Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
Author: Subject: Propofol Problems
JnPS
Hazard to Self
**




Posts: 89
Registered: 29-7-2016
Location: PA, USA
Member Is Offline

Mood: Umpolung

[*] posted on 10-11-2016 at 18:42
Propofol Problems


So in my earlier thread "At home aromatic substitutions" I expressed my desire to perform this synthesis and want to first off thank everyone who helped me find procedures and gave tips/tricks even though just telling me to UTFSE seemed justified XD

I tried following the synthesis outlined here: https://www.scribd.com/doc/207709451/Propofol-Synthesis

However after running the first transformation I didn't end up with any product in the organic layer after evaporating off the DCM. Would the p-phenolsulfonic acid co-distill with the DCM as it evaporated? I wanted to isolate it to take an IR before proceeding to the next step. I was planning doing a friedel-crafts alkylation instead of the procedural alkylation using IPA.

The setup I used for the reflux is fairly straightforward. 3-neck RBF, thermometer, condenser, addition funnel. I ran it for 3 hours at 100C as the procedure calls for. Let it sit for a week, and the reaction mixture was a syrupy, faintly yellow, but clear liquid before using the sep funnel to extract the product. What might have happened?

As a side note, I am planning on following a different synthesis: https://www.researchgate.net/publication/263977007_Commercia...
I want to follow the reaction with TLC to make sure product is forming without the need to isolate it before removing the -COOH protecting the para position. Anybody know of good solvent systems for developing the TLC plates when following this reaction? I was planning on testing out a 70/30 toluene/MeOH along with a few others or just using plain ethyl acetate.



[Edited on 11-11-2016 by JnPS]
View user's profile View All Posts By User
Maroboduus
National Hazard
****




Posts: 257
Registered: 14-9-2016
Location: 26 Ancho Street
Member Is Offline

Mood: vacant

[*] posted on 11-11-2016 at 11:39


I'm not about to pay to read that.

But even though I haven't read it, your post reads to me like you're really out of your depth here.
You should really learn a LOT more about chemistry in general before you make your own propofol.
View user's profile View All Posts By User
JnPS
Hazard to Self
**




Posts: 89
Registered: 29-7-2016
Location: PA, USA
Member Is Offline

Mood: Umpolung

[*] posted on 11-11-2016 at 14:42


You can see the pathway without paying for the full article, my organic prof is helping me but I'll agree I am pretty green in this field and might be out of my depth. Could you be more specific about what I should look into? I've already passed two years worth of undergraduate chemistry with a 4.0 so I'd like some guidance towards what I should be studying
View user's profile View All Posts By User
halogen
National Hazard
****




Posts: 372
Registered: 18-4-2004
Member Is Offline

Mood: No Mood

[*] posted on 11-11-2016 at 15:09


TLC my foot. You're not looking to optimize and squeeze out extra percent yield. Simply extracting as salt and weighing will give you an idea of how many propyl groups you tacked on. And you're separating anyway - right?



F. de Lalande and M. Prud'homme showed that a mixture of boric oxide and sodium chloride is decomposed in a stream of dry air or oxygen at a red heat with the evolution of chlorine.
View user's profile View All Posts By User
Tsjerk
International Hazard
*****




Posts: 1744
Registered: 20-4-2005
Location: Netherlands
Member Is Offline

Mood: Mood

[*] posted on 12-11-2016 at 01:31


In this case, or in any case actually, TLC is not used to squeeze out an extra procent. TLC is hardly quantitative. The idea is, as JnPS already says, to see if there is any reaction going one and if so to make a rough estimation of how far it is.

Besides, how would you determine the number of propyl groups tacked on? Are you going to weigh the individual molecules? Are you going to titrate somehow? Something you can do with TLC with the right running solvents though.

[Edited on 12-11-2016 by Tsjerk]
View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2003
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 12-11-2016 at 19:22


TLC of most organics works best with ethyl acetate and hexane, often 25, 50 and 100% EtOAc are good choices, I often start at 50:50 for the first try. Once the plate has run for 3-4 minutes,I usually try it and often use some iodine on silica gel to stain the plate. UV also works with F254 plates, other good stains are PMA, permanganate, and vanillin, those all need heat to develop, a hotplate or heatgun can work for that. You might be able to use white gas or kerosene instead of hexanes. Good luck.

