Sciencemadness Discussion Board

Arecoline extraction

killer_lapin - 11-12-2013 at 13:41

Hi guy,

Few months ago I've extracted some arecoline from betel nuts. I just wanted to share it with you since I've used a common extraction technique which can work with other compounds as well.

I grounded the dry nuts and puted them in 10% KOH and start an hydrodistillation.
<img src="https://24.media.tumblr.com/81327048997e6e9fa73b326710fe51b4/tumblr_mxnv60gKVW1t7vuido3_1280.jpg" width="800" />

I from the turbidity could clearly see that there was something in the distillate. After what I've extracted the distillate twice with ether and setted up an HCl bubbler.

<img src="https://24.media.tumblr.com/5e3dcf180f5b74966f4e635512d31836/tumblr_mxnv60gKVW1t7vuido2_1280.jpg" width="800" />

Then there was this fine precipitation of the arecoline hydrochloride.

<img src="https://31.media.tumblr.com/b49f1e71128633321deea8c7d1081e46/tumblr_mxnv60gKVW1t7vuido1_1280.jpg" width="800" />

Sadly the hydrochloride crystals were to fine to get a nice powder after filtration, it all stayed on the cellulose filter.It still have some betel nuts around and if you have idea to improve the process I may try it again. ( And sorry for the large pictures I'll do better next time I make a post)

<!-- bfesser_edit_tag -->[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: reduced image size(s)]

[Edited on 11.12.13 by bfesser]

Crowfjord - 11-12-2013 at 14:11

Nice. It would be interesting to do a TLC on the freebase extract. I suspect there may also be a small amount of guvacoline (nor-arecoline I suppose one could call it, the N-demethyl analog) present. I have also wondered to what extent dimers, oligimers and polymers would form from Michael reaction between the areca alkaloids in an extraction like this.

killer_lapin - 11-12-2013 at 15:02

Good idea to do a TLC, I haven't tought of that! Most of the alkaloid of this plant wouldn't show with UV, but I'think I still have Iodine on silica gel which would reaveal the arecoline and guvacoline.

Nicodem - 13-12-2013 at 10:36

Quote: Originally posted by killer_lapin  
I grounded the dry nuts and puted them in 10% KOH and start an hydrodistillation.

That does not make sense. How could a methyl ester survive such treatment? And what's the reference for this isolation?

killer_lapin - 13-12-2013 at 11:01

Methyl esters are quite resistant, usualy LiOH is used because it coordinate with the carbonyl and helps the hydrolysis.
The 10% KOH idea comes from The Alkaloïds Vol I-Chemistry and physiology. They used a much complex procedure, I've cutted corners because I've read somewhere that it was steam volatile but the amine needs to be deprotonated.
But you may also be right wich would explain why I had so little product. Next time I could try with K2CO3 insted of KOH. I can put the actual procedure if you want.

Edit: it was actally moisten with 10% KOH(from the alkaloids) then i added water to have a sufficient volume to steam distill.



[Edited on 13-12-2013 by killer_lapin]

Nicodem - 14-12-2013 at 07:06

Quote: Originally posted by killer_lapin  
Methyl esters are quite resistant, usualy LiOH is used because it coordinate with the carbonyl and helps the hydrolysis.

You are very wrong. Methyl ester, particularly the aliphatic ones, hydrolyze in mater of minutes to one hour in single phase 10% aq. KOH. You can be sure that this is going to be very fast at 100 °C.
Quote:
The 10% KOH idea comes from The Alkaloïds Vol I-Chemistry and physiology. They used a much complex procedure, I've cutted corners because I've read somewhere that it was steam volatile but the amine needs to be deprotonated.

Yes, post the whole procedure. Also, in the future make sure you provide references even when you make adaptations to the published ones.
Quote:
But you may also be right wich would explain why I had so little product. Next time I could try with K2CO3 insted of KOH. I can put the actual procedure if you want.

You only need a buffer to maintain about neutral pH. You don't need a strong base. K2CO3 also readily hydrolyzes methyl esters at the water boiling point. Try with NaHCO3 or Na2HPO4.

killer_lapin - 15-12-2013 at 14:43

Here is the actually extraction methode for arecoline. It's complexe so you can understand why I tried a simple hydrodistillation.

