light" low-nicotine cigarettes may actually be more unhealthy than the ordinary ones. But then it's more dangerous to handle if it's something like fentanyl with 100x M potency, and it probably has to be synthesized in a way where the final product is already a dilute solution when it is formed.
 
Sorry to slip this in CC Krokodil. I think Krokodil is about as low as it is possible to go.

Krokodil isn't primarily desomorphine. DOI: 10.1134/S1061934808040096 and a flurry of Tass stories has shown Kg blocks of the stuff being seized and three important things to note.

1) Compound 1 is deoxymorphine-D (Bentley's terminology) and thus the product (mixture of actives) could be considered as upto > x11 M.
2) More than one chemist/group has optimized their route (84-98% yield) and actually scaled it.
3) They appear to use an A/B workup on the raw product (not a B/A because non-phenolic compounds aren't removed) so solvent reuse.

I'm not entirely clear about the legal situation of deoxymorphine-D (compound 1) in light of someone seemingly trying to go for that product. It seems to me that making it harder to extract the codeine from the generic co-codaprin or co-brufen is the simplest move. Nobody wants to HAVE to invest but I would hope that manufacturers have at least considered it. Some very useful statistical data for the European scene here. http://www.emcdda.europa.eu/data/stats2017/ppp_en which suggests that Michael's idea of 2 qualities of H becoming the new normal (china white & brown smoking heroin) sold in a different manner and to a different demographic seems to be happening. White snorting heroin costing up to ?240 compared with just ?70 for smoking heroin, something that will retail at ?2000/g or more (T? closer to cocaine) per gram is going to attract the worst people. An entire house filled with cannabis for 3 months or a 24/29 set of glassware that fits into a box and is only used occasionally?

HR agencies are using fentanyl urine-tests as fentanyl tests but I have no idea if they will be able to detect the above compounds but anyone used to brown could end up extremely dead.
 
I'm not entirely clear about the legal situation of deoxymorphine-D (compound 1) in light of someone seemingly trying to go for that product. It seems to me that making it harder to extract the codeine from the generic co-codaprin or co-brufen is the simplest move.

Over here we have OTC codeine cough syrups, but they contain a lot of ammonium chloride which acts as a pH buffer - you would have to add a lot of NaOH in it to convert the codeine to freebase form and if you add a bit too much it suddenly raises the pH so much that it probably destroys the codeine.
 
Well basification with NaOH of the ammonium chloride would permit an equilibrium to be established between NH3(g) and NH4Cl/NaOH, which due to the volatility of ammonia, would permit it's being continuously removed, such as under vacuum in order to push things to the right, and avoid any sudden PH jumps. Plus the quantity of NH4Cl present in the mixture will be listed, won't it? it is an active ingredient? so one could not only remove it, but calculate the quantity of hydroxide required to displace all the ammonia.

Well, roughly at least, as NH4Cl and codeine aren't going to form a neat, precise, orderly line to wait their respective turns for a hydroxide molecule, but at least to a point one could get a fair idea of when to start basifying slowly, aliquot-wise with NaOH/KOH.

Clubcard, regarding extraction-resistant codeine products....don't encourage the buggers, they might actually do it. Depriving a lot of clandestine chemists who AREN'T half-arsed hacks in russian slums. I don't want to see it ruined as a precursor for everybody, just because of the trouble some individuals cause. What about people wanting to demethylate it instead, to create their own heroin, prope, or other morphine derivatives? why should everybody suffer for the actions of a few?

What needs to be done isn't fucking up precursors for people. It's been shown already that this does not work. Look at the crap the yanks pulled in their filthy little war, in the case of pseudoephedrine/ephedrine. Fouling up pills with all manner of crap, povidone, crospovidone mixtures; polyampholyte gakks that contaminate glassware and cause problems in acid-base extractions of all sorts by messing with the PH at which compounds enter polar and nonpolar phases, croscarmellose, you get the idea.

