Sciencemadness Discussion Board

How stable is Methyl/Ethyl Iodide in alcohols?

FireLion3 - 21-2-2018 at 12:17

I want to perform an in situ Finkelstein reaction with Ethyl Bromide in Ethanol or Methanol, and use the formed Ethyl Iodide to alkylate a stubborn Aniline. I attempted the alkylation already at 100c for 48 hours in Heptane under pressure, and even though it was homogeneous, the reaction only went to about 10% completion. I imagine using an Alkyl Iodide would solve this issue, but I am concerned about the stability of Ethyl Iodide in either Ethanol or Methanol. I would use Ethanol, but I only have Methanol on hand right now.

[Edited on 21-2-2018 by FireLion3]

SWIM - 21-2-2018 at 21:23

Wouldn't using a polar, aprotic solvent have been more likely to work than heptane?

It's good stuff for halogen exchanges too.

Maybe acetone?

Melgar - 21-2-2018 at 23:06

You need sodium iodide for the Finkelstein reaction, and more importantly, acetone. Due to the coincidence that iodide ions fit neatly into a cage of acetone molecules, sodium iodide has an anomalously high solubility in it. Potassium iodide works too, just a lot slower. Hell, sodium chloride will even dissolve in methanol, at least a little. I'm not sure where you got the idea to use methanol.

Maybe read this:

http://www.ch.ic.ac.uk/rzepa/blog/?p=439

[Edited on 2/22/18 by Melgar]

FireLion3 - 22-2-2018 at 05:13

I would like to use Acetone, but wouldn't that condense with my aniline as I mentioned in my post? Plus I would be worried that the boiling point of acetone would limit the rate of my reaction, seeing as the aniline was very resistant at 100c to ethyl bromide for 48 hours.

The biggest role of Acetone with the Finkelstein is to help drive the reaction forward by precipitation of the other halogen salt. In situ finkelstein reactions do not require this, and can often work even with just a catalytic amount of iodide ion.
Quote: Originally posted by SWIM  
Wouldn't using a polar, aprotic solvent have been more likely to work than heptane?

It's good stuff for halogen exchanges too.

Maybe acetone?


I should given more information. I don't currently have any polar aprotic solvents on hand which Sodium Iodide would be soluble in, such as DMSO or DMF. I have some THF but not enough to run the reaction and I'm not sure about Sodium Iodides solubility.


When I used Heptane, I wasn't attempting an in situ finkelstein reaction, but just attempting to alkylate the (secondary) aniline with Ethyl Bromide. As far as alkylations go with alkyl halides, this is fairly standard, as the salt will precipitate from the solution... which did occur, however the yield was very low, likely due to how crowded and unreactive my aniline is.

Quote: Originally posted by Melgar  
You need sodium iodide for the Finkelstein reaction, and more importantly, acetone. Due to the coincidence that iodide ions fit neatly into a cage of acetone molecules, sodium iodide has an anomalously high solubility in it. Potassium iodide works too, just a lot slower. Hell, sodium chloride will even dissolve in methanol, at least a little. I'm not sure where you got the idea to use methanol.


The idea for methanol (or ethanol) was because they are the only solvents I have available that dissolve sodium iodide, and I figured wouldn't interfere with the reaction (as acetone might via condensation)

The end solubility of everything doesn't matter, because I will be able to easily separate the alkylated aniline from the salts in the solution. The reason I don't want to deal with isolating the Iodide is because of how Ethyl Iodide readily decomposes upon exposure to air and light, so I figured generating it in situ would work best.

I've seen this technique used before in other alkyl halide alkylations, often by using a catalytic amount of iodide ion to drive the reaction forward.



-----

So is it known if alcohols react at any appreciable rate with alkyl iodides? I realize Ethyl Iodide is often produced in Ethanol from HI, but I'm unsure as far as reactivity with the solvent goes.



[Edited on 22-2-2018 by FireLion3]

Melgar - 22-2-2018 at 19:28

Normally though, chlorine will replace bromine, and bromine will replace iodine, when halogens are bonded to carbon. Carbon-iodine bonds are very weak, which is why they're more reactive. Carbon-bromine bonds are a bit stronger, but still not hard to break. Carbon-chlorine bonds are usually quite difficult to break, and are generally quite strong. Carbon-fluorine bonds are the strongest bonds that carbon can form.

So to get iodine to replace a stronger halide bond, there has to be a pretty powerful effect pushing things in the opposite direction. For the Finkelstein reaction, this effect is the huge solubility difference between sodium iodide and sodium chloride in acetone.

The condensation between amines and acetone is reversible, and tends not to favor the condensation product.

Also, reactions that don't work with a certain solvent, don't suddenly start working because "that's the only solvent you had". You should know better. ;)

FireLion3 - 22-2-2018 at 20:35

What I was worried about with the condensation was that the water generated via the condensation would then react with the ethyl halide, thus removing the water and driving the condensation forward (eliminating the reversibility). I imagine Ethyl Iodide would react rather rapidly with even trace amounts of water at elevated temperature.
Quote: Originally posted by Melgar  

Also, reactions that don't work with a certain solvent, don't suddenly start working because "that's the only solvent you had". You should know better. ;)


Lol of course, that is why my goal was to form the Alkyl Iodide in situ to elevate the reactivity. It is a pretty common technique. I actually found some TBAI when digging through my chemicals, so I'm going to use that as a substitute for Sodium Iodide. Finding a solvent that dissolves TBAI will be very easy. This should provide enough of a catalytic iodide ion to effectively drive the reaction forward.

I've used TBAB in the past to elevate the reactivity of a less reactive Alkyl Chloride, and I did find come across some references of using catalytic amounts of Iodide ions in a similar manner.

I'll report back how it ends up going with TBAI as a catalyst.