{"version":"1.0.0","segments":[{"speaker":null,"startTime":3,"endTime":5.85,"body":"hello and welcome to Innovate and React."},{"speaker":null,"startTime":6.18,"endTime":11.97,"body":"I am Kevin Hares, and thisepisode will explore how solvents"},{"speaker":null,"startTime":11.97,"endTime":16.11,"body":"can activate reactants andallow more efficient reaction."},{"speaker":null,"startTime":17.34,"endTime":22.235,"body":"Today I'm with Nicholas Jankowski,please tell us a bit about yourself."},{"speaker":null,"startTime":22.49,"endTime":23.09,"body":"Nick: Hello, Kevin."},{"speaker":null,"startTime":23.19,"endTime":27.95,"body":"I studied with you, so we, uh, learnedfrom each other from university."},{"speaker":null,"startTime":28.12,"endTime":34.43,"body":"I, um, then joined the organicchemistry department for my PhD."},{"speaker":null,"startTime":35.348,"endTime":40.658,"body":"Professor Krause's working group worksin metal catalysis, for example, gold"},{"speaker":null,"startTime":40.658,"endTime":45.428,"body":"catalysis, or mostly gold catalysis, andYeah, in the recent years he, uh, took a"},{"speaker":null,"startTime":45.428,"endTime":51.658,"body":"turn more into sustainable chemistry in,which we explore water soluble catalysts,"},{"speaker":null,"startTime":51.658,"endTime":54.778,"body":"for example, or micellar catalysis."},{"speaker":null,"startTime":54.778,"endTime":58.738,"body":"Uh, in my master's thesis I did somemicellar catalysis and this opened the"},{"speaker":null,"startTime":58.738,"endTime":61.678,"body":"field for catalysis for me in, uh, yeah."},{"speaker":null,"startTime":62.643,"endTime":64.763,"body":"In terms of academic research."},{"speaker":null,"startTime":64.963,"endTime":71.663,"body":"And, um, I was sure I wanted to,explore more in my PhD and especially"},{"speaker":null,"startTime":71.673,"endTime":75.023,"body":"in how to optimize reactions,which was a big part of it."},{"speaker":null,"startTime":75.323,"endTime":81.053,"body":"And also I wanted to do organicchemistry, basically really, um,"},{"speaker":null,"startTime":81.073,"endTime":84.393,"body":"build something from scratch andhave some reaction mechanisms going."},{"speaker":null,"startTime":84.963,"endTime":91.973,"body":"Kevin: Yeah, so also catalysis, which wetalked about in the last episode, but this"},{"speaker":null,"startTime":91.973,"endTime":99.358,"body":"time since it's more organic chemistrydriven It's much more complex molecules."},{"speaker":null,"startTime":99.358,"endTime":106.288,"body":"Last time we had the aldol reaction, whichis just two simple aldehydes combining"},{"speaker":null,"startTime":106.798,"endTime":113.608,"body":"and There we don't have to look into manyFunctional groups and stuff like that."},{"speaker":null,"startTime":113.688,"endTime":122.088,"body":"So you mentioned that the optimizationthat will also be one part and first"},{"speaker":null,"startTime":122.088,"endTime":127.233,"body":"of all what molecules did you look at?"},{"speaker":null,"startTime":127.838,"endTime":132.568,"body":"Nick: So, um, my professor likedto first build up some interesting"},{"speaker":null,"startTime":132.568,"endTime":137.028,"body":"substrate molecules and then, um, dothe last step as a gold catalysis."},{"speaker":null,"startTime":137.068,"endTime":144.388,"body":"Um, for me, it wasn't gold, but, uh, well,so therefore I synthesized,  propagilic"},{"speaker":null,"startTime":144.388,"endTime":149.058,"body":"amides,  which is also quite, for mepersonally, it's nothing that special."},{"speaker":null,"startTime":149.428,"endTime":157.643,"body":"They are built up from alkynes and amines,which are then,   subjected to a amide"},{"speaker":null,"startTime":157.668,"endTime":160.408,"body":"reaction forming the propagylic amide."},{"speaker":null,"startTime":160.428,"endTime":164.818,"body":"And this could then cyclizedto oxazols  or oxazolines."},{"speaker":null,"startTime":165.818,"endTime":168.368,"body":"Um, yeah, that was my main topic."},{"speaker":null,"startTime":168.698,"endTime":171.518,"body":"I explored different othersubstrate molecules as well."},{"speaker":null,"startTime":171.518,"endTime":177.148,"body":"For example, allenes, which are even moredifficult to synthesize  well, someone"},{"speaker":null,"startTime":177.158,"endTime":182.858,"body":"who specializes in natural products willlaugh, but, uh, to do four steps, or four"},{"speaker":null,"startTime":182.858,"endTime":188.318,"body":"steps in thesis before you do the, uh,cyclization step, it's, yeah, well, um,"},{"speaker":null,"startTime":188.808,"endTime":192.388,"body":"some would say a waste of time, but thenagain, they are interesting molecules,"},{"speaker":null,"startTime":192.403,"endTime":194.243,"body":"Kevin: Yeah, yeah, exactly."},{"speaker":null,"startTime":194.993,"endTime":201.693,"body":"In my synthesis in my PhD for theligand synthesis, it was also like"},{"speaker":null,"startTime":201.903,"endTime":208.133,"body":"same amount, like four steps or so, butthe actual reactions we looked at were"},{"speaker":null,"startTime":208.133,"endTime":210.453,"body":"then usually  one or two steps at most."},{"speaker":null,"startTime":210.453,"endTime":214.063,"body":"So that's the completeopposite of the spectrum."},{"speaker":null,"startTime":214.663,"endTime":215.213,"body":"But."},{"speaker":null,"startTime":215.568,"endTime":220.528,"body":"You get with more steps to much morecomplicated molecules and these are"},{"speaker":null,"startTime":220.998,"endTime":227.048,"body":"usually used for pharmaceuticalsand plant protection  which have"},{"speaker":null,"startTime":227.048,"endTime":229.168,"body":"then a lot of functional groups."},{"speaker":null,"startTime":229.678,"endTime":236.758,"body":"So here the catalysis is even moredifficult because you have to see that"},{"speaker":null,"startTime":236.758,"endTime":245.553,"body":"you address only one functional group inyour case, the amide cyclization, right?"},{"speaker":null,"startTime":245.553,"endTime":249.573,"body":"So the oxazoles, um,what are they used for?"},{"speaker":null,"startTime":250.723,"endTime":250.973,"body":"Nick: Yeah."},{"speaker":null,"startTime":250.973,"endTime":260.333,"body":"So, um, to make it short, really, they aresome,  examples which are in the terms of"},{"speaker":null,"startTime":260.703,"endTime":266.663,"body":"pesticides and there are some promisingcandidates in pharmaceuticals and so on"},{"speaker":null,"startTime":266.663,"endTime":272.003,"body":"but as far as I know, there's not a realpharmaceutical right now on the market"},{"speaker":null,"startTime":272.303,"endTime":276.593,"body":"then again, it's a structural motivewhich you find in nature and therefore"},{"speaker":null,"startTime":276.593,"endTime":280.193,"body":"it has the potential to Be discovered"},{"speaker":null,"startTime":280.293,"endTime":286.783,"body":"The oxazoles are hetero cyclics whichhave the O in position 1 in the 5 ring"},{"speaker":null,"startTime":286.813,"endTime":294.203,"body":"and the N Nitrogen in position 3, butthere are other types which are isomers"},{"speaker":null,"startTime":294.203,"endTime":297.423,"body":"where the Positions are 1 and 2 basically."},{"speaker":null,"startTime":297.423,"endTime":299.418,"body":"Right at the  besides each other."},{"speaker":null,"startTime":299.428,"endTime":304.678,"body":"Those, uh, are much more likely tobe found in pharmaceuticals nowadays."},{"speaker":null,"startTime":304.798,"endTime":309.788,"body":"And there are lots and lots ofchemistry being done to build them"},{"speaker":null,"startTime":309.808,"endTime":314.808,"body":"in interesting pathways so thatthere's no  selectivity issues."},{"speaker":null,"startTime":315.599,"endTime":321,"body":"Kevin: how would you synthesize themin the, I would say, conventional"},{"speaker":null,"startTime":321,"endTime":325.8,"body":"way when you just use organicchemistry and not catalysis?"},{"speaker":null,"startTime":327.275,"endTime":330.905,"body":"Nick: Yeah, oxazoles can befound in natural products."},{"speaker":null,"startTime":330.935,"endTime":335.655,"body":"So, um, they have been isolatedfrom plants and marine life."},{"speaker":null,"startTime":335.995,"endTime":340.345,"body":"Um, for example, there are somestudies being done on primprinine"},{"speaker":null,"startTime":340.355,"endTime":344.455,"body":"or texamine, which are, uh,which have an oxazole motive."},{"speaker":null,"startTime":344.505,"endTime":346.765,"body":"So they once rehydrocycle in there."},{"speaker":null,"startTime":347.705,"endTime":354.315,"body":"And, they were found to have some kind ofimprovement at, uh, with hyperactivity or"},{"speaker":null,"startTime":354.405,"endTime":357.825,"body":"they are working against,  tuberculosis,"},{"speaker":null,"startTime":358.33,"endTime":358.65,"body":"Kevin: Mhm."},{"speaker":null,"startTime":358.835,"endTime":359.745,"body":"Nick: uh, bacteria."},{"speaker":null,"startTime":360.025,"endTime":364.335,"body":"So there's that, but as far as Iknow, uh, really a pharmaceutical"},{"speaker":null,"startTime":364.385,"endTime":367.025,"body":"agent is not currently in place."},{"speaker":null,"startTime":367.85,"endTime":371.74,"body":"Maybe that's the reason why there'sa kind of research gap where you"},{"speaker":null,"startTime":371.74,"endTime":375.17,"body":"can fit in nicely a,  PhD thesis."},{"speaker":null,"startTime":375.44,"endTime":376.58,"body":"And, well, there we are."},{"speaker":null,"startTime":376.72,"endTime":377.11,"body":"We are."},{"speaker":null,"startTime":377.6,"endTime":378.12,"body":"Kevin: Yeah, nice."},{"speaker":null,"startTime":378.16,"endTime":385.13,"body":"But, uh, oxazoles, they then showbiological activity because they are found"},{"speaker":null,"startTime":385.14,"endTime":388.49,"body":"in, plants and marine life, as you said."},{"speaker":null,"startTime":388.98,"endTime":392.28,"body":"But it's probably in very lowconcentrations, so we have to"},{"speaker":null,"startTime":392.87,"endTime":396.71,"body":"synthesize them if we want to usethem as, pest control or something"},{"speaker":null,"startTime":396.72,"endTime":399.35,"body":"like that, or antibacterial agents."