Ethanol is one of the few solvents that's not only safe to drink, it's actually fun to drink. The German Bad Guy Party had to go to great lengths to prevent their rocket scientists from drinking their stock of rocket fuel.
The crazy part about that Russian/German soldiers drinking rocket fuel thing is that them switching to methanol to "fix" the issue didn't immediately slow them down outside medically.
A compilation of these guides with a classification system for the various advantages and disadvantages would have been a great asset to my lab days. So much of this is not taught and just learned the hard way or by lab tribal knowledge.
As a pharmaceutical process development chemist, your solvent list is one of the main reasons why so many of us are needed. The toxicities of many of your favorites preclude using them anywhere near the end of a Active Pharmaceutical Ingredient synthesis. Sometimes, the R&D scientist needs to consider the downstream implications - will your product have any potential use in humans or animals??
it sucks because some of them are such good solvents - HFIP will be realized as likely the best solvent in chemistry unless a better fluorinated alcohol is discovered, but it is super toxic, and almost impossible to get rid of every last trace of it - amazing solvent though.
Also this isn't related to your comment, but I would absolutely LOVE to make a video with footage of a process development lab - maybe after >6 months or so. As you highlight, most researchers aren't aware of what actual process chemistry looks like, and I would love to help bring that world to chemists everywhere
@@That_Chemist HFIP (1,1,1,3,3,3-Hexafluoropropan-2-ol) isn't that toxic? I can name 5 solvents I use daily that are orders of mangitude more acutely toxic.
@@That_Chemist Problem is that most of us in R&D are so focused on that, so even if we have an understanding of what goes on "downstream" in precess chem, it rarely enters our mind. Not meant to sound careless, that's just the reality of things - it is also a matter of workload. As in your example with HFIP. What should we use instead? Not much comes to mind.
Ethyl alcohol by far is the chemists friend. Organic solvent for my first lab experiments. Potable at my professor's (lab) group meetings at the local tavern. Several of my chemist friends brewed beer, etc. My first training on GC was determining ethyl alcohol % in beer.
I get to work with dichloromethane. It's pretty cool, we use it to dissolve polymer residue. The big drawback is that it dissolves nitrile gloves. Luckily it is not too horrible.
It's an alkylating reagent, which unfortunately isn't recognized by most chemists. It reacts with amines, even tertiary amines already at room temperature and my guess ist that is is probably rather carcinogenic. But industry doesn't want to see this... .
I work with it occasionally, either repackaging it or blending it to make wood stripper. It can cause burns, but it also evaporates super fast. Also it smells good, not that you should be smelling it too much
An idea for a future episode: can you explain the 5 most complicated reactions you have done in your career? Like reactions you have done with very sensitive reagents or which had a very advanced work up. Especially these that can only be carried out upon complete oxygen and moisture exclusion? Would be highly interesting
When I selected solvents for commercial production I had to take all those other factors into account (tox, enviro, emissions, fate in ground water etc.). The guys in the plant were always pleased when I rolled out a new project and the solvent that smelled good. With those criteria in mind Tert-butyl alcohol had good acceptance. DMF was hated. Since our reactive byproducts were water quenched it was always important to have a good quenching properties - boiling point, density, and not emulsify. Alkanes were the best by those criteria, alcohols and ethers were not. Trace THF in water makes the mixture flammable so that complicated downstream designs. Heavier that water solvents were more or less banned from consideration due to the nightmare of dealing with those in ground water. Good review- Loved it! BTW - I'm racking my brain - one time we toll processed something in a solvent that had a warning that it could cause testicluar atrophy - it will come to me eventually.
16:53 Oh my boy DCM. Once I did a synthesis of a TMS-substituted ester, which entailed wrestling for two weeks with the purification process. In one of the many (flash) columns attempts, I was looking through NMR data of the eluted fractions and scratching my head as to where the hell did the product go - as it turned out the target ester (and a lot of residual palladium) was stuck at the top of the sillica column, not budging one inch in the flow of hexane eluent. After washing it out with DCM and running several more columns with DCM-based solvent mixtures (including perhaps three dozen TLCs to test them out first) I finally got my compound. This one occasion also refreshed my appreciation for solvents that don't boil at r.t. and drip out of the pipette I'm using to pick it up - DCM and Et2O were assholes to handle, but at least they were easy to rotovap. Also shout-out to DCM's 1.33 g/ml density. Having the organic phase be heavier than water is such a pleasant property to work with in solvent extractions.
I use THF at work every day. One time I was working near someone who was using it and didn't have my respirator on. The venitlation in the building is excellent and I was several feet away, and it still gave me a headache and made me feel a little sick for the next couple hours. Always wear your PPE when working with or even near hazardous materials.
even if some of the specific opinions make my head spin, your tier list videos are my favorite of your content (which is saying something, bc your content is generally great) and one of my favorite pieces of content online period! thanks for the good work!
