Making Cyrene: the Next Common Solvent?
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- čas přidán 18. 09. 2022
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Levoglucosenone synthesis:
www.orgsyn.org/demo.aspx?prep=...
Hydrogenation of levoglucosenone:
sci-hub.se/pubs.acs.o...
and
sci-hub.se/doi.org/10...
www.rsc.org/suppdata/cc/c4/c4... - Věda a technologie
![Making Dibenzo[a,e]cyclooctene - an Emerging Ligand?](http://i.ytimg.com/vi/_2FNaCZldE4/mqdefault.jpg)
![Making Dibenzo[a,e]cyclooctene - an Emerging Ligand?](/img/tr.png)
Great video! Glad to see you include the links in the video description!
hey TC, glad you recommended this channel :)
Wholesome
We've got 2L of this in my lab, its really not that great(Smells nice though). High boiling and doesn't work in alot of reactions we've tried. Interesting synthesis nonetheless once again!
What does it smell like?
@@kid_missive Niceness
Niceness makes me think of the smell of unperfumed fresh linen and grocery store fresh freezer smell.
Doesnt allow Grignard or lithium base reaction I bet ?
@@thomasrussell4674 linen that has gotten wet and dried a bit too slow smells like moldy crotch
Interestingly enough I’ve worked on a project with one of the creators of Cyrene! Made some cool enamines and explored their reactivity!
Like the enamine with piperidine, reacted with 3-methoxyphenylmagnesium bromide? ;*[}
@@stevengill1736 we tried pyrrolidine, dibutyl amine and morpholine with a series of electrophiles such as haloalkanes and Micheal acceptors. I saw your episode in Hamiltons pharmacopeia and loved your passion for the art which is organic chemistry :)
Keep your friends close, and your enamines closer!
I wonder if it's compatible with PLGA? (probably the world's most expensive plastic- US$200-300 per gram!)
This is quite interesting for me; we're synthesizing peptides via solid phase synthesis and are currently looking for alternatives specifically for NMP but mid-term for DMF too. Issue is that some of our reactants, specifically some oligopeptides with loads of protection groups, are quite stubborn when you want to dissolve them. Works absolutely fine with DMF and with NMP too, but the need for green solvent technically has reached my department 10 years ago and in actuality nobody did anything to prepare for needed changes and now everyones like *surprised pikachu face* because we don't find a proper replacement. I haven't heard of Cyrene before and I'm pretty sure it wasn't tried by anyone here yet, so I'll order some Cyrene, try it on a small scale myself and then maybe save the day.
Not very green, but trifluoroethanol and hexafluoroisopropanol are apparently very good at dissolving stubborn peptides, or so I've heard
@@adrianpip2000 if it's not green it's not an option, since the only reason we are replacing them is the requirement to use a green solvent
I've actually tried it earlier this year for an amide synthesis and haven't had great success. This solvent was not compatible with our catalyst FeCl3, neither with the starting materials (a simple carboxylic acid and 2-aminoethyl acrylate). Just tarred up at elevated temperatures.
Another solvent you could try is DMPU. If I recall it is a "green". We have used it to replace HMPA, and I have also tried to use it a few times to replace DMF. I am not sure how good it actually is, as usually, I would use the DMPU when I had tried all of my other solvents. For perspective, I worked with polycyclic aromatic hydrocarbons/ heterocycles, so if I was using DMPU it was because I could not get any of my usual solvents to dissolve the "boulders" I have made Edit:(by saying this I am meaning I would use it as a last resort, and more often than not this route would end up abandoned). I have let some of the peptide people in our department use it, but I do not really know what ended up happening.
Try GMO for the peptide synthesis.
This is as if a speed runner started chemistry -- crazy to see such an insane process so quickly and still in such detail
I think that green solvent hasn't to be non-toxic. DMF for example is relatively dangerous, but it can be recycled easily and rapidly breaks down in environment. Also methanol for me is "greener" than ethanol because it doesn't form an azeotrope with water so it doesn't require calcium oxide or benzene or something else to get dry
I must say this channel works really hard.. The production plant with green smoke made me chuckle.
With my chem eng hat on my first reaction is "Why is this so expensive if it's made of cellulose?"
Then I see the first step is "Add a load of powder to another load of powder" and my second reaction is "OK, let's not shut down the DMF plant just yet" 😂
Edit: 2:28 yep, that's par for the course with carbohydrate chemistry! I'm surprised this stuff is only €200 per litre 😂
Edit 2: OK here comes the separation step involving chromatography 😂This is a pilot plant designer's worst nightmare!