The ground areca nut (in 500-kg. lots) is moistened with 250 kg. of 10% aqueous
potassium hydroxide, dried and successively refluxed for 2 hours with three portions of
ether. The combined extract is concentrated to 80 L. and the water that separates is
removed. The concentrate is then divided into portions of convenient volume and to
each 50% acetic acid is added with stirring until a turbidity appears. After vigorous
stirring, water (1 L.) is added and the ether removed by distillation. After the last trace
of ether has been removed, the warm aqueous solution is allowed to cool overnight in
evaporating dishes. The solid fat which rises to the surface is collected, melted, and
stirred with several 1L. portions of water, each time allowing it to cool and decanting
the water to recover the base retained by the fat. The combined acidic aqueous extract
is filtered and extracted with ether to remove suspended and nonbasic material, then
saturated with potassium carbonate, shaken with three portions of ether, and dried over
anhydrous potassium carbonate. The mixture of bases, recovered after removal of the
ether, is sufficiently pure to be used directly for the isolation of pure arecoline as its
hydrobromide. The bases are dissolved in twice their weight of absolute ethanol, the
solution filtered, cooled, and made slightly acid by the addition, with stirring, of a 50%
ethanolic solution of hydrogen bromide. The crystalline hydrobromide separates on
the addition of ether to incipient turbidity followed by clarification with a few drops of
ethanol. The solution is cooled for 24 hours and the crystalline salt is filtered and washed
first with an ethanol-ether mixture, and then with ether. The arecoline hydrobromide
thus obtained, when dried at 60°, melts at 170°.

Edit: procedure from The Alkaloïds Vol I-Chemistry and physiology p.171

[Edited on 15-12-2013 by killer_lapin]

bfesser - 15-12-2013 at 15:39

Please cite a reference when you copy-paste procedures and such.

Crowfjord - 16-12-2013 at 17:06

It's interesting that they do it that way. I wonder why they handled the fat manually rather than acidifying and defatting with a solvent. If I was to try the arecoline extraction (had I not found an established procedure), I would wet with acid, defat with naphtha or petroleum ether (or similar), then basify and extract with a non-polar (like ether). After that, I like what they do in the above reference. Does anyone know if there is an advantage to salting with HBr rather than HCl or other acid? I've noticed that commercial arecoline is usually sold as the hydrogen bromide salt. There must be a reason.

DJF90 - 17-12-2013 at 01:43

It could be that the hydrochloride salt is hygroscopic/deliquescent. There are many factors involved in salt selection, and even more if you're considering pharmaceutical salts.

bfesser - 17-12-2013 at 06:05

<a href="http://www.scribd.com/doc/35979437/The-Alkaloids-Chemistry-and-Physiology-Volume-1-1950#page=180" target="_blank">The Alkaloids - Chemistry and Physiology - Volume 1 (1950)</a> <img src="../scipics/_ext.png" />

[Edited on 17.12.13 by bfesser]

BillyRubin - 21-12-2013 at 22:51

FWIW: "A general procedure for extracting fresh plant tissues and fractionating into different classes according to polarity was described by Harborne in 1998."
-illustrated in Phytochemical Techniques by N. Raaman, ISBN 81-89422-30-8

Many other detections and isolations are detailed also.

Calculating amount of solvent required

metalayer - 10-1-2014 at 09:41

Is there a general method or equation for determining the quantity of a solvent (DCM in my case) needed to extract x moles of a compound?

Thanks

Mailinmypocket - 10-1-2014 at 09:44

Research the solubility of said compound in DCM

metalayer - 10-1-2014 at 10:35

I can't find the solubility anywhere. Compound in question is Arecoline Hydrobromide.

Is there a way to calculate its solubility in DCM if I know its solubility in another solvent like diethyl ether?

