Alkylation of Cyclohexanone
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- เผยแพร่เมื่อ 4 มิ.ย. 2024
- Correction: Methyl iodide bond is not normally polarized. C and I electronegativity are too similar. The bond is polarizable. Which eventually results in the same effect as if it were polarized, only it first requires encountering a molecule which can make it that way. It seems that this is a common mistake, considering halogens are normally known for their electronegativity.
Happy easter! You are blessed by a new video. This time, some half-disastrous organic synthesis (yay). I'm working on two other projects now which are even more disastrous so i have to see when that will be done :-).
Support my channel: / chemiolis - วิทยาศาสตร์และเทคโนโลยี
I really like how you showed the assembly of your setup. It helps us that dont have degrees In chemistry. Thanks so much for the great videos. Keep em coming.
Even for us that have already a chemistry degree, these videos are super helpful and educative.
My man is clandestine
The reaction theory and mechanics is educational and one of best of all chem channels.
as someone who only had an honestly pretty poor HS chem class, your deeper explanation of what you are trying to accomplish and how it happens is amazing. I never learned so much of this about polarity and whatnot and its really cool to learn about
Yep, and we thought inorganic chemistry was fun in HS reacting sodium with water. lol Organic chemistry is even more fun, it's like Lego building by attaching molecules to phenols in their Ortho, Meta, and Para positions. Sometimes using protective groups to avoid side reactions.
You teach O-chem wonderfully. The visualization of chemistry as armed muggings is very effective.
You should continue making other basic organic chemistry reaction,i would like to see izomerisation of butane for example
What do you mean by butane isomerization?
@@slimp4644 from n-butane to isobutane
@@alext552 but if it is an n-alkane, can it still isomerize?
@@slimp4644 yeah, you can catalyze the isomerization pretty easily. its a common industrial process
Important note (if a bit semantic): resonance does *not* mean that the molecule "resonates" between the two resonance structures. Instead, it's a hybrid of the two. This is sort of like how a mule doesn't resonate between a donkey and a horse- it's a hybrid of the two animals.
Resonance is awful anyway, its not hard to describe the conjugation present using basic Huckel theory.
@@benwhitehair5291 but that hybridization is hard to draw. The whole point of resonant structures is to give (1) a parseable drawing and (2) a way to explain how the hybrid behaves.
Nice to see a new chemistry channel doing some higher level syntheses! Chemistry TH-cam is swamped with general chemistry level videos or videos where the audio/visuals are so bad you can't bring yourself to watch it. This is the first video of yours I've seen, but I went ahead and gave you a follow because I'm optimistic about your future content!
My two pieces of constructive criticism:
1. Maybe up the tempo that you're speaking at and the energy you put into your voice. It can make any presentation more exciting to watch. Don't go overboard with it like some TH-camrs though.
2. Iodine actually isn't very electronegative! The difference between it and carbon is minimal. The reason alkyl iodides are so reactive is because Iodine is so large and polarizable that it's an amazing leaving group!
Keep up the great work! Looking forward to seeing more of your videos
Any organic synthesis video posted on TH-cam for future chemistry students and current students is always a blessing
Hope your channel grows bigger, you deserve it.
nice to see a new player in the youtube chemistry realm, I really liked the simple way you explained the reaction mechanism without much fuss, easy to understand for amateurs too I assume.
You have a new sub in me, since I'm genuinely scared to be haunted by yellow chemistry. Started a new job in solid phase synthesis of peptides two months ago and in two of the three synthesis I did so far, the yellow was haunting me through the entire process, combined with the pungent aroma of thioanisole and ethanedithiol in one case...making the full Ex&F S4N4 experience! :(
I agree, while NileRed and some others are fun, there's a bit too much showmanship going on. Chemiolis cuts to the chase and presents great reactions with well illustrated theory and mechanics.
Really enjoy the videos, currently studying for A-levels and going for a degree in Chemistry later this year. Considering starting my own chem setup sometime soon, any beginner reactions/ processes you’d recommend?
