Heterocyclic compounds are always cute, and have also cute names due to Hantszch-Widman (or something like that) nomenclature rules. Imagine 1,2 diazete, Thiirane, Oxepine, or even Oxetane. So cute 😂
In the 1970s I made an oxetane intermediate in the synthesis of a pheromone. I started with butyraldehyde and 1-pentene, and reacted them under UV light in acetonitrile solvent. This resulted in the formation of a longer molecule with an oxetane ring in its middle.
just a suggestion: when showing the structures of the compounds and blurring the background like at 1:35, try darkening the footage so that the white text is easier to make out. it's hard to see the small white lines on a background that is nearly the same color.
Nice video! Wondering why the first step is necessary since in theory you should generate the same alkoxide intermediate from 1-chloropropanol if you treat that with base. Oxetanes are cool molecules, though they can be a pain to work with in pharmaceuticals. They tend to ring open under acidic conditions (ie stomach acid or even silica gel) due to their strain. However, they have interesting properties and can be used as ketone bioisosteres! 😊
I was wondering the same thing, though I don't think cyclization would proceed with just Et3N as a base. Making the acetate and treating it with hydroxide liberates alkoxide readily. You could definitely just use NaH and use the chloroalcohol directly, can also prepare the iodide for even better reactivity via Finkelstein.
Try polymerizing oxetane with Lewis acids - a rather interesting reaction, and if you pass acetylene through a polymerizing mass, you get an even more interesting product.
Thank you so much for showing the mechanisms! They make it so much easier to understand. But theres no way that Oxetane is stable right? The first thing I thought when I saw the structure was steric hindrance. I kinda put this in the same catagory as cyclopropane.
Nilered is like "these funny chemicals look similiar, wondering how you can turn each into another" and you are "oh i saw an interesting molecule model/graph in my textbook, wondering how it looks like in practice"
You sometimes fill your flask and separatory funnel too full. I think it make it hard to shake or mix the mixture effectively or to prevent overflow, when high exotherm reactions take place.
Just a question, How come you cant just react 3-chloro propanol in basic conditions, causing the negative oxygen to preform a sn2 reaction with the 3 carbon and forming oxetane?
Probably because the sp3-carbon bound to the chlorine gets closer to the collapsing ether bond, through the attraction of the chlorine to the carbonylcarbon
@@lukassorowka2672 Is this really a concerted reaction? I would assume it is a two step reaction, forming an alcoholate, which than reacts in an intramolecular SN2 reaction. This would be similar to the formation of oxetane using 3-chloro-propan-1-ol, but the reaction of the hydroxide as nucleophile with the carbonyl center is much more attractive in contrast to do a SN2 or E2 reaction at the C-3/C-2 Carbon directly. Therefore, the formation of undesired sideproducts is lower when using 3-chloropropyl acetate compared to 3-chloro-propan-1-ol.
@@a830485a I never said that its concerted. It is in fact as shown in the last third of the video a two step reaction. The coordination of the chloride to the carbonylcarbon is just my assumption on why the reaction with the 3-Chloroacetate rather takes place in an intramolecular fashion, while the williamson ethersynthesis probably leads to more polymerisation, as somebody already suggested as a reply here, because the sp3-carbon on the hydroxy-group isn't that electrophilic. But nevertheless I agree with you in that sense that the reaction with 3-Chloroacetate yields less side products because of the more electrophilic carbonylcarbon which avoids the E2/Sn2. Btw you can try all day long to yield Oxetane from 1-chloro-propan-1-ol, that won't work 😆. You need 3-Chloro-1-propanol as stated by chemiolis already
Thank you sir for your educational illustration. There is a question in my mind regarding the synthesis Dose the oxatane molecule synthesize by [2.2] cycloaddation using Paterno-Buchi reaction Could the started materials be formaldehyde with Ethene ? Thank you sir
My only comment is that the mechanism for the first reaction implies that the 3-chloro-1-propanol is still protonated in the presence of the triethylamine when the acetyl chloride is added. It's probably already a salt with the protonated triethylamine making the mechanism 1 step simpler. Good video!
hey why do you separate the organic layer and aqueous layer both through the bottom of the separatory funnel? the organic layer is gonna be contaminated from that and reduce yield.
I was wondering if the final mechanism might be sn2 displacement of the chloride for hydroxide which is then deprotonated under the basic conditions. This O- then kicks off the acetate in another SN2 reaction?
Good video! As always, thanks for the mechanism. I was wondering, why do you convert the alcohol to the acetate initially, if you are putting it in such highly basic conditions afterwards anyway? Couldn't you just put the alcohol into the potassium hydroxide directly?
