Diacetyldihydromorphine (Improved Diamorphine/Heroin analog)

[Dextro .45]

Diacetyldihydromorphine (also known as Paralaudin, dihydroheroin, acetylmorphinol) is a potent opiate derivative developed in Germany in 1928 which is rarely used in some countries for the treatment of severe pain such as that caused by terminal cancer, as another form of diacetylmorphine (also commonly known as Heroin). Diacetyldihydromorphine is fast-acting and longer-lasting than diamorphine, with a duration of action of around 4-7 hours.[1]

Diacetyldihydromorphin

This would be the ULTIMATE Heroin opioid in pharmaceutical glass ampoules for IV/IM/SC injection Germany has the best drugs on earth…..it’s Faster acting & Longer lasting than Diacetylmorphine (Heroin) Some professional pharmaceutical laboratory could synthesize this molecule like one would bake a cake 100% purity in a multi use glass 60ml bottle 100kg (220 lbs) of pure API compounding HCL powder in a large secure drum/container in a dark cold cellar I would LOVE to inject pharmaceutical grade powder of this with Pharma Cocaine HCL Why hasn’t this amazing Diamorphine improved analog not been illicitly synthesized and available for bulk purchase

 

[Dextro .45]

Dibenzoylmorphine is an opiate analogue that is a derivative of morphine. It was developed in the early 1900s after first having been synthesised in 1875 in the UK by the CR Alders Wright organisation at Bayer, along with various other esters of morphine, but was never used medically, instead being widely sold as one of the first "designer drugs" for around five years following the introduction of the first international restrictions on the sale of heroin in 1925. It is described as being virtually identical to heroin and morphine in its effects, and consequently was itself banned internationally in 1930 by the Health Committee of the League of Nations, in order to prevent its sale as an unscheduled alternative to diacetylmorphine.[1] However, it still continues to occasionally be encountered as a result of home manufacture from morphine by drug users.[2]

Another amazing ester of the Morphine alkaloid …..I should’ve went to university and got a doctorate in organic chemistry and pharmacology. With a professional pharmaceutical laboratory and unlimited access to precursor chemicals, opium alkaloids and every single CII controlled substances known to man

Making the purest of the purest API salts to administer anyway I saw fit

 

[AlsoTapered]

Actually no, tests show that 6-MAM (6-monoacetyl morphine) is the active metabolite in heroin and when you remove the 7,8 double-bond, de-esterification happens faster. Dihydromorphine IS longer acting but in this case esterification was to make dihydromorphine more soluble.

The 3,14-diacetyl derivative of oxymorphone is noted to be x4 more potent than the parent drug - try looking around there.

 

[G_Chem]

I’ve tried 6-benzoylmorphine and its dihydro cousin. My experiences for both can be found on here.

I found 6-benzoyldihydromorphine to have a stimulating opiate effect very much resembling oxycodone, also less histamine release. Regular 6-benzoylmorphine was pretty much like heroin but with less rush and longer legs.

I’m honestly surprised we don’t see benzoylmorphine more with how easy it is to make.

-GC

 

[AlsoTapered]

Dibenzoylmorphine was trialled in UK hospitals and was considered to have almost no clinical advantage. The ONLY advantage was that those 2 benzoyl groups increase the MW of the drug so much, weight for weight it was the same potency as morphine... oh, and I presume it's onset was faster.

I'm looking for the reference for you right now.

 

[JackARoe]

Does one need poppys to create Diacetyldihydromorphine? If not why the &$&% would street dealers resort to fentanyl and zylazine? (I know strength, but xylazine does not fit what people want from the street) Seems this would be a good street drug for the upper distributors to make. Unless poppies are needed.

 

[G_Chem]

Does one need poppys to create Diacetyldihydromorphine? If not why the &$&% would street dealers resort to fentanyl and zylazine? (I know strength, but xylazine does not fit what people want from the street) Seems this would be a good street drug for the upper distributors to make. Unless poppies are needed.

Yup, it would most likely be synthesized from morphine. The highest yield is to first do the esterfication followed by the hydrogenation, doing it in reverse will create more impurities.

Fentanyl is so common because it doesn’t need poppy alkaloids to make.

-GC

 

[AlsoTapered]

But dihydromorphine is a commercially available compound so why would you go via a 2 step route?

