Sciencemadness Discussion Board - Straight to base extractions

Straight to base extractions

koopatroopa023 - 22-5-2009 at 03:26

When extracting alkaloids from plant material, I understand that it is usually gone about by an acid base extraction. I also know that straight to base extractions work just as well, however I do not understand how this process works without using the acid. Could someone please enlighten me? Thanks!

pHzero - 22-5-2009 at 08:21

Erm I'm not entirely sure of the sciencemadness rules, but I don't think drug talk's allowed here.

DJF90 - 22-5-2009 at 09:13

Alkaloids arent always "drugs" pHzero... take caffiene for instance.

I dont see how just a basic extraction will yield your alkaloid. Normally acid is added to the organic extract, forming the ionic "ammonium" salt, which is extracted into the aquous layer (where ionic compounds usually reside). The other non-amine compounds stay in the organic layer which is discarded. Then base is added, forming the free amine, which is insoluble in water, but soluble in an organic solvent (ether is usually a good choice). The amine can therefore be extracted either by filtration of the precipitate (the amine), or adding an organic solvent such as ether and discarding the aqueous layer. The organic extract can then be dried, filtered (to remove the drying agent) and evaporated to yeild the amine.

Ozonelabs - 22-5-2009 at 09:33

pHzero, please get your facts right before accusing people of drug-preparation/extraction. Alkaloids, as DJF90 has said are not always drugs or drug precursors.

We stand in the same field of thought as DJF90- the principles of alkaloid extraction are not present. We do have a copy of a book entitled: 'The Plant Alkaloids' which we are happy to post, however tropane ring alkaloids as well as iso-quinoline alkaloids are discussed, hence permission from a moderator will need to be given first as we aren't sure whether or not it will be appreciated.
Not having read the entire book, we aren't sure how much use it will be, but its one more potential reference.

pHzero - 22-5-2009 at 11:41

Ok, sorry for making assumptions. It just seemed strange that someone should join the board and their first post be asking how to extract alkaloids without explanation - that, i think, is how morphine's extracted from poppies to make heroin...

DJF90 - 22-5-2009 at 11:45

Yes and also how cocaine and other alkaloids are extracted. However the original poster made no reference to any specific compound and so we have to assume he is not up to mischief.

Sandmeyer - 22-5-2009 at 15:03

Quote: Originally posted by DJF90

Yes and also how cocaine and other alkaloids are extracted. However the original poster made no reference to any specific compound and so we have to assume he is not up to mischief.

Even if he wanted to know about the extraction of cocaine from the plant material, so what? It is probably already well documented in scientific journals, does it become "mischief" when the ordinary citizent want to see the information? Well, he should have googled before posting, but that's another issue.

Quote: Originally posted by DJF90

Alkaloids arent always "drugs" pHzero... take caffiene for instance.

Caffeine is a drug, it is a CNS stimulant, as such it is addictive, you can read more about its mechanism of action here: http://en.wikipedia.org/wiki/Caffeine

[Edited on 22-5-2009 by Sandmeyer]

DJF90 - 22-5-2009 at 15:07

Sandmeyer: You're misunderstanding what I said. There is a reason for the quote marks...

Pomzazed - 22-5-2009 at 17:35

This might be possible if the alkaloids is in the form of salt in the plant itself, forming ammonium ions with organic acid.

DJF90 - 22-5-2009 at 19:07

Pomzazed: In this case if you try to do the extraction with an organic solvent then you'll get everything but the alkaloid. If instead you extract with water, then theoretically the ammonium salts will go into solution. A base can then be added to cause precipitation of the free amine.

Nicodem - 22-5-2009 at 23:28

Quote: Originally posted by DJF90

Pomzazed: In this case if you try to do the extraction with an organic solvent then you'll get everything but the alkaloid. If instead you extract with water, then theoretically the ammonium salts will go into solution. A base can then be added to cause precipitation of the free amine.

Most extraction of alkaloids start with extracting the dried biological sample using an organic solvent, most commonly methanol or ethanol. Salts of alkaloids are generally well soluble in lower alcohols. Another method to treat the biological sample is to extract it with chloroform or other such solvent with the addition of a couple % of conc. aqueous ammonia. This crude extract is then treated by one of the many separation techniques like extractions, recrystallizations, chromatography, etc..

