Were you able to guess the key reaction? Let me know how you liked the video, and if you have any suggestions! Massive thank you to all my supporters: www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
Please show me a video of you making CONOLIDINE. Not clonidine. CONOLIDINE is a calcium channel blocker. New syntheses have been published using gold based catalysts.
Well man I grew up in a rough place and that was also a big practical introduction to the science for me as well... and I would later go to a university to study chemistry formally. Everybody's gotta start somewhere. Stay safe, my guy.
As a biochemist that only took Orgo 1 and 2 these videos always make my mouth water for some proper introduction to Organic chemistry at such a level. Now im just wondering what books or videos to go to because I know university courses wont be here for another semester
Im actually in the process of creating a theory and more importantly practice book for organic synthesis. Unfortunately with the pace Im going, this is gonna take some more months at least! What topics or questions are of particularl interest to you?
@@totalsynthesis that sounds cool! Well pretty much all commonly utilized organic chemistry in pharma specifically. Topics where I notice im most lacking is prochirality and in general stereoselective synthesis. Could you maybe recommend a general book? I have a bachelors degree in biochemistry but I missed out on anything beyond Orgo 1&2. Currently pursuing my masters degree.
Thank you so much! Perhaps I would like to get more practice on ring opening or closing reactions. It made my mind blown when I was in the advanced orgo class
1:13 I'm glad you covered this; water-mediated bonding is fascinating on its own; being able to map favorable and unfavorable waters that occupy a cavity is an extremely powerful tool in drug design that isn't really covered in the standard array of undergrad medchem/biochem texts.
The flat molecule just seems so suitable for a cross-coupling cascade, but when I see the bromofuran, I knew at once that some D-A is going to happen to effect the benzene ring.
Did something similar to that in an internship a few years ago. It was a DA reaction between a benzyne, derived from 1,2,4,5-tetrabromo benzene and some furan derivative. Way cool!
You're the Best! I found your videos so fascinating! What book would you recommend to a graduate chemistry student who is endangered by an exam of advanced organic chemistry? I'm starting by watching your videos and doing the synthesis my self! Thank you!
Thanks so much! What topics do you need to focus on? Kinda depends (Btw, Im in the process of creating a chemistry problem solving ebook but thats taking more time than you likely have haha)
@@totalsynthesismainly multistep synthesis and retro synthetic approach, I don't know if I'm doing it wrong, but I tend to focus on single processes problems and when I'm in front of difficult multi step synthesis I panic a bit... And I've never experienced such thing in any other class like physics or math... Maybe I'm doing it wrong... Thank you so much anyway for your videos! And the answer!
Here are some examples of how non-contradictory infinitesimal/monadological frameworks could potentially resolve paradoxes or contradictions in chemistry: 1) Molecular Chirality/Homochirality Paradoxes Contradictory: Classical models struggle to explain the origin and consistent preference for one chiral handedness over another in biological molecules like amino acids and sugars. Non-Contradictory Possibility: Infinitesimal Monadic Protolife Transitions dsi/dt = κ Σjk Γijk(n)[sj, sk] + ξi Pref(R/S) = f(Φn) Modeling molecular dynamics as transitions between monadic protolife states si based on infinitesimal relational algebras Γijk(n) that depend on specific geometric monad configurations n. The homochiral preference could emerge from particular resonance conditions Φn favoring one handedness. 2) Paradoxes in Reaction Kinetics Contradictory: Transition state theory and kinetic models often rely on discontinuous approximations that become paradoxical at certain limits. Non-Contradictory Possibility: Infinitesimal Thermodynamic Geometries dG = Vdp - SdT (Gibbs free energy infinitesimals) κ = Ae-ΔG‡/RT (Arrhenius smoothly from monadic infinities) Using infinitesimal calculus to model thermodynamic quantities like Gibbs free energy dG allows kinetic parameters like rate constants κ to vary smoothly without discontinuities stemming from replacing finite differences with true infinitesimals. 3) Molecular Structure/Bonding Paradoxes Contradictory: Wave mechanics models struggle with paradoxes around the nature of chemical bonding, electron delocalization effects, radicals, etc. Non-Contradictory Possibility: Pluralistic Quantum Superposition |Ψ> = Σn cn Un(A) |0> (superposed monadic perspectives) Un(A) = ΠiΓn,i(Ai) (integrated relational properties) Representing molecular electronic states as superpositions of monadic perspectives integrated over relational algebraic properties Γn,i(Ai) like spins, positions, charges, etc. could resolve paradoxes by grounding electronic structure in coherent relational pluralisms. 