Triphenylmethanol Synthesis via Grignard Reaction

Hello and welcome to my garage. Tonight I'm going to be preparing triphenylmethanol via the Grignard reaction. Now this is a very common undergraduate organic chemistry experiment that I unfortunately never got the chance to do. Now the Grignard reaction is famously fussy and extremely sensitive to moisture. And alkyl or aryl halide, in this case bromobenzene, is treated with magnesium in very dry diethyl ether or tetrahydroxyl. hydropurine, generating the organometallic reagent phenylmagnesium bromide. Now this is a carbanion equivalent and a very powerful nucleophile, so it rapidly reacts with electrophiles. In this case, my electrophile is going to be ethylbenzoate, which reacts with one equivalent of phenylmagnesium bromide to generate benzophenone, and then reacts with a second one to generate the... alkoxide of triphenyl methanol, which on acidic workup gives the triphenyl methanol itself. So all the reagents I'm using for this have been recently distilled and dried. The bromobenzene I'm using was dried over calcium chloride and distilled, and the ether I'm using was fractionated from starting fluid and dried over sodium, then distilled through a... torch-dried distillation apparatus into a torch-dried receiving flask and immediately sealed in dry bottles. Because moisture is so detrimental to this reaction, a standard procedure is to flame dry the glassware, which involves heating it up with an open flame, in this case my propane torch, and that removes adsorbed water from the surface of the glass. and generally you start at the bottom and work your way up. I have a very large apparatus here so to help myself along I'm going to be using my vacuum pump to draw air through the system while I heat and as you can see at the top of my Libig condenser there I have a calcium chloride drying tube through which the air is drawn drawing it before it passes through the air inside of the vessel. So the point of this is to remove adsorbed water and remove all moist air from the apparatus. I have the stopcock on the addition funnel open and the vacuum tap goes into the top of that. So air is going to be coming down the condenser, mostly up through here, and air from this flask will be removed less smoothly and more slowly than the rest of the apparatus. But the current of air here should provide a somewhat decreased pressure in the same way an aspirator does to help draw that air out of this lower flask. So I'm going to start heating here, then heat the flask up and do the addition funnel. Alright, I have a stir bar hiding here. I don't need it yet, I'll need it later in the reaction. But it's obviously not fireproof, so I've hit it. it up in the condenser, which I baked dry in an oven above the boiling point of water for about an hour. You could do that with the whole apparatus, but flame drying is convenient and fast. So I'm going to turn on my pump, I'm going to start flame drying, then I'll cut the video out and I'll come back when it's nice and cool. Alright, so the vacuum takeoff was removed and replaced with a stopper, and as the apparatus fully cools, dry air is going to be drawn in through that calcium chloride adapter and into the system. So, we have our essential... reagent magnesium here in this mortar and pestle. This is 2.43 grams or 100 millimoles of fresh magnesium turnings and I got these from gallium source.com thanks to nerd rage for that great spot basically on one of his videos actually I think they sent stuff in order to get them to give them the spot, but they're an excellent company to deal with. I also got sodium from there. Now the surface of this magnesium has a thin layer of oxide on it, which will inhibit the reaction. So I'm just going to crush it up a bit with the pestle to expose fresh magnesium surfaces. Alright, there we go. It's just a little finer. And one of the more famous ways to kickstart a greenyard that's being fussy is iodine. Now I have this solid iodine here. I made sure it warmed up to room temperature. I normally store it in the freezer, but if I were to open this bottle it would be cold. moisture would condense onto the iodine which might foul up the reaction. So I'm just going to take the flask off briefly, transfer the magnesium into it, and then put in a very small crystal of iodine and attach it back to the apparatus. All right. Put that magnesium in there. Just a key to grease. Alright, it's all in there. Alright, a very small crystal of iodine. Looks like I lost a little piece of magnesium there. Alright. Alright, now iodine will rapidly corrode steel parts, so you want to use glass or plastic spatula here. Alright, I've just added one small crystal in there. Now we can get this attached back to the apparatus before any more moist air gets in there. Okay. Now the following trick comes from the paper An Improved Preparation of a Grignard Reagent from JChemEd, Volume 64, page 179. And it says that if you... Actually... flame dry the glass with the magnesium iodine present you sublime the iodine onto the magnesium making it much more reactive now since I was drawing air through the apparatus where they don't I would have carried off all the iodine vapor but I'm gonna just reheat it again to do the same sort of thing here A good amount of time to heat is until you get purple vapor from the iodine, which is just starting to happen. Okay, I'm about to use ether which means at this point. There's absolutely no flames or ignition sources whatsoever to be used Because a rapid it readily forms explosive mixtures with air and that would be a very bad thing indeed. Alright so I'm just going to briefly remove the stopper from the top of the addition funnel and going to transfer in this which is 15.70 grams of bromobenzene dissolves in 25 milliliters, sorry 20 milliliters of sodium-dried diet olefser. Whoa, shit. Oh god. I forgot to close the stopcock. Okay, that was what I hoped not to do, but it looks like the reaction is working, which is excellent. However, I have to start up the condenser to keep that boiling ether in there. Alright, I'm slowly adding the remainder of the bromobenzene solution that I didn't accidentally dump into the reaction flask, drop by drop to maintain the reaction. And after that, I'm going to add in an additional 12. 