},{"speaker":null,"startTime":400.57,"endTime":400.9,"body":"Nick: Right."},{"speaker":null,"startTime":401.57,"endTime":405.11,"body":"There's, uh, one, which is Oxaprozin,uh, which is a pharmaceutical"},{"speaker":null,"startTime":405.57,"endTime":412.01,"body":"but , as far as I know, um, oneof the one or two only candidates."},{"speaker":null,"startTime":414.115,"endTime":418.685,"body":"Kevin: Yeah, but there's room formore, because once they have shown"},{"speaker":null,"startTime":419.245,"endTime":422.995,"body":"that they're biologically active, allthe drug discovery tools, I guess,"},{"speaker":null,"startTime":423.535,"endTime":429.515,"body":"will them up, and then there might befuture applications, and it is already"},{"speaker":null,"startTime":429.525,"endTime":432.765,"body":"good to have a synthesis plan for them."},{"speaker":null,"startTime":433.925,"endTime":439.175,"body":"And how would you synthesize them inthe classical organic chemistry way?"},{"speaker":null,"startTime":440.605,"endTime":446.755,"body":"Nick: Yeah, some name-reactions,obviously, we are talking"},{"speaker":null,"startTime":446.755,"endTime":447.17,"body":"about organic chemistry."},{"speaker":null,"startTime":447.17,"endTime":450.675,"body":"There are two possibilities, one is,uh, Robinson Gabrielle Synthesis and the"},{"speaker":null,"startTime":450.675,"endTime":452.535,"body":"other one the Fisher oxazole synthesis."},{"speaker":null,"startTime":453.205,"endTime":458.455,"body":"The first one, Robinson Gabrielleuses a dehydratization, um, agent,"},{"speaker":null,"startTime":458.515,"endTime":460.555,"body":"something like a very strong acid."},{"speaker":null,"startTime":460.955,"endTime":465.165,"body":"For example, sulfuric acid or tylenolchloride, um, they can be used."},{"speaker":null,"startTime":465.195,"endTime":468.465,"body":"They are starting withsome, um, amide structure."},{"speaker":null,"startTime":469.14,"endTime":473.65,"body":"As well as I had it and then thereis another ketone group in the"},{"speaker":null,"startTime":473.66,"endTime":478.22,"body":"molecule, which is then combinedand by the exclusion of water, the"},{"speaker":null,"startTime":478.22,"endTime":480.51,"body":"ring is formed from an oxazole."},{"speaker":null,"startTime":481.26,"endTime":487.48,"body":"For the Fischer oxazole synthesis, youalso use an acid for the reaction and"},{"speaker":null,"startTime":487.49,"endTime":490.75,"body":"also displacement with water takes place."},{"speaker":null,"startTime":490.78,"endTime":497.77,"body":"You need aldehyde for it,  mostly aromaticones and also aromatic, uh, cyanhydrides."},{"speaker":null,"startTime":498.89,"endTime":502.28,"body":"And those combine thento the oxazole as well."},{"speaker":null,"startTime":503.015,"endTime":508.585,"body":"Kevin: they all sound like, they areitself very reactive, but now you"},{"speaker":null,"startTime":508.585,"endTime":512.965,"body":"say they need harsh conditions tohave the specific reaction, I guess."},{"speaker":null,"startTime":514.24,"endTime":514.67,"body":"Nick: Right."},{"speaker":null,"startTime":515.05,"endTime":517.57,"body":"They need quite harsh reaction conditions."},{"speaker":null,"startTime":517.6,"endTime":521.75,"body":"Um, the problem also is  youneed at least for Fisher oxazole"},{"speaker":null,"startTime":521.77,"endTime":527.17,"body":"synesis, mostly aromatic ones, soyou're limited in your substituent."},{"speaker":null,"startTime":527.95,"endTime":532.36,"body":"And for the other one,dehydration,  can also take place"},{"speaker":null,"startTime":532.36,"endTime":534.3,"body":"in other, structures as well."},{"speaker":null,"startTime":534.3,"endTime":539.35,"body":"So, at the late stage, um, cyclizationmethods, this,  cannot be done."},{"speaker":null,"startTime":540.07,"endTime":543.87,"body":"Um, most, uh, not most of thetime, but at least it's a concern"},{"speaker":null,"startTime":544.195,"endTime":547.325,"body":"Kevin: So late stage in this contextmeans that you have already a lot"},{"speaker":null,"startTime":547.325,"endTime":551.665,"body":"of reaction steps, and then lateron you want to close the ring."},{"speaker":null,"startTime":551.665,"endTime":554.015,"body":"That's not really possiblewith this kind of reaction."},{"speaker":null,"startTime":554.24,"endTime":554.52,"body":"Nick: yeah,"},{"speaker":null,"startTime":554.645,"endTime":554.935,"body":"Kevin: got it."},{"speaker":null,"startTime":555.96,"endTime":556.22,"body":"Nick: yeah."},{"speaker":null,"startTime":556.53,"endTime":561.84,"body":"And, uh, well, there was an idea formy professor and he was like, okay,"},{"speaker":null,"startTime":562.24,"endTime":567.83,"body":"you see in,  the last, decades or so acolleague, Hashmi from, um, Heidelberg,"},{"speaker":null,"startTime":568.19,"endTime":574.47,"body":"he published a lot of gold catalysis and,uh, on the sub on this kind of reaction"},{"speaker":null,"startTime":574.75,"endTime":580.81,"body":"steps,  from propagilic amides like Iused, and then, uh, cyclized with, uh,"},{"speaker":null,"startTime":580.82,"endTime":583.65,"body":"gold to the oxazoles or oxazolines."},{"speaker":null,"startTime":585.025,"endTime":589.415,"body":"And my professor was like, okay,  asfar as I know, there's not really a"},{"speaker":null,"startTime":590.115,"endTime":597.175,"body":"mild acidic, reaction, maybe we can,look into this, um, because, yeah,"},{"speaker":null,"startTime":597.175,"endTime":602.795,"body":"well,  obviously if you use acidic,reaction conditions, it's mostly not"},{"speaker":null,"startTime":602.795,"endTime":606.945,"body":"so expensive as to use a gold catalysiswith special ligands and so on."},{"speaker":null,"startTime":607.535,"endTime":609.955,"body":"Kevin: But with the conventionalway, you have usually a lot"},{"speaker":null,"startTime":609.965,"endTime":612.175,"body":"of waste production, right?"},{"speaker":null,"startTime":612.205,"endTime":615.965,"body":"When you use, uh, quantitativeamounts of acid, you end up"},{"speaker":null,"startTime":616.035,"endTime":617.485,"body":"with a lot of salts in the end."},{"speaker":null,"startTime":618.005,"endTime":620.515,"body":"So that's why you usuallywant the catalysis."},{"speaker":null,"startTime":621.845,"endTime":625.775,"body":"Nick: Yeah right   the gold catalysisis, uh, um, yeah, maybe I talk about"},{"speaker":null,"startTime":625.775,"endTime":627.695,"body":"the history before my project again."},{"speaker":null,"startTime":627.765,"endTime":627.995,"body":"Yeah."},{"speaker":null,"startTime":628.045,"endTime":632.595,"body":"Starting with those reactions, uh, likeRobinson, Gabriel and Fischer oxazole,"},{"speaker":null,"startTime":632.595,"endTime":638.465,"body":"um, synthesis they require lots andlots of material, which then goes"},{"speaker":null,"startTime":638.465,"endTime":640.555,"body":"to waste, which is not sustainable."},{"speaker":null,"startTime":641.005,"endTime":643.265,"body":"Therefore, catalysis isthe next obvious step."},{"speaker":null,"startTime":643.825,"endTime":647.505,"body":"Going into, producing lesswaste by catalysis because"},{"speaker":null,"startTime":647.525,"endTime":648.995,"body":"you only need, what is it?"},{"speaker":null,"startTime":649.025,"endTime":650.665,"body":"1 percent or so of it."},{"speaker":null,"startTime":650.675,"endTime":652.855,"body":"And then there's a reaction taking place."},{"speaker":null,"startTime":653.835,"endTime":659.105,"body":"Um, much more sustainable, comes witha cost obviously, while this is maybe"},{"speaker":null,"startTime":659.105,"endTime":666.328,"body":"not always,  this much of an advantagein a, In a lab scale, uh, if it would"},{"speaker":null,"startTime":666.328,"endTime":670.248,"body":"be done in, industrial settings,it's a, yeah, no brainer basically"},{"speaker":null,"startTime":670.613,"endTime":674.188,"body":"Kevin: Yeah, when you talk abouttons and tons of product produced"},{"speaker":null,"startTime":674.188,"endTime":679.228,"body":"in the chemical industry, then youobviously also have a lot of salts."},{"speaker":null,"startTime":679.248,"endTime":685.668,"body":"And also in the large scale production,dealing with salts and solid material"},{"speaker":null,"startTime":685.738,"endTime":690.968,"body":"is much more difficult than when youhave everything in the liquid phase."},{"speaker":null,"startTime":692.493,"endTime":693.163,"body":"Nick: yeah, right"},{"speaker":null,"startTime":693.333,"endTime":697.423,"body":"Kevin: So now, um, we have the catalysis."},{"speaker":null,"startTime":698.833,"endTime":705.003,"body":"And for oxazoles, there are also differentkinds of,  catalytic reactions possible."},{"speaker":null,"startTime":705.573,"endTime":709.953,"body":"You already mentioned gold,and, um, if I hear correctly,"},{"speaker":null,"startTime":709.953,"endTime":712.513,"body":"also acid catalyzed reactions,"},{"speaker":null,"startTime":713.663,"endTime":718.523,"body":"Nick: Yeah, right there are some otherexamples you can use nickel for example,"},{"speaker":null,"startTime":718.523,"endTime":726.513,"body":"you can use copper uh iodine Or bases,yeah Depending on which structural"},{"speaker":null,"startTime":726.513,"endTime":731.083,"body":"motive you have obviously, but thereare some different possible ways."},{"speaker":null,"startTime":731.133,"endTime":734.683,"body":"I would not say it's quite easy to makebut there are lots of ways to do it."},{"speaker":null,"startTime":735.073,"endTime":739.717,"body":"Kevin: But maybe they are limited, asyou said, when they, depending on the"},{"speaker":null,"startTime":739.717,"endTime":742.127,"body":"structural motive, you can choose one."},{"speaker":null,"startTime":742.127,"endTime":744.917,"body":"It would be nice to havelike a more general tool."},{"speaker":null,"startTime":745.587,"endTime":752.697,"body":"Transition metal catalysts usuallyhave a high selectivity and high yield."