> chemistry > acides > acide-butanoïque-butyric-acid > how-to-make-butyric-acid-grignard-reaction-nilered

How to make Butyric Acid (Grignard Reaction)

NileRed - 2014-11-15

The bromopropane that I used was made in this video: http://youtu.be/9eaWqvZZcig

In this video I will be demonstrating the Grignard reaction to produce butyric acid.

The Grignard reaction is a very interesting reaction which can be used to form new carbon-carbon bonds.

The final yield was 2.66g of butyric acid, or about 49%.

Trevor McElhenny - 2015-12-08

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!

Ярослав Майборода - 2020-04-02

@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.

winnerandloser - 2020-04-06

The low yield is because of several factors from my experience:

- use of a bad condenser (short, liebig, not ice-cold water). You want to use a condenser with as big internal volume as possible (long alihn with ice-cold water works great)

- by repeatedly losing so much ether during the reagent formation you increase the concentration of PrBr too much, which will lead to formation of n-hexane by coupling of an unreacted bromopropane mollecule with the already formed grignard reagent. This is favored by high concentrations of alkyl halide and high temperature.

- after the grignard reagent formation stops being exothermic it is best to reflux it some more with external heat for some time. This will finish the reaction, which, although exothermic, doesn't go to completion with its own heat.

- in general it is also good practice to reflux the mixture after addition of the carbonyl - although this doesn't apply here, as the carbonyl is a gas and isn't present in the reaction mixture unreacted

- contrary to others I don't think opening the stopper to add ether jeopardizes the reaction too much, it IS water-sensitive, but the amount of water vapor in the volume of gas inside the flask is miniscule

I have performed a grignard reaction to make isobutyric acid by dumping dry ice into the grignard reagent/ether solution through the condenser and I got a 53% yield after distillation while using all of the practices I described before, but any criticism is welcome.

Christian Ferralli - 2020-04-09

@spiderdude2099 THF is the go-to solvent for grignards in industry.

spiderdude2099 - 2020-04-09

Christian Ferralli yeah I imagine that the lower vapor pressure, and flammability are more desirable on a large scale. And it doesn’t have the disubstitution problem that dioxane does.

Kevin Tate - 2020-08-02

spiderdude2099 I can not go into full details because of a confidentiality agreement but I can say I have made grignard reactions using Dry THF. The yields were very good. One time we had a power outage during the reaction and one big thing I noticed was even though we lost power the grignard continued as if the agitator was still running. We lost all cooling as well so we hooked up a tap water line into the jacket and prayed until the power came back. Oh the memories.

Grak70 - 2018-01-19

Are you in school? Where are you getting access to NMR?

TheBackyardScientist - 2014-11-16

Man, im jealous of you!! :p  You really do a great job, congrats on all your views and subscribers :)

NileRed - 2014-11-16

haha thanks! I appreciate it :)

scienceprimo - 2014-11-16

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.

Bisqwit - 2019-09-13

I’m a long-time subscriber of yours but this video was just recommended to me on the YouTube 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!

Talon/Reptar - 2015-10-02

Do you have a screen shot of the NMR still?

Tim Burch - 2019-05-01

Yeah, let's see the NMR spectra

Random Experiments - Experimente und Synthesen - 2014-11-16

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! :)

NileRed - 2014-11-16

Hmm, I didn't know that! That could explain some things.

Random Experiments - Experimente und Synthesen - 2014-11-16

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.

NileRed - 2014-11-17

I imagine you could, I don't really see why not. Molecular sieves would be better to use though.

Samantha Burke - 2020-04-28

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?

Patrick Sweetman - 2018-02-18

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.

Martin Hlousek - 2016-05-10

Sick Video yet again!!! where do you get your apparatus from???

alexandre simon - 2018-02-21

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 ^^

David Glass - 2017-12-23

How do you come up with the volumes for the washings and extractions?

SinisterMinister - 2015-05-15

from you videos i get the feeling that the washing and purifying step at the end is always the one that takes the most time of the whole synthesis

Talon/Reptar - 2015-10-02

Do you have access to a sonicator? I usually use it to get those last bit off of the flask to increase yield.

Alice Raspii - 2019-03-27

Nerd, what a great idea

OpitcalTex - 2014-11-16

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.

NileRed - 2014-11-17

I am glad that you are excited about chemistry! :)

Nickolas Steel - 2014-11-15

Looks good bud!

