I learned this reaction in O-chem but never preformed it. I like that they teach you tons of reactions that don't involve building carbon carbon bonds. It gives you a sense of how powerful this reaction is. So to finally see it well, I won't lie, it makes me really excited.
I’m actually using this video for my Chem project where I’m going to be transforming erucic acid into (Z)-9-Tricosene through multiple steps including grignard!
I’m a long-time subscriber of yours but this video was just recommended to me on the UA-cam front page, so I watched it. Interesting how much your production quality has increased in five years, yet the overall style is still the same!
Maybe the pink is some transition metal (like iron III) contamination from the hydrochloric acid, the drying agent, or perhaps the magnesium. Transition metal salts might not be apparent in the NMR spectrum, and their colors are strong enough that the associated butyrate ion would only be present in trace amounts.
When a Grignard-Reaction is done, the alkyl halide is often diluted with dry ether before the addition. It is added dropwise, to keep the solution only slightly boiling. When the boiling gets to strong the Grignard reagent is able to react with the alkyl halide to form a larger molecule (in this case n-hexane). There's also the possibility that a ketone is formed as a byproduct, which could lead to a lot of side reactions. Nevertheless, nice presentation! :)
Nice video! I believe your low yield arises due to the method of CO2 addition. Typically, the Grignard reagent would be added to a large excess of CO2 (pouring rxn mixture onto dry ice) to increase the probability that the Grignard only reacts with CO2. Bubbling the CO2 through the Grignard reagent increase the probability that a second molecule of Grignard will react with the carbonyl on the intermediate forming the geminal diol, heptane-4,4-diol, upon acidic work up, which I think would be quite soluble in the aqueous phase. Good video though! Keep em coming!
+Trevor McElhenny thanks for the input! I will be doing a grignard again at some point, so we shall see what the yield is for that one :). I just ran out of ether though, so it has to wait.
+Trevor McElhenny i believe that the low yield was because you remove the glass stopper to add more ether instead the add with a needle just next to the hose with the co2, the moisture in the air was the trouble i guess, for the rest damn i wish do some reactions like this regards from mexico
Arman 25 typically, no you can't. If there are alternatives they would likely be other ethers. It needs to be a nonpolar solvent that is incredibly inert but not like hexane or benzene since the ether also has metal chelating properties that drive the reaction forward. In fact even though the Grignard reagent is notated commonly as R-MgX it actually exists as a tetrahedral organometallic complex with the ether roughly of the form (R-MgX)(Et2O)2. You MIGHT and I'm only saying might, get away with THF or dioxane as they are also ethers with metal chelating properties. Also, you can't use DCM because it will react with the magnesium just like the bromoalkane and generate side products and polymers. Edit: I looked it up and dry anhydrous THF is an acceptable alternative, for the reasons stated above. Dioxane can also be used but leads to an interesting effect where instead of two ether molecules forming the complex (R-MgX)(Et2O)2 it causes the Grignard reagent to rearrange forming MgX2 and (R-Mg-R)(Et2O2) the corresponding magnesium dihalide which crashes out and the dioxane complexed diakylmagnesium species. I'm not 100% sure but I believe this compound can still be used in a Grignard reaction due to its powerful alkylating properties. You may however, have a higher than normal chance of creating disubstituted products due to the reagent having 2 alkyl groups in close proximity to the molecule they attack.
@@spiderdude2099 it's also possible to use a MTBE as a solvent, but it won't dissolve ROOMgBr salt. So the product will form a crystalline mass at the bottom of the flask, and it's will be hard to stir it well, using the magnetic stirrer. THF has the same usability as a Et2O in this case. It also gives a [THFMgHal]+ R- complexes, so there is no problems with using this. The only thing, that thf is highly hygroscopic solvent, so it's will be a good idea to use some kind of water adsorber, like H2SO4(conc.) in a bubble counter, or anhydrous CaCl2/MgSO4/Na2SO4 as a shutter if there is no way to use innert atmosphere such as Ar or N2.