I love all these tier list videos you make! They’re entertaining to watch, and I can follow along decently okay, even as someone whose formal chemistry education ended over a decade ago, in high school, with AP Chem. (Btw, we had an amazing class with an amazing teacher; I don’t doubt we learned a fair bit more than other classes at the same level.) The ranking criteria used aren’t always the most… rigorous, lol. (With some of my favorites being “S-tier because it’s in soda”, “D-tier because drugs”, and of course the perennial fallback of “uhhh, too lazy, I really just want to talk about the next chemical… first letter of its name, perfect!” 😝) What I find most impressive is how broad and diverse a set of chemicals you’re able to cover each time. It’s cool both in the sense of _wow, I learned about quite a few different interesting chemicals I wasn’t familiar with before!_ but also _wow, this guy really knows his stuff and can just sorta speak extemporaneously about all these various things with ease, at a pace that’s pretty impressive!_ 👨🔬👍
@@That_Chemist Oh yeah so I just remembered something about that awesome chemistry class I was in. I have a brief story to tell. At the end of the year, after the AP exams, we each got to do some sort of project of our own involving a synthesis, or demonstration, or whatever, that we chose personally. And we had a bunch of books and binders of stuff (a bit on the older end of things, I think) filled with various procedures and demos and whatnot that we could browse to find something that piqued our personal interests. Right, so, the project I ended up doing, was making some explosives! Specifically, in one of the books or binders, there was a good (and probably fairly old) procedure for making peroxyacetone! That seemed pretty awesome to me: I get to use some of that cool 30% hydrogen peroxide that leaves the peculiar white stains on your hands and comes in that funky bottle with the built-in accordion section (to be really accommodating of the peroxide, and give it the freedom to maybe decide that it actually wants to suddenly decompose all at once BEFORE it’s chemistry time, maybe because it’s just more comfortable that way). And I get to use acetone, which is kinda neat because, similar to hydrogen peroxide, it’s a readily accessible “normal” type of thing. And after some steps that I can’t really remember anymore, I end up with this cool white powder that makes fireballs, which I would set off with a lit-match-on-a-yardstick, or even a hammer impact! (Oooh, impact sensitivity! Cool!) Some years later, I made a bit of a discovery. Something along the lines of “uh-wait a minute, hang on… why does the Wikipedia article on this cool stuff I remember making in high school chemistry class, mostly talk about… like… terrorists and stuff? Oh god, it literally says verbatim that ‘TATP … has been used as the explosive of choice in several terrorist bomb attacks since 2001’…” So uh, yeah, I now feel… different… about my choice of project. I guess it’s affirmatively not a problem that I don’t remember what the prep steps were, because writing them in a TH-cam comment would probably violate… some rules. I’m guessing. Lol. I suppose my ultimate thoughts, in summary, are that it was a cool project, and there wasn’t anything wrong with it per se (that I know of). I just happened to be unlucky and choose one of, you know… one of the less-good possible choices in terms of “does this thing have good cred, or a notably sketchy reputation?”. (I want to go back and rewatch the explosives video again-super awesome collab btw 😛-because I’m reasonably sure you either skimmed over TATP et al kinda super quick or just plain didn’t include them, because… reputations. 😐)
@@That_Chemist If the numbers in my lab report are correct, and my chemistry math skills still work, it would appear that (after some smaller initial samples) I eventually produced “six or eight” 200 mL test tubes “and in each used twice the quantities recommended”. I think that means I potentially had somewhere on the order of 31-41 g of TATP and/or DADP in that test tube rack. (Likely much less, as I reckon my yield was not near 100%. So maybe let’s just randomly guess 25-75%; in which case it’d have been “only” about 10-23 grams.) Much to my dismay, Derek Lowe has an article on TATP from 2017. In which he talks about how it is “a substance that I definitely won’t work with” (uh oh), then elaborates that the only reason he didn’t make an official Things I Won’t Work With post for it was due to its “unfortunate significance” (oh no), and describes how a student unintentionally made perhaps as much as 40 g of it by accident, apparently necessitating a bomb squad (wtf). Also he adds that 40 g theoretical is “too much by any reasonable person’s definition”, and says making or handling this kind of quantity “is an invitation to be killed without warning”. Apparently I supposedly had like 30 or 40 g theoretical. *Intentionally.* 🤯 In my lab report I described that a “small pile” of “a few grams” of the stuff produced a fireball “perhaps 50 centimeters in diameter”. 😐 It didn’t seem overly violent, as far as I remember. 🤔 Kinda like, I dunno, the sort of fiery spectacle from burning hydrogen bubbles. Just not as slow. Since it’s, you know, an actual primary. Maybe I didn’t successfully make the actual stuff, and that’s the only reason I’m here today. I dunno. Also in my lab report, I remark about how I left one batch of the stuff to dry on filter paper in the fume hood over the weekend; and upon returning Monday, the filter paper was still there, but nothing was on it. So either it spontaneously detonated (the intentional detonations didn’t mar the filter paper, so it seemed distinctly possible), or possibly it all sublimated away (it does seem to have a high vapor pressure but I’ve forgotten everything about how to estimate whether it’s plausible for the rate to indeed be high enough for that to happen). 🫠
EG can actually be quite useful for affinity separations of very similar compounds when in a solution with water, and with heptane. I have had a lot of success using its cousin, PG with a water cosolvent and an immiscible heptane phase to separate compounds with different amounts of alcohol groups that are otherwise structurally identical. The problem of course was that it needs a mol-dist to remove the solvent afterwards, so its usability depends on having some very specific equipment that most labs just won't have.
I had a fellow grad student who did a prep and then took An NMR of his product. There were ethanol peaks, which he had expected, but then a bunch f small peaks, ethyl acetate, n-butyl peaks, 2-propanol peaks, and he wondered whence they came. He did not know that "Reagent Grade Ethanol (denatured)" had all that crap in it. His ignorance was more disturbing than were his spectra. I really appreciated your solvents discussion (more than the Tier classification. It was a good introduction to a lot of unfamiliar solvents. I have always thought of CO2 as nor-nor-acetone, ( 1,1-methanedione ) for exam[ple, it softens vulcanized rubber and solvent crazes acrylic plastic. Also, if you use it to pressurize tires, it rapidly diffuses right through the rubber, so the inflation doesn't last long. Really enjoyed the video! 👍
Acetonitrile may not have been everyone's favorite solvent. But when it comes to reactions, oh lord the wonders you can do by refluxing things with it!
Another important property of 2-methylTHF is that it has a much lower freezing point than plain old THF. So if you have a reaction you need to do at a lower temperature than THF can tolerate (and lower than you can go with a dry ice cold bath), but still needs the solvating properties of THF, then that's another situation where 2-methylTHF can be really useful.
During my training I worked a lot with diethyl ether and pentane, since we were mostly working at -80C. Did a lot of ether/pentane columns too. And let me tell you, the suck ass. Especially in summer. What's an AC anyway? Ever did an ether/pentane column at 30C room temperature? The only good thing was that my supervisor realized very quickly that they didn't work, so I could usually go home early over that summer. Great solvents. S-tier for allowing me to enjoy nice summer days.
All you need is DMSO, agua, and some ACN as reagent for cycloadditions… Oh, yeah and some hexane for hexane/agua mixtures… So, with 4 solvents you can do any chemistry imaginable 😉😝
Water seems like the safest of all the solvents because it’s not toxic, and since it’s basically the ash from burning hydrogen, it’s not flammable either, but It does have am extremely low freezing point of 0*C/32*F so that might be a bit of a problem in some applications
6:15 - CO2 is pretty polar ? I thought it was the classic example for a nonpolar molecule as a counterexample to H2O, IIRC it was the 2nd molecule we learned about regarding polarity because it gets the Idea accross very well if you compare it and H2O
CO2 has no dipole moment but it does have a quadrupole moment, i.e. the charge is not spherically distributed, the negative charge is more on the end Os. This is important for interactions with other molecules -- say, for making a solution or when CO2 binds to the enzyme RuBisCO, which is what fixes carbon in plants.
