Opioids Codeine Freebase Extraction and Caffeine Removal

[sekio]

Converting Opioid Pills to Freebase Alkaloid
Canadian Tylenol 1 Version

Supplies needed

Reagents
4x200 count bottle of Acetaminophen 325mg/Caffeine 15mg/Codeine 8mg tablets
Sodium carbonate anhydrous (see below for preparation)
Magnesium sulphate anhydrous (see below for preparation)
Dichloromethane (preferred), chloroform, or ethyl acetate. (do not substitute naptha, toluene, et cetera)
It is important that the solvent used be of good purity – do not use “nail polish remover” or “paint stripper”. Chloroform can be synthesized from bleach or pool hypochlorite, and acetone.

For prep'n of codeine phosphate -
Phosphoric acid
Acetone

Equipment
Mortar and pestle
Sieve
Two litre vessel, like a beaker or bucket (solvent resistant)
Another one-litre vessel, glass or HDPE (solvent resistant)
pH paper or meter (optional)
Buchner filter funnel and aspirator, or gravity funnel (Buchner funnels will make your life so much easier)
Separatory funnel and stand, or cannula/pipette (Again, seperatory funnels will make your life easier.)
Evaporation apparatus (water bath with ventilation)

Preface

This is a quick and fairly easy procedure for extracting excellent quality codeine freebase from commercial Tylenol 1 tablets. I noticed there was only my scribbled notes on doing so in a dusty corner of ADD and decided to do a real writeup for the Canadian opiophiles out there. Of course this process does not need to be run with 800 pills, you can scale it up or down as you wish. Just make sure to scale the quantities of all the solvents, and the sodium carbonate for basification.

Some people are going to complain this is a long-ass write up, or that it's too hard, or there's too much equipment involved. If you want to do a half-assed extraction, be my guest, but it will not produce halfway as nice results. As to supplies - Generic pills work great. This procedure works best when run with dichloromethane, and the proper equipment (vaccum filter funnel and sep-funnel) – one can get away with “normal” filtration and cannula/decantation to separate phases, but proper equipment makes life easier.

You will want to source out dichloromethane or chloroform for this procedure, as ethyl acetate is a relatively poor solvent for caffiene and codeine base when compared side-by-side. It will work, however. Naptha, hexanes, gasoline, toluene, ether, etc... will not work anywhere near as nicely. The diligent among you may modify this extraction to "make it work" though. Check the very bottom for a solubility matrix, and use your head.

Safety First

Wear protective gear (gloves, lab coat or substitute, safety glasses, and suitable footwear) when working with solvents.
Ethyl acetate is flammable, and has vapour heavier than air. Avoid open flames and sparks.
Work in a ventilated area when working with toxic or flammable solvents.
Extraction of codeine may not be legal in your jurisdiction – this information provided for academic purposes only.

Step Zero. Preparation of anhydrous salts

Sodium carbonate:
Bake sodium bicarbonate out in a glass pie pan or casserole dish. Set your oven to at least 450 degrees F and let it cook for several hours, or until it no longer loses mass upon continued drying. Crush and sieve it into an airtight labeled container.

Magnesium sulphate:
Bake magnesium sulphate out as per the above procedure. Crush it finely, sieve it, and store it in an airtight labeled container.

Step one. Crude water extraction.

The first step we are going to perform is a simple cold water extraction, to remove the pill binders that form a sludgy mess.

Crush your pills in the mortar and pestle and sieve out a fine powder into a large container. Add about a litre of water – approximately 1 to 1.25 ml per pill. (Using ice cold water, freshly decanted from crushed ice, will work even better.) Stir it around for 10 minutes so to ensure all the pill bulk is extracted.

Set up your funnel to filter the pill muck. Filter and save the clear, to sightly cloudy aqueous layer. You can extract the filter cake again with more water if you like, but it is not necessary.

The result is a clear to cloudy solution containing opiate in salt form, caffeine (if present), and a small amount of other impurities. The cloudiness is not an issue, but if you are anal about ensuring extraction, chill it down to ice cold temperatures (but not freezing), and refilter to remove some more acetaminophen and other junk.

Step two. Removal of caffeine.

We will now remove the substantial quantity of caffeine in Tylenol 1's, by solvent extraction – leaving the codeine, still in salt form in the water. You can skip this step if you are using Tylenol 3 as feedstock.

If you are using a seperatory funnel, set up a stand to hold it. Add the aqueous pill extract to the funnel.

Dichloromethane or chloroform solvent wash:
Add 250ml of dichloromethane or chloroform. Mix thoroughly with the aqueous layer, allow it to settle, and remove the organic phase, which contains caffeine, from the bottom of the solution.

