I must say, I'm very glad to have found your channel! I really like your presentation style and content. Since I'm planning to pursue a PhD in a near future, learning about some less common reactions is very handy. I think you will certainly get a lot of following with your skills
At 2:14, couldn't the akyl chloride of the 2-chloroacetyl chloride also undergo an FC alkylation in addition to the FC acylation? I imagine this could result in FC alkylation byproducts as well as polymerization
@@ThatChemistOld I'll be honest I've never done an FC alkylation (but it's been on the radar as a concerning potential side reaction). I thought the process was rather quick though. From the original FC report (cited in this review 10.3762/bjoc.6.6), it seems the reaction was nearly instantaneous upon the addition of AlCl3, at room temperature ostensibly.
@@AlphaNumeric123 with benzyl groups sure, but not usually with other groups (tertiary chlorides will as well, but those are synthetically rare beyond tBuCl)
@@ThatChemistOld It's an interesting exercise to consider, so this is all in good fun. Hugely respect your channel and success. I don’t think FC alkylations necessarily need to be used with extreme conditions. The initial discovery was made by serendipity, with non-forcing conditions,[1] and primary alkyl halides can undergo FC alkylation at subzero temperatures.[2] There’s even an “ancient” report that my proposed side reaction does occur.[3] In a more forcing condition with an activated aromatic system, the alpha-haloketone does undergo alkylations at scale,[4] which at least indicates it should be a consideration when planning the reaction (heating, duration, concentration), I think. Alpha-halomethylketones is a 1,2-dieletrophile (two vicinal partial positive charges), so to your point this may be even less activated. The t-butylbenzene is slightly activated compared to benzene (hyperconjugation), but of course the FC acylation is far faster/favoured, so my guess is that the acylation deactivates the aromatic system for further substitution (in classic FC fashion), but I don’t think alkylation side reactions are impossible.f [1] 10.1007/978-3-642-01053-8_101 [2] 10.1021/jo01190a003 [3] Bulletin de la Societe Chimique de France, 1897, (3)17, p. 508 [4] 10.1039/SP238
You can change the default colour pallets - I have included the ChemDraw style sheet that I use for my lectures in the Discord #resources channel (the style includes the pallet)
presumably - you would probably be better off just isolating the amine as a salt, and then use formaldehyde and reduce the imine - I have seen reductions of isocyanates/isothiocyanates to formamides/thioformamides, but the conditions are typically obscure inorganic reductants
Hey now, methylamines are more than just drugs :P I would rather use this method to make something like halostachine or long chain aliphatic amines rather than eschweiler-Clarke. Imine formations always give me trouble
i really like the simplicity of your presentation, please leave it as it is because is a very distinctive trait and n effective trademark
Thank you!
I must say, I'm very glad to have found your channel! I really like your presentation style and content. Since I'm planning to pursue a PhD in a near future, learning about some less common reactions is very handy. I think you will certainly get a lot of following with your skills
Thank you!!
At 0:39, how do we avoid the aldol condensation on the other alpha carbon of the acetone in step 2?
At 2:14, couldn't the akyl chloride of the 2-chloroacetyl chloride also undergo an FC alkylation in addition to the FC acylation? I imagine this could result in FC alkylation byproducts as well as polymerization
I haven't ever seen this reported in the literature - in general FC alkylations are pretty harsh reactions
@@ThatChemistOld I'll be honest I've never done an FC alkylation (but it's been on the radar as a concerning potential side reaction). I thought the process was rather quick though. From the original FC report (cited in this review 10.3762/bjoc.6.6), it seems the reaction was nearly instantaneous upon the addition of AlCl3, at room temperature ostensibly.
@@AlphaNumeric123 with benzyl groups sure, but not usually with other groups (tertiary chlorides will as well, but those are synthetically rare beyond tBuCl)
@@ThatChemistOld It's an interesting exercise to consider, so this is all in good fun. Hugely respect your channel and success. I don’t think FC alkylations necessarily need to be used with extreme conditions. The initial discovery was made by serendipity, with non-forcing conditions,[1] and primary alkyl halides can undergo FC alkylation at subzero temperatures.[2] There’s even an “ancient” report that my proposed side reaction does occur.[3] In a more forcing condition with an activated aromatic system, the alpha-haloketone does undergo alkylations at scale,[4] which at least indicates it should be a consideration when planning the reaction (heating, duration, concentration), I think. Alpha-halomethylketones is a 1,2-dieletrophile (two vicinal partial positive charges), so to your point this may be even less activated.
The t-butylbenzene is slightly activated compared to benzene (hyperconjugation), but of course the FC acylation is far faster/favoured, so my guess is that the acylation deactivates the aromatic system for further substitution (in classic FC fashion), but I don’t think alkylation side reactions are impossible.f
[1] 10.1007/978-3-642-01053-8_101
[2] 10.1021/jo01190a003
[3] Bulletin de la Societe Chimique de France, 1897, (3)17, p. 508
[4] 10.1039/SP238
What programme do you use to draw your pretty mechanisms? I didn't think Chemdraw has cool colours haha
You can change the default colour pallets - I have included the ChemDraw style sheet that I use for my lectures in the Discord #resources channel (the style includes the pallet)
Can the isocyanic acid which you wrote in blue be reduced to a methylamine with lah or red-al?
presumably - you would probably be better off just isolating the amine as a salt, and then use formaldehyde and reduce the imine - I have seen reductions of isocyanates/isothiocyanates to formamides/thioformamides, but the conditions are typically obscure inorganic reductants
according to people in my discord, yes it should work!
nice eye, Walter white :p
Hey now, methylamines are more than just drugs :P I would rather use this method to make something like halostachine or long chain aliphatic amines rather than eschweiler-Clarke. Imine formations always give me trouble
@@bobsagely812 you can also take the primary amine and use CDI to get the isocyanate
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