Raver's Patented Miracle A/B extraction
That's a joke son, don't 'ya get it..?

The acid base extraction: Simplicity itself for the wary...

The acid base extraction is the mainstay of alkaloidal separation and in almost all cases is the simplest way to achieve decent purity and good yield. There are other ways to be sure, but this is the one that can be done with minimum equipment, OTC chemicals and little practical lab experience...

The most important step in this process is the initial extraction... It doesn't matter how well you do the final steps if you have not obtained the alkaloid in decent amounts during the initial separation.

1. A) Processing the plant material:
   
   Plant material frozen when wet is desirable, it grinds the cell walls of the biomass and facilitates the extraction of the alkaloids from it. Dried material is then ground to a somewhat fine, relatively even powder. Material that is to coarse will trap some of the constituents, and that which is ground to dust is often more difficult to filter, and when it is steeping becomes dense, packing itself into the bottom the extraction vessel making itself more difficult to work with.

 

1. B) Extracting:
   
   You may or may not wish to do a NPS extraction of soluble fats before beginning the A/B extraction... Though never complete, this often serves to eliminate the worst of the emulsions and defatting later on... It is often a good idea, especially when working with naturally fatty/oily biomaterial, or in larger extractions.. Simply soak the material in a very nonpolar solvent such as petroleum ether or xylene for a few minutes, decant the NPS and allow the biomass to dry... Though some product may be lost in this step, it is often a very small fraction, as the alkaloids are usually bound to an organic acid to begin with, and not in the freebase form. If concerned, evaporate the solvent and store for later re-extraction...

 

1. a) The basic conversion of bound salts: (Optional)

This is an optional step that may or may not increase yields on your extractions... In some plants it is an invaluable tool, in others, it may well be wasted... It is up to the reader to find out by trial and error, though because of its simplicity, it is recommended...

The material is placed in a pot and brought to a slight simmer with the lid on, with just enough aqueous base to cover it by around an inch or so. The material must be occasionally stirred, to increase the amount of contact with with fresh hot solvent. Simply steeping the material in the solution may work to some degree, but is poor technique. Yields can be increased by moving the biomaterial to some degree.

The basic solution doesn't need to be particularly basic. A pH of around 8 is usually sufficient. Aqueous ammonia is adequate, but K or NaOH is far better. Such bases as sodium bicarbonate may work to some degree, but have been found to be inadequate.

This step converts the alkaloid acid salts that are the naturally occurring form of the alkaloid into its insoluble basic salt. It may seem contradictory as a first step, but it is far easier to convert the bound alkaloidal salt to its base, and then to it's hydrochloride salt than it is from one acidic salt to another...

*notes on extraction vessel*

A crockpot is ideal, though any ceramic or stainless steel pot will work, though bottom heat may scorch the biomass resting at the bottom of the pot... Heating is uneven... With a crockpot, you can cover it and let it go for however long you would like with no fear of scorching and ruining the extraction...

DO NOT use aluminum, as it will react with the acid or base to some degree, though this will most likely be eliminated in latter steps, some may wish to avoid this altogether...

1. b) The aqueous acidic extraction of alkaloidal matter from the plant:
   
   Now that you have the basic slurry in the pot, add acid slowly to the mixture with frequent stirring until it reaches a pH of roughly 3... Bring the heat of extraction to a low simmer, and then cover, rechecking the pH after 1/2 hour. Frequently the pH will have risen slightly, due to the reaction of the acid to the bases trapped in the biomass... Readjust pH to around 2-3, reheat to simmering, and cover... Frequently stir the mixture to allow the plant material constant contact with the acidic solution... After 2-3 hours (during which time additional water is added to keep volume constant), decant the acid, and add additional fresh HCl (aq) again to cover the biomass by several inches... Allow to simmer 3-4 hours... Decant and combine acidic solutions... If desired, the frugal may re-extract again, but the addition of acid is usually unnecessary on the third and final simmer... Enough acidic solution remains in the biomass to make it fairly acidic, and many of the remaining alkaloids will already be in their water soluble acid salt... Lightly simmering the remaining solution over a long period of time ensures complete extraction in most all cases...

 

Allow to cool...

 

*A Note on Acids*

IMHO, no other acid has the efficiency or utility of HCl... It is easily obtained, and by far the best... Other acids will work, but vinegar and lemon juice are poor choices at best... They carry contaminants and are far less effective at liberating the alkaloids... If they are to be used, seriously consider the initial optional base soak, as these acids may be too weak to liberate the naturally bound organic salts of alkaloids...

1. c) Filtering: The mess...
   
   Decant the majority of the solution, and obtain the rest by pressing through cloth, such as T-Shirt material... Allow the solution to stand, and carefully decant so as not to disturb the precipitated materials...