CO2 is pretty nonpolar, yes. Used to extract cannabinoids so definitely nonpolar, as butane and propane are the other primary solvents used for thc and cbd (other than ethanol of course, which gives lower yields). You need to use supercritical CO2 extraction.
I work with triterpenes and for me are the best friends DCM, EtOAc, THF. And thanks for reminding me of Tol-Py azeotrope. I am currently doing acetylation in pyridine, so i can try it.
I love TFE (trifluoroethanol) due to the fact that oxygen gas is pretty soluble in TFE. So if you have to use O2 atmosphere it is pretty damn good. Sometimes I have to make DCM-MeOH 0->50% column, but if I am using DCM-ammonia MeOH it is less painfull. So I pretty love ammonia.
Dmso can be removed by extractions, no problems for it! But i'am really surprising by the fact it's not miscible with ethers! I will try it the next time! Thanks for the tips!
Anhydrous ammonia deserves a much higher position, in my judgement. It is, I would argue, the nitrogen analog of water, and is special through analogy to this most critical of solvents; it is a shadow of H2O, and hence, a shadow of the solvent of life. The reason we don't use ammonia more often (whenever we need a highly-polar solvent) is that water does exist. If there was no such thing as water, then ammonia would claim its rightful place. As silly as it is to contemplate a universe where water does not exist, I believe ammonia is being unfairly penalized due to the existence of its more-famous chemical cousin. As much as ammonia's volatility is an annoyance when using it as a solvent, this same volatility is a Godsend when one needs to remove it.
CO2 is actually SSS. Chiral SFC lets you separate complex enantiomers mixtures on large scale, in the industry we don't even bother with asymetric synthesis methods anymore as a result For pyridine, I don't recall having issues removing this solvent. I would run sulphonyl chloride coupling reactions in pyridine (cool 30 min reactions, acts as solvent, base and catalyst), vap off a good bit (in a rotavap under a fumehood, otherwise your lab mates will lynch you) and get rid of the rest with a mildly acidic work up (usually pure water at ph 5 does the job).
Ammonia is a solvent used to grow high purity gallium nitride crystals. My favorite solvent is chloroform as it dissolves a lot of nonpolars, is very heavy, and boils at a low temperature. As far as the best one, its the one that disolves stuff, and doesnt interfere. 🤓
Acetone is cool because it rips apart anything that's organic and polar. Isopropanol is like acetone, but doesn't rip apart polymers such as plastics so you can clean plastics from residues and such. But the most useful will always be water, able to rip salts apart into its constituent ions.
To me some really high boiling point solvents have their uses. Sometimes hard to get rid of but they have their uses. Not very common so selection is limited in most labs without specifically ordering.
I'd like to add that HMPA and DMPU are good solvents, but pretty toxic, for dissolving lithium salts aggregates. Like in the enol reactions, the HMPA/DMPU can prevent aggregation of multiple enolates to the same lithium center
The DMF is kinda hard to remove but is easer to remove it with DCM, but some times I saw DMF peaks in a mas spectrum, so indead is hard to remove Also is one of the best solvents for peptide synthesis in column, because it dosolves really good all the aminoacids and couplers
AS I mentioned elsewhere in the comments, there is an azeotrope between n-heptane and DMF. When using heavy solvents, using azetropic distillation when possible is very effective.
I'm bit concerned with HFIP in S tier list due to corrosive and highly volatile nature but it's still best in terms of having great H-bonding properties...
I have not seen a chemist that hasn't been fucked over by water ever. Even ppm of water in the department central N2 killed some reactions. My grudge is real and my yields are poor. Water should belong in F
"but we're not considering toxicity here" Meanwhile in the EU, toxicity is the very first thing that is considered. So goodbye benzene, DMF, chloroform, DCM, methanol, nitromethane, toluene and any of the fluorinated stuff in consumer products. Heck even in the lab we rarely use chloroform and I'm yet to use benzene as a solvent
Also, acetone may be gone from consumer applications in a few years because it's listed as an explosive precursor. But whoever is stupid enough to make a bomb out of TATP would most likely only hurt themself
Benzene is „the solvent that shall not be named“ here, yeah, but chloroform? That’s very common.. heck, my first orgchem lab EVER had a synthesis which needed like 300ml of chloroform
@@avagadrhoe768 I've had a whole beaker of methanol (it says "toxic on skin contact") spilled over my hand, rinsed it quickly and literally nothing happened. We also had lab assistants who didn't knew that (semi-)dilute acids cause chemical burns more quickly than concentrated. You can get conc sulfuric acid on your skin, as long as you wash it off quickly, nothing happens. These chemicals _can_ be dangerous, but I feel like their level of scariness is vastly overestimated. Just, you know, don't be an idiot
I use isopropanol pretty much every day, I love using the stuff and its probably my favorite solvent. Except the rare occurrence when the vapors decide to deflagrate in my face, my beard and eyebrows are actually singed a bit right now from that very thing happening...
Ultrapure water is such a good solvent that it can actually be hazardous- there is a story of a guy visiting Super-Kamiokande in Japan who accidentally got a bit of his unusually long hair in the water and ended up with it falling out the next day...
Actually, this video is very important, and to be more specific sir please upload one by one row from all of them. My work is on HFIP and need some information.
Not a chemist but I dabble in chemical processes to make things (resin 3d printing, etching metals, anodizing) I really appreciate ethanol as a solvent for its human compatability. It makes relatively few vapors, isnt irritating or toxic in any reasonable quantity, its just a joy to have around
Someone said to me once that "heptane was better than hexane in a particular situation because it was more selective" . Then on the contrary someone who got a 1st in chem said "pentane, hexane, heptane. It all makes very little difference it all depends on the boiling point you're after. So Pentane is ideal for most chemistry extactions when your after a non polar solvent." Is anyone right or wrong in this and could someone explain a bit more or link me to a video which can fill me in more. Thank you in advance.
