[dcobice]

dear all,

I would like to know if anyone can help me with this reaction ( conditions etc...)

thanks a lot

diego

[AlphaScent]

Must show an attempt at your work.  It is part of the forum rules. 

What do you think is happening?

What type of reaction is happening?

[dcobice]

Must show an attempt at your work.  It is part of the forum rules. 

First of all, I apologise for this.
What do you think is happening?
What I think is a nucleophilic substitution of the H of the protected hydrazine to Iodine of the diiodopropane with HI as by-product. I did the reaction at RT adding the hydrazine ( drop by drop) to the diiodo solution to control the kinetics avoid formation of potential dimers. The problem is that the reaction did not work (controlled by GCMS). I used ACN as solvent.
Do you think with temperature ( 60-80C) of adding a base as TEA (as catalyst) will improve the reaction kinetics ? what solvent recommends? I was thinking DMF, but them, how can I recover the material?

Thanks



What type of reaction is happening?

[AlphaScent]

Ok so your conditions were:

Dropwise addition of boc-protected hydrazine to 1,3-diiodopropane at RT??

You didnt add any triethylamine and raise the temperature??

The last part of your response I am confused about.

Cheers.

[dcobice]

Yes, my condition were as you have described.
I did not add any base and the reaction was performed at RT.
Using the aforementioned conditions I did not get any product at all. I have monitored the reaction by GCMS.
In order to push the reaction, my questions were:
1) should I use a base as catalyst such as TEA, or an inorganic one? to facilitate the proton removal from the hydrazine?
2) should I increase the temperature? how much?
3) which solvent work best, protic o non-protic? considering temperature and product recovery from solvent.

Sorry if i was not clear.

cheers,

Diego
 

[AlphaScent]

Yea no problem, just always good to have the facts straight. 

I am interested greatly in this question and do not have a straight forward answer for you but maybe we can work through it.

Things to consider:

1)  The reaction is a Sn2 type of reaction with hydrazine compound being the nucleophile.  Polar aprotic solvents work best for these types of reaction.  Acetonitrile seems to be a good choice because the problem may not lie in the solvent.  THF may be a good option.

2) You have a good idea of adding the hydrazine to excess diiodomethane to hinder the didisplacement (not really dimerization).  Your issue with using triethylamine as your base is that with alkyl halides, especially iodo compounds, the triethylamine can be readily alkylated to form the quaternary ammonium salt.

3) have you thought of trying to form the nuclephile first?  Using a cannula to add it to an addition funnel and then add it dropwise to the excess diiodopropane in acetonitrile.  If you were to try this, I would cool the reaction at minimum to 0 degrees.

4)  My concerns are I do not know how acidic the proton on question is.  Is TEA even a strong enough base.  Maybe you have to use butyl lithium??  Also, how stable is that anion going to be? 

I am sorry if I am not giving you what you are looking for but I would like to work it out.  Are you working off of a paper?

Cheers

[AlphaScent]

Here is a scheme I came up with using THP bromide and then making a leaving group from an alcohol.

[AlphaScent]

https://www.google.com/search?um=1&hl=en&q=list%20of%20t-butyl%20carbazate%20reactions&bav=on.2,or.r_cp.r_qf.&bvm=bv.49784469,d.dmg,pv.xjs.s.en_US.MpiVkF51mpA.O&biw=1280&bih=699&ie=UTF-8&sa=N&tab=iw&ei=SFTwUeaBI7bk4AO6roDgDA

The second paper down may be useful.

[dcobice]

thanks a lot for your input!, I will have a look at the synthetic scheme and the paper and I will get back to you. i have also found that the are doing the reaction in protic solvent 95% ETOH ( 100C) or even in water with K2CO3, I found this in a book.
Is this possible? as most of sn2 reactions are carried out in non-protic solvents....

thanks a lot for your help.
cheers,

[dcobice]

hi there,

Thanks a lot, BuLi/THF works pretty well. Yield was around 60%, I got some by-products, I am sorting this out with prep-LC.
Thanks a lot for your input and suggestions.

cheers,

d