Quat/Dequat

[fencamfamine]

I'm familiar with the usual examples quaternizing & dequaternizing amines but I cannot find any good papers that would give me some kind of insight as to what groups are lost on dequat (like are some groups lost preferentially). I think they are, but I don't have a paper on it.

I noticed that my medication for my IBS (a spasmolytic) had an N-ethylbromide (I assume so it won't cross BBB) but I realized that I didn't know about metabolism of said nitrogen. It would just be nice to know what my body could be making of this stuff!

-F-

 

[sekio]

Formation of a quaternary amine salt is easy as pie compared to "dequaternization" as you put it. N-ethylbromide is really just N-ethyl with a bromide counterion.

Dequaternization, as far as I know, lends itself to oxidising the heavier chains to aldehydes and the lighter chains to amines. This is at least the case in strong oxidising environments with PTC's like hexadecyltrimethylammonium salts.

I would assume that MAOI deals with quats the same way it deals with other amines. Either that or liver enxymes oxidise it, or it's just eliminated in urine/feces due to the polar nature of a charged ammonium cation.

Things like N-isopropylatropine (ipatropium) are "partially metabolized to ester hydrolysis products, tropic acid and tropane. These metabolites appear to be inactive". I would guess the body does the same to other quats.

 

[fencamfamine]

^I also think it's the lighter that end up as amines - the trouble is, I have no actual reference to the details. It seems that it was something briefly covered in class, never to be mentioned again.

I can only assume that their isn't very much selectivity because I've not seen it used as a route to change the character of a tertiary amine.

 

[sekio]

To be honest, I think it's a bit of a free-for-all when it comes to busting quats apart. Either that or an interesting problem for a grad student somewhere.

 

[vecktor]

many chemical techniques remove small tert alkyl first, then methyl then ethyl or isopropyl. leaving a dealkylated amine, it is usually driven by the stability of the resulting cation and frequently by the volatility of the resulting alkyl halide in what is the reverse of the quaternization reaction chemical reactions of this type are all reversible. There are however lots of variations with the reaction conditions being easily modified to encourage elimination to alkene or rearrangement over dealkylation
metabolic reaction is the other way round with the largest group being removed by being oxidised to the carbonyl or similar oxidation state species.

 

[Hyperthesis]

Sounds like trying to turn ipratropium bromide into a useful synthesis precursor. Since when are synthesis-related questions allowed here?

 

[vecktor]

Sounds like trying to turn ipratropium bromide into a useful synthesis precursor. Since when are synthesis-related questions allowed here?

for a second I thought that but the resulting material would be easier to just buy from some chindian.
if it strays into real synthesis discussion it will be killed, at the moment it is theoretical organic chemistry or metabolism.

 

[Hyperthesis]

OK, thanks for clarification!

 

[fencamfamine]

Sounds like trying to turn ipratropium bromide into a useful synthesis precursor. Since when are synthesis-related questions allowed here?

I simply mentioned it because that is what made me think of it. I asked for any GENERAL reference because I couldn't find any. I don't believe I even mentioned WHAT the material was. FYI ipratropium bromide doesn't bear an ethyl bromide, neither is it used for IBS.

I have found an number of examples in which on N-methyl can be exchanged for another via quat/dequat but there is no discussion of the underlying reaction.

It is the underlying kinetics that interests me - not practical synthesis. Everybody recites by rote 'quaternary amines do not pass the BBB because they carry a charge' but at least some central activity has been seen in a vast number of such compounds. I guess that there is some metabolism going on, but not what.

It just seems odd that such a basic & widely known reaction is, seemingly, so poorly understood...