Asymmetric Organocatalysis: The 2021 Nobel Prize
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- čas přidán 24. 11. 2022
- Correction for 9:15 - I meant to say non-polar.
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In this video I am following a method which uses asymmetric organocatalysis with the catalyst L-Proline. This method (from 2022) is a prime example of how the discovery of organocatalysis in 2000 is still used today and how the 2021 nobel prize shined a light on it. In the procedure, a bicyclic enal is synthesized, which is a key intermediate for the synthesis of several relevant hormones in medicine.
Procedure:
www.orgsyn.org/demo.aspx?prep=... - Věda a technologie
Should this be a series? 🤔
YES
Yes. It should be
Of course
I think it should be. I generally can't think of a practical use the first time I see a lot of these Nobel Prizes, but these videos help me understand how simple and useful they can be.
Definitely
Great video! For water removal with toluene, you definitely need Dean-Stark.
As for column... sorry to say that but it looked bad. There are two ways to pack column, dry and wet one, before you were packing wet (slurry, tapping and so on), second is dry, you put dry silica into column and then flush it with solvent to moment when it is packed and uniform. You did something in between, silica was to dry to put any sample on it. it should be flushed with clean solvent before to equilibrate it. that is why there we so many streaks and not nice bands .
I followed how they did it in the procedure
@@Chemiolis Seriously? pretty strange i would say personally, I never meet with such preparation of column, only wet and dry (personally I am dry preparation guy)
true is that details about chromatography separation are often very... lacking, like only eluent system (and it is not always all data) and no diameter, height of stationary phase and so on
@@Chemiolis The thing that confuses me is the added water to the silica gel.
The easiest way is to do a wet packing with hexanes. You take the proper amount of silica in an erlenmeyer, and add a bunch of hexanes. Stir the slurry thorouly and make sure that there is no air bubbles.
Add the slurry to the column, and wash the sides of the column with hexanes. Always have excess solvent on top of the silica when inside the column.
Also, for better separation, you could try to do a solid addition (basically dissolving your sample in a bit of DCM and add some sillica. Evaporate DCM and you end with a dry free flowing powder that you add to your column)
@@ejkozan i was also confused that they did it this way, but I just followed it, maybe they just didn’t mention it correctly idk.
@@ejkozan yeah the paper is weird - "Pre-treated wet silica gel was prepared by adding H2O (25 mL) to silica gel (50 g; Sigma-Aldrich technical grade, 40-63 µm) (33% w/w) inside a sealable container. The container lid was closed, and the mixture was shaken vigorously until a uniform consistency was obtained (this process is exothermic, and care should be taken when venting the container). The wet silica gel was then allowed to stand for 1 h prior to use."
I'm not going to pretend I know what the heck you did. But it was sure fun to watch. I'm definitely learning more and more with every video. 👍🏻
I worked on a multicomponent organocatalytic synthesis, and yes it's works great.... When you find the good catalyst.
In organocatalysis there is a lot of work in catalyst design. There is not a lot of thing working well with proline hahaha....
(Maruoka catalysts..... I saw you behind your expensive price !)
But yes the Nobel prize deserve well McMillan and List ;)
you are a great inspiration, overtly. Through your very educational videos you remind me why organic chemistry is one of a kind
thank you
I have never studied Proline catalyzed reaction in my bachelor and your videos are useful to visual the lab procedure and I always finish everyone of them learning something new.
Ty for your work.
What a great organic chemist you are!
Very special - as always.
Better than Nile Red hands down
The projects aren't as ambitious and the material is less accessible to us untrained laypeople... but uploading more than once a year is a big positive for a channel.
Great video! This reaction is a pain. It took several years to optimize the conditions to give >30% yield, but it did not scale up well. Also the exact polymorph of proline surprizingly matters. But you cannot expect a clean reaction when the starting material is as reactive as the product)
What does polymorph means?
I believe it was Hajos and Parrish first discovered the application of proline in the catalysis of asymmetric aldol reactions in 1971 while working in industry.
Then this reactivity was rediscovered by MacMillan and List who then first actually properly created organocatalysis, by creating catalysts that are derivates of prolines and other aza heterocycles.
Maaan, its amazing things u r doing. Thank u.