@@That_Chemist EPA method for extraction of PCBs in soil used Soxlet extraction using Isooctane. More selective than Heptane because branched chain. BP 110°C. "Octane rating" (free radical inhibition) Isooctane defined as 100 and Heptane octane rating is zero.
chemically very little difference but, n-pentane is too volatile and smell quite strongly om my opinion. n-Hexane, though the most widely used because of flash chromatography is toxic. it is metabolized into hexan-2,5-dione which is the toxic component. n-Heptane is a little heavier so more difficult to remove but it forms azeotropes with many other way more difficult to remove solvents, including pyridine and DMF. In industrial laboratories we prefer to use n-heptane (less volatile and less toxic) as well as methylcyclohexane. Cyclohexane is also quite good there but its "high" meting point (7 ºC) could be a problem in an industrial process.
@@sylvainlectard7377 I think you are using tech grade pentane which has added odorant. "Chemically pure" (chromatography grade) Pentane doesn't have added odorant. Alcohol tax is charged for Chromatography Grade Ethanol because it is eminently drinkable.
Do you know why it is commonly called MTBE? By all accounts, it should be tert-butyl methyl ether, if we are to use proper alphabetical priority. Aldrich also lists it that way, but I've never seen anyone refer to it as TBME.
There are quite a few solvents that inhabit the same general space as DMF and DMSO, of "I want to dissolve everything, including various metal salts, workup be damned!", but which are therefore very annoying to use. N-methyl pyrrolidone, propylene carbonate, sulfolane, and of course, HMPA (i.e. "liquid cancer"). I also wonder if triethyl amine would deserve recognition here if only for use as an additive in column chromatography of basic compounds. Overall, reasonable placements for everything. Pyridine can still go to hell~
11:26 Ah, yes, acetone. One of my favourite solvents. Turns ABS plastic to liquid, then back to solid because it's so volatile that it evaporates out of the plastic. Dissolves the pine gum off my car. It's so volatile and such a good solvent that it absorbs through my skin and dissolves my liver and kidneys right out of my body. Acetone is among the best of the best. Anything that can't kill you isn't very good at its job. To hell with your biodegradable, low VOC crap. I'm sticking to acetone, 35% H2O2 and 12M HCl. Also, low conductive DI water for polar stuff. Wish I could get CCl4 at the hardware store.
In order for carbon dioxide to be usable as a solvent though, you have to make it go supercritical which seems a bit difficult to do, it needs to be pressurized all the way to 1,073 psi (7.4 MPa if using metric), it’s critical temperature of of 87.9*F (31.89*C) shouldn’t be too hard to reach though assuming you’re starting from room temperature
I disagree with leaving toxicity out of the rating. Mandatory safety precautions at my workplace definetly play a major role in which solvents I choose to work with and I regularly use non-ideal solvents because they are less toxic. For example, I regularly substitute CPME for Toluene because CPME has less servere hazard statements. We've also phased out diethyl ether almost completely, becuase we would have to monitor it for peroxide buildup every other month Something which we are not required to do with tert-butyl-methyl-ether, because it barely forms peroxides.
Hello, thank you very much for your videos. Please tell me what is the best way to dissolve POM in a 3D printed part. It is used as a polymer binder in 17-4 metal filament. I found that dichloroethane and tetrahydrofuran work if you heat them to 60 degrees, but apparently these are very dangerous substances, and you should not start working with them without understanding the chemistry. Especially with tetrahydrofuran.
Ethanol is S tier. How many of these solvents can readily extract active compounds from plant matter and still be immediately safe for human consumption
Ethanol is one of the few solvents that's not only safe to drink, it's actually fun to drink. The German Bad Guy Party had to go to great lengths to prevent their rocket scientists from drinking their stock of rocket fuel.
The crazy part about that Russian/German soldiers drinking rocket fuel thing is that them switching to methanol to "fix" the issue didn't immediately slow them down outside medically.
love the TOS-compliance of “German Bad Guy Party”. never knew that just plain ethanol was used as rocket fuel!
That also applies to "Torpedo juice" during WWII.
Well it is a carcinogen, so not so safe
Yep the V2 rocket used 75%ethanol/25%water and liquid oxygen
151 rum and LOX, not really but the ratios are the same.
A compilation of these guides with a classification system for the various advantages and disadvantages would have been a great asset to my lab days. So much of this is not taught and just learned the hard way or by lab tribal knowledge.
Then make sure you share it!
So ... we need a tier list of these tier lists?
This dude isn't smart enough for that.
As a pharmaceutical process development chemist, your solvent list is one of the main reasons why so many of us are needed. The toxicities of many of your favorites preclude using them anywhere near the end of a Active Pharmaceutical Ingredient synthesis. Sometimes, the R&D scientist needs to consider the downstream implications - will your product have any potential use in humans or animals??
it sucks because some of them are such good solvents - HFIP will be realized as likely the best solvent in chemistry unless a better fluorinated alcohol is discovered, but it is super toxic, and almost impossible to get rid of every last trace of it - amazing solvent though.
Also this isn't related to your comment, but I would absolutely LOVE to make a video with footage of a process development lab - maybe after >6 months or so. As you highlight, most researchers aren't aware of what actual process chemistry looks like, and I would love to help bring that world to chemists everywhere
@@That_Chemist HFIP (1,1,1,3,3,3-Hexafluoropropan-2-ol) isn't that toxic? I can name 5 solvents I use daily that are orders of mangitude more acutely toxic.
@@That_Chemist Problem is that most of us in R&D are so focused on that, so even if we have an understanding of what goes on "downstream" in precess chem, it rarely enters our mind. Not meant to sound careless, that's just the reality of things - it is also a matter of workload. As in your example with HFIP. What should we use instead? Not much comes to mind.
Ethyl alcohol by far is the chemists friend.
Organic solvent for my first lab experiments. Potable at my professor's (lab) group meetings at the local tavern. Several of my chemist friends brewed beer, etc. My first training on GC was determining ethyl alcohol % in beer.
awesome haha
I'm surprised the fluorine chemist didn't mention HF! Also, Hg is a decent solvent too depending on the type of chemistry you are doing...
I get to work with dichloromethane. It's pretty cool, we use it to dissolve polymer residue. The big drawback is that it dissolves nitrile gloves. Luckily it is not too horrible.
It's an alkylating reagent, which unfortunately isn't recognized by most chemists. It reacts with amines, even tertiary amines already at room temperature and my guess ist that is is probably rather carcinogenic. But industry doesn't want to see this... .
