Org Prep Daily

November 2, 2009

Easy Iodination of Alkynes

Filed under: krest17, procedures — milkshake @ 8:23 pm


The question was: how to perform this reaction in a clean way (no column purifications, no distillations), cheap (if possible, no Ag salts or any other expensive metals), easy (if possible, no Ar and no Schlenk flasks, open air, solvents from bottles), scalable (well, this combines first three I guess), general (yes, I needed a library of these compounds with different functional groups and had no desire to develop different procedures for each of them separately).
Quick look in SciFinder showed two procedures as mostly used and welcomed by scientists; (a) using silver nitrate and NIS (posted on this website some time ago by Chris Douglas  (b) deprotonation with nBuLi in THF or Ether under Ar followed by quench with I2. Obviously, they could not meet my criteria. First approach required using of Ag salts and not so cheap and stable NIS, second one needed anhydrous conditions, cooling, flammable nBuLi and yes – Schlenk flasks and Schlenk line. It is not like I could not do it and I do have Schlenk line under my hood, but… sometimes 10-15 min more in SciFinder can save a lot of pain in the neck.
So, I found procedure from Scott E. Denmark (Tetrahedron 2004, 60, 9695) for the desired iodination in MeOH/H2O using KOH as a base and I2 to deliver I+. Although, this procedure was used only for omega-OH acetylenes, which could be the trick, I decided to give a shot. Reaction worked as a magic – easy, open flask, no cooling or heating, all reactants are cheap and could be found in any lab, water from tap and methanol from bottle. Yields are generally over 80% and no column needed. Below are some selected substrates I did.


Here is the magic procedure:

To a solution of alkyne (50 mmol) in MeOH (50 mL) was slowly added an aqueous solution of KOH (2.5 equiv) in water (10-12 mL) at rt. (I tried recommended 0°C and did not find any difference). After 10 min I2 (1.5 equiv.) was slowly added within 3-5 min at rt (I tried recommended 1.1 equiv. but could not reach full conversion). The mixture was diluted with H2O and extracted with pentane. The combined organic layers were concentrated and filtered through 3-5 cm plug of silica gel. Silica gel was washed with pentane till disappearance of spot of product on TLC. Pentane was evaporated and … that’s it. For all substrates I did so far purity of product was >95% by NMR and GC.

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