Has it stopped meth manufacture or use? has it bollocks, what it has done is to make it more difficult for the small timers who would likely be producing just their own, or to satisfy a group of comrades, and thus shift the balance of production over to the bigger, far more organized, well armed and vicious cartels who just import the pseudo from china, etc. and who, unlike mom'n'pop shop type cottage-enterprise meth manufacture and distribution, have little problem with chopping off people's heads, crucifying people, other nasty things of that sort.

And hey it hasn't even stopped enantiopure precursor being available on the smaller scale, just look at the likes of using brewer's yeast to convert benzaldehyde.

(and failing that of course, people extracting ephedra, or if they can't get the pseudo/ephedrine, just going via P2P routes, which are legion, and making racemic product.)

In the meantime of course, laws got passed restricting purchases, demanding ID, limiting number of sales/total weight of PSE per month that make it inconvenient and stressful for those who intend to use it medically, as it is sold for, and potentially even have people wrongfully convicted just for having PSE pills, sulfuric acid, NaOH and glassware in the same home, whether or not there was ever any evidence of manufacture/sale/use, (although of course, I view all drug convictions as wrongful, but you know what I mean)
 
For phenolic phenanthracine opioids (like morphine and desomorphine), the calcium salt is usually crashed out using CaOH and the solid added to saturated NH4Cl solution to precipitate the freebase but from the expert samples, non-phenolics turn up but they all bare a basic nitrogen hence my guess. Don't forget that codeine is itself a class B drug and thousands of empty packets is a bit of a give away and involving the kind of people who will go into smurfing is more or less ensuring that you will be spotted. 6-deoxymorphine-D is not in the MoDA and I suggest that since it wasn't covered by Russian law last time I looked, someone had caught on. It's just an analysis of data and a response that I keep on lots of trends so Michael can provide HR data because it can potentially happen anywhere in Europe. The last thing I am doing is providing a practical 'how to' guide. If it does become a chronic issue then test-strips and so on need to be designed.
 
Don't forget that codeine is itself a class B drug and thousands of empty packets is a bit of a give away and involving the kind of people who will go into smurfing is more or less ensuring that you will be spotted.

If someone were to convert the morphine/codeine into something a lot more potent, such as first converting it to desomorphine/oxymorphone and then putting something better in the place of the N-methyl, a very large amount of the precursor wouldn't be needed. Enough could be obtained even by extracting from unwashed poppy seeds. Probably easier than obtaining the phenethylamine, ethyl acrylate, sodium metal, etc. for fentanyl synthesis.

Edit: LC, the other ingredients in the codeine cough preparation will probably not make it difficult to extract the codeine if you have proper equipment, but it will make it more problematic for an amateur who's used to only extracting DXM and eyeballing a few grains of solid lye to add to the DXM medication. Also, I think the presence of the alkene double bond in codeine makes it more prone to be attacked by an overly alkaline solution than DXM is.
 
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If someone were to convert the morphine/codeine into something a lot more potent, such as first converting it to desomorphine/oxymorphone and then putting something better in the place of the N-methyl, a very large amount of the precursor wouldn't be needed. Enough could be obtained even by extracting from unwashed poppy seeds. Probably easier than obtaining the phenethylamine, ethyl acrylate, sodium metal, etc. for fentanyl synthesis.

Edit: LC, the other ingredients in the codeine cough preparation will probably not make it difficult to extract the codeine if you have proper equipment, but it will make it more problematic for an amateur who's used to only extracting DXM and eyeballing a few grains of solid lye to add to the DXM medication. Also, I think the presence of the alkene double bond in codeine makes it more prone to be attacked by an overly alkaline solution than DXM is.

No - illicit fentanyl is almost entirely made via the 'Seigfried Method' (DEA Microgram) so it's just 2 steps (plus workup). The precursors are items of commerce. Codeine is not a good starting material for potent phenanthracine opioids although several [POM]s are but even if you have them, it's a LOT of work. I mean a LOT. Yields and mechanical losses make it a pointless exercise. Desomorphine is about as far as it's feasible to go but that's quite far enough to pose a real threat and scaling that means smurfing thus a bunch of muppets WILL know or guess at what you are doing and will happily turn you in next time they are copped with a ?10 bag.
 
