Your channel reminds me of the early days of Nilered, which I love. I love his more detailed projects he does nowadays too but these detailed synthesis and purification videos are what I really love.
@@duncanfox7871 honestly, I feel like it’s just cuz he’s got a lot of projects going at once. He’s also got that podcast with himself, William osman, and other guests which I’m sure takes some time. I really don’t get all the hate I’ve been seeing recently. Any chemist should know these projects take time. Also, people need to chill about him doing more fun "meme" projects. It's obvious he enjoys doing more fun projects that fulfill him rather than ones with intensively academic applications.
@@duncanfox7871 Ahh okay. Yeah I don't know anything about him other than he's a Canadian but that was my own experience as a Canadian young person into chemistry. I never did home science again after school, just ended up focusing on other things.
This is without a doubt the best chemistry video on UA-cam. Chemistry, pure chemistry at least, is a pain in the ass. You very nicely have shown that. I really like the chromatography you did. Purification is not something most UA-cam chemist do or show. You just won the title for that, and you managed to do so with a useless compound. Of course. Doesn't matter
Honestly, I love seeing the purification. I hate doing it, with a god damn passion, but there's something Oddly Satisfying about seeing column chromatography, or getting nice separation on TLC, or nailing those NMR peaks.
I think a potential reason for the low yield is the degradation of the tetrakis(triphenylphosphine) palladium catalyst, it's very oxygen sensitive and because you don't use much, any air in the reaction mix at all will kill the reaction. When I do Suzuki reactions, I put the aryl bromide and the boronate into the flask, vacuum/argon 3x, put Pd(pph3)4 in, vacuum/argon 3x, degas the toluene by freeze/pump/thaw in a separate container, then cannulate the toluene in. I have a stock solution of K2CO3 which I bubble argon through before adding by cannula. I know it takes a while and there are probably much more simple ways but I find that this can give me isolated yields of above 85% with minimal catalyst loading for complex couplings.
Finally a proper column chromatography chem video on amateur chemistry side of youtube. Btw usually the w/w ratio of product mixture to silica gel is 1:50 up to 1:150 so your column is not too big. Also for some column work consider using gradient in your elution.
@Edward Elizabeth Hitler I think this one is more suited for interested professionals. Often hard to follow for an amateur, nearly impossible to recreate...
For thin layer chromatography, I can recommend using phosphomolybdic acid as universal stain detection reagents (black spots on a yellow background, plates are stored for a long time) or an anisaldehyde reagent (multi-colored spots, but change colors and fade over time). Irradiation of the UV plate or permanganate solution often does not show all substances or show negligible impurities.
Great video! I think the low yield of biphenyl may also be due to oxygen - I would recommend doing at least 3 vacuum/N2 cycles before charging the catalyst and phosphine.
A separate video for making Trimethyl borate that includes the trials and tribulations, and concludes with the successful separation of the methanol and Trimethyl borate? YES PLEASE!
Thank you for this video. I learned a lot and really enjoyed how you discussed your deviations from the paper and your take on the results. Your explanations and process using tlc and column chromatography was by far one of the most informative and detailed I've come across while trying to learn about it. Subscribed with thanks from Canada
A most satisfying video. It seems organic synthesis techniques haven’t changed much in the 60 years since I did my graduate studies. Thanks for sharing.
Thanks to you I have just recovered my love for chemical and pharmaceutical research... in my country it is difficult to study pharmaceutics and at my job I got tired of washing so many HPLC tubes that I hated Chemistry. But you reminded me what I like. Congratulations for your content bro
Wonderful! This was great to watch, and also I noticed you had one of those fancy jacketed spiral short paths, I was considering buying one but I didnt, seems like I might regret it as it'll be great for very volatile stuff XD. Can't wait to see what you do next
Your chemistry videos are very neatly done. I especially liked how well you could determine the different compounds in the TLC plates. I'd love to see the reaction mechanisms behind the synthesis. For future videos could you perhaps quickly talk through the mechanisms? Or just flash a picture on screen so those interested could pause and study them.