Instead of adding heaps of drying agent I have been running my work-up through a glass pipette filled with drying agent - a mini column. It uses much less drying agent and is easier to wash out for entrained residues. This works so well that I am surprised to see professional chemist youtubers drying using bucketfulls of material.
wow I did a grignard in lab class and it didn't worked that well at all. we did it on testtube scale, and even with some iodine we had to put it in an ultrasonic bath for 5-10 minutes then rub the tube in our hands to give it enough heat to start making the grignard reagent. First atempt was a complete fail, I think I added the rest of the bromobenzene too quickly and killed the reaction, second atempt was very hard to get started but eventually worked out ok.
I've seen that pink color before, although I don't recall the reaction. The guy that runs MOC told me that such things are generally actually very small amounts of metal impurities. For some reason I want to say that the suspected source ended up being the lye.
When you added the ether at the end (x3) and then extracted the butyric acid, how did you separate the two? Wouldn't the butyric acid be in ether because it is ether soluble?
What would the pH of the concentrated hydroiodic acid be? And what does it react with that other strong acids do not? (Other than the reactions that lead to meth, of course...)
When you do this kind of addition on CO2 with grignard reagents, there are equilibrium between the first addition product of the grignard reagent over CO2 and 1 or 2 extra equivalents of the grignard reagent. So if your CO2 isn't in excess at any moment, your risk the formation of the bi-addition ketone product and even further with a tertiary alcool ( both formed after hydrolysis indeed). You can draw the mechanisms if you wish, it's a bit odd and counter-intuitive but pretty satisfying ^^ The first addition of the grignard over CO2 is pretty fast and the two others equilibrium are much slower but in the case of a large excess of the grignard you'll end up with a mixture of the 3 product at the end. So just use Dry ice if you want better yields ^^
Amazing video!! I would really like to try this synthesis; however, I do not have ether. Is there another solvent I could use in place of ether, or would that cause the reaction to fail?
Ian McClellan-Johnson you typically have to use some kind of ether. Thf, and dioxane work for most reactions and I’ve heard that DCM can be used but with slightly reduced yields. The ether coordinates to the Grignard reagent and that’s why it’s used, it stabilizes it and facilitates full formation of the reagent when it reacts with the magnesium. Just FYI, if dioxane is used you can have a slightly higher risk of the dual addition product because instead of existing as the complex (et2O)2 MgXR it exists as (dioxane)(MgXR)2
In 3:52 you mentioned filtering to get rid of the unreacted magnesium, but wouldn't the acid react with it to form a soluble MgCl2 and is it possible to filter it before adding the HCl to get rid of the magnesium metal when we add it in excess?
John spartin Indole-3-butyric acid is completely different. It has a benzene ring, with an indole ring attached and a -COOH group on that indole. It is a plant hormone, but I don't know what exactly it does.
Grignard reagent is a very strong nucleophile, shouldn't that cause further addition of Grignard reagent leading to formation of 4-heptanone (dipropyl ketone) as the major product????
CO2 is a stronger electrophile than the carboxylate, carboxylates are even less reactive than ketones to nucleophilic addition. The reaction that you say is happening though, only in really small amounts. I'd say that a major concern would be the grignard reacting with traces of water or other protic substances, or with leftover alkyl halide via SN2 reaction.
+Ben Canon No, I don't think it comes from Iodine, since this Grignard-reaction started spontaneosly. There was no addition of Iodine necessary. Nevertheless, there are only a couple of Iodine-crystals needed, which will completely react with the excessive Magnesium in the further course. There is no free Iodine left in the reworking step later.
Definitely not, grignard reactions are expensive, very difficult to perform outside of a professional lab and notoriously unreliable. Plus, you'd need the corresponding bromide, and that doesn't seem to be really common.
I have always been interested in chemistry and I like teaching and making films. I started working in a lab, so I started doing some experiments, then I started filming them.
wow I did a grignard in lab class and it didn't worked that well at all. we did it on testtube scale, and even with some iodine we had to put it in an ultrasonic bath for 5-10 minutes then rub the tube in our hands to give it enough heat to start making the grignard reagent. First atempt was a complete fail, I think I added the rest of the bromobenzene too quickly and killed the reaction, second atempt was very hard to get started but eventually worked out ok.