I'm also interested to know what impurities you think hydrogenation of morphine forms. Please don't get me wrong, I'm not disputing what you say, I just don't understand it. In nations like Japan ONLY dihydrocodeine and dihydromorphine are used. Codeine and Morphine are just not in use - that's why their is a large commercial supply. Why would dibenzoylation of that be an issue?

I DID look but couldn't find any references.

It does make me laugh that PharmaCompass shows that legally produced morphine costs x8 the price of that from Afghanistan Sure, the legit stuff WILL be purer, but x8 seems a BIG profit margin.

For contrast methadone is $680/Kg...

 

[G_Chem]

I’d have to dig through the refs when I have the time. Years ago I researched this extensively and that was what I found.

And you can do the esterfication on the dihydromorphine all the same with still fairly decent yields and purity but not quite as good as the other way around. Let me look quick, I have a rough idea of what ref it might’ve been.

Another interesting note, the hydrogenation doesn’t need any pressure.

-GC

 

[AlsoTapered]

I’d have to dig through the refs when I have the time. Years ago I researched this extensively and that was what I found.

And you can do the esterfication on the dihydromorphine all the same with still fairly decent yields and purity but not quite as good as the other way around. Let me look quick, I have a rough idea of what ref it might’ve been.

Another interesting note, the hydrogenation doesn’t need any pressure.

-GC

Yeah - I know you don't state things without a solid foundation but I didn't know about this and I cannot figure what the impurities might be. The 6-OH could be reduced, I guess. now THAT WOULD be a lot more potent (desomorphine). Why not look at patents of DHM synthesis to see if the 6 is protected - that would make a strong case.

But MAYBE your reference is from long time past (DBM was first made in 1926 when chemistry wasn't so well explored) because I know DHC is made directly from codeine in something like a 97% yield and I think the 3% is just unreduced codeine....

I guess dimers would be possible.... if I remember the pre-WW2 papers I vaguely remember are correct.

 

[JackARoe]

But dihydromorphine is a commercially available compound so why would you go via a 2 step route?

See that's what I am talking about!! LOL Careful AT2, too much technical detail is not condoned here. But I can tell that you would whip it up in a logical way.

But here is the thing. Fentanyl needs to go. We have future children we need to think of. People that are still 10-20 years away from the street dope still. But wouldn't it be nice if the path was set that street dope goes back to opiates for them. Not strong synthetic opioids. People are going to use something. Make it safer. So I often wonder if any of these can be made in a labratory like fentanyl. I don't need the details though. lol

 

[AlsoTapered]

If the only opiate on the market was opium, things would be MUCH safer.

Ironically, sufentanil (x5 more potent than fentanyl) is a lot safer. The TI for fentanyl is 270, for sufentanil 15700.

Like the atom bomb, you cannot uninvent fentanyl and next the nitazense and I could just keep going. There are tens of thousands of chemicals in the potency range of fentanyl. That's why I destroyed my thread on the PMDPP class. It turned out to be even easier to make and was some x30000 M.

NO WAY do I ever want to be known as the guy to make that stuff known to clandestine chemists,

If it's too potent to eyeball, it's too potent... but a standard strength opium on the market would, I believe, have a great impact on opioid deaths. Yes, you could eat a matchbox sized lump of it and OD, but smoked it's impossible.

 

[sekio]

I actually have a lot of experience with this particular drug (dihydroheroin / diacetyldihydromorphine) simply because I found it was actually easy to make from codeine in high yield thanks to this paper, and I happened to work in a lab during the day (which I had access to on off-hours).
For the specifics on the synthesis, check out this post.

The quick version is, T1s are extracted with a modified CWE, the caffeine removed with DCM, and then basified and extracted with ether to yield pure codeine.
Then it is hydrogenated using catalytic transfer hydrogenation with ammonium formate (or whatever your favourite H₂ source is) to dihydrocodeine in quantitative yield. (Codeine is too acid sensitive for a good demethylation.)
Finally, the dihydrocodeine is reacted with a slight excess (2.5mol) of (anhydrous) hydrogen bromide in glacial acetic acid, which simultaneously performs three reactions: it forms the HBr salt, it demethylates the methyl ether to a phenol and methyl bromide, and it catalyses ester formation with acetic acid.
The end result is an almost quantitative conversion of dihydrocodeine freebase into (functionally) dihydroheroin hydrobromide. (The major product is actually 6-acetoxy-dihydromorphine, which is the active metabolite of dihydroheroin anyway, and produces comparable effects)