},{"speaker":null,"startTime":753.377,"endTime":758.477,"body":"How do they compare, like inthis case, gold, uh, with the"},{"speaker":null,"startTime":758.477,"endTime":760.037,"body":"other catalytic reactions."},{"speaker":null,"startTime":760.962,"endTime":761.302,"body":"Nick: Yeah."},{"speaker":null,"startTime":761.552,"endTime":766.232,"body":"Um, one really advantage of goodcatalysis is that usually you"},{"speaker":null,"startTime":766.232,"endTime":769.102,"body":"have really selective reactions."},{"speaker":null,"startTime":769.132,"endTime":774.302,"body":"Um, they are not, um, this manyfunctional groups reacting with it."},{"speaker":null,"startTime":774.352,"endTime":777.922,"body":"in my working group, usually you havesomething like an allene structure,"},{"speaker":null,"startTime":777.922,"endTime":780.562,"body":"alkynes and so on, which are activated."},{"speaker":null,"startTime":782.282,"endTime":785.192,"body":"That's a whole nother topicfor nickel, for example, which"},{"speaker":null,"startTime":785.192,"endTime":787.092,"body":"just goes with everything."},{"speaker":null,"startTime":787.102,"endTime":790.602,"body":"Then you have selectivity issuesand have to find the right reaction"},{"speaker":null,"startTime":790.602,"endTime":797.002,"body":"conditions,  which produce justyour,  product selectively, um, as"},{"speaker":null,"startTime":797.002,"endTime":799.362,"body":"well as basis or acid catalysis."},{"speaker":null,"startTime":799.362,"endTime":799.452,"body":"Yeah."},{"speaker":null,"startTime":799.562,"endTime":802.062,"body":"They react with a lotof functional groups."},{"speaker":null,"startTime":802.122,"endTime":807.082,"body":"So the more you have in your molecule,the more you're likely to produce,"},{"speaker":null,"startTime":807.102,"endTime":808.772,"body":"by products which you don't want."},{"speaker":null,"startTime":808.982,"endTime":811.617,"body":"Um, in the lab you need Yeah."},{"speaker":null,"startTime":811.967,"endTime":814.867,"body":"you need so much of separation techniques."},{"speaker":null,"startTime":815.227,"endTime":818.897,"body":"Kevin: Those would be better forlike the early stage reactions,"},{"speaker":null,"startTime":818.897,"endTime":823.717,"body":"when you just have some functionalgroups and then you use them."},{"speaker":null,"startTime":823.997,"endTime":830.167,"body":"But in the end you want high selectivity,because also when you have already a lot"},{"speaker":null,"startTime":830.167,"endTime":835.937,"body":"of steps and then you lose a big chunk ofyour product because of low reactivity,"},{"speaker":null,"startTime":835.947,"endTime":838.747,"body":"it also destroys a lot of your work."},{"speaker":null,"startTime":840.257,"endTime":840.737,"body":"Nick: Right."},{"speaker":null,"startTime":841.992,"endTime":847.432,"body":"And, uh, full disclaimer, I'm not entirelysure how well my project fits in there."},{"speaker":null,"startTime":847.612,"endTime":847.892,"body":"Yeah."},{"speaker":null,"startTime":848.182,"endTime":852.022,"body":"So, um, so to speak, uh,it's a work of pure science"},{"speaker":null,"startTime":852.262,"endTime":852.552,"body":"Kevin: Yeah,"},{"speaker":null,"startTime":853.362,"endTime":857.382,"body":"Nick: and, um, Yeah, that'sa full disclaimer at first."},{"speaker":null,"startTime":857.412,"endTime":861.932,"body":"I'm not entirely sure how well it's,um, with every functional group."},{"speaker":null,"startTime":862.212,"endTime":866.412,"body":"The scope, uh, you have inuniversity is, uh, also somewhat"},{"speaker":null,"startTime":866.432,"endTime":872.952,"body":"limited, but I think it just givessome small edge in, in some ways."},{"speaker":null,"startTime":873.132,"endTime":873.342,"body":"Yeah."},{"speaker":null,"startTime":873.702,"endTime":874.772,"body":"Kevin: it's a different concept."},{"speaker":null,"startTime":874.772,"endTime":877.442,"body":"We will, uh, talk about this in a moment."},{"speaker":null,"startTime":878.762,"endTime":886.827,"body":"Well, first one last question about thegold, because you wanted to substitute"},{"speaker":null,"startTime":886.907,"endTime":889.117,"body":"the gold with different strategy."},{"speaker":null,"startTime":889.667,"endTime":894.347,"body":"Um, what are the problemswith the gold catalysis?"},{"speaker":null,"startTime":894.357,"endTime":899.187,"body":"So we talked about all the, the benefitsthat we have, like high selectivity, high"},{"speaker":null,"startTime":899.187,"endTime":905.267,"body":"yield, and you can do this in a late stagesynthesis, but what are the downsides?"},{"speaker":null,"startTime":907.042,"endTime":910.482,"body":"Nick: Uh, so we use homogeneouscatalysis for, uh, these reactions."},{"speaker":null,"startTime":910.572,"endTime":915.642,"body":"And,  with this you always go or findyourself in some kind of separation"},{"speaker":null,"startTime":915.752,"endTime":920.442,"body":"issues,  in the lab scale, maybethis is not off this much trouble,"},{"speaker":null,"startTime":920.602,"endTime":924.302,"body":"but, uh, later in industrialprocesses, it's, yeah, a headache"},{"speaker":null,"startTime":924.392,"endTime":924.772,"body":"really."},{"speaker":null,"startTime":925.222,"endTime":928.732,"body":"Kevin: column chromatographyis not really a thing in  high"},{"speaker":null,"startTime":929.362,"endTime":929.802,"body":"amounts."},{"speaker":null,"startTime":931.082,"endTime":935.422,"body":"Nick: Yeah, and right in, inpharmaceuticals there are limits in"},{"speaker":null,"startTime":935.422,"endTime":941.632,"body":"which, uh, how many trace amounts of, uh,metalls, uh, can be found or maybe found."},{"speaker":null,"startTime":941.762,"endTime":945.642,"body":"And, um, so you really want to exclude"},{"speaker":null,"startTime":946.142,"endTime":947.602,"body":"Kevin: you really want to avoid them?"},{"speaker":null,"startTime":947.652,"endTime":951.402,"body":"Nick: Yeah, I think that'sreally the point in, uh, if you,"},{"speaker":null,"startTime":951.402,"endTime":954.692,"body":"if you do a homogeneous metalcatalysis, you really need to find"},{"speaker":null,"startTime":954.702,"endTime":956.802,"body":"good ways to separate catalyst."},{"speaker":null,"startTime":956.827,"endTime":961.037,"body":"So while in lab scale you cando homogeneous catalysis really"},{"speaker":null,"startTime":961.037,"endTime":964.877,"body":"well, it's, uh, oftentimes,difficult in industrial settings."},{"speaker":null,"startTime":964.957,"endTime":969.027,"body":"The separation, is quite difficultbecause, as you said, you cannot do"},{"speaker":null,"startTime":969.027,"endTime":973.147,"body":"some columne chromatography or it's atleast very, very expensive to do so."},{"speaker":null,"startTime":974.292,"endTime":978.002,"body":"To get, uh, down to traceamounts, you often need multiple"},{"speaker":null,"startTime":978.012,"endTime":981.742,"body":"steps of,  crystallization,which is also time consuming"},{"speaker":null,"startTime":982.872,"endTime":986.862,"body":"Kevin: that's also the reasonwhy still some of these old"},{"speaker":null,"startTime":986.892,"endTime":991.212,"body":"conventional organic synthesis arestill carried out in large scale."},{"speaker":null,"startTime":991.662,"endTime":995.332,"body":"Because they simply don't have a metalwhich you have to take care of later."},{"speaker":null,"startTime":996.012,"endTime":1001.852,"body":"If there is some acid left youcan deal with it and adjust the"},{"speaker":null,"startTime":1001.852,"endTime":1005.072,"body":"pH and filter out the salt or so."},{"speaker":null,"startTime":1005.682,"endTime":1011.297,"body":"But the metals are reallydifficult to get out completely."},{"speaker":null,"startTime":1011.297,"endTime":1016.927,"body":"So there are always some PPMs left,but I think for some metals it's even"},{"speaker":null,"startTime":1016.947,"endTime":1022.267,"body":"like PPB level, which you have to makesure that there is not more than this."},{"speaker":null,"startTime":1022.547,"endTime":1023.817,"body":"And that's really difficult."},{"speaker":null,"startTime":1024.277,"endTime":1030.487,"body":"So yeah, in this case, the bestway is to not use the metal."},{"speaker":null,"startTime":1031.807,"endTime":1036.257,"body":"And how did you try totackle this problem?"},{"speaker":null,"startTime":1037.622,"endTime":1040.252,"body":"Nick: maybe I start, uh, from scratch."},{"speaker":null,"startTime":1040.252,"endTime":1044.872,"body":"So when I wanted to start my PhD, Italked with my professor about my topic."},{"speaker":null,"startTime":1045.532,"endTime":1047.742,"body":"I wanted to do some optimization work."},{"speaker":null,"startTime":1047.742,"endTime":1049.602,"body":"So catalysis would be nice."},{"speaker":null,"startTime":1050.472,"endTime":1053.302,"body":"I wanted to exploresome kind of reactions."},{"speaker":null,"startTime":1054.022,"endTime":1057.652,"body":"Um, and he was like,okay, I think about it."},{"speaker":null,"startTime":1057.712,"endTime":1063.472,"body":"And when we talked later about it, hecame up with a interesting story of how."},{"speaker":null,"startTime":1065.237,"endTime":1069.677,"body":"When we did alenes, um, back in theday, you had to be really careful"},{"speaker":null,"startTime":1069.677,"endTime":1077.477,"body":"with your NMRs, because the alenescyclize in,  chloroform, because the"},{"speaker":null,"startTime":1077.477,"endTime":1081.347,"body":"chloroform really slowly produces HCl."},{"speaker":null,"startTime":1083.132,"endTime":1086.462,"body":"And this is enough tosometimes cyclize it."},{"speaker":null,"startTime":1086.772,"endTime":1092.842,"body":"When they tried to replicate it in thelab, they found that the only sure way"},{"speaker":null,"startTime":1092.842,"endTime":1099.592,"body":"to make it is use chloroform and then putanhydrous hydrogen chloride gas into it."},{"speaker":null,"startTime":1100.467,"endTime":1101.207,"body":"Kevin: Interesting."