I'd say to just do what you like, though it is quite a difficult hobby since it is expensive and for a lot of things u need a fume hood. Doing some experiments with gasoline and benzene outside should be pretty fun, just make sure it is safe enough. I can't recommend 'dangerous' stuff because all the other chemists will come and kill me :-)
@@Chemiolis Of course I wont do anything dangerous… yet ;). I might just start with some basic distillations and see where it takes me, maybe aspirin synthesis could be quite fun and I love how the crystals form at the end, involves some pretty useful physical chem skills too. I feel like the more procedures I do, the more equipment I will accumulate which will lead to more experiments in the future so starting will be the best thing for it. Thanks for the advice though!
Some nice and easy suggestions: Organic Chem: synthesis of the pleasant-smelling ester, methyl salicylate (Oil of Wintergreen). Inorganic Chem: demonstration of the various colourful oxidation states of Vanadium (you'd need ammonium metavanadate and zinc metal granules). Alternatively: the Belousov-Zhabotinsky (BZ) oscillatory reaction involving iodine species (the 'Iodine Clock' reaction). Natural Product Extraction: extraction of eugenol from eucalyptus leaves by steam distillation
@AR A fun, and relatively safe chemical reaction is reacting Elmer's White Glue with boric acid in an aqueous solution. I'm not 100% sure of the concentration of the boric acid solution, but you will be able to chemically transform the sticky liquid Glue into a ball of silly putty-like substance. Be sure to wear safety glasses, acrylonitrile gloves, and other appropriate PPE when performing this reaction and all other chemical reactions/experiments, and trear all chemicals/chemical compounds with the appropriate level of respect, because they are all potentially hazardous materials if not handled appropriately!
Just try not to go to jail. It's easier than you think in a lot of the world. :)
its very good seeing the actual setup for reactions. we learn so much in orgo about what happens "theoretically", but not much about the actual equipment used, conditions, etc.
The animations are a really fun way to show the reaction. Well done!
One of the best chem youtubers out there
Nice video, it's like going through an organic preperation book with having all your notes from the lab journal already included.
Perhaps the most accurate depiction of C-C bond formation to date
Such a great video. I really like when you mention what the chemicals smell like. That is very interesting to me. I wonder if this chemical is considered an aromatic? It sounds like it smells wonderful. I like chemical smells for some reason.
Thank you. The compound isn’t considered aromatic, there are specific rules that determines if it has aromaticity.
Aromaticity is a bit of a misnomer, aromatic molecules don't have to smell aromatic. Google aromaticity and or Hückel's rule.
@@richardwiersma I did Google aromatic awhile ago. It had examples of things like the chemicals in gasoline and things like toluene. Google also mentioned the the rings of an aromatic. I am just learning the very very beginning of chemistry. So bear with me. I will look up the other thing you mentioned right now. And thank you for replying. It helps me to learn more! ☺️
@@tracybowling1156 yes, isn't it interesting?, (organic) chemistry!
@@Chemiolis- As an alternative, I was wondering if it's possible to nitrate the cyclohexanone in its Ortho position, then methylate it with something like methyl iodide?
The visualization of how you mangle that molecule was entertainingly interesting🤣. Great job😎 keep it up, pal!👍
This was a good video, I always prefer when videos go through the effort of showing things like the mechanism of a reaction and the purpose/use of the dean stark trap rather than just doing the synthesis, hope you continue on building a channel with good videos like this
If you're gonna use argon for a constant flow, I'd strongly recommend an economisier regulator with a flowmeter and a check valve for on top of the aparatus. For argon flow you should really only need at most 1 litre per minute, probably a lot less, .25-.5 litres per minute should be enough to just keep air out. Nitrogen would be much more economical too. At .25 litres per minute argon flow that's only 360 litres of argon @ 1 barA for 24 hours flow which shouldn't be too expensive. With no flowmetre and economiser on the regulator you'll be pissing argon out the line.
Yes his "schlenk" technic always makes me sweat.
Thank you for showing the footage of the set-up!
Really great Video. One advice I have for you is not to directly drop larger stirr bars into the flask like at 8:13 or even worse at 12:37 where there is nothing in between to slow it down. I‘ve seen several students break their flasks that way. Just tilt the flask and let the stirr bar slide down on the side
the best mechanism ever
Nice video. Reminds me of my work in grad school. I'm retired now.