Why doesnt adding 3-bromopropanol to some strong base such as sodium t butoxide work? 3 bromo propanolate should always be in low concentration and depending on the amount of solvent t butoxide could also be?
as the other commentor said, clayden warren is pretty much the org chem bible :) I saw another one called Reaction Mechanisms in Organic Chemistry by Metin Balci, seems to be a good one
The hydroxide was added as a nucleophile for the hydrolysis of the ester, to form the oxetane in a consecutively intramolecular SN2-Reaktion. The oxetane has already been distilled during the reaction. KOH had no purpose for the distillation itself and the excess of it remained as leftover.
@@a830485a Thanks for taking the time to reply, my confusion was that at 7.30 he adds additional hydroxide to his crude product even though none of the starting material should be in this flask as far as I can tell? does this react with the unwanted allyly alcohol/ other side products or something ? sorry if I've misunderstood!
@@harryparr4879 Ah okey, now I understand your question. The crude distillation product contained still starting material, therefore the KOH is added. The boiling point for the product is around 50 °C, the starting material is around 70 °C and the allyl alcohol is around 100 °C, while the reaction takes place at 140-150 °C. In the first distillation you only get rid of the high boiling fractions. In the second distillation the product gets properly separated via the vigreux column.
the best, most clickbating title would be "The guy who made smell of dirt makes the smallest square ever". Oh boy this video would get so many views and interactions
Difference in boiling point of Oxetane and vynilalcohol is great, but... many-many-many liquids are forming azeotropes. And this makes really hard or impossible task to separate liquid substances by fractional distillation. :(
@@dimaminiailo3723 The keyword is "Probably". Till you have specific research reports you can't state. I checked references about different azeotropes: binary, ternary, quaternary and many substances form azeotropes when no one could ever expect it. So.. better to do some research. I synthesized oxetane derivatives from oxiranes, but they where crystalline substances and were easy purifiable.
Why would the KOH not deprotonate the alpha protons, turning it into an enolate? Do esters just not form enolates favorably? Couldn't it then do an intramolecular annulation which uses the chlorine as a leaving group?
That could happen very well, but as you already said esters don't get enolised that easily especially by a relatively weak base like KOH compared to LDA f.e. But all these side-reactions can explain the bad yield of this reaction
I'm not sure if it's possible for KOH to do that, and also if it could I have a feeling it would be called something other than an enolate with that other oxygen, like a vinyl ether oxide or something although I'm sure it's not that, but even if it can I'm sure it would hydrolyze the ester much faster than it would take an alpha proton in this case.
because the hydroxy anion is a much better nucleophile than it is a base. also you may consider looking up the pKa values. I do not have the exact values in mind right now (for C-H of an ester), but i guess the deprotonation is just much slower than the nucleophilic attack.
@@Torteufelyeah I ended up looking at the Pkas of the conjugate bases. If I remember correctly alpha protons on esters sit at around 25(so less acidic than ketones or aldehydes), so @lukassorowka2672 was spot on about LDA being a good choice in enolizing esters.
![Making [1.1.1]Propellane](http://i.ytimg.com/vi/iTlRvQuIyqE/mqdefault.jpg)
![Making Dibenzo[a,e]cyclooctene - an Emerging Ligand?](http://i.ytimg.com/vi/_2FNaCZldE4/mqdefault.jpg)
SQUARE
jahaha yhe flashbacks begin
When octanitrocubane? (Pls dont explode my car for this comment)
Only 5 more of these and you'll have a cube!
@@dankmemes3447 Heptanitrocubane has a more efficient crystal packing and consequently a higher density, might be a better explosive.
it's cubane man!
Thats some high tier square chemistry here
Yellow Chem bad
Bars🔥
Shut up! It's just a fashion sector so, "everyone can participate".
Next project is making a microscopic Rubik's Cube out of Cubane and Oxetane. hehe
"ignites cutely" I love the vibe of these latest videos 😂
You know you now have to make cubane, right?
In the middle of a Ph.D thesis
MaxfieldMD is plowing through that synthesis, he's nearly done.
He might actually finish it and not fck around like SOMEONE we all know...
@@hesitant1757 a physics PhD thesis
@@drasiella ):
"You ever see a molecule and think... Wtf it's so cute... Cute"
Yes, Cubane.
