Heroin funds terrorism, Fentanyl is poison, both are illegal - the middle way?

[clubcard]

Just today a friend, an Afghan HR worker was nearly killed in a bombing in Kabul. On one hand The Taliban (enemy of the US) are the Mujahideen (supported by the US) and in both cases, heroin pays for the weapons - so don't forget that the US government cares more about proxy wars than organized crime (The Taliban ARE a form of organized crime). The world has now been blighted by ever more dubious fentanyl analogues with so many companies in China & India supplying these technically legal poisons. Cayman Chemicals is a HUGE supplier and my only thought on this is that I know, so does the DEA. Just why they carry on unmolested I don't know but I'm sure many theories exist. One might be that 3-F fentanyl isn't covered by the UK MoDA and I suspect continually changing novel agents doesn't give a window to launch a large legal action.

The question is, are all opioids equally dangerous? We have the figures:

TI (LD50/ED50)

Methadone - 12
Meperidine - 28
Morphine - 76
Fentanyl - 300
Sufentanil - 25000

Professor Helmut Schmidhammer carried out QSAR studies on a whole host of phenanththracine derivatives with truly huge TIs. In fact, several examples show a ceiling to the respiratory depression. In addition, BIMU8 has been shown to reverse the respiratory depression caused by etorphine and carfentanil but even without that, we truly can produce opioids with an ED50 around that of etorphine and the LD50 around that of codeine. Imagine - you could eyeball something and while yes, you will pass out (with the attendant risks) but you won't stop breathing or inhale vomit and turn blue.

About 6 years ago I ran a large training set that included allylprodine, 14-cinnamyloxycodeinone, Sufentanil, 14-MeO metopon, 14-phenylpropoxymetopon, the etonitazene derivative ((2S)-2-(4-methoxyphenyl)-2-{1-[2-(diethylamino)ethyl]-5-nitro-1H-benzimidazol-2-yl}ethanamide), (1S,4R)-4-dimethylamino-4-(4-bromophenyl)-1-[2-(furan-2-yl)ethyl]-3,3-dimethylcyclohexanol (BDPC derivative), Ro4-1539, etorphine, 8-Carboxamidocyclazocine (and the substituted amides listed in the work of Mark P. Wentland), 1-[1-(furan-2-ylmethyl)-4-(3-hydroxyphenyl)piperidin-4-yl]propan-1-one (with 3-(1,3-dimethyl-4-propylpiperidin-4-yl)phenol - ring-substitution of ketobemidone yields an agonist & antagonist isomtric pair which is why no papers list the potent derivatives), N-[(2R)-1-(3,3-dimethylpiperidin-1-yl)propan-2-yl]-N-phenylacetamide (overlays α,3-dimethyl fentanyl. If you were going to put a 3, put a 3,3 for x2 activity), Tlidine, 1-{1-[(1S)-1-(furan-2-yl)ethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one, N-(3,3-diphenyl-4-oxohex-1-yl)-7,8-benzo-3-azaspiro[5.5]undecane

and padded it out with a large series of potent but quite unknown compounds (see Opiates by R. Lenz et al). All of the above is in the work of Lenz and/or other references provided.


Here are some useful links so you may check my work and correct and improve it:

https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1958-01-01_4_page007.html
http://www.pnas.org/content/pnas/73/11/4215.full.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137165/
https://encrypted.google.com/patents/DE60026883T2?cl=de (look at references cited)
https://patents.google.com/patent/US3464994
Prepn: Ziering et al., J. Org. Chem. 22, 1521 (1957); Lee, Ziering, US 2798073 (1957 to Hoffmann-La Roche)
US4960788 (Pyrrolidone-2 compounds and their use for central analgesic activity)
RTI-4614-4: An analog of (+)-cis-3-methylfentanyl with a 27,000-fold binding selectivity for mu versus delta opioid binding sites (Life Sciences Volume 48, Issue 23, 1991, Pages PL111-PL116)


Anybody who would take the time to download CHARMM (J Mol Model (2011) 17:477–493 gives details on how to apply 3D QSAR to the named compounds) can do the same as me.