},{"speaker":null,"startTime":1101.437,"endTime":1106.947,"body":"So, if you use just normal, uh,hydrochloric acid, then it wouldn't work."},{"speaker":null,"startTime":1107.36,"endTime":1112.685,"body":"Nick: Right, then you getsome kind of ketones, mostly."},{"speaker":null,"startTime":1113.805,"endTime":1116.045,"body":"And not the cycle we wanted back then."},{"speaker":null,"startTime":1117.215,"endTime":1120.345,"body":"So he asked me to look into this."},{"speaker":null,"startTime":1120.355,"endTime":1127.385,"body":"He had one paper from Jeffrey Aube, um, inwhich he used, uh, hexafluoroisopropanol"},{"speaker":null,"startTime":1127.425,"endTime":1133.315,"body":"and a sacrificial agent to produce,anhydrous, uh, HCL in-situ."},{"speaker":null,"startTime":1134.385,"endTime":1135.925,"body":"Um, this is where I started."},{"speaker":null,"startTime":1136.165,"endTime":1138.395,"body":"And, I then synthesized the allenes."},{"speaker":null,"startTime":1138.715,"endTime":1143.375,"body":"Which I then subjected to the methodof Aube, it is acetyl chloride in"},{"speaker":null,"startTime":1144.085,"endTime":1150.765,"body":"HFIP, which then undergoes a, um, yeah,sacrificial reaction to produce HCl,"},{"speaker":null,"startTime":1151.785,"endTime":1153.595,"body":"which is the active molecule then."},{"speaker":null,"startTime":1154.039,"endTime":1156.439,"body":"Kevin: What is the HFIP?"},{"speaker":null,"startTime":1157.575,"endTime":1159.015,"body":"Nick: Uh, hexafluoroisopropanol."},{"speaker":null,"startTime":1160.125,"endTime":1160.515,"body":"Right."},{"speaker":null,"startTime":1160.535,"endTime":1165.415,"body":"Um, you know, isopropanol, so,um, rubbing alcohol oftentimes"},{"speaker":null,"startTime":1165.445,"endTime":1168.025,"body":"called  in the U. S. for example."},{"speaker":null,"startTime":1168.795,"endTime":1174.685,"body":"There are six of the, hydrogensare, exchanged for fluorine atoms."},{"speaker":null,"startTime":1174.875,"endTime":1181.54,"body":"So you have, uh, two CF3 groups inthere, which have a very strong inductive"},{"speaker":null,"startTime":1181.54,"endTime":1186.3,"body":"effect, and therefore you have adifferent reactivity for the molecule."},{"speaker":null,"startTime":1186.96,"endTime":1193.55,"body":"And most importantly, it pulls theelectrons to the fluorine because of high"},{"speaker":null,"startTime":1193.55,"endTime":1198.16,"body":"electron negativity, and therefore youhave a strong effect On the alcohol group,"},{"speaker":null,"startTime":1198.51,"endTime":1200.29,"body":"Kevin: Which makes it more acidic?"},{"speaker":null,"startTime":1200.34,"endTime":1202.63,"body":"Nick: Which makes it more acidic, right."},{"speaker":null,"startTime":1203.38,"endTime":1211.2,"body":"Kevin: And then, you are using this,As your solvent and then the acidic"},{"speaker":null,"startTime":1211.2,"endTime":1213.89,"body":"solvent takes care of the reaction or"},{"speaker":null,"startTime":1215.23,"endTime":1220.28,"body":"Nick: Right, um, so there, thereis in recent times, there's a lots"},{"speaker":null,"startTime":1220.28,"endTime":1225.19,"body":"of, um, literature, being producedusing HFIP as a solvent because"},{"speaker":null,"startTime":1225.19,"endTime":1227.18,"body":"it has some interesting effects."},{"speaker":null,"startTime":1227.68,"endTime":1233.14,"body":"Which come from the special structure,or the special, effects in there."},{"speaker":null,"startTime":1233.42,"endTime":1239.14,"body":"And for example, um, Aube, in, in hispaper, he used it for Schmidt reaction."},{"speaker":null,"startTime":1239.56,"endTime":1241.26,"body":"Kevin: What is the Schmidt reaction?"},{"speaker":null,"startTime":1242.35,"endTime":1247.435,"body":"Nick: um, I shouldn't talk about reactionsif I don't want to explain them, huh?"},{"speaker":null,"startTime":1248.275,"endTime":1255.755,"body":"Okay, so basically, it's also somekind of you have a ketone and azide"},{"speaker":null,"startTime":1255.885,"endTime":1256.225,"body":"all right."},{"speaker":null,"startTime":1256.285,"endTime":1261.855,"body":"So, um, yeah, he used  this for theSchmidt reaction, um, intramolecular one."},{"speaker":null,"startTime":1262.115,"endTime":1266.865,"body":"And so the, the main catch is usuallyyou need stoichiometric amounts of"},{"speaker":null,"startTime":1267.105,"endTime":1269.345,"body":"acid in there, very strong acids."},{"speaker":null,"startTime":1269.945,"endTime":1277.055,"body":"But, in his reaction, the HFIP, wasused as a solvent and he found that"},{"speaker":null,"startTime":1277.425,"endTime":1279.825,"body":"it's coordinating on the ketone group."},{"speaker":null,"startTime":1280.735,"endTime":1285.575,"body":"Which then, yeah, leads to a betteror easier way of activating it."},{"speaker":null,"startTime":1286.555,"endTime":1290.795,"body":"And therefore the reaction, uh, cantake place in milder conditions."},{"speaker":null,"startTime":1292.35,"endTime":1299,"body":"Kevin: And this kind of acidactivation can also be used for the"},{"speaker":null,"startTime":1299.843,"endTime":1302.823,"body":"cycloisomerization that you looked into."},{"speaker":null,"startTime":1303.495,"endTime":1303.929,"body":"Nick: Right."},{"speaker":null,"startTime":1303.929,"endTime":1308.639,"body":"Kevin: And how is this similarto the gold catalysis or is"},{"speaker":null,"startTime":1308.639,"endTime":1311.229,"body":"this similar to gold in any way?"},{"speaker":null,"startTime":1311.474,"endTime":1317.354,"body":"Nick: Maybe I would, uh, take  some stepback,  and start again with, uh Aleens."},{"speaker":null,"startTime":1317.594,"endTime":1319.644,"body":"So that's my first project."},{"speaker":null,"startTime":1319.824,"endTime":1325.034,"body":"Um, so the Aleens I then subjectedto the method of Aube basically"},{"speaker":null,"startTime":1325.224,"endTime":1326.954,"body":"and looked into, what happens."},{"speaker":null,"startTime":1327.374,"endTime":1331.564,"body":"And the first thing I learnedis if you just do it like that,"},{"speaker":null,"startTime":1331.594,"endTime":1333.344,"body":"it's turns to a brown sludge."},{"speaker":null,"startTime":1334.699,"endTime":1339.899,"body":"Um, the brown sludge really,  is some kindof, yeah, following me around, I think."},{"speaker":null,"startTime":1340.089,"endTime":1344.699,"body":"Um, so through the four years ofmy PhD, I had so much brown sludge."},{"speaker":null,"startTime":1344.929,"endTime":1349.659,"body":"I would go as far as to say thatone third of it was just, just that."},{"speaker":null,"startTime":1349.659,"endTime":1355.279,"body":"And, yeah, yeah, great."},{"speaker":null,"startTime":1355.289,"endTime":1356.619,"body":"Don't look, look even further."},{"speaker":null,"startTime":1356.949,"endTime":1358.309,"body":"And, um, yeah."},{"speaker":null,"startTime":1358.899,"endTime":1362.929,"body":"When we found reaction conditionswhich worked, it was,  not really"},{"speaker":null,"startTime":1363.009,"endTime":1366.039,"body":"this high of, academic, uh, merits."},{"speaker":null,"startTime":1366.069,"endTime":1370.529,"body":"It was like, okay, well, you do anacid catalyzed reaction and that's"},{"speaker":null,"startTime":1370.549,"endTime":1374.219,"body":"not so special because there'sno special reactivity in it."},{"speaker":null,"startTime":1374.959,"endTime":1379.209,"body":"You still had to do columnchromatography and so on."},{"speaker":null,"startTime":1379.219,"endTime":1380.659,"body":"And it was like, okay."},{"speaker":null,"startTime":1380.659,"endTime":1384.299,"body":"Really you're limited to aspecial substrates of the Alenes."},{"speaker":null,"startTime":1384.319,"endTime":1389.502,"body":"You don't, you use a just normal,acid pathway and then you have"},{"speaker":null,"startTime":1389.542,"endTime":1390.852,"body":"also the separation issues."},{"speaker":null,"startTime":1391.347,"endTime":1395.037,"body":"Kevin: it is possible, but doesn'treally offer any advantage over the"},{"speaker":null,"startTime":1395.802,"endTime":1396.232,"body":"Nick: right."},{"speaker":null,"startTime":1396.312,"endTime":1397.342,"body":"So I scrapped this."},{"speaker":null,"startTime":1398.697,"endTime":1400.717,"body":"Kevin: Well, that's also part of research."},{"speaker":null,"startTime":1400.727,"endTime":1403.547,"body":"Sometimes you have to pull the string and."},{"speaker":null,"startTime":1404.537,"endTime":1410.167,"body":"Yeah, decide to, that it's enoughand then you can focus your, your"},{"speaker":null,"startTime":1410.167,"endTime":1413.187,"body":"work onto other more promising work."},{"speaker":null,"startTime":1414.807,"endTime":1415.137,"body":"Nick: right."},{"speaker":null,"startTime":1415.207,"endTime":1420.127,"body":"And this was then, uh, for the,propagitic amide, uh, cycloisomerization."},{"speaker":null,"startTime":1420.207,"endTime":1423.697,"body":"Um, I had the substrates frommy master's thesis, already."},{"speaker":null,"startTime":1423.757,"endTime":1427.437,"body":"So I could just, uh, threw themtogether and then look into it."},{"speaker":null,"startTime":1427.497,"endTime":1430.027,"body":"And,  so that was really nice."},{"speaker":null,"startTime":1430.922,"endTime":1435.812,"body":"And I found that there is a pathway,so it's not catalytic, unfortunately."},{"speaker":null,"startTime":1435.872,"endTime":1440.102,"body":"So you have to get, more than oneequivalent of, uh, acid in there,"},{"speaker":null,"startTime":1440.542,"endTime":1442.562,"body":"but at least you could cyclize it."},{"speaker":null,"startTime":1442.572,"endTime":1447.782,"body":"So,  objective one missed, not catalytic,but the other one was okay, but it works."},{"speaker":null,"startTime":1448.022,"endTime":1449.977,"body":"So let's look further into it."},{"speaker":null,"startTime":1450.537,"endTime":1455.097,"body":"And when we looked into this, uh, thenext step was obviously,  go back to"},{"speaker":null,"startTime":1455.097,"endTime":1457.007,"body":"literature and seek what you can find."