That's the last thing you wanna from a chick in bed "Oh look at that little cute thing!!" ha-ha-ha
Yes, ortho-Carborane
Thank you for including mechanisms, they are some of the best parts of your videos to me.💛
they are great, i dont understand a single thing from listening to the explanation but the mechanism really helps
Heterocyclic compounds are always cute, and have also cute names due to Hantszch-Widman (or something like that) nomenclature rules.
Imagine 1,2 diazete, Thiirane, Oxepine, or even Oxetane. So cute 😂
Only humans would look at a little bundle of atoms in a square shape and call it cute, but I am HERE FOR IT.
0:28 “I add in 183 mills of stinky, fishy triethylamine” 😂
You: it's cute
Me: I can hear the constant internal screaming from the bond strain
same bro
oxetane is very cute! Personally, although much more common, I find furans very cute too. Especially 2,5-disubstituted furans. They look so happy.
In the 1970s I made an oxetane intermediate in the synthesis of a pheromone. I started with butyraldehyde and 1-pentene, and reacted them under UV light in acetonitrile solvent. This resulted in the formation of a longer molecule with an oxetane ring in its middle.
“I put a label on it to match its cuteness”😂😂😂
oooh look at those angles, imagine the explosivity
We got the square, now we need the cube.
just a suggestion: when showing the structures of the compounds and blurring the background like at 1:35, try darkening the footage so that the white text is easier to make out. it's hard to see the small white lines on a background that is nearly the same color.
Babe wake up new chemiolis video just dropped
my gf if she was a molecule:
2:29 Forbidden fruit smoothie.
1:27 looks like stick men rioting :)
Nice! Finally, a square!
Nice video! Wondering why the first step is necessary since in theory you should generate the same alkoxide intermediate from 1-chloropropanol if you treat that with base.
Oxetanes are cool molecules, though they can be a pain to work with in pharmaceuticals. They tend to ring open under acidic conditions (ie stomach acid or even silica gel) due to their strain. However, they have interesting properties and can be used as ketone bioisosteres! 😊
This is why I love chem video comments
I was wondering the same thing, though I don't think cyclization would proceed with just Et3N as a base. Making the acetate and treating it with hydroxide liberates alkoxide readily. You could definitely just use NaH and use the chloroalcohol directly, can also prepare the iodide for even better reactivity via Finkelstein.
Not gonna lie, dropping funnel at angle looks cursed.
Try polymerizing oxetane with Lewis acids - a rather interesting reaction, and if you pass acetylene through a polymerizing mass, you get an even more interesting product.
Thank you so much for showing the mechanisms! They make it so much easier to understand.
But theres no way that Oxetane is stable right? The first thing I thought when I saw the structure was steric hindrance. I kinda put this in the same catagory as cyclopropane.
How do you find the synthesis recipe for such an obscure molecule?!?! I’m intrigued. Love ur vids
Thankfully all these reactions are captured in databases and searchable by drawing the reaction. Ochem research would be brutal without it.
@@KakashiBallZ Thats dope
@@KakashiBallZ could you share some of the databases that allow search by structure?
@@siiluviilu sci finder and reaxys are some of the most used for Ochem
wow i literally got a reaxys ad at the end and didn’t think anything of it until i read this comment
Oxetane: "uwu, I'm just a tiny widdle heterocycle in a big world"
*burns cutely*
Why did you make Oxetane?
It looks cute.
😂
Nilered is like "these funny chemicals look similiar, wondering how you can turn each into another" and you are "oh i saw an interesting molecule model/graph in my textbook, wondering how it looks like in practice"
Have you ever thought of making one of these thermochromic molecules?
It's quite a good idea for a video
You sometimes fill your flask and separatory funnel too full. I think it make it hard to shake or mix the mixture effectively or to prevent overflow, when high exotherm reactions take place.
I love all these exotic chemical synthesis, each time I discover something new ! :D
The product burns cutely❤❤
Wholesome cute content
Nitpicky detail: the condenser at 4:52 is not a Dimroth condenser, but a Vigreux
the dimroth condenser is set up after the vigreux :-)
@@Chemiolis Ahh, I see!
Thank you for this cute video.
Just a question, How come you cant just react 3-chloro propanol in basic conditions, causing the negative oxygen to preform a sn2 reaction with the 3 carbon and forming oxetane?
Why don t you do a Williamson reaction ? Just bring the 1-chloro-propan-1-ol to a boil with some NaOH ? (Real question from a chemistry student)
Because you're more likely to polymerize imho.
Probably because the sp3-carbon bound to the chlorine gets closer to the collapsing ether bond, through the attraction of the chlorine to the carbonylcarbon
Reaction also works with 3-chloro-1-propanol and KOH directly, but is even lower yielding.
