Special Topic - NaH Makes Solvents EXPLODE! (IOC 34)

[@kingnotail3838]

Not gonna lie lie, I've used NaH in all of these solvents, and heated up to 100 deg. C, and nothing bad happened. I do accept there are risks though. Now I just use NMP ;D

[@BradSchmor]

I've done reactions with NaH in DMF many times, even at high temperatures. I think they two big issues here are concentration and a large stoichiometric excess. I had a series of 2-aminobenzthiophenes I made by cyclizing the precursor O-bromo compound, using NaH in DMF on the thioamide. Depending on the aromatic substituents I needed to reach 80 or even 140 C to shove them along. But - I only had perhaps a 5 mol% NaH excess, and we are talking about maybe 1 g NaH in 40 mL solvent. One example just wouldn't go, so I cranked it to 190 C in NMP. Worked! But thank you for bringing this up. Somtimes, not even close to enough thermal hazard analysis is done on reactions before they are scaled up. It is expensive and slow, but oh so necessary.

[@namesurname5911]

One of unsolved mysteries of my not entirely finalized PhD work is the one unexpected product in alkylation of bisimide, involving NaH in DMF. Got an x-ray and about 100 mg. of byproduct and never got to repeat the results. We did improve the yield of the desired alkylation product, though.

[@ThatChemistOld]

Weird!

[@Wailn_]

I used to make alkyl azoles alot and often used NaH in DMF as that's what the postdoc in the group did - I had no idea about the dangers. Very interesting video!

[@ThatChemistOld]

Thanks!

[@TheMeninwhit]

One time I tried to alkylate a dihydroxy diformylbenzene and went NaH DMF Me2SO4 (big fun), got the allylated compound with loss of a formyl. Nice

[@ThatChemistOld]

where did the allyl group go?

[@danlukyanov5122]

Yeah, it may be a problem. For example, alkylation of 2,3-dihyrdoxybenzaldehyde with different alkyl bromides using NaH/DMF afforded shitty reaction mixtures, but with NaH/DMSO yields were about 60-70% (selectively in 3-position, almost no 2-alkylated, 2,3-dialkylated as a main impurity). Alkyl sulfates, as for me, are not a good choice in combination with NaH, especially for phenols. Better use MeI in this case. What exactly the dimethoxy diformylbenzene you need? I have synthesized 1,4-dimethoxy-2,5-diformylbenzene and 1,3-dimethoxy-4,6-diformylbenzene many times, and it is more convenient to prepare it by double formyl introduction to the corresponding dimethoxybenzene.

[@DavidRobertsonUK]

I've seen procedures involving these mixtures countless times in papers.

[@ThatChemistOld]

which is exactly why the paper (that I discuss) brings the topic up!

[@sreejitghosh9441]

Please include more special topics like this

[@dlvivlviv]

I set up lots of reactions of NaH in DMF. Everything worked great so far.

[@ThatChemistOld]

and I have made benzynes from anthranilic acids dozens of times, but I still use a blast shield every time, and plan for the worst

[@romanpolanski4928]

In your practice question, are you sure you would obtain the syn-bromide by treating the syn-diol with Ph3P and CBr4? I would have thought it would prefer to make an epoxide by intramolecular displacement of the activated phosphorus species by the neighbouring OH group.

[@ThatChemistOld]

It’s possible - it likely would depend on the solvent and the conditions

[@acetophenone820]

Man, I've said the same thing about water vs. DMSO for years. I can't believe the onset temps are so damn low for such commonly prescribed conditions.

[@konstantinkonstantinov7078]

When i make Na2Te2 I use Te+NaH in NMP (analogue of DMF/DMA) but this made me scare a little bit.

[@jozefnovak7750]

Super! Thank you very much!

[@thiocarbamoyl]

My PI has tasked me with reproducing a fairly straightforward 3-step synthesis developed in the lab previously, the middle step of which involves ~1mol% NaH in DMF at r.t. This video and the papers it references have made me very hesitant to attempt this. How should I broach this topic with my (relatively hotheaded) PI?

[@ThatChemistOld]

Put the paper on his desk

[@pakey423]

I've worked with the DMF/NaH combination a couple of times now. Luckily, I've never had any problems, but every time I work with this mixture, it unnerves me because I know what might happen. It's a kind of PTSD from my student days when a NMR-tube almost 'exploded' after trying to take a NMR of an acylchloride in d6-DMSO....... ....2 other chemicals that don't like to be mixed....... ;-)

[@ThatChemistOld]

Oh no!

[@pakey423]

@@ThatChemistOld I just remembered: it was ethyl chlorothioformate. Something with a horrible smell that already likes to decompose in the presence of traces of moisture. But with DMSO the decomposition was way more violent...