As for the reaction, the phenol/sulfonic acid might not dissolve in the DCM unless the pH is very low, it should be very water soluable, due to 2 polar groups. It will certainly not evaporate under any normal conditions, it should have a high BP also due to polarity. The route does not even show how they so the sulfonylation. How did you do it and work it up?

[Edited on 13-11-2016 by Dr.Bob]
View user's profile View All Posts By User
JnPS
Hazard to Self
**




Posts: 89
Registered: 29-7-2016
Location: PA, USA
Member Is Offline

Mood: Umpolung

[*] posted on 12-11-2016 at 20:28


Thanks DrBob, I'll try the ethyl acetate and hexane mixtures.

As for the sulfonation: I added 9.425g (about 0.1 mol) phenol and a stir bar to a 3-neck rbf with the above-mentioned hardware and added roughly 4x the molar amount of phenol worth of concentrated sulfuric acid in the addition funnel (23mL). I then heated the phenol to 40C to melt it and started stirring it. I then slowly added the sulfuric acid drop-wise. The complete addition took about 30 minutes. I then raised the temperature to 100C and held it there to reflux for 3 hours. After 3 hours I turned off the heating and let the mixture set for a week as the procedure suggested.

I then followed their sep funnel work up procedure: First I added an aqueous solution of sodium acetate (10g in 100mL water) to the reaction mixture to make it basic and pull the proton off the sulfonyl group making it water soluble and most likely to stay in an aqueous layer. Then after transferring this to a sep funnel I washed with DCM to remove any phenol that did not react. Then I added 50mL of 6M HCl to reprotonate the phenolsulfonic acid and make it soluble in DCM. I then did three 35mL washings with DCM and retained the organic layer. I then used a hot water bath to evaporate off the DCM and take an IR of any phenolsulfonic acid that should have been made but instead I was left with an empty beaker smelling faintly of DCM :(

Maybe I didn't add enough HCl to lower the pH and the product remained in the aqueous layer? 50mL of 6M should have been able to do that though, no?
View user's profile View All Posts By User
AvBaeyer
International Hazard
*****




Posts: 500
Registered: 25-2-2014
Location: CA
Member Is Offline

Mood: No Mood

[*] posted on 12-11-2016 at 21:15


Just in case anyone cares,
AvB



Attachment: Propofol Synthesis.pdf (412kB)
This file has been downloaded 183 times

View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2003
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 13-11-2016 at 16:36


Did you check the first DCM layer to see if the product went into the first DCM wash, instead of just unreacted phenol? I think that sodium acetate may not have been basic enough, but not sure. Just one thing to check.
View user's profile View All Posts By User
JnPS
Hazard to Self
**




Posts: 89
Registered: 29-7-2016
Location: PA, USA
Member Is Offline

Mood: Umpolung

[*] posted on 14-11-2016 at 04:28


I did not but I think you're right, in retrospect I only calculated the amount of acetate needed to deprotonate the theoretical yield of product and forgot about neutralizing the leftover sulfuric acid as well. Damn, what a beginner's mistake....well you live & learn I guess.

Thanks for pointing that out DrBob I'll try running the first method on a smaller scale at some point in the future and see if I can get any product by using a more basic solution.

Thank you AvBaeyer for sharing the full article! :)
View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2003
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 15-11-2016 at 19:03


You might need a stronger base than acetate as well. Good luck.
View user's profile View All Posts By User
Maroboduus
National Hazard
****




Posts: 257
Registered: 14-9-2016
Location: 26 Ancho Street
Member Is Offline

Mood: vacant

[*] posted on 15-11-2016 at 19:54


You might also benefit from this new, high-tech stuff they have for judging if a solution has been made basic.

It's these little strips of paper that turn blue when you put them in a basic solution.
And if the solution is acidic, they turn red!

Pity that organic Professor who's 'helping you' didn't mention them. Or that those nifty little items didn't come up during your 2 years of college chemistry.

View user's profile View All Posts By User
Metacelsus
International Hazard
*****




Posts: 2334
Registered: 26-12-2012
Location: Cambridge, MA
Member Is Offline

Mood: Double, double, toil and trouble

[*] posted on 15-11-2016 at 21:20


Sorry for being pedantic, but you shouldn't stick pH strips directly in the solution under test. The preferred method is to take a clean glass rod, dip it in the solution, and then touch it to the paper.