4) Molecular Machines/Motor Paradoxes Contradictory: Inefficiencies and limitations in synthetic molecular machines intended to mimic biological molecular motors like ATP synthase, kinesin, etc. Non-Contradictory Possibility: Nonlinear Dissipative Monadologies d|Θ>/dt = -iH|Θ> + LΓ|Θ> (pluralistic nonet mechanics) LΓ = Σn ζn |Un> rather than isolated molecular wavefunctions, where infinitesimal monadic sink operators LΓ account for open-system energy exchanges, could resolve paradoxes around efficiency limits. The key theme is using intrinsically pluralistic frameworks to represent molecular properties and dynamics in terms of superpositions, infinitesimals, monadic configurations, and relational algebraic structures - rather than trying to force classically separable approximations. This allows resolving contradictions while maintaining coherence with quantum dynamics and thermodynamics across scales. Here are 4 more examples of how infinitesimal/monadological frameworks could resolve contradictions in chemistry: 5) The Particle/Wave Duality of Matter Contradictory: The paradoxical wave-particle dual behavior of matter, exemplified by the double-slit experiment, defies a consistent ontological interpretation. Non-Contradictory Possibility: Monadic Perspectival Wavefunction Realizations |Ψ> = Σn cn Un(r,p) Un(r,p) = Rn(r) Pn(p) Model matter as a superposition of monadic perspectival realizations Un(r,p) which are products of wavefunctional position Rn(r) and momentum Pn(p) distributions. This infinitesimal plurality avoids the paradox by allowing matter to behave holistically wave-like and particle-like simultaneously across monads. 6) Heisenberg's Uncertainty Principle Contradictory: The uncertainty principle ΔxΔp ≥ h/4π implies an apparent paradoxical limitation on precise simultaneous measurement of position and momentum. Non-Contradictory Possibility: Complementary Pluriverse Observables Δx Δp ≥ h/4π Δx = Σi |xiP - xP| (deviations across monadic ensembles) xP = ||P (pluriverse-valued perspective on x) Reinterpret uncertainties as deviations from pluriverse-valued observables like position xP across an ensemble of monadic perspectives, avoiding paradox by representing uncertainty intrinsically through the perspectival complementarity. 7) The Concept of the Chemical Bond Contradictory: Phenomonological models of bonds rely paradoxically on notions like "electronic charge clouds" without proper dynamical foundations. Non-Contradictory Possibility: Infinitesimal Intermonadic Charge Relations Γij = Σn qinj / rnij (dyadic catalytic charge interactions) |Ψ> = Σk ck Πij Γij |0> (superposed bond configuration states) Treat chemical bonds as superposed pluralities of infinitesimal dyadic charge relation configurations Γij between monadic catalysts rather than ambiguous "clouds". This grounds bonds in precise interaction algebras transcending paradoxical visualizations. 8) Thermodynamic Entropy/Time's Arrow Contradictory: Statistical mechanics gives time-reversible equations, paradoxically clashing with the time-irreversible increase of entropy described phenomenologically. Non-Contradictory Possibility: Relational Pluriverse Thermodynamics S = -kB Σn pn ln pn (entropy from realization weights pn) pn = |Tr Un(H) /Z|2 (Born statistical weights from monadologies) dS/dt ≥ 0 (towards maximal pluriverse realization) Entropy increase emerges from tracking the statistical weights pn of pluriversal monadic realizations Un(H) evolving towards maximal realization diversity, resolving paradoxes around time-reversal by centering entropics on the growth of relational pluralisms. In each case, the non-contradictory possibilities involve reformulating chemistry in terms of intrinsically pluralistic frameworks centered on monadic elements, their infinitesimal relational transitions, superposed realizations, and deviations across perspectival ensembles. This allows resolving apparent paradoxes stemming from the over-idealized separability premises of classical molecular models, dynamically deriving and unifying dualisms like wave/particle in a coherent algebraic ontology.
You could oxidize the methyl side-chain instead of making the bromide, then reductive amination. I cant understand why a benzyl bromide would give any problem, just treat the final produkt with ammoniak in a solvent and convert and trace to the benzyl amine then remove tris with a simple acid wash
In this case its actually preferable to have low solubility as the slow dissolution in the lung creates a depot effect and might allow for more long acting administration
