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Iodine is widely used in pharmaceutical synthesis as a reactive handle for Functional Group Interconversion (FGI). It is rarely carried through to the final product, although examples of iodine-containing APIs are slowly increasing. I can be used as a radioactive label.
Typically, carbon-iodine bonds are created through electrophilic attacks on substituted bonds. I2 is the weakest electrophile of all the molecular halogens, so is often activated, otherwise more reactive sources of I+ have to be generated. Electrophilic iodination is reversible under strongly acidic conditions. Oxidation can be a side reaction with electrophilic iodination reactions. Iodine can be introduced via SN2 type processes using the iodide anion. HI is a strong reducing agent, so care should be taken when using this reagent in the presence of reducible functionality.
Green Criteria for Iodination
- Large molar excesses of reagents should be avoided if possible.
- For electrophilic iodination, the least reactive I+ reagent should be used.
- Reagents with lower mass intensity should be used if possible.
- Catalysis with Ag and Hg metals should be avoided if possible.
- The use of high impact (re)oxidants like Ag salts, Selectfluor, etc. should be avoided.
- Hypervalent iodine reagents (can be generated in situ) can be explosive.
- Organoiodides/poly iodinated organics can be persistant and bioaccummulative.
- Waste steams containing organoiodides/HI can be difficult to treat.
- Process has no major safety issues and the generation of hazardous waste is minimized and controlled
- Solvents should be chosen to minimize any potential safety and environmental impact.
- See also:
Adams, J. P.; Alder, C. M.; Andrews, I.; Bullion, A. M.; Campbell-Crawford, M.; Darcy, M. G.; Hayler, J. D.; Henderson, R. K.; Oare, C. A. Development of GSK's reagent guides – embedding sustainability into reagent selection. Green Chem. 2013, 15(6), 1542-1549.