25 milliliters of diethyl ether, and then allow it to remain warm with a warm water bath for 15 minutes to ensure that the formation of the Grignard reagent is complete. Alright, I'm sorry I said it wrong. It's after the reaction mixture stops boiling, you apply a warm water bath for 15 minutes to reflux the ether and drive the reaction to completion. As you can see, most of the magnesium has been consumed in the reaction. Only a small pile remains at the bottom. Okay, so now we get to add our electrophile, the ethyl benzoate. But first I'm going to use this stir bar. that I've been hiding up in the condenser. And I'm going to bring that down with the magnet and let it down into the flask. And I'm going to begin gentle stirring. Okay. And here I have 7.51 grams, which is 50 millimoles of ethyl benzoate, and it's dissolved in 15 milliliters of ether. And I'm going to pour this into the addition funnel, as with the other materials, and add it drop by drop into our Grignard reagent. Ethyl benzoate has this great smell. It's slightly grapey but also a little minty. If you took a dime tap cold medicine as a kid it smells a lot like that. So I'm just now going to begin the addition very slowly. Okay, so at this point the reaction is completely done and I no longer have to maintain and moisture free environment So I'm just going to go ahead and remove the flask All right and interestingly It has actually formed a biphasic mixture and it's a little difficult to see at that angle. But as you can see, I have a lighter sort of tan upper layer and a lower browner layer. Alright, and for workup, I'm now going to just add this to some acidic solution, in this case 0.5 molar sulfuric acid. I have 100 mL of it here and I've added I added 25 grams of ice. I'm just going to swirl the reaction mixture and pour it into that. This is going to react with the magnesium halo alkoxides in there. Most importantly, with the alkoxide form of the triphenylmethanol that we've generated. All the inorganic junk will extract into the acid layer for the most part. We'll do a wash in the sept funnel later. But the organic matter will remain in the ether layer on the surface. So I've swirled up the two layers, and I'm just going to pour it in. Alright, and I've washed out the flask with a small amount of dilute sulfuric acid and the heavy fizzing is because a lot of magnesium was still in there I'm gonna pour that in And lastly I've given it a little rinse with about five mils of ether I'm gonna add that into there as well I'm going to let that sit and let the two layers clear. Alright, so I've gone ahead and transferred the biphasic reaction mixture into this 250ml separatory funnel. And despite letting it sit for quite a while, the two phases have not completely cleared yet. So I'm going to go ahead and... and say good enough and I'm going to drain off the lower aqueous layer into this waste beaker. Now this consists mostly of magnesium salts, sulfite, bromide, and small amounts of ethanol. Alright, so next up I'm going to give our crude mixture here a wash with 50 milliliters of 1 molar sulfuric acid. You can see those little bits of magnesium fizzing pretty strongly right there, which is a good thing. I'm just going to put the stopper in this, shake it up nicely to efficiently wash the ether layer. And because ether is so volatile and also because I'm producing small amounts of hydrogen, it's very, very important to vent this a lot. I'm just going to let that sit and phase separate for a moment. I'm going to remove the stopper so pressure doesn't build up. I'm just going to drain off that lower layer of sulfuric acid. And for our last wash, I have your 50 milliliters of saturated sodium chloride brine. Again, make sure you vent. I don't know if you can see it, but the organic phase is now crystal clear and that's because the saturated brine solution absorbs water very readily from the organic phase. It's not as efficient a drying agent to say magnesium sulfate or calcium chloride but it does a good job on rough workup and the small droplets suspended in it that we're making it cloudy were presumably water from the earlier washes all right so I'm gonna drain off that last layer of brine So I transferred the ether layer here to this 250 milliliter Erlenmeyer, where I've had it drying over some anhydrous magnesium sulfate for about 15 minutes or so. And what I have to do now is just... remove that desiccant by simple gravity filtration. I have a folded up piece of filter paper here and unfortunately you have to sort of hold it in place while you pour. Once it's wet it'll stay in place. So all the ether solution is now passed through that piece of filter paper. And I'm just going to take a little bit more ether and rinse off the filter paper to keep any product adhering to it from being lost. And also to wash off the desiccant in the filter paper so it doesn't trap any of the solution. Okay, and the last step here is to recrystallize. Now, the solution contains our product, the triphenylmethanol. It also contains a byproduct, a diphenyl, or biphenyl, sorry. And it contains... unreacted ethyl benzoate. Now the diphenyl, sorry, triphenyl methanol and the biphenyl are both solids while the ethyl benzoate is a liquid. So crystallization will remove the ethyl benzoate, but it won't necessarily separate the other two if we use the wrong solvent. Now, biphenyl is much more soluble in saturated aliphatic hydrocarbons than the triphenylmethanol is. So the solvent of choice is ligroin, or if you watched my previous video, the video on hexanes, which can stand in and is in fact essentially the same thing as ligroin, at least. for the 40 to 60 degree fraction. So I have 