Again very exotic and elaborate.
The yield is good, despite the expected impurities. How to get rid of it in industrial production?
Never heared of the substance before. I just found it at Merck.
It is gratifying that the solvent is so compatible with health and environment - the by-products (furfural) are less so...
Speaking of compatible solvents: I've heard good things about lactic acid esters (at least where esters are suitable as solvents). Also smell really good. Unfortunately, I have never been able to separate them because of the high boiling point and my limited equipment options.
Would that be something for this channel? Or is that already too easy?
Interesting synthesis, and any green solvent is always welcome :)
As for synthesis, using bisulfite to form adduct with furfural and washing it out should be helpful. Then maybe column could be deleted from preparation or just filtration through short pad of siica to leave behind tar/very polar products could be used. As for reduction I suspect that with bigger scale substrate and forming cyrene could be solvents for reaction (no need for ethyl acetate) for so called neat reaction. And if you like more interesting hydrogen sources for reduction (hydrogen can be more problematic) just add hydrazine, it works wonderfully with Pd/C :P
But the levoglucosanone also has a ketone
@@ficolas2 And? you are asking about reduction or adduct formation? adduct form only with aldehydes and some methyl ketones and reduction will work, it is just other source of hydrogen but catalyst stays the same
It would be interesting to study the interaction of hydrazine with the compound that was subjected to catalytic hydrogenation in this video. The fact is that on the one hand it is a cyclic acetal, and on the other hand an unsaturated ketone. Unsaturated ketones readily react with hydrazine to form pyrazolines. Pyrazolines, in turn, can decompose upon heating with the release of nitrogen and the formation of cyclopropanes. If the acetal fragment is retained during such transformations, a very interesting product can be obtained, which can also be a solvent. Having no ketone group, it will be much more convenient to use. Also, to obtain such a compound, catalytic hydrogenation on platinum metals is not required.
Cool video I like it! but seems odd to call this a “green solvent” when it takes several L of solvent to make a few mL of the “green solvent”. Guessing industry optimized it but would love to see how “green” their methods are. I mean just because it’s made from plants doesn’t mean it’s green right?
Green solvents are less toxic or hazardous to the environment--even if it takes a ton of plants to make, it's better because waste management is simpler and less dangerous to do
@@dextmo6890 but if a green solvent uses nongreen solvents to produce, is it really green?
Exactly. Moreover, nobody really knows about the recyclability, yet. It seems to be in the same case like Ionic Liquids, which are touted as "green" just due to the fact that most of them have low vapour pressure, but in reality, the energy input required to recycle is enormous.
Greenwashing so you can sell something worse as a more expensive premium product 🤣
@mrmax35 You know that those solvents can be, like ... reused, right? You don't use them up during the process
Great video. I'm curious if Cyrene will dissolve stirfoam and of course I wonder if Cyrene is flammable
This is interesting, I've seen this before and I was even thinking of making levoglucosenone myself!
PEG is a surprisingly accessible chemical for the amateur: at least in Canada, pharmacies just sell pure PEG by the bottle as a laxative.
I always learned to add your product on the silica, let it run until the eluent reaches the silica and only then top it off with sand. I believe this way it is easier to limit band broadening.
Was thinking the same thing. Sand was taught to be on top to avoid mixing of the product layer by reckless solvent addition. Running the product phase through the sand and into the silica in theory shouldnt change that much (?), but who can say if all of your product molecules really made it fully through the sand and into the silica so you dont get backmixing and band broadening when you add fresh solvent on top that will disturb the sand.
You should show some reactions, like formation of ureas, substituting Cyrene in for other solvents
This is useful if you have a Kraft paper plant and everyone should have one of those
I've worked with Cyrene before, it's okay I guess but it tends to brown at elevated temperatures, even without oxygen present. I once did a reflux with Cyrene under nitrogen on the Schlenk line, and even before the hour was done, the whole thing burned into tar. Even well below the boiling point it can get very dark. Apparently the lab I worked in even had tried NMR and a number of other methods on the burnt cyrene and found nothing. The color tends to stain things too. The Cyrene also tended to be very wet, which was inconvenient.
However in some cases it can actually act as a reducing agent, allowing for the rather unique circumstance of the solvent to double as a reducing agent. The mechanism for this is not yet known, as far as I know, but I've seen it do this with my own eyes, and the paper on this is probably still in the works.