Decant the solution through a coarse filter, such as folded cheesecloth or any similar material... Then filter again through successively finer meshes, often by repeated folding of cheesecloth, and then filter paper...

DO NOT just dump it into a coffee filter, you'll be dealing with a hell of an intractable filtration if that is done.. Surprisingly, several layers of cheap, industrial toilet paper can serve to screen out the finest particles... Damn well too...

1. d) Defatting the acidic solution:

If the volume of the acidic solution is large, it is often prudent to evaporate off the water by light simmering, until a workable volume is attained...

Take the cooled acidic solution, and allow it to sit... Insoluble material will precipitate out... Carefully decant the solution, attempting to leave as much of this behind as possible... Optionally, filtration via coffee filter may be used, or even better, suction filtration...

To the acidic solution, add 10% by volume of a fairly NPS, such as petroleum ether or xylene.. Repeat this 3 times, or until little or no emulsion forms, or until a small droplet evaporated on glass leaves no residue... Discard these washes...

1. e) Basification:

Add aqueous NaOH until the pH of the extraction reaches ~10... It is unnecessary to have the pH any higher, as well as potential harmful to some molecules, and lower may decrease yields due to incomplete conversions of the salts...

Stir the solution frequently, and bring to simmer for 15 minutes or so, ensuring the conversion of salts to their freebase...

Check the pH after the time of simmering and stirring...

 

Allow to cool...

 

 

1. f) Extraction of the freebase alkaloids:

Heat the basic solution to just below boiling, and then add non-iodized NaCl to the solution, until you see no more can be dissolved...

There should be a small amount remaining in the bottom of the flask... This saturates the solution, and increases the solubility of the freebase in the solvent, effectively driving it out of solution...

*Solvent choice*
All NP solvents are not equal... Any may be used, but the more polar the solvent, the more readily the freebase will dissolve in it... IMHO, the desirability of these NPSs are ranked as: Chloroform > Dichloromethane > Ethyl Ether > Xylene > Benzene > Hexane > Petroleum Ether (HBF)

But, this may vary subtly as the the structure of alkaloid of interest...

Extract the basic solution 3 times with roughly 10-20% of the volume in NPS... Actually, this may be repeated with smaller amounts of NPS until the NPS extracts no more material... Often 4-5 extractions with 10% NPS, test by dripping a little of the solvent on a mirror, and see if it has no residue...

[Editor's note: 4-5 extractions with 10% of the volume is generally better than 2-3 with 30% of the volume. The reason for this is that the rate of diffusion between the solvents is based in part on the difference in relative concentrations.

Each time fresh solvent is added, the ratio of dissolved alkaloids approaches infinity, as the new NPS has NO dissolved alkaloid at the start. This drives the diffusion rapidly at the start. With more smaller washes, this state exists for a longer period of time. ]

TLC, of course, is best...

Now add 10% of the solutions volume of dH2O and stir thoroughly... This helps clean up your solution from contamination locked in the water still in the NPS...

Repeat with a solution of brine if g) is skipped, and preferably dry the organic fraction over MgSO4, or epsom salts...

 

*Emulsions*

The method of mixing is fairly important, as intractable emulsions are often formed with violent shaking... These will hopefully be impacted by our previous defatting, but are inevitable, and often difficult to deal with...

The best method is by gently, yet thoroughly swirling the solution and solvent in a separatory funnel, inverted, with the stopcock open to vent pressure... If a sep funnel is unavailable, then this can be duplicated in a mason jar, etc... If an emulsion forms, gently stirring, running hot water over the funnel, or applying liberal amounts of shaken salt may well be of assistance..

 

1. g) Extraction of the Alkaloids from the nonpolar solvent: (Optional)

This is another hassle saving step... Re-extract the NPS/alkaloid solution with dilute aqueous HCl, 3 times, with 25% the volume... This will leave more contaminants in the NPS if they are still there to eliminate... Base the acidic solution as above, and re-extract as above... This often significantly cleans up the remaining product, though it may not be needed...

1. h) Evaporation of solvent:

Pretty self explanatory, but a few caveats:
No open flames, good ventilation and such... Last thing anyone needs is you poisoning yourself or burning your house down, when you are so close to pure product..! Keep the heat down, and watch out for electrical appliances, as they can spark, and destroy your extraction, as well as burning your house down...

1. i) HCl Salt (Optional)

Now you have all that clean product, but you realize that it is in freebase form... Good for smoking perhaps, depending on the compound, and still orally active, as your stomach is full of HCl, which will convert it for you...

But you want crystals...

Take the freebase up in a very NPS, often an ether/hexane 1:3 is excellent, but other combinations may not be without their charm..