@@lukassorowka2672 Is this really a concerted reaction? I would assume it is a two step reaction, forming an alcoholate, which than reacts in an intramolecular SN2 reaction. This would be similar to the formation of oxetane using 3-chloro-propan-1-ol, but the reaction of the hydroxide as nucleophile with the carbonyl center is much more attractive in contrast to do a SN2 or E2 reaction at the C-3/C-2 Carbon directly. Therefore, the formation of undesired sideproducts is lower when using 3-chloropropyl acetate compared to 3-chloro-propan-1-ol.
@@a830485a I never said that its concerted. It is in fact as shown in the last third of the video a two step reaction. The coordination of the chloride to the carbonylcarbon is just my assumption on why the reaction with the 3-Chloroacetate rather takes place in an intramolecular fashion, while the williamson ethersynthesis probably leads to more polymerisation, as somebody already suggested as a reply here, because the sp3-carbon on the hydroxy-group isn't that electrophilic. But nevertheless I agree with you in that sense that the reaction with 3-Chloroacetate yields less side products because of the more electrophilic carbonylcarbon which avoids the E2/Sn2. Btw you can try all day long to yield Oxetane from 1-chloro-propan-1-ol, that won't work 😆. You need 3-Chloro-1-propanol as stated by chemiolis already
most kawaii chemical :3
Thank you sir for your educational illustration. There is a question in my mind regarding the synthesis
Dose the oxatane molecule synthesize by [2.2] cycloaddation using Paterno-Buchi reaction
Could the started materials be formaldehyde with Ethene ?
Thank you sir
My only comment is that the mechanism for the first reaction implies that the 3-chloro-1-propanol is still protonated in the presence of the triethylamine when the acetyl chloride is added. It's probably already a salt with the protonated triethylamine making the mechanism 1 step simpler. Good video!
Unironically a pretty good review of my org 2 section on carboxylic acid derivatives
the only thing cuter than this molecule is your love of short path vaccum distillation
hey why do you separate the organic layer and aqueous layer both through the bottom of the separatory funnel? the organic layer is gonna be contaminated from that and reduce yield.
I was wondering if the final mechanism might be sn2 displacement of the chloride for hydroxide which is then deprotonated under the basic conditions. This O- then kicks off the acetate in another SN2 reaction?
for a square molecule this is process surprisingly simple
Would the alyll alcohol side reaction be reduced if you used a more exotic strong organic base that is sterically hindered?
Missed opportunity to call it Box-etane
if you pause it around @1:37 it looks like a cool face behind the formula..
Did you add a stabilizer like BHT? Or put it in a fridge?
that oxetane won’t be very cute once it turns the iodine test purple-brown 😂
Now make it with the oxygen in the top left.
Why cubes and squares are so cuuute XD
Heyy yaa what the fcuk broo ! 🤨😂 How is it possible ?!
@@archerszandala357 Magic XD
We all know that hexagons are the bestagons but I get your point. Also it's not yellow which is good.
0:04 thats benzene for me for some reason
Good video! As always, thanks for the mechanism. I was wondering, why do you convert the alcohol to the acetate initially, if you are putting it in such highly basic conditions afterwards anyway? Couldn't you just put the alcohol into the potassium hydroxide directly?
It works with the alcohol directly, but it has poor yields. Acetate works better.
"DCM" -- specify the components of initialisms and acronyms the first time you use them: dichloromethane (DCM).
I've been always curious how robust oxetane is.
Why doesnt adding 3-bromopropanol to some strong base such as sodium t butoxide work? 3 bromo propanolate should always be in low concentration and depending on the amount of solvent t butoxide could also be?
Very nicely done.
a tiny crumb of what looks like 60 fps at 3:55 👀
60 fps in general would be cool
Great job
How the frick do you afford dumping entire bottles of sigma chemicals into your reactions?
Show us how to make C10H15N
Can you use basic medium with 3 chloro 1 propanal and do some NGP type reaction?
bromo-dragonfly is cute, especially after you take some bromo-dragonfly
Bro... Vasoconstrictors are not cute. 💀💀💀
@@CHCH-Au he's a bad boy, i can fix him...
Did you recover the Et3N from the aqueous waste?
be there of be square molecule.
Hi! I really like your videos. Can you suggest me some books on mechanisms? I know basics but I stuck in complex molecules.
Clayden Greeves and Warren
as the other commentor said, clayden warren is pretty much the org chem bible :) I saw another one called Reaction Mechanisms in Organic Chemistry by Metin Balci, seems to be a good one
Thanks for your suggestions! I'll definitely check them out.
