I'm running into some unexpected difficulties alkylating aniline. The compound I am working with is 4-Methoxy-N-methylaniline. I need to either
methylate or ethylate the nitrogen, avoiding overalkylation to a quaternary salt. I figure I can't readily go the formaldehyde imine route due to
likely resin formation. The catalytic routes I found using methanol or dimethyl carbonate all require solid-acids, which I fear would disrupt the
methoxy group.
I've been looking into is using an alkyl halide such as Ethyl Bromide, but I am unsure if a quaternary salt might form. I can't find much information
on how readily anilines form quaternary salts.
I recall a few writeups that mention Benzylaniline reacting with Benzyl Chloride in the presence or absence of Carbonate to form Dibenzylaniline, but
I am unsure how this would compare to using a simple alkyl halide. In those write ups they do not mention if any quats are formed when using Benzyl
Chloride.
[Edited on 24-4-2017 by Lillica]clearly_not_atara - 24-4-2017 at 13:33
They do, but less easily than aliphatic amines. I believe that methyl iodide is usually used for quaternization of aniline. Generally quaternization
is slower than alkylation of the secondary amine. Ethyl bromide is less reactive than benzyl chloride and consequently less prone to quaternization. I
think it will work fine.CuReUS - 25-4-2017 at 06:16
I figure I can't readily go the formaldehyde imine route due to likely resin formation.
do you have any refs for the resin formation ? because IMO,an eschweiler clarke is the best way to get what you want.
That's what I figured too, I'm planning on making some dimethylaniline for dyestuffs soon using the Eschweiler-Clarke so I'd
certainly hope it works.clearly_not_atara - 25-4-2017 at 09:23
Formaldehyde + aniline does indeed result in Friedel-Crafts alkylation over nitrogen alkylation:
Perhaps someone can clue me in here. I found a post by Nicodem (link below) saying that anilines can easily achieve n,n-alkylation because their
quaternary salts easily transalkylate, so using a stochiometric amount of alkylating agent could in theory achieve near complete n,n-alkylation. http://www.sciencemadness.org/talk/viewthread.php?tid=22274#...
Would I be able to just reflux my n-alkylated aniline with equiv bromoethane in a suitable solvent (pentane) and have it go to completion, in spite of
the salt precipitation? My intuition suggests yes, but I am unsure.
In some of these aniline alkylations, I read the authors commonly reflux the aniline/alkylating agent with sodium bicarbonate solution. I can see how
this would work but I would want to avoid going this route because it will certainly decompose some of my ethyl bromide, leading to incomplete
alkylation. Due to the high molecular weight of my compound, the only feasible way I can imagine separating it would be with chromatography, which I
can't presently do. Crystallization is feasible, but could be very tedious without knowing the ratios of secondary and tertiary amine.
So would it be feasible to have the reaction go to completion without a base present, with the salts precipitating? I imagine as the salts
precipitate, the secondary and tertiary amines will be continuously swapping in and out of solution, eventually allowing the reaction to go to
completion, but it's just speculation.
About methylating aniline with formaldehyde
I encountered a paper yesterday (to which I didn't save the reference) which involved producing n,n-dimethylaniline by alkylating aniline with excess
formaldehyde solution, in the presence of a base. They tested several bases and I believe they found triethylamine to be the most efficient, giving a
yield 80%+, whereas other bases yielded lower, with side products being resinous, I presume. If I find the paper again I will link it. clearly_not_atara - 28-4-2017 at 18:24
In order to dialkylate you will need at least one equivalent of base I'm afraid. Sodium carbonate usually works. PTC is not required in this case as
the reactants are neutral.
I think it has a good chance of working if the reaction is performed how you describe with a base.
[Edited on 29-4-2017 by clearly_not_atara]Lillica - 28-4-2017 at 18:42
My aniline (mentioned in original post) is already monoalkylated, so would I be able to get away without using any base since it only needs to be
alkylated once?
I'm assuming you're saying that a base is required for a one pot dialkylation only because after 1-equiv of alkylations has occurred, all of the amine
will be in salt form in the aqueous phase, unable to react with the alkyl halide in the organic?
