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Current time:0:00Total duration:11:13

Video transcript

we've done a lot of aldol condensations and in particular we've looked at the mechanism in great detail in this video we're gonna think about doing things in Reverse so we're going to start with a retro aldol reaction and see how that way of thinking can apply to retrosynthesis and so let's start with cinnamaldehyde right here and if we do a retro aldol reaction the mechanism is pretty much the exact reverse of an aldol condensation and so if we got a base like sodium carbonate we're going to form benzaldehyde and acetaldehyde cinnamaldehyde is the molecule that gives cinnamon its smell and benzaldehyde smells like almonds and so this is a pretty cool experiment to do you can start with the molecule smells like cinnamon and end with a molecule that smells like almonds let's analyze our cinnamaldehyde starting compound here to see how we would form those products we know the carbon next to our carbonyl is our alpha carbon we know the carbon next to that is the beta carbon and so looking at the structure right we know that there's a hydrogen attached to our alpha carbon like that so if we think about breaking this double bonds right we can see this this two carbon set up over here on the right for acetaldehyde right so those are the two carbons and this is the hydrogen that's bonded to to that alpha carbon there looking at the structure again on the right we know that there are two more hydrogen's bonded to that alpha carbon and so therefore if we're doing things in Reverse so we can think about adding two hydrogen's to this alpha carbons let me go ahead and draw two hydrogen's right here so I'm just gonna write h2 and then we can think about adding an oxygen to the beta carbon so we can think about adding h2o I know there's already a hydrogen on that beta carbon so I could think about this being the hydrogen on that carbon alright and then if I add an oxygen to that carbon that would be this oxygen right here so just a way of thinking in Reverse right adding water right breaking your double bond and adding an oxygen and two hydrogen's will is one way of thinking about forming your product here so or you could think about the reverse you could think about losing water from this portion and sticking these two fragments together to give your aldol condensation product so once again this way of thinking can be can be very so if you're trying to retro synthesize something so if you're thinking in Reverse so for example let's say a question on a test was show how you could synthesize this enon here so once again we're going to need to do the same kind of analysis we're going to find our alpha carbon right here this is our alpha carbon and this is our beta carbon alright so attached to our alpha carbon alright we know that there's a hydrogen right here so we're going to think about breaking this double bond alright so let's go ahead and draw a retrosynthesis arrow here so we're going to break that double bond so on the left okay we're going to have our benzene ring we're going to have our carbonyl here and then we're going to have a hydrogen attached to this carbon attached to our alpha carbon and remember we're going to add two hydrogen's to our alpha carbon so we're going to add two hydrogen's to our alpha carbon and that would give us the ketone that we would need right for our beta carbon we know there's already a hydrogen attached right here and so we're going to add an oxygen to this beta carbon on the left so it's just our way of thinking about it so over here on the right we're going to have we're going to have our carbonyl alright and then we're adding an oxygen alright we're adding an oxygen right here and then we had that hydrogen so let me go ahead and draw in that hydrogen in blue and then we can go ahead and draw our ring so we have our ring right here and then we have our nitro group coming off over here so just to check ourselves and make sure that this is the right way of thinking about it in Reverse if we take water from this portion right and stick those two fragments together then that would give us our conjugated enone product over here on the left and so that's again one way of thinking about how to do these sorts of problems and so if they if they wanted you to give some some reaction conditions here you could go ahead and draw what you would need right so you'd say I need to start with this ketone all right like this and then I would also need an aldehyde so I'm redrawing the for nitro benzyl to hide product all right so we have four nitro pens aldehyde like this alright so this compound this ketone of course is this compound right here and then for nitro benzyl dehyde here is the same one that we drew right here so if you take those two right and you and you put them together you should form your conjugated enone because remember thinking about your alpha protons right there are no alpha protons on our 4 nitro benzyl behind right so this this carbon right here doesn't have any alpha proton so the only source for alpha protons would be this carbon right here this is your only alpha carbon with alpha protons on it so in terms of in terms of what else we would need we would need a base right to do our aldol condensations so we could add something like sodium hydroxide as our base and we could we could create a solution of sodium hydroxide in water and then also ethanol so if you if you took this ketone right in this aldehyde and use these reaction conditions you should form this conjugated enone as your major product and so that's how to how to synthesize it so once again thinking in