hydroxamic acid

Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid ({{chem2|C6H5\sC(\dO)\sNH\sOH}} or {{chem2|Ph\sC(\dO)\sNH\sOH}}, where Ph is phenyl group), the overall equation is:{{cite journal|author1=C. R. Hauser |author2=W. B. Renfrow Jr |title=Benzohydroxamic Acid|journal=Org. Synth.|year=1939|volume=19|page=15|doi=10.15227/orgsyn.019.0015}}

:{{chem2|C6H5\sC(\dO)\sO\sCH3 + NH2OH → C6H5\sC(\dO)\sNH\sOH + CH3OH}}

Hydroxamic acids can also be synthesized from aldehydes and N-sulfonylhydroxylamine via the Angeli-Rimini reaction.{{cite book |last1=Li |first1=Jie Jack |title=Name Reactions: A Collection of Detailed Reaction Mechanisms |date=2003 |publisher=Springer |location=Berlin, Heidelberg, New York |isbn=978-3-662-05338-6 |page=9 |edition=2nd}} Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilated amides to hydroxamic acids, although yields are only about 50%.{{cite journal|year=1979|pages=2481–2487|title=The oxidation of trimethylsilylated amides to hydroxamic acids|first1=Stephen A.|last1=Matlin|first2=Peter G.|last2=Sammes|first3=Roger M.|last3=Upton|journal=Journal of the Chemical Society, Perkin Transactions 1|doi=10.1039/p19790002481 }} In a variation on the Nef reaction, primary nitro compounds kept in an acidic solution (to minimize the nitronate tautomer) hydrolyze to a hydroxamic acid.Smith (2020), March's Organic Chemistry, rxn. 16-3.

A well-known reaction of hydroxamic acid esters is the Lossen rearrangement.{{cite book |last1=Wang |first1=Zerong |title=Comprehensive organic name reactions and reagents |date=2010 |publisher=John Wiley & Sons, Inc. |isbn=9780471704508 |pages=1772–1776}}

File:Ferrichrome.svg| Ferrichrome

File:Deferoxamine-2D-skeletal.png |Deferoxamine

File:Rhodotorulic acid.svg|Rhodotorulic acid

File:Fe(hydroxamate)3.svg|Fe(III) complex of triacetylfusarinine{{cite journal|last1=Hossain|first1=M. B.|last2=Eng-Wilmot|first2=D. L.|last3=Loghry|first3=R. A.|last4=an der Helm|first4=D.|title=Circular Dichroism, Crystal Structure, and Absolute Configuration of the Siderophore Ferric N,N',N"-Triacetylfusarinine, FeC₃₉H₅₇N₆O₁₅|journal=Journal of the American Chemical Society|year=1980|volume=102|issue=18|pages=5766–5773|doi=10.1021/ja00538a012}}

The conjugate base of hydroxamic acids forms is called a hydroxamate. Deprotonation occurs at the {{chem2|\sN(\sOH)\s}} group, with the hydrogen atom being removed, resulting in a hydroxamate anion {{chem2|R\sC(\dO)\sN(\sO−)\sR'}}. The resulting conjugate base presents the metal with an anionic, conjugated O,O chelating ligand. Many hydroxamic acids and many iron hydroxamates have been isolated from natural sources.{{cite book|chapter=Natural and Biomimetic Hydroxamic Acid based Siderophores|author=Abraham Shanzer, Clifford E. Felder, Yaniv Barda|

editor = Zvi Rappoport, Joel F. Liebman|year= 2008|doi=10.1002/9780470741962.ch16|series=PATAI'S Chemistry of Functional Groups|title=The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids|pages=751–815 |isbn=9780470512616}}

They function as ligands, usually for iron.{{Cite journal

| doi = 10.1070/RC1979v048n10ABEH002422

| issue = 10

| pages = 948–963

| last = Agrawal

| first = Y K

| title = Hydroxamic Acids and Their Metal Complexes

| journal = Russian Chemical Reviews

| year = 1979

| volume = 48

| bibcode = 1979RuCRv..48..948A

| s2cid = 250857281

}} 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.{{cite journal |last=Miller |first=Marvin J. |title=Syntheses and Therapeutic Potential of Hydroxamic Acid Based Siderophores and Analogues |journal=Chemical Reviews |date=November 1989 |volume=89 |issue=7 |pages=1563–1579 |doi=10.1021/cr00097a011}}

Ligands derived from hydroxamic acid and thiohydroxamic acid (a hydroxamic acid where one or both oxygens in the {{chem2|\sC(\dO)\sN(\sOH)\s}} functional group are replaced by sulfur) also form strong complexes with lead(II).{{cite book|last1=Farkas|first1= Etelka|last2=Buglyó|first2=Péter|chapter= Chapter 8. Lead(II) Complexes of Amino Acids, Peptides, and Other Related Ligands of Biological Interest|pages= 201–240

|publisher= de Gruyter|date= 2017|series= Metal Ions in Life Sciences|volume=17|title=Lead: Its Effects on Environment and Health|editor1-last=Astrid|editor1-first= S.|editor2-last=Helmut|editor2-first=S.|editor3-last=Sigel |editor3-first= R. K. O.|doi=10.1515/9783110434330-008|pmid= 28731301|isbn= 9783110434330}}

