Make Chlorotoluene (mixture of isomers) 1st step in making Pyrimethamine
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- čas přidán 25. 04. 2016
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How to make chlorine gas: • Make Chlorine Gas (fixed)
Fractional distillation of lacquer thinner to obtain toluene: • Fractional Distillatio...
In this video we demonstrate the synthesis of chlorotoluenes.
In the first process we react 4 moles of chlorine (2 moles of chlorine gas) with 500mL of toluene and 10g of steel wool in a flask with a reflux condenser. We then remove the steel wool and wash the chlorotoluenes with water and a saturated solution of sodium bicarbonate. Then we fractionally distill the organic layer to obtain chlorotoluenes in the boiling range of 135-170 Celsius.
In the second process we mix 125g of anhydrous ferrous chloride and 500mL of toluene. With vigorous stirring we add a total 160g of trichloroisocyanuric acid by 10g every 15 minutes or slower if the reaction begins to reflux. After the last addition the mixture is stirred overnight and then the organics are recovered using a dean stark trap and 500mL of water as the carrier solvent. The organic layer is then fractionally distilled to obtain chlorotoluenes as before.
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To those people that think my videos are cheap to make and that i'm rolling in ludicrous profits, this is why i keep begging for money: Failure, after failure, after failure, after failure...
+NurdRage Its expected. My (limited) understanding of Chemistry makes it seems like a science that is 90% science and 10% voodoo and dark magic. Add making these videos possible for non-professional chemists to follow and you have an even harder problem. Thank you producing these videos, and thanks for the dedication to your viewers.
+Carson Page Vodoo and dark magic? xD All my teachers : Boom that's how you solve it , Class : MAGIIICI.
+NurdRage I think there's a preconceived notion that you have a very high paying job with your degree and can pay for the equipment used in the videos out of pocket easily.
Would you be able to do a video about manganese dioxide thermite using manganese dioxide from lantern batteries
Because that's how science and scientists work.
"I'll detail that in another video if there's enough interest."
NR, I get so excited when I see one of your videos come up, it doesn't really matter what the content is.
agreed, but ferric chloride is very interesting!
As a former chemistry graduate I can't thank you enough for these videos. They're incredibly informative, intellectually stimulating and of course, entertaining. The inevitable failures are all worth it. Keep it up!
I wish you would sell t-shirts that say "Greetings fellow Nurds" and have your NurdRage logo. I would feel like the coolest "nurd" in the world wearing that!
yaaaaay Awesome idea
or "Crushing your expectations"
Id own them!
Dude... That's what I call Dedication!!!
+Anamnesia abso-fucking-lutely!
You should use broken glass pipettes as short segment of tubing when you want to dip the end of in in a liquid.
I applaud anyone who does there best in order to make accessible a process mostly out of reach for amateur chemists. Right on.
Spending over $1,000 in 2 months just to produce this 12 minute video?
You are indeed dedicated.
I tell people all the time: I could literally synthesize your $50,000/yr drug for like maybe $1000.... I'm the bad guy all the sudden.... This guy is doing very good things! Extremely complicated things.
Wooow!
In Organic chemistry classes we didn't learn how to proceed when anidrous Iron Chloride was not available!
Again, thanks NR!
I mean, I don't know what science guys are on about. This is just ordinary magic.
Amazing vid. I love your task-oriented style. If I ever get my chem equipment, I'm doing this process.
Now that I'm in a chemistry class in school, I actual follow what he is doing!
I'm quite certain that it's all post-commentary, but the absolute deadpan (helped by the voice changer) when your chlorine gas tube dissolved in the hot toluene was still pretty funny.
Also, I do not envy your having to clean out the fumehood when your anhydrous ferrous chloride/trichloroisocyanuric acid setup ran away from you - that mix resembles ceramic slip, at least when you showed it being poured into a filter, and the way it seemed to be depositing on the side of the flask during the reaction doesn't help.
Nothing is better than a nurdrage video after exams are done.
Incredible. Thank you for your dedication and work.
I don't understand much of his videos but i still watch them. I don't know why.
Even though I don't get half of what's going on most of the time, I still enjoy watching the reactions take place. One of these days I am going to make myself some beautiful blue copper sulfate crystals.