But my own 'I like to draw random molecules) isn't random and is provided in SMILES for easy import (and preventing idiots copying and using the structure).

O[C@H](CN3CC[C@@]24CCCC[C@@]4(OC)[C@H]3Cc1ccc(O)cc12)c5ccco5

So, why the above? Well μ2/κ3/δ agonism (with sub-nm affinity) provide huge potency but more importantly, the agent is a δ partial agonist and a κ1/κ2 antagonist so respiratory depression is vastly reduced. If you look at the UNODC link and the references you will see that Janssen produced a series of lengthy papers on different classes of opioids with the ED50 & LD50 being amongst the most prominent pieces of data. Would anyone be surprised that the LD50 of Ro4-1539 is actually slightly HIGHER than levorphanol (increase MW)? So that's a x60 increase in the TI right there. I'm sure everyone has taken a good look at the metopon data and already know of the circa 2500 TI. This isn't some secret. This is research from world class teams with huge amounts of experience and papers with tremendous impact factors.

Can I state on pain of death that the material is benign? Well, I would be willing to IV 10mg of it and considering it's about x3400 morphine, by rights that should kill me outright but I'm prepared to take what I consider a pretty low risk test.

The next, obvious point is 'how the hell can that be made! Reaxys lists 11 steps! It's pie in the sky, idiot, nobody CAN make it!'

Not so. A combinational route from legal, commercially available precursors is a total of 6 steps. Not 1->2->3->4->5->6 because that would still be crazy. 1->2->3 & 4->5->6 ===> 3+6->7->8 i.e. 3 x 2 steps. We don't discuss synthesis on this site for a host of very good reasons. I think I can reasonably state that the key step is dequaternization of an amine using sodium thiophenolate.

Have I sampled this one? No. Have I sampled some of the novel high-potency ones? Yes. Back when it was all 100% legal in the UK. I don't break the law. That is my thing. I don't thrill at outsmarting the police and security services. I just don't break the law and that really, really does piss them off. Have I made bad decisions? Yes. Just 1 but people were harmed and I had a nervous breakdown. 1 person harmed is 1 to many for me so I have I hope been honest and even-handed while echoing the words of Dr. Dave 'BE CAREFUL'.

 

[clubcard]

BTW will everyone cut-n-paste the above to a local device. NO, I'm not babylon but I am aware that the Karma Police software is slowly removing data from places like Wiki. I spent 2 years with Reaxys adding the original patent data to EVERY psychoactive and now it's gone... and if you look back, it never EXISTED i.e. they have hacked Wiki so you cannot look backwards. When the Novichok attack happened, all of the old posts (including the CAS I added) disappeared and had never been... every old version was identical to the latest version...

So, if enough people know the answers (and I've been posting on every class you will note) then a whole generation (of safer things) will occur and by sheer dent on novel scaffolds, the DEA loses. I don't want to see people being killed or dying over heroin (see above) or cocaine (posted legal 1-step coke alternative on nocaine thread). Choose to think I'm an idiot but please make sure that the data remains extant.

And for those who asked, yes, there are 2 sources of the Eunoia Disc & can PM you. Delia Venus Wyn is credited on the thing but who the hell she is I don't know.

 

[Limpet_Chicken]

You should re-up the novichok data clubcard. Re-up it and not only that, take screencaps and screencaps of edit-revisions, as well as alerting wikipedia itself, so they can do something about that. That way, if you have definitive proof, you can shove it in the faces of those who would censor the information and PROVE that nefarious parties have been jewing with the data.