I found it to be a close analog to "real" heroin, which unfortunately was a rarity at the time I was attempting this. That said, for a tolerant opioid user, 50-100mg IV was a pretty solid high, and a habitual fentanyl user friend of mine almost OD'ed off of IVing 300mg at once. Generally speaking, the few opioid-using people in my friend circle at the time thought pretty highly of it, given this was during the rise of fentanyl in dope. One enterprising individual even used it to make fake "lean" (corn syrup, water flavouring mix, diphenhydramine, and dihydroheroin - he was previously using real codeine but when he realized he can use 1/20th of the amount of material with dihydroheroin it was no question), which I'm told sold well (he even bought a bunch of "official" cough syrup bottles), so it certainly works orally, and produces typical opioid effects.

Curiously, it was found that the HBr salt actually was smokeable off of foil, and did not need freebasing or provoke any sort of negative reactions.

Is it the ultimate heroin opioid? Probably not. Is it abusable and fun? Yes. Realistically though it's not too different from heroin, it has some slight pharmacokinetic differences and may be slightly less potent, but who knows.

And yes, it is fun with cocaine. I make a point of never IVing but an IM shot of dihydroheroin mixed with cocaine (or IM dihydroheroin plus smoked freebase) is a grand old time. It's not anything world-changing, but it is worth giving a try.

 

[AlsoTapered]

CTH- cute.

I was interested to know why 'lean' seems to be popular in African-American culture and ITHINK it's a genetic difference that means a lot more codeine/dihydrocodeine is converted into morphine/dihydromorphine.

It was when I first heard a DJ Screw mix and was elated by the sheer talent of the guy... then I discovered he was dead, he had fatally ODed on lean.

Now I think the official fatal dose of codeine is said to be about 600mg and is due to seizures and other forms of toxicity, not the usual reason people die from too much of an opiate BUT I am prepared to bet that the figure came from Europe (it's not even a mg/kg figure - so it's VERY vague).

But I was keen to note how safe sufentanil and 14-ethoxymetopon both are. They are both noted as being very potent analgesics and yet their TIs are simply VAST. No prizes for realizing that the methoxymethyl of sufentanil and ethoxy of 14-ethoxymetopon overlay perfectly.

I suggest that they either favour mu1 and/or NOP receptors over mu2.

There is even an etonitazene derivative that is some x4 as potent as an analgesic but with a TI about x100 it's parent. In that case I KNOW it's because it's a joint mu1/NOP ligand.

So we CAN design strong, safe opioids.... I just don't know if they are euphoric but since I'm in constant pain I'm not too concerned about abuse potential.
Now the HBr salt being smokable.... so does the HBr dissociate from the molecule or is the MP unexpectedly low. I mean, most people I would say 'well, impurities lower MP' but I can hardly try that on sekio because (s)he does quality work.... it's a riddle wrapped in a mystery inside an enigma.

 

[sekio]

CTH- cute.

1. It's safer. No gaseous H₂. You could even do it in water if you had time to waste shifting between salt and freebase, or a higher alcohol, if methanol worries you. Just don't smoke directly over it and you'll be fine. And the formate decomposes into CO₂ and H₂O, which are both fire suppressants.
2. It's easier. Again, no need for either a H₂ generator or tank, instead dump in anywhere from 3 to 7 eq of formate and stir for ~1h at RT. It evn works with "Pd/C on celite" (scraped off the top of the filter at the end of workup).

You are more than welcome to piss around with a Parr hydrogenator. My father would have done that, but I know better.

I was interested to know why 'lean' seems to be popular in African-American culture

Where I live (Vancouver, Canada) there are comparatively few people of African extraction. A lot of Asians though.

The thing that most people forget is that the main active drug in the cough syrup actually isn't the codeine - it's the promethazine. If you lack tolerance to them, any of those oldschool centrally-acting H₁ antagonists will have you struggling to stay awake, even without the opioid. And of course, as we all know, combining antihistamines with opioids generally increases the intensity. The combination is way more intense than the opioid alone.

Also, codeine generally has a ceiling effect, I believe the playground rumours state the max effective dose is about 200mg. So it was an unintentional "benefit" to his knockoff lean - you could always increase your dose (and opioid tolerance) further...

