[Shomei]

Dear All,

This is a basic organic chemistry question (experimental question). I have forgotten the procedure and there are no books available in english or in my language in the university where I am currently.

I would like to substitute a primary alcool function located on an alkyl chain with a Br atom.
I would like to use HBr to do this, but I am unsure of the workup. - I know such compounds can be purchased, mine is different : there are fluorine atoms on several positions in the chain, at least 3 CH2 away from the alcool.

I did put 5g (partially fluorinated)alkyl-OH under high stirring with 4 eq. (mol) of concentrated HBr. (It is a 2 phase mixture)
But then, how do I treat the mixture to get the product ? I would like to avoid having ionic impurities as much as possible.

I was planning on :

1. Go to neutral solution with KOH.
2. Extraction of the organic layer with ether or DCM

Is there a better way to proceed ?

Thank you for your time.

[Dan]

I'd neutralise with a weaker base, like NaHSO₄, because with a base as strong as KOH there is a big risk of overshooting the end point of neutralisation and getting elimination of HBr etc. Aqueous/organic extraction should remove the ionic impurities and leave your haloalkane in the organic layer.

You could also try an Appel reaction

[Shomei]

Thank you very much for your answer and for your time.
I will do as you suggested.

[Shomei]

I have two additional questions:

1. What do you think of sodium bicarbonate in replacement for NaHSO4 ?
2. In this substitution reaction (Alkyl-OH -> Alkyl-Br) with HBr, do you know which solvent is usually used ? Currently, in my situation this is a two phase reaction which does not seem to be very effective...

Obviously, I cannot use ether for the extraction. Is there a risk with DCM ?

Thank you very much for your time and your answers.

[Dan]

1. Should be fine
2. I'm not sure, check the literature. What solvents are you using now? Neat starting material and HBr-AcOH or aqueous HBr? I guess DCM should be fine - glycosyl bromides can definitely be made with HBr-AcOH in DCM.

Due to my systems always containing somewhat acid labile groups I have never used HX for ROH -> RX transformations. I have personally only ever done ROH -> RI transformations of this type and have used either the Appel reaction or a two step procedure via a sulfonate ROH -> ROTf -> RI (ROMs and ROTs are cheaper alternatives to ROTf), both methods work well and are homogeneous.

[Shomei]

Thank you for your answer.

Right now, it is just the partially fluorinated alkyl-OH tail (oil) with concentrated HBR. This is a two phase mixture that I let under high stirring for two days.

Also, once the reaction is finished, when I do the workup, I can't see the compounds on TLC. I only have access to UV and  iodine. I have ordered vanillin (I don't know if it will work) and will get it in two weeks. I can not access molybdenum based compounds (to much paperwork for my boss). CBr4 is also out of bounds. However, I can have SOBr2 in two weeks. I will check for HBr-AcOH, thank you.

So, I don't know how to proceed with the purification. Also, the total amount of raw oil is about 4 mL, so distillation with the glassware at my disposal is not achievable. I will never get anything.

How do you proceed in such situation ? (when you can't see your compounds on TLC) ?

[Dan]

Right now, it is just the partially fluorinated alkyl-OH tail (oil) with concentrated HBR.

Conc HBr in what solvent? Conc aqueous HBr?

Also, once the reaction is finished, when I do the workup, I can't see the compounds on TLC. I only have access to UV and  iodine.

You could try a permanganate stain, that's usually very sensitive. Check out this pdf

http://isic2.epfl.ch/webdav/site/lcbp/users/181574/public/TLC_Visualization_Reagents.pdf

CBr4 is also out of bounds. However, I can have SOBr2 in two weeks.

Br₂ and a base will probably work in place of CBr₄, although that's not a nice compound either. We routinely use I₂/imidazole for Appel reactions rather than CI₄.

I will check for HBr-AcOH, thank you.

There's a pretty good chance your compound will dissolve in AcOH so this may be the way to go - and you can always add a bit of DCM. We use a commercially available solution of 33 wt. % HBr in acetic acid to make glycosyl bromides.