Separation of chlorotoluene isomers (para and ortho) 2nd step in making Pyrimethamine
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- čas přidán 5. 07. 2016
- In this video we show how to separate the isomers of chlorotoluene into para and ortho components.
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As I become to understand organic chemistry more and more I have discovered your a damn genius in synthesis routes. Anybody can synthesize something from a lab supplier but it take a real genius to experiment with at home chemicals and come up with there own method. This is beaitiful.
That's the difference between being a chemist and being a chemical engineer.
I agree! This guy is a genius. I think he looked at the Pyrimethamine molecule and used some retrosynthesis magic on it to come up with his own pathway. I only do chemistry as a hobby, but I hope one day I get as good as this guy!
This kind of shit was the exact stuff they tested me on in college orgchem. The hardest problems on the test by far would be questions like this:
*Shows some really complicated molecule*
“You have access to benzene and any organic chemical with 3 carbons or less and any reagent or catalyst you may need. Show a complete scheme to make this final product with each step and reagent detailed.”
It REALLY pushes both your knowledge of common organic reactions and memory of what reagents do what.
I just wanted to say thank you. Your channel got me interested in chemistry back in '09 during high school, and I finally got started on my bachelor's degree (and master's eventually) in chemical engineering!
Let's hope the next steps are a lot less arduous and messy
Sure hope so
After watching this, i started wondering if it is possible to use this method to separate xylenes?
They won't be, but neat vid, man.
NurdRage, what do you think about Cody's Lab latest video where he shoots mercury bullets inside of a private mine? I really like the guy but it seems kind of a dumb shit to do and you are kind of the voice of reason so your thought on that would be appreciated!
NurdRage this is very noble if you are doing what it looks like all my chemistry is used for evil though.
I'm an EE and I have No idea what's going on, per usual. But I still love watching your videos, guy.
Same.This chemistry stuff is beyond me,so I'll stick to pixie-wranglin'. Still love it though.
+PhattyMo you must do a pretty skookum job at pixie wrangling
I can't wait to see the end result. Watching these videos are immensely satisfying.
This video went over my head. Congrats! :D Usually I can follow everything you say and do but this one was tough.
I cringed when i watched the black gunky sulfonates coat the insides of your distillation apparatus. Not fun.
Great video NurdRage!
keep up the good work! i really want to see your success in making pyriethamine
I was looking for a good way to separate ortho/para-toluidine, i think this freezing method will work with that as well. Thanks for sharing!
I never have any idea what you're saying but it's cool to watch these reactions and your voice is funny 😄
Very nice video! Almost reminds me of the time you made Luminol!
I was making Dioxane with antifreeze and sulfuric acid and I got the same black boil-over but mine went into a graham condenser and it fried the condenser.
Literally never understand a single thing you are saying but still love the videos
Anyone else like listening to these as background noise? I occasionally tune back in until he says something I can't understand then fade back out again. Very soothing.
why in gods name do i enjoy these videos? i barely graduated high school! Im too stupid to know anything beings said. i get like 1 ou7t of every 10 things described.
BUT....its still fasinating.
Same here. I graduated college at least but majored in nothing to do with chemistry. just when i think i grasp simple chemistry, him or "nile red" comes out with a video and im like wtf is going on. I know what trinitrotolune is, but what is has to do with Chlorotoluene , i have no idea
Watching science is cool. That's why.
Toluene is a common name for a benzene ring with a methyl group substituent. Trinitro- means there are 3 nitro groups on the benzene ring (in addition to the methyl); chlorotoluene has a chlorine substituent.
Hi, love your videos. Do you think it is possible to pre separate (mb even fully separate with washings?) the products using the different freezing points?
