Dear Salaah,

I believe the formation of difficult-to-separate mixtures is unavoidable, considering there does not seem to be any strong preference to iodinate at the 2 and 7 positions at this stage.

If you consider the dihydroxylated compound, it is more electron-rich; and so more reactive towards electrophiles. I find it difficult to estimate wether it will functionalize ortho or para to the phenolic oxygen; but the reaction will definitely be easier. You may be able to improve solubility by protecting the phenolic groups; eg with PMB or TIPS.

It may be possible to go via the bromide (aryl bromides are usually easier to prepare). Consider: http://www.organic-chemistry.org/abstracts/literature/090.shtm

Good luck on your efforts to synthesize this compound!

Dear Dera,

Thank you s much for your interest. In case of protecting the phenolic group, the reaction will be directly oriented to para positions instead of ortho ones.(you can differentiate between ortho and para orientiation by 13CNMR and HMBC).

Actually, I am focusing on synthesizing ortho- derivatives to be used in modulation of bioactive DNA structures. This is really after performing moleculer modelling for such structures.Furthermore, Bromo derivative have already been synthesized before and I would like to innovate a new synthesizing method.

I really appreciated your efforts.

Base mediated iodination usually works quite well for selective orthoiodination.

DIPA and KOH are relatively poor choices as bases. The free NH is likely to interfere and hydroxides are far too nucleophilic.

Try with DBU, diisopropylethylamine, or NaH/THF.

What happens in reactions 1 to 3?

Is any of your desired product being formed in TFA? Monitor it by TLC, use a slow addition of TFA/NIS to anthraquinone in TFA in an ice salt bath.

Have you tried using AcOH/NaOAc and NIS?

Oxone and potassium iodide in MeOH/H2O may be worth a try.

Dear Eric,

Actually, Concerning reactions 1 to 3, nothing is changed  through following the reaction by  TLC.

In Case of TFA, It is very difficult to select the structures, you have a variety of orientation of Iodine ( maybe you have di- and/or tri-iodanation process in addition to mono-iodinations.(TFA is considered as  a strong activator for NIS to liberate I)

Nice idea to perform DBU.

Selection of TLC solvents can be a good way to differentiate between multiply iodinated systems. I would recommend DCM/toluene as being likely to show the greatest difference as the pi stacking and polarisation functions have a greater contribution. Also try visualising with a stain that gives different colours such as vanillin or p-anisalde. The change in electronics on the aromatic ring should affect colouring.

Use an excess of TFA/NIS and see if it converges on a single product. It is possible to reductively remove the excess iodine groups with NaOH/Na2SO3