In organic chemistry, hydroxamic acids are a class of organic compounds having a general formula R− C(=O)−N(−OH)−R' bearing the functional group − C(= O)− N(−O H)−, where R and R' are typically organyl groups (e.g., alkyl or aryl) or hydrogen. They are amides (R−C(=O)−NH−R') wherein the nitrogen atom has a hydroxyl (−OH) substituent. They are often used as metal chelators. [1]
Common example of hydroxamic acid is aceto-N-methylhydroxamic acid (H3C−C(=O)−N(−OH)−CH3). Some uncommon examples of hydroxamic acids are formo-N-chlorohydroxamic acid (H−C(=O)−N(−OH)−Cl) and chloroformo-N-methylhydroxamic acid (Cl−C(=O)−N(−OH)−CH3).
Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid (C6H5−C(=O)−NH−OH or Ph−C(=O)−NH−OH, where Ph is phenyl group), the overall equation is: [2]
Hydroxamic acids can also be synthesized from aldehydes and N-sulfonylhydroxylamine via the Angeli-Rimini reaction. [3] Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilated amides to hydroxamic acids, although yields are only about 50%. [4] 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. [5]
A well-known reaction of hydroxamic acid esters is the Lossen rearrangement. [6]
The conjugate base of hydroxamic acids forms is called a hydroxamate. Deprotonation occurs at the −N(−OH)− group, with the hydrogen atom being removed, resulting in a hydroxamate anion R−C(=O)−N(−O−)−R'. 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. [8]
They function as ligands, usually for iron. [9] 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. [10]
Ligands derived from hydroxamic acid and thiohydroxamic acid (a hydroxamic acid where one or both oxygens in the −C(=O)−N(−OH)− functional group are replaced by sulfur) also form strong complexes with lead(II). [11]
Hydroxamic acids are used extensively in flotation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing. [12] [13]
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]
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In organic chemistry, hydroxamic acids are a class of organic compounds having a general formula R− C(=O)−N(−OH)−R' bearing the functional group − C(= O)− N(−O H)−, where R and R' are typically organyl groups (e.g., alkyl or aryl) or hydrogen. They are amides (R−C(=O)−NH−R') wherein the nitrogen atom has a hydroxyl (−OH) substituent. They are often used as metal chelators. [1]
Common example of hydroxamic acid is aceto-N-methylhydroxamic acid (H3C−C(=O)−N(−OH)−CH3). Some uncommon examples of hydroxamic acids are formo-N-chlorohydroxamic acid (H−C(=O)−N(−OH)−Cl) and chloroformo-N-methylhydroxamic acid (Cl−C(=O)−N(−OH)−CH3).
Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid (C6H5−C(=O)−NH−OH or Ph−C(=O)−NH−OH, where Ph is phenyl group), the overall equation is: [2]
Hydroxamic acids can also be synthesized from aldehydes and N-sulfonylhydroxylamine via the Angeli-Rimini reaction. [3] Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilated amides to hydroxamic acids, although yields are only about 50%. [4] 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. [5]
A well-known reaction of hydroxamic acid esters is the Lossen rearrangement. [6]
The conjugate base of hydroxamic acids forms is called a hydroxamate. Deprotonation occurs at the −N(−OH)− group, with the hydrogen atom being removed, resulting in a hydroxamate anion R−C(=O)−N(−O−)−R'. 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. [8]
They function as ligands, usually for iron. [9] 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. [10]
Ligands derived from hydroxamic acid and thiohydroxamic acid (a hydroxamic acid where one or both oxygens in the −C(=O)−N(−OH)− functional group are replaced by sulfur) also form strong complexes with lead(II). [11]
Hydroxamic acids are used extensively in flotation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing. [12] [13]
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]
{{
cite book}}
: CS1 maint: multiple names: authors list (
link)