Excellent video! Was not aware of this clever method of separation. Interesting that freezing out does not work at all. Wonder if it could be possible to effect crystallization by adding a 3:d solvent to get a more dilute solution and perhaps allow crystals to form. I have used a household freezer for similar and found that the thermostat is adequate for temperature control, it just takes a long time to settle. Another lab tip for this is the small ice cream making pots for household use. They are insulated and use a salt to keep low temperatures for many hours. The one I found is 20cm dia and has a teflon coated inside.
"Clever method" is his middle name
Would converting the orthochlorotoluene sulfonates back to orthochlorotoluene under reduced pressure decrease the temperatures needed enough to avoid some of the decomposition reactions?
So cool to see all my abstract learning become physical. Toluene is an orthro/para director because of methyl groups ability to hyper conjugate and form a better set of carbonation resonance structures to support the positive charge. Thus, the mixture of two ismomers..That's what I got from my orgo class at uni anyway...does this sound right?
Yep sounds about right.
Quick question, does the directing effect of the Cl on the ring not effect the placement of the S03 group? Is sterics just way more significant?
Like the EE guy, I'm physics and I have no idea what's going on but KEWL and keep it up.
Could the sulfonated Chloro-Toluene not be precipitated by adding base?
Would it be any easier or possible to start with the chlorination of benzene and then methylating the chlorobenzene?
I wonder if freeze distillation would work for this mixture?
9:07 Though wouldn't saving it still be useful for later runs?
Can you do a video about the extraction of pure barium nitrate from sparkelers
If a lot of decomposition is occurring at the hot distillation step at 10:20, would steam distillation allow recovery without as much decomposition?
What exactly is the red stuff in the sulfuric acid?
Could you make a video of creating synthetic opal
Is it a friedel krafts reaction?
Hi nurdrage, I know this has nothing to do with the video, but if one uses platinum electrodes with a magnetised iron core and run electrolysis through them, will it then make more energy aka. make more hydrogen and oxygen, then is required for electrolysis?
Could you do a video where you separate aspartame into phenylalanine and methanol?
Could the difference in freezing points be used to separate the isomers?
Freeze the mixture and thaw till one isomer liquifies?
Given how much work this was, wouldn't column chromatography be a faster and safer alternative, with a better yield?
That overflow is why you need that borescope? :D
I have been looking forward to this video for a while. (He says writing the comment before watching...)
Will this method be suitable for separating xylenes? (Ok, I'll watch it now.)
Hey NurdRage! I absolutely love your amazing channel, but why did you use sulfonation instead of crystallization? The melting points of o and p chlorotoluenes differ significantly, so crystallization might be a viable option.
As shown in the video it doesn't work. The mixture remains liquid when there is a lot of the o-chlorotoluene.
please make a video about synthesise cryolite from flourite or make a video about making pure aluminum oxide
nice!
Could this work for xylene?
Organic chemistry, the discipline of making tar, and a small amount of useful product.
Can you please show how to make crystals of ferrous sulfate?
Hello Nurdrage,
I'm trying to isolate some bitumen from a piece of asphalt.
Using hot water made it soft, but it didn't separate from the gravel.
Acetone doesn't seem to work either.
Do you have any advice? (with household chemicals?)
Thanks
Hexane or toluene?
What's nuclemanecresin spectroscopy?
Hey nurdrage,can you do gallium vs molten alluminium plsssss
Your voice remind me if handal from thor lol xD great video
I was with you up to "hello fellow nerds".
You can't use fractional distillation under reduced pressure?
nope
The chemistry of this is beyond me, but I enjoyed the video nonetheless.
I wonder, would you send your final pyrimethamine product to a micro biology lab to test if your product is pure enough to kill some protozoa?
i would but i need to find such a lab that would be willing to collaborate.
so once you make the Pyrimethamine, are you going to make some methamphetamine?
