Using the Grignard Reaction to Make Tertiary alcohols

[@from_mind_to_myons1561]

You always have to be very gentle to your Grignard. My organic chemistry professor recommends gently petting the Grignard before starting, works very well if the moon is in the right position

[@gablaw9490]

That comment made my day xD

[@Metalhammer1993]

and My professor said, to not bother with it: It's an asshole anyway. You can let it know, you hate it, before you started, it will hate you just the same (which covers with my own experience^^)

[@bromisovalum8417]

You have to give the RBF a kiss too.

[@christopherleubner6633]

Right, it helps to add a single crystal of iodine when making your griganard reagent. Also dry your solvent with something strong that combines with water chemicals and removes dissolved oxygen like calcium hydride and freshly bake the glassware with a slow flow of argon.❤

[@flomojo2u]

NurdRage this is why you are a legend in the amateur chemistry community! Seriously, this obviously took an extremely long time to prepare and I know I’m not alone in this appreciation, great work!

[@raptor4916]

Great work, one trick I've learned to get a Grignard started is to add 2ml of your starting alkyl halide then cup the flask in your hand till you feel the flask starting to heat up and you get a very gentle reflux then proceed as normal.

[@NurdRage]

Next big project will likely be on making fuels.

[@garonadjarian196]

Good idea

[@ALizardInCrimpson]

Please do

[@user-nd1km9bc6j]

yes plz do it

[@brandoncollins6095]

Flag this hey you've taught me soooo much in ahead of my chemistry class and know so much more than everyone else bc of you I'm 16 I'm a nurd

[@borttorbbq2556]

Sound cool i look forward to them great video by the way

[@MtKybalion]

i've been watching your vids for so long and never really understood what you're talking about but since i started college last fall taking gen chem and now organic chem; it feels good know like 1% of what you're talking about.

[@Unterhosegotti]

Rss Reader isnt complicated

[@evilplaguedoctor5158]

I recommend the youtuber, Tyler DeWitt, he (for me anyway) makes things just click and make sense.

[@bdnugget]

Nice, the first hit on that sigma page was isopropylmagnesium chloride/ lithium chloride complex, my favourite reagent for making Grignards. Works really fast and easy, also on stubborn halides via transmetallation. It's known as the "Turbo Grignard" :-)

[@science_and_anonymous]

You should make a video completely devoted to solvents like their nicknames,how they're used,polarity and easy way to find them

[@redmadness265]

3 years and no likes?

[@synthol9635]

Dropping tiny bit of iodine seems to activate rxn really well for me, produced so magnesium iodide also removes that last traces of water. Great vid thanks for posting!

[@-Kerstin]

This episode was amazing. Glad to see that you have been actively making videos since the last episode. You sure put a lot of work into this one. I think it would be great if you could do a video with illustrations explaining for dummies how the laboratory glassware you use work. Also a "ELI5" on chemical notation or at least color code your illustrations so I have a chance of understanding what squiggly line is what compound. :D

[@alllove1754]

Very very good to see you posting tutorials again. Missed you man, missed you

[@chemistryscience4320]

The best Grignard video I've seen in years! Here in Argentina it is almost impossible to make Grignards, so I have seen such an incredible video that it almost makes me feel what it is to make one,i whanted to do these reaction for years now !! But the research lab where im added does not do these reaction so often. Thanks for this super long and amazing chemistry video :)

[@chemicalmicrobe]

Need to go to Lima. So fucking dry there, the Li will probably leap into the RX!

[@Dakktyrel]

I love this channel. I'm not a chemist but seeing the science in action is mesmerizing.

[@hoseja]

Wow, that's a LOT of content, could have easily been like three separate less insanely dense videos IMHO. Great stuff!

[@danielf.7151]

I was wondering where you got those huge chunks of ice from. Then I remembered: canadian winter.

[@nunyabisnass1141]

Also known as just canada to those that live there. Anyway, i occasionally run the few reactions i know how that are also exothermic, in the winter because its easier in this way. Its also a great time for crystallization from stubborn or dangerous solvants you don't want to put in your freezer.