Now the HBr salt being smokable.... so does the HBr dissociate from the molecule or is the MP unexpectedly low

I imagine it's a similar situation to smoking methamphetamine hydrochloride: it dissociates as it vaporises and presumably immediately recombines, producing an aerosol of liquid/solid droplets suspended in hot air.

I never bothered to get a MP. I had access to a GCMS instead, so used that as a means of purity testing.

I personally think this synthesis is brilliant for a few reasons:
1. Relative simplicity. 2 steps, both easy reactions. No heating mantle needed. (I used a water bath for the HBr)
2. Cheap, accessible precursors. Codeine here is $9-15 CAD per 1.2g freebase at any pharmacy. Pd/C is probably the most expensive but almost any other hydrogenation catalyst should work. (I never tried i.e. P1 nickel). HBr in acetic is tricky to prepare but not impossible, and can be used in excess.
3. Fast. The whole reaction, from pills to product, can be done in 4-6h if you have your shit together and the right tools.
4. Almost 100% yield, no side products, tolerant to presence of small amounts of possible impurities (APAP, caffeine). Can (with practice) be run blind (no analysis of intermediate products) but I don't recommend it!
5. The US government funded it.
5b. Ken Rice was an author (bless his soul)
6. It produces a strong opioid, but not too strong. Like I said, my (opioid tolerant) friend IV'd 300mg (=600mg morphine IV) and needed nothing more than a stiff slap around the face to arouse.

 

[Gaz_hmmmm]

1. It's safer. No gaseous H₂. You could even do it in water if you had time to waste shifting between salt and freebase, or a higher alcohol, if methanol worries you. Just don't smoke directly over it and you'll be fine. And the formate decomposes into CO₂ and H₂O, which are both fire suppressants.
2. It's easier. Again, no need for either a H₂ generator or tank, instead dump in anywhere from 3 to 7 eq of formate and stir for ~1h at RT. It evn works with "Pd/C on celite" (scraped off the top of the filter at the end of workup).

You are more than welcome to piss around with a Parr hydrogenator. My father would have done that, but I know better.


Where I live (Vancouver, Canada) there are comparatively few people of African extraction. A lot of Asians though.

The thing that most people forget is that the main active drug in the cough syrup actually isn't the codeine - it's the promethazine. If you lack tolerance to them, any of those oldschool centrally-acting H₁ antagonists will have you struggling to stay awake, even without the opioid. And of course, as we all know, combining antihistamines with opioids generally increases the intensity. The combination is way more intense than the opioid alone.

Also, codeine generally has a ceiling effect, I believe the playground rumours state the max effective dose is about 200mg. So it was an unintentional "benefit" to his knockoff lean - you could always increase your dose (and opioid tolerance) further...


I imagine it's a similar situation to smoking methamphetamine hydrochloride: it dissociates as it vaporises and presumably immediately recombines, producing an aerosol of liquid/solid droplets suspended in hot air.

I never bothered to get a MP. I had access to a GCMS instead, so used that as a means of purity testing.

I personally think this synthesis is brilliant for a few reasons:
1. Relative simplicity. 2 steps, both easy reactions. No heating mantle needed. (I used a water bath for the HBr)
2. Cheap, accessible precursors. Codeine here is $9-15 CAD per 1.2g freebase at any pharmacy. Pd/C is probably the most expensive but almost any other hydrogenation catalyst should work. (I never tried i.e. P1 nickel). HBr in acetic is tricky to prepare but not impossible, and can be used in excess.
3. Fast. The whole reaction, from pills to product, can be done in 4-6h if you have your shit together and the right tools.
4. Almost 100% yield, no side products, tolerant to presence of small amounts of possible impurities (APAP, caffeine). Can (with practice) be run blind (no analysis of intermediate products) but I don't recommend it!
5. The US government funded it.
5b. Ken Rice was an author (bless his soul)
6. It produces a strong opioid, but not too strong. Like I said, my (opioid tolerant) friend IV'd 300mg (=600mg morphine IV) and needed nothing more than a stiff slap around the face to arouse.

Another thing about promethazine is that it’s a cyp2d6 enzyme inducer, so it helps turn more codeine into morphine.

The ceiling dose for codeine seems to be either 400mg or 450mg in a single dose but in the BNF the max they’ll prescribe you in a day is either 300mg or around 350mg but obviously spread out over the day.

What does TI mean and what is celite?