Anyway, there are numerous examples one can find in the literature and without knowing what (type of) alkaloid(s) extraction is being discussed any guesswork discussion in this thread is complete nonsense. Besides, what is "straight to base extraction" supposed to mean anyway? That is why I'm moving this thread to the Beginnings section just like I do with any such lazily and vaguely formulated questions posted without a single reference. I still do not understand why people insist in asking questions posed in such a way as to remain non-answerable?

PS: About this topic of whether discussion about drugs is allowed or not... I do not even understand where the doubt arises. About 30% of all thread in the Organic chemistry section is either directly or indirectly connected with drugs, legal or illegal (this is not a law forum so we make no distinction). The confusion might arise from the forum policy that does not allows kewlish, profit related or lazy posting. For some reason about 90% of those interested in drugs, and about 99% of those interested in illegal drugs, are either kewls, demented, lazy and/or greedy, which is why drug related post often end up in Detritus (not due to the topic itself). Threads where drugs are discussed coherently in a scientific manner are welcome. The same policy is valid also in the Energetic materials section.
pHzero, you are new here and you obviously know less about the forum culture than most of others who had more experience. So, next time you have doubts, use the post report button and/or leave it to the moderators.

koopatroopa023 - 23-5-2009 at 02:40

Hey everyone, thanks for trying to be so helpful. Perhaps I should be more clear on my line of thought. Take for example the extraction of Dimethyltriptamine from various plants. I am not trying to make this specifically about illegal drugs, but this is the only example I can think of at the moment. I have read that simply adding a base to water up to a pH of around 9-13, and then adding that to plant material will work just as well as acidifying and then adding the base to raise the pH back up. I found this strange that this would work without acidifying, and I thought I'd ask a more academic board than to seek elsewhere for answers that would only pertain to that specific alkaloid. It works, but I do not fully understand why this can be done. I assume that this is not some singular phenomenon pertaining to only this one alkaloid, but would also work for all alkaloids and possibly other compounds found in various plant materials. Thanks so much for any help with grasping why this can be done.

koopatroopa023 - 24-5-2009 at 11:00

Hey back again, here's the two extractions of the same compound, but one with the standard acid-base extraction process, and the other with the "straight to base" process

Acid base extraction: http://www.erowid.org/chemicals/dmt/extraction_guide1/dmt_ex...
Straight to base extraction: http://www.erowid.org/plants/mimosa/mimosa_chemistry1.shtml

Hopefully this will help people understand where my predicament is. Both of these work, I just don't see how the straight to base extraction does. Any help understanding would be wonderful. Thanks again.

Arrhenius - 24-5-2009 at 11:35

The 'straight to base' extraction would probably not be the first choice of a professional desiring to isolate plant alkaloids. By definition, an alkaloid contains atleast one amine nitrogen and an aromatic ring. It's all a matter of what you're extracting your alkaloid away from.

If you throw in a bunch of base, grind up whatever plant, and extract with a non-polar solvent, you'll extract basic compounds (such as alkaloids) and acidic compounds (such as tannins, etc.) will remain in the basic aqueous layer. You will also extract neutral compounds into the organic layer by this procedure. However, if you extract your plant into dilute aqueous acid, wash with organic solvent (removes neutral + acidic compounds, e.g. carboxylic acid containing molecules, tannins, etc.), basify the resulting aqueous fraction to pH>10 and extract with organic solvent, this final organic extract will contain ONLY (theoretically) basic compounds such as your alkaloids, and fewer neutral compounds.

koopatroopa023 - 24-5-2009 at 15:01

Thank you Arrhenius, that was quite informative. Now my question is if you don't acidify first does the compound go straight to freebase form in the basic aqueous layer? Or does it somehow go into its salt form and then its freebase form before going into the organic layer?

Arrhenius - 24-5-2009 at 15:26

Alkaloids probably exist in both salt form(many possible counter ions) and as free bases in their source plant etc. Technically, if you put them in a neutral solution of water, most will be protonated as +HNR3 or +H2NR2 ammonium salts with a hydroxide counterion. By adding excess base, it pushes the equilibrium towards NR3 or HNR2 species (free base) which is organosoluble.

koopatroopa023 - 24-5-2009 at 15:36

Much appreciation Arrhenius, that really helped me grasp what was happening.