[@benearhart1224]

I think you should recommend using BHT and 3A sieves for ether. It's a more professional approach and will most likely be more resilient to being left exposed to air for times longer than necessary.

[@JoshuaNicoll]

I used your method with Magnesium to make sodium, I'm not in a hurry to do that again, it was pretty volatile, so I think I'll just watch these from now on.

[@samorakaos3695]

It was a great experiment. I enjoyed it very much. You really do justice to chemistry. As a chemist, I learn a lot from you. If you come to Turkey, I would definitely like to meet you.

[@graywolf2600]

Really putting that heating element to work there!

[@Gyzmodium]

Right on. I've been waiting for someone to take this on. Perhaps you'll answer all of our speculations once and for all. I'll be looking forward to the alkalai metals video.

[@germanwidow8322]

Amazing video , nurdrage is back !

[@martinheidegger1125]

You are a very gifted & etp chemist. I first took the liberty to check my Merck Index then went to a public University close to my home and checked the appropriate chemical journal "The Tetrahedron Letters," I believe and was wondering if you could do a Lab video on the synthesis of "ethyl 2-chlorovinyl ethynyl carbinol" if you could be so kind.

[@benearhart1224]

Hi, I love your videos. You should get a Fischer Isotemp. I suspect that is what NileRed uses. I have one and it's got up to 1500 RPM stir and a top temperature of 550C. You can boil off water incredibly fast with it. I can do some calcining with it as well as distill sulfuric acid. I do have to resort to foil on distillations occasionally but the thing you can do with those is take advantage of the large plate size and put an insulating wall around the edges. I have a set of little concrete bricks that are 1" x 1" footprint and .5" tall made from an ice tray. They are made of Portland cement, were given a week to cure under water, and whenever they start to show wear I give them a day spa in sodium silicate solution. They might as well be rocks now. Anyway, it's quick to rearrange them based on what you are doing. I can send you a picture if you like. You just arrange the wall around the flask and the concrete holds the heat in. It's is a bit pricey but you'll forget about that soon enough. I use mine for one thing or another everyday.

[@hkkhgffh3613]

Even with holding da thing called phd this is always exciting! Wicked!

[@Grak70]

I love your channel. Nilered and ChemPlayer are fantastic, but I love how you explain things practically. Would you consider doing a whole video devoted to workup schema, especially when one is going into uncharted territory?

[@RaExpIn]

Getting a Grignard reaction to begin reacting can be quite a pain... I used a very small amount of iodine in my last synthesis to etch the magnesium. If you don't need your product free of traces of iodine this is another way to get it to run.

[@haralduryngvijuliusson786]

You can also add a pinch of iodine into the reaction mixture to kickstart the grignard reagent reaction, that way the waiting period wont be that long and the risk of thermal runaway is lower.

[@durshurrikun150]

Or 1,2 Dibromoethane. They are used as activators for this reaction. Or you can use Rieke Magnesium, but i don't think that's easy to get.

[@Abdcwyxz]

If the halogenated alkyl group is relatively cheap, use 2 to 3 equivalents of Grignard for 1 equivalent of ketone. To initiate the Grignard, start with 1 mol% of iodine with the magnesium. Add 5 to 10% of the the halogenated alkyl. If nothing happens, add more iodine (2 to 5 mol%), wait 2-3 mins. Then add the halogenated alkyl dropwise. If nothing happens then you have a problem with your reagents or your solvent is really low quality and junks the reaction before the initiation. Tips: - Wash the magnesium with dilute HCl then oven dry it. - Use THF as solvent, dry it on sodium and distill it. It should be completely anhydrous - Make sure that the reagents are above 95% purity - Iodine works as an activator for the magnesium AND as a visual indicator. If the reaction goes from brown (iodine) to colorless, it means that the initiation is done and the reaction is going.

[@DrPhysician]

Distilling for a week? That is the new definition of "dedication". GET ON IT, WEBSTER!!!

[@doublenikesocks]

A little late, anyways, steam distillation is also used in a oil refining to lower the vapor pressure of light boiling components to improve separation and allow for reduced reflux ratios/shorter distillation columns.

