Making Cursed Oxygen Benzene - Pyrylium

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In this video I am making Pyrylium Tetrafluoroborate, a unique oxonium containing heterocycle that is very useful for the transformation of heterocyclic amines. It's currently used quite little due to its price, availability and knowledge about what it can be used for. The introduction and wide adoption of new reagents in chemistry is quite slow.
Procedure:
orgsyn.org/demo.aspx?prep=v10...
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[@moertelruehrer]

I often used HBF4 * Et2O in my PhD thesis and every single time I ordered it from Sigma, I got a new shade of "orange", but I never had such a dark brown like you did :D

[@Chemicator]

using different equivalent of reagents can affect the colour🤔

[@cezarcatalin1406]

You could use perchloric acid instead.

[@fukpoeslaw3613]

You're lucky it's not yellow chemistry.

[@williambouthillier8611]

I've had so much dirty fucking chemicals from Sigma so far I've lost count, especially the very reactive reagents that are sold in ether solutions, things like LDA, LiHMDS or Vinylmagnesium Bromide in THF. Especially that last one, we had to return a shipment of 4 bottles which were already almost inactive directly upon receiving them, as shown by titration. When the replacement bottles came in, the first bottle worked fine for a few months, but the 3 other bottles went to shit in less than a year without even opening them, so we ended up making the grignard ourselves which also boosted our reaction yield from 95%. I believe they add some special mixture of additives like stabilizers & corrosion inhibitors for ether solvents to avoid peroxide formation and that is what gives it this kind of color, just like the inhibited sulfuric acid you can find at the hardware store. Its utter trash because it they made it so that you can't preserve your reagent even if you use it carefully, because it will just go bad once the additives activity is depleted and the side-products start reacting with the reagent themselves. On the other hand, commercial reagents stored in Toluene or Hexanes solutions aren't usually colored like this and they also don't degrade as fast IME.

[@Felixkeeg]

@@cezarcatalin1406 I guess the product wont like water. otherwise you could also use HBF4 in water

[@wabibunny]

the thumbnail made my head hurt. thanks Chemiolis

[@MolecularPlayground]

That genuinely made me laugh. Especially the thanks at the end. There was so much going on in the thumbnail!

[@lagomoof]

The closest I get to (not) doing chemistry is knowing to not mix bleach and ammonia, so I'm patting myself on the back for noticing that if the long molecule can close into a ring, it might also happily attach to other long molecules instead. And as I was wondering about how that was avoided, there was a mention of those very polymeric side products needing to be filtered out.

[@T3sl4]

Indeed, the combination of enes and oxygen groups at extreme pH (high in this case, but low also works), sounds like the setup to an aldol reaction, notorious for making oligomeric products (from yellow to brown and tar); enes themselves can polymerize in the right conditions, too. The relatively high yields are quite encouraging despite this!

[@josephr5804]

Generally ring closing is preferred over polymerization in a concentration dependent way. Of course the kinetics and thermodynamics of the particular reactions matter but this is generally true..

[@Siyuan_Li]

josephr is right - basically by doing the reaction at "low" concentration you decrease the likelihood of two molecules bumping into each other. for this particular case it also seems that quickly adding the acid speeds along the cyclisation event relative to polymerisation - his description has a link to the procedure with details in the footnotes

[@fmdj]

I'm a very bad non-chemist too, and I think I understand very well that feeling of satisfaction when getting a correct intuition in a very unfamiliar domain. Didn't happen to me in this vid though, hats off to you 😅

[@linyuchen5627]

Nice work! Btw,the azulene(blue hydrocarbon) can be obtained by reacting the Pyrylium ion with NaCp. I think that's interesting

[@ligmabaldrich485]

yayy more synthesis vids 🤩 can we expect any inorganic or organometallic synth vids in the future?

[@informalchipmunk5775]

Grignard supremacy...

[@wherethisflowerblooms1559]

he did uranocenes

[@ligmabaldrich485]

@@wherethisflowerblooms1559 I am aware - would like to see more interesting reactions on the inorganic side

[@Lukesab3r]

Once again, I learned something new and am happy. Thanks for making my day!!!

[@Psychx_]

Btw, the 'sch' in Schlenk (or German words/names in general) is read as 'sh' in English - i.e. like "shell", "sharp", "shallow", etc.

[@davidfetter]

I'm pretty sure the Dutch guy has his own reasons to pronounce things the way he does. Maybe lay off people for stuff like this.

[@fmdj]

​​@@davidfetter buh, I didn't pay attention to the wrong pronunciation here if wrong it was indeed, but I think it's good to point these things out in general, as long as it's done in a friendly way. I don't think anyone wants to keep making the same mistakes over and over again. I for one would prefer to be (kindly) corrected should I find myself in a similar situation.