Sodium carbonate would be much better than sodium acetate for your purposes.

[Edited on 11-16-2016 by Metacelsus]




As below, so above.
View user's profile View All Posts By User
Maroboduus
National Hazard
****




Posts: 257
Registered: 14-9-2016
Location: 26 Ancho Street
Member Is Offline

Mood: vacant

[*] posted on 15-11-2016 at 21:23


No, I just didn't bother to go back and correct that, but I agree.
Done that way it even works with organic solvents if the paper is already wet.

EDIT: I also of course concede that litmus paper not 'new' or 'high tech', but that was said for ironic effect.

[Edited on 16-11-2016 by Maroboduus]

I'm still pretty amazed the subject didn't come up earlier in the thread.


[Edited on 16-11-2016 by Maroboduus]
View user's profile View All Posts By User
Tsjerk
International Hazard
*****




Posts: 1744
Registered: 20-4-2005
Location: Netherlands
Member Is Offline

Mood: Mood

[*] posted on 16-11-2016 at 01:24


Was that condescending tone necessary? I'm pretty sure JnPS knows how to measure pH. All you do is saying JnPS is in over his head without giving any advice (besides telling to not even bother trying).

Condescending his supervisor is besides shortsighted as you have no idea of their working relation, also completely irrelevant for the discussion about how to synthesize proposal.

"If you can't say something nice, don't say nothing at all." -Thumper

I know I'm also not really nice in this topic, but I was surprised in this topic by two people who from the start are completly and utterly negative and hostile, while I don't see anything wrong about the whole topic.


[Edited on 16-11-2016 by Tsjerk]
View user's profile View All Posts By User
Maroboduus
National Hazard
****




Posts: 257
Registered: 14-9-2016
Location: 26 Ancho Street
Member Is Offline

Mood: vacant

[*] posted on 16-11-2016 at 09:52


If JnPS knows how to measure Ph then it's pretty strange that he didn't do it.

He doesn't have a 'supervisor'. Everything he's done on this came from information he was spoon-fed here on various threads.

He says he's got his professor of organic chemistry helping him to make a very dangerous drug, but this professor apparently told him to get his information from a website like this instead of using the literature.

And does he ask this professor what went wrong with his reaction? Either he came here instead because there is no professor, or his 'professor' is incapable of seeing the glaring errors in the synthesis he's working from. In which case he's no professor.




@Tsjerk, you have mis-characterized my initial post. I told him to learn some more chemistry before he tries to make his own drugs. That is vastly different from telling him to not even bother trying.

(You have also mis-characterized your own post. You were very reasonable and polite in your posts here. )













View user's profile View All Posts By User
JnPS
Hazard to Self
**




Posts: 89
Registered: 29-7-2016
Location: PA, USA
Member Is Offline

Mood: Umpolung

[*] posted on 16-11-2016 at 11:03


I'm surprised my prof didn't mention that but he's a busy guy so he just glanced at the procedure and let me go through it in his lab so I'd have a proper fume hood. The procedure didn't give any concentration or amount of sodium acetate so I just figured enough to deprotonate the theoretical yield would be sufficient.

I should have measured the pH in hindsight, you're absolutely right. But I only have access to the lab once a week and for a limited time. It didn't say to measure the pH so I didn't. I wanted to finish the extraction before I got locked out of the lab. I'll know better next time. Thank you for reminding me to stay humble, that's the joy of chemistry, just when I think I know what I'm doing I make the dumbest of mistakes :)

My prof doesn't know about this site at all for the record I just didn't know where else to look that I didn't have to pay to go through. Plus the expertise here and years of experience are a great resource which, looking back, I guess I abused. I'll try and exhaust other resources before posting here in the future.
View user's profile View All Posts By User
Tsjerk
International Hazard
*****




Posts: 1744
Registered: 20-4-2005
Location: Netherlands
Member Is Offline

Mood: Mood

[*] posted on 16-11-2016 at 14:36


Oké, I get your point Maroboduus, but I still think not measuring the pH here is a beginners mistake which doesn't deserve a post like you posted.