 

[clubcard]

You should re-up the novichok data clubcard. Re-up it and not only that, take screencaps and screencaps of edit-revisions, as well as alerting wikipedia itself, so they can do something about that. That way, if you have definitive proof, you can shove it in the faces of those who would censor the information and PROVE that nefarious parties have been jewing with the data.

Done - I have a STACK of footage and so do a couple of journalist friends. Nothing private goes into any digital media EVER. Pencil, paper, 1-time pad is how to use a cut-out to order stuff.

 

[arcarsenal]

Can you explain this hack and this 'KarmaPolice' you are talking about? I've been out of the loop for a while, and this seems important...

 

[clubcard]

https://en.wikipedia.org/wiki/Karma_Police_(surveillance_program)


Everything you post, every E-mail you send, every search result - it is ALL monitored and edited. I've sent E-mails that never arrived, searches for items I PUT ONTO THE WEB that don't yield results and posts even on here that don't appear...

 

[emkee_reinvented]

Thank's for gathering this clubcard, and for Brian Jones Massacre never heard of em. Hope you have opened a few more eyes on the Big Brother era we are in.

I have not much to add, but love to try some orallly effective opiates. Tilidine or Dextromoramide just to fullfill my curiousity. To bad painkillers are rarely prescribed over here, ain't even an OTC product containing codein in useable ammounts. So it's Kratom, Heroin or buying Metadone from an addict when one serioulsy needs a fix. The last 2 not being a option IMO that leaves Kratom for toothaches.

 

[Limpet_Chicken]

The really low dose codeine or dihydrocodeine products are still usable (here its 8/500 codeine/APAP or 7.5mg DHC/500 APAP) using cold water extractions, and at least in the case of DHC, it can be extracted and made into more useful things if not used directly.

 

[emkee_reinvented]

Codeinefosfaathemihydraat, 0,5 mg per ml sirop, on the product information. The drug bible "Pharmacotherepeutical Kompas', great naming, used by the docs over here says 0,39mg per ml. I assume they count only the codein part and abstract the phosphatehemihydraat, I could be wrong though but you pick up a lot of information on this site:

Bronchicum Extra Sterk Natterman (als fosfaat) OJG consumercare bv:

Strenght
0,39 mg/ml
ammount
100 ml, 200 ml
contains ethanol 10 mg/ml. And per ml: 280 mg honey, 270 mg saccharose and 140 mg glucose.


The other OTC option:

Melrosum Extra Stenght Natterman (fosfaat) Vemedia bv
form sirop, again.
Strenght
0,39 mg/ml
ammount
100 ml
contains ethanol 10 mg/ml. And per ml: 280 mg honing, 270 mg saccharose en 140 mg glucose.


In Belgium OTC sales of codeine, ethylmorphine and dihydrocodeine tablets were stopped in 2012, France followed in 2017. So be prepared the last I know was before I would even have thought about it, the OTC codeine tablets in the Netherlands were restricted OTC available. You could buy one pack of 30 tablets of 10 or 20 mg every 6 months. I read that after OTC sales completely ended. If this is a trend your island is next.

 

[Limpet_Chicken]

We still have a few OTC opioid meds. The strongest are the cough syrups (codeine linctus, codeine phosphate 600mg/200ml, J.collis Browne's mixture (20mg morphine/100ml bottle), terpin and codeine linctus (1mg/directed serving stronger than codeine linctus, tastes like shit, full of pine oil, its like sucking on an air-freshener) and the other one, is Gee's linctus, reasonably strong, tincture of opium-based)

Then there are co-codamol and variants, 8mg/500mg APAP, paramol-7.46mg dihydrocodeine tartrate/500 APAP, and a higher strength ibuprofen/codeine tablet formulation, never used them, can't remember how much codeine is in those. And one other liquid, pulmo bailly, codeine/guiacol in liquid form, tastes fucking awful and it stinks to high heaven and the bowels of hell both.