I think the electronegativity argument at 1:12 for explaining why the carbon of MeI is electrophilic is flawed. Iodine is the least electronegative halogen, yet MeI is the most potent methylating agent. If your argument was true, MeF would be the most reactive. I think using the X-CH3 bond dissociation energies would be a better explanation, as the BDE decreases when going from F to I.
Also could add an argument about polarizability of the compound. i.e, iodine is a rather large atom that can easily polarize when subjected to a charged species.
You're forgetting about bond strength. The methylation occurs because of electronegativity but because the CH3-I bond is so weak compared to a CH3-F bond it means that the iodine can be kicked off easily. So he's right but a bit of nuance may have helped
@@neillcoetzer9133 I am not sure if that is a reply to my comment, but BDE=bond dissociation energy.
@@TheBackyardChemist yeah I commented before reading all the way through mb
Man you have entirely replaced NileRed regarding fun Organic synthesis and/or extractions. Been enjoying all your content lately
Oh we definitely need more lectures in that animation style. OChem would be so much more fun
Fantastic set up!
This might be a silly question, but why didn’t you just add base to remove the alpha hydrogen to make an enolate ion, then that would alkylate the alpha carbon?
Excellent chemistry ⚗
Alkylations are heavy duty reactions. Very nicely done.
Great explanation, im interested in all small synthesising steps, Keep it up!
Great video. Are you thinking about doing product analysis by boiling point, refractive index, IR, etc?
subbed for the explosions when showing the mechanism
A Dean-Stark apparatus typically has a petcock on the bottom of the collection tube.
Excellent video!
Great video! I love those lab jacks, I have the exact same ones. Missing clips on my little red one though
You need a split support ring for your sep funnels so you don't have to jiggle around getting the petcock through the ring. You can just cut a segment out of a standard ring for this purpose.
Could the solid stuff in the second step have been over alkylated amine salts?
Surely the enamine formation was the critical step that lowered your yield. It could be monitored for completion with TLC and also to increase yield you can use the Soxhlet apparatus filled with molecular sieves or other suitable desiccant to dry the reaction mixture and drive the enamine formation to completion. That and maybe use a bit larger eq of MeI in methylation step to increase yield.
Why not simply form the enolate and then do an SN2 reaction so no need for an enamine? is it because its simply not as effective?
If you need argon due to some tiny leaks, a balloon is good and cheap one. Put balloon of argon in gas connector. It allows temperature changes to change volume too without problems of closed system. If you have some tiny leaks you may need to change the balloon over long time. It will not consume argon as a constant flow and you avoid things getting evaporated away with flowing argon too.
You probably lost a lot of material in the distilling step. When the temperature difference of compunds is smaal like say 15C or so, you get a lot of product distilled as a mixture, especially without a column to help in separation. Simple distillation takes you only so far. (Dead volume if always a problem with columns and small volumes though).
that explosion at 50 secs ... :D
very nice montage and procedure :D
The way he drops in his stirr bars makes me anxious.
What about reacting cyclohexanone with an alkoxide base to make the enolate and reacting that with methyl iodide
LDA or another amide base would work as well, but I think that would be overkill
Alkylation of enolates requires strongly electrophilic halides, like, allyl halides, benzyl halides, alpha-halogen carbonyls, with other halides there's significant competition with oxygen alkylation to give enol ethers.
@@michaelsambor5286 Why though? It's the general procedure used in the lab if you want to generate the enolate in a stereoselective and complete way.
Wherever you live are you actually able to buy reagents as a civilian? Or do you do this through a university or work?
The carbon-iodine bond is barely polarized. Their electronegativities are almost equal. Rather, the said bond is polarisable
In general the process could be reduced to just only two steps. I’m not sure about how easy to get a chemical called Brederick reagent or dmf dma, but those are available in stock.
First step, using dmf dma, dmf as solvent, u get enamine.
Second step. After recrystalisation in mtbe, add 0,2 equivalent of pd/c in hydrogen atmosphere(EtOAc solvent should be used). After all, u get 80-90 percent clean product, that can be used for the next step.
I did this synthesis, but using tetrahydropyranon instead of cyclohexanone
The pleasure of opening a new reagent
How would you do it with para-piperidinon?