What does it smell like? I would guess somewhat ether-like?
Cubane next👀
Must it be stored in brown Glas with inert gas?
Ok so you synthesized it. Does it have any further use?
Your channel is epic
I thought the exact opposite from the ring strain and thought it was an inhumane molecule, 😂
why there was no ether synthesis just like combined grignard reagent.
"what are you looking for in a girlfriend?"
Idk probably someone who reminds me of oxetane
Thlse kinks in the tubes to the condenser can't be the best
I probably just missed it, but in the final distillation what was the purpose for the hydroxide? Really nice video btw
The hydroxide was added as a nucleophile for the hydrolysis of the ester, to form the oxetane in a consecutively intramolecular SN2-Reaktion. The oxetane has already been distilled during the reaction. KOH had no purpose for the distillation itself and the excess of it remained as leftover.
@@a830485a Thanks for taking the time to reply, my confusion was that at 7.30 he adds additional hydroxide to his crude product even though none of the starting material should be in this flask as far as I can tell? does this react with the unwanted allyly alcohol/ other side products or something ? sorry if I've misunderstood!
@@harryparr4879 Ah okey, now I understand your question. The crude distillation product contained still starting material, therefore the KOH is added. The boiling point for the product is around 50 °C, the starting material is around 70 °C and the allyl alcohol is around 100 °C, while the reaction takes place at 140-150 °C. In the first distillation you only get rid of the high boiling fractions. In the second distillation the product gets properly separated via the vigreux column.
"...Cute, cute as a bottom..." (Talking Heads)
That looks like it can form some cute peroxides in a hurry tho...
the best, most clickbating title would be "The guy who made smell of dirt makes the smallest square ever". Oh boy this video would get so many views and interactions
Why did you use acetyl chloride instead of acetic anydride?
we need to crowd fund you a rotovap
Curious, why did you use shortpath distillation? Easier cleanup?
yes it's just simple
how about Cl-CH2CH2CH2-OH under high dilute basic condition?
Considering it's got unfavourable bond angles, I was expecting it to burn a little more vigourously than that, but it looked like IPA :(
1:21 why is it staring at me?
thought you were going to eat it at the end
Is it still a perfect square?
Can't you close the ring with just the chloroalcohol and base?
Yes, but the reaction is worse.
Difference in boiling point of Oxetane and vynilalcohol is great, but... many-many-many liquids are forming azeotropes. And this makes really hard or impossible task to separate liquid substances by fractional distillation. :(
Oxetane and allyl alcohol don't form an azeotrope probably, they have rather different bp's and mix together
@@dimaminiailo3723 The keyword is "Probably". Till you have specific research reports you can't state. I checked references about different azeotropes: binary, ternary, quaternary and many substances form azeotropes when no one could ever expect it. So.. better to do some research. I synthesized oxetane derivatives from oxiranes, but they where crystalline substances and were easy purifiable.
Vynil alcohol is just a tautomer for acetaaldehyde
very cute indeed
Oxetane is cute but I prefer oxane because we all know hexagons are the bestagons
What does it taste like?
Amazing job well done how are you
Why would the KOH not deprotonate the alpha protons, turning it into an enolate? Do esters just not form enolates favorably? Couldn't it then do an intramolecular annulation which uses the chlorine as a leaving group?
That could happen very well, but as you already said esters don't get enolised that easily especially by a relatively weak base like KOH compared to LDA f.e. But all these side-reactions can explain the bad yield of this reaction
I'm not sure if it's possible for KOH to do that, and also if it could I have a feeling it would be called something other than an enolate with that other oxygen, like a vinyl ether oxide or something although I'm sure it's not that, but even if it can I'm sure it would hydrolyze the ester much faster than it would take an alpha proton in this case.
because the hydroxy anion is a much better nucleophile than it is a base. also you may consider looking up the pKa values. I do not have the exact values in mind right now (for C-H of an ester), but i guess the deprotonation is just much slower than the nucleophilic attack.
@@Torteufelyeah I ended up looking at the Pkas of the conjugate bases. If I remember correctly alpha protons on esters sit at around 25(so less acidic than ketones or aldehydes), so @lukassorowka2672 was spot on about LDA being a good choice in enolizing esters.
alpha hydrogens on esters have a pKa of 25, KOH is too weak of a base to be able to effectively deprotonate esters
dude 7:56 makes me nervous af
can you make hexagon next video ? :D
Bro you forgot to include the smell test
weird, not ether-like but more aromatic
What does it smell like?
So cute