I work with it occasionally, either repackaging it or blending it to make wood stripper. It can cause burns, but it also evaporates super fast. Also it smells good, not that you should be smelling it too much
An idea for a future episode: can you explain the 5 most complicated reactions you have done in your career? Like reactions you have done with very sensitive reagents or which had a very advanced work up. Especially these that can only be carried out upon complete oxygen and moisture exclusion? Would be highly interesting
When I selected solvents for commercial production I had to take all those other factors into account (tox, enviro, emissions, fate in ground water etc.). The guys in the plant were always pleased when I rolled out a new project and the solvent that smelled good. With those criteria in mind Tert-butyl alcohol had good acceptance. DMF was hated. Since our reactive byproducts were water quenched it was always important to have a good quenching properties - boiling point, density, and not emulsify. Alkanes were the best by those criteria, alcohols and ethers were not. Trace THF in water makes the mixture flammable so that complicated downstream designs. Heavier that water solvents were more or less banned from consideration due to the nightmare of dealing with those in ground water. Good review- Loved it! BTW - I'm racking my brain - one time we toll processed something in a solvent that had a warning that it could cause testicluar atrophy - it will come to me eventually.
16:53 Oh my boy DCM. Once I did a synthesis of a TMS-substituted ester, which entailed wrestling for two weeks with the purification process. In one of the many (flash) columns attempts, I was looking through NMR data of the eluted fractions and scratching my head as to where the hell did the product go - as it turned out the target ester (and a lot of residual palladium) was stuck at the top of the sillica column, not budging one inch in the flow of hexane eluent. After washing it out with DCM and running several more columns with DCM-based solvent mixtures (including perhaps three dozen TLCs to test them out first) I finally got my compound. This one occasion also refreshed my appreciation for solvents that don't boil at r.t. and drip out of the pipette I'm using to pick it up - DCM and Et2O were assholes to handle, but at least they were easy to rotovap.
Also shout-out to DCM's 1.33 g/ml density. Having the organic phase be heavier than water is such a pleasant property to work with in solvent extractions.
For deuterated solvents, I would say benzene-d6 and THF-d8 are legends in the field of organometallic chemistry.
my man is back!!! you solvate my heart ❤️
I use THF at work every day. One time I was working near someone who was using it and didn't have my respirator on. The venitlation in the building is excellent and I was several feet away, and it still gave me a headache and made me feel a little sick for the next couple hours. Always wear your PPE when working with or even near hazardous materials.
even if some of the specific opinions make my head spin, your tier list videos are my favorite of your content (which is saying something, bc your content is generally great) and one of my favorite pieces of content online period! thanks for the good work!
Thank you for your kind words :)
You cant believe how much I'm learning from your videos
Glad to hear it :)
THF-d8 and pentane treat me so well, pretty much everything I work with dissolves in either one or the other
I love all these tier list videos you make!
They’re entertaining to watch, and I can follow along decently okay, even as someone whose formal chemistry education ended over a decade ago, in high school, with AP Chem. (Btw, we had an amazing class with an amazing teacher; I don’t doubt we learned a fair bit more than other classes at the same level.)
The ranking criteria used aren’t always the most… rigorous, lol. (With some of my favorites being “S-tier because it’s in soda”, “D-tier because drugs”, and of course the perennial fallback of “uhhh, too lazy, I really just want to talk about the next chemical… first letter of its name, perfect!” 😝)
What I find most impressive is how broad and diverse a set of chemicals you’re able to cover each time.
It’s cool both in the sense of
_wow, I learned about quite a few different interesting chemicals I wasn’t familiar with before!_
but also
_wow, this guy really knows his stuff and can just sorta speak extemporaneously about all these various things with ease, at a pace that’s pretty impressive!_
👨🔬👍
Thank you for your kind comment :)
@@That_Chemist Oh yeah so I just remembered something about that awesome chemistry class I was in. I have a brief story to tell.
At the end of the year, after the AP exams, we each got to do some sort of project of our own involving a synthesis, or demonstration, or whatever, that we chose personally. And we had a bunch of books and binders of stuff (a bit on the older end of things, I think) filled with various procedures and demos and whatnot that we could browse to find something that piqued our personal interests.
Right, so, the project I ended up doing, was making some explosives! Specifically, in one of the books or binders, there was a good (and probably fairly old) procedure for making peroxyacetone! That seemed pretty awesome to me: I get to use some of that cool 30% hydrogen peroxide that leaves the peculiar white stains on your hands and comes in that funky bottle with the built-in accordion section (to be really accommodating of the peroxide, and give it the freedom to maybe decide that it actually wants to suddenly decompose all at once BEFORE it’s chemistry time, maybe because it’s just more comfortable that way). And I get to use acetone, which is kinda neat because, similar to hydrogen peroxide, it’s a readily accessible “normal” type of thing. And after some steps that I can’t really remember anymore, I end up with this cool white powder that makes fireballs, which I would set off with a lit-match-on-a-yardstick, or even a hammer impact! (Oooh, impact sensitivity! Cool!)
Some years later, I made a bit of a discovery. Something along the lines of “uh-wait a minute, hang on… why does the Wikipedia article on this cool stuff I remember making in high school chemistry class, mostly talk about… like… terrorists and stuff? Oh god, it literally says verbatim that ‘TATP … has been used as the explosive of choice in several terrorist bomb attacks since 2001’…”
So uh, yeah, I now feel… different… about my choice of project. I guess it’s affirmatively not a problem that I don’t remember what the prep steps were, because writing them in a TH-cam comment would probably violate… some rules. I’m guessing. Lol.
I suppose my ultimate thoughts, in summary, are that it was a cool project, and there wasn’t anything wrong with it per se (that I know of). I just happened to be unlucky and choose one of, you know… one of the less-good possible choices in terms of “does this thing have good cred, or a notably sketchy reputation?”. (I want to go back and rewatch the explosives video again-super awesome collab btw 😛-because I’m reasonably sure you either skimmed over TATP et al kinda super quick or just plain didn’t include them, because… reputations. 😐)
Oh god, I still have the lab report file
@@That_Chemist If the numbers in my lab report are correct, and my chemistry math skills still work, it would appear that (after some smaller initial samples) I eventually produced “six or eight” 200 mL test tubes “and in each used twice the quantities recommended”. I think that means I potentially had somewhere on the order of 31-41 g of TATP and/or DADP in that test tube rack. (Likely much less, as I reckon my yield was not near 100%. So maybe let’s just randomly guess 25-75%; in which case it’d have been “only” about 10-23 grams.)