Mainly interested in the DHC myself though, its hard to find codeine or terpin and codeine now, and also hard to find Gee's linctus, although the pulmo bailly stuff and J.collis Browne's mixture are both widely sold. Will take the codeine or Gee's linctus if I can find them, I still know one place that does Gee's linctus, although I have to go to the city center to buy it (I presume that isn't classed as sourcing, given it doesn't name anywhere more than 'the center of a city'), otherwise its the DHC I'm interested in, since it can be demethylated and esterified in a single reaction, using 30% anhydrous hydrogen bromide in glacial acetic acid once extracted in a CWE, taken up in a suitable solvent as the freebase, the solution dried over anhydrous sodium or magnesium sulfate, filtered, the drying agent washed with a little more solvent and then refluxed in the HBr in GAA. The HBr selectively cleaves the methyl ether at the 6-position, whilst with HBr being a strong acid, its able to catalyze the Fischer esterification of the newly formed dihydromorphine intermediate, with the GAA used as solvent, forming 6-monoacetyldihydromorphine in excellent yield (95% or so) of 6-monoacetyldihydromorphine, then using methanol to strip the GAA as methyl acetate via vacuum distillation.

Might not be much DHC per pill, but with boxes of 32 tablets, and 40-50 boxes, accumulated over time, then it mounts up.

 

[sekio]

This is bordering on synthesis discussion, but I must mention that the demethylation of DHC only works in acetic acid (no other solvent). Acetic acid is used because the conjugate acid of H2O limits aqueous HBr's acidity.

And, of course, if DHC is not availiable it can be "easily" made by CTH of codeine.

 

[Limpet_Chicken]

Presumably it would work in other neat carboxylic acids, as long as they are liquid in consistency at 90-100 'C though (E.g propionic acid)...something that will have to be tried, given the rather special nature of dipropionylmorphine, I should think 6-monopropionyldihydromorphine plus a little dihydro-prope dope as side product would be quite something, given how intense and euphoric 6-AcO-DHM is.

GAA is also present not just as a solvent, but to provide the carboxylic ester group though, which couldn't happen even were HBr acidic enough in aqueous solution, you can't very well have a hydroxyl ester of an alcohol or phenol now can you?

 

[clubcard]

The dibenzoate ester is simple because it's BP is well above that of water driving it to the right. Removing product is the key-step so I won't be going into that one.

sekio - there is a very simple catalyst mentioned in a patent by David X. Wang (got to be a fake name, surely?) that appears to allow more readily available solvents. I believe 22% HBr is the ideal. Since nobody is going to acquire enough DHC to make it useful (mechanical losses being what they are), it's not practical. Interesting perhaps, but when buying the product is cheaper than making it... who would bother?

 

[emkee_reinvented]

Did he say something about bordering synth discussion.

It keeps amazing me how much you both know on this subject, and oh did I miss out on the OTC stuff, I was in paris before 2017.

Codeine ammount in our sirop 78mg vs 600mg's in your"s. The morphine and Opium version's sound tuff but are actually less effective I as I understood. Oral Morphine would require a more hefty dose to equal 600mg's of Codein I presume.

 

[sekio]

Actually, what I said earlier was incorrect, of course you can use aqueous HBr to demethylate DHC too, it's just much tougher to isolate the shite from the black goo you'll make. And a slower reaction.

 

[clubcard]

Actually, what I said earlier was incorrect, of course you can use aqueous HBr to demethylate DHC too, it's just much tougher to isolate the shite from the black goo you'll make. And a slower reaction.

DXW's work avoids... but why would someone scrabble together the DHC when cost makes it so.... well, costly? I guess applying one of his papers and then the other you get x7ish M but the cost goes up AGAIN. I love it, it's all possible... just pointless I read with eye to check we wouldn't be seeing this. We haven't.

 

[Limpet_Chicken]

Anyone got a link to that paper? or at least a DOI number?

As for the product itself..why would someone make it? because its euphoric as hell, and packs a fuck of a rush, real knock your socks off stuff.

