[kriggy]

Hi guys,
I have 4 compounds with structures shown bellow:

The thing is, that I dont know the position of the bromine in compound D (it was done by bromination of compound A while the others had the substituents present in starting compounds). The thing is that I cant distinguish between the indazole NH and the amidic NH surely in compound D.
Those protons in all four compounds have roughly same chemical shift (13,3+-0,1 and 11,3+-0,1). If I then run NOESY on compound B and C and identified which proton is which, would it be reasonable assumption that chemical shifts of those protons would be same in compound D so I could identify the position of the bromine atom?

[discodermolide]

Would a ¹H-¹³C correlation not help identify where the bromine is sitting?

[kriggy]

Im not sure how. I know that the ring on which it is bonded has 1,2,4 substitution pattern but I cant identify the specific ring position. The structure D is most likely since I used 1,7eq of NBS and a) there was about 85% of monobrominated product and it is single product b) the benzimidazol-2-on ring doesnt seem to have that different reactivity between those two carbons in para positions to the nitrogens (therefore with such an excess of NBS there would be both isomers IMO).

[Dan]

Those protons in all four compounds have roughly same chemical shift (13,3+-0,1 and 11,3+-0,1). If I then run NOESY on compound B and C and identified which proton is which, would it be reasonable assumption that chemical shifts of those protons would be same in compound D so I could identify the position of the bromine atom?

I think it's reasonable to assign the NHs in D based on analogy to B and C. The shifts are different enough that bromination will not swap the order. Then once you know where the indazole NH is, you can hopefully track NOESY correlations in D to find the Br position.

Also, if you can fully assign the aromatic protons in A (but I'm guessing probably not), deuterolysis (reductive dehalogenation with deuterium) of D will give you an answer.

It looks like D should be crystalline though, can you get an X-ray structure?

[kriggy]

I dont have it anymore and sadly dont have time to make it again and then try to crystalize (submitting thesis next week and still dont have it written fully and checked by my PI).

Thanks for anwers guys

[Irlanur]

Did you not run an HMBC?

[kriggy]

Yes I did but I still cant put it together. Ive never realy done something like this.

[Irlanur]

Is there no Carbonyl-proton coupling?

[kriggy]

Carbonyl is coupled only to the NH next to it. Thent here are more couplings from the NH but it seems to be that one needs to be either 2 or 5 bonds and Imn ot sure how likely is that. Im going to talk to my supervisor today so I think well figure it out somehow.

[Irlanur]

If you see a carbonyl-NH coupling you now which NH is which. Then you should see a coupling from a quaternary carbon to the NH, from there you should be able to go on (as long as the peaks are resolved...)

[kriggy]

The problem is that we saw couplings to both quarternary carbonsbut we figured it out somehow. I think for being 100% sure we would need a X-ray structure but for masters thesis it is good enough. Thanks for help guys

showing HMBC correlations