Making Ethyl Vinyl Ketone (Grignard reaction & Allylic oxidation)
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- čas přidán 25. 05. 2022
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Preparation of grignard reagent, doing a grignard reaction with ethyl mgbr and acrolein, protonating the product and then oxidizing with activated mno2 to make ethyl vinyl ketone
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Find the updated and successful procedure to ethyl vinyl ketone in this video: czcams.com/video/bl7K3lRPLYo/video.html
As some others have pointed out, MnO2 oxidations can be tricky. I know of a few cases in our lab where the commercial stuff was very inconsistent, so many ppl seem to recommend preparing it yourself and use it relatively fresh. It can also very much depend on the substrate, so if you've tried MnO2 oxidation on another substrate before, it might just be that this one needs very active MnO2 to work. Also, a quick mention about TLC results (if you have any plates) could be nice. In any case. Still, very nice video :))
I know a bit of an unconventional method that always gave me decent yields when making aldehydes.
Put the alcohol and the manganese dioxide in a glass jar (yes, a thick old jar) and then add some glass marbles or ceramic bearing balls. Close the lid, put it at an angle and start rolling it like a ball mill. Depending on how reactive and how viscous your alcohol is, it could take from a few hours to a few days.
You can always use a Collins or a Swern (although it is stinky) oxidation that can tolerate acid-sensitive functional groups!
Fétizon is also a possibility
I feel the pain about loosing glassware. It never feels any better breaking a piece. Sorry this one didn't work out for ya!
Great video. I share your pain regarding the MnO2 oxidation as I've tried this before on a different substrate. It turns out that the MnO2 oxidations are highly capricious and dependent on the manner in which the MnO2 is activated and oxidative ability can vary from batch to batch. Good luck with whatever you have planned next! Maybe a cheeky Silica column purification would be an idea for another video; perhaps with some coloured compounds?
Thanks! I definitely plan on doing column chromatography in future videos.
@@Chemiolis
I know the double bond might reduce the rate of the reaction but have you considered the Fétizon oxidation ? It’s mild and very selective to the point that it can’t even oxidise aldehydes.
@Chemiolis sir you might have chose oppenauers oxidation with Al( isopropoxide)3 and acetone , this rxn is so selective that it only oxidises 2 degree alcohol , neither 1 nor 3
Oh! I almost forgot. Try using acrylonitrile instead of acrolein in the Grignard reaction. That would give you the ketone right away (after hydrolysis of the imine).
Great idea! And it’s cheap as well, i might try this! Even with low yield it can be a lot cheaper than buying the EVK
@@Chemiolis Would be great, if you tried it! I am looking forward for your next video. 🙂
Yeah, acrolein is a bitch to use, with grignard reactions it can also have conjugated addition.
The nitrile pathway is way better because grignard reagents do not add on imines.
Crying in yellow chem :((
I've studied so much about Grignard reactions by in Org Chem in college and is nice to see how it is on practice. Is crazy how we learn about all these reactions in class without ever realizing the pain and the process when actually doing it IRL.
Very good channel, been following for a while, interesting every time!
Mno2 oxidation is tricky imo. I have oddly enough had luck with mno2 from our local pottery store. Yields aren't amazing but they can be good. A little bit of acid can speed things up. The worst part is when you have to use alot the stir bars I have don't hold up and get stuck. Great video man that was really unique to see and very cool!
Very nice attempt! MnO2 is a bitch. Unsaturated carbonyls are often pretty elusive. Had some problems with both recently. Don’t give up! I would probably try PBC or IBX as an oxidizer. And I know it sucks working with acrolein, but to distill a couple of times never hurts. Wish you luck with a new attempt!
long time subscriber here.. your vids are great reminds me of my organic lab days
The preparation of MVK, EVK, PVK - ROS V1, (Reagents for Organic Synthesis Volume 1) is a great reference book to read.
Interesting video. It seems that your acrolein survived. I might suggest that you save everything until you get your product. You could put your manganese dioxide in a Soxhellet extractor and run it a while. A Soxhelet extractor is a useful gadget but I guess you need to replace your vacuum distillation apparatus first. Soxhellet extraction may make your product appear. You could use pentane as your solvent to avoid degrading your product.
You could also make some 2,4 dinitophyhadrazine reagent. (The explosivity of this 2,4 dinotrophylhydrazine is blown out of proportion.) Test a small alloquate of your solution. If you get a yellow, yellow-orange, orange or red precipitate recrystallize it from ethanol and do a meting point. The derivative has a specific melting point. This might detect where it went. If you don't have a melting point apparatus you should look into one. Melting points identify a substance and the sharper they are the better.
