Sciencemadness Discussion Board

isopropyl bromide

Magpie - 2-5-2006 at 12:52

I tried to make isopropyl bromide today without benefit of a procedure. It was a total failure. :(

I placed 25 mL of Safeway grade 99% isopropyl alcohol in a 250mL RBF. To this I added 110mL of 48%HBr made previously. I set this up with a condenser and refluxed for 2 hours. All I ended up with was some oily looking drops on the inner wall of the RBF in the vapor space.

I did not use H2SO4/NaBr as the laboratory manual I had said that this will not work with secondary alcohols as they will undergo elimination. It specifically stated that 48%HBr can be used instead.

So, does anyone have any ideas about what I did wrong? Any help will be gratefully appreciated. ;)

PainKilla - 2-5-2006 at 12:59

I used:

90ml H2SO4
50ml Isopropanol
52g NaBr
15ml H2O

Mix all stuff but H2SO4 in flask, slowly drip in H2SO4 over a half hour period or so, and reflux for an hour and a half (including the drip process), and distill directly. The distillate comes off at exactly 59C. I had excellent yields using this method (80%.) I don't know about it not working.... as it worked absolutely fine for me.

Just to note, this stuff is interestingly volatile. I kept the 37ml I got from this in a tightly stopped flask... I checked on it recently (it's been about a month) and there is only a small amount left! I wasn't happy about that so keep it stoppered heh. Other than that though, it's a pleasant synth to do :).

[Edited on 2-5-2006 by PainKilla]

garage chemist - 2-5-2006 at 13:19

You need to distill it.
I have done ethyl bromide with HBr acid and I didn't see any product in the reaction mix. But as I distilled it I got a good yield of heavy liquid that wasn't miscible with water (you have to wash it, it contains residual ethanol and HBr).

Sandmeyer - 2-5-2006 at 14:29

Originally posted by PainKilla
I kept the 37ml I got from this in a tightly stopped flask... I checked on it recently (it's been about a month) and there is only a small amount left!

[Edited on 2-5-2006 by PainKilla]

It happened to me as well but with methyliodide, I kept it in a tightly secured plastic container but it seems to have the ability to go via plastic. I have made so many incidents with alkylhalides that I'm happy to be alive.

PainKilla - 2-5-2006 at 15:32

Sandmeyer: Damn, this is absolutely worrying. Isopropyl bromide is one thing, but methyl iodide :o. I will have to make a note to store this in glass flasks, and then like wrapped. I wonder if my DNA is isopropylated since that means I was breathing in it's vapors :X. (Cancer in 20 years? I hope not)

Also to add, I don't see any reason to mess with the HBr route, the H2SO4/NaBr is very easy, you don't even need to watch the reaction, just set the H2SO4 to drip at a steady rate and go read a book :). After 1.5 hours, distill and you are done. (Well aside from washing etc but that's child's play)

[Edited on 2-5-2006 by PainKilla]

Magpie - 2-5-2006 at 15:42

Thanks very much for the responses. I was in a mood to throw away my reactant mix but something told me not to. I will distill it and see what I get! ;)

But now I don't know how to store it. A bottle with a ground glass stopper is probably the best that I have. I do have corks, but no Parafilm.

Sandmeyer - 2-5-2006 at 16:03

Impossible! How long does it take approximately before one gets cancer from this stuff, can't really be 25 years, right? Maybe the riscs are exaggarated.


PainKilla - 2-5-2006 at 16:14

Well, I just said 20 randomly, but I think we may be safe, (well me at least :( )

"In a study designed to look only for lung tumors after short- term, high exposure, Poirier et al. (1975) gave groups of 10 male and 10 female strain A/Heston mice a total of 13 intraperitoneal injections (3 injections/ week) of 7, 17.5, or 35 mmol/kg (648, 1620, or 3240 mg/kg) 2- chlorobutane in tricaprylin. Untreated and tricaprylin-treated mice were used as negative controls, and urethane-treated mice were used as positive controls. Survival of animals in the low-, mid-, and high-dose groups was 75, 75, and 50%, respectively."

So, I figure, low dose.... 75% survival rate :).

You may have to be slightly more worried though :(. It's alright, I quite sure you didnt douse yourself in it like they do for the tests ;).

mantis - 3-5-2006 at 04:03

you have to add H2SO4 to the HBr-Isopropanol mix. The strong acid is needed as catalyst.

garage chemist - 3-5-2006 at 04:13

HBr is a stronger acid than H2SO4. Go look up the pKs values.

H2SO4 can increase the yields with primary alcohols (water removing effect), but secondary and tertiary alcohols must be esterified without H2SO4 because they otherwise yield the alkene due to dehydration.

Nicodem - 3-5-2006 at 12:08

I used a modification of what Weston and later Holt used to prepare ethyl bromide. It works well on IPA even if only one equivalents of NaBr and H2SO4 are used. Higher alcohols require excess of NaBr and H2SO4. With the bellow procedure and without reagents excess isobutanol gave only a 33% yield of isobutyl bromide.

Isopropyl bromide
200ml of 35% H2SO4 was boiled down to a volume of approximately 70ml (didn’t want to waste conc. H2SO4 by diluting it so I rather concentrated the cheap diluted one to the concentration of about 75%). This sulfuric acid was then added drop wise from an addition funnel to 75ml of isopropanol while stirring. Meanwhile portions of sodium bromide were added from time to time, 95g in total. The addition of H2SO4 was regulated in a way to keep the temperature of the mixture about 20°C (cooling is advised). The reaction mixture was left overnight and the next day it was distilled from a boiling water bath. The fraction distilling at 65°C was collected. The approximately 70ml of heavy liquid was washed with 2*70ml water to remove isopropanol, dried over CaCl2 and filtered. It amounted to 84.3g of a high density, volatile, colorless liquid (76% of theory).

[Edited on 3-5-2006 by Nicodem]

Magpie - 3-5-2006 at 14:33

Today I distilled the product of yesterday's HBr/IPA reflux using simple distillation. Production of a 2-phase distillate started at 50C and continued to 100C. At 100C production fell way off and I stopped.

After washing the distillate once with 25mL H2O and then once with 25ml of 5%NaHCO3 I ended up with 13.3mL of a clear, dense liquid smelling somewhat like chloroform. I now have it drying over CaCl2 and will distill it later.

Yield before drying and final distilling:

%yield = (13.3mL)(1.31g/mL)(60.10/mole)(100%)/[(123.00/mole)(25mL)(0.99)(0.785g/mL)] = 43.8%

I don't know if my relatively low yield indicates that this method is inherently inferior, or is just the result of working with a small quantity of IPA (25mL). It is probably more labor intensive as I had to produce the 48%HBr first.

But I'm very happy to see that the intended product was produced even though the yield is quite modest. ;)

[Edited on 3-5-2006 by Magpie]

Edit 2: Distilled dryed produc today. All distillate came over at a steady 58.5C confirming the identity as isopropyl bromide.

[Edited on 4-5-2006 by Magpie]

PainKilla - 3-5-2006 at 14:38

Nice, glad everything worked out. I highly reccomend trying it the way I did. Once my exams are over, I will be making it again, if you feel like waiting the week or so I'll post my results (but the ones that are up work excellently.) There really is no advantage using HBr... from a practical and safeties point of view. (Especially with such high yields via H2SO4/NaBr)

flyingbanana - 25-6-2006 at 08:44

is isopropyl bromide "good enough" for williamson ether synthesis, or should you do finkelstein on it to make the iodide first?