[barcrphd]

i am trying to synthesize the following ligand for quite a long time. but i could not get it as of yet. i am thinking of giving it a fresh try. but not before getting some suggestions from you people..

please suggest your ideas....

[saltyf]

I think this can be extremely difficult, for the CH2-Br moiety can easily reaction with the primary amine via an intramolecular SN2 mechanism.

[barcrphd]

ofcourse, it is difficult, but not due to the problem that you have suggested. infact, this is the target ligand. but i dont want it in this form. ok, to avoid confusion, i will give a new structure. see the following structure. even this will do. i will then remove the phthalimide protection to generate the amine.

[HP]

I suggest you following synthesis:
Ethylene triamine + phatalymide -->protection of both primary NH2 groups as your own suggestion..
Next Michael addition of CH2=CHCOOH(acrylic acid) to free secondary amine obtaining the coresponding beta-amino carboxylic acid derivate.
Then you may try Borodin reaction (known also as Hunsdiecker or Hunsdiecker-Borodin reaction)  of Ag-salt this carboxylic acid with Br2/CCl4 to desired product beta-ethylbromo aduct + AgBr.
Whish you success !

[wereworm73]

I'd stay with the phthalimide version since you don't have strongly nucleophilic groups on the same molecule as the brominated carbon. 

The problem with the bromoderivative of diethylene triamine is that the NH₂ groups can do a nucleophilic attack on the brominated carbon.  Because of this, these molecules can react with themselves to form piperazine derivatives (or polymers, if the NH₂ group and the brominated carbon are on different molecules).

[barcrphd]

i am really not able to understand why this secondary amine is so reluctant to N-alkylation with 1,2 dihalo compounds. i tried using NaH, K2CO3, KHCO3 etc under different experimental conditions. alas... not even trace of a new product. some times this N-alkylations are so easy that it turns out to be a problem, sometimes when we want them to proceede they dont.

[wereworm73]

Could you show us your proposed synthesis?  You might be getting an unwanted side reaction somewhere.

For instance, if you do a Gabriel synthesis with a 1,2-dihaloethane as one of your steps, you may end up with a 1,2-diphthalimide derivative that won't allow any alkylation reactions (recommend using an excess of 1,2-dihaloethane if you want to avoid this product).  Or if you're trying to deprotonate the phthalimide with a nucleophilic base (like NaOH) but 1,2-dihaloethane is also in the same flask, then you'd have a 1,2-diol with poor leaving groups.

Also for your final product, I just realized that the tertiary nitrogen in the center may still react with a halogenated carbon from a neighboring molecule, forming a dimer.  If it's okay for the nitrogen in the center to be quarternary, then you might want to put a protecting group on there so your final product can't react with itself.

[barcrphd]

The proposed synthesis scheme is attached below. if you could suggest some modification that will be great.

[HP]

You may try also reaction your NH derivate wirh Grignard for example with CH3MgI
R2NH + MeMgI --> R2N:-MgI + CH4 gas (Tserevitinov method)
Then R2N:- MgI + BrCH2CH2Br--> your product + MgBrI
Keep stechiometry reagents strictly 1 : 1 though bisubstituate product possible also then...

[wereworm73]

  Are you sure you're getting a diphthalimide derivative from Step 1?  The triamine doesn't have any good leaving groups.

[barcrphd]

You may try also reaction your NH derivate wirh Grignard for example with CH3MgI
R2NH + MeMgI --> R2N:-MgI + CH4 gas (Tserevitinov method)
Then R2N:- MgI + BrCH2CH2Br--> your product + MgBrI
Keep stechiometry reagents strictly 1 : 1 though bisubstituate product possible also then...

this seems to be a good idea. let me see if it works. thanks HP

[barcrphd]

Are you sure you're getting a diphthalimide derivative from Step 1?  The triamine doesn't have any good leaving groups.

the first step works fine. it is a reported procedure and the NMR and mass suggests that the product is formed.