I also wouldn't call propofol a drug as there is little recreational use for it. Apperently some people have been experimenting with it, but the dose effect curve is steep and abuse is quite unlikely. The same and better effects can be reached with stuff saver and easier available. To make long short, it would be absolutely stupid to inject (it is not orally active) self-made propofol and expect to wake up afterwards.
View user's profile View All Posts By User
j_sum1
Administrator
********




Posts: 4918
Registered: 4-10-2014
Location: Oz
Member Is Offline

Mood: Metastable, and that's good enough.

[*] posted on 16-11-2016 at 14:58


Quote: Originally posted by Tsjerk  
Oké, I get your point Maroboduus, but I still think not measuring the pH here is a beginners mistake which doesn't deserve a post like you posted.

I also wouldn't call propofol a drug as there is little recreational use for it. Apperently some people have been experimenting with it, but the dose effect curve is steep and abuse is quite unlikely. The same and better effects can be reached with stuff saver and easier available. To make long short, it would be absolutely stupid to inject (it is not orally active) self-made propofol and expect to wake up afterwards.

Which begs the question of why JnPs is interested in making it.

I get that it is an interesting compound and interesting synth. But if you have limited knowledge, limited access to a lab and limited time such that you omit basic practices, then you are biting off more than you can chew IMO. For a product that you cannot practically use... I think I would look elsewhere for an interesting project.

OTOH, thanks for posting. I am at the level where I learn a lot from reading these things and especially if they contain rookie mistakes.




View user's profile View All Posts By User
Maroboduus
National Hazard
****




Posts: 257
Registered: 14-9-2016
Location: 26 Ancho Street
Member Is Offline

Mood: vacant

[*] posted on 16-11-2016 at 19:53


Quote: Originally posted by Tsjerk  
Oké, I get your point Maroboduus, but I still think not measuring the pH here is a beginners mistake which doesn't deserve a post like you posted.

I also wouldn't call propofol a drug as there is little recreational use for it. Apperently some people have been experimenting with it, but the dose effect curve is steep and abuse is quite unlikely. The same and better effects can be reached with stuff saver and easier available. To make long short, it would be absolutely stupid to inject (it is not orally active) self-made propofol and expect to wake up afterwards.


Yes, maybe you're right about my manners, I'll watch that.
But this guy really smells wrong to me in many ways.

Everything I have read about propofol indicates it is quite dangerous.
It is also now quite famous in the US since Michael Jackson died from the stuff. His doctor was attacked for his decision to let his patient self administer this compound, so it seems to be of a very different risk potential from ordinary sedatives.

I do not feel this way about many drugs. If it were LSD, DMT, Valium, babituric acid derivatives; even if it were methamphetamine I would not feel so strongly.

PCP, heroin, 4-methoxyamphetamine, home made meperidine, some of the more powerful fentanyl derivatives, scopolomine, propofol. There are a few like these I feel strongly about.

But even with these I would not have reacted as I did unless I had a strong concerns for other reasons. I may be wrong, but I do not believe it is at all likely.

Thanks for the explanation elsewhere about chloride in nitric acid. Most of my chemistry was learned in the 20th century, so it still needs much refreshing. (well, to be honest it was always a little spotty).



View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2003
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 16-11-2016 at 19:57


Lidocaine is another more classic synthesis to do in many organic classes, I made it and also TA' that lab in gradual school, so that is very doable, and unless you slather it all over your body or inject it, it is reasonably safe. A woman her covered her whole body with it before some sort of laser hair removal and had a heart attack and died, so it is possible to over do, but not easy. But propafol is not that complex, so not an unreasonable target. Better than many other targets here. Just don't inject it (or anything else you make in a home lab, if you have much sense, unless you are an expert.)
View user's profile View All Posts By User
zed
International Hazard
*****




Posts: 1761
Registered: 6-9-2008
Location: Great State of Jefferson, City of Portland
Member Is Offline

Mood: Semi-repentant Sith Lord

[*] posted on 23-11-2016 at 15:54


Yup! Seems to me, that both Michael Jackson and Brittany Murphy, were fond of using this material, for obtaining truly resting sleep. Well, rest in peace, rockin' rollers. R.I.P..
View user's profile View All Posts By User

  Go To Top