Hydroxamic acids are used extensively in flotation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing.{{cite journal |last1=Marion |first1=Christopher |last2=Jordens |first2=Adam |last3=Li |first3=Ronghao |last4=Rudolph |first4=Martin |last5=Waters |first5=Kristian E. |title=An evaluation of hydroxamate collectors for malachite flotation |journal=Separation and Purification Technology |date=August 2017 |volume=183 |pages=258–269 |doi=10.1016/j.seppur.2017.02.056}}{{cite journal |last1=Jordens |first1=Adam |last2=Cheng |first2=Ying Ping |last3=Waters |first3=Kristian E. |title=A review of the beneficiation of rare earth element bearing minerals |journal=Minerals Engineering |date=February 2013 |volume=41 |pages=97–114 |doi=10.1016/j.mineng.2012.10.017|bibcode=2013MiEng..41...97J}}

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.{{citation needed|date=July 2022}}

{{reflist|30em}}

• {{Cite journal

|doi=10.1016/0022-1902(70)80604-2

|issn=0022-1902

|volume=32

|issue=6

|pages=1949–1962

|last=Fouché

|first=K. F.

|author2=H. J. le Roux

|author3=F. Phillips

|title=Complex formation of Zr(IV) and Hf(IV) with hydroxamic acids in acidic solutions

|journal=Journal of Inorganic and Nuclear Chemistry

|access-date=2009-04-24

|date=June 1970

|url=http://www.science-direct.com/science/article/B758S-48M3JS8-NH/2/906cec1e859eacb47bf1f0efcd27e5cc

|archive-url=https://archive.today/20130104204633/http://www.science-direct.com/science/article/B758S-48M3JS8-NH/2/906cec1e859eacb47bf1f0efcd27e5cc

|url-status=dead

|archive-date=2013-01-04

|url-access=subscription

}}

• {{Cite journal

|doi=10.1016/0022-1902(66)80023-4

|issn=0022-1902

|volume=28

|issue=12

|pages=2961–2967

|last=Barocas

|first=A.

|author2=F. Baroncelli

|author3=G. B. Biondi

|author4=G. Grossi

|title=The complexing power of hydroxamic acids and its effect on behaviour of organic extractants in the reprocessing of irradiated fuels--II : The complexes between benzohydroxamic acid and thorium, uranium (IV) and plutonium (IV)

|journal=Journal of Inorganic and Nuclear Chemistry

|access-date=2009-04-24

|date=December 1966

|url=http://www.science-direct.com/science/article/B758S-48GWMMM-8P/2/0e24f83e069f7473d7b0663eea4f8302

|archive-url=https://archive.today/20130104153552/http://www.science-direct.com/science/article/B758S-48GWMMM-8P/2/0e24f83e069f7473d7b0663eea4f8302

|url-status=dead

|archive-date=2013-01-04

|url-access=subscription

}}

• {{Cite journal

|doi=10.1016/0022-1902(65)80420-1

|issn=0022-1902

|volume=27

|issue=5

|pages=1085–1092

|last=Baroncelli

|first=F.

|author2=G. Grossi

|title=The complexing power of hydroxamic acids and its effect on the behaviour of organic extractants in the reprocessing of irradiated fuels--I the complexes between benzohydroxamic acid and zirconium, iron (III) and uranium (VI)

|journal=Journal of Inorganic and Nuclear Chemistry

|access-date=2009-04-24

|date=May 1965

|url=http://www.science-direct.com/science/article/B758S-48N50RN-2W/2/fc4a67c10211cd748add5daa51bb55ff

|archive-url=https://archive.today/20130104213629/http://www.science-direct.com/science/article/B758S-48N50RN-2W/2/fc4a67c10211cd748add5daa51bb55ff

|url-status=dead

|archive-date=2013-01-04

|url-access=subscription

}}

• {{Cite journal

|doi=10.1016/0022-1902(81)80652-5

|issn=0022-1902

|volume=43

|issue=11

|pages=2971–2973

|last=Al-Jarrah

|first=R. H.

|author2=A. R. Al-Karaghouli

|author3=S. A. Al-Assaf

|author4=N. H. Shamon

|title=Solvent extraction of uranium and some other metal ions with 2-N-butyl-2-ethyl octanohydroxamic acid

|journal=Journal of Inorganic and Nuclear Chemistry

|access-date=2009-04-24

|year=1981

|url=http://www.science-direct.com/science/article/B758S-48M3SCR-152/2/723dc6c17d83f6266314116734ae71e8

|archive-url=https://archive.today/20130104171746/http://www.science-direct.com/science/article/B758S-48M3SCR-152/2/723dc6c17d83f6266314116734ae71e8

|url-status=dead

|archive-date=2013-01-04

|url-access=subscription

}}

• {{Cite journal

| issue = 17

| pages = 1266–1268

| last = Gopalan

| first = Aravamudan S.

|author2=Vincent J. Huber |author3=Orhan Zincircioglu |author4=Paul H. Smith

| title = Novel tetrahydroxamate chelators for actinide complexation: synthesis and binding studies

| journal = Journal of the Chemical Society, Chemical Communications

| year = 1992

| doi = 10.1039/C39920001266

|url=https://zenodo.org/record/1230022}}

• {{Cite journal

| doi = 10.1016/S0040-4020(01)86981-7 | issn = 0040-4020

| volume = 50 | issue = 9 | pages = 2657–2664

| last = Koshti | first = Nirmal |author2=Vincent Huber |author3=Paul Smith |author4=Aravamudan S. Gopalan

| title = Design and synthesis of actinide specific chelators: Synthesis of new cyclam tetrahydroxamate (CYTROX) and cyclam tetraacetonylacetone (CYTAC) chelators

| journal = Tetrahedron

| date = 1994-02-28

| url = https://zenodo.org/record/1259713

}}

{{Authority control}}

Category:Functional groups