2,4 dinotrophylhydrazine is a 2,4 dinitrophenyl group attached to a hydrazine and is useful for making 2,4 dinitophenyl hydrazones which are relatively high melting derivatives of carbonyl compounds. The melting points are quite specific for a given ketone or aldehyde. This was used to identify which aldehyde or ketone you had.
There is a fancy reagent you can make with ethanol, 2,4 dinotrophylhydrazine and phosphoric acid and the reagent is positively nonexplosive. Or you can dissolve the 2,4 dinotrophylhydrazine in ethanol and use that. (This is how we usually did it.)
Wet chemistry is not used so much now but for what you are doing it would be useful to follow you product as you proceed.
I don't know the melting point for the derivative you would make. I don't have the derivative book either. There used to be books of the melting points of derivatives and their were a number of them.
Explosivity of 2,4 Dinotrophylhydrazine
This is blown out of proportion by political fear mongers (my opinion). To be a problem the 2,4 dinotrophylhydrazine would have to be dry and dirty. (Older containers had steal caps and rust would make the compound unstable especially if dry. The container should never be thrown or dropped, however. There is less shock through modern plastic containers and no rust from the lid = Much less apt to explode.
Hope these ideas help. Good job on the acrolein!
I am a chemist myself (retired). I used to make crown ethers.
For some reason those allylic oxidations with MnO2 are extremely finicky. The only time I've had any success with it, was when it was freshly prepared, from permanganate, within minutes of the oxidation. For some reason (it seems to involve particle morphology and potentially also different allotropic forms), it just doesn't seem to store very well, even if it was prepared and stored in a glovebox.
You also *need* to follow this reaction with TLC.
Finally, I would suggest trying a run with the addition of a mild co-oxidant (such as acetone) together with the freshly prepared oxide, potentially buffering the reaction, or if all else fails, adding some form of phase transfer catalyst.
That's odd, i haven't done this type of reaction before, but it came fresh out of the bottle, bought last week! It should have done something since my alcohol wasn't there anymore, i think the product is just annoyingly sensitive.
@@Chemiolis If you lost yield because of adsorption onto the excess MnO2 then you might try reducing it to Mn^2+
Great video. I just love your videos cause they're high quality 😍.
Can you post a video on making bromoethane.
I think bromoethane is made with ethene and HBr, for now i don't work with gas reactants, but maybe in the future.
Very nice video, I always love to see a grignard reaction, and the oxidation step is quite interesting too. How many run have you done?
I did it two times
MnO2 oxidation is your hurdle. Mate buy some TLC plates or make your own (much cheaper) so you can observe the oxidation reaction and drive it to completion before distillation. It is of utmost importance to check the reaction for conversion when doing any organic synthesis.
Maybe the Oppenauer oxidation will work? It seems to be pretty useful, although aluminium isopropoxide is a rare or hard to prepare reagent. (if you are interested, there is a method of its preparation with electrolysis instead of mercury)
If it uses a base in the reaction i think it won’t work. This a,b-unsaturated ketone is too sensitive, that is why i chose mno2, which is supposed to work very well with allylic compounds
@@Chemiolis Aluminium isopropoxide is a weak Lewis acid, not a base (although it can accept a proton). It might look like a base due to the name similarity with potassium isopropoxide ot something else.
This oxidation guaranteed works on unsatureted substrats (allylic or propargylic systems) according to 10.1021/ja063842s. One of them looks almost the same as yours.
@@dimaminiailo3723 I looked quickly online and saw that it is often used together with base which is why i mentioned it. I think it could work with the literature u gave. Someone else recommended a one-step route to get the ketone instantly after Grignard, which eliminates the need for oxidation (if it works at least), which i might try sometime, also only requires me to buy 1 cheap reactant extra which is very nice.
@@Chemiolis TCCA? I have never heard about the direct oxidation of alcoholates
Very nice video! Can’t believe you heated a Grignard very risky stuff right there
It just didn't want to start properly so i had to force it a litte, it worked fine. It was only like 30-40 C, with heat loss that's probably the same as some labs have as room temperature
@@Chemiolis very true! I mentioned before, if you ever try this again use an initiator in the form of a very small iodine crystal.
A surprisingly simple way to start a Grignard is to dry stir the Mg turnings while flame drying the flask in vacuum. It grinds off the oxide layer enough to expose some fresh Mg. In the lab course I was supervising 7 out of 8 Grignards started without any issues. And guess what the failed one didn't do :)
cool
In theory, the desired ketone can be obtained by employing nitrile (acrylonitrile) in the Grignard reaction
Idea:
1) Benzoin-esque condensation between acetaldehyde and diethyl carbonate with cyanide catalyst, giving 2,3,4-pentantrione.
