help with reaction conditions

[DFC]

Dear all,

 

I am trying to make this compond ( attached) and I am not getting anywhere. I have done the reaction by Dropwise addition of boc-protected hydrazine to 1,3-diiodopropane at RT using ACN as solvent and a catalytic base ( NaHCO3).

Can you recommend any other reaction media? Suggestions?

Reaction.pdf

[Knumbnuts]

I notice you are not using a base to remove the HI. So first pick a base.

I think you may see a lot of di-alkylation here, perhaps some cyclisation as well.

Add the hydrazine to the di-iodide. This may help avoid di-alkylation.

You can also use ethanol as the solvent or DMP or THF, etc.

[DFC]

HI Knumbnuts,

 

Thanks a lot for your reply, which base you recommned to use if I use THF or ETOH as solvent?, at catalytic o stoichiometry?

Do you think temperature will improve?

 

thanks

 

D

[Horza2002]

Hi there,

 

I think there is an inherant problem with this reaction. When undergraduates are taught about making amines, the first thing you are told is that you can't make them from alkyating a NH₂...the monoalkylated nitrogen is more reactive than the unalkylated nitrogen due to the electron donating properties of the alkly chain. I would expected that you would eventually end up the the tetraalkylated amine instead of your desired monoalkayted.

 

Additionally, if you add to strong a base to this reaction, you will deprotonate the Boc N-H (it is rather acidic due to the electron withdrawing properties of the adjacent carbonyl). If that happens, then you are going to end up alkyating the wrong nitrogen atom.

 

You could potentially make the dianion (deprotonate the Boc nitrogen and the NH₂) with two equivalents of BuLi and then try adding one equiv of the iodide, but I expect you will get cylisation and a mixture of products.

 

The main issue with this reaction is the diiodide...is it essential that you do this? If not, then I would suggest adding a few more steps into the scheme and introduce the second iodide after you have alkylated the hydrazine

[Knumbnuts]

HI Knumbnuts,

 

Thanks a lot for your reply, which base you recommned to use if I use THF or ETOH as solvent?, at catalytic o stoichiometry?

Do you think temperature will improve?

 

thanks

 

D

 

 

HI Knumbnuts,

 

Thanks a lot for your reply, which base you recommned to use if I use THF or ETOH as solvent?, at catalytic o stoichiometry?

Do you think temperature will improve?

 

thanks

 

D

Temperature will make it worse. As a base I was thinking of diisoproplyethylamine 1.1 equivalents.

[DFC]

Hi there,

 

I think there is an inherant problem with this reaction. When undergraduates are taught about making amines, the first thing you are told is that you can't make them from alkyating a NH₂...the monoalkylated nitrogen is more reactive than the unalkylated nitrogen due to the electron donating properties of the alkly chain. I would expected that you would eventually end up the the tetraalkylated amine instead of your desired monoalkayted.

 

Additionally, if you add to strong a base to this reaction, you will deprotonate the Boc N-H (it is rather acidic due to the electron withdrawing properties of the adjacent carbonyl). If that happens, then you are going to end up alkyating the wrong nitrogen atom.

 

You could potentially make the dianion (deprotonate the Boc nitrogen and the NH₂) with two equivalents of BuLi and then try adding one equiv of the iodide, but I expect you will get cylisation and a mixture of products.

 

The main issue with this reaction is the diiodide...is it essential that you do this? If not, then I would suggest adding a few more steps into the scheme and introduce the second iodide after you have alkylated the hydrazine.

 

Hi there,

 

Thanks a lot for your comments, I would consider to add more steps and try to do the reaction with only one iodine. I will see how it goes.