Great to see you back on CZcams, NR. You have a lot of followers but not all of us have cash to spare. There are other ways for you to monetize your content - product sponsors, paid reviews, etc. Ben from Applied Science seems to be onto something. Thanks for these videos!
Are you trying to show us how to make Pyrimethamine to get back at Martin Shkreli for raising the cost of Daraprim? If so, I think this a wonderful project you're embarking on. You rock.
+Luck Bull-fucking-shit. Martin Shkreli is a douchebag, and while I agree that the scientists who create life-saving drugs should receive their proper due, more people are affected by the rise in prescription drug costs than just those without insurance. What about those *with* insurance who can no longer afford the medication? Should they just fuck off and die? What about people on Medicare for whom these drugs are not covered? Should they just fuck off and die too?
+Luck What the fuck are you talking about? Do you really believe this?
+Luck Actually you're the one who should do some research. The drug was patented in 1951 (I actually looked up the patent myself to direct my synthesis). The patent long since expired and there is NO "legal obligation" to make the scientists any money... most (if not all) of whom are already dead. Martin Shrekli wasn't even born when the patent for this drug expired and yet he gets to decide who should pay for it and at what price? How about NOBODY pays more than the cost of production and everybody gets a life saving drug because they need it? Sounds a heck of a lot better to me. The scientists who created it have already been compensated during the original patent and even if they weren't, there is no legal obligation now that that patent has expired, and even less of a moral obligation since they are all dead.
Additionally, why is it that the insurance company has to pay an unfairly high price? Just because they're insurance companies? Guess where the costs go... to the people that pay for their insurance. So Martin Shitface is still stealing from the people. If you're so up on your high horse that the rich should pay to the poor then Martin Shkreli who is a millionaire and also a CEO (or was) should himself be forced to pay.
Shaving profits from an insurance company is itself not a justifiable reason to raise prices on them. NO ONE, rich or poor, deserves to have money taken from them just because they have money. How would you feel if the bank called and said "Your bank account is too large, so we've taken out most of your money."
Meanwhile, a scientist like me who spent decades of his life studying this stuff and actually trying to make a difference in the world through brute force research and hard work gets paid less than even a low-level exec. If high drug prices are supposed to be good for scientists then where is my fucking money? I don't have any so i guess drugs must be cheap... oh shit! they aren't! What's wrong with this picture? Martin Shkreli and the unfortunately large percentage of CEOs just like him are what's wrong.
+joemonster55 If there is no fiscal reward for creating such drugs, what future scientists will endever to creat them?
+RagingDong Martin Shkreli is not a scientist, he did not create this drug nor is he compensating those that did... primarily because they're all dead of old age. The drug was patented in 1951 and has long since expired. The original creators had ample time to profit their creation. This argument "for the scientists!" is moot because they already had their patent and they are now dead.
That looked so much like delicious chocolate milk at 8:00
FayzK that's more like delicious liquid cancer. But, although toluene is highly carcinogenic (and chlorotoluene is even worse) it has a pleasant sweet-minty smell.
Really fantastic video, thank you.
Your videos are highly appreciated! thank you :)
6:44
that's a strange way to make a latte
Excellent vid - thanks!
You should write a book on chemistry. You have a lot of knowledge and it would get you a lot of money for your videos.
This
Was
Awesome
Thank you :-)
I think the reason direct tcca reaction works best is due to the size of the electrophile’s leaving group (cyanuric acid), which makes substitution in the ortho positions a little more sterically hindered. Nevertheless the 2:1 ratio of ortho to para positions means the ortho isomer is inherently favored.
Hey, awesome video!
Very interesting. if I had the resources to do this I would totally try.
A use glass tubing B that is so overcomplicated you can also use bubbling chlorine gas into toulene and reacting it with a mercury vapor light C you can use Benzyl alcohol and hydrochloric acid and reflux with boiling stones to make benzyl chloride or other words Chlorotoulene
Wow its been a minute seance you uploaded a vid man!
my class did an endothermic reaction it was fun it was yeast peroxide and water and dish detergent
Very interesting videos. Please keep up the good work.
Could you please use structural diagrams as trying to work out what C3N3O3Cl3 etc. is is tricky while watching the video.
dont think like that, u are really great
NR, I will watch any science video you make.
i understood about 5% of that.
well played NR.
lolol
Every year you should make a video that compiles all the footage of the messes you have made that year :D!!!