2) Reduce with NaBH4.
3) Eliminate and isomerize under dehydrating acidic conditions to more stable conjugated product.
Another idea:
1) Benzoin cross-condensation between propionaldehyde and acetaldehyde to 3-pentone-2-ol.
2) Eliminate.
Oh! You need to become familiar with horseradish. Magnificent with beef.
What you can try, is buying 3-pentanone, do an alpha-bromination in acidic condition (should only do on addition) and after that you heat the thing in pyridine or another base and you should observe the elimination because it is (I think) the only irreversible reaction in the pot.
I tried this, it doesn’t work. The compound doesn’t do very well in the presence of base and heat, polymerizes most likely, and almost impossible to separate from pyridine with the similar boiling points.
Wait you did not decant the magnesium after gringard? Is that legal?
Very nice !!!! I would suggest that it is possible for the michael product to be produced in the first step, since itis not protected ...
I'm curious about selective dehydrogenation to form double bonds and wonder if those exotic Molybdenum catalysts could be used to afford the R-ivinyl ketone? Nice synth here and it must be so very toxic as mvk is a 4 on that scale (worst).
I think it could work depending if the process can be done at low temperatures and without base. I did see literature about reacting MVK with formaldehyde in the presence of piperidine hcl and niobium oxide to get a mixture of ethyl vinyl ketone and methyl isopropenyl ketone, but it was done in a pressure vessel at 6+ bar.
why the grignard didnt make a tertiary alcohol and stop in the secondary?
What did the TLC say about the second step? Any new clean spots? Unlike others, I had a good experience of MnO2 oxidation, although it was a much more robust reaction...either benzylic alcohol to aldehyde or hydroquinone to quinone, much easier. Also, I am surprised with your luck with the first step, I would expect you to have a lot of impurites due to competing 1,4-addition of the Grignard. Well done! :)
I belive grignard without any additives like PhSH prefer 1,2 additions over 1,4 additions.
I wouldn't really worry about trichloromethane, with the somewhat higher boiling point than dichloromethane, less vapour comes off it, and really, they're both not good for you. Neither are confirmed human carcinogens but the fact both are suspected, is not great. I always look for alternatives to either, and usually if no viable option exists I just don't do the reaction or synthestis, but I only make soaps and perfumes so I have the advantage of just being like "well I can't make it, so I can either use something else or buy it directly". I understand that's not always an option
Is there a reason that you heated the Grignard to start the reaction rather than using an iodine crystal or crushing the magnesium to expose the metal and start the reaction? That’s the way I learned in school that a Grignard reaction is started.
I just did it to speed it up, i also started the stirring with the stir bar which will scrape the magnesium similar to crushing.
youtube chemists are allergic to analytical chemistry i would love to see some purity tests and then finding out what the impurities are and the reaction pathways
Usually i do some TLC off cam, but unfortunately most proper analytical chemistry requires very expensive equipment. If i was NileRed i would have bought a HPLC already
@@Chemiolis even nilered started in his dads garage
And btw sigma is very expensive,you should search for a better source
It seems only sigma sells it in my country, also i can't order from everywhere.
dammit,
Ligma Balldrich strikes again with overpriced stuff
How does it smell 1 penten 3 ol?
It's not pleasant, all i can say, doesn't smell like anything i know
How Did you ordered from TCI ?!
Can only be done through a company
Is the Evk ethylene vinyl ketone a cancer causing chemical ?
It is not carcinogenic, but it is toxic and irritating
why did this get sent to my notifications 8 times?
Not sure, did it show different titles? I changed it a few times.
Use Mannich reaction
Hey! make some videos about extracting precious metals from the electronics parts
I want to, but it takes a long time to save up parts and tear electronics down.
@@Chemiolis I could mail you some parts containing gold/palladium/silver/platinum
@@365Condoms That would be great, but It depends, how much is estimated to be in these parts? It's important that the scale is neither too small nor too large.
How do you buy chemicals? Almost all companies will not sell to individuals.
I order through a company
@@Chemiolis that's it? No other information?
Thin layer chromatography so that you can follow your progress, could have used Brady's reagent for detecting the ketone on a think layer chromatographic strip for instance.
How mouch do you hate yourselve? Acrolein!!!!!
Do you work at a lab as I see you can order from sigma?
Yes, my own. Set up through a company, then if you have official registration u can order there. A lot of chemicals also require declaration forms where you need to specify use and fill in your details. Sometimes also your passport info for things like 50% peroxide and sometimes 'proof of expertise' aka a chemistry degree.
@@Chemiolis that’s pretty cool
make metyl ethyl ketamine
It is expensive 😂