[@socratesm.5632]

DMSO readily reacts with electrophiles. Acyl chlorides, anhydrides, oxalyl chloride,etc. That's the basis of sulfonium-type oxidations like Swern... Interesting to see that sulfoxides are strikingly different than sulfones which are hard to monodeoxygenate. Any one knows a good method to reduce sulfones into sulfoxides?

[@1992kleenex]

Nice to know that part of my master could've been a disaster

[@ThatChemistOld]

It's surprising how common it is to see DMSO and NaH used - I'm working on an episode on Corey-Chaykovsky reactions, and most reactions on Reaxys use NaH in DMSO...

[@1992kleenex]

@@ThatChemistOld It is incredibly good at keeping polar compounds in solution as you rightly pointed out in the video. So I think it has to do with it being a great go to when you are working with polar reactants. Sort of like how benzene was used for everything back in the day as a go to solvent.

[@ThatChemistOld]

plus the H2 is easily removed from the reaction - no competing nucleophiles

[@danielaustin7643]

NaH/DMF at 120C is such a common condition

[@tramixor3202]

Hello. I work in life sciences and we use boiling DMSO as a solvent for Polyethylene terepthalate. Is boiling pure DMSO safe?

[@simedinson984]

I just realized i have been running a reaction in Dmf with 20 % NaH and was like why does the procedure state keep it under 40 C now i know will start doing my additions to it more slowly

[@ThatChemistOld]

Low and slow, and better yet use a cosolvent!!!

[@simedinson984]

@@ThatChemistOld Yea i did the addition at 0 c with DMC as reagent and co solvent but Yea was an interesting realisation

[@Martin-rb4np]

2:47 "Massive consequences, someone could even have gotten killed, injured or potentially fired." i feel that the prioritization of severity is a little reversed here :D

[@ThatChemistOld]

Lmao

[@Auroral_Anomaly]

A day in the life of sodium hydride: >shows up >ignites randomly >explodes when quenched >refuses to elaborate further >leaves

[@Calilasseia]

An alternative title for this video ... "How to Turn Your Bomb Calorimeter Into an Actual Bomb" ...

[@crabcrab2024]

I guess everything said also applies to KH... Nice video anyway! Thank you.

[@ThatChemistOld]

presumably - working with KH at all is sketchy; I know a local research lab that burned down from an undergrad who tried to quench KH improperly

[@crabcrab2024]

@@ThatChemistOld yeah, this stuff is notorious, but it works much better than NaH in almost all cases .

[@romanpolanski4928]

KH is vastly more reactive and more dangerous than NaH. I wouldn't put it anywhere near DMF and DMAC, though I have used it to make potassium dimsyl without problem.

[@socratesm.5632]

Interesting how Calcium makes it so much safer. I've distilled DMF from CaH2 countless times. And I always add buttloads of it... a little decomp. takes place and CO and Me2NH are detected. I'm curious to know what did the authors say about the fate of nitrogen atom? Also Me2NH ?

[@ThatChemistOld]

In the reaction scheme I show what products they reported - as far as I can tell, it's more of a shockwave from the sudden pressure increase from the exotherm that causes the issue, rather than the production of lots of gas

[@prakashbishnoi6593]

Very informative videos

[@ThatChemistOld]

Thank you!

[@samiraperi467]

I'm here for the explosions, the other chemistry is just a bonus.

[@GuaranaMontana]

Can you please write the solvents out? Thank you!

[@ThatChemistOld]

i'm not sure what you mean

[@danlukyanov5122]

NaH/DMF reactions smell with amines and some another shit after several hours at 50-60 C. However, on lab scale, if you do not seal your vessels but use CaCl2 tube or Ar inlet, it is nothing to warry about.

[@kevinli9525]

I fucking love these videos

[@Azuredemon_LKA]

NaH : " I'd Explode"

[@elementbr]

NaH and DMF makes me angry, as a process chemist. Got angry at many a MedChemist over the years.

[@ThatChemistOld]

good! keep them as safe as possible!!

[@elementbr]

@@ThatChemistOld Oh, I do. NaH/DMF is slowly being swapped out for Li-HMDS/THF; which is the 1st thing I'd do anyway if a MedChem prep came my way.

[@joeylawn36111]

"Should I mix sodium hydride with DMSO or DMF?" *NaH!*

[@ThatChemistOld]

lmao

[@xiaoshengxu4148]

Dr. Chemist, I am developing some pharmaceutical product. I want to work with you. You help me design the synthesis route. I do experiment. If you agree, please let me know your email. I will send to you the chemical name to be developed.

[@ThatChemistOld]

my contact info is on my youtube info page - otherwise you can reach out to me on the discord