Well done. I think I'm starting to see why some of these new fangled drugs cost so much. The R&D to come up with this stuff must be somewhat akin to banging one's forehead against a stone wall in an effort to knock down the pyramids of Giza. You don't even know if you're banging your head against the correct wall, let alone what combinations of thrust vs. parry will actually knock down the structure.
this is the first video of yours that i did not understand... i failed Orgo in college
Why you didnt just freeze the isomeric mix? If there is such a huge difference in melting points, you could be able to just separate them as with nitrotoluenes. Freezing and filtering the para isomer.
right now are you just synthsis the reagents for pyrimethamine? when will you actualy make this drug?
He'll make it when he has all the precursor chemicals he needs to make it. I personally don't know what all he needs (because I don't know what reactions he's going to do in the synthesis of it), but a lot of them seem to need multiple reactions to create and purify, and he wants to show each step, so we get a lot of individual videos that go into stuff like separating isomers.
The synthesis of the para- chlorotoluene can probably be considered a starting point for the actual synthesis of pyrimethamine - it starts the structure with the chlorine hanging on one end of an aromatic ring and a carbon (albeit bonded to three hydrogens) hanging off the other end - that carbon will end up as part of the second aromatic ring.
ok thank you i got it
Next will be the converion of this into a benzyl halide, most likely preformed by some radical method. Of which the benzylic halide can then be displaced by cyanide. Condensation of this benzyl cyanide with an ester of propionic acid and another condensation with guanidine furnishes pyrimethamine if all goes well and my scribbles are sensible.
my first (naive) thought prior to watching the vid would have been some sort of fractional crystallisation; is this not an option given the difference in melting points? great vid as always ^^
maybe not practical with the very low melting points of the mixture
They dissolve too well in each other. I found that they either don't freeze at all, or freeze completely.
I might have better luck if i had a precision temperature controlled freezer so i could say set it to exactly --5 Celsius or similar. Even if i did, this stuff will melt again very quickly on the warm filter paper. So i'd have to temperature control that too. It's so much hassle to get fractional crystallization right when working with sub-zero temperatures that i didn't bother. Sulfonation is rather laborious and messy, but also very forgiving of errors and robust even if you samples full of impurities and contaminants.
Column chromatography helps in those cases :p but still a lot of solvent and work involved not to mention TLC plates :(
Timothy Morrison TLC plates = cancer
3:59 im no chemist (unfortunately), but those molecular diagrams seem odd... The two bonds right in the center of the benzene ring - is there a name for that kind of bond?
It's a shorthand way of representing all compounds with R functional group in any position on the ring. Basically, instead of drawing all combinations of the diagram with the chlorine and sulfonic acid groups in different positions, you can just draw them sticking out of the center.
@@SignalDitch Thanks! I forgot I left this comment and had the same question again, lol. So I Googled it a little harder and found a Chemistry Stack Overflow post that I think has the same answer: chemistry.stackexchange.com/questions/114602/for-a-benzene-shown-in-a-skeletal-structure-what-does-a-substituent-to-the-cent
Thanks for posting an answer. Usually my questions go unanswered in YT comments.. haha.
@@SignalDitch Hah... Found another SO thread with the same question, and this one even has NurdRages video in the screenshot to the question.. lol
chemistry.stackexchange.com/questions/54765/structural-representation-of-substituted-benzene
Could you make Chlorine Triflouride? I'm interested in seeing how it reacts with different metals, glasses, and salt.
Not only that but it's almost asking for NurdRage to potentially kill himself.
isnt that the gas that spontaneously combusts in contact with air?
I was joking, even the nazis were afraid of that shit.
It's likely, yes, since fluorine is a very "greedy" element, stripping some of the electrons from other elements it comes into contact with for it's own.
NurdRage=HowToBasic Confirmed
If the freezing point of the two isomers is some 42C apart, why not separate or at least enrich the mixture by fractional freezing? In the colonial days, some settlers made a drink called apple jack. It was hard apple cider that was partially frozen and had the water ice removed, enriching the remaining liquid in both un-fermented apple cider and ethanol. I believe around 35% ABV was relatively easily achievable. Could you use an apparatus with dry ice and variable insulation to try to keep the temperature around -10C or so and remove the p-toluene solid? Seems like it could be cheaper, faster, and more simple then all this acid and boiling.
doesn't work
Why?
