[rolnor]

I have a dialkylaminoethyl ether R1R2NCH2CH2OAr and it is much more difficult to hydrolyze the ether-bond in this molecule than it is to hydrolyze the ether-bond in R1R2CHCH2CH2OAr. My only explanation for this is that the nitrogen gets protonated and this positive charge repells any proton from protonating the ether-oxygen. Is this possible? Is not the charge on nitrogen too far away from the oxygen to have this effect? I suppose the only way to prove this is to run some ab-initio calculations? I should say also that i use refluxing hydrobromic acid. R1 and R2 are simple alkyl.

[clarkstill]

I'd say the protonation of the amine is certainly the culprit. The inductive effect can certainly travel through 2 x CH2s. Also, there will be a stabilizing hydrogen bond between the oxygen lone pair and protonated nitrogen, further decreasing it's basicity. In short - i'm not massively surprised!

[rolnor]

Is it possible to see this in a molecular modeling software somehow? I have used PC-Model from Serena Software before but I have not looked into this molecule-system yet.
If ab initio calculations are neccesary it will be more complicated.
I checked now on PC-Model but the atom-charges in this non-conjugated type of system is fixed as far as I can see. I have Spartan -06 but I am no expert on ab initio I am afraid.
The hydrogen-bond thing is interesting, it forms a six-membered ring so it is likely to occur but this is a system with refluxing hydrobromic acid, I wonder if this would not break such a bond?

[wildfyr]

refluxing hydrobromic acid

Oy!

[rolnor]

Yea, its a stable m-f! I can cleave it with refluxing hydroiodic acid, it takes 2 hours.

[rolnor]

I ran my molecules in Spartan and the ESP electrostatic potential for the oxygen atom is higher in protonated R1R2NCH2CH2OCH2CH2CH3 then in the free base, this mean that it is easier to protonate the oxygen in the free base. It is probably a significant difference.

[hollytara]

We work with polyethylenimine -  it usually will only protonate on 1/3 of the Nitrogens at normal pH values.  If you have a basic N two carbons away from a much less basic O, the protonated on N form will drastically change the basicity of the O - the two + charges do not want to be so close together. 

I had very good luck cleaving ethers (on a small scale) with BI3.  It is nasty stuff and you need a glove box to keep it dry, but it will cleave those aryl ethers in high yield and very quickly.  We would hit the aryl ethers with a little of that stuff, work up with water and get phenols in minutes.

[wildfyr]

We work with polyethylenimine -  it usually will only protonate on 1/3 of the Nitrogens at normal pH values.  If you have a basic N two carbons away from a much less basic O, the protonated on N form will drastically change the basicity of the O - the two + charges do not want to be so close together. 

I had very good luck cleaving ethers (on a small scale) with BI3.  It is nasty stuff and you need a glove box to keep it dry, but it will cleave those aryl ethers in high yield and very quickly.  We would hit the aryl ethers with a little of that stuff, work up with water and get phenols in minutes.

And a new user comes out of left field with one heck of an option!

[rolnor]

Excelllent! This explain what I have seen. I have cleaved my ether with BBr3 and its no problem, I just wanted to explain WHY its so difficult to do it with a proton acid. Thank you, I give you a "Molesnack".