[@bdnugget]

You can isolate ketones using cadmium grignards on esters, they're milder than magnesium ones and stop at the ketone stage. Think Gilman came up with that one in the sixties. 2 R-MgX + CdCl2 -> Cd-R2 + 2MgClX to make your cadmium Grignard. Much healthier than usual Grignards.

[@durshurrikun150]

Actually, organocadmium compounds are much more toxic than grignard reagents, but you can use organozinc compounds or other milder organometallic compounds.

[@bdnugget]

@@durshurrikun150 yeah no shit, it was sarcasm

[@james225g]

I love these videos.

[@BranFlakesR1337]

we used thf, a three arm flask, and a syringe for our setup

[@p.f.3014]

Great chemistry! Thank you!

[@skarsilverheart3238]

I find it interesting you are now making these alcohols, all to essentially redo one of your very first video's of making potassium metal. You never got Sodium to work, but you did make potassium metal using Magnesium, potassium hydroxide, and I think the T amyl alcohol. one of my fave vids, though you have long since taken it down.

[@bigboineptune9567]

He hasn't taken it down, it's unlisted.

[@TommyCallaway]

Quote: "....I'm going to do some amateur research in creating potassium.." - Bro, i get it, you're way smart.

[@humr2346]

we were taught at school that you need to add a little bit of I2 to start reaction between magnesium and alkylhalogenide.

[@bromisovalum8417]

Once I succeeded in making the EtMgBr grignard reagent using diethyl ether that was only dried over solid NaOH and next 3A molecular sieves.

[@Frdyan]

This channel and NileRed should do a crossover episode ~

[@ladmad9196]

how can chemists do a crossover?

[@ravenous9577]

They talk a lot alike...

[@Cajuu]

My favorite anime crossover (yeah that was a joke)

[@smokekushdaily5570]

Caju explosivo just don't that meme is dead and is cringey as fuck.

[@rpearson]

I think they might be the same person.

[@f800gt76]

I did tri-phenylmethanol through Grignard reaction at university. I remember how sudden it starts to react, ether is boiling, spilling to condenser and you are changing heater to ice bath since reaction is quite exothermic )

[@Anamnesia]

Just a comment, not a criticism; I didn't think you'd be delving into *organic chemistry* ? I think it's great that you are, but I thought I recalled you stating this in one of your previous videos, or perhaps that it wasn't your specific field of interest/research/knowledge... Whatever videos you make, I'll watch them through 100%, adblocker off! Keep going... 👍🏼 💯

[@NurdRage]

Grignards are really basic chemistry. They're taught in second year in canada, basically lowest level in a chemistry degree. So every chemist knows them, even chemists completely outside the field like computational chemists. Something more complex, like a Suzuki coupling, is definitely specialized and i wouldn't touch it.

[@rosk860]

that is true, also most organic chemists use quite often metal in their synthesis, "pure" organic chemistry without metals is possible, but are often very old chemitry that have been extensively described.

[@rosk860]

i am in a master degree of molecular and supramolecular chemistry, and nearly every applications studied relies at some point or another on metals catalysis or enzymes catalysis

[@TheBackyardChemist]

In my (admittedly very limited) personal experience, Suzuki couplings work quite well, but the reagents are expensive and more or less hard to make. Not to mention you need a super expensive palladium catalyst and a tank of argon or nitrogen to provide an oxygen-free environment. Not that hard if you have the proper equipment, but costly.

[@rosk860]

i'm not sure about the oxygen sensitivity of this reaction, i remember some metalocatalysed coupling are, but i can't remember which... suzuki coupling and other palladium catalysed are widely used in industry and research labs for their "power" beside the fact that palladium as rhodium and ruthenium availability is going lower and lower. I never tried to conduct any of these reaction for now, but according some of my teachers and PhD friends, they seems to work quite well with often few optimization. What would be the expensive reagents ? beside Pd salth.... (sorry if english isn't perfect !)

[@fryingdutchman8921]

Great video. I know that the vapor pressure of these large alcohols should be low but do they smell like something at all?