P.S.
Tha oldschool wolvorine -- breaks my heart.
Another excellent video :)
I love when im halfway through the video and see liters of black liquid and think to myself "alright well that was a good attempt" then you pull it out in the end what a chad chemist
It’s crazy how many times two different people discover the same thing at the same time lol
I was thinking the same, as if the ideas float arouind..
@@petkotzvetkov6528 They kinda do. Inventions are made because there is a demand, so it's possible from the beginning for several groups of people to start working on similar projects. Finally, the technological and intellectual prerequisites for the invention become available at a certain time, benefiting these groups of people simultaneously. They don't have to know about each other.
@@georgejanzen774 But the examples are so many that this can not explain it all.. and with chemistry and physics there is not so many groups working... I wish you health and luck friend!
Benjamin List will give a lecture at my university in January, I'm pretty excited :D
Great job sir
"short path distillation" is a favored phrase on this channel lol. Ive watched a few videos and that is something i hear a lot on here. lol
When will we see the rotovap? How much would a decent one cost u, and are those AliExpress one's any good? Also does IKA have like a cybermonday/blackfriday sale?
This was excellent. Any idea why the succinaldehyde yield was only 42 percent? Did it actually come over during the toluene and water removal? Did it polymerize and not come over at all?
Some came over after the toluene, I wasn’t paying 100% attention and some of it made it over before I swapped it. Part of it also polymerized yes, but it was relatively minor, seeing the residue that was left behind.
It's true, MEK (methyl ethyl ketone) substitute is EtAc (ethyl acetate). Cheers on cool synthesis here 👍
Hey Man love your videos.are you dutch?
Do an Q&A
Which compounds usually elute first in a cloumn chromatography (polar or nonpolar first)? Shouldn't the non-polar compounds come first, since the polar ones are more strongly bound to the silica gel?
You are right, I wrote it down wrongly in my script and it accidentally made it in
And here I thought the added water flipped the script .,
it is up to your solvent system. if you choose water as the eulent polar compounds come first
You shouldn't do a wet pack column with water when using silica gel since water will dissolve silica gel. It is also an extremely strong eluent in normal phase so your column wasn't equilibrated when you loaded it hence the poor seperation. Flash columns should usually be wet loaded with hexane or diethyl ether since silica gel is incompatible with aqueous eluents. When aqueous eluents are needed a derivatized silica like RP-C18 silica should be used or an alternative like alumina.
Maybe do chiral resolution (not exactly organic synthesis though).
Good idea. Could make something like a chiral imine (probably sulfinimine would be best since that's chiral) and measure the two diastereomers as a means to get ee. Then taking optical rotation on the aldehyde to see if it's the (-) or (+) enantiomer.
I feel like you need a longer column. That will probably help with your seperation.
I actually used the same column diameter and silica amount as in the literature!
Then looks like we have a critique of the literature! Nice.
where do u live? mb someone has an NMR somwhere near u? or someone could share silufol with u? Maaan, U r soooo cool, i just want sombody to do it even better.
Очень интересно:)
Why did it take so long for what seems like simple chemistry like this to be discovered?
The limitation in the past was charactising what was synthesised. Once you have techniques like NMR organic chemistry really advanced as all the products, side products could be identified.
Actually this was discovered in 1971, however it wasn't really studied as the yield and ee weren't that great.
Only in the last 2 decades organocatalysis started really coming about
This guy doing postdoc level work man !
3:40 That's fucked up, my man. Well done.
I think if there's a chemist out there who can figure out the strange and terrible chemical composition of a McDonald's chicken McNugget, they definitely deserve a Nobel prize. Extra credit if they can definitively say why, even with the frankensteinian mix of chemicals, it's still delicious.
It's extra delicious if you nitrate it first.
It's the silicone oil I think...
I wonder what the LD50 is on McNuggets
Carlos Barbas will also be remembered :(
Next synthesis of atropine from succinaldehyde 😅
Just give it to a TU/e student that does chemical engineering 🧐
Oh look another Rhodium Archives meme reagent lmfao
Buy a rotovap.
a rotovap is just a short path distillation for people who enjoy spending too much for lab apparatus.
Please donate
Rotavaps cost a lot.