Pyro - 10-1-2014 at 10:44

Not calculate, but you can speculate.

why not use ether?
If acquiring DCM isn't a problem, just use a large excess. Then just Distill/evaporate the DCM off

Bot0nist - 10-1-2014 at 10:54

Take 10ml of DCM and put it in a beaker on top of your mag stirring hotplate. Take an accurate temperature measurement. Add a stirbar and begin stirring. Slowly add your compound untill no more will dissolve at that temp. Then raise/ lower the temp, with fresh DCM and do it agian. Plot all your data and make a solubility curve, then post it for the world to benefit.

[Edited on 10-1-2014 by Bot0nist]

metalayer - 10-1-2014 at 11:23

Thanks for your responses, I'm on the right track now.

Pyro - 10-1-2014 at 12:18

I assumed that since he wants to extract it he doesn't have any to test solubility

Bot0nist - 10-1-2014 at 12:21

I thought as much too, but he could perhaps do a small extraction with a large excess of DCM, or ether, then plot a solubility curve for DCM to do the bulk of the extraction more efficiantly...

blogfast25 - 11-1-2014 at 07:01

Quote: Originally posted by Bot0nist  
Take 10ml of DCM and put it in a beaker on top of your mag stirring hotplate. Take an accurate temperature measurement. Add a stirbar and begin stirring. Slowly add your compound untill no more will dissolve at that temp. Then raise/ lower the temp, with fresh DCM and do it agian. Plot all your data and make a solubility curve, then post it for the world to benefit.

[Edited on 10-1-2014 by Bot0nist]


Do you realise just how volatile DCM is? Without a refluxer you're likely to lose most of it to evaporation quite quickly, even more so if you're going to heat it. The lowest setting on a hot plate is likely to cause it to boil!

[Edited on 11-1-2014 by blogfast25]

Bot0nist - 11-1-2014 at 10:12

Sorry, that slipped my mind. Maybe follow chemikids advice and chill the glassware first. Use an icebath and start at 0°c and work up from there.

Pyro - 11-1-2014 at 10:15

reflux...

just use a condenser or a flask cooled with AN/Ice water, that is supposed to go as low as -30*C

Mailinmypocket - 11-1-2014 at 10:24

This might be helpful to you:

Attachment: Arecoline.pdf (100kB)
This file has been downloaded 896 times

Freebasing with NaOH

metalayer - 30-1-2014 at 09:24

I am trying to follow a synthesis which involves making freebase Arecoline from Arecoline Hydrobromide. The synth suggests using sodium bicarbonate to freebase, but I have found that creates horrible emulsions and makes extremely difficult to separate phases. Could I use NaOH instead?

Thanks

DraconicAcid - 30-1-2014 at 09:43

Arecoline is an ester- a strong base like sodium hydroxide could hydrolyze it to the sodium salt of arecaidine. Try extracting the arecoline with a solvent that's immiscible with water (arecoline is soluble in chloroform; that might work). The only trouble is that arecoline is very water-soluble, so you'd need a lot of salt in the water to drive it into the organic phase.

metalayer - 30-1-2014 at 12:55

Quote: Originally posted by DraconicAcid  
Arecoline is an ester- a strong base like sodium hydroxide could hydrolyze it to the sodium salt of arecaidine. Try extracting the arecoline with a solvent that's immiscible with water (arecoline is soluble in chloroform; that might work). The only trouble is that arecoline is very water-soluble, so you'd need a lot of salt in the water to drive it into the organic phase.


Chloroform is difficult for me to obtain, any other suggestions for solvents? DCM failed so badly (arecoline solubility was shit) I think it might have been a mistake in the article.

Regarding freebasing with NaOH - could it work with a weak solution? I found an article with this procedure -
Quote:

The free base of arecoline was prepared and purified by repeated extraction of aqueous arecoline hydrobromide solution (adjusted to pH 10 by 2M NaOH) with petroleum ether [20]. All other chemicals and solvents were of analytical reagent grade. (Formulation optimization of arecoline patches,Pao-Chu Wu et al)

Crowfjord - 30-1-2014 at 15:49

I don't see why using sodium hydroxide solution should be a problem. You can minimize ester hydrolysis by basifying slowly with good mixing, keeping the solution cool during addition of hydroxide, and extracting soon after the desired pH is reached.