[@ExemplaryLigas]

I remember when you upload a video where you show how to make potassium metal i never know if youtube or you got out the video, regards from Mexico

[@AllChemystery]

have you tried the synthesis of potassium via dioxane like you did with the sodium? i have tried it 3 seperate times with no result. there most certainly was potassium present in the MgO/K slag and i could see it when the dioxane was firstly added to the flask however this is where it stopped. no K metal formed like it did in your sodium experiment.

[@SlmKBatero69]

You should try to extract more product from the aqueous layer, specially for the smaller alcohols. Use a little brine and a little volume of ether to clean the layer.

[@owencoyne6223]

For the prodigal Son Returns DILLY! DILLY!

[@kesakhan]

Why not use a brine wash followed by mag/sodium sulphate to dry your ether once the workup is done? Dean-Stark seems a little overkill.

[@ejkozan]

I though the same, but i suppose it is connected with waste production: remember, brine, sulphate, anything like that generate cost, cost for disposal of chemical waste. With Dean-Stark it uses energy, but without generating wastes, especially on this nice, big scale. From my view, vacuum distillation would be more effective than steam one, but besides that, this was pretty green chemistry from waste point of view.

[@FPengu1n]

the Dean-Stark seems more to remove water during the distillation to ensure the product / ether distillate has reduced water content. Additionally the use of washing steps produces Aq. waste which builds up pretty quick on scale.

[@eyecanseeyoueverywhere9688]

I did this in college lab a few months ago, i made 2-methyl-2-hexanol

[@gamingmarcus]

I'm not at the end of the video yet but one thing I'd recommend if you are making tertiary alcohols is to either use very dilute acid or even better ammonim-chloride solution because elimination happens very easily with tertiary alcohols. E: ok nvm you mentioned it in the video Your activatoin method seems to work just fine. In the lab we first put in a tiny amount of iodine and let it react.

[@eivilcow33]

I'm somewhat surprised that the larger alcohols aren't destroyed by high temperature. They seem to be incredibly resilient.

[@MrWizzardx3]

Grignards are a pain to do, but so useful.

[@xdoods]

You have some timing. I literally *just* learned about Grignard reactions in my OChem class.

[@sjn7220]

Very nicely done. Did you try vacuum distillation for your last alcohol?

[@RepublikSivizien]

I learned it to put just a wee bit ether at the beginning, so the ether is just slightly above the magnesium. Then we add a ›safe‹ amount of the halogen compound, heating it with our hands while stirring, until the reaction starts. Now we slowly add the rest of the halogen compound, now diluted in ether, so the ether is ›safely‹ boiling. This way you do not have to worry, that the reaction suddenly runs away, because the reaction is already running and in some kind of ›equilibrium‹. Oh, and I think it is cleaner to add water/10%-HCl to the mixture and not the other way around, but this is just my opinion. If this reacts to heavily, you probably still have a huge amount of grignard-reagent in your mixture, so use more acetone/*. There should be no reason to use too much acetone/*?

[@MisterLepton]

I’ve tried the reaction before wherein KOH in a specific type of oil (I couldn’t afford it so I tried mineral oil) is heated with magnesium and a tertiary alcohol (I used tert-butyl), with slight pressure kept using a balloon on top of a fractional distillation column. I couldn’t get the reaction to start. I got the idea from the sciencemadness.org forum many years ago and some people appeared to pull it off. A good portion of the posters were suspicious of it being a “troll”. Good luck!

[@MisterLepton]

My pictures are still on that original thread over there I’m sure. But I don’t want to connect the two identities so...

[@swirlingabyss]

I went to college at a very humid university. They didn't let us do a thourough drying regimen, and the Grignard lab always failed.

[@ExplosionsAndFire]

n i c e

[@石头-d4f]

A way of doing grignard reactions with wet solvent and reagents is to use an ultrasonic bath, but yields are usually lower.

[@firstmkb]

I was thinking about using ultrasonic for *something* the other day. What does it work well for? Lower yields don't sound like much of a benefit.

[@durshurrikun150]

There have been people who managed to do a grignard reaction in water with good yields, there are some papers about that.

[@石头-d4f]

@@durshurrikun150 I would like to see these papers.