There aren’t many, if any, home chemists on UA-cam that are attempting such interesting reactions. Ie. Nitrogen atmosphere, dry ice bath, etc.. Very cool.
Good video dude! Always love to see some proper chemistry. (I am always down for more commentary as to why certain conditions would be necessary /possible side reactions)
I can imagine the separation would have been better with a slightly lower DCM concentration in your eluent. As a rule of thumb, your product spot should never migrate more than halfway up your TLC plate, and probably considerably less if you are working under concentrated conditions. Simply not enough theoretical plates to get good separation if your spots migrate that quickly.
Great Video again! Bit of of nit pick but typically you refer to the solvent system for standard phase flash-chromatoraphy by Non-polar to Polar solvent i.e Hexanes:EtOAC 6:1. The Rf or retention factor of the product you were after was a little high as well for the first purification, typically wanty lower than 0.5 with 0.2-0.3 Rf being optimal. For loading a sample wet, adding a layer off sand on top About half a cm is enough will help you not disturb the bed.
Add sand to the top of your column before loading it. Just "schelpenzand" for birds you can get at pet store is pretty pure stuff and cheap. Add a royal layer and never be scared of yeeting your compound or eluent on there anymore
Very special... And unbelievable many worksteps. For at last 260 mg... I guess that must have been more pain than fun... 😥 I'm not sure if the steps directly on the hotplate destroyed too much...
I used to audit pharmaceutical companies manufacturing Active Pharmaceutical Ingredients (APIs). It’s similar to these techniques only on a massive scale!
UV light is not good for most boronic species and probably contributed to the poor yield. For Suzuki, I always load solids, vacuum purge with inert gas, then degas my solvent before adding it to avoid poisoning the catalyst. Really cool video and love your channel, definitively will be trying Epin for my next Suzuki.
so i watched this earlier today and then just went down a wikipedia rabbit hole that involved cyclizine, which has diphenylmethyl instead of biphenyl, a methylated piperazine, and has derivatives with other side chains in two places. i’m on two of them, and zyrtec is another and is a recognizable otc drug that is also a cyclizine derivative. it would be cool to see a third video involving PhB(Epin) to create cyclizine or a derivative
I failed chemisty in college. Warned teacher I would blow up the lab, burn a hole in the floor, or give my classmates cancer. I appreciate chemistry videos. Pursued business and English degree! THANK YOU!
What kind of capillary did you used for spotting on all the tlc plates? Caus the spots are looking rater large? Why not do Vakuum destilling first before the whole lc procedures, especially since PhB precipitates out ?
Awesome Video! Great work and very nice execution of the synthesis! Do you have acces to an NMR? It makes the whole process of confiming the desired product way easier:)
If you use some of the recommended steps in the coupling reaction and use 2,6 dibromopyridine stoichometrically instead of bromobenzene, I would be very interested in the result of that experiment.
13:24 why you not put reference probes of PhB(Epin) and Epin to see their Rf and clearly understand what substance produces what stain? You have pretty much free space in between your probes to put references.
Not sure how I got here but I'm honestly not complaining just a bit confused..what's some uses for this? is he just making it because it's just fascinating which I can completely understand, but is he making if for another project that I can't find?😅
Aren’t your TLCs super concentrated ? At least the ones before the column … And no sand on top of the column ? At my uni we always put sand on top of the silica gel to deposit the product
How did you ensure that addition was equimolar? Did you ensure the molar concentrations were the same in each addition funnel? That way 1 drip is roughly the same molar equivalent?
Yes I drip them steadily, but the phmgbr a bit faster. As long as there is no extreme excess present it should still be fine (in procedure they do in portions of 20 ml or so)
You need to make it urself since it is not commercially available, see previous video where I made it. There might be alternative methods to what I did.
Hi, could you please be so kind as tell me how you got the cannula needed for the Grignard reaction? They seem completely inaccessible to amateur chemists due to their very high price. Thanks!