30 milliliters of those hexanes here. I'm going to add them to our ether solution. Now the hexanes have a higher boiling point than the ether, so I have here an extremely low hot plate. Do not use open flame. This is just warm enough to boil the ether. I'm going to put this on the hot plate. and allowed the ether to evaporate until I just start to get clouding in the solution due to triphenylmethanol crystallizing. Then I'm going to put it into an ice bath and let it finish crystallizing out. All right, so ether was evaporated from the solution. I ended up putting a small stir bar in there to provide agitation. And when it hit about 50 milliliters of solution volume remaining, the solution suddenly got cloudy. I took it off the heat. I removed the stir bar and I covered it in foil and placed in an ice bath after it had cooled down to room temperature and as you can see a Significant amount of nice crystalline product has formed on the bottom there and we're going to vacuum filter that off from the supernatant and just want to get a clean spatula and take the foil off at this point and I'm just going to break up the solids, get them into suspension so I can pour them easily onto the filter plate. I'm going to turn on my pump, give them a swirl, and pour it onto the filter plate. So I kind of forgot to adjust the camera there, so I don't really have any footage of that filtration. I mean, I have footage, there's just nothing on screen going on. But I sucked those crystals out. dry and then wash them with two seven and a half mil portions of cold hexanes and I drew air through the product and it dries pretty quickly because hexanes are very volatile and that gave gave me 4.81 grams of crude triphenylmethanol. I set that aside. And probably because some of the ether and the filtrate boiled off under vacuum, and also because it was diluted with the hexanes from the wash, a decent amount of crystals had formed in the lower flask, despite giving the product almost a day to crystallize in an ice bath. So I decided to... boil down that liquid to try and get a second crop of crystals. Well, its volume was about 50 milliliters, so I boiled it down to half that, 25, and it clouded a little bit, but on cooling I didn't get any solid product. Now there definitely was solid product before, so what I did was I diluted it with just a little bit of hexanes, and even after adding just one dropper full, which is about 2.5 milliliters of crystals, I immediately got some crystal form. So I kept adding hexanes and more and more crystals crashed out. I kept adding hexanes, I'm not even sure how much it was, but until obvious crystal formation had pretty much come to a stop. And then I suctioned those. dry as well. I rinsed them with a little bit of hexanes and dried them and that gave me an additional 1.31 grams of product. Now I kept these separate from the first crystals because they're obviously probably going to be a lower purity and I took melting points of both. The first sample melted from 158 to 160 Celsius, and that's really good considering the literature melting point is 160 to 163. At most, I have a few percent of impurities in there, but not a whole lot. And for my purposes, it's probably pure enough. The second crop, though, was a lot lower melting and significantly broader. It melted from 151 to 156 Celsius. So I recrystallized that by dissolving it in a minimum of boiling ether, which was 12.5 mils. I then added an equivalent amount of hexanes. I boiled it down to half volume, effectively evaporating most of the ether, cooled it in an ice bath, collected the crystalline product by vacuum filtration, rinsed it with a little hexanes, and I'd recovered 1.03 grams of product, which is about an 80% recovery, and the melting point had increased significantly, and in fact it matched the first crop of crystals. So at that point I had no problem combining the two. And that gave me my final product here, 5.84 grams of triphenylmethanol, which represents a 45% yield. And now that's a little low for the Grignard reaction. OrgSyn has a prep of triphenylmethanol, but you won't find it called that. It's called triphenylcarbinol there, and it's in Collective Volume 3, page 830. and they get an 89-93% yield. My yield of 45.0% is more along the lines of an average undergrad organic chemistry lab student, most likely. But to be fair, with my working conditions, it's pretty hard to properly dry everything for a successful high-yielding Grignard. My ether probably could have been drier, I should have dried it with sodium benzo phenol and ketal under an inert atmosphere. Instead I just reflux it with some sodium slices and then distilled it. There may have been a little bit of water in my ethyl benzoate. I didn't use an inert atmosphere where the granule reacts with oxygen and carbon dioxide, so I probably lost some product there. There's a whole number of things that could have gone slightly wrong and all of that added up to a significant loss in yield. But still, I ran a green yard in my garage. If I said I was upset, I would be actually upset. absolutely lying because this is not necessarily an easy reaction by any standard. So I think we will do a mechanism now. First, I'm going to cover the mechanism by which we actually form the Grignard reagent, and then I'll do the reaction with the carbonyl later. Alright, so you have your bromobenzene, or alkyl halide. or other aryl halide and you have magnesium. Magnesium is an elemental metal it has two valence electrons and if it loses both of them it has an octet so it's favorable for it to lose the electrons. electrons, so we're actually going to go by a radical process, one electron at a time, which is called a single electron transfer, or SET mechanism. So we're first going to transfer one electron from the magnesium, and one from the bromine, and one from that bomb there. And the result of this is that we get a phenyl radical. and MgBr, which is a plus one oxidation state magnesium. It still has a valence