Ethyl acetate solvent wash:
Add 750ml of ethyl acetate. Mix thoroughly with the aqueous layer, allow it to settle, and remove the organic phase, which contains caffeine, from the top of the solution. (If you're using a sep-funnel, drain the water layer on the bottom off. Discard the remaining organic phase, and reload the water solution into the funnel. Watch out for the stopcock.)

Repeat the solvent wash once more, for a total of 2 washes. You can save the solvent and evaporate it to yield caffeine, theoretical yield 12.8 grams. Otherwise, discard it.

Rinse out the vessel you used for the pill extraction, and place the water layer into it, if you were using a separatory funnel.

Step 3. Basification and extraction of codeine.

We will now remove the phosphate counterion of codeine phosphate, making water-insoluble codeine freebase, which is removed by solvent extraction.

Add approximately 50 grams of anyhdrous sodium carbonate to the aqueous water phase, stir until no more of it is dissolving, test the pH to ensure it is 11 or higher, and decant it (if there is a significant amount of undissolved salt). A small amount of undissolved salt is fine - add some extra water to dissolve it.

Repeat the solvent wash procedure above, with 3x250ml dichloromethane/chloroform, or 3x300ml ethyl acetate, this time running it 3 times, and saving all the solvent washes (which contain codeine base), Discard the water layer which now contains only useless junk.

Step 4. Evaporation of codeine base solution

We will now remove traces of water from the codeine base in solution, by complexing it out with magnesium sulphate, and remove the solvent via evaporation to yield the final freebase alkaloid.

Add a few teaspoons (dichloromethane) or several tablespoons (ethyl acetate/chloroform) of anhydrous magnesium sulphate, and stir until it no longer clumps (5 minutes). Filter the hydrated magnesium sulphate off and discard it.

Evaporate your solvent off. Chloroform and dichloromethane are toxic if inhaled. Ethyl acetate is flammable and a respiratory irritant. So do this either outside, or in a well ventilated area – preferably on a water-bath or other non sparking heat source if you're using ethyl acetate.

Codeine base precipitates as a slightly pink tinged white fluffy crystal. It has a low melt point and smells distinctly “flowery”. It is substantially pure codeine as determined by most analytical methods. The major impurity is expected to be caffeine. The theoretical yield of codeine base is 74.5% of the mass of codeine phosphate extracted. Actual observed yields of crude product may be as much as 200% due to caffeine contamination, poor technique, etcetera – though this is mitigated by washing well with solvents, and using the chlorinated solvents rather than ethyl acetate. A more typical yield is 100% of theory, 90% approximate purity).

Store your codeine in a cool dry place away from moisture. It should remain good for many years.

One can either eat this codeine freebase (it is approximately 1.3x stronger by weight than codeine phosphate), smoke it (inefficient, better in a freebase pipe), or dissolved in an acidic solution for IM injection/drinking/plugging. (If you are injecting or plugging, please adjust the pH after adding codeine base to an acid solutiuon so as to not ruin your veins).
Do not IV codeine as it can cause severe negative reactions.

Step 5. (optional). Salting of codeine base to codeine salts

This step converts the water-insoluble codeine freebase to water-soluble codeine phosphate. It is only neccesary if you want to make a water solution of codeine – otherwise it is more work for a messier product.

Dissolve codeine base in a minimum volume of acetone, dissolve an equimolar amount of e.g. Phosphoric acid in acetone as well. Combine the two solutions, and remove the very hygroscopic crystals of codeine phosphate that precipitate. These should be stored alongside dessicant, or as a solution in either ethanol or bacteriostatic water, as they will readily turn into a messy puddle if left to their own devices.

Waste disposal

Chloroform and dichloromethane are halogenated solvents that can release toxic gases if burned. They can be discarded as paint stripper/solvent at many local garbage/recycling facilities.

Ethyl acetate is broken down into ethanol and acetic acid, and can be flushed down the sink with copious quantities of cold water (small amounts), incinerated, or discarded as solvent waste at a municipal waste facility.


Facts and Figures

Solubilities (in mg/ml solvent)

N/S = Not Soluble, S = Soluble (undetermined)
In many cases these are the mazximum concentration, typical concentrations achievable easily will be 75% or less

 

[The.Ghost]

Just a few thoughts:

If you're using a Buchner funnel, you will also need a suitably sized filter flask and a rubber adapter to get a seal between the two. After putting the paper in the funnel and applying the vacuum, run some water through it before putting in your slurry to ensure a good seal.

Chloroform is nasty stuff. The acetone / hypochlorite reaction generates a significant amount of carbon tetrachloride byproduct, and that stuff is toxic / carcinogenic / CNS depressing / etc. I would advise against that route.

If you choose to use halogenated solvents, don't pour them down the sink. Being heavier than water, they will collect in the drain trap. They're also bad for the environment. Dispose of them properly.