},{"speaker":null,"startTime":1457.037,"endTime":1462.707,"body":"If, is there any, um, acid catalysisor acid, promoted reaction really?"},{"speaker":null,"startTime":1462.847,"endTime":1465.447,"body":"And there is, so there are possibilities."},{"speaker":null,"startTime":1465.457,"endTime":1469.107,"body":"For example, you could, use my,model substrate later in the"},{"speaker":null,"startTime":1469.107,"endTime":1473.627,"body":"optimization and just throw itin a pure, uh, sulfuric acid."},{"speaker":null,"startTime":1473.977,"endTime":1476.287,"body":"It works, but only for 50%."},{"speaker":null,"startTime":1476.497,"endTime":1480.977,"body":"So at least this, type is also limitedbecause of the sulfuric acid, but"},{"speaker":null,"startTime":1480.977,"endTime":1483.697,"body":"also uses lots and lots of acid in it."},{"speaker":null,"startTime":1483.917,"endTime":1489.493,"body":"Kevin: And has low selectivity, only halfof it is converted to the desired product"},{"speaker":null,"startTime":1490.063,"endTime":1490.133,"body":"Nick: Yeah."},{"speaker":null,"startTime":1490.133,"endTime":1490.343,"body":"Right."},{"speaker":null,"startTime":1492.047,"endTime":1492.397,"body":"Right."},{"speaker":null,"startTime":1492.657,"endTime":1496.267,"body":"And yeah, there, there aresome other types again."},{"speaker":null,"startTime":1497.272,"endTime":1499.302,"body":"every reaction has its limitations."},{"speaker":null,"startTime":1499.842,"endTime":1504.442,"body":"And then we were like, okay, but there'snothing, which is like the a universal"},{"speaker":null,"startTime":1504.592,"endTime":1506.212,"body":"solution for this kind of problem."},{"speaker":null,"startTime":1506.212,"endTime":1514.972,"body":"So we looked deeper into it and wehad then, the HFIP as a solvent."},{"speaker":null,"startTime":1515.292,"endTime":1522.632,"body":"We had, um, acetyl chloride a sacrificialdonor and used this in, the reaction."},{"speaker":null,"startTime":1523.742,"endTime":1528.902,"body":"It worked out, uh, at a lot of substrates,different,  groups, but we were limited"},{"speaker":null,"startTime":1528.902,"endTime":1531.602,"body":"to terminal propag, amides at first."},{"speaker":null,"startTime":1531.932,"endTime":1538.012,"body":"So, um, the alkyne is a terminal one,having, only one site substituted."},{"speaker":null,"startTime":1539.002,"endTime":1542.532,"body":"With this we had, yeah,really a great success."},{"speaker":null,"startTime":1542.662,"endTime":1547.642,"body":"Different, uh, substrates andyou have two possible Yeah."},{"speaker":null,"startTime":1547.922,"endTime":1549.362,"body":"Purification strategies."},{"speaker":null,"startTime":1549.572,"endTime":1552.482,"body":"The first one is welljust removes the solvent."},{"speaker":null,"startTime":1552.542,"endTime":1553.892,"body":"The HCl goes with it."},{"speaker":null,"startTime":1554.102,"endTime":1558.462,"body":"Uh, the acetyl chloride or the,acidic acid, which is,  also"},{"speaker":null,"startTime":1558.462,"endTime":1560.262,"body":"formed when water is there."},{"speaker":null,"startTime":1560.862,"endTime":1563.962,"body":"You can just, uh, getit out, with a rotovap."},{"speaker":null,"startTime":1564.163,"endTime":1565.053,"body":"Kevin: that's easy,"},{"speaker":null,"startTime":1565.212,"endTime":1569.082,"body":"Nick: Yeah, and then you're leftwith,  oxazole salt, basically they,"},{"speaker":null,"startTime":1569.182,"endTime":1572.912,"body":"the HCL salt and yeah, it was pure 99%."},{"speaker":null,"startTime":1573.262,"endTime":1575.842,"body":"The NMRs are really, really beautiful."},{"speaker":null,"startTime":1575.842,"endTime":1577.762,"body":"There's nothing in there,just your molecule."},{"speaker":null,"startTime":1578.342,"endTime":1581.962,"body":"Kevin: It's always satisfyingto have a very pure NMR."},{"speaker":null,"startTime":1582.912,"endTime":1583.752,"body":"I can relate."},{"speaker":null,"startTime":1583.802,"endTime":1590.667,"body":"Nick: Um, uh, one of the, um, Peerreviewer for the paper later said like"},{"speaker":null,"startTime":1590.677,"endTime":1593.467,"body":"a really nice experimental nice NMRs."},{"speaker":null,"startTime":1593.747,"endTime":1595.987,"body":"Uh, so that was really good"},{"speaker":null,"startTime":1596.992,"endTime":1597.342,"body":"Kevin: Nice."},{"speaker":null,"startTime":1597.532,"endTime":1602.032,"body":"So you had a great starting point,which showed that it works for"},{"speaker":null,"startTime":1602.092,"endTime":1607.352,"body":"a lot of different substrates,but it was still in the start."},{"speaker":null,"startTime":1607.362,"endTime":1614.532,"body":"So you had probably not thebest conversion yet or,   what"},{"speaker":null,"startTime":1614.542,"endTime":1616.273,"body":"was still to be optimized?"},{"speaker":null,"startTime":1616.273,"endTime":1617.216,"body":"Mm hmm."},{"speaker":null,"startTime":1617.667,"endTime":1621.227,"body":"Nick: Okay, so with the model substrate,I did the first reactions in a microwave,"},{"speaker":null,"startTime":1621.437,"endTime":1623.687,"body":"because,  well, time is money, also."},{"speaker":null,"startTime":1624.237,"endTime":1628.377,"body":"And, um, there the reactionworks in under one hour."},{"speaker":null,"startTime":1629.052,"endTime":1633.152,"body":"But, I wanted to do, or my, myprofessor was like, yeah, that's fine."},{"speaker":null,"startTime":1633.232,"endTime":1636.702,"body":"But then again, it's not thatyou are doing, it's a special"},{"speaker":null,"startTime":1636.752,"endTime":1638.052,"body":"kind of super reaction."},{"speaker":null,"startTime":1638.282,"endTime":1642.062,"body":"Do it the conventional way, then youhave more of a selling point in it."},{"speaker":null,"startTime":1642.492,"endTime":1646.962,"body":"Everyone should, or should use it,or should be able to use it, right?"},{"speaker":null,"startTime":1647.572,"endTime":1649.232,"body":"So I, uh, got back to the bench."},{"speaker":null,"startTime":1650.137,"endTime":1653.397,"body":"And, um, yeah, I looked intoit with design of experiments."},{"speaker":null,"startTime":1653.897,"endTime":1658.267,"body":"This was something I learned about in mymaster's thesis or not the thesis, but"},{"speaker":null,"startTime":1658.317,"endTime":1663.777,"body":"in, in the, um, in my practical coursein your department, actually, in the"},{"speaker":null,"startTime":1663.827,"endTime":1668.097,"body":"technical chemistry department at ouruniversity, where you really have, yeah."},{"speaker":null,"startTime":1668.637,"endTime":1673.687,"body":"You can use statistics for the analysis,and, um, you don't need to do every"},{"speaker":null,"startTime":1673.877,"endTime":1679.417,"body":"possible reaction in every possible way,but you can, um, apply statistics and go"},{"speaker":null,"startTime":1679.417,"endTime":1681.807,"body":"with less reactions, which is quite nice."},{"speaker":null,"startTime":1681.977,"endTime":1686.757,"body":"Kevin: Yeah, DOE is short fordesign of experiments, right?"},{"speaker":null,"startTime":1686.827,"endTime":1687.127,"body":"Nick: Yeah."},{"speaker":null,"startTime":1687.127,"endTime":1694.257,"body":"And, um, I found this tremendouslyhelpful in my work in the master's thesis."},{"speaker":null,"startTime":1694.257,"endTime":1696.637,"body":"I really, I didn't use it then."},{"speaker":null,"startTime":1697.107,"endTime":1699.087,"body":"because of time constraints."},{"speaker":null,"startTime":1699.227,"endTime":1702.987,"body":"I had  very long, synthesisbefore I could apply it."},{"speaker":null,"startTime":1703.387,"endTime":1707.047,"body":"Um, and therefore, yeah, I, Iskipped it, but I really wanted"},{"speaker":null,"startTime":1707.047,"endTime":1708.697,"body":"to do it in my in my PhD thesis."},{"speaker":null,"startTime":1709.477,"endTime":1714.527,"body":"Kevin: Also,  one, really goodadvantage of the DOE is that you can"},{"speaker":null,"startTime":1714.537,"endTime":1720.957,"body":"find the optimal point and not justthe local optimum point, because"},{"speaker":null,"startTime":1721.427,"endTime":1728.807,"body":"sometimes you screen in different,steps and then you say, okay, this"},{"speaker":null,"startTime":1730.542,"endTime":1733.082,"body":"three equivalents of this reagent."},{"speaker":null,"startTime":1733.112,"endTime":1734.892,"body":"It's the perfect amount."},{"speaker":null,"startTime":1736.212,"endTime":1740.912,"body":"The actual optimum is at 2.8and that you would never find"},{"speaker":null,"startTime":1740.942,"endTime":1743.722,"body":"with the, just the screening."},{"speaker":null,"startTime":1744.182,"endTime":1745.882,"body":"So this is also a big advantage."},{"speaker":null,"startTime":1746.322,"endTime":1754.192,"body":"Um, but why is the DOE not used thatmuch in the organic synthesis research?"},{"speaker":null,"startTime":1754.692,"endTime":1759.362,"body":"Nick: I, I think it's just fromhistoric, pathway, basically."},{"speaker":null,"startTime":1759.362,"endTime":1764.002,"body":"So the, the historic,  way to do, uh,kind of optimization in the lab was,"},{"speaker":null,"startTime":1764.052,"endTime":1769.432,"body":"OFAT, um, approach, so one factor ata time, you would go first and select"},{"speaker":null,"startTime":1769.432,"endTime":1775.312,"body":"your,  Yeah, whatever it is basicallyyour equivalence of one reagent or the"},{"speaker":null,"startTime":1775.312,"endTime":1780.702,"body":"type of base or something like thatyou would use Just one you would just"},{"speaker":null,"startTime":1780.712,"endTime":1784.912,"body":"vary one of the factors and then gothrough and yet as you said you you're"},{"speaker":null,"startTime":1784.912,"endTime":1792.112,"body":"likely to miss the true optimum likethat and it's also not really concise."},{"speaker":null,"startTime":1792.252,"endTime":1796.482,"body":"And if you have a large numberof factors, it's really helpful."},{"speaker":null,"startTime":1797.232,"endTime":1801.422,"body":"Kevin: You use design of experimentsfor your reactions and, um, what"},{"speaker":null,"startTime":1801.932,"endTime":1803.822,"body":"parameters did you optimize?"