[João Paulo Fernandes]

I'm trying to do a reaction between an alkyl iodide (a little bit unstable) and piperazine, in order to obtain the monoalkylated piperazine. However, I'm having trouble obtaining a good yield and controlling the mono/dialkylation ratio. Could anyone help with suggestions?I've tried to do the reaction with 2 eq. of piperazine monohydrochloride in EtOH, and a yellow solid was formed. However, the product seems to stay in the aqueous phase during the workup... How can I obtain it from the aqueous solution without extract the piperazine?

[Archer]

Piperazine in dirt cheap, mono-protect with an amide or BOC (which ever best suits your substrate). You will get low yields but no matter.

When you alkylate an amine the starting material generally has a higher affinity to mop up the HI produced in the reaction. So your product is more likely to form a quaternary salt.

[gerrad1888]

I can give you a reference,just see it,it may help you

http://dx.doi.org/10.1021/op300026r | Org. Process Res. Dev. 2012, 16, 748−754

(mod edit, please do not post complete references, citations are good enough)