Reverse let's do another one this one's a little bit different because we don't have an e known or an email as our target compound we have an aldol as our target compound but we can use the same kind of thinking we can find our carbonyl and identify the carbon next to that as being our alpha carbon and then thinking about this as being our beta carbon right and we know that this is the bomb that forms so we can think about breaking this bond and and we know alright we know that we have a hydrogen on this carbon right here is i'm just going to see by and stick it into there so when I think about retrosynthesis right and go ahead and draw my retrosynthesis arrow in here so on the left alright I can see on the left that I'm going to have this carbon two three four and five right so I have these five carbons right here so I'm gonna go ahead and draw those in alright so we have our carbonyl and then we have our five carbons and then I already had this this carbon it this hydrogen I should say in magenta and we're only going to add one hydrogen this time so let me go ahead and draw on one hydrogen in green because this isn't the this isn't the conjugated product right we stopped at the aldol for thinking about it in Reverse and so we're not going to add two hydrogen's we're only going to add one here and so what else would we need so over here on the right let's think about the fact that there is hydrogen attached to this carbon right here and then how many carbons would we have for our other compound 1 2 3 & 4 so we have we need a four carbon carbonyl right and there's a hydrogen attached to it so a four carbon carbonyl so let me go ahead and draw that in 1 2 3 4 and then we have this hydrogen in blue to it and so now we've identified right thinking about it in Reverse what compounds we would need to form this aldol product we would need this ketone and this aldehydes but in terms of in terms of actually synthesizing the aldol compound on the Left we have to be a little bit careful about how to do it we need to do a directed aldol addition here so let's think about starting with this ketone alright so think about starting with this ketone here so I'm gonna go ahead and redraw it and draw in a slightly different way all right so that's this ketone right here and into that ketone we're going to add Lda right so we're going to form a lithium enolate here and once we formed our lithium enolate then we can add our aldehyde so in the second step we can add our aldehyde here so talked about this in earlier video so we add our aldehyde as a four-carbon aldehyde all right so we're going to add butanol and then that's going to give us a lithium alkoxide right so we need to we need to protonate the alkoxide so in the workup we can add some water here and that would give us our aldol product so that would give us this so that is the way to synthesize our aldol product so let me go ahead and draw it in here alright so we would form this okay so a directed aldol addition let's do let's do one more of this retrosynthesis approach and let's think about how to make this molecule so this is a little bit different than before okay but we can do our same steps we can identify our alpha carbon right that one next to our carbonyl and then our beta carbon is the one next to that right so we could think about breaking this double bond alright and an ad and adding two hydrogen's to our alpha carbon right so let's go let's go ahead and do that so we're going to break that double bond and add two hydrogens to the alpha carbon so thinking about this in terms of retrosynthesis we have a ring here alright and then let me go ahead and draw this over here we would have two hydrogen's over here let me go ahead and get some more room all right so probably easier to think about adding your oxygen to your beta carbon first so let's do that all right we know we're going to add an oxygen to our beta carbon so let's go ahead and put in our oxygen on our beta carbon I'll do that in green all right and then we're going to think about adding two hydrogen's to our alpha carbon so we're going to draw in our alpha carbon like that and we're going to add two hydrogen's I'm going to put those in green like this all right there's gives a little bit more room and then we would have our carbonyl like that and then we would have let's make sure to count your carbons when you're doing these all right so let's go ahead and show those carbons so this carbon right here is this carbon alright and then this carbon is this one right here and then on this carbon our carbonyl one is right here and so you can see this is actually an intramolecular aldol condensation so if you think about losing water right here right and sticking those two fragments together you would form this compound on the left and so this is a pretty cool reaction all right we could we could redraw this right so on an exam right you might I mean you could draw it like that but most of the time you would see it in a different conformation all right so you would see you would see the compound looking like this let me go ahead and draw that all right so identify your carbons carbon in magenta is the one right here all right carbon in blue is the one right here and the carbon in red is the one right here which has your carbonyl and then we'll go ahead and make our alpha carbon right here green so this carbon right here so this must have been this must have been your starting compound right and so if you add a base right you could convert you can convert this molecule into your target compound and so once again an intramolecular aldol condensation and we'll talk on more detail about those in the next video