Chemistry Problem Set #1

At work, every Wednesday we have a problem set to solve. I will try to solve them and write down the solution here (I will loose my papers if I write them down on a paper-block, here I can always go back and look).

So, the target molecule for this week is (1)

(1)

It did not look like something difficult, especially if you think about the parent scaffold (2)

(2)

So, I started to think how to make the parent scaffold (2) and then go back to the target. So, retro-synthetically I was thinking that you would need to have 2-(aminomethyl)aniline and react it with some kind of carbonyl with good leaving groups (like L1-CO-L2). Some brainstorming and google search gives me CDI (carbonyldimidazole)

Anyway. They usually are not happy with one-step answers, but want you to go further back. So, how to make the 2-(aminomethyl)aniline? Well. I guess you could do something like having a bromide where the aminomethylgroup is (i.e. having a bromomethyl instead of amino, and yea, the aniline should be a nitro group which can be reduced with iron dust). Well, they say one image says more than 1000 words and it is very truth in chemistry. This is the route I would choose:

a) AIBN, NBS in CHCl3. b) NH3 in... something aprotic. Maybe neat NH3 (?). c) Reduce the NO2, Fe-dust in ethanol and NH4Cl is quite normal to use here. Or  Zn(Hg) in HCl

Well, I guess there are other routes. I found this papers (here and here) in which other routes are conducted (and the molecule looks a bit different).

Do not have much more time now so I will have to do the rest later :).

And here is the rest of the exercise. So, the target molecule can be synthesized in a different way. Here is a short retrosynthetic analysis

And the mechanism for this is a one-pot reaction (click on the image to see it clearly), but you can also isolate the imidine and then react it with the nitromethane

One thing I was wondering for my self... why does the methoxi do not attack the imidine carbon? I have to check the paper and see what they say about it (do not have the paper with me at the moment)