electron. So the typical course of this reaction is that the magnesium then donates a second electron, the radical gives its electron, and we finish forming. the phenyl magnesium bromide. However, there's the possibility for a side reaction since we're generating radicals. Let's say two of these came together instead of reacting with the magnesium. Well... They could certainly dimerize, and the result of that would be our impurity, biphenyl. However, I'm pretty sure that this is not the main pathway by which biphenyl is produced in this reaction. It actually occurs later on. And now for the reaction of the Grignard Reagent with our ester. So I'm going to draw our ethyl benzoate here. It's a carbonyl. If you've watched my other videos or taken organic chemistry, chemistry. You know that carbonyls are a good electrophile. Esters are not the best because they have this electron donating alkoxy group there. Ketones are actually better. But we had have our phenyl magnesium bromide in solution. And that's a carbanion equivalent. It should stick out like a big giant red sore thumb. That is going to definitely be the nucleophile. So you formally have to break this magnesium carbon bond there. So I'm just going to push electrons to that carbon there. And then you have a phenyl carbon ion, which is going to come up and attack at that carbonyl, push electrons up, and we get that ever-present four-membered intermediate. It seems to turn up in almost every single reaction. Alright, right there. And the only possible leaving group here is really the ethoxide there. So you get electrons pushed down from that oxygen and you eject ethoxide. And this generates a ketone, benzophenone. The phenyl ring is significantly less electron donating than the ethoxy group. So this is actually a... better reactant for a Grignard reagent than the original product. So the rate of reaction of the intermediate here with additional phenylmagnesium bromide is higher than with unreacted ethyl benzoate. So a second equivalent, I'm just going to use the same one, is going to come in, same deal, push up electrons. And I'm just going to abbreviate them with pH because I don't want to draw all the rings. I'm lazy. Alright, and what you get is a tertiary alkoxide with a magnesium Br- Sorry, Br+, counter-anion. And this is what we have in solution until the acidic workup. which protonates that alkoxide and gives us our final product, the triphenylmethanol. And now the question of where that biphenyl comes from. Most labs will simply tell you that when you have phenylmagnesium bromide and extra extra bromobenzene around, you'll generate biphenyl. Now, if that worked so well, that it was a significant competing reaction, you wouldn't be able to form grignards in the first place, because so much of them would be consumed in that side reaction. The only way these two could directly react is through what's called a nucleophilic aromatic substitution, and that would require the phenylcarbanion to attack at an SN2 carbon. generating this kind of wacky looking intermediate here and then you'd eject bromide to give biphenyl. Now this is certainly not impossible it probably happens to a small extent but this is This is not a very stable intermediate at all. However, it can be stabilized by electron withdrawing groups on the ortho and para positions with an unsubstituted alkyl halide like aryl halide. like bromobenzene, the reaction is almost non-existent. So this is probably not at all the path that it goes by. Now I did some reading, and what it turns out to be... is I believe that the main source of biphenyl is from transition metal contaminants. And now this could be stuff that was left on the glassware, trace quantities in the reagents themselves, if you use a spatula or a scupula or something. And the ones that actually work best if you're trying to intentionally couple are nickel and palladium. And in that case, it's called a Kumada coupling. But other transition metals like chromium, copper, iron isn't so good, cobalt's not bad. But a wide array of transition metals can catalyze this coupling. And what happens is you have some metal and you have your bromobenzene here. And metals are pretty good at coordinating with their d-orbitals. And what, since this is a zero-valent metal, it has electrons to spare just like the magnesium did before. And it will donate two of them to form a bond there. That bond will break and form a bond there. And what we'll get is a now oxidized metal. It's now formally a plus two with a phenyl group. and a bromine. The next step is called a transmetallation. What happens is this is where the phenylmagnesium bromide comes in. The phenylmagnesium bromide will jump by, grab the bromine, and give the... metal it's phenyl group bromine is a harder Lewis Lewis base than the phenyl is so this transition metal cation which is a softer Lewis acid than the magnesium cation is will prefer to have the phenyl group so what you get is a diphenyl metal of some sort Again, this is in the plus two state. Alright, now we can sort of visualize where we're going from here. It's the reverse of the first step essentially. Electrons will jump from one of these bonds back to the metal, and the other bond will donate its electrons to connect. the two benzene rings forming the biphenyl. At the same time the metal is reduced back to the zero oxidation state, this is called the reductive elimination, and you're left with biphenyl. Now, reportedly, early researchers into the Grignard reaction had serious issues with very high yields of biphenyl when trying to make phenylmagnesium bromide. And I believe this is because their magnesium was not very pure. Now, as time has gone on, our metallurgy skills have gotten better. We can produce very pure metals. But chances are, if you're not using a super pure material, that's where some of the metal contamination may be coming from. from. So that's the preparation of triphenylmethanol by the Grignard reaction. Thanks for watching.