[@s8nbutgerman209]

I thought this was a that chemist video with that thumbnail XD Not disappointed tho, great upload as always

[@MandrakeFernflower]

The color of blueberries is from an oxonium salt

[@user-xj8wy4uu1q]

Source?

[@Chemicator]

Awesome👌 investigating aromatisity of Pyrylium is an interesting topic

[@Felixkeeg]

Funny, I recently thought about using this in my research. I immediately noped out when I see the price. Looked up the synth and understood why it was so expensive. Couldn't be fucked to do it though. This reagent really has to enable some really otherwise tricky transformation to be worth the price.

[@fmdj]

I understood approximately nothing but for some reason I like this.

[@tess7656]

😂😂😂😂 Amazing thought was just me

[@szalonydoktor]

Very nice work

[@Jokke13th]

Excellent video!

[@evosticks]

For real, all this chemistry you explained are really complicated to me... I couldn't think or figure out this on my own.. I could learn a lot from you.

[@phil9916]

u learn this stuff in university, it takes 3 years..

[@4-Methylaminorex]

This channel is amazing! 👍 👌

[@chemistrycapital]

Agree about the chemistry! Haven’t seen it used too much in medchem papers

[@SlinkyD]

I ain't a chemist, unless you count my food experiments concerning flavor, but your comment section reads like the world's best gang. Regular words then a head scratcher all ova the place & its all coherent. Still don't know what it means. If I get that base knowledge, my brain might explode from linking it all together in one moment.

[@hammerth1421]

To be fair, this is really advanced. Chemiolis is one of the most advanced chemistry KZbinrs who aren't straight up filming in a university lab.

[@r9341-tss1]

With the collapse of the hemiacetal to an aldehyde in the first step, it's easier to just draw the N-C bond moving to take a proton from the solvent than draw it converted, although realistically it doesn't matter like you said.

[@williambouthillier8611]

I totally love the fact that you now justify orally almost all your written mechanisms🤩! It shows that you care a lot about the theory and the subtle implications of mechanistic arrows

[@williambouthillier8611]

FYI, for the cyclization mechanism's first protonation, just know that for a 5 membered-6 electrons anionic system, the negative charge coefficient is usually bigger on the central atom, which makes it the most nucleophilic positions, and you might expect protonation to happen there first. Of course, you would then generate the enol form by acid catalysis right after so it doesn't actually affect the mechanism but its a good thing to take note of. That is actually why a Birch Reductions in Ethanol/Ammonia generates unconjugated dienes! The kinetic protonation happens on the central carbon of the 5-membered conjugated (radical)-anion rather than at the extremity which would actually give a more stable, conjugated product.

[@elnombre91]

You can also use pyrilium salts to make phosphabenzenes, although unfortunately the synthesis is horrible as it requires P(SiMe3)3, an expensive, pyrophoric liquid.

[@joshg.6536]

I love the explanations and the content :D do u got some analytics from this? Would be interesting to know

[@chanheosican6636]

Cool video!

[@GarryDumblowski]

For the workup, since the crude mixture is such a dark black color I kind of wish you had used a white background so it's a bit easier to see what's going on.

[@mmmhorsesteaks]

Is this the work of Josep Cornella?

[@EthnobotanikFAQ]

I wanted to mention him as well. He is the author of the linked orgsyn procedure but his name really should have been mentioned since you can find all the different substitution possibilities searching his name.

[@ajc558]

Ochem is so much fun, I miss it

[@palamalama]

I absolutely love the mechanisms!! How many equivalents of fluoroboric acid are you adding relative to the enol? Asking because why doesn't the water produced during the cyclisation cause ring opening again? Is it sequestered by the excess acid? Or what do you think?

[@Chemiolis]

Pyryliums are stable in acid, so yes the protonation of water by the acid prevents it from reacting

[@rodrigomack13]

Is this compound hard to make because of the final workup where air exposure is minimized?

[@fenggao9655]

Please tell us where to buy the filter funnel that was used in 11:03 for filter air sensitive product!

[@Psychx_]

Could the cyclization and elimination step also be performed with p-TSA that contains trace amounts of H2SO4?

[@hammerth1421]

Probably not. I think you need the BF4 as a counter ion, pyrylium sulfate probably isn't stable.

[@Psychx_]

​@@hammerth1421 My question was more focused on the tosylate, which is also a particularily stable counterion. There's no p-TSA that doesn't contain trace amounts of sulfuric acid though. According to the literature, there are at least substituted pyrylium derivatives that have been isolated as tosylates: DOI 10.1016/j.molstruc.2019.127325 I don't know through which mechanism the counterion stabilizes the pyrylium, but by the looks, it's probably something along the lines of being a good lewis base and poor nucleophile at the same time.