@@wingl5841 actually, no. cannulas and needles are not interchangeable in 100% of the cases cannulas are usually much longer than needless and have larger id, they are also made out of different, more resistant materials, you can bend them and most importantly they are meant to be reusable
Make sure to check out part 1 if you want to know how I made some of the necessary reagents! ua-cam.com/video/c6hZi6UonAE/v-deo.html
Your channel reminds me of the early days of Nilered, which I love. I love his more detailed projects he does nowadays too but these detailed synthesis and purification videos are what I really love.
@@duncanfox7871 honestly, I feel like it’s just cuz he’s got a lot of projects going at once. He’s also got that podcast with himself, William osman, and other guests which I’m sure takes some time. I really don’t get all the hate I’ve been seeing recently. Any chemist should know these projects take time.
Also, people need to chill about him doing more fun "meme" projects. It's obvious he enjoys doing more fun projects that fulfill him rather than ones with intensively academic applications.
Finishing school, and getting more experience in the research community I'd imagine. Also home chemists get in trouble all the time.
@@duncanfox7871 Ahh okay. Yeah I don't know anything about him other than he's a Canadian but that was my own experience as a Canadian young person into chemistry. I never did home science again after school, just ended up focusing on other things.
This is without a doubt the best chemistry video on UA-cam. Chemistry, pure chemistry at least, is a pain in the ass. You very nicely have shown that. I really like the chromatography you did.
Purification is not something most UA-cam chemist do or show. You just won the title for that, and you managed to do so with a useless compound. Of course. Doesn't matter
Burn
Honestly, I love seeing the purification. I hate doing it, with a god damn passion, but there's something Oddly Satisfying about seeing column chromatography, or getting nice separation on TLC, or nailing those NMR peaks.
AFTER A DAY OF RUNNING THE COLUMN?!?! I salute you my friend!
Bravo! Very impressive.
Also, 18:02 - damn, that's a huge stir-bar to flask ratio...
I think a potential reason for the low yield is the degradation of the tetrakis(triphenylphosphine) palladium catalyst, it's very oxygen sensitive and because you don't use much, any air in the reaction mix at all will kill the reaction.
When I do Suzuki reactions, I put the aryl bromide and the boronate into the flask, vacuum/argon 3x, put Pd(pph3)4 in, vacuum/argon 3x, degas the toluene by freeze/pump/thaw in a separate container, then cannulate the toluene in.
I have a stock solution of K2CO3 which I bubble argon through before adding by cannula.
I know it takes a while and there are probably much more simple ways but I find that this can give me isolated yields of above 85% with minimal catalyst loading for complex couplings.
I can second that! Not all of the Pd cross coupling complexes are sensitive tho, but this one in particular is.
Most suzuki I’ve seen use Pd(dppf)Cl2, I only use pd(pph3)4 when I do anhydrous pd coupling (sonogashira, carbonylative coupling)
@@kel000001 Can I ask where you guys work that let you do these types of thing as a job?
@@sebastians7346 University. I’m a PhD student
@@kel000001 oh sweet. What’s your current project, if you don’t mind me asking?
Finally a proper column chromatography chem video on amateur chemistry side of youtube. Btw usually the w/w ratio of product mixture to silica gel is 1:50 up to 1:150 so your column is not too big. Also for some column work consider using gradient in your elution.
Proper? lol
Finally. A good chemistry channel.
@Edward Elizabeth Hitler I think this one is more suited for interested professionals.
Often hard to follow for an amateur, nearly impossible to recreate...
@Edward Elizabeth Hitler PMC is not on YT anymore. Nurdrage barely uploads. Never heard of thyzoid
What about nurdrage? He is great.
What a hot take
Nile red, explosions and fire, extractions and ire, Cody's lab all excellent
For thin layer chromatography, I can recommend using phosphomolybdic acid as universal stain detection reagents (black spots on a yellow background, plates are stored for a long time) or an anisaldehyde reagent (multi-colored spots, but change colors and fade over time). Irradiation of the UV plate or permanganate solution often does not show all substances or show negligible impurities.