Pomzazed - 24-5-2009 at 22:22

Arrhenius;
Thanks for posting that. It was basically what I tried to say but at the time i posted I was a bit sneezy and may posted a not-quite-comprehensible sentence.

Rich_Insane - 26-5-2009 at 16:17

Most alkaloids aren't drugs.

I will use an alkaloid that is a precursor for this example, but only as an example (and I may be wrong).

Lysergic acid is an alkaloid extracted from the ergot fungus. Since it is a carboxylic acid, it will react with a base, forming a salt. This salt is water soluble. So the answer yes, but if you are working with an acidic alkaloid. And if you want a really pure product, you probably have to go further, and do more research. I know that some people do a solvent extraction with methanol, then dichloromethane, then do the acid base extraction. Many alkaloids are extracted with kerosene, like cocaine, and others.

Many plants already have the salt of the alkaloid already (as Arrhenius said).

Keep in mind however, that not all alkaloids are amine-containing. Caffiene does not contain amine, but just nitrogen. And some extracts from plants have no nitrogen at all, but that's a different matter.

You have to do some research more or less on the structure of your alkaloid.

DJF90 - 26-5-2009 at 18:36

Caffeine has TWO tertiary amine nitrogens. Granted, they are part of a ring system, but that does not stop them from being amines.

Rich_Insane - 26-5-2009 at 19:10

Sorry, I meant it didn't have any primary or secondary amine groups.

Some terpenes are not amines, they are fully carbon and oxygen sometimes.

Nicodem - 26-5-2009 at 23:33

The structure of caffeine does not have any amino groups. It has 4 nitrogens, two of which are amide nitrogens, one is an sp2 hybridized nitrogen, and one has its lone electron pair incorporated in an aromatic resonance system; but it has no amine nitrogens. Check its structure: http://en.wikipedia.org/wiki/Caffeine

Lysergic acid is not an alkaloid and it is not extracted from fungi/plant material. It made by hydrolysis of ergot alkaloids. The definition of what is an alkaloid and not is part of convention, not about chemical properties. The only thing that alkaloids need to be, is to be present in living organisms, to contain at least one nitrogen and not to be already classified into other groups (for example, amino acids or nucleic bases can not be called alkaloids because they are already classified otherwise). Therefore, alkaloids need not to be amines, they can be anything from pyridines to amides, but always containing nitrogen. It thus also true that alkaloids need not to be bases. For example, the pKa of caffeine is about 0, which is barely more basic than water. Colchicine is even less basic, and so on. Morphine is even a base and an acid at the same time. Even the wikipedia entry for alkaloids (http://en.wikipedia.org/wiki/Alkaloids) is in conflict with itself. It claims that alkaloids are "naturally occurring chemical compounds containing basic nitrogen atoms" yet it gives caffeine as an example of an alkaloid!

Bromide - 27-5-2009 at 12:49

Quote: Originally posted by DJF90

Caffeine has TWO tertiary amine nitrogens. Granted, they are part of a ring system, but that does not stop them from being amines.

You sure you didn't mean to write that caffeine has THREE tertiary amine nitrogens?

TIETSE - 27-5-2009 at 13:23

koopatroopa023 look for this book:

The Technology and Chemistry of Alkaloids‎
de Frank E. Hamerslag - 1950

Rich_Insane - 27-5-2009 at 16:42

I'm sorry, I forgot all about the fact that lysergic acid is from Ergotamine. However, i am sure there are carboxylic acid alkaloids, I just can't think of any off the top of my head. I would think that those Nitrogens are just Nitrogens in a ring (like Pyridine, which has 1). The two on the Benzene side of the ring are amides, am I right? Alkaloids were a generic term given a while ago to substances found in plants that could be used medically. So the current definition from dictionary.com is: Any of a large class of organic, nitrogen-containing ring compounds of vegetable origin and sometimes synthesized, some of which are liquid but most of which are solid, that have a bitter taste, that are usually water-insoluble and alcohol-soluble, that combine with acids without the loss of a water molecule to form water-soluble hydrochlorides, hydrobromides, or the like, and that usually exhibit pharmacological action, as nicotine, morphine, or quinine.