Aditya Varma - 2017-03-24

where do you buy septums?. also chemglass is awesome

Ian McClellan-Johnson - 2015-02-21

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?

spiderdude2099 - 2020-03-18

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

cameron Gibbs - 2016-02-01

what about a proper reflux condenser

replyvideos 101 - 2016-07-09

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...)

iNsaNiTY_Crona - 2017-03-08

replyvideos 101 HI has a pH of under 0. And it's mainly used for reduction.

Erwin Rommel - 2018-03-20

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

David Nelson - 2018-10-13

Fuuuuuuuu! Nevermind

JIMMI - 2014-11-17

Can you do a video on trimethyl borate please?

NileRed - 2014-11-18

Ill add it to the list!

JIMMI - 2014-11-18

my brother and i are looking forward to it!!!

satchel frost - 2016-02-12

Have you dabbled in fluorine chemistry? Try some SF5 or CF3 stuff.

satchel frost - 2016-02-12

P.S. You're making me jealous I want to get into grad school already

Touch784 - 2020-03-13

RIP tons of ether....

Anon - 2014-11-16

Looking forward to the nickel video.

NileRed - 2014-11-16

whick nickel video? i am not sure what you mean :p

John Doe - 2014-11-18

@Nile Red getting nickel metal from US nickles

NileRed - 2014-11-18

ahhh k! I forgot :p

OhighO Skater - 2020-07-14

You are the bees knees

Angelo Napolitano - 2017-05-06

Where did you buy that 14/20 100 ml 3 neck round bottom flask??

B Real - 2017-11-02

Explosive Chemistry ebay or Amazon.

hafabagle - 2019-09-13

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?

TheChemistryShack - 2014-11-15

Is the excess HCl just used to push the equilibrium to the right?

NileRed - 2014-11-16

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)

TheChemistryShack - 2014-11-16

yeah that was what I meant thx

codeartha - 2016-05-21

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.

codeartha - 2016-05-21

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.

Holden Saaring - 2019-04-19

Manganese impurity, probably

Fezziiwig - 2014-11-15

What was the final yield based on bromopropane?

NileRed - 2014-11-15

I dont know of the top of my head, but I think something bad like in the 10-20% range.

NileRed - 2014-11-16

Actually the yield was 49%!

User THC - 2017-04-21

You could salt out water phase to increase yield.

bahadır carbaş - 2018-08-27

Hi, can i produce IBA this way? Yield? İ need a kg per week...

Pietro Tettamanti - 2018-10-25

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.

Kevin Byrne - 2015-03-23

I'd never seen anyone create a carboxylic acid by bubbling CO2 through a Grignard reagent.  
BTW, you might mention that butyric acid smells like rancid butter or body odor.

Sammy Masters - 2020-01-31

the color is related to the chriality of the compound its has a chiral center at carbon 1

Justin Koenig - 2017-11-26

... why not get a Dimroth cooler? they're like 50 bucks...

Jermaine Race - 2019-07-23

I've always wondered this myself, but for some reason they are far, far less common.

meanbubbles - 2014-11-15

What made you start making these videos? 

NileRed - 2014-11-16

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.

TheMacntiger - 2014-11-18

@Nile Red what were you working ? Do they let you do these experiments ?

NileRed - 2014-11-19

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. 

mike yost - 2018-12-13

@NileRed what they didnt teach you at the university. To keep out water, teflon is A+. Teflon sleeves for the joints, or krytox teflon grease, or glindemann sealing rings of teflon. Just make sure whatever reaction doesnt react with the teflon, it creates a virually gas tight anti water seal for your glassware

Alan Bayman - 2014-11-15

I'm not a chemist, but maybe the pink stuff was from something in the tap water? Copper?

NileRed - 2014-11-16

All water used was distilled water :)

Ben Canon - 2015-03-02

I imagine the pink color could be iodine. That's the only thing I can think of.

196Stefan2 - 2016-01-04

+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.

iNsaNiTY_Crona - 2017-03-08

Ben Canon He probably used a previously contaminated chemical. Maybe the bromopropane.

Lost One - 2015-02-19

Is this acid anything like Indole-3-butyric acid ? And if so what's the difference in extracting them ?

iNsaNiTY_Crona - 2017-03-08

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.

عبدالرحمن ياسر شعبان ١٧١٠١٣٥ - 2018-06-08

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????

Pietro Tettamanti - 2018-10-25

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.

Lorenzo Follador - 2016-09-28

+NileRed why vent while mixing?

Lorenzo Follador - 2016-10-04

Due to evaporation, only?