Good question. I'm not really sure. Just when you freeze them they don't solidify to start the separation.
Regardless of their melting points, the p isomer is still soluble in the o isomer.
Usually I can follow your videos pretty well, but here you lost me.
hey can you show how potassium is made chlorate or perchlorate I don't care all I know is it was some electrolysis reaction. I know it can be used for bad stuff so just leave some steps out so no one can follow how you did it.
I'm curious why you didn't use the difference in melting point of the two isomers to separate them. Even if that didn't get you perfect separation, wouldn't that have let you get better yield with further processing?
Because they don't separate, they freeze completely or not at all.
For a second there I thought NurdRage was asking himself a question XD
+NotSoLogical same
About how long did this project take you? seems like she took some good man hours.
I'm a noob at chemistry sorry, but why was there no meta form present in the isomers?
is unstability the only reason?
He originally made the chlorotoluenes by chlorinating toluene. Toluene is a benzene ring with a methyl group attached, and the methyl group is what's known as an ortho-para-directing substituent, meaning that chlorination of the meta-position is highly unfavored and the reaction will pretty much only yield para and ortho.
The reason for this is kind'o complex, so if you want to know you should read about "directing effects in electrophilic aromatic substitution" =D
TheySmashedAnHourglass can we say that its due to absence of resonance at meta position?
yep. on toluene it´s a bit hard to see why, due to it´s positive inductive effect, but if you took phenol you´d easily see the resonance structures. (well the phenolate anion is better for demonstration purposes.) you´ll see that the negative charge will always land on either an ortho or the para position due to conjugated double bonds. that´s the mesomeric effect. the one that´s easy to see. inductive effect only lends electron density to the ring not an entire pair of electrons, but the rules remain the same.
that´s why chloro toluene has no meta form. there is no stable meta-form if you have any positive effect on your system. you´ll see why if you let´s say try to draw nitro benzene. that´s a meta dirigent as it takes an entire electron pair out of the ring. and in that case the ortho and para positions become inaccessible leaving only the meta product
Basically the methyl group isn't strongly electrophilic and more freely gives up electrons. The aromatic ring is electrophilic because the negative charge which would be caused by it taking in another electron is stabilized through resonance. An electron is "taken" from the methyl group, and an observation of the resonance structures produced shows that a negative charge centered around the p- and o- positions is much more stable than one centered around the m-positions in this case. The electron-rich aromatic ring then reacts with an electrophile such as ferric chloride to give up its extra electron. This involves a few steps, but leaves neutral chlorotoluenes.
The methyl group is an ortho para director. This is due to electronic effects. Looks up "electrophilic aromatic substitution"
The ortho is more favoured than para. This is because methyl group donates by inductive donation which is a weaker form of electron donation than lone pair resonance. Normally the para position is more favoured to do steric effects (getting new substituents away far away from other ones makes less repulsion between groups) but in this case the ortho is favoured because there's not as much electron density reaching the para position as there would be if there was lone pair resonance
I have a few personal question about chemsitry and I could use some help, do you have an email address I could contact you at?
Winston, is that you?
This man graduated from wizard school
you should do a video where you expose pork (with the skin on) to various acids.
You should check out Nile Red's videos. He has a few videos that are just like this!
bluesun128 including of course his own hand
This has nothing to do with the video, but I don't know how else to contact you. What ways are there to obtain pure, or relatively pure, iron? I don't have many chemicals. However, I do have the ability to work with very high temperatures. Because of this, I thought of a thermite reaction. If I did a thermite reaction, would impurities in the iron oxide be removed or transfered into the final iron? Also, what steps could be taken to prevent the iron from oxidizing and carburizing as it cools to room temperature? If there are any other relatively simple reactions I could do instead of a thermite reaction, I would really appreciate a pointer to it. Again, sorry for being off topic of the video, and if you have an email that would be better to discus this, I can move on to that.