Why can't we just deprotonate the ketone with a bulky base to form the enolate? We don't have bond strain since it's 109.5 degrees? I thought we add secondary amines to carbonyls that have bond strain?
Since that carbon was already nucleophilic at high pH, was the pyrrolidine used to protect the oxygen?
Be careful, the methyliodide is considered as apolar.
Because the C-I bond isn't really polarized.
Why is MeI a good electrophile? It's because that I- is an excellent leaving group and not because of polarization of the bond.
Since iodine has many electron shells, the negative charge density is diminished (aka spread around). That's what we call polarizability. The more that the charge is spread around, the more stable it is. More stable charge means better leaving group.
Since iodine is highly polarizable, it becomes a great leaving group, hence the great electrophilicity of organoiodide compounds
Where did you get that round bottom flask to hotplate adapter at 8:03?
I bought it second hand, it’s called a ‘drysyn’
Oh hey, I remember learning about this sort of reaction in my lower div ochem classes
Other youtubers: lamborghini huracan,
Chemiolis: 10l argon cylinder
I like the vid. I was wondering why you tried to create the enamine instead of just forming the enolate? That would’ve removed the whole isolation of the enamine via distill and you could’ve just done the reaction all in one pot under argon to give a really good yield (given that you have syringes and septums).
Anyways keep up the good videos!
Enamines are less likely to over-react. The enamine distillation was optional if the procedure was done properly under argon. Since the enamine has such a high boiling point, the solvent and pyrrolidine are usually distilled off under vacuum and the residue with the enamine and cyclohexanone is used to continue. I didn't see much literature that went for the enolate route on this one.
Great Video Tutorial, I Hope Next Time You Can Kindly Please Make A Video On The Synthesis Of alpha-Toluic acid 😄😁🙏🙏 Thank You
Well, the electronegaivity of iodine and carbon doesn't really differ that much. The reason why iodine is a great leaving group in SN2 reaction is because of the polarizability.
Strontmooi, wat gebruik je om videos te editen? Ik ben er meestal veel te lui voor en pomp het gewoon rauw op Jijbuis
Ik gebruik Premiere pro :-)
It was very interesting how you showed the mechanisms of attaching the methyl group. I think you could have alittle more in depth to what each step was. But other then that good video
When does an imine form and when an enamine?
the editing was hilarious 😂
Been hitting the chemistry videos, love your opening pathway animation and talkthrough... Could you think or know a channel who turns real world items into other useful chemicals, sorta like alchemy. I know treated pee,charcoal and sulfur.,., wood ashes and tallow,.,. Egg shells vinegar acetone production... Just useful chemistry... I like knowing the mechanisms but think we all need courses on old school chemistry🎉🎉🎉
No grease on those glass joints?
Very interests video
What is argon for?
make sure to point the valve away from you when opening a pressurized gas valve in case of failure you dont get shot in the chest with shrapnel, although the risk is less with argon than acetalyne its nice to be consistent
It's a racemate, a mixture of stereoisomers, right? Maybe the two isomers smell differently?
Yes the mixture should be racemic, i haven’t seen any stereoselective syntheses of this compound nor any isolation. I think it should be a 50/50 racemate. It could be that they smell different like many stereo isomers, but i don’t know for this specific compound.
nice vid, why just not use base to pick up the alpha proton of the carbonyle
that’s what im sayin
Is it me or does that stir bar look like it has had some serous wear, I've never seen one so worn. Awesome channel, it will grow I think, TH-camrs seems to like chemistry👍
ortho position is not granted, you can have meso (low percentage) and para position (20%)
Cool!
I wanted to get good separation between BP 156 and BP 163 C so I set up a short path, he says.
Alpha carbon effect?
Share how you gain possession of these nice reagents...that's what I'm interested in. Never add an alkylating reagent all at once. It's just amateurish.
Couldn't this have been done in one step through enolization? By adding a mineral acid it can enolize and then attack the CH3I. That or a 1:1 ratio of LDA to cyclohexanone followed by CH3I. What you did is still a pretty cool route to getting the product though.
Hmm I did just realize the problem with the acid would be a potential side reaction between the CH3I and the water
same thought here, just about to raise that in the comment and found out that we just happens to share the same ideas (my idea would be LDA first, CH3I second)
LDA?