And wouldn't be seeing this? don't bet on that

 

[clubcard]

It's in a patent - one you have.

 

[sekio]

Club, the person in the patent is Peter X. Wang, not David.

Limpy, try US4667037 for a "rate-enhanced" demethylation, this patent is for the synthesis of nalbuphine but presumably is close enough.

I'm pretty sure the anhydrous-HBr-in-carboxylate is superior in a few ways, both in terms of rate of reaction, producing a "more active" product with better BA, but also better recovery of a cleaner product... HBr in AcOH or CH₃CH₂COOH can be removed by evaporation easily whereas aqueous HBr requires extraction with halogenated solvents.

 

[clubcard]

Club, the person in the patent is Peter X. Wang, not David.

Limpy, try US4667037 for a "rate-enhanced" demethylation, this patent is for the synthesis of nalbuphine but presumably is close enough.

I'm pretty sure the anhydrous-HBr-in-carboxylate is superior in a few ways, both in terms of rate of reaction, producing a "more active" product with better BA, but also better recovery of a cleaner product... HBr in AcOH or CH₃CH₂COOH can be removed by evaporation easily whereas aqueous HBr requires extraction with halogenated solvents.

I do apologize sekio. I look quite the fool.


I remain incredulous of the fact that neither α-chlorocodide (or dyhydro of?) nor dihydrothebaine (or tetrahydro of?) has turned up. The former needs a reagent that needs an end-use form (when in bulk, I presume, I didn't for 1L of it) while the latter uses 'the ecofriendly methylating agent' as I believe the sales patter goes. I think I speak for us all when I say that alkylating agents are a double-edged sword. While I enjoy convenient methylation of N & Os, I'm not keen on those N & Os being my body or the autoignition of the alternatives :-D

Peter also deals with that rearrangement that has excited the minds of people who can buy boxes of co-codamol [P]. The original German based yield on BRSM and I've read a dozen further patents where the eternal triad of 'reduce then oxidize' vs 'oxidize then reduce' vs 'rearrange'. I enjoy reading patents where the commercial importance means that managers grudgingly give the chemists a sliver of the pie that the marketing division doesn't like dividing. Incremental efficiency fought in the realm of chemical engineering.

I'm of the opinion that phenolic (or bioisostere) opioids are the better bet. Janssen wrote 7 or 8 volumes (Scribd) each on a different class of opioid and the phenanthracenes are the original and still the best. There comes a point (at under x10M in my opinion) where adding potency decreases euphoria and the % profit doesn't keep on increasing so much. While we may use potency as a metric, I think TI should be adopted. We now appreciate the different types and subtypes of receptors and understand why certain moieties increase activity and/or decrease acute toxicity but it's still a market being taken over by phenylpropanamides - and those with a lower TI I note. CC are now offering 3F-fentanyl which sits outside the MoDA and norsufentanil which sits outside US law (as I understand it). While sufentanil is a step in the right direction, we do know of compounds with truly gigantic TIs as well as sufficient grunt that it isn't going to harm the pocket of the average Mexican narco-terrorist.

Do you think it's arrogance, ignorance, indifference, incompetence or avarice that has meant that the average street H is more likely than not to have a fentanyl derivative in it? I would have thought that people NOT ending up in A&E or worse would be a pretty good way of keeping a low profile but it doesn't seem to be a consideration. I see that in the US mandatory minimum sentencing for fentanyl precursors is being enacted but I am left wondering when someone will write 'The Siegfried Route: The Next Generation'. Microgram has traced back the entire fentanyl crisis to a 300 word 'recipe' from 1997. But then they have also said 'it's all coming from China' or 'it's all coming from Mexico' or 'It's all coming from Canada' or 'It's cooks within the US' or whatever is politically expedient for that day of the week.


Now I remember why I posted (beyond the apology). I found a neat blog: http://brsmblog.com/