[wereworm73]

I was wondering...if you added 2 equivalents of 1,4-dichlorobutane or 1,5-dichloropentane to ammonia, would you get spirocyclic derivatives of pyrrolidine (or piperidine, in the case of dichloropentane)?  Or would the added dichloroalkanes instead crosslink with other ammonia molecules, causing a polymerization reaction?  Since these dichloroalkanes are primary alkyl halides and the angle strain of pyrrolidine/piperidine should be reasonably low, I think the spirocyclic derivative reaction is possible, especially if the concentration of ammonia & the dichloroalkanes are low (to minimize the chances of a dichloroalkane molecule reacting with 2 ammonia molecules instead of one). 

What do you think?

[plu]

Just to clarify: by spirocyclic, do you mean multiple fused rings?  If so, how is this possible with the reagents you specified?

[wereworm73]

By spirocyclic, I meant two rings of pyrrolidine (or piperidine) are sharing just the 4^o nitrogen.  Hypothetically, one end of the dichloroalkane would add to the ammonia, and then the other end would do an intramolecular reaction on the nitrogen to form a heterocyclic ring.  Since the nitrogen can be quaternary, another dichloroalkane molecule could add to it in the same way, forming the second ring of the spirocyclic compound. 

[movies]

That's a really cool idea!!  I don't know if forming the second ring would be all that favorable though.  It might just sit as the alkyl bromide, but you might be able to overcome that inertia.  The bis(pyrrolidine) one should be better than the larger ring one.  I think that you could probably avoid polymerization if you ran the reaction relatively dilute.

You might have a problem with the formation of 4 equivalents of HBr though.  It might end up just protonating one of the amine intermediates and then you are stuck.  Adding another base might get a little complicated because you would probably increase the occurence of elimination from your alkyl halides.

[HP]

Theres known synthetic route similar of described by you in which in 1964 is synthesized  drug for brest cancer therapy called "Spiridazine" by the following scheme:
reaction of two moles 1,4-bis(beta-chloroethyl)-piperazine--> yes the formed this reaction compound have two quaternary amonia groups formed as you propose Can someone draw the reaction?

[wereworm73]

Theres known synthetic route similar of described by you in which in 1964 is synthesized  drug for brest cancer therapy called "Spiridazine" by the following scheme:
reaction of two moles 1,4-bis(beta-chloroethyl)-piperazine--> yes the formed this reaction compound have two quaternary amonia groups formed as you propose Can someone draw the reaction?

I wasn't able to find spiridazine on Google, but it looks like the reaction would create a dispiropiperazine ring between two other piperazines.  Does this reaction go on to form a long chain of spiropiperazines?

[wereworm73]

Whoa, if that reaction does what I think it does, then maybe halogenated halves of large crown ethers could add to piperazine to form an spirocyclic polymer that can catch anions AND cations!  That could be an awesome catalyst...or if you can trap organometallic reagents in the ether rings and reel in carbanions toward the 4^o nitrogens, maybe that could set up a type of polycatenane reaction.

[HP]

What reaction you think will work for your crown ether functionalization to piperazine rings? And yes the name "spiridazine" dont work in google-this is the name of the drug in bulgarian and i dont know its proper name in english, so if someone have some idea pls enlight us...I was thinking about polymer or oligomer formation but in the original paper i have its shown only dimer form.

[wereworm73]

Well, I'd oligomerize glycoxide and 1,2-dichloroethane (perhaps controlling this reaction with small amounts of X-CH₂CH₂Cl, with X as an initially poor leaving group to be treated later--I wouldn't want the halogenated ether to curl in on itself or polymerize too much).  So I'd should end up with something like this at first:

X-(CH₂CH₂O-CH₂CH₂-O-)_n-CH₂Cl

Then isolate the molecules with the desired n-value from the mixture, convert it to a dichloride, and add 2 equivalents of it to piperazine.  It should work similar to an alkylation reaction with ammonia, though most likely at a much slower rate due to the size of the dihalides (even though they're still 1^o).  One end of the dichloride species should add to one nitrogen on a piperazine ring while the other end adds to a nitrogen from a nearby piperazine molecule. So in between piperazine rings, it would basically look like this:

(CH₂CH₂O-CH₂CH₂-O)_n-CH₂CH₂
  /                                            \
>N                                          N<
  \                                           /
(CH₂CH₂O-CH₂CH₂-O)_n-CH₂CH₂

[HP]

Your idea not bad and theorethycaly would work well with PEG oligomeric derivatives and piperazine. To obtain you PEG(X)2 i sugest halogentaion of some low molecular PEG(OH)2 with the system CCl4/P(Ph)3 because the obtained PEG(Cl2) is water soluble but PO(Ph)3 not Whish you success in synthesis and keep us inform how it works!

[wereworm73]

CCl₄/P(Ph)₃, eh?  Thanks for the tip! 

I also thought of doing the oligomerization reaction inside the cavity of a cucurbituril
macromolecule so it can limit the size of the PEG derivatives, though it would need to capture anions instead of cations...

[movies]

CCl₄/P(Ph)₃, eh?  Thanks for the tip! 

That transformation is known as the Appel Reaction, by the way.

[HP]

Appel reaction indeed. I know it works with CBr4/P(Ph)3 but not very sure about reactivity CCl4 in this reaction...

[movies]

I think Cl is okay too, although it is more common with Br and I.

[HP]

For example: CCl4 + P(Ph)3 + ROH --> CHCl3 + PO(Ph)3 + R-Cl
Detai mechanism is:
CCl4 + P(Ph)3 --> P+(Ph)3Cl and -: CCl3 which attack R-OH and form the chloroform with its H-athom.
I am thinking for the chlorofom formed. Do you think its possible it to further react with P(Ph)3 if in excess and with alcohol molecule i mean:
CHCl3 + P(Ph)3 -->P+(Ph)3Clr and -:CHCl2  Is this carbenium anion stable or such reaction possible  What about -:CCl3 ?
Then -:CHCl2 + R-OH + P+(Ph)3Cl --> CH2Cl2 + PO(Ph)3 + R-Cl
Dichlormethylene formed...
Also is possible side reaction of recombination (i am not sure the right phrase) of two -:CCl3 moles to Cl3C-CCl3 (hexachlor ethylene)?
And for last can ROH react with -:CCl3 by this way:
R-O-H + -:CCl3 --> R-O:-(P+(Ph)3Cl ) + HCl + :Cl2 (dichlorocarbene formed)? Really mess reaction if yes
Cheerz!