And alkyl or aryl halide, in this case bromobenzene, is treated with magnesium in very dry diethyl ether or tetrahydroxyl. hydropurine, generating the organometallic reagent phenylmagnesium bromide. Now this is a carbanion equivalent and a very powerful nucleophile, so it rapidly reacts with electrophiles. In this case, my electrophile is going to be ethylbenzoate, which reacts with one equivalent of phenylmagnesium bromide to generate benzophenone, and then reacts with a second one to generate the... alkoxide of triphenyl methanol, which on acidic workup gives the triphenyl methanol itself.

So all the reagents I'm using for this have been recently distilled and dried. The bromobenzene I'm using was dried over calcium chloride and distilled, and the ether I'm using was fractionated from starting fluid and dried over sodium, then distilled through a... torch-dried distillation apparatus into a torch-dried receiving flask and immediately sealed in dry bottles. Because moisture is so detrimental to this reaction, a standard procedure is to flame dry the glassware, which involves heating it up with an open flame, in this case my propane torch, and that removes adsorbed water from the surface of the glass. and generally you start at the bottom and work your way up.

I have a very large apparatus here so to help myself along I'm going to be using my vacuum pump to draw air through the system while I heat and as you can see at the top of my Libig condenser there I have a calcium chloride drying tube through which the air is drawn drawing it before it passes through the air inside of the vessel. So the point of this is to remove adsorbed water and remove all moist air from the apparatus. I have the stopcock on the addition funnel open and the vacuum tap goes into the top of that.

So air is going to be coming down the condenser, mostly up through here, and air from this flask will be removed less smoothly and more slowly than the rest of the apparatus. But the current of air here should provide a somewhat decreased pressure in the same way an aspirator does to help draw that air out of this lower flask. So I'm going to start heating here, then heat the flask up and do the addition funnel. Alright, I have a stir bar hiding here.

I don't need it yet, I'll need it later in the reaction. But it's obviously not fireproof, so I've hit it. it up in the condenser, which I baked dry in an oven above the boiling point of water for about an hour. You could do that with the whole apparatus, but flame drying is convenient and fast. So I'm going to turn on my pump, I'm going to start flame drying, then I'll cut the video out and I'll come back when it's nice and cool.

Alright, so the vacuum takeoff was removed and replaced with a stopper, and as the apparatus fully cools, dry air is going to be drawn in through that calcium chloride adapter and into the system. So, we have our essential... reagent magnesium here in this mortar and pestle.

This is 2.43 grams or 100 millimoles of fresh magnesium turnings and I got these from gallium source.com thanks to nerd rage for that great spot basically on one of his videos actually I think they sent stuff in order to get them to give them the spot, but they're an excellent company to deal with. I also got sodium from there. Now the surface of this magnesium has a thin layer of oxide on it, which will inhibit the reaction. So I'm just going to crush it up a bit with the pestle to expose fresh magnesium surfaces. Alright, there we go.

It's just a little finer. And one of the more famous ways to kickstart a greenyard that's being fussy is iodine. Now I have this solid iodine here.

I made sure it warmed up to room temperature. I normally store it in the freezer, but if I were to open this bottle it would be cold. moisture would condense onto the iodine which might foul up the reaction. So I'm just going to take the flask off briefly, transfer the magnesium into it, and then put in a very small crystal of iodine and attach it back to the apparatus.

All right. Put that magnesium in there. Just a key to grease.

Alright, it's all in there. Alright, a very small crystal of iodine. Looks like I lost a little piece of magnesium there. Alright. Alright, now iodine will rapidly corrode steel parts, so you want to use glass or plastic spatula here.

Alright, I've just added one small crystal in there. Now we can get this attached back to the apparatus before any more moist air gets in there. Okay. Now the following trick comes from the paper An Improved Preparation of a Grignard Reagent from JChemEd, Volume 64, page 179. And it says that if you...

Actually... flame dry the glass with the magnesium iodine present you sublime the iodine onto the magnesium making it much more reactive now since I was drawing air through the apparatus where they don't I would have carried off all the iodine vapor but I'm gonna just reheat it again to do the same sort of thing here A good amount of time to heat is until you get purple vapor from the iodine, which is just starting to happen. Okay, I'm about to use ether which means at this point. There's absolutely no flames or ignition sources whatsoever to be used Because a rapid it readily forms explosive mixtures with air and that would be a very bad thing indeed. Alright so I'm just going to briefly remove the stopper from the top of the addition funnel and going to transfer in this which is 15.70 grams of bromobenzene dissolves in 25 milliliters, sorry 20 milliliters of sodium-dried diet olefser.

Whoa, shit. Oh god. I forgot to close the stopcock.

Okay, that was what I hoped not to do, but it looks like the reaction is working, which is excellent. However, I have to start up the condenser to keep that boiling ether in there. Alright, I'm slowly adding the remainder of the bromobenzene solution that I didn't accidentally dump into the reaction flask, drop by drop to maintain the reaction. And after that, I'm going to add in an additional 12. 25 milliliters of diethyl ether, and then allow it to remain warm with a warm water bath for 15 minutes to ensure that the formation of the Grignard reagent is complete. Alright, I'm sorry I said it wrong.