Add drop wise as concentrated HCl as you can lay your hands on... Stir rapidly, checking the pH as you go... The way to do this, is to saturate a strip of pH paper with dH2O, and then use the stirring rod to drip the organic solvent onto it... You may well see the HCl salt precipitating out of solution, but it may also be NaCL... Crystal structure is different, and the taste is not bitter...

It is unnecessary to lower the pH to less than about 5-6...

If the alkaloid has not crashed out, try putting it in the refrigerator, and if that does not work, the freezer... Or add a crystal of product in, by putting in a microspat, pulling out a bit of solvent, allowing it to dry, and adding to solution... Often crystals will form on it... Or scratch the sides of the glass... Sometimes this works... The hard part is that this is an art, not a procedure, and you will just have to play with it...

The problem with this method, is that you are adding water to the mixture, and it may well solvate all your product... In this case, evaporate the whole mess to dryness, and then wash several times with ice cold acetone... This will get rid of some of the acidic crystals and leave your product...

*The best way is to saturate Et2O with HCl gas, and then adding it to the NPs of freebase, the crystals crash out white and snowy...*

 

More details to be added, if anyone is interested...

Recrystallization:

This is an often tricky but highly rewarding technique that lets you see your product in it's full glory... The basic idea is to dissolve your product and any remaining contaminants in the bare minimum of hot solvent that they are both soluble in... The product needs to be only slightly soluble, and the impurities far more so...

Choice of solvent is often difficult, but there are a few standard tricks that can be used, and a few good starting places...

Often, anhydrous isopropyl alcohol is an excellent starting choice... Bring it just to boiling on a flameless, sparkless medium, and add it to the hydrochloride salt of your product... Keep adding with rapid stirring until all of it dissolves... If it does not all dissolve, keep it hot, and slowly add near boiling anhydrous ethanol until it does...

Once it is all dissolved, allow it to cool completely to room temperature... It is a mistake to cool it in the fridge or freezer, as this can cause over rapid crystallization and may trap impurities...

If no crystallization occurs at room temperature, then take a small amount of fluid out and allow it to evaporate, forming crystals. Ass these to the cool solvent, and wait to see if any crystallization occurs...

If it does not, then place the solution in the fridge, and wait until it cools completely... If again, no crystals form, then you try the freezer...

See how this is more of an art than a science..?

OK, best case, you are looking at your snowy white product, worst case, it's still there, but dissolved in alcohol...

Here's what you do in the worst case scenario:

You need to put acetone in the freezer, and let it reach 0 C... Then you add it to your ice cold solution, in excess of your solvent... About 200%... You should see the solution grown turbid and cloudy... That is your product "crashing out" of solution...

Allow the whole mess to sit until the solution becomes clear... Your product should have settled out of solution to the bottom of the flask... Carefully decant off extra solvent so as not to disturb the product... When you get down to the last dregs, pour it through a filter... Your clean hydrochloride salt should remain on the filter...

There is still product in solution... Evaporate it down to eliminate alcohol to a small fraction of it's current volume, and then flood it with ice cold acetone... The majority of remaining product would crash out...

*If IPA or EtOH does not work, try other solvent systems... It really depends on the alkaloid in question...

 

Additional purification techniques:

One of the better is to reflux your product in a solution of alcohol, with the addition of activated charcoal... Activated charcoal can be found in any aquarium store, but will need to be ground to a fine powder...

Refluxing is basically just bringing the solution to a light boil, but the flask is fitted with a condenser... This isn't entirely necessary unless you are using a flame, or working near electrical equipment...

After 10 minutes or so, take off the heat, and allow the solution to cool...

If you let the flask settle for a while, most of the charcoal will fall to the bottom, and much if not all of the colored material will then be gone....

Carefully decant the solution so as not to disturb the precipitated carbon, and filter either through a pad of celite or silica, or through our old friend cheap, industrial toilet paper, folded several times and resting over a funnel...

This method only works if the product if relatively clean, and only contaminated by colored compounds...

Some, but not much, of the product may remain trapped on the carbon... Washing it with ethanol or methanol is usually sufficient to retrieve it...

Two more methods are Sublimation, and Column Chromatography, both extremely useful, and only slightly more complicated...

Tips for Breaking Emulsions

When trying to break up an emulsion, there are few methods better than carefully, lovingly greasing up the top hole of the separatory funnel and slowly, gently inserting a battery-operated vibrator. A low moan may be uttered if one is in the mood. Works like a charm!

Amazing what you learn hanging out with old synthetic methodology chemists ;->

And to think we wasted money on a sonicator...

Another good way is to hang the sep funnel about 6-12 inches over a flask, and to let the dual layers run out with the stopcock at full open... The impact often breaks the emulsion up quite a bit...

Also running the whole thing through suction filtration can break it up pretty damn well...

Raver...

flying wire for the soul