The experiments for this were that expensive?!?!? :O!!!!!
i whish you would show more of the tries when it doesnt work or something goes wrong, could have made one video twice as long. that woukd be great. what you think is just boring, we love to see, maybe something to think about. Love your content btw!
great video as always. pyrimethamine's an interesting target!
our you going to show how to separate the para-chlorotoluene and ortho-chlorotoluene in a future video?
What company did you send your samples to? I was looking for a NMR company for a research project for next year
what is that stir bar made of? it seems it is very non-reactive
+BlueBeamProductions it's coated in PTFE, also known as Teflon.
Do you use the same vacuum grease you showed in your lab equipment video when distilling/refluxing solvents like toluene ?
Please do make a video on anhydrous ferric salts
Wondering if a similar setup could be used to make CCL4 ?
Which of the multi-step reagant would be difficult to obtain?
can i use any catalysts instead of steel/iron chloride maybe ticl4,boron trichloride,benzoyl peroxide,aluminium chloride,iodine-precatalyst, peroxidisulfate or tatp
are alternative chlorinating agents usable maybe tcca , iodine trichloride ,hypochlorite, chlorine dioxide-probably no,or chlorosuccinamide
Would using bromine and (with Ferrous bromide catalyst) work better to make the para-product? because the larger bromine atom would have more stearic hindrance in the ortho position than chlorine would, I thought that might increase yield of para-prodcut.
Or course, getting bromine would probably be more expensive. . .
Or high temperature pipette tubing ( glass) can be used to prevent melting of the tubing.
Could you add a directing group like SO3, then use steam distilation in conc acid to remove them? I've used this method to make 2 nitro resorcinol
Hey ! Can i have the procedre for the 50% H2SO4, TCCA, Toluene method?? i need to make some o-chlorotoluene - so this is perfect!
Nurdrage can chlorotoluene be used as a solvent like toluene? Or does the chlorine atom interfere?
Do a video about creating plated through pcb vias
Any chance to make a video about formaldehyde by some oxidation of methanol?
hi guys, i have an easy question, how did you connect a type K probe to your 3-way destillation adapter? what did you use?
i want to use high accuracy temperature electronic thingy (you can get it on ebay...with arduino (it's 1-wire protocol)
i don't need high accuracy but i like good and cheap setup
if you used testtube or so, how you made sure the thermal-contact was correct?
i'm from germany so any idea where to get it? i know you germans are reading this :)
I heard you can put TCCA and toluene in dichloromethane and that will do chlorination much more easily but you need a protic acid to start the reaction.
What camera do you use?
Any idea of a synthetic route involving FRS of the methyl group to BnCl, followed by getting it some steric hindrance, such that the Cl will sub on the 4 position instead of the 2, and then removing the bulky group later? Just wondering if it's legitimate...
@3 mins
Would having base present to protect the hose mess up the reaction? My organic chemistry is super weak (I'm more of a solid-state crystal-engineering guy) so there's probably something obvious I'm missing (like reacting with FeCl3?).
edit: but then you could probably just use a weak base like bicarbonate...?
BTW I'm definitely interested in how you would make anhydrous FeCl3 but I'm interested in all of your videos. Cheers
You're doing God's work my dude :P
It would be fantastic if you showed how to make anhydrous ferric chloride!
is it possible to separate cl-toluenes by freezing?
You might get more traction with your fundraising via bitcoin if you just stuck your wallet address in a QR code on the outro screen somewhere. A majority of bitcoin users now use mobile wallets for most of their transactions and (this is the part I may be way off base on) I don't think you videos are the type of videos most people watch on a mobile device. So scanning a QR code with our phone camera is a lot more convenient and thus more likely to be acted upon.
A single wallet you reuse a lot to receive funds is not ideal for security necessarily, but for the purpose of getting donations it works, is efficient, and is very low risk overall.
Yes indeed what he said ! Good luck .
Could you explain why is your major product ortho-chloro-toluene? The reaction suggests that the para position would be favored, as it has no streric hidrance whereas the ortho positon has the methyl right beside each carbon in the ring. Thanks!