Arrhenius - 27-5-2009 at 17:58

What molecule are you talking about Rich_Insane? If caffeine, it's not really proper to call Nitrogens 5 or 7 "amide" nitrogens. Technically, the functional group is not really an amide, and not really a urea, but it doesn't matter. The only important thing to note is that given the presence of the carbonyls, the nitrogens have increased SP2 character, and are thus less basic than a tertiary amine. Caffeine can definitely be isolated by acid/base extraction; I can vouch.

As for arguing what an alkaloid is, who cares. The above discussions of acid/base vs. just base extraction of alkaloids is merely a discussion of how one would approach the extraction of a basic compound versus an acidic compound. Alkaloid or not, you can use that general approach. If an alkaloid contains acidic and basic moieties, you're probably best off simply using repeated extraction with organic solvent. Just because a molecule contains a basic or acidic moiety does not mean it will behave well in an acid/base extraction

That being said it is quite possible that lysergic acid hydrochloride - alkaloid or not - is water soluble. I don't know. But the molecule has so much other non-polar spinach hanging off the nitrogen that you would be better off extracting with organic solvent.

I don't really know what you're getting at with the alkaloid definition.

[Edited on 28-5-2009 by Arrhenius]

Rich_Insane - 27-5-2009 at 19:46

The definition states that all alkaloids can be made a hydro(halogen).

If I were to extract an alkaloid, I would if it is polar or not, do extractions first by grinding and washing the material, then adding a polar solvent (separate the material, depending on if your alkaloid is polar or non-polar), add a non-polar solvent and separate, do an acid-base extraction, repeat steps, and finally recrystallize.

As for caffeine, I was just guessing the the people above were right. I initially assumed that caffeine had no amide groups. The SP2 is where 2 electrons go to the P shell, forming a hybrid orbital, am I right (I'm trying not to make stupid mistakes)? So the reason the amine is more basic is because it is a proton acceptor and that nitrogen there in the ring cannot accept protons as well?

The reason there is SP2 is because the Carbon in the Carbonyl shares 4 e with the Oxygen, and in order to bond with the nitrogen, it needs to hybridize?

If I were doing an extraction i would not go straight base, because the alkaloid may or may not do anything, and would still remain in a whole bunch of mucilage. I would do solvent extractions, precipitate the proteins with alcohol once the matter is finely grinded, and dissolve the lipids somewhere in the process with chloroform.

When I was extracting melanin from Shewanella and Aspergillus (which is slightly different from plants, but there are similarities), I did at least 5 freeze-thaw cycles to break down the cells, which is extremely important. I would do this for a few hours, then I did a quick centrifuge. I'm not sure if that's feasible, but it's not too hard to obtain a cheap centrifuge (microcentrifuge). Then I vortexed the mixture. After that I added chloroform to dissolve lips from the cell wall. Centrifugation yielded this debris. Keep a cycle of this. Then add isopropanol under heat to cause proteins to precipitate and denature. I'm not sure how well this applys toplants; You want to destroy the cellulose cell wall, so you need something for that.

The above only applies, however if the alkaloid is intercellular. If it is found floating around in the vascular tissue, then you have to ensure a crude cellular destruction and dissolve proteins and lipids (then proceed with acid/base, polar/nonpolar extractions).

DJF90 - 27-5-2009 at 20:04

The reason the "amide" and "imide" nitrogens are non basic is due to the canonicals that can form, involving the carbonyl group. The lone pair on the nitrogen is delocalised onto the carbonyl, thus reducing the ability as a base; thus amides are essentially neutral.

Rich_Insane - 27-5-2009 at 20:40

What do you mean by canonical?

So what you are saying is that the lone pair on the nitrogen is distributed in the whole nitrogen-carbonyl group thus disabling the Nitrogen's ability to accept the proton?

DJF90 - 27-5-2009 at 21:29

Thats exactly what I am saying. A canonical is a resonance form, but the *true* structure is neither canonical, merely somewhere in between (as we don't know for certain).

Look under "amide properties" on this page:
http://en.wikipedia.org/wiki/Amide

[Edited on 28-5-2009 by DJF90]

chemrox - 27-5-2009 at 21:40

I'm curious about two things: is coffee acidic or basic? I've never checked but CO2 is acidic and does a good job extracting caffeine from unroasted beans in supercritical state.

What does "kewl" or "kewlish" mean??

