Disconnecting with a sneaky furan?

[@milesgantcher344]

Some of the best chemistry content on the internet. Keep it up

[@CasualChemistry]

🙂 Thanks! I really appreciate the feedback and more content on the way

[@topkekfilmproductions3464]

Just what i needed after a long day in the lab. thanks bro

[@CasualChemistry]

:) No worries. Recorded the source video a while back and finally got around to editing it down.

[@romo1099]

Can always get lost in the sauce of heterocyclic chemistry but love how you've pieced it all together. Thank you for putting your thoughts so clearly on paper :)

[@CasualChemistry]

Thanks for the feedback :). Agreed this is a topic that can get confusing with different routes and ordering and often far too many curly arrows.

[@PorcusCrassus]

I always get so excited when you post. Keep up the awesome work!

[@CasualChemistry]

Thanks! 🙂 More on the way soon

[@randomlyusernamed]

Loving these videos, watching them in lab while working. Brings back memories of things I've forgotten and used to really like about organic chemistry. Slowly convincing myself to go back to academia. Thanks!!

[@CasualChemistry]

Thanks for the feedback 🙂 More on the way - I really like working through these sorts of topics

[@adrianromaniuk1544]

I'm speechless. Best chemistry rationale I've ever seen - without using fancy words, chemistry and overall waffle. Good work!

[@CasualChemistry]

Thanks for the feedback! Thats exactly the style I’m going for with these videos 🙂

[@kurama6877]

I love how you add “simple” details (like the amine preference at 1:05) that most people would leave out, it really makes the channel feel like content that any level of chemistry student can enjoy and benefit from

[@CasualChemistry]

🙂 Thanks for the feedback - that’s definitely my intention with these comments. I’m also trying to be careful to explain any initialisms/acronyms in case there’s different conventions in place around the world.

[@marcus3419]

great video as always, yours is some of the best chemistry content i know

[@CasualChemistry]

Thanks 🙂 it’s been my plan to try and add something that was missing in the science video space. More content on the way

[@nemilikondasravankumar3166]

Very good explanation for each every step.. TQ so much for your efforts

[@CasualChemistry]

Thanks 🙂

[@I_XuMuK_I]

18:10 I've never seen SnCl2 used like this without acidic conditions. Wouldn't it hydrolyse the nitrile? Or are there other set of conditions this reduction can work in?

[@CasualChemistry]

In acid I think it probably would go for the nitrile as well, I agree, but this nitro only reduction occurs when you’re just in a polar organic solvent like EtOAc or EtOH. A mechanism probably starts by attaching the nitro oxygens to the Sun centre.

[@I_XuMuK_I]

@@CasualChemistry didn't know that. Thanks this might actually help me with my work.

[@CasualChemistry]

Cool - fingers crossed. Other metal di chlorides sometimes work too, and also some classes of phosphines I believe

[@Felixkeeg]

@@I_XuMuK_I Fe / NH4Cl in MeOH/H2O 9:1 at 80°C is my goto nitro reduction protocol. Don't forget to degas the solvent before adding the iron. Mild enough to leave aryl nitriles alone. Can't speak for alkyl nitriles though

[@suneelgaur5246]

Great video! I learnt a lot from this.

[@CasualChemistry]

Thanks 🙂 glad it was helpful

[@Some_Tomfoolery]

Great work! Am new to your channel and trying to learn retro synthesis

[@CasualChemistry]

🙂 Thanks. I’ve been working to trying to cover some range with my retrosynthesis videos as there weren’t many similar resources out there - hopefully you can find a useful mixture of intro to advanced level videos

[@Felixkeeg]

That furan is really a nifty trick, very nice! Can you not avoid the Ullmann coupling altogether by doing SNAr of the imidazole with 3,4-Difluoronitrobenzene?

[@CasualChemistry]

Hmm - this is a good point. I’ve never seen a reaction like this achieved in the literature though. Perhaps the imidazole anion is not punchy/hard enough (probably could roughly characterise by pKaH)

[@Felixkeeg]

@@CasualChemistry Fair enough. I think imidazole reacts with Sanger's reagent at least though. I'll see if we have some 3,4-difluoronitrobenzene in the lab tomorrow, kind of curious now

[@aurelius388]

Transforming the aryl bromide into the corresponding Grignard reagent, with F ortho to it, would have me worried about benzyne formation (around 13:30).

[@CasualChemistry]

I think it’s safe under normal type conditions. The C-F bond enthalpy is very high and F- isn’t the best leaving group - I’d swap it for a bromide or triflate if I wanted the benzyne.

[@derkapuzenkiwi6504]

Would it be possible to to do a Pinner-type reaction to get from the nitrile to the hydroxyamidine? Then you could just heat the reaction in a second step to make an intramolecular SNAr

[@CasualChemistry]

Good question - but I don’t think it’ll work so well as the molecular orbitals probably can’t react and at the same time provide a place for charge to go if that particular SNAr is wanted (perhaps more plausible if the nitro was still on as well. To get the O into the pi star of the ring, it has to be able to get properly out of the plane and I don’t think there’s enough flexibility. Even if it twists, then the C=N bond would be out of plane which isn’t good for the SNAr

[@Abdcwyxz]

Wouldn't the acid chloride react with the NH2 on the benzioxazole?

[@CasualChemistry]

Yes - so the order of steps needs to be considered carefully. Use of the nitrile avoids this issue in the forward synthesis

[@triklettriklerbu1592]

hello there, excellent video. I've been studying chemistry as a pastime for a long time but I have no understanding how reactions with heterocycles work. Are there any books, useful reactions, or resources that you could recommend?

[@CasualChemistry]

It’s a topic that sometimes can seem super big when getting started, but in reality not so broad of learning patterns rather than named reactions etc - I definitely was pitching this video (hopefully as spotting patterns in eg carbonyl chemistry as I think that’s good for broader learning. When I was getting into this the Oxford Chemistry Primer on heterocycles was my main one and I think still stands up well for the basics of ring synthesis. But do note that transition metal chem (mainly Pd) transformed this field in recent decades. The primer book is out of print but often cheap on eBay, but also eBook versions exist

[@triklettriklerbu1592]

@@CasualChemistry thank you for the suggestion and quick answer, really appreciate it. I just took a look at the pdf and seems really good.

[@cedt3468]

Wouldn't that be more efficient to create the bond between the pyrazole moeity and the benzisoxazole using N-arylation (Chan-Lam or Buchwald) ? That would be more convergent and would by-pass the problem of regioselectivity as hydrazine without substituant can be used to create the pyrazole ring.

[@cedt3468]

Amazing content by the way. Very useful and well explained

[@CasualChemistry]

Thanks 🙂

[@CasualChemistry]

Fair - I’m sure there are other routes for sure. I’ve stayed with a very classical one here that was used on an industrial scale synthesis in reality. I’ve tried to justify the logic but I’ll admit the route might also be preferred cos of ease of purification stages etc just as much as convergency/step-count.

[@cedt3468]

@CasualChemistry That makes sense! Thank you for taking the time to reply and give additional details. Very appreciated!

[@mariappanarumugam9838]

well explained

[@CasualChemistry]

Thanks 🙂

[@hellothere3163]

OwO