organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

, hydroxamic acids are a class of

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

s having a general formula bearing the

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

, where R and R' are typically

organyl group In organic and organometallic chemistry, an organyl group (commonly denoted by the letter " R") is an organic substituent with one (sometimes more) free valence electron(s) at a carbon atom.. The term is often used in chemical patent literatur ...

s (e.g.,

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...

aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...

) or

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

. They are

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

s () wherein the

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atom has a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

()

substituent In organic chemistry, a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. The suffix ''-yl'' is used when naming organic compounds that contain a single bond r ...

. They are often used as

metal A metal () is a material that, when polished or fractured, shows a lustrous appearance, and conducts electrical resistivity and conductivity, electricity and thermal conductivity, heat relatively well. These properties are all associated wit ...

chelators. Common example of hydroxamic acid is aceto-''N''-methylhydroxamic acid (). Some uncommon examples of hydroxamic acids are formo-''N''-chlorohydroxamic acid () and chloroformo-''N''-methylhydroxamic acid ().

Synthesis and reactions

Hydroxamic acids are usually prepared from either

esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

s by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid ( or , where Ph is

phenyl group In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula , and is often represented by the symbol Ph (archaically φ) or Ø. The phenyl group is closely related to benzene and can be viewed as a benzene ...

), the overall equation is: : Hydroxamic acids can also be synthesized from

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

s and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilated

s to hydroxamic acids, although yields are only about 50%. In a variation on the Nef reaction,

primary Primary or primaries may refer to: Arts, entertainment, and media Music Groups and labels * Primary (band), from Australia * Primary (musician), hip hop musician and record producer from South Korea * Primary Music, Israeli record label Work ...

nitro compounds In organic chemistry, nitro compounds are organic compounds that contain one or more nitro functional groups (). The nitro group is one of the most common explosophores (functional group that makes a compound explosive) used globally. The nitr ...

kept in an acidic solution (to minimize the nitronate tautomer) hydrolyze to a hydroxamic acid. A well-known reaction of hydroxamic acid esters is the Lossen rearrangement.

Coordination chemistry and biochemistry

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 The conjugate base of hydroxamic acids forms is called a hydroxamate. Deprotonation occurs at the group, with the

atom being removed, resulting in a hydroxamate

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

. The resulting conjugate base presents the metal with an anionic, conjugated ''O'',''O'' chelating ligand. Many hydroxamic acids and many

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

hydroxamates have been isolated from natural sources. They function as

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

, usually for iron. Nature has evolved families of hydroxamic acids to function as iron-binding compounds ( siderophores) in

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. They extract iron(III) from otherwise insoluble sources (

rust Rust is an iron oxide, a usually reddish-brown oxide formed by the reaction of iron and oxygen in the catalytic presence of water or air moisture. Rust consists of hydrous iron(III) oxides (Fe2O3·nH2O) and iron(III) oxide-hydroxide (FeO(OH) ...

minerals In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid substance with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2011): M ...

, etc.). The resulting complexes are transported into the cell, where the iron is extracted and utilized metabolically. Ligands derived from hydroxamic acid and thiohydroxamic acid (a hydroxamic acid where one or both

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

s in the functional group are replaced by

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

) also form strong complexes with

lead Lead () is a chemical element; it has Chemical symbol, symbol Pb (from Latin ) and atomic number 82. It is a Heavy metal (elements), heavy metal that is density, denser than most common materials. Lead is Mohs scale, soft and Ductility, malleabl ...

(II).

Other uses and occurrences

Hydroxamic acids are used extensively in flotation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing. Some hydroxamic acids (e.g.

vorinostat Vorinostat (International Nonproprietary Name, rINN), also known as suberoylanilide hydroxamic acid (suberic acid, suberoyl+aniline, anilide+hydroxamic acid abbreviated as SAHA), is a member of a larger class of compounds that inhibit histone de ...

, 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.

Synthesis and reactions

Coordination chemistry and biochemistry

Other uses and occurrences

References

Further reading