},{"speaker":null,"startTime":1805.687,"endTime":1807.177,"body":"Nick: Yeah,  my reaction was quite simple."},{"speaker":null,"startTime":1807.407,"endTime":1811.747,"body":"You have an internal reaction youhave your solvent in different"},{"speaker":null,"startTime":1811.747,"endTime":1816.797,"body":"concentrations, temperature, time,and yeah, the sacrificial donor."},{"speaker":null,"startTime":1817.337,"endTime":1822.227,"body":"So,  the main factors Iidentified,  was obviously the"},{"speaker":null,"startTime":1822.287,"endTime":1824.477,"body":"equivalents and the temperature."},{"speaker":null,"startTime":1824.977,"endTime":1831.337,"body":"Then you have,  the minor ones, whichare concentration and, um, time is"},{"speaker":null,"startTime":1831.337,"endTime":1836.797,"body":"always a factor you, depending on,uh, in which direction you want to go,"},{"speaker":null,"startTime":1836.797,"endTime":1839.767,"body":"you can optimize for it or not really."},{"speaker":null,"startTime":1840.337,"endTime":1843.777,"body":"For me, for example, Ilooked into these factors."},{"speaker":null,"startTime":1843.787,"endTime":1846.077,"body":"It's a small design, so it's."},{"speaker":null,"startTime":1846.782,"endTime":1852.332,"body":"Equivalents of sacrificial donor, thetemperature, concentration, and time."},{"speaker":null,"startTime":1853.952,"endTime":1856.202,"body":"And with this, you have just four factors."},{"speaker":null,"startTime":1856.462,"endTime":1857.932,"body":"You could do a full design."},{"speaker":null,"startTime":1858.472,"endTime":1863.542,"body":"Um, I, um, so it's twoto the power of four."},{"speaker":null,"startTime":1863.572,"endTime":1866.362,"body":"So it's 16, 16 reactions is quite okay."},{"speaker":null,"startTime":1866.692,"endTime":1867.582,"body":"You can do it in a lab"},{"speaker":null,"startTime":1867.952,"endTime":1872.422,"body":"Kevin: Yeah, but if you have a lot of,uh, purification steps and all that,"},{"speaker":null,"startTime":1872.422,"endTime":1877.622,"body":"that also is time consuming, so youmaybe want to reduce those as well."},{"speaker":null,"startTime":1878.122,"endTime":1883.062,"body":"Nick: Yeah, right So but forme at least it was low enough"},{"speaker":null,"startTime":1883.092,"endTime":1885.212,"body":"that I choose a different way."},{"speaker":null,"startTime":1885.212,"endTime":1891.412,"body":"I didn't do a screening design But Idid an optimization really so a response"},{"speaker":null,"startTime":1891.412,"endTime":1897.232,"body":"surface where you get a curve of thereaction so you have three points instead"},{"speaker":null,"startTime":1897.232,"endTime":1903.692,"body":"of two and with this I optimize thereaction and Got something about like"},{"speaker":null,"startTime":1905.742,"endTime":1910.232,"body":"Yeah, two equivalents, uh, 80degrees Celsius and, uh, one and"},{"speaker":null,"startTime":1910.232,"endTime":1911.742,"body":"a half hours of reaction time."},{"speaker":null,"startTime":1912.772,"endTime":1916.182,"body":"Kevin: What starting yield didyou get before the optimization?"},{"speaker":null,"startTime":1916.202,"endTime":1919.722,"body":"And what was then theresult of the optimization"},{"speaker":null,"startTime":1920.802,"endTime":1924.702,"body":"Nick: Now before the optimizationI was, uh, under a hundred percent."},{"speaker":null,"startTime":1924.702,"endTime":1930.642,"body":"It was like, I don't know, 70 or so,uh, 60 depending on, different factors."},{"speaker":null,"startTime":1930.822,"endTime":1935.402,"body":"Um, with the DOE I also foundsome  systemic error in which"},{"speaker":null,"startTime":1935.402,"endTime":1937.037,"body":"was, closing of the vessel."},{"speaker":null,"startTime":1937.717,"endTime":1940.757,"body":"Uh, so you really had to makesure it's really airtight."},{"speaker":null,"startTime":1940.847,"endTime":1944.877,"body":"Otherwise you would losesome, um, some of the HCL"},{"speaker":null,"startTime":1945.712,"endTime":1945.922,"body":"Kevin: Oh,"},{"speaker":null,"startTime":1945.977,"endTime":1951.617,"body":"Nick: Yeah, it has to be a closed vesselthen, with this, after the optimization,"},{"speaker":null,"startTime":1951.637,"endTime":1954.337,"body":"uh, I've got over 99 percent yield, so"},{"speaker":null,"startTime":1954.822,"endTime":1955.092,"body":"Kevin: great."},{"speaker":null,"startTime":1955.482,"endTime":1959.112,"body":"Not really, not really better possible."},{"speaker":null,"startTime":1960.187,"endTime":1964.457,"body":"Nick: Yeah, and as I said, umpurification usually was just to remove"},{"speaker":null,"startTime":1964.507,"endTime":1970.047,"body":"the solvent for the high hydrogenchloride salt Or do a basic wash up of"},{"speaker":null,"startTime":1970.047,"endTime":1972.127,"body":"it and then you had the free oxazole"},{"speaker":null,"startTime":1973.327,"endTime":1973.567,"body":"Yeah."},{"speaker":null,"startTime":1973.602,"endTime":1974.782,"body":"Kevin: It's also very convenient."},{"speaker":null,"startTime":1975.672,"endTime":1978.582,"body":"When you compare the hours andhours for column chromatography"},{"speaker":null,"startTime":1978.602,"endTime":1980.402,"body":"and in other syntheses"},{"speaker":null,"startTime":1980.422,"endTime":1981.547,"body":"Nick: yeah"},{"speaker":null,"startTime":1983.542,"endTime":1987.882,"body":"Kevin: You used also different,acid, donors, uh, in your reactions."},{"speaker":null,"startTime":1988.632,"endTime":1991.542,"body":"Um, which was the best one?"},{"speaker":null,"startTime":1993.087,"endTime":1997.947,"body":"Nick: Right for every if you wantto do some kind of this optimization"},{"speaker":null,"startTime":1997.947,"endTime":2002.427,"body":"stuff you should better workon is this really a Good one."},{"speaker":null,"startTime":2002.777,"endTime":2007.417,"body":"Is this really the best you can canachieve so you would Always choose"},{"speaker":null,"startTime":2007.417,"endTime":2012.797,"body":"to do control studies Doing thesame type of reaction in without"},{"speaker":null,"startTime":2012.807,"endTime":2017.207,"body":"the solvent or the special kind ofsolvent isopropanol, for example."},{"speaker":null,"startTime":2017.737,"endTime":2023.727,"body":"For me you get a lower yield in it  Youwould go do something like,  using the"},{"speaker":null,"startTime":2023.727,"endTime":2028.697,"body":"normal acid variant,  the hydrous HCl,which is then in DCM, for example,"},{"speaker":null,"startTime":2030.087,"endTime":2034.817,"body":"there you also get the reaction going,but also not so selectively,  then"},{"speaker":null,"startTime":2034.817,"endTime":2038.717,"body":"you have,  some different reagents,uh, the sacrificial donor could also"},{"speaker":null,"startTime":2038.717,"endTime":2044.057,"body":"be TMS chloride, so trimethylsilyl,chloride, which is also undergoing the"},{"speaker":null,"startTime":2044.067,"endTime":2047.307,"body":"sacrificial reaction with,  with HFIP."},{"speaker":null,"startTime":2048.657,"endTime":2050.967,"body":"Um, this one worked as well."},{"speaker":null,"startTime":2051.157,"endTime":2056.817,"body":"So,  this would have been also, a goodreagent for this type of reaction."},{"speaker":null,"startTime":2058.557,"endTime":2060.537,"body":"Kevin: But that was notoptimized for, right?"},{"speaker":null,"startTime":2061.282,"endTime":2063.362,"body":"Nick: Yeah, it was justa control studies, right?"},{"speaker":null,"startTime":2064.842,"endTime":2065.132,"body":"Right."},{"speaker":null,"startTime":2065.432,"endTime":2069.372,"body":", so with this you test your waythrough it also without a reagent,"},{"speaker":null,"startTime":2069.382,"endTime":2072.982,"body":"for example You would also makesure that you really have to use it"},{"speaker":null,"startTime":2074.051,"endTime":2079.793,"body":"Kevin: And then, uh, after you optimizedthe reaction, you used the optimized"},{"speaker":null,"startTime":2079.833,"endTime":2084.593,"body":"conditions for all different kindsof substrates and achieved a quite"},{"speaker":null,"startTime":2084.593,"endTime":2087.143,"body":"impressive scope for this reaction."},{"speaker":null,"startTime":2087.743,"endTime":2091.623,"body":"In the beginning, we mentioned thata lot of these reactions were very"},{"speaker":null,"startTime":2091.623,"endTime":2095.693,"body":"limited in terms of uh, the substrates."},{"speaker":null,"startTime":2095.864,"endTime":2100.054,"body":"Nick: Yeah, so to the scope,  wetry to use different ones."},{"speaker":null,"startTime":2100.104,"endTime":2105.574,"body":"You always want to have some kind of,uh, different,  effects on the system."},{"speaker":null,"startTime":2105.964,"endTime":2108.184,"body":"So we substitute it at the, uh."},{"speaker":null,"startTime":2108.754,"endTime":2114.274,"body":"At the amide site for,  yeah,different aromatic ones, different"},{"speaker":null,"startTime":2114.604,"endTime":2116.494,"body":"atic ones you want to use."},{"speaker":null,"startTime":2116.524,"endTime":2120.004,"body":"Um, maybe very steric  substitutes."},{"speaker":null,"startTime":2120.004,"endTime":2124.564,"body":"For example, we use adamantylor an, uh, lauryl chain."},{"speaker":null,"startTime":2124.594,"endTime":2127.384,"body":"So C- eleven I hope it was the right one."},{"speaker":null,"startTime":2127.924,"endTime":2133.084,"body":"And also you have some kind of electroniceffects there, using, uh, Flourine groups,"},{"speaker":null,"startTime":2133.104,"endTime":2136.644,"body":"using, um, nitro groups, and so on."},{"speaker":null,"startTime":2136.924,"endTime":2140.514,"body":"And with this yeah, you would,you'd try to test your reaction"},{"speaker":null,"startTime":2140.514,"endTime":2141.974,"body":"if it's really worthwhile to do."},{"speaker":null,"startTime":2143.654,"endTime":2148.664,"body":"So, the basic, uh, the very basicone, cooking real cooking one,"},{"speaker":null,"startTime":2149.289,"endTime":2154.929,"body":"Give it your student if he hassome Some good hands in synthesis."