It's after the reaction mixture stops boiling, you apply a warm water bath for 15 minutes to reflux the ether and drive the reaction to completion. As you can see, most of the magnesium has been consumed in the reaction. Only a small pile remains at the bottom.

Okay, so now we get to add our electrophile, the ethyl benzoate. But first I'm going to use this stir bar. that I've been hiding up in the condenser. And I'm going to bring that down with the magnet and let it down into the flask. And I'm going to begin gentle stirring.

Okay. And here I have 7.51 grams, which is 50 millimoles of ethyl benzoate, and it's dissolved in 15 milliliters of ether. And I'm going to pour this into the addition funnel, as with the other materials, and add it drop by drop into our Grignard reagent. Ethyl benzoate has this great smell. It's slightly grapey but also a little minty.

If you took a dime tap cold medicine as a kid it smells a lot like that. So I'm just now going to begin the addition very slowly. Okay, so at this point the reaction is completely done and I no longer have to maintain and moisture free environment So I'm just going to go ahead and remove the flask All right and interestingly It has actually formed a biphasic mixture and it's a little difficult to see at that angle. But as you can see, I have a lighter sort of tan upper layer and a lower browner layer. Alright, and for workup, I'm now going to just add this to some acidic solution, in this case 0.5 molar sulfuric acid.

I have 100 mL of it here and I've added I added 25 grams of ice. I'm just going to swirl the reaction mixture and pour it into that. This is going to react with the magnesium halo alkoxides in there. Most importantly, with the alkoxide form of the triphenylmethanol that we've generated.

All the inorganic junk will extract into the acid layer for the most part. We'll do a wash in the sept funnel later. But the organic matter will remain in the ether layer on the surface. So I've swirled up the two layers, and I'm just going to pour it in.

Alright, and I've washed out the flask with a small amount of dilute sulfuric acid and the heavy fizzing is because a lot of magnesium was still in there I'm gonna pour that in And lastly I've given it a little rinse with about five mils of ether I'm gonna add that into there as well I'm going to let that sit and let the two layers clear. Alright, so I've gone ahead and transferred the biphasic reaction mixture into this 250ml separatory funnel. And despite letting it sit for quite a while, the two phases have not completely cleared yet. So I'm going to go ahead and...

and say good enough and I'm going to drain off the lower aqueous layer into this waste beaker. Now this consists mostly of magnesium salts, sulfite, bromide, and small amounts of ethanol. Alright, so next up I'm going to give our crude mixture here a wash with 50 milliliters of 1 molar sulfuric acid.

You can see those little bits of magnesium fizzing pretty strongly right there, which is a good thing. I'm just going to put the stopper in this, shake it up nicely to efficiently wash the ether layer. And because ether is so volatile and also because I'm producing small amounts of hydrogen, it's very, very important to vent this a lot. I'm just going to let that sit and phase separate for a moment.

I'm going to remove the stopper so pressure doesn't build up. I'm just going to drain off that lower layer of sulfuric acid. And for our last wash, I have your 50 milliliters of saturated sodium chloride brine.

Again, make sure you vent. I don't know if you can see it, but the organic phase is now crystal clear and that's because the saturated brine solution absorbs water very readily from the organic phase. It's not as efficient a drying agent to say magnesium sulfate or calcium chloride but it does a good job on rough workup and the small droplets suspended in it that we're making it cloudy were presumably water from the earlier washes all right so I'm gonna drain off that last layer of brine So I transferred the ether layer here to this 250 milliliter Erlenmeyer, where I've had it drying over some anhydrous magnesium sulfate for about 15 minutes or so. And what I have to do now is just... remove that desiccant by simple gravity filtration.

I have a folded up piece of filter paper here and unfortunately you have to sort of hold it in place while you pour. Once it's wet it'll stay in place. So all the ether solution is now passed through that piece of filter paper. And I'm just going to take a little bit more ether and rinse off the filter paper to keep any product adhering to it from being lost. And also to wash off the desiccant in the filter paper so it doesn't trap any of the solution.

Okay, and the last step here is to recrystallize. Now, the solution contains our product, the triphenylmethanol. It also contains a byproduct, a diphenyl, or biphenyl, sorry.

And it contains... unreacted ethyl benzoate. Now the diphenyl, sorry, triphenyl methanol and the biphenyl are both solids while the ethyl benzoate is a liquid.

So crystallization will remove the ethyl benzoate, but it won't necessarily separate the other two if we use the wrong solvent. Now, biphenyl is much more soluble in saturated aliphatic hydrocarbons than the triphenylmethanol is. So the solvent of choice is ligroin, or if you watched my previous video, the video on hexanes, which can stand in and is in fact essentially the same thing as ligroin, at least.

for the 40 to 60 degree fraction. So I have 30 milliliters of those hexanes here. I'm going to add them to our ether solution. Now the hexanes have a higher boiling point than the ether, so I have here an extremely low hot plate.