Much to my dismay, Derek Lowe has an article on TATP from 2017. In which he talks about how it is “a substance that I definitely won’t work with” (uh oh), then elaborates that the only reason he didn’t make an official Things I Won’t Work With post for it was due to its “unfortunate significance” (oh no), and describes how a student unintentionally made perhaps as much as 40 g of it by accident, apparently necessitating a bomb squad (wtf). Also he adds that 40 g theoretical is “too much by any reasonable person’s definition”, and says making or handling this kind of quantity “is an invitation to be killed without warning”.
Apparently I supposedly had like 30 or 40 g theoretical. *Intentionally.* 🤯
In my lab report I described that a “small pile” of “a few grams” of the stuff produced a fireball “perhaps 50 centimeters in diameter”. 😐
It didn’t seem overly violent, as far as I remember. 🤔 Kinda like, I dunno, the sort of fiery spectacle from burning hydrogen bubbles. Just not as slow. Since it’s, you know, an actual primary.
Maybe I didn’t successfully make the actual stuff, and that’s the only reason I’m here today. I dunno.
Also in my lab report, I remark about how I left one batch of the stuff to dry on filter paper in the fume hood over the weekend; and upon returning Monday, the filter paper was still there, but nothing was on it. So either it spontaneously detonated (the intentional detonations didn’t mar the filter paper, so it seemed distinctly possible), or possibly it all sublimated away (it does seem to have a high vapor pressure but I’ve forgotten everything about how to estimate whether it’s plausible for the rate to indeed be high enough for that to happen).
🫠
EG can actually be quite useful for affinity separations of very similar compounds when in a solution with water, and with heptane. I have had a lot of success using its cousin, PG with a water cosolvent and an immiscible heptane phase to separate compounds with different amounts of alcohol groups that are otherwise structurally identical. The problem of course was that it needs a mol-dist to remove the solvent afterwards, so its usability depends on having some very specific equipment that most labs just won't have.
I had a fellow grad student who did a prep and then took An NMR of his product. There were ethanol peaks, which he had expected, but then a bunch f small peaks, ethyl acetate, n-butyl peaks, 2-propanol peaks, and he wondered whence they came. He did not know that "Reagent Grade Ethanol (denatured)" had all that crap in it. His ignorance was more disturbing than were his spectra. I really appreciated your solvents discussion (more than the Tier classification. It was a good introduction to a lot of unfamiliar solvents. I have always thought of CO2 as nor-nor-acetone, ( 1,1-methanedione ) for exam[ple, it softens vulcanized rubber and solvent crazes acrylic plastic. Also, if you use it to pressurize tires, it rapidly diffuses right through the rubber, so the inflation doesn't last long. Really enjoyed the video! 👍
Acetonitrile may not have been everyone's favorite solvent. But when it comes to reactions, oh lord the wonders you can do by refluxing things with it!
Another important property of 2-methylTHF is that it has a much lower freezing point than plain old THF. So if you have a reaction you need to do at a lower temperature than THF can tolerate (and lower than you can go with a dry ice cold bath), but still needs the solvating properties of THF, then that's another situation where 2-methylTHF can be really useful.
You could be talking about anything and I would listen to you... A true "golden voice"
This is my favorite chemistry Channel. I thank you because, I frequently laugh at least once while watching them
During my training I worked a lot with diethyl ether and pentane, since we were mostly working at -80C. Did a lot of ether/pentane columns too. And let me tell you, the suck ass. Especially in summer. What's an AC anyway? Ever did an ether/pentane column at 30C room temperature? The only good thing was that my supervisor realized very quickly that they didn't work, so I could usually go home early over that summer. Great solvents. S-tier for allowing me to enjoy nice summer days.
Hahaha
All you need is DMSO, agua, and some ACN as reagent for cycloadditions… Oh, yeah and some hexane for hexane/agua mixtures… So, with 4 solvents you can do any chemistry imaginable 😉😝
100%
Run a grignard then? 😅
Pretty certain that Figueroa has figured out how to do Grignard’s in agua…
You also need the magic 3:1 chloroform:agua
Water seems like the safest of all the solvents because it’s not toxic, and since it’s basically the ash from burning hydrogen, it’s not flammable either, but It does have am extremely low freezing point of 0*C/32*F so that might be a bit of a problem in some applications
Is it benzene? I bet it's benzene. It's back, baby!
Benzene activated the Australian Chemist neurons
What about n-propane? That was always my favorite for cannabis extraction-in a past life.
For 21 minutes of gibberish, this video was really good!
DMF was thr solvent I worked with on my BSc back in 2014 for my dissertation. Fun!
Pyridine: Yeah, solvent. But you will reek for days!
absolutely!
6:15 - CO2 is pretty polar ? I thought it was the classic example for a nonpolar molecule as a counterexample to H2O, IIRC it was the 2nd molecule we learned about regarding polarity because it gets the Idea accross very well if you compare it and H2O
see the desc
@@That_Chemist oh thats neat I was not aware of that
CO2 has no dipole moment but it does have a quadrupole moment, i.e. the charge is not spherically distributed, the negative charge is more on the end Os. This is important for interactions with other molecules -- say, for making a solution or when CO2 binds to the enzyme RuBisCO, which is what fixes carbon in plants.
CO2 is pretty nonpolar, yes. Used to extract cannabinoids so definitely nonpolar, as butane and propane are the other primary solvents used for thc and cbd (other than ethanol of course, which gives lower yields). You need to use supercritical CO2 extraction.
Oh you explained it in the comments, duh
I am very much enjoying ethanol right now while watching this video. Trying to dissolve my problems.
Carbon Disulfide autoignites at 100C or the spark when pouring between vessels.
CS2 is a heavy vapor that requires good fume hood suction.
DCM is my favorite so far. It's been so good to me.
H2O is a great solvent
When Soda is not on the list
At least water was put into S-tier. It is in soda after all :D
You know, I rarely comment here, but I must admit, that this channel is awsome! Keep up the good work!
Thank you :)
I work with triterpenes and for me are the best friends DCM, EtOAc, THF. And thanks for reminding me of Tol-Py azeotrope. I am currently doing acetylation in pyridine, so i can try it.
pyridine can fairly easily be removed by aqueous acid washes - if your product is lipophilic enough.