DJF90 - 27-5-2009 at 21:48

chemrox: The term kewl is discussed somewhere on the forum; UTFSE. Alternatively check the urban dictionary (just google "urban dictionary").

Coffee is a chemical mixture; it may contain both acidic and basic components. Caffeine however, the main alkaloid in coffee, should be basic by my reasoning. Supercritical CO2 I dont think is acidic; I believe its utilisation to extract caffeine from coffee beans comes from its solvent abilities (just like how ethanol is hardly basic, but is a better solvent than water for many organic compounds).

Arrhenius - 27-5-2009 at 22:13

DJF90: I've never heard the term 'canonical' in US chem books. I presume, from your drawing, that it's the same as a 'resonance form' or 'resonance structure. You're correct about the real structure being somewhere in between everything we can draw, but I do believe high level quantum mechanics can predict electronic structures quite well.

Chemrox: Coffee is acidic from tannic acids and phosphorus acids (supposedly).

Rich_Insanity: DJF90's explanation of why it has SP2 character looks pretty good. Ya, centrifugation works miracles with plant extractions. I don't think you necessarily need to break apart cell walls to extract chemicals from within. Sometimes breaking up plant material too much just gives a lot of chlorophyll in the extract. I've even used aqueous acid refluxes to facilitate extractions. There really are lots of options. Very seldom can you crystallize a desired product from an extract though; at least not as a pure product.

DJF90 - 27-5-2009 at 23:25

Arrhenius: Yes I believe it is another way of saying the same thing. Look at this following link under the heading "Resonance" (I believe this is a page from MSU - Michigan state university if I am not mistaken, meaning that this is not just a UK term as I had once thought):

http://www.cem.msu.edu/~reusch/VirtualText/intro3.htm

Having the chlorophyl extracted with the desired material I imagine is quite problematic (at the very least a pain in the arse). If I remember correctly though, chloroform is useful for solvent extractions because it extracts only a minimal amount of chlorophyl. At least I think it was chloroform.

Generally for obtaining a crystalline product, the organic extract is dried with a drying agent, filtered into a flask and the solvent removed either by distillation or by use of a rotory evaporator. Once most/all of the solvent is removed, if crystallisation hasnt started yet it can be initiated using an ice bath and "scratching" with a glass rod. The crystalline precipitate can then be removed from the flask and recrystallised 2-3 times to yeild a pure product.

Nicodem - 27-5-2009 at 23:37

Caffeine, for example, does not form hydrochlorides in aqueous solutions since it is barely ten times more basic than water which essentially means that the solvent more than efficiently competes for the protons and if you remove the solvent the HCl will be removed as well. I think it forms some, though unstable, "salts" from diethyl ether, kind of like some amides can. I do not know where anybody got the idea that caffeine can be purified using an acid extraction - none of its lab or industrial extractions use any such procedure.

Rich_Insane, if you would have read my previous post you would have noticed that alkaloids need not to be basic. Colchicine is completely neutral and yet it is a classical alkaloid. Morphine has the pKa of 9.9 in its neutral form and is thus a weak acid even when the nitrogen is not protonated (even though an acid it is still considered as one of the most classical alkaloids!). This essentially means that morphine can be extracted from a nonpolar solvent using aqueous NaOH, like you would otherwise extract an acid.

PS1: The names or the orbitals are in low caps. There are no "S", "P" or "SP2" orbitals, only "s", "p" and "sp2" orbitals.

PS2: "Canonical" means something similar to formalistic, that is the minimum not yet completely false form of something that is otherwise too complex to be described to fit the reality. The canonical forms are determined by conventions and rules rather than by the models fitting the reality. In reality chemical structures are always canonical except when determined by single crystal XRD and even then they are only real for the structure the compound has when crystalline. The term "canonical" is an ubiquitous term in science and mathematics: http://en.wikipedia.org/wiki/Canonical

Rich_Insane - 28-5-2009 at 17:31

Caffeine is extracted by supercritical CO2 or a nonpolar solvent (methylene chloride) (there are other methods, but as far as I know these are the main extraction methods.

It depends on what alkaloid you are working with. There are several classes of alkaloids, since it is a broad category.

Random - 26-3-2011 at 07:27

What about taking grinded coffee and soaking it in dillute HCl to dissolve caffeine from it as caffeine hydrochloride, filtering it and then adding a base to make caffeine again water insoluble? Would that work?