Do not use open flame. This is just warm enough to boil the ether. I'm going to put this on the hot plate. and allowed the ether to evaporate until I just start to get clouding in the solution due to triphenylmethanol crystallizing.

Then I'm going to put it into an ice bath and let it finish crystallizing out. All right, so ether was evaporated from the solution. I ended up putting a small stir bar in there to provide agitation. And when it hit about 50 milliliters of solution volume remaining, the solution suddenly got cloudy. I took it off the heat.

I removed the stir bar and I covered it in foil and placed in an ice bath after it had cooled down to room temperature and as you can see a Significant amount of nice crystalline product has formed on the bottom there and we're going to vacuum filter that off from the supernatant and just want to get a clean spatula and take the foil off at this point and I'm just going to break up the solids, get them into suspension so I can pour them easily onto the filter plate. I'm going to turn on my pump, give them a swirl, and pour it onto the filter plate. So I kind of forgot to adjust the camera there, so I don't really have any footage of that filtration.

I mean, I have footage, there's just nothing on screen going on. But I sucked those crystals out. dry and then wash them with two seven and a half mil portions of cold hexanes and I drew air through the product and it dries pretty quickly because hexanes are very volatile and that gave gave me 4.81 grams of crude triphenylmethanol.

I set that aside. And probably because some of the ether and the filtrate boiled off under vacuum, and also because it was diluted with the hexanes from the wash, a decent amount of crystals had formed in the lower flask, despite giving the product almost a day to crystallize in an ice bath. So I decided to...

boil down that liquid to try and get a second crop of crystals. Well, its volume was about 50 milliliters, so I boiled it down to half that, 25, and it clouded a little bit, but on cooling I didn't get any solid product. Now there definitely was solid product before, so what I did was I diluted it with just a little bit of hexanes, and even after adding just one dropper full, which is about 2.5 milliliters of crystals, I immediately got some crystal form.

So I kept adding hexanes and more and more crystals crashed out. I kept adding hexanes, I'm not even sure how much it was, but until obvious crystal formation had pretty much come to a stop. And then I suctioned those. dry as well.

I rinsed them with a little bit of hexanes and dried them and that gave me an additional 1.31 grams of product. Now I kept these separate from the first crystals because they're obviously probably going to be a lower purity and I took melting points of both. The first sample melted from 158 to 160 Celsius, and that's really good considering the literature melting point is 160 to 163. At most, I have a few percent of impurities in there, but not a whole lot.

And for my purposes, it's probably pure enough. The second crop, though, was a lot lower melting and significantly broader. It melted from 151 to 156 Celsius.

So I recrystallized that by dissolving it in a minimum of boiling ether, which was 12.5 mils. I then added an equivalent amount of hexanes. I boiled it down to half volume, effectively evaporating most of the ether, cooled it in an ice bath, collected the crystalline product by vacuum filtration, rinsed it with a little hexanes, and I'd recovered 1.03 grams of product, which is about an 80% recovery, and the melting point had increased significantly, and in fact it matched the first crop of crystals. So at that point I had no problem combining the two. And that gave me my final product here, 5.84 grams of triphenylmethanol, which represents a 45% yield.

And now that's a little low for the Grignard reaction. OrgSyn has a prep of triphenylmethanol, but you won't find it called that. It's called triphenylcarbinol there, and it's in Collective Volume 3, page 830. and they get an 89-93% yield. My yield of 45.0% is more along the lines of an average undergrad organic chemistry lab student, most likely. But to be fair, with my working conditions, it's pretty hard to properly dry everything for a successful high-yielding Grignard.

My ether probably could have been drier, I should have dried it with sodium benzo phenol and ketal under an inert atmosphere. Instead I just reflux it with some sodium slices and then distilled it. There may have been a little bit of water in my ethyl benzoate. I didn't use an inert atmosphere where the granule reacts with oxygen and carbon dioxide, so I probably lost some product there. There's a whole number of things that could have gone slightly wrong and all of that added up to a significant loss in yield.

But still, I ran a green yard in my garage. If I said I was upset, I would be actually upset. absolutely lying because this is not necessarily an easy reaction by any standard.

So I think we will do a mechanism now. First, I'm going to cover the mechanism by which we actually form the Grignard reagent, and then I'll do the reaction with the carbonyl later. Alright, so you have your bromobenzene, or alkyl halide.

or other aryl halide and you have magnesium. Magnesium is an elemental metal it has two valence electrons and if it loses both of them it has an octet so it's favorable for it to lose the electrons. electrons, so we're actually going to go by a radical process, one electron at a time, which is called a single electron transfer, or SET mechanism.

So we're first going to transfer one electron from the magnesium, and one from the bromine, and one from that bomb there. And the result of this is that we get a phenyl radical. and MgBr, which is a plus one oxidation state magnesium.