},{"speaker":null,"startTime":2155.199,"endTime":2157.469,"body":"Yeah And this worked really well."},{"speaker":null,"startTime":2157.489,"endTime":2162.029,"body":"So I had also they are very highconversion rates and isolated"},{"speaker":null,"startTime":2162.039,"endTime":2165.839,"body":"yields up to 99 also as well"},{"speaker":null,"startTime":2166.823,"endTime":2170.883,"body":"Kevin: a great new tool forthe synthesis of oxazoles."},{"speaker":null,"startTime":2171.838,"endTime":2177.558,"body":"Which is then a big advantage comparedto all the other reactions which are"},{"speaker":null,"startTime":2178.098,"endTime":2183.368,"body":"limited and then you have to basicallyfor each new product see okay which"},{"speaker":null,"startTime":2183.368,"endTime":2188.558,"body":"reaction can I use which reaction mightbe problematic and now you can just use"},{"speaker":null,"startTime":2188.828,"endTime":2197.584,"body":"your synthesis protocol and it workswith most or many at least, substrates,"},{"speaker":null,"startTime":2197.664,"endTime":2203.514,"body":"Nick: yeah, it's it's uh workssubstrates And I think it can be used"},{"speaker":null,"startTime":2203.514,"endTime":2206.154,"body":"for for some Different reactions."},{"speaker":null,"startTime":2206.204,"endTime":2211.104,"body":"Yeah, also a part of, um, organicchemistry, um, organic chemistry."},{"speaker":null,"startTime":2212.129,"endTime":2214.589,"body":"Is oftentimes that you lookinto the reaction mechanism."},{"speaker":null,"startTime":2214.989,"endTime":2216.159,"body":"Uh, I did it as well."},{"speaker":null,"startTime":2216.169,"endTime":2221.159,"body":"So you wanted to see where's thehydrogen attacking most likely,"},{"speaker":null,"startTime":2221.429,"endTime":2224.339,"body":"where is, um, where is it going?"},{"speaker":null,"startTime":2224.339,"endTime":2227.289,"body":"Is this incorporatedinto the molecule or not?"},{"speaker":null,"startTime":2227.569,"endTime":2232.199,"body":"Is it true catalytic as this, oris it just a promoted reaction?"},{"speaker":null,"startTime":2232.699,"endTime":2238.859,"body":"I would like to look into this and weused some different, um, substitute"},{"speaker":null,"startTime":2238.859,"endTime":2242.189,"body":"for this as well as deuterated HFIP"},{"speaker":null,"startTime":2242.809,"endTime":2248.109,"body":"Kevin: Deuterated one to seeif the proton comes from the"},{"speaker":null,"startTime":2248.119,"endTime":2250.948,"body":"solvent or from the acid donor."},{"speaker":null,"startTime":2252.313,"endTime":2252.613,"body":"Nick: Yeah."},{"speaker":null,"startTime":2252.613,"endTime":2252.923,"body":"Right."},{"speaker":null,"startTime":2252.933,"endTime":2256.293,"body":"We suspected, um, becauseof the work from Aube."},{"speaker":null,"startTime":2256.813,"endTime":2261.213,"body":"That the hydrogen comes from thesolvent and, uh, it also makes a"},{"speaker":null,"startTime":2261.213,"endTime":2265.393,"body":"lot of sense really and we wantedto look if it's incorporating where"},{"speaker":null,"startTime":2265.393,"endTime":2267.633,"body":"we thought it would and it does."},{"speaker":null,"startTime":2267.643,"endTime":2276.123,"body":"So, what we see is that the, acid, um,activates the alkyne and, then there's a"},{"speaker":null,"startTime":2276.333,"endTime":2282.473,"body":"nucleophilic reaction so, the amide, um,Oxygen atom is attacking at the, at the"},{"speaker":null,"startTime":2282.473,"endTime":2290.093,"body":"alkyne and, uh, therefore the deuterium orhydrogen is incorporated into the molecule"},{"speaker":null,"startTime":2290.783,"endTime":2293.763,"body":"at the site of the former alkyne bond."},{"speaker":null,"startTime":2295.928,"endTime":2304.828,"body":"Kevin: the activation of the triple bondhappens through polarization, right?"},{"speaker":null,"startTime":2305.158,"endTime":2305.698,"body":"So"},{"speaker":null,"startTime":2306.648,"endTime":2310.958,"body":"the acid, uh, does asimilar job to the gold."},{"speaker":null,"startTime":2310.958,"endTime":2316.918,"body":"Usually the gold would also activatethis triple bond and then make the"},{"speaker":null,"startTime":2316.978,"endTime":2319.018,"body":"nucleophilic attack more easily."},{"speaker":null,"startTime":2319.798,"endTime":2322.128,"body":"And the acid does the samejob or is it different?"},{"speaker":null,"startTime":2323.123,"endTime":2325.013,"body":"Nick: Uh, no, you're,you're perfectly right."},{"speaker":null,"startTime":2325.653,"endTime":2330.183,"body":"Um, so the acid is activating,there,  You could argue it"},{"speaker":null,"startTime":2330.223,"endTime":2332.203,"body":"works  like the goat as well."},{"speaker":null,"startTime":2332.463,"endTime":2336.963,"body":"So, um, with a gold as well, youdon't see a cationic species."},{"speaker":null,"startTime":2337.523,"endTime":2341.613,"body":"And you also don't see itfor, for the hydrogen attack."},{"speaker":null,"startTime":2341.963,"endTime":2346.166,"body":"Um, you would, it wouldresult in a vinyliden cation."},{"speaker":null,"startTime":2346.211,"endTime":2350.591,"body":"cation and this one is really,would have been really unstable."},{"speaker":null,"startTime":2350.981,"endTime":2355.161,"body":"Therefore you, uh, only have theactivation at an immediate,  concerted"},{"speaker":null,"startTime":2355.161,"endTime":2357.341,"body":"reaction with it, not a stepwise one."},{"speaker":null,"startTime":2358.691,"endTime":2358.941,"body":"Yeah."},{"speaker":null,"startTime":2358.991,"endTime":2361.811,"body":"And, uh, this also,  is anagreement with literature."},{"speaker":null,"startTime":2362.061,"endTime":2369.681,"body":"Kevin: What I asked myself also when Iread about the mechanism is, when you use"},{"speaker":null,"startTime":2369.681,"endTime":2379.211,"body":"the HFIP, the reaction works, and whenyou don't use it, but use another acid,"},{"speaker":null,"startTime":2379.231,"endTime":2381.241,"body":"you get the brown sludge you mentioned."},{"speaker":null,"startTime":2381.776,"endTime":2381.966,"body":"Nick: Yeah."},{"speaker":null,"startTime":2382.601,"endTime":2389.321,"body":"Kevin: What is the role of the HFIPin this mechanism specifically?"},{"speaker":null,"startTime":2389.341,"endTime":2389.406,"body":"The HFIP."},{"speaker":null,"startTime":2389.506,"endTime":2390.566,"body":"Nick: So please bear with me."},{"speaker":null,"startTime":2390.566,"endTime":2395.073,"body":"It's really,  yeah, somethingwe, we don't really know."},{"speaker":null,"startTime":2395.353,"endTime":2399.783,"body":"We did not see anything like that, or Ihad to study for this where we really see"},{"speaker":null,"startTime":2400.113,"endTime":2402.023,"body":"that's the effect and you can pinpoint it."},{"speaker":null,"startTime":2402.483,"endTime":2407.203,"body":"Uh, we think that, it has a strongability of doing hydrogen bonds."},{"speaker":null,"startTime":2407.203,"endTime":2411.313,"body":"So there are some  stabilizingeffects on different groups."},{"speaker":null,"startTime":2411.563,"endTime":2417.593,"body":"And, um, for example, in Aubes' studies,they found, um, to job plots that"},{"speaker":null,"startTime":2417.603,"endTime":2421.323,"body":"it's really, um, bridging to ketones,"},{"speaker":null,"startTime":2421.708,"endTime":2421.768,"body":"Kevin: um,"},{"speaker":null,"startTime":2422.403,"endTime":2426.293,"body":"Nick: uh, via hydrogen bonding, andyou could argue that, here as well,"},{"speaker":null,"startTime":2426.313,"endTime":2432.343,"body":"so every site, which has some kind ofnegative,  or partial negative charge."},{"speaker":null,"startTime":2432.393,"endTime":2436.663,"body":"So yeah, you, you could argue that everysite which is, negatively charged, uh,"},{"speaker":null,"startTime":2436.733,"endTime":2443.213,"body":"also can, be stabilized by this,  kind ofhydrogen bonding, but yeah, we, we didn't,"},{"speaker":null,"startTime":2443.243,"endTime":2445.543,"body":"uh, do a lot of extensive studies on this."},{"speaker":null,"startTime":2445.573,"endTime":2449.683,"body":"It was more for us or for me personallythat we wanted to explore the reaction"},{"speaker":null,"startTime":2449.683,"endTime":2454.483,"body":"more and the mechanism stopped wherewe thought it would be sufficient."},{"speaker":null,"startTime":2455.103,"endTime":2455.313,"body":"Yeah."},{"speaker":null,"startTime":2455.668,"endTime":2456.498,"body":"It's all about time,"},{"speaker":null,"startTime":2456.568,"endTime":2462.058,"body":"Kevin: Yeah, Yeah, I think that couldbe a PhD thesis on its own, just to"},{"speaker":null,"startTime":2462.058,"endTime":2465.208,"body":"find out the precise reaction mechanism."},{"speaker":null,"startTime":2466.048,"endTime":2472.848,"body":"But it still is a very interestingconcept that this solvent makes a"},{"speaker":null,"startTime":2472.848,"endTime":2477.318,"body":"catalytic reaction possible, whichis not possible when you just use"},{"speaker":null,"startTime":2477.318,"endTime":2479.548,"body":"the acid that is created in situ."},{"speaker":null,"startTime":2481.048,"endTime":2487.108,"body":"Nick: Yeah, just as a disclaimer, again,my work is not, not catalytic , in its"},{"speaker":null,"startTime":2487.108,"endTime":2489.908,"body":"own, so it's really, uh, it's promoted."},{"speaker":null,"startTime":2490.378,"endTime":2492.098,"body":"We didn't achieve a catalytic reaction."},{"speaker":null,"startTime":2492.098,"endTime":2497.803,"body":"It was quite , yeah not failure,that's the strong, but, uh, we were"},{"speaker":null,"startTime":2497.823,"endTime":2501.863,"body":"a bit displeased maybe that, uh, wedidn't get down to catalytic amounts."},{"speaker":null,"startTime":2502.143,"endTime":2506.083,"body":"You have to use over stoichiometricamounts, but not the great"},{"speaker":null,"startTime":2506.093,"endTime":2508.093,"body":"excess,  which was,  before this."},{"speaker":null,"startTime":2508.603,"endTime":2512.623,"body":"Um, so there's that, but, yeah,nevertheless, it's not really"},{"speaker":null,"startTime":2512.623,"endTime":2514.123,"body":"catalytic, unfortunately."