[@tengkuariffshahshahrir605]

Is it possible to just filter off the magnesium oxybromide instead of titration? It would save some trouble

[@jhyland87]

0:52 did you make that image? Pretty detailed. Very neat.

[@haos0423]

i think the upper layer(now the et2o) should be poured out from the top. plus, maybe you can add a very tiny amount of I2 , this should make the reaction(the preparation of RMgBr) start very quickly.

[@Lunch_box]

Holy shit he's got one hell of a bong

[@noname-80lbs]

Master! Master!!

[@justusfelix2441]

What camera do you use for your videos? Nice video!

[@bromisovalum8417]

I have entertained the idea of using DHEA and MeMgI as substrate to make methandriol (just for shits 'n giggles because I have DHEA supplement capsules lying around) but decided not to because I'm not sure of the legality of the end product. Also when using homemade methyl iodide it might be advantageous to expose it to sunlight a day before, the traces of iodine generated by the yellowing of the product might help in starting the Grignard.

[@bromisovalum8417]

The cool thing about methandriol is that it is insoluble in practically anything.

[@justastranger6564]

Fun Fact: t-Amyl Alcohol, when sufficiently purified, is safe to consume and has effects similar to Ethyl Alcohol. It is several times more potent, however, and requires dilution. Do not consume home-made stuff, you don't know how pure it actually is and what is still floating around in it.

[@starlight4649]

Chemistry, microbiology, engineering, and architecture are all just evolutions of playing with legos It's just the size and shape of the legos change. In the case of chemistry, you can't see your legos but they're zipping around incredibly fast in everything around us

[@adnansafar7008]

You could have added iodine to help start the grignard reagent formation

[@durshurrikun150]

Did you do any other reaction involving organometallic compounds? Such as the Heck reaction and other type of couplings or any other?

[@erikdimitrov8140]

How do you think 2-methoxybenzylmagnesium chloride would react with acetone? I mean the normal way or there will be some rearangment?

[@durshurrikun150]

There wouldn't be any rearrangements. Ethers are tolerated by grignard reagents.

[@OneCentChemist]

Out of curiosity, why did you remove the water with the dean stark apparatus and not use a drying agent such as magnesium sulfate?

[@mduvigneaud]

I have a question about copper(II) chloride... should I send you a message here on YT, on Patreon, should I post it as a comment on the earlier video about the chemical recovery...

[@thomasgarbe8354]

in some reaction towards biotin we made Grignard-catalyst from magnesium and ... -- was it iodine?

[@sottile211]

Can you think about making a video on 1-(Dimethylamino)-2-chloropropane Hydrochloride Cas#4584-49-0

[@p.f.3014]

I noticed hexadecan-1-ol is easily available and very cheap?

[@spectra-man]

Can you do a video on making carbamate of the alcohol using trifluoroacetic acid and sodium cyanate?

[@spectra-man]

I tried this here: www.orgsyn.org/demo.aspx?prep=CV5P0162 and it only works sometimes given the same conditions (I want to know why). I'd love to see you try this with one of the tertiary alcohols you made.

[@GMCLabs]

Hey what ever happened to your video on making potassium metal. I remember it was KOH, Mg, some type of solvent and a tertiary alcohol. KZbin flag that one or something? I found another video of someone using lamp oil, but there video isn't as good as yours was.

[@9firewire]

Can you do a video on extracting and identifying chemicals in plants??

[@darianballard2074]

Love all your video's

[@stephenjacks8196]

Hindered alcohols, turpentine (can distill alpha-pinene). Pinacol reaction (with Mg), reduce ketone, hindered sec alcohol. Still think you need triglyme.

[@WC0012]

I always sublime Iodine with the Magnesium turnings. Was suprised you Skipped that.

[@drmunazza3617]

Why are all of your distillations not using 24/40 joints?

[@jaredgarden2455]

It would be cool to see you then recycle the magnesium hydroxide/halide and then process it down to shavings and then reuse them.

[@rickydona919]

I just recently started cleaning copper pennies in a vinegar, hydrogen peroxide solution and left one of the pennies in the solution for two days and the liquid turned blue, can you tell me what happened and can you do a video on whether you can separate the copper from a penny and convert it into pure copper metal?