[@davidfetter]

You got over 6 minutes in before before the short-path condenser! Is this a new record?

[@THYZOID]

THAT is truly cursed. Like wtf?

[@sssleon3320]

1 min after upload awww yeahhhh here we go again lads

[@jogandsp]

Just FYI 4:26 bottom right structure has a proton it shouldn't on N

[@lukassorowka2672]

3:23 no, the first structure is wrong. If you bind the sulfurtrioxide to the pyridine via a covalent bond like shown here, you have to break one S=O double-bonds resulting in a negative charge on one of the oxygens. And in the next step you form a neutral imine so the k+ just coordinates with the previously formed alcoholate.

[@zonex001]

This is my target too.

[@lumpygasinavacuum8449]

Could selling instructions on . Onion markets? Can you teach lysergic chems?

[@Rashadrus]

Cool! Can you make (2,2,6,6-tetrmethil-piperydin-1-il)oxyl? Orange colored stable radical.

[@douro20]

You mean TEMPO? I think he considers it boring compared to its unhindered cousin ABNO.

[@seraphpegasus]

3:21 the hydroxide attacks the pyridine at the 2-position I agree - but breaking that C-N bond SN2-style... :/

[@e_gorrr]

That's normal when N atom attached to some strong acceptor group

[@satindra.r]

@@e_gorrr I don't understand how the hydroxide can break and aromatic ring while doing SN2 on a sp2 carbon at 40C just because there is a strong acceptor, i tried searching for it but couldn't find any, do you have any sources?

[@dagurorarinsson2827]

can you make tretnoin?

[@viorp5267]

I WANT IT

[@sammygeez.]

It's really helpful that you show the mechanisms, but my professor wouldn't like that you change the cis double bonds from the ring starting material into trans double bonds and back wherever. It would be more accurate to draw them as cis bonds, which I'm sure you already know, but probably harder to interpret for the viewer, so maybe a note would be helpful to say what's going on with regard to that.

[@Chemiolis]

I don’t take into account any cis, trans, E/Z or any kind, only if it is specifically relevant. Same for stuff as SN1, SN2 which is seemingly never relevant outside of school. ;)

[@hxcdanny3x]

5:28 nice and swirly

[@Slowly_Going_Mad]

Is it just me or have you been changing your pfp here lately. Anyways great video as always.

[@PyroRob69]

B is boron, Be is beryllium. I am assuming you are using boron.

[@chengkaigoh5101]

U must be spying on me,I was thinking of pyrridine and pyrrole and was wondering if there’s smth similar but with oxygen or other elements and u drop this

[@Ithirahad]

Pyrylium sounds like a material from a fantasy RPG, not a real ion.

[@DallinEarl]

Would you be interested in purchasing some uranium crystals for a video?

[@snakebite1033]

Exited to see what you use it for! Btw the HBF4 Et2O colour should be okay, as its safety data sheet and technical data sheet say it can be dark yellow or even brown yellow to orange. Considering you are close to literature yields the stuff seems to holding up fine. But with low temp storage of reactive reagents, I don't usually have much faith once it has been open for some time.🥲

[@jjeanniton]

Pyrylium+ BF4- 😊

[@oldboyneverrichagain1113]

everyone who orders from sigma says it's really expensive

[@samuelbright8713]

Hi

[@MoxxoM]

Jesus, that's a lot of solvent used.

[@Samarno9.0]

Is that chicken fart chemical hell?

[@27.minhquangvo76]

I think you should also make "legal sulfur benzene". it's actually thiophene.

[@durshurrikun150]

False. Thiophene is an aromatic 5 membered cycle. "Sulphur benzene" is thiopyrilium

[@27.minhquangvo76]

@@durshurrikun150 I mean that is the "illegal sulfur benzene". Although it's 5-membered, thiophene much resembles benzene in many of its properties, so that's why it had "-phene" in its name.

[@27.minhquangvo76]

On the other hand, thiopyrylium can only exist as a cation, so it's "illegal" to exist "on its own".

[@durshurrikun150]

@@27.minhquangvo76 It's not illegal, it's just difficult to isolate like pyrillium. Yes and it also has different properties.

[@durshurrikun150]

@@27.minhquangvo76 This is nonsense. So what if it needs counter ions?

[@Grak70]

Ligma Baldrich strikes again.

[@Auroral_Anomaly]

Tetravalent oxygen is so illegal.

[@williambradley611]

Like this comment

[@tomascernak917]

Use bigger flask😂.

[@nocturnhabeo]

How is this video both great chemistry and subtle shitpost!