For the nitration reaction in the synthesis you showed in the last couple seconds of the video, why does the nitro group add para to the methyl group? Is it because of the inductive abilities of the methyl group? Does it create a partial negative in the para position that allows it to be nucleophilic towards the positively charged nitronium ion?
Love your videos! Will be donating soon! Thanks!
Effectively, yes
dude you're a badass
Wouldn't the dissolved tubing add impurities to your final product?
I read some patents that say the catalyst makes a difference to the ratio. Apparently SbCl3 better favours p-chlorotoluene.
How much chlorine canbe absorbed by toluene at a time or what should be the flow rate of chlorine in this expt
It's been a long long time since I did organic chemistry but I wonder if you could improve your yield of the para product by using a different starting compound. If you could transform the methyl to a t-butyl or some other bulky group I'd guess you'd get a lot more para product. Obviously you've got to then get rid of the protecting group but it might be a way of improving your over all yield.
Is there a reason that the o-chlorotoluene is preferentially produced over p-chlorotoluene? Looking at steric effects, the para form should be the major product, and in terms of electronic effects (resonance/electron density distribution of the transition state), wouldn't the ortho and para forms be nearly equal (in terms of transition state)? Was just curious since the textbooks that I've read have usually stated that the para product is the one that is preferentially made. Thanks!
The reason is simple: There are 2 ortho positions, and only one para one. If there were no stearic effects, it should substitute at a 2:1 o:p ratio. Stearic effects are actually small, since methyl is a small group, so 60:40 is very reasonably expected.
How about reacting hydrochloric acid with p-cresol? I think this may work too.
Hey Nurdrage, long time watcher. I was just curious as to why you are trying to make pyrimethamine in an amateur laboratory? Is it just a goal you set yourself? or are you attempting to independently come up with a low cost synthesis?
+OrgoOgro I think is a response to that fucker who raised the price of the drug
I cannot help but notice your complete aversion to column chromatography. Back when I was working in an organic chemistry lab, column chromatography was probably the most significant purification step we used. I mean sure, proper TLC plates are a bit on the expensive side and one can use up a lot of solvents, but usually solvents can be redistilled.
could you try photochlorination of toluol in the gasphase?
A reflux setup with uv-lamps and heating according to the boiling point of the different chlorides should yield relative pure products in theory.
Is there a difference between 4-chlorotoluene and p-Tolylchlorid? is it the same molecule?
could one dry the Cl2 with dry CaCl2?
Wholly jebuuuusss, you have been reading my thread on science madness (I think) I feel importantish :)
How do you intend to synthesize the acetonitrile from this, also you should do the guanidine and triethyl orthoformate syntheses on your channel that would be awesome. Could you perhaps use N-chlorosuccinimide or N-chlorophthalimide as a chlorinating agent to get the para chlorotoluene due to the steric crowding, or does using a halogenating agent such as these change the predominating position at which it would attack the ring?
+jared garden Pretty sure he's already done the trimethyl orthoformate synthesis video.
I would like to ask, if anyone knows:
Would and ice batch in the second method help to cool an exothermic burnout?
Also could we use a separation funnel so we would just drip drops into our solution?
TCCA is solid!!!
he said that water messes things up
i think ice bath should help a bin...if you don't have much time you can use it
+mattibboss thank ya
How much does it cost per sample to get it nmr tested?
Maybe you can increase yield of p-chlorotoluene by lowering temperature of reaction?
Steel wool is lightly coated with oil, it's best to wash it before using.
@Gerry Murphy
True, but when I make Ferric Acetate, it's help for me to know.
Does the water not react with the c-cl bond? I thought washing with water would convert the product into an alcohol like it does with other chlorides.
Depends, usually you need an alkali hydroxide like sodium hydroxide forming NaCl and the alkyl/aryl alcohol, some work with water tho
Some feedback: It would help if you showed the structures rather than just the formulas when you talk about reactions. I had to google trichloroisocyanuric acid, for example.
Could you demonstrate the different operations of a Dean-Stark apparatus?
It may be very simple, but it's interesting. Especially since the Dean-Stark apparatus you showed here seems completely different from the Dean-Stark apparatus mentioned in my introduction chemistry course (university level). It was only mentioned briefly there, but that version seemed more like an overly complicated fractional distillation setup. Yours seems to fill a purpose. I'm overcome with curiosity.