Acetone, being a ketone, is reactive towards acids. I would use another solvent for salting.

 

[sekio]

Chloroform is nasty stuff. The acetone / hypochlorite reaction generates a significant amount of carbon tetrachloride byproduct, and that stuff is toxic / carcinogenic / CNS depressing / etc. I would advise against that route.

I see. Also, not everyone will want to run the messy bucket synthesis to make a litre of chloroform...
The other option for the "lay man", then, is to distill/seperate dichloromethane from e.g. paint stripper. It may be known as "methylene chloride" in that situation. I also bet trichloroethane, or similar moderate polarity water-immiscible solvents would do the job. That can be sourced as dry cleaning fluid.

But realistically, small amounts of contaminating CCl4 and CHCl2 will not effect extraction. Codeine/caffeine, to my knolwedge, is poorly soluble in the relatively nonpolar carbon tetrachloride when compared to chloroform/dichloro. And you should of course be working with solvents outside, or in a ventilated area (see Safety First).

For the sake of caution and consistency, it is a good idea to let your codeine base dry in a warm, dark place if you have used chlorinated solvents, to ensure that there is a minimum of residue left.

The savvy among you may have noticed that an alternate procedure with different solvents goes like so:
1. Crush and soak pills, filter water off.
2. Add sodium carbonate to water.
3. Extract with toluene/ether to remove codeine freebase. Evaporate solvent

Do be wary that toluene is a very "heavy" solvent and will take ages to evaporate completely. Use a minimum volume. The end product may not be as pure as expected if made with this simplified method, but it should procude base of acceptable quality.

 

[tricomb]

Thankyou very much Sekio, I'll work on adding this to the OD Directory.

 

[AlphaMethylPhenyl]

Yeah this is amazing...

 

[Survival0200]

Thank you!

 

[Madrus]

Would this also work to remove caffeine from heroin?

 

[Cloudnothings76]

Also if you really want to make the codeine very pure, you could take the final freebase and add a good bit of warm Ether. caffiene is insoluble while the codeine freebase is. Then filter and evaporate.

OR an even preferrable way to do it, would be, crush your pills, then add a few hundred milliliters of dried Acetone. Stir this for a while and then filter. This will rid the caffeine at the beginning. And this is also how you could get rid of Caffeine from street Heroin.

 

[clubcard]

For anyone who can obtain ibuprofen + codeine/dihydrocodeine/hydrocodone, ibuprofen is profoundly insoluble in water - 210 grams/tonne @ STP. Anyone who wants to remove a phenolic opioid from a solution can do so by forming to calcium salt using Ca(OH)2. That's how they extract M from opium. It works both ways such as tilidine + naloxone (for example). I will now try to obtain the unspecified data....

DOI: 10.1021/je990124v

I have discovered an effort-saving modification of sekio's superbly written technique. Paracetamol (acetaminophen) is much more soluble in acetone than water. Codeine phosphate, on the other hand, is utterly insoluble in acetone. Finely crushed co-codamol (cheapest brand is best brand) dropped into 5mL/tablet of acetone instantly disappear in cold acetone. If you filter out the solids and let them dry, you end up with the codeine phosphate + some of the inert binders. That means further purification can be carried out in much smaller volumes of solvent. One tip - if the pills are shiny then THAT is the source of the pasty texture so simply pouring through a fine kitchen sieve leaves the gloop behind and after just a few minutes drying, you have material that is a crumbly amorphous powder.

From a solvent management point-of-view, if you put the acetone into a freezer then much of the paracetamol will drop out. Filter than out and you can reuse that acetone many times. I used $1.87/L industrial grade so I still extracted into DCM and back into a minimal amount of (ACS) 37% hydrochloric acid.

Pravda has a few stories on multi-Kg batches of illicit codeine & many 100s of grams of Krokodil being seized and from the description (packages found), it sounds like super-smurfing. Great idea, only you and 50 of your most trusted confederates know what's going on.

I should add that an offshoot of krokodil research suggests that iodine readily adds to the aklene in the C-ring of codeine. I haven't particularly looked how you would reduce that but it looks like it might be a reasonable way to convert codeine into the much more robust dihydrocodeine for which sekio has given a brief overview on the 3-demethylation & 3,6-diacetylation of. Not my field but at least it ISN'T to do with making krokodil. As soon as you take a close look at the chemistry underlying the synthesis of codeine you will note that the PI3 adds to the 6,7 and/or 8 position of the molecule. Research is now ongoing into the toxicity of these species. Bluntly, it looks like you can't clean it and the impurities will kill you.

For an insight into I2 & alkenes, search for +pinene +iodine to see how readily I2 adds to an alkene. It isn't pretty, it looks unavoidable and it looks like really bad news.