[@bigboineptune9567]

The hydrogen peroxide reacted with the copper to form copper oxide, which then reacted with the acetic acid to make copper acetate.

[@andywells8125]

how do you get good yield of a ketone reacting a Grignard with an acid halide, avoiding a second equivalent giving a tertiary alcohol?

[@Thee_Sinner]

A method that doesn't use fire is better? Guess we see things differently here.

[@psychedelicmonkey55]

As long as you like explosions too :)

[@tmfan3888]

y do u always dilute the ketone with ether when adding it 2 the grignard? isnt the grignard reagent already pretty dilute?

[@jakebaldwin1308]

My man said, “chemical voodoo” lol

[@Somestupiedbudee]

but can i drink it?

[@ThePharphis]

I was wondering if inorganic carbonates also work. I'm guessing no?

[@1st_ProCactus]

Can you turn that into OMgBrO :D

[@joshuacleverley3929]

NaBrO

[@1st_ProCactus]

NiCe

[@medexamtoolscom]

ThAt'S PuRe GeNiUS.

[@BeepingSheep]

medexamtoolsdotcom I'm diene

[@elephystry]

No I don’t think so, because magnesium is in group two and will attach two groups unlike group one. I think you could make mg(bro2)2 though.

[@Unterhosegotti]

Why arent you using a round bottomed flask?

[@MohammedMohammed-eb2yk]

ياصديقي كيف نعمل الهاليدات

[@dontquestionjustbelieve5757]

hi i am 13 and when I grow up I want to become an electrochemist so is it ok to do some more videos on electrochemistry?

[@williamackerson_chemist]

Could you substitute diethyl ether with 1-4-dioxane?

[@CatboyChemicalSociety]

can you use polyols for alkali metal synthesis like erythritol and xylitol??

[@janapewen362]

Why doesnt magnesium react with 2 bromohexane to make duodecane and magnesium bromide

[@raptor4916]

Alperen Bırçak it does actually its just very very slow unless theres catalyst, usually iirc a Copper(I) salt, this is becuase the carbon in a alkyl halide doesn't have a partial positive charge on it like a carbonyl does making it much less reactive

[@jakubobuch2123]

It does have a partial positive charge and it is used in Wurtz reaction, which is almost the same but uses sodium instead of magnesium, so the organometalic reagent is more reactive.

[@durshurrikun150]

@@jakubobuch2123 the Wurtz coupling requires more stringent reaction conditions and more reactive organometalling compounds, such as organosodium. Grignards are far less reactive than such organometallic compounds and thus don't react with organohalides. You don't really have the issue of coupling reaction with grignard or organolithium, except maybe with very reactive organohalides such as allylic halides or benzylic halides.

[@durshurrikun150]

@@raptor4916 Tecnically, grignard reagents and organolithium compounds are hard nucleofiles and tend to react with hard electrofiles such as C-N and C-O multiple bonds, with polarized double bonds. Organic halides are soft nucleofiles, so they don't react with grignard reagents or organolithium compounds. With copper you form an organocuprate of either Magnesium or Lithium a M+CuR2- specie, which are also called Gilman reagents and are softer nucleofiles, therefore they react preferentially with organic halides or with electron poor alkenes( enones for example). And this reaction doesn't follow the typical Sn2 reaction pathway. The first step is the formation of a Cu(III) species, which immediatly later does a reductive elimination to generate the coupling product and a CuR species.

[@raptor4916]

@@durshurrikun150 I was simplifying for the cheap seats

[@Mcng2343]

Can you try to make 2-methal 2- butanol

[@valentin-razvanlupu4868]

Can you try doing a barbier reaction?

[@CarrotSlat]

Can anyone give me an alternative way to make a tertiary alcohol from an alkylhalide other than through the use of Grignard reagent?

[@yacobgugsa2524]

Are you going to publish a paper on your research in making alkalide metals from Grignard-sourced tertiary alcohols?

[@NurdRage]

nope, it's already been researched and patented by others. I'm basically just redoing old chemistry. Nothing novel that can be published anew.