+Quimica Ciencia Thanks! And if I did that, I could melt it down in more controllable conditions. Finding a crucible for it may be difficult, since carbon would migrate out of one made out of graphite I assume
Ah, be careful of oxidation though!
+RagingHammer Oxidation during electrolysis? While it's in the furnace I could keep oxygen out without much issue
how about a ceramic crusible? or maybe a clay one? graphite is obviously out of question.
Electrolysis is kind of super inefficient, so maybe it's better to just disolve steel in some acid and then see what can you add to make the iron presipitate. Electrolysis will work but it will take a lot of energy nd be super slow. Tried making rust like that and it takes forever.
+Laharl Krichevskoy Ceramic is what I thought of too, I'll have to look into them. I like the acid idea. If I dissolved low carbon steel in HCl, would I be able to precipitate pure iron out? Or would it come out as low carbon steel again?
what is this used for?
Making a drug called pyrimethamine
+The Chemistry Kid damn what is it similar to?
+Keani Lee it is used to treat AIDS, it isn't used as an addictive drug
+The Chemistry Kid ok that's man
+99 problems he said in one of his Q&As it is an antiprotozone and AIDS treatment
Do you use a voice changer?
Yes
i always thought "melting point" would be more accurate than "freezing point" because of the possibility of super cooling.
Hi
I know some of these words
have you ever made psychedelics ? by request? for the sake of science? :D
amazing video, but I think this experiment is a bit too long for me.
wow at 750 a pill you are gonna be rich!
The point of him doing all this isn't to make money. It's to get back at the company that is making this drug and selling it for such a ridiculous price, by showing that almost anyone with knowledge in chemistry can produce it for relatively cheap with chemicals that are readily available.
Sup😁
why do you use a voice changer on your videos?
i dont think he does
He most certainly does, and unfortunately I think it makes him hard to understand sometimes.
Coment #8
Quick question: *Are you Iron Man?*
18th comment
FIRST
nurd was first 😂
3 minutes late bro! ;)
phew made me thirsty
boy that was a lot of info lol
sofa
here's a crazy question - WHY are you trying to make Pyrimethamine? just for fun? :-D i know it's been involved in the scandal where its price rose by 5000%
I believe he is making it because of the scandal but not 100% sure
yeah, he said that in a previous video
well that's the thing - he DIDN'T! :-D I believe there are only 2 videos in this series on making pyrimethamine: this one and the one (=step 2) on sodium cyanide (=step 1). It's not mentioned in this video and I watched the NaCN video yesterday and he doesn't give any reason there either! that's what actually led me to post the question in the first place... is it in yet another video?
+Jan Simacek He did once mention thst he was trying to make pyrimetaminr because some "jackass ceo jacked up the prices"
I know you get this many times NurdRage, however I do have a critique. The Voice Modulator. Your videos are full of really cool and exciting content and some of it can be very educational. however sometimes its hard to both understand you, and to get engaged in your content. Perhaps it may be helpful to maybe tune the Voice Modulator a little bit, not to damage your anonymity, by completely turning it off, but maybe so you sound more clear. For example, anyone who may not have English as their first language could perhaps have issues understanding your content at all. Maybe you could change it to widen your fan base? However, Again this is just some constructive criticism that i think would greatly improve your channel and also improve how your information is transferred to the viewer.
Always making carcinogens
Make methamphetamine :D
then some Lysergic acid diethylamide, i heard that is quite the chemistry process.
LSD making is really interesting. But it wouldn't be great for a video because many steps are light sensitive and you need to do it in darkroom. I recommend reading Practical LSD manufacture by Uncle Fester. And while you on it you can read Secrets of methamphetamine manufacture (also by Uncle Fester)