Hydroxamic acid

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The general structure of a hydroxamic acid

A hydroxamic acid is a class of organic compounds bearing the functional group RC(O)N(OH)R', with R and R' as organic residues and CO as a carbonyl group. They are amides (RC(O)NHR') wherein the NH center has an OH substitution. They are often used as metal chelators.

Synthesis and reactions[edit]

Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid, the overall equation is:[1]

C6H5CO2Me + NH2OH → C6H5C(O)NHOH + MeOH

Hydroxamic acids can also be synthesized from aldehydes and N-sulfonylhydroxylamine via the Angeli-Rimini reaction.[2]

A well-known reaction of hydroxamic acid esters is the Lossen rearrangement.[3]

Coordination chemistry and biochemistry[edit]

In the area of coordination chemistry, hydroxamates are excellent ligands.[5] They form by deprotonation of hydroxamic acids, Hydroxamates bind to metals ions as bidentate ligands, forming five-membered MO2CN rings. Nature has evolved families of hydroxamic acids to function as iron-binding compounds (siderophores) in bacteria. They extract iron(III) from otherwise insoluble sources (rust, minerals, etc.). The resulting complexes are transported into the cell, where the iron is extracted and utilized metabolically.[6]

Ligands derived from hydroxamic acid and thiohydroxamic acid also form strong complexes with lead(II).[7]

Other uses and occurrences[edit]

Hydroxamic acids are used extensively in flotation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing.[8][9]

Some hydroxamic acids (e.g. vorinostat, belinostat, panobinostat, and trichostatin A) are HDAC inhibitors with anti-cancer properties. Fosmidomycin is a natural hydroxamic acid inhibitor of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP reductoisomerase). Hydroxamic acids have also been investigated for reprocessing of irradiated fuel.

References[edit]

  1. ^ C. R. Hauser and W. B. Renfrow, Jr. (1939). "Benzohydroxamic Acid". Org. Synth. 19: 15. doi:10.15227/orgsyn.019.0015.CS1 maint: uses authors parameter (link)
  2. ^ Li, Jie Jack (2003). Name Reactions: A Collection of Detailed Reaction Mechanisms (2nd ed.). Berlin, Heidelberg, New York: Springer. p. 9. ISBN 978-3-662-05338-6.
  3. ^ Wang, Zerong (2010). Comprehensive organic name reactions and reagents. John Wiley & Sons, Inc. pp. 1772–1776. ISBN 9780471704508.
  4. ^ Hossain, M. B.; Eng-Wilmot, D. L.; Loghry, R. A.; an der Helm, D. (1980). "Circular Dichroism, Crystal Structure, and Absolute Configuration of the Siderophore Ferric N,N',N"-Triacetylfusarinine, FeC39H57N6O15". Journal of the American Chemical Society. 102 (18): 5766–5773. doi:10.1021/ja00538a012.
  5. ^ Agrawal, Y K (1979). "Hydroxamic Acids and Their Metal Complexes". Russian Chemical Reviews. 48 (10): 948–963. Bibcode:1979RuCRv..48..948A. doi:10.1070/RC1979v048n10ABEH002422.
  6. ^ Miller, Marvin J. (November 1989). "Syntheses and Therapeutic Potential of Hydroxamic Acid Based Siderophores and Analogues". Chemical Reviews. 89 (7): 1563–1579. doi:10.1021/cr00097a011.
  7. ^ Farkas, Etelka; Buglyó, Péter (2017). "Chapter 8. Lead(II) Complexes of Amino Acids, Peptides, and Other Related Ligands of Biological Interest". In Astrid, S.; Helmut, S.; Sigel, R. K. O. (eds.). Lead: Its Effects on Environment and Health. Metal Ions in Life Sciences. 17. de Gruyter. pp. 201–240. doi:10.1515/9783110434330-008. ISBN 9783110434330. PMID 28731301.
  8. ^ Marion, Christopher; Jordens, Adam; Li, Ronghao; Rudolph, Martin; Waters, Kristian E. (August 2017). "An evaluation of hydroxamate collectors for malachite flotation". Separation and Purification Technology. 183: 258–269. doi:10.1016/j.seppur.2017.02.056.
  9. ^ Jordens, Adam; Cheng, Ying Ping; Waters, Kristian E. (February 2013). "A review of the beneficiation of rare earth element bearing minerals". Minerals Engineering. 41: 97–114. doi:10.1016/j.mineng.2012.10.017.

Further reading[edit]