I learned this reaction in O-chem but never preformed it. I like that they teach you tons of reactions that don't involve building carbon carbon bonds. It gives you a sense of how powerful this reaction is. So to finally see it well, I won't lie, it makes me really excited.
I am glad that you are excited about chemistry! :)
I’m actually using this video for my Chem project where I’m going to be transforming erucic acid into (Z)-9-Tricosene through multiple steps including grignard!
I’m a long-time subscriber of yours but this video was just recommended to me on the UA-cam front page, so I watched it. Interesting how much your production quality has increased in five years, yet the overall style is still the same!
Man, im jealous of you!! :p You really do a great job, congrats on all your views and subscribers :)
haha thanks! I appreciate it :)
instablaster
Hmm 🤔
@@NileRed Merry Christmas!!
I have a question: why nobody uses a Grignard reagent with F? Such as CH3CH2MgF?
Maybe the pink is some transition metal (like iron III) contamination from the hydrochloric acid, the drying agent, or perhaps the magnesium. Transition metal salts might not be apparent in the NMR spectrum, and their colors are strong enough that the associated butyrate ion would only be present in trace amounts.
When a Grignard-Reaction is done, the alkyl halide is often diluted with dry ether before the addition. It is added dropwise, to keep the solution only slightly boiling. When the boiling gets to strong the Grignard reagent is able to react with the alkyl halide to form a larger molecule (in this case n-hexane). There's also the possibility that a ketone is formed as a byproduct, which could lead to a lot of side reactions. Nevertheless, nice presentation! :)
Hmm, I didn't know that! That could explain some things.
I would be interested in the fact, if it's possible to use ether that has been dried with CaCl2 or even NaSO4. I always used sodium to dry ether.
I imagine you could, I don't really see why not. Molecular sieves would be better to use though.
Nice video!
I believe your low yield arises due to the method of CO2 addition. Typically, the Grignard reagent would be added to a large excess of CO2 (pouring rxn mixture onto dry ice) to increase the probability that the Grignard only reacts with CO2. Bubbling the CO2 through the Grignard reagent increase the probability that a second molecule of Grignard will react with the carbonyl on the intermediate forming the geminal diol, heptane-4,4-diol, upon acidic work up, which I think would be quite soluble in the aqueous phase.
Good video though! Keep em coming!
+Trevor McElhenny thanks for the input! I will be doing a grignard again at some point, so we shall see what the yield is for that one :). I just ran out of ether though, so it has to wait.
+Trevor McElhenny i believe that the low yield was because you remove the glass stopper to add more ether instead the add with a needle just next to the hose with the co2, the moisture in the air was the trouble i guess, for the rest damn i wish do some reactions like this regards from mexico
NileRed hi. can I use anything else instead of ether like ethyl acetate?
Arman 25 typically, no you can't. If there are alternatives they would likely be other ethers. It needs to be a nonpolar solvent that is incredibly inert but not like hexane or benzene since the ether also has metal chelating properties that drive the reaction forward. In fact even though the Grignard reagent is notated commonly as R-MgX it actually exists as a tetrahedral organometallic complex with the ether roughly of the form (R-MgX)(Et2O)2. You MIGHT and I'm only saying might, get away with THF or dioxane as they are also ethers with metal chelating properties. Also, you can't use DCM because it will react with the magnesium just like the bromoalkane and generate side products and polymers.
Edit: I looked it up and dry anhydrous THF is an acceptable alternative, for the reasons stated above. Dioxane can also be used but leads to an interesting effect where instead of two ether molecules forming the complex (R-MgX)(Et2O)2 it causes the Grignard reagent to rearrange forming MgX2 and (R-Mg-R)(Et2O2) the corresponding magnesium dihalide which crashes out and the dioxane complexed diakylmagnesium species. I'm not 100% sure but I believe this compound can still be used in a Grignard reaction due to its powerful alkylating properties. You may however, have a higher than normal chance of creating disubstituted products due to the reagent having 2 alkyl groups in close proximity to the molecule they attack.