+R Johnson I have a whole video on my channel on the dean stark apparatus. czcams.com/video/jxgpLp279Yc/video.html
NurdRage I missed that. Thank you for the link!
Did you try turning clorobenzene into paraclorotholuine or using cloroxylene instead of clorobenzene?
8:08 that reminds me of hot chocolate... Btw great video NurdRage!
How does the NMR tell you the ratio of the two isomers? Wouldn't you need to use other methods like liquid-gas chromatography?
+Collin Bardini The para- chlorine is more upfield (to the right) than the ortho- chlorine isomer. By the two peaks in the spectra you can determine the ratio of each derivative. The results show 0.70 signal of para- to every 1 signal of ortho- isomer so there is no need for any other method of analysis.
+Collin Bardini Integration of each peak will give you the area under the curve. Modern NMR software can easily be used to set an integration value to a peak. Every other peak will then give a value relative to the set value. This value directly represents how many protons (For proton NMR that is) are contained in a given peak.
p-chlorotoluene has symmetry around 1 axis and will give two doublets. Peak splitting is caused by through-space magnetic interactions called spin coupling. The ortho substituted toluene will not have any symmetry and should give two doublets and two triplets. Now all you have to do is pick a peak, integrate and set the value. The doublets will have integrations of 2 protons each for the para isomer. This number compared to the integration value for any peak from the ortho isomer will give the correct ratio of isomers.
Vincent Martinez +T. B Thanks guys! I appreciate the responses. We actually covered this today in my O chem class when trying to find the ratio between hofmann and zeitsev products via NMR.
p-chlorotoluene has a Much higher melting point than the other two. Why not chill the mixture down to solidify out the p-chlorotoluene or freeze all of it then slowly bring it back up until the other two melt and seperate it? Would that be effective?
+Everett McGee no
+NurdRage: I certainly would agree that most solid/liquid fractional separation methods yield low results in the manner being described initially; but I had been intrigued by the idea of it and continued digging, and recently came across a US patent from the early 1940's (US 2296458 A) which outlines an emulsion suspension facilitated method used to successfully separate many organic mixtures of plant oils into their essential components, based on differences in their melting point. The patent goes into reasonable detail and includes a diagram of the apparatus, it may be of interest.
You havent tried non-iron catalysts like AlCl3 or ZnCl2?
+Marcin Goławski It will happen slowly with Zn, it gonna form weaker lewis acid ZnCL2....
Paradichlorobenzene in mothballs might be of some interest to you. I have no idea what that interest might be. The dollar store has it falling off the shelves usually.
is my drain cleaner sulfuric pure if it is clear? It says 93-99% concentrate sulfuric acid
The buffers used don't affect the color of the sulfuric acid.
Is it possible to separate them by cooling it? 4-chlorotoluene has a melting point of 7°C vs 2-chlorotoluene with the melting point of -35°C
+GingyPno123 no. Freezing point depression takes effect and the mixture remains liquid even down to -10 C.
+GingyPno123 ????? no? they just melt together.
Could you also generate the chlorine through electrolysis of salt water?
+Impossibear Yes you can, but you would need more complex hardware to separate and collect the gasses.
We want to see how to make anhydrous ferric chloride!
Woah
some sources say that the p-Chlorotoluene has a melting point of 7°C and that the other isomers around -40° shouldnt crystallisation by freezing be the simplest way of separating them?
+Dalitas D I assume crystallization would trap some of the unwanted isomer and isn't so much an easy separating technique rather than purifying technique.
I think chromatography is the way to go, here. Possible silica column, reduce vol + wetload and elute? Not sure, guess we'll see!
+Dalitas D unfortunately no. Freezing point depression takes effect and the liquid remains liquid even down to -10 C.
+NurdRage ah yes of course, it's never that easy, is it?
hell I've even done work about that haha
how do you know if you only have 2 or 4 chlorotoluene instead of 2,4 dichlorotoluene and 2,4,6 trichlorotoluene
boiling points.
Nurdrage full chemistry course. I'll donate an initial 50 cents to get you going.
Dam I got excited when I thought the title said "Make Chloroform".
He does that in another video
I am interested