},{"speaker":null,"startTime":2514.588,"endTime":2514.738,"body":"Kevin: Yeah."},{"speaker":null,"startTime":2514.768,"endTime":2515.038,"body":"Okay."},{"speaker":null,"startTime":2515.128,"endTime":2521.838,"body":"So that was the plan, but the, thereaction mechanism in theory could be"},{"speaker":null,"startTime":2522.688,"endTime":2528.028,"body":"catalytic, but maybe some futureimprovements will get to the point"},{"speaker":null,"startTime":2528.028,"endTime":2531.348,"body":"that it will be, uh, catalytic."},{"speaker":null,"startTime":2531.438,"endTime":2534.678,"body":"What do you think is the futureof this kind of reactions?"},{"speaker":null,"startTime":2536.283,"endTime":2540.673,"body":"Nick: Mm. Yeah, so you youbasically scratching on the is"},{"speaker":null,"startTime":2540.673,"endTime":2545.823,"body":"this really a sustainable solutionand I  from my perspective now,"},{"speaker":null,"startTime":2545.823,"endTime":2548.243,"body":"I would argue it is really not."},{"speaker":null,"startTime":2548.593,"endTime":2553.363,"body":"It was an interesting topic to do researchon but it's not really sustainable."},{"speaker":null,"startTime":2553.413,"endTime":2560.633,"body":"So you use a fluorinated alcohol to usethe reaction  yeah, as everyone knows,  I"},{"speaker":null,"startTime":2560.633,"endTime":2569.938,"body":"think the european union is  going down onall fluorinated, uh, substances right now."},{"speaker":null,"startTime":2569.948,"endTime":2574.938,"body":"So I think this was a bit, um,yeah, it, it, it will be outdated."},{"speaker":null,"startTime":2575.048,"endTime":2576.958,"body":"Basically this type of reaction as well."},{"speaker":null,"startTime":2577.458,"endTime":2582.588,"body":"I would look into different kinds ofpossibilities to do this reaction."},{"speaker":null,"startTime":2582.588,"endTime":2587.008,"body":"For example, if you could do it inwater, it would be interesting as well."},{"speaker":null,"startTime":2588.473,"endTime":2591.023,"body":"When I first tried it, it didn't work out."},{"speaker":null,"startTime":2591.093,"endTime":2593.083,"body":"So you get other reaction products."},{"speaker":null,"startTime":2593.153,"endTime":2596.793,"body":"So the cyclization doesn'thappen, but, hydratization."},{"speaker":null,"startTime":2597.348,"endTime":2601.308,"body":"Kevin: So swap out the HFIPwith water and do the reaction."},{"speaker":null,"startTime":2601.503,"endTime":2604.363,"body":"Nick: yeah, something like thiscould be, uh, could be done."},{"speaker":null,"startTime":2604.373,"endTime":2609.883,"body":"Or if you had some, uh, kindof other solvent type in there."},{"speaker":null,"startTime":2610.373,"endTime":2612.683,"body":"Maybe this is something worthwhile."},{"speaker":null,"startTime":2613.103,"endTime":2617.863,"body":"Also, from a sustainable perspective,most of my amides are solids."},{"speaker":null,"startTime":2617.993,"endTime":2621.853,"body":"So ball milling would beinteresting to do, um,"},{"speaker":null,"startTime":2623.078,"endTime":2626.498,"body":"Kevin: So a complete differentkind of, uh, reaction set up."},{"speaker":null,"startTime":2626.923,"endTime":2629.303,"body":"Nick: yeah, at least wouldbe interesting, right?"},{"speaker":null,"startTime":2629.543,"endTime":2631.353,"body":"We know it works in organic solvents."},{"speaker":null,"startTime":2632.353,"endTime":2636.098,"body":"So this one,  it's always there as well."},{"speaker":null,"startTime":2636.348,"endTime":2641.838,"body":"And you could go to a different kindof, catalysts, for example, you could"},{"speaker":null,"startTime":2641.878,"endTime":2645.168,"body":"do, um, you could swap out the solvent."},{"speaker":null,"startTime":2645.278,"endTime":2648.188,"body":"Yeah, there are lots ofpossibilities to, to work on this."},{"speaker":null,"startTime":2650.688,"endTime":2656.608,"body":"But for me personally, I would say,unfortunately, my type of PhD work"},{"speaker":null,"startTime":2656.718,"endTime":2659.888,"body":"will not be, not see the great future."},{"speaker":null,"startTime":2660.698,"endTime":2666.688,"body":"Kevin: That is often the case with thisvery basic research where you do the"},{"speaker":null,"startTime":2666.698,"endTime":2674.408,"body":"research more out of curiosity and  tryto find out why things are happening and"},{"speaker":null,"startTime":2676.158,"endTime":2682.598,"body":"this might not have a direct applicationat some point but i'm sure it will lead"},{"speaker":null,"startTime":2682.608,"endTime":2689.028,"body":"to other discoveries which use the sameconcept in another way which is the"},{"speaker":null,"startTime":2689.028,"endTime":2695.888,"body":"whole point of of this basic research ithink it has its own importance although"},{"speaker":null,"startTime":2695.888,"endTime":2698.028,"body":"it might not have direct application"},{"speaker":null,"startTime":2699.728,"endTime":2702.738,"body":"Nick: Yeah, if you look intothe, uh, unknown, you cannot"},{"speaker":null,"startTime":2702.748,"endTime":2703.838,"body":"be certain what you find."},{"speaker":null,"startTime":2703.968,"endTime":2704.408,"body":"Kevin: exactly"},{"speaker":null,"startTime":2704.868,"endTime":2705.168,"body":"Nick: Right."},{"speaker":null,"startTime":2706.158,"endTime":2709.908,"body":"Kevin: Okay, that's a greatnote to summarize this episode."},{"speaker":null,"startTime":2710.448,"endTime":2716.788,"body":"And in the next episode, we willlook into another topic of your"},{"speaker":null,"startTime":2717.418,"endTime":2723.318,"body":"PhD thesis and all the learningsyou took away from this work."},{"speaker":null,"startTime":2724.985,"endTime":2725.725,"body":"Nick: Thank you very much."},{"speaker":null,"startTime":2725.725,"endTime":2726.015,"body":"Yeah."},{"speaker":null,"startTime":2726.375,"endTime":2730.895,"body":"That's really something, uh, importantfor me that there are so many things"},{"speaker":null,"startTime":2730.895,"endTime":2736.335,"body":"you learn,  through this and yeah,that's really, everyone can, can tell"},{"speaker":null,"startTime":2736.335,"endTime":2740.275,"body":"you stories about their Phd, whatthey learned about themselves and, um,"},{"speaker":null,"startTime":2741.078,"endTime":2745.388,"body":"Kevin: Sometimes more importantthan the scientific discoveries."},{"speaker":null,"startTime":2745.438,"endTime":2745.808,"body":"Nick: Think so."},{"speaker":null,"startTime":2746.06,"endTime":2749.34,"body":"Kevin: Another thing youcan learn from is the past."},{"speaker":null,"startTime":2749.92,"endTime":2755.38,"body":"And that is what your podcast isabout, also related to chemistry."},{"speaker":null,"startTime":2757.37,"endTime":2760.14,"body":"Nick: Yeah, then someshameless self plugging of me."},{"speaker":null,"startTime":2761.39,"endTime":2766.08,"body":"Yeah, I also have a podcastUnfortunately not for the English"},{"speaker":null,"startTime":2766.08,"endTime":2770.49,"body":"listeners it's in German, so I hopeyou could understand my bad accent,"},{"speaker":null,"startTime":2770.87,"endTime":2774.07,"body":"but Yeah, my podcast is in German."},{"speaker":null,"startTime":2774.07,"endTime":2775.71,"body":"It's called Alles ist Chemie."},{"speaker":null,"startTime":2775.83,"endTime":2782.91,"body":"So all is chemistry and it exploresabout Chemistry and it's his history"},{"speaker":null,"startTime":2783.38,"endTime":2789.51,"body":"So starting in the early ages ofmankind with fire, we explore, to now."},{"speaker":null,"startTime":2789.703,"endTime":2794.083,"body":"I'm currently at episode eight andhad a very long break in between now."},{"speaker":null,"startTime":2794.103,"endTime":2799.423,"body":"I prioritize different, topics in mylife right now, so a new job and so on."},{"speaker":null,"startTime":2799.775,"endTime":2799.925,"body":"Kevin: Yeah."},{"speaker":null,"startTime":2799.965,"endTime":2804.105,"body":"Maybe we can also incorporatethat into the next episode"},{"speaker":null,"startTime":2804.185,"endTime":2806.345,"body":"about, uh, learnings for life."},{"speaker":null,"startTime":2810.528,"endTime":2813.408,"body":"Nick: I'm glad, uh, yeah,we can do this, right?"},{"speaker":null,"startTime":2813.678,"endTime":2817.858,"body":"I can say that there's a newepisode, um, which is scripted."},{"speaker":null,"startTime":2817.948,"endTime":2819.348,"body":"I will start it up again."},{"speaker":null,"startTime":2819.768,"endTime":2820.488,"body":"So I'm really happy"},{"speaker":null,"startTime":2820.525,"endTime":2820.615,"body":"Kevin: Yeah."},{"speaker":null,"startTime":2820.615,"endTime":2821.425,"body":"Great to hear this."},{"speaker":null,"startTime":2821.445,"endTime":2826.135,"body":"I will be looking forward tolisten to your new episode as well."},{"speaker":null,"startTime":2826.655,"endTime":2830.175,"body":"And then, yeah, thankyou all for listening."},{"speaker":null,"startTime":2831.225,"endTime":2834.245,"body":"And we will come back to thistopic in the next episode."},{"speaker":null,"startTime":2836.298,"endTime":2836.708,"body":"Nick: Thank you."},{"speaker":null,"startTime":2837.468,"endTime":2837.828,"body":"Bye."},{"speaker":null,"startTime":2837.828,"endTime":2842.868,"body":"Kevin: If you have an interestingtopic to discuss in the podcast or have"},{"speaker":null,"startTime":2842.868,"endTime":2849.888,"body":"an idea for a topic with a guest youwould like to hear, then let me know."},{"speaker":null,"startTime":2849.938,"endTime":2851.168,"body":"Send me an email to."},{"speaker":null,"startTime":2851.701,"endTime":2855.571,"body":"podcast@innovateandreact.com."},{"speaker":null,"startTime":2856.311,"endTime":2861.411,"body":"If you like this episode, pleaseconsider following on wherever"},{"speaker":null,"startTime":2861.411,"endTime":2863.421,"body":"you're listening to this podcast."},{"speaker":null,"startTime":2863.921,"endTime":2865.991,"body":"Until next time, stay curious."}]}