So cool! I've never seen this before and I hope you can keep doing things like this :)
This was excellent. Thanks for posting it.
Multiple steps. Multiple problems solved. And showcasing a range of important techniques.
Great video! I think the low yield of biphenyl may also be due to oxygen - I would recommend doing at least 3 vacuum/N2 cycles before charging the catalyst and phosphine.
A separate video for making Trimethyl borate that includes the trials and tribulations, and concludes with the successful separation of the methanol and Trimethyl borate?
YES PLEASE!
Thank you for this video.
I learned a lot and really enjoyed how you discussed your deviations from the paper and your take on the results.
Your explanations and process using tlc and column chromatography was by far one of the most informative and detailed I've come across while trying to learn about it.
Subscribed with thanks from Canada
A most satisfying video. It seems organic synthesis techniques haven’t changed much in the 60 years since I did my graduate studies. Thanks for sharing.
Thanks to you I have just recovered my love for chemical and pharmaceutical research... in my country it is difficult to study pharmaceutics and at my job I got tired of washing so many HPLC tubes that I hated Chemistry. But you reminded me what I like. Congratulations for your content bro
Wonderful! This was great to watch, and also I noticed you had one of those fancy jacketed spiral short paths, I was considering buying one but I didnt, seems like I might regret it as it'll be great for very volatile stuff XD. Can't wait to see what you do next
Your chemistry videos are very neatly done. I especially liked how well you could determine the different compounds in the TLC plates. I'd love to see the reaction mechanisms behind the synthesis. For future videos could you perhaps quickly talk through the mechanisms? Or just flash a picture on screen so those interested could pause and study them.
What a wonderful workup. Thank you
There aren’t many, if any, home chemists on UA-cam that are attempting such interesting reactions. Ie. Nitrogen atmosphere, dry ice bath, etc.. Very cool.
Holy crap you're next level! Subbed
8:26 We all have been there.
Good video dude! Always love to see some proper chemistry. (I am always down for more commentary as to why certain conditions would be necessary /possible side reactions)
DUDE, you rock.
Keep updating your very scientific based work.
I can imagine the separation would have been better with a slightly lower DCM concentration in your eluent. As a rule of thumb, your product spot should never migrate more than halfway up your TLC plate, and probably considerably less if you are working under concentrated conditions. Simply not enough theoretical plates to get good separation if your spots migrate that quickly.
Great Video again!
Bit of of nit pick but typically you refer to the solvent system for standard phase flash-chromatoraphy by Non-polar to Polar solvent i.e Hexanes:EtOAC 6:1.
The Rf or retention factor of the product you were after was a little high as well for the first purification, typically wanty lower than 0.5 with 0.2-0.3 Rf being optimal.
For loading a sample wet, adding a layer off sand on top About half a cm is enough will help you not disturb the bed.
"but when it still did not come out, I abused the flask..."
Pain felt.
Add sand to the top of your column before loading it. Just "schelpenzand" for birds you can get at pet store is pretty pure stuff and cheap. Add a royal layer and never be scared of yeeting your compound or eluent on there anymore
I just loved the video, this is pure chemistry!
What a great work!
Very special...
And unbelievable many worksteps.
For at last 260 mg...
I guess that must have been more pain than fun... 😥
I'm not sure if the steps directly on the hotplate destroyed too much...
Nice to see column chromatography used as a separating method here on youtube. Good job!
Love your channel! Great video. I for one would love to see the purification of trimethyl borate.
8:26 did the flask concent?
I used to audit pharmaceutical companies manufacturing Active Pharmaceutical Ingredients (APIs). It’s similar to these techniques only on a massive scale!
UV light is not good for most boronic species and probably contributed to the poor yield. For Suzuki, I always load solids, vacuum purge with inert gas, then degas my solvent before adding it to avoid poisoning the catalyst.
Really cool video and love your channel, definitively will be trying Epin for my next Suzuki.
