2-Iodoxybenzoic acid, oxidations

IBX acid or 2-iodoxybenzoic acid is an organic compound used in organic synthesis as an oxidizing agent. This periodinane is especially suited to oxidize alcohols to aldehydes. The IBX acid is prepared from 2-iodobenzoic acid, potassium bromate and sulfuric acid.^[1]

2-Iodoxybenzoic acid

The reaction mechanism for an oxidation of an alcohol to an aldehyde according the so-called hypervalent twisting mechanism^[4] involves a ligand exchange reaction replacing the hydroxyl group by the alcohol followed by a twist and a elimination reaction.

The hypervalent twisting mechanism during conversion of methanol to formaldehyde: a) ligand exchange reaction (activation energy 9.1 kcal/mol (38 kJ/mol), b) hypervalent twist 12.1 kcal/mol (51 kJ/mol), c) elimination 4.7 kcal/mol (20 kJ/mol)). There is steric repulsion between protons in red.

The reaction mechanism for this glycol cleavage is based on initial formation of an adduct between 10-I-4 IBX and DMSO to an 12-I-5 intermediate 3 in which DMSO acts as a leaving group for incoming alcohol 4 to intermediate 5. One equivalent of water is split off forming 12-I-5 spirobicyclic periodinane 6 setting the stage for fragmentation to 7. With hydroxyl alpha protons presents oxidation to the acyloin competes. Trifluoroacetic acid is found to facilitate the overall reaction.

IBX is also available as silica gel or polystyrene bound IBX. In many application IBX acid is replaced by Dess-Martin periodinane which is more soluble in common organic solvents. A sample reaction is a IBX oxidation used in the total synthesis of eicosanoid:^[6]

IBX acid oxidation of alcohol to aldehyde key data: a) IBX, DMSO, THF, 4h, 94% chemical yield (Mohapatra, 2005)

References

1. Boeckman, R. K. Jr., Shao, P.; Mullins, J. J. (2000), “Dess-Martin periodinane: 1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one”, Org. Synth. 77: 141; Coll. Vol. 10: 696
2. Frigerio, M.; Santagostino, M.; Sputore, S. (1999). “A User-Friendly Entry to 2-Iodoxybenzoic Acid (IBX)”. Journal of Organic Chemistry 64 (12): 4537–4538. doi:10.1021/jo9824596.
3. Dess, D. B.; Martin, J. C. (1991). “A Useful 12-I-5 Triacetoxyperiodinane (the Dess-Martin Periodinane) for the Selective Oxidation of Primary or Secondary Alcohols and a Variety of Related 12-I-5 Species”. Journal of the American Chemical Society 113 (19): 7277–7287. doi:10.1021/ja00019a027.
4. Su, J. T.; Goddard, W. A. III (2005). “Enhancing 2-Iodoxybenzoic Acid Reactivity by Exploiting a Hypervalent Twist”. Journal of the American Chemical Society 127 (41): 14146–14147. doi:10.1021/ja054446x. PMID 16218584.
5. Gallen, M. J.; Goumont, R.; Clark, T.; Terrier, F.; Williams, C. M. (2006). “o-Iodoxybenzoic Acid (IBX): pK_a and Proton-Affinity Analysis”. Angewandte Chemie International Edition 45 (18): 2929–2934. doi:10.1002/anie.200504156. PMID 16566050.
6. Mohapatra, D. K.; Yellol, G. S. (2005). “Asymmetric Total Synthesis of Eicosanoid” (pdf). Arkivoc 2005 (3): 144–155.

thanks to DR WILL WATSON OF SCIENTIFIC UPDATE ON A WARNING

Beware, IBX can explode, see C&E News, 1990, vol 68, issue 29 page 3. A stabilised non-explosive formulation of IBX mixed with benzoic acid and phthalic acid is available from Simafex, see Org. Lett., 2003, 5, 2903.

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