@@spiderdude2099 it's also possible to use a MTBE as a solvent, but it won't dissolve ROOMgBr salt. So the product will form a crystalline mass at the bottom of the flask, and it's will be hard to stir it well, using the magnetic stirrer. THF has the same usability as a Et2O in this case. It also gives a [THFMgHal]+ R- complexes, so there is no problems with using this. The only thing, that thf is highly hygroscopic solvent, so it's will be a good idea to use some kind of water adsorber, like H2SO4(conc.) in a bubble counter, or anhydrous CaCl2/MgSO4/Na2SO4 as a shutter if there is no way to use innert atmosphere such as Ar or N2.
Are you in school? Where are you getting access to NMR?
I get to do this in my O-chem lab next week, so this was really interesting to watch!
This is so old I wouldn't wonder to hear Niles vocal change lol
Instead of adding heaps of drying agent I have been running my work-up through a glass pipette filled with drying agent - a mini column. It uses much less drying agent and is easier to wash out for entrained residues.
This works so well that I am surprised to see professional chemist youtubers drying using bucketfulls of material.
wow I did a grignard in lab class and it didn't worked that well at all.
we did it on testtube scale, and even with some iodine we had to put it in an ultrasonic bath for 5-10 minutes then rub the tube in our hands to give it enough heat to start making the grignard reagent.
First atempt was a complete fail, I think I added the rest of the bromobenzene too quickly and killed the reaction, second atempt was very hard to get started but eventually worked out ok.
I've seen that pink color before, although I don't recall the reaction. The guy that runs MOC told me that such things are generally actually very small amounts of metal impurities.
For some reason I want to say that the suspected source ended up being the lye.
I could think more about magnesium. Some metallic impurity, since many metals come in a generic form ...
After just finishing Orgo 1, I’m so happy that I can understand what’s going on
You could salt out water phase to increase yield.
When you added the ether at the end (x3) and then extracted the butyric acid, how did you separate the two? Wouldn't the butyric acid be in ether because it is ether soluble?
What would the pH of the concentrated hydroiodic acid be? And what does it react with that other strong acids do not? (Other than the reactions that lead to meth, of course...)
replyvideos 101 HI has a pH of under 0. And it's mainly used for reduction.
pH depends on concentration of the acid. It is not dependent on the identity of the acid. The property you are looking for is pKa not pH
Do you have a screen shot of the NMR still?
Yeah, let's see the NMR spectra
When you do this kind of addition on CO2 with grignard reagents, there are equilibrium between the first addition product of the grignard reagent over CO2 and 1 or 2 extra equivalents of the grignard reagent. So if your CO2 isn't in excess at any moment, your risk the formation of the bi-addition ketone product and even further with a tertiary alcool ( both formed after hydrolysis indeed). You can draw the mechanisms if you wish, it's a bit odd and counter-intuitive but pretty satisfying ^^
The first addition of the grignard over CO2 is pretty fast and the two others equilibrium are much slower but in the case of a large excess of the grignard you'll end up with a mixture of the 3 product at the end.
So just use Dry ice if you want better yields ^^
Is the excess HCl just used to push the equilibrium to the right?
Generally the excess HCl is used to make sure that all (almost) of the intermediate is hydrolyzed. (assuming that is the part you are asking about)
yeah that was what I meant thx
Sick Video yet again!!! where do you get your apparatus from???
where do you buy septums?. also chemglass is awesome
Looks good bud!
Do you have access to a sonicator? I usually use it to get those last bit off of the flask to increase yield.
Nerd, what a great idea
Amazing video!! I would really like to try this synthesis; however, I do not have ether. Is there another solvent I could use in place of ether, or would that cause the reaction to fail?
Ian McClellan-Johnson you typically have to use some kind of ether. Thf, and dioxane work for most reactions and I’ve heard that DCM can be used but with slightly reduced yields. The ether coordinates to the Grignard reagent and that’s why it’s used, it stabilizes it and facilitates full formation of the reagent when it reacts with the magnesium.