The cloudiness could also be some celite particles. Did you flush the filter with some solvent before filtering through your product?
This seems incredibly complicated, I like it.
A new ... Non-toxic, Renewable, Biodegradable ... Solvent
Are we supposed to ignore this whole production process?
Well ... It will be fiiiiiiiiine:) Hehehee
Thanks for the entertaining and informative video, Chemiolis:)
Thank you! But I did not understand what the use of methanol was in the beginning, if you let it evaporate. And hydrogen in a rubber ballon will diffuse through the membrane until the next day and won´t be available for the process.
Great video again! Consider doing a dry load when doing column chromatography. Its much easier and you get a cleaner seperation :).
To do this - simply add the appropriate amount of silicagel to your product until it is soaked up and a dry powder. You add the dry load on top of your silicagel, then sand and gently fill up with solvent. DONE!
Hey there! I was curious , what is the diameter of the column you are using? It looks great spherical silica and gram scale reactions!
It is 53mm effective diameter and 610mm effective length
@@Chemiolis oh my gosh you replied! Thank you so much!!
@@Chemiolishi
Next step how to sell Cyrene
Any idea of the electrochemical Window of cyrene? Or the ability to dissolve typical electrolytes for cyclic volltametry?
There is some data on the electrochemical stability of Cyrene™, though it is not in the public domain. Overall, there are indications that Cyrene™, specifically its carbonyl moiety, is not stable at certain voltages, but an extensive study has not been undertaken. Cyrene™ has been used extensively in electronic applications (production of components/devices for batteries), but as far as I am aware, there is nothing in the public domain about its use as part of a device (electrolyte for example).
Why is methanol mixed in at the beginning, if you later wait for it to all evaporate?
Does it help with the mechanical mixing of the powders?
It helps to more evenly spread the sulfuric acid, otherwise it is hard to spread since it is so little.
Thanks! That makes a lot of sense to me.
How does this compare with Hexane? Hexane is commonly used in food processing, and it would be great to have a non-toxic, non-carcinogenic substitute.
(I'm not a chemist, so please pardon my ignorance)
The properties of this solvent are too different from hexane so it can’t be used as a substitute.
I wonder why it has taken so long to get new solvents, green or otherwise, to use for new processes which give much better results!
Is it because we have used the old solvents for so long we don't realize the improvements new solvents and processes may give us?
I, unfortunately, may not get to see or use any of these new solvents or processes, as I am old and may not last much longer.
But it is nice to see others trying out the new solvents and processes!
Green solvent often have a high boiling point so they don't work well for many processes. Especially for things like paint where you want the solvent to evaporate quickly to avoid runs or have the paint dry, so you can move on to the next manufacturing step. Then there is cost. DMF and some of the others are already substitutes for the really nasty stuff. Everyone has heard of the mad hatter from Alice in wonderland. That is because of the mercury and formaldehyde exposure causing hatmakers to go mad.
Do you characterize your compounds? If so can you show how? :)
Where did you get your heating mantle??? I've been wondering this a while.
It’s Asynt Drysyn, they are sold on VWR
@@Chemiolis thank you!! I searched vwr for a good 40 minutes but couldn't find it, but I just did with your reference.
I hope it comes down in price. It would be a great substitute for what we use in my lab.
You should use Schlenk technique to do the reduction, this pseudo inert procedure makes my heart bleed, especially when you apply vacuum to a liquid. On another note if you can't determine the purity how can you determine your yield and claim, that it is quantitative. If you can still see yur starting material via TLC the reaction can not be quantitative. Furthermore, if you suppose that water is present in your product just add a little Na2SO4 to remove the water.
Cool stuff ! A Graham condenser oblique ? I think not.
Nice video.
It's a Graham condenser with opposite working, you see in the spiral there is refrigerant, so oblique is not a issue.
@@tonytrade Thanks for pointing that out.
I'd think the need to consume so much cellulose doing this wouldn't be much of an issue considering there's tons of paper meant for "recycling" that realistically just goes to landfill. Some paper is also un-recyclable because the cellulose isn't long chain enough to really retain usable properties after recycling, but that wouldn't be an issue if you're using it as a chemical feedstock.
get this man a rotary evaporator
using 2+ litres of solvents to make 1.75g of solvent. Super green.
That's not the industrial process though
Interesting. I always love seeing little difference people have while running columns/synthesis. One question: Why do you use short pass distillation instead of a rotovap? Seems like it would be much faster to use a rotovap, especially when removing EA.