Why can't you use the acid properties of the hydrogen in position 2 of the carbonyl to form a carbanion and proceed to a nucleophilic substitution?
Do you mean by directly adding a base? If so, youll likely end up doing aldol instead. The selectivity would be awful
@@benwhitehair5291 fuuuuck you're right. I think if the solution is dilute enough and with the base added dropwise it should work?
You can alkylate the alpha carbon all the same with the enamine, the enamine is safer because it is milder, however you are going to need strongly electrophilic halides because the less reactive ones tend to attack the nitrogen forming the imminium ion.
Even methyl iodide generates significant byproducts of N-alkylation
Why couldn’t you have just used a base to convert the ketone to a nucleophilic enolate for the methylation, bypassing the enamine synthesis step? That surely would still have given the same regioselectivity as only the more acidic alpha hydrogen would’ve been extracted due to resonance stabilisation of the resulting enolate. Or am I missing something?
Pretty much only done with LDA as base at low temp, otherwise poor regioselectivity it seems. So enamine was my next best option.
@@Chemiolis interesting, thanks for correcting me! What would happen then if the base deprotonated a non-alpha hydrogen? Surely the carbanion formed would be very unstable due to no resonance stabilisation?
@@LUCASHOMINID That simply doesn't happen, because of no resonance stabilization.
The base deprotonates at the alpha position because those protons are the most acidic.
Also, the bases used to generate enolates, amides such as LDA are not strong enough to deprotonate alkyl protons.
lovee ittt
lol the graphics, they were perfect
Is there any concern for over reaction? In theory this could react three more times. And I’m guessing this reaction has no enatioselectivity-is that a problem for you?
Using the enamine route mostly prevents overreacting since it is milder compared to other routes. I only wanted a single substitution, which seemed to have worked. Afaik there is not really a good method to get only 1 enantiomer, it will just be 50/50 racemate most likely which is not really a problem for me.
@@Chemiolis thanks for the response and content!
You could have made enolate of cyclohexanone and attacked the methyl iodide
In enamine chemistry, the primary methyl maybe attacked by lone pair of Nitrogen resulting in side pdt and lower yield
NICEEEEEEEE
Could you maybe do a video on how to extract nicotine from the leftovers of cigarettes and cigarette filters?
I don’t smoke nor does anyone i know so i can’t really do it. Buying cigarettes would thus be a huge waste of money for me. It would be the same procedure as extracting it from tabacco, which is relatively simple, procedure is online.
I've never put the wrong fraction back into a sep funnel, just like I've never forgotten to close the stopcock. 😏
The sound effects are pure earrape
Where is your accent from?.. it sounds like Limbourguish.
My dutch is very hollandish 🤷🏻♂️ so ABN
Congrats very impressive video. Just one Chemical missing, Bromobenzene XD, one step further and you´d had PCPy ;)
Why not just deprotonate the alpha hydrogen with NaH or LDA and use the akylhaldide? much less work
NaH should be avoided, it could reduce the ketone.
Thx lord for DEAN STARKS WOW
Captions are missing,otherwise very good vid
Purify the toluene that you extracted in the last video, would be great to see it
It’s only distillation and drying on sieves, very simple.
couldn’t you just use lda thf and thenalkylate with methyl iodide. hit the alpha carbon or some shit
good old stork enamine alpha halogenation
Nek minnit he starts using anhydrous HF to alkylate stuff 💀💀
Even dom nu ...maak je de moluculs op deze formgeving ook zo
love the video . but and i cant stress this nuff... u moste check soundlevels when u add effect .. i shat my pants like 5 times , dont do that to us man ;P thx in forhand
Inspired by NileRed
At 0:53 you shouldn't put two electron on the carbon and a negative charge as you did. That way it looks like a carbene with a negative charge ! I understand that you wanna show that the 2 electrons are located on the carbon.
Also at 8:42, the solid is probably pyrolidinium iodide or a salt of your enamine which is to be expected.
Anyway, always nice to see basic organic chemistry video! It could be nice if from the 2-methylcyclohexanone you make a video about kinetic control and thermodynamics control alkylation.