Just FYI, if dioxane is used you can have a slightly higher risk of the dual addition product because instead of existing as the complex (et2O)2 MgXR it exists as (dioxane)(MgXR)2
How do you come up with the volumes for the washings and extractions?
the color is related to the chriality of the compound its has a chiral center at carbon 1
NO. There aren't any chiral centers in butyric acid.
In 3:52 you mentioned filtering to get rid of the unreacted magnesium, but wouldn't the acid react with it to form a soluble MgCl2 and is it possible to filter it before adding the HCl to get rid of the magnesium metal when we add it in excess?
RIP tons of ether....
Looking forward to the nickel video.
whick nickel video? i am not sure what you mean :p
Nile Red getting nickel metal from US nickles
ahhh k! I forgot :p
Is this acid anything like Indole-3-butyric acid ? And if so what's the difference in extracting them ?
John spartin Indole-3-butyric acid is completely different. It has a benzene ring, with an indole ring attached and a -COOH group on that indole. It is a plant hormone, but I don't know what exactly it does.
Great video. Looks like a big pain in the ass to do though 😂
Where’d u get the needles? They’re huge! I’d hate getting a shot from those!😂
Can you do a video on trimethyl borate please?
Ill add it to the list!
my brother and i are looking forward to it!!!
Where did you buy that 14/20 100 ml 3 neck round bottom flask??
Explosive Chemistry ebay or Amazon.
I like older nilered videos more because it's more info over the jokes and giggles.
... why not get a Dimroth cooler? they're like 50 bucks...
I've always wondered this myself, but for some reason they are far, far less common.
What was the final yield based on bromopropane?
I dont know of the top of my head, but I think something bad like in the 10-20% range.
Actually the yield was 49%!
I'm not a chemist, but maybe the pink stuff was from something in the tap water? Copper?
All water used was distilled water :)
You are the bees knees
Grignard reagent is a very strong nucleophile, shouldn't that cause further addition of Grignard reagent leading to formation of 4-heptanone (dipropyl ketone) as the major product????
CO2 is a stronger electrophile than the carboxylate, carboxylates are even less reactive than ketones to nucleophilic addition. The reaction that you say is happening though, only in really small amounts. I'd say that a major concern would be the grignard reacting with traces of water or other protic substances, or with leftover alkyl halide via SN2 reaction.
This vid was shown in my ochem 2 class :O
Have you dabbled in fluorine chemistry? Try some SF5 or CF3 stuff.
P.S. You're making me jealous I want to get into grad school already
what about a proper reflux condenser
I imagine the pink color could be iodine. That's the only thing I can think of.
+Ben Canon No, I don't think it comes from Iodine, since this Grignard-reaction started spontaneosly. There was no addition of Iodine necessary.
Nevertheless, there are only a couple of Iodine-crystals needed, which will completely react with the excessive Magnesium in the further course. There is no free Iodine left in the reworking step later.
Ben Canon He probably used a previously contaminated chemical. Maybe the bromopropane.
All that for a drop of blood
Hi, can i produce IBA this way? Yield? İ need a kg per week...
Definitely not, grignard reactions are expensive, very difficult to perform outside of a professional lab and notoriously unreliable.
Plus, you'd need the corresponding bromide, and that doesn't seem to be really common.
it's cherry flavored
What made you start making these videos?
I have always been interested in chemistry and I like teaching and making films. I started working in a lab, so I started doing some experiments, then I started filming them.
Nile Red what were you working ? Do they let you do these experiments ?
Yes, I was actually doing this as a test of the grignard on this scale. I was just working at a university. I don't work there anymore though.
Yo dawg, can I get a rip??
Fuuuuuuuu! Nevermind
wow I did a grignard in lab class and it didn't worked that well at all.
we did it on testtube scale, and even with some iodine we had to put it in an ultrasonic bath for 5-10 minutes then rub the tube in our hands to give it enough heat to start making the grignard reagent.
First atempt was a complete fail, I think I added the rest of the bromobenzene too quickly and killed the reaction, second atempt was very hard to get started but eventually worked out ok.