I don’t have a rotavap so i’ll have to do with short-path vac distill
Sad that it is so expensive. 119€/100ml from Sigma. Would love to try it out because I am curious about the electrochemical stability 🧐
The electrochemical window of cyrene is small, the anodic window reaches up to 1.2 V vs Ag/Ag+.
That hydrogen next to the carbonyl and on the acetal carbon myst be quite reactive.
Hello can anyone can help me to learn on how should I stard to understand those kind of chemical reactions, please. I want to know this knowledge.
Can it be ethanol in place of methanol?
What is the purpose of the PEG?
Why use a reflux condenser?
So what is the purpose of the PEG here?
I tell you, whomever figured out how to do all of this is a freaking genius!
And add to that fact, that you actually understand AND can do the procedure is mind blowing to me. You are very intelligent. And you should be very proud of yourself! ☺️
Fuck yeah, green chemistry!
It would be a really cool project I would definetly recreate, but the tar... I hate tar.
can't enjoy organic chemistry without some delicious tar. sometimes, when no one looks, I sprinkle some organic reactant onto a heated hotplate to see it char, because sadly the organic synthesis we do at our lab is 100% tar-free :(
@@covodex516 or just add sulfuric acid to sugar
RIP vaccuum pump, you did your job well 🙏
1:40 😭
Did you really used a metal spatula and H2SO4?
Stupid question here. Why why did you say "hexanes" and not just simply "hexane"? Did the liquid you add is not a homogeneous solution?
Hexanes refers to a mixture of C6 alkanes, which contains n-hexane but also 2-methyl-pentane among others. Their polarity is pretty much the same, therefore it is not necessary to use more expensive pure n-hexane for column chromatography.
There are several shapes 6 carbons can make, all with quite similar boiling points. They are distilled off from petroleum and sold together.
We have a saying in our lab: You can do anything with cyrene except dissolve stuff.
Nice job. You should at least measure bp and refractive index
(2:00)
"Hello everyone. Today we will be making piss from cocaine."
((I'm sorry))
You just used ~800 mL of petroleum solvents to make 1-2 mL of "green" solvent.
*Uses liters of hexane, methanol, sulfuric acid, ethyl acetone, and pyrophoric catalysts.*
I have produced a less toxic solvent. Great success.
Greenwashing, eh? Key thing is to move the messy production far away (to some remote country) and use "green solvent" at home. However, if cyrene proves useful, I guess they find cleaner ways to synthesise it. Some fermentation by GMO bacterias, perhaps.
My dad would have loved this method, frufrunal. That would have made him laugh for sure.
But what does it smell like??
The smell is very mild, its vapor pressure is quite low. I don’t know how exactly to describe it, but it is quite familiar smelling and the smell isn’t very surprising. Something you would expect after just having burned a lot of cellulose.
NMP is much less toxic than DMF, if I remember correctly. Just a minor remark.
🙂
Argel Tal likes this
I went too far on heating and i got acetone
Great for a video, thanks! Period.
If we can teach bacteria to produce it - maybe. Otherwise is it sooooooo "green". I mean, yeah, you get it shipped from xyz remote country and tell everybody "green" is your chemistry. Master level hypocrisy typical of our times.
its not good to say its a common solvent . we shouldn't forget about the carbonyl group which can react in most nucleophilic additions .
cool
GVT dudes having trouble distinguishing if he wants to poison people or not
That comma should not be there its supposed to be a period😮
palladium + hydrogen
Next step: how to sell Cyrene
ok this was an extremely weird procedure
the sand and silica was interesting haven't seen that before.
Green solvent, that requires chromatography with $hitloads of solvents, LOL!!!
should have shown all the waste...
Tedious and expensive procedure for a not so complicated formula. Eric Drexler's self replicating universal assemblers are screaming to be discovered:)
Well, I see why it's expensive.
Yeld just horrible. In such case this synthese will be priceless.
Mechanism or it didn't happen!
Anyone here being forced to use cyrene in their labs yet?
acetal + carbonyl group + high boiling point... yeah nobody will ever use this instead of THF, Et2O or dioxane sorry bro
No.
Looks like someone discovered midjourney. Isn’t it amazing?!
I don't wanna
........NOPE,IT'LL REMAIN AS LUXURY
=MIND ALL THESE STEPS,HORRIBLE!!!.................
#Least green solvent ever made or discovered 😂🙈
1.8grams of solvent from liters of other solvents and a few KWh of electricity 🤣
Talk about greenwashing and soing more harm to the environment than just using some other solvent