I have never seen a hotplate stirrer frozen before xD
I really like how the phenel-B Epin drawing looks like a spider. 😀
so i watched this earlier today and then just went down a wikipedia rabbit hole that involved cyclizine, which has diphenylmethyl instead of biphenyl, a methylated piperazine, and has derivatives with other side chains in two places. i’m on two of them, and zyrtec is another and is a recognizable otc drug that is also a cyclizine derivative. it would be cool to see a third video involving PhB(Epin) to create cyclizine or a derivative
I failed chemisty in college. Warned teacher I would blow up the lab, burn a hole in the floor, or give my classmates cancer. I appreciate chemistry videos. Pursued business and English degree! THANK YOU!
What kind of capillary did you used for spotting on all the tlc plates? Caus the spots are looking rater large?
Why not do Vakuum destilling first before the whole lc procedures, especially since PhB precipitates out ?
Ahhhh, I read this paper about a month ago. Can't wait to try it to make polymers.
Awesome Video! Great work and very nice execution of the synthesis!
Do you have acces to an NMR? It makes the whole process of confiming the desired product way easier:)
Wonderful! Good skills and interesting ideas. What else do you need?
If you use some of the recommended steps in the coupling reaction and use 2,6 dibromopyridine stoichometrically instead of bromobenzene, I would be very interested in the result of that experiment.
You should set up a compressor system so you can run flash chromatography, it would save you a ton of time when you have to run a column.
Well, if we reacted phenyl bromide directly with PhBr after making PhMgBr, wouldn't the final product still be produced?
13:24 why you not put reference probes of PhB(Epin) and Epin to see their Rf and clearly understand what substance produces what stain? You have pretty much free space in between your probes to put references.
Not sure how I got here but I'm honestly not complaining just a bit confused..what's some uses for this? is he just making it because it's just fascinating which I can completely understand, but is he making if for another project that I can't find?😅
Aren’t your TLCs super concentrated ? At least the ones before the column …
And no sand on top of the column ? At my uni we always put sand on top of the silica gel to deposit the product
You choice of base for the SM coupling was quite questionable, as well as using heterogeneous conditions. Et3N would be much better here.
Damn, nice cannula transfer. That isn’t always for the faint of heart.
Could phenyllithium be used in place of the phenylmagnesium bromide or is it too reactive?
How did you reduce the palladium in situ?
How did you ensure that addition was equimolar? Did you ensure the molar concentrations were the same in each addition funnel? That way 1 drip is roughly the same molar equivalent?
Yes I drip them steadily, but the phmgbr a bit faster. As long as there is no extreme excess present it should still be fine (in procedure they do in portions of 20 ml or so)
Did it smell like Dowtherm (the industrial heat transfer fluid which contains biphenyl)?
I’m planning to use Epin soon. Where do you get the diol from?
You need to make it urself since it is not commercially available, see previous video where I made it. There might be alternative methods to what I did.
You really got to listen to catch all the humor ,@ ~8:30 ... *Then* *abuse* the *flask* ... I'd love to see comments like that in a published paper
good vid
Hi, could you please be so kind as tell me how you got the cannula needed for the Grignard reaction? They seem completely inaccessible to amateur chemists due to their very high price. Thanks!
Yes they are hard to find somehow but I bought from fengtecex (synthware). You need a company tho, idk where they sell it without
@@Chemiolis Thanks a lot! 🙏
You can use a syringe and needle. Cannula is just convenient and a little safer
@@wingl5841 actually, no. cannulas and needles are not interchangeable in 100% of the cases
cannulas are usually much longer than needless and have larger id, they are also made out of different, more resistant materials, you can bend them and most importantly they are meant to be reusable
Why not try dry vacuum colum chromatography ?
Thanks
Sorry if I missed it but how did you obtain EPin?
See previous video
What type of plates did you use for tlc?
alugram xtra sil g/uv254
"I abused the flask.." 🤣🤣🤣
Ph do be eepin' tho.
based
someone should buy you a rotavap😁
cool
Worter
PhB(epin), more like PhB(epic).
Boop