[MOF]

Hello everybody,

I am facing from quite some time a reaction that I cant successfully run. The reaction is this one:

1,3-propanediol --> 1.NaH, dry THF, Ar atmosphere --> 2. TBAB, Allyl Bromide

The workup of the reaction is as follows:

1. Quench with water
2. Dilute with EtOAC
3. Washing with HCl, Water, Brine
4. Concentration at rotavapor
5. distillation under reduced pressure

This should afford a colorless oil, according to literature. (DOI: 10.1002/anie.200353225)

Well, at step 4 i get a yellow oil which cant be distillated under reduced pressure. The boiling temperature reported is 55C at 10mmHg. I tried the distillation many times and raised the T until 104C under vigorous stirring. The liquid seemed boiling but no distillate was being recovered.

I ran this reaction in different ways, with and without Ar atmosphere, but i am not able to collect any purified product. When not in Ar atmosphere, the mixture turned brown upon addition of the allyl bromide which is not happening under Ar protection, making me surmising some kind of side reactions are happening in the presence of air.
I also tried to purify it by flash chromatography but from the TLC plate there's a huge stain being carried with the solvent front no matter the polarity of the solvent.

I attached the NMR spectra of the crude product. Thanks in advance for any help you could give me.

[phth]

Are you sure that the allyl bromide is good (NMR can be deceptive), and are you sue the NaH is good? You could have allyl alcohol/bromide and NaH/NaOH in dry solvent...

https://www.sigmaaldrich.com/spectra/fnmr/FNMR003932.PDF

https://www.sigmaaldrich.com/spectra/fnmr/FNMR009215.PDF

Radical reactions are more facile  in the presence of oxygen. NaH can produce radicals.

[wildfyr]

Could we get integration on the NMR? Also, what solvent is it in? I don't see chloroform or DMSO. I'm also pretty sure you have plenty of ethyl acetate left in that crude product. And hexane as well, thats whats 0.9-1.5. Might be THF too, its a little hard to suss out since I don't know the NMR solvent. You should run this in CDCl3, then compare the shifts closely to the SDBS catalogue NMRs. This will give you an indication of the conversion as you get disappearance of one of the characteristic shifts at the reactive site. (like 3.93 for allyl bromide)

Also, I'll point out that they use the TBAI not TBAB. I think this may be to increase the reactivity of allyl bromide in addition to acting as a surfactant. You get halide exchange to the ally iodide which is more reactive than allyl bromide. It seems likely one of those things that shouldn't matter frankly, an alkoxide should easily react with allyl bromide, but perhaps this is necessary.

I think you have very little propane diol left, one if its peaks is at 1.81.

[wildfyr]

Also, I second that your NaH could be garbage. And check the allyl bromide by NMR in CDCl3. If its impure you can fractionally distill the allyl bromide to purify it. Your NMR does look more like allyl alcohol, though once again that is NMR solvent dependant.

[MOF]

I am sorry for my inaccuracy on the description and thanks for the prompt replies.

The NMR solvent is CDCl3. Ethyl acetate may still be there so I will try to remove it in some other way. Concerning Hexane, i dont know how it can be in the reaction mixture (maybe side reactions of the double bond?) (I will provide the integration as soon as i get to the lab.)

Yes, they used TBAI but in storage we had just TBAB, which i dont think it would make a big difference in reactivity because, as said, the methoxide is a quite strong nucleophile and that carbon attached to the Br also is quite electrophilic.

Why do you say that the NaH that i used is not good? Actually i could give it a try and change for a new one to see if there is some difference.

Regarding the synthesis route, the product may be made in different ways but these reactants are related to the project i am working to, so they can't be changed.

[wildfyr]

If it's Cdcl3 why is there no residual chloroform peak? Did you remove it? If it's not hexane then such a peak is associated with oligomerized polyolefins (such as allyl). Or, more likely, it's from the NaH which is usually stored as an 65% in mineral oil dispersion. If you aren't accounting for this impurity it may be another source of issues. Your equivalents of NaH will be wrong.

NaH not being good is a matter of experience. It's a reagent that goes bad easily unless stored very carefully. It's also pretty hard to tell how bad it's gone unless a reaction isn't working. I wonder why they used 3 eq of NaH rather than 2.

As a model reaction you could dry to react dry ethanol or n propanol similarly to make sure things are working without complication.

[MOF]

Yes, i worked the spectrum out with Mnova software, thus eliminating the peaks related to the small impurities and the solvent. Here is the complete spectrum with all the peaks and the integrations.

Actually, I thought that some oligomerization of the bromide since there is an excess of it in the reaction, but i couldnt figure out which peaks to account for impurities since the mixture looked pretty difficult to interprete. I will try the control reaction with the alcohols and see if it works out well with that NaH.

[rolnor]

The catalytic power of TBAI is muck stronger, you should use that.

[OrganicDan96]

since NaH normally is supplied as a suspension in mineral oil, if the oil is giving impurities then you should was it by placing the amount you need into  your dry reaction flask under nitrogen and add THF, give it a swirl and syringe the THF off. repeat this a few times to wash off all the oil.

[MOF]

Thank you very much for your kind suggestions. I have run the reaction again and after distillation NMR confirmed that I got the product. The only problem is that from the paper they said "colorless oil", while my product is yellowish... Anyway thanks again, now i can go on with the next step.

[wildfyr]

What did you change to get the correct product?

[MOF]

I just run the reaction again being very careful to keep it away from air and distilled the product as they said. The NMR is below. Actually there is still some solvent which is being evaporated in the oven under vacuum, i think there is still some ethyl acetate.

[OrganicDan96]

I have had products that are supposed to to be a white solid but was quite yellow when in fact the NMR couldn't be cleaner so colour can mean nothing