I love TFE (trifluoroethanol) due to the fact that oxygen gas is pretty soluble in TFE. So if you have to use O2 atmosphere it is pretty damn good.
Sometimes I have to make DCM-MeOH 0->50% column, but if I am using DCM-ammonia MeOH it is less painfull. So I pretty love ammonia.
Dmso can be removed by extractions, no problems for it!
But i'am really surprising by the fact it's not miscible with ethers! I will try it the next time!
Thanks for the tips!
It’s hard to get rid of every last bit without a column though
DMSO is A-S tier for short peptides with 10-20 amino acid sequences, well, at least some of them. Actually it depends on what the sequence is.
Thanks for the reupload bro ♥️
Anhydrous ammonia deserves a much higher position, in my judgement. It is, I would argue, the nitrogen analog of water, and is special through analogy to this most critical of solvents; it is a shadow of H2O, and hence, a shadow of the solvent of life. The reason we don't use ammonia more often (whenever we need a highly-polar solvent) is that water does exist. If there was no such thing as water, then ammonia would claim its rightful place. As silly as it is to contemplate a universe where water does not exist, I believe ammonia is being unfairly penalized due to the existence of its more-famous chemical cousin. As much as ammonia's volatility is an annoyance when using it as a solvent, this same volatility is a Godsend when one needs to remove it.
CO2 is actually SSS. Chiral SFC lets you separate complex enantiomers mixtures on large scale, in the industry we don't even bother with asymetric synthesis methods anymore as a result
For pyridine, I don't recall having issues removing this solvent. I would run sulphonyl chloride coupling reactions in pyridine (cool 30 min reactions, acts as solvent, base and catalyst), vap off a good bit (in a rotavap under a fumehood, otherwise your lab mates will lynch you) and get rid of the rest with a mildly acidic work up (usually pure water at ph 5 does the job).
Ammonia is a solvent used to grow high purity gallium nitride crystals. My favorite solvent is chloroform as it dissolves a lot of nonpolars, is very heavy, and boils at a low temperature. As far as the best one, its the one that disolves stuff, and doesnt interfere. 🤓
Acetone is cool because it rips apart anything that's organic and polar. Isopropanol is like acetone, but doesn't rip apart polymers such as plastics so you can clean plastics from residues and such. But the most useful will always be water, able to rip salts apart into its constituent ions.
To me some really high boiling point solvents have their uses. Sometimes hard to get rid of but they have their uses. Not very common so selection is limited in most labs without specifically ordering.
I'd like to add that HMPA and DMPU are good solvents, but pretty toxic, for dissolving lithium salts aggregates. Like in the enol reactions, the HMPA/DMPU can prevent aggregation of multiple enolates to the same lithium center
I’m glad you mentioned cannabinoids in reference to CO2 😉
The DMF is kinda hard to remove but is easer to remove it with DCM, but some times I saw DMF peaks in a mas spectrum, so indead is hard to remove
Also is one of the best solvents for peptide synthesis in column, because it dosolves really good all the aminoacids and couplers
AS I mentioned elsewhere in the comments, there is an azeotrope between n-heptane and DMF. When using heavy solvents, using azetropic distillation when possible is very effective.
I'm bit concerned with HFIP in S tier list due to corrosive and highly volatile nature but it's still best in terms of having great H-bonding properties...
It’s so dang good
DMSO can carry solutes through skin. It's used in some topical medications to make them absorb faster.
Lol, I love acetone and ipa so much I have two flask on display in my living room.
I thought for sure carbon dioxide would go in S Tier, since it's essential for soda pop.
TRUE
I have not seen a chemist that hasn't been fucked over by water ever. Even ppm of water in the department central N2 killed some reactions. My grudge is real and my yields are poor.
Water should belong in F
"but we're not considering toxicity here"
Meanwhile in the EU, toxicity is the very first thing that is considered. So goodbye benzene, DMF, chloroform, DCM, methanol, nitromethane, toluene and any of the fluorinated stuff in consumer products. Heck even in the lab we rarely use chloroform and I'm yet to use benzene as a solvent
Also, acetone may be gone from consumer applications in a few years because it's listed as an explosive precursor. But whoever is stupid enough to make a bomb out of TATP would most likely only hurt themself
Benzene is „the solvent that shall not be named“ here, yeah, but chloroform? That’s very common.. heck, my first orgchem lab EVER had a synthesis which needed like 300ml of chloroform
i'm pretty sure i've inhaled over 300mL of chlorinated solvents over my professional chemist and schizo drug fiend careers and im (relatively) fine
@@moropikkuu We do use chloroform in a lab from time to time, but for many applications we substitute it with DCM
@@avagadrhoe768 I've had a whole beaker of methanol (it says "toxic on skin contact") spilled over my hand, rinsed it quickly and literally nothing happened.
We also had lab assistants who didn't knew that (semi-)dilute acids cause chemical burns more quickly than concentrated. You can get conc sulfuric acid on your skin, as long as you wash it off quickly, nothing happens. These chemicals _can_ be dangerous, but I feel like their level of scariness is vastly overestimated. Just, you know, don't be an idiot
Dichloromethane is easily the best solvent to use for separating the bioactive ingredients from phytomedicinals.
I use isopropanol pretty much every day, I love using the stuff and its probably my favorite solvent. Except the rare occurrence when the vapors decide to deflagrate in my face, my beard and eyebrows are actually singed a bit right now from that very thing happening...
Ultrapure water is such a good solvent that it can actually be hazardous- there is a story of a guy visiting Super-Kamiokande in Japan who accidentally got a bit of his unusually long hair in the water and ended up with it falling out the next day...
Solvent tier lists? Instant subscription on TH-cam and Patreon
You are the best!
pyridine dissolves in water, so its easy to remove it by washing the product with water.
6:12 CO2 is polar???
Carbon disulfide. Four words: white phosphorus water gun...
Mn2O7 water gun
@@That_Chemist gonna have to make it out of glass, and doesn't that stuff just sometimes say fuck it and explosively decompose for no apparent reason
I was hoping you would rate glycerol, I find it an okay solvent, does the job and adorable.
Isopropanol is great stuff, essential if you work with electronics.
"I quite enjoy ethanol" Yeah I bet you do ;D
Dioxane (and Diglyme) complexes Sodium so Sodium Borohydride and Sodium Aluminum Hydride are somewhat soluble.