No - illicit fentanyl is almost entirely made via the 'Seigfried Method' (DEA Microgram) so it's just 2 steps (plus workup). The precursors are items of commerce. Codeine is not a good starting material for potent phenanthracine opioids although several [POM]s are but even if you have them, it's a LOT of work. I mean a LOT. Yields and mechanical losses make it a pointless exercise. Desomorphine is about as far as it's feasible to go but that's quite far enough to pose a real threat and scaling that means smurfing thus a bunch of muppets WILL know or guess at what you are doing and will happily turn you in next time they are copped with a ?10 bag.

Ok, I haven't really though about the practicalities of producing something like this... Maybe some kind of etorphine synthesis from thebaine would allow a production of a large number of opioid doses from a small number of opium poppies, but then you can't be sure whether the high kappa affinity of etorphine makes it less euphoric than more typical opioids.
 
No - 2 steps is about the practical limit with only certain LSD routes taking 3. The workup & mechanical losses make it hopeless. GIGO means it. It isn't like other things aren't possible but it's working out what items of commerce one can acquire legally and even then, making stuff covered by the MoDA is asking to spend 20 years in prison. That's the limit - items of commerce.
 
Who keeps the packets? Just burning the refuse on that scale out in the middle of nowhere will do the trick.

And smurfing needn't involve anyone else. Just someone patient enough to walk all round a city (or two or three) with a backpack, and do so a few times over a few months.

Patience keeps mouths shut, because there are none to do the speaking, save that of the chemist, who by nature, is not going to go squealing=D
 
Doesn't etorphine also have epsilon-OR activity? don't know much about the epsilon OR, but don't agonists strongly potentiate MOR agonists, like DOR agonists do?

That said, who the fuck wants to work with etorphine? and of them, who will survive it? and of their customers, who will survive more than a single dose.

Even fentanyl is more forgiving. Not sure for etorphine, but in highly opioid tolerant patients, the human dose for dihydroetorphine is just 2ug, orally.

(dihydroetorphine is used in tablet form in china for opioid tolerant patients doing a detox like we use methadone, it's made in 2 microgram tablets)

Quite surprised me to find that out, and no mistake. Knowing the way the chinese and other far eastern countries usually are regarding drugs, users, etc. I'm surprised they are so civilized as to allow detox at all, rather than just tying people to a lamp post and executing them by firing squad. Hell, burning at the stake wouldn't terribly surprise me.
 
That said, who the fuck wants to work with etorphine? and of them, who will survive it? and of their customers, who will survive more than a single dose.

As I said in some earlier message, that kind of compounds should in my opinion be made in a way where the product is immediately a dilute solution when it's ready. Let's say someone wants to produce carfentanil. The final step is to convert the carboxylic acid precursor to the methyl ester. So, you first dissolve a few mg:s of the precursor in 100 ml of methanol, add small amount of sulfuric acid, and reflux to form the ester. After that, add water and some weak alkali to get the pH to an acceptable value, distill off the methanol and you're done.

I hope this wasn't too much of synthesis discussion - after all it's more like synthesis harm reduction...
 
Smurfing might seem fun but it palls after a few weeks.

As for people who want carfentanil - they get the Chinese to make it for them. Swap the N-phenylethyl for an N-2-(2-furyl)-ethyl moiety and it's legal in China. Simple as. NOBODY in Europe is making anything more complex than fantanyl. If you have a lab capable of doing all of the above with the workups then it's much easier to go for something novel. There are totally novel ligands that are reliably active but the buyers know nothing. Wiki is the only data source which is why I presume that of the 800 articles I have added a patent to, 50% have had the patent removed.... with no history of it EVER being on the article. Often the Wiki rip-offs have the previous Wiki version so I know they are about.

OT people are aware of the commonality of the butyrophenone/diphenylbutylpiperidine neuroleptics and opioids? Janssen used the same scaffolds to find the QSAR of both.
 
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