It still has a valence electron. So the typical course of this reaction is that the magnesium then donates a second electron, the radical gives its electron, and we finish forming. the phenyl magnesium bromide. However, there's the possibility for a side reaction since we're generating radicals.

Let's say two of these came together instead of reacting with the magnesium. Well... They could certainly dimerize, and the result of that would be our impurity, biphenyl.

However, I'm pretty sure that this is not the main pathway by which biphenyl is produced in this reaction. It actually occurs later on. And now for the reaction of the Grignard Reagent with our ester. So I'm going to draw our ethyl benzoate here.

It's a carbonyl. If you've watched my other videos or taken organic chemistry, chemistry. You know that carbonyls are a good electrophile. Esters are not the best because they have this electron donating alkoxy group there. Ketones are actually better.

But we had have our phenyl magnesium bromide in solution. And that's a carbanion equivalent. It should stick out like a big giant red sore thumb. That is going to definitely be the nucleophile.

So you formally have to break this magnesium carbon bond there. So I'm just going to push electrons to that carbon there. And then you have a phenyl carbon ion, which is going to come up and attack at that carbonyl, push electrons up, and we get that ever-present four-membered intermediate. It seems to turn up in almost every single reaction.

Alright, right there. And the only possible leaving group here is really the ethoxide there. So you get electrons pushed down from that oxygen and you eject ethoxide.

And this generates a ketone, benzophenone. The phenyl ring is significantly less electron donating than the ethoxy group. So this is actually a...

better reactant for a Grignard reagent than the original product. So the rate of reaction of the intermediate here with additional phenylmagnesium bromide is higher than with unreacted ethyl benzoate. So a second equivalent, I'm just going to use the same one, is going to come in, same deal, push up electrons. And I'm just going to abbreviate them with pH because I don't want to draw all the rings.

I'm lazy. Alright, and what you get is a tertiary alkoxide with a magnesium Br- Sorry, Br+, counter-anion. And this is what we have in solution until the acidic workup. which protonates that alkoxide and gives us our final product, the triphenylmethanol. And now the question of where that biphenyl comes from.

Most labs will simply tell you that when you have phenylmagnesium bromide and extra extra bromobenzene around, you'll generate biphenyl. Now, if that worked so well, that it was a significant competing reaction, you wouldn't be able to form grignards in the first place, because so much of them would be consumed in that side reaction. The only way these two could directly react is through what's called a nucleophilic aromatic substitution, and that would require the phenylcarbanion to attack at an SN2 carbon. generating this kind of wacky looking intermediate here and then you'd eject bromide to give biphenyl.

Now this is certainly not impossible it probably happens to a small extent but this is This is not a very stable intermediate at all. However, it can be stabilized by electron withdrawing groups on the ortho and para positions with an unsubstituted alkyl halide like aryl halide. like bromobenzene, the reaction is almost non-existent. So this is probably not at all the path that it goes by. Now I did some reading, and what it turns out to be...

is I believe that the main source of biphenyl is from transition metal contaminants. And now this could be stuff that was left on the glassware, trace quantities in the reagents themselves, if you use a spatula or a scupula or something. And the ones that actually work best if you're trying to intentionally couple are nickel and palladium.

And in that case, it's called a Kumada coupling. But other transition metals like chromium, copper, iron isn't so good, cobalt's not bad. But a wide array of transition metals can catalyze this coupling.

And what happens is you have some metal and you have your bromobenzene here. And metals are pretty good at coordinating with their d-orbitals. And what, since this is a zero-valent metal, it has electrons to spare just like the magnesium did before.

And it will donate two of them to form a bond there. That bond will break and form a bond there. And what we'll get is a now oxidized metal.

It's now formally a plus two with a phenyl group. and a bromine. The next step is called a transmetallation. What happens is this is where the phenylmagnesium bromide comes in.

The phenylmagnesium bromide will jump by, grab the bromine, and give the... metal it's phenyl group bromine is a harder Lewis Lewis base than the phenyl is so this transition metal cation which is a softer Lewis acid than the magnesium cation is will prefer to have the phenyl group so what you get is a diphenyl metal of some sort Again, this is in the plus two state. Alright, now we can sort of visualize where we're going from here. It's the reverse of the first step essentially. Electrons will jump from one of these bonds back to the metal, and the other bond will donate its electrons to connect.

the two benzene rings forming the biphenyl. At the same time the metal is reduced back to the zero oxidation state, this is called the reductive elimination, and you're left with biphenyl. Now, reportedly, early researchers into the Grignard reaction had serious issues with very high yields of biphenyl when trying to make phenylmagnesium bromide. And I believe this is because their magnesium was not very pure.

Now, as time has gone on, our metallurgy skills have gotten better. We can produce very pure metals. But chances are, if you're not using a super pure material, that's where some of the metal contamination may be coming from. from.

So that's the preparation of triphenylmethanol by the Grignard reaction. Thanks for watching.

Transcript for:Triphenylmethanol Synthesis via Grignard Reaction

Transcript for:
Triphenylmethanol Synthesis via Grignard Reaction