Shocked that deuterated-deuterated chloroform didn't make the list, appalling Figueroa erasure
true!
I like ethanol too
What are you smoking where CO2 and benzene are polar
Benzene is quadrupolar and CO2 may not have any net dipole, but the C=O bonds are polar, so CO2 is good at dissolving polar molecules (e.g. caffeine)
And what about N-methylpyrrolidone and HMPA?
They barely missed the cut
Because of the birch reduction of pseudoephedrine into methamphetamine I would give anhydrous ammonia an F too
Actually, this video is very important, and to be more specific sir please upload one by one row from all of them. My work is on HFIP and need some information.
Just send me a DM on discord and I’d be happy to help
Great video, man :D
Not a chemist but I dabble in chemical processes to make things (resin 3d printing, etching metals, anodizing)
I really appreciate ethanol as a solvent for its human compatability. It makes relatively few vapors, isnt irritating or toxic in any reasonable quantity, its just a joy to have around
Someone said to me once that "heptane was better than hexane in a particular situation because it was more selective" .
Then on the contrary someone who got a 1st in chem said
"pentane, hexane, heptane. It all makes very little difference it all depends on the boiling point you're after. So Pentane is ideal for most chemistry extactions when your after a non polar solvent."
Is anyone right or wrong in this and could someone explain a bit more or link me to a video which can fill me in more. Thank you in advance.
I would say that there is little difference
@@That_Chemist EPA method for extraction of PCBs in soil used Soxlet extraction using Isooctane. More selective than Heptane because branched chain. BP 110°C. "Octane rating" (free radical inhibition) Isooctane defined as 100 and Heptane octane rating is zero.
chemically very little difference but, n-pentane is too volatile and smell quite strongly om my opinion. n-Hexane, though the most widely used because of flash chromatography is toxic. it is metabolized into hexan-2,5-dione which is the toxic component. n-Heptane is a little heavier so more difficult to remove but it forms azeotropes with many other way more difficult to remove solvents, including pyridine and DMF. In industrial laboratories we prefer to use n-heptane (less volatile and less toxic) as well as methylcyclohexane. Cyclohexane is also quite good there but its "high" meting point (7 ºC) could be a problem in an industrial process.
@@sylvainlectard7377 I think you are using tech grade pentane which has added odorant. "Chemically pure" (chromatography grade) Pentane doesn't have added odorant. Alcohol tax is charged for Chromatography Grade Ethanol because it is eminently drinkable.
@@sylvainlectard7377 Old school. For routine non-polar extraction, many labs use liquid CO2 apparatus. Easy peasy and no fire hazard.
How do you
Put DMA below DMF?!? Wash it with a 2% LiCl solution and it washes right away. It’s so nice.
Do you know why it is commonly called MTBE? By all accounts, it should be tert-butyl methyl ether, if we are to use proper alphabetical priority. Aldrich also lists it that way, but I've never seen anyone refer to it as TBME.
There are quite a few solvents that inhabit the same general space as DMF and DMSO, of "I want to dissolve everything, including various metal salts, workup be damned!", but which are therefore very annoying to use. N-methyl pyrrolidone, propylene carbonate, sulfolane, and of course, HMPA (i.e. "liquid cancer"). I also wonder if triethyl amine would deserve recognition here if only for use as an additive in column chromatography of basic compounds.
Overall, reasonable placements for everything. Pyridine can still go to hell~
Always wanted to try using propylene carbonate but never got a chance
11:26 Ah, yes, acetone. One of my favourite solvents. Turns ABS plastic to liquid, then back to solid because it's so volatile that it evaporates out of the plastic. Dissolves the pine gum off my car. It's so volatile and such a good solvent that it absorbs through my skin and dissolves my liver and kidneys right out of my body. Acetone is among the best of the best. Anything that can't kill you isn't very good at its job. To hell with your biodegradable, low VOC crap. I'm sticking to acetone, 35% H2O2 and 12M HCl. Also, low conductive DI water for polar stuff. Wish I could get CCl4 at the hardware store.
I unironically like working with teratogens, it makes being infertile a bonus LOL
DMSO is S TIER
In order for carbon dioxide to be usable as a solvent though, you have to make it go supercritical which seems a bit difficult to do, it needs to be pressurized all the way to 1,073 psi (7.4 MPa if using metric), it’s critical temperature of of 87.9*F (31.89*C) shouldn’t be too hard to reach though assuming you’re starting from room temperature
I've always been sad Benzene is Group 1, just because of how pretty the molecular structure is (esp. for a hydrocarbon). C6H6... Simple, yet elegant.
I always wonder why people don’t consider the environmental impact of solvent choices
I disagree with leaving toxicity out of the rating. Mandatory safety precautions at my workplace definetly play a major role in which solvents I choose to work with and I regularly use non-ideal solvents because they are less toxic.
For example, I regularly substitute CPME for Toluene because CPME has less servere hazard statements.
We've also phased out diethyl ether almost completely, becuase we would have to monitor it for peroxide buildup every other month Something which we are not required to do with tert-butyl-methyl-ether, because it barely forms peroxides.
💡6:13 Google says carbon dioxide is nonpolar and I agree.
Ammonia should be E tier for solvated Electrons
True
Water is my favorite, I need it to live
Hello, thank you very much for your videos. Please tell me what is the best way to dissolve POM in a 3D printed part. It is used as a polymer binder in 17-4 metal filament. I found that dichloroethane and tetrahydrofuran work if you heat them to 60 degrees, but apparently these are very dangerous substances, and you should not start working with them without understanding the chemistry. Especially with tetrahydrofuran.
You could try 2-methyl tetrahydrofuran
Ethanol is S tier. How many of these solvents can readily extract active compounds from plant matter and still be immediately safe for human consumption
True
Watching this as I attempt a carbylamine test on glycine.
Good luck!
@@That_Chemist ended up with a bad smelling product. So. Success? I guess.
Which solvent would be the best to extract the freebase of cocaine after an amonnia tritation? Ether, Chloroform, Hexane, or another?
Ammonia belongs in S tier because of Solvated Electrons
Forgot unripe banana water
You should do best dueterated solvents🎃
It’s so niche tho
I like carbon tetrachloride because its fun to empty antique fire extinguishers in my backyard
I have missed HMPA.