 

[Hexenstahl]

Diacetyldihydromorphine (also known as Paralaudin, dihydroheroin, acetylmorphinol) is a potent opiate derivative developed in Germany in 1928 which is rarely used in some countries for the treatment of severe pain such as that caused by terminal cancer, as another form of diacetylmorphine (also commonly known as Heroin). Diacetyldihydromorphine is fast-acting and longer-lasting than diamorphine, with a duration of action of around 4-7 hours.[1]

Diacetyldihydromorphin

This would be the ULTIMATE Heroin opioid in pharmaceutical glass ampoules for IV/IM/SC injection Germany has the best drugs on earth…..it’s Faster acting & Longer lasting than Diacetylmorphine (Heroin) Some professional pharmaceutical laboratory could synthesize this molecule like one would bake a cake 100% purity in a multi use glass 60ml bottle 100kg (220 lbs) of pure API compounding HCL powder in a large secure drum/container in a dark cold cellar I would LOVE to inject pharmaceutical grade powder of this with Pharma Cocaine HCL Why hasn’t this amazing Diamorphine improved analog not been illicitly synthesized and available for bulk purchase

Good thing my friend is a nurse. I'll tell her to look out for this sexy chemical. If she ever finds it -> steal it for me -> me be tryin' dis -> imma report here how it was

 

[Neuroprotection]

interesting thread, I made a similar one a few years ago about the simple dihydromorphine compound. apparently, as has been previously said, it is longer-lasting and more potent than traditional morphine. it is also more stable due to the absence of the double bond which is broken and saturated by the addition of two extra hydrogen atoms to the morphine molecule. Dihydromorphine is used in experiments to study binding to the Mu opioid receptor.
From the very little information I was able to find on its behavioural effects, it is similar to morphine but slightly more sedating, less euphoric and has higher anti-convulsant activity. I think this compound and it’s analogues would be more suited for opioid maintenance rather than recreational use, unless you have a very high tolerance. i’ve come across discussions about how opioid potency doesn’t necessarily correlate to euphoric potential, and I’ve also read that morphine and heroin still produce the greatest euphoria of all opioids. A suggestion to explain this could be that The structure of morphine allows it to interact with several receptors in a way that we don’t yet understand. A more interesting explanation is that these compounds relatively weaker Mu binding affinities and faster binding/unbinding kinetics May lead to more activating and euphoric responses. i’m not a neuroscience expert, so please forgive me for any mistakes I have made and please correct me.

 

[AlsoTapered]

Unlike codeine, dihydrocodeine is active in it's own right - it isn't purely a prodrug. Some nations (e.g. Japan) ONLY use dihydrocodeine and dihydromorphine because of it's longer duration of action and because some Asians are poor metabolizers so codeine's action is variable across the population.

Given the price difference, evidently the conversion of codeine to dihydrocodeine can be scaled, is cheap and is high-yielding. Various patents give different routes.

So Japanese papers would be the most enlightening presuming they have English language translations or the reader is fluent in Japanese.

Both dihydrocodeine and dihydromorphine are considered less euphoric than their parent compounds. Likely this is due to their MOR1/MOR2/MOR3 activity being slightly different.

Someone investigated dihydrocodeine-6-sulfate which was found to be x8 more active than dihydrocodeine and dihydromorphine-6-sulfate some x6 dihydromorphine in activity. I don't think the underlying reason was explored.

 

[AlsoTapered]

BTW codeine-6-acetate is toxic, specifically it's a convulsant. Some years ago I noted that US heroin overdoses in areas where black-tar heroin predominated was SEASONAL. I'm guessing that it's because poppies opium poppies harvested in spring contain more codeine and as far as I can tell, the production of black tar doesn't remove the codeine very well and so levels of codeine-6-acetate in seizures mirrored the overdose rate.

Now I've NEVER seen a DEA or other paper ever elude to this fact. DEA papers provided qualitative data on black-tar heroin and other sources data gave month-by-month data on fatal overdoses... but nobody commented.

I concluded long ago that the DEA isn't REALLY interested in prevented drug deaths. It only exists because drugs are controlled and as a result they have a vested interest in continuing a 'war' in which they are losing... BADLY.

If the introduction of fentanyl is referred to as an 'epidemic' then what term does one apply to carfentanil, an opioid that isn't even well studied in man beyond the estimate that it's about 100 times more potent as an analgesic.