In
organic chemistry, an oxime is an
organic compound belonging to the
imines, with the general
formulaRR’C=N−OH, where R is an organic
side-chain and R' may be
hydrogen, forming an aldoxime, or another organic
group, forming a ketoxime. O-substituted oximes form a closely related family of compounds. Amidoximes are oximes of
amides (R1C(=O)NR2R3) with general structure R1C(=NOH)NR2R3.
Oximes are usually generated by the reaction of
hydroxylamine with
aldehydes (R−CH=O) or
ketones (RR’C=O). The term oxime dates back to the 19th century, a combination of the words oxygen and imine.[1]
Structure and properties
If the two side-chains on the central carbon are different from each other—either an aldoxime, or a ketoxime with two different "R" groups—the oxime can often have two different geometric
stereoisomeric forms according to the
E/Z configuration. An older terminology of
syn and anti was used to identify especially aldoximes according to whether the R group was closer or further from the hydroxyl. Both forms are often stable enough to be separated from each other by standard techniques.
Oximes have three characteristic bands in the
infrared spectrum, whose wavelengths corresponding to the stretching vibrations of its three types of bonds: 3600 cm−1 (O−H), 1665 cm−1 (C=N) and 945 cm−1 (N−O).[2]
In aqueous solution, aliphatic oximes are 102- to 103-fold more resistant to hydrolysis than analogous hydrazones.[3]
Preparation
Oximes can be synthesized by
condensation of an aldehyde or a ketone with
hydroxylamine. The condensation of aldehydes with hydroxylamine gives aldoximes, and ketoximes are produced from ketones and hydroxylamine. In general, oximes exist as colorless
crystals or as thick liquids and are poorly soluble in water. Therefore, oxime formation can be used for the identification of
ketone or aldehyde functional groups.
The
hydrolysis of oximes proceeds easily by heating in the presence of various
inorganic acids, and the oximes decompose into the corresponding ketones or aldehydes, and hydroxylamines. The reduction of oximes by
sodium metal,[10]sodium amalgam,
hydrogenation, or reaction with
hydride reagents produces
amines.[11] Typically the
reduction of aldoximes gives both primary amines and secondary amines; however, reaction conditions can be altered (such as the addition of
potassium hydroxide in a 1/30 molar ratio) to yield solely primary amines.[12]
In general, oximes can be changed to the corresponding
amide derivatives by treatment with various acids. This reaction is called
Beckmann rearrangement.[13] In this reaction, a
hydroxyl group is exchanged with the group that is in the anti position of the hydroxyl group. The amide derivatives that are obtained by Beckmann rearrangement can be transformed into a
carboxylic acid by means of hydrolysis (base or acid catalyzed). And an amine by Hoffman degradation of the amide in the presence of alkali hypoclorites. Beckmann rearrangement is used for the industrial synthesis of
caprolactam (see applications below).
The Ponzio reaction (1906)[14] concerning the conversion of m-nitrobenzaldoxime to m-nitrophenyldinitromethane using
dinitrogen tetroxide was the result of research into
TNT analogues:[15]
In the
Neber rearrangement certain oximes are converted to the corresponding alpha-amino ketones.
In their largest application, an oxime is an intermediate in the industrial production of
caprolactam, a precursor to
Nylon 6. About half of the world's supply of
cyclohexanone, more than a million tonnes annually, is converted to the oxime. In the presence of
sulfuric acidcatalyst, the oxime undergoes the
Beckmann rearrangement to give the cyclic amide caprolactam:[18]
Metal extractant
Oximes are commonly used as ligands and sequestering agents for metal ions.
Dimethylglyoxime (dmgH2) is a reagent for the analysis of nickel and a popular ligand in its own right. In the typical reaction, a metal reacts with two equivalents of dmgH2 concomitant with ionization of one proton.
Salicylaldoxime is a
chelator in
hydrometallurgy.[19]
Amidoximes such as polyacrylamidoxime can be used to capture trace amounts of
uranium from sea water.[20][21] In 2017 researchers announced a configuration that absorbed up to nine times as much
uranyl as previous fibers without saturating.[22]
Other applications
Oxime compounds are used as antidotes for
nerve agents. A nerve agent inactivates
acetylcholinesterase by phosphorylation. Oxime compounds can reactivate acetylcholinesterase by attaching to phosphorus, forming an oxime-phosphonate, which then splits away from the acetylcholinesterase molecule. Oxime nerve-agent antidotes are
pralidoxime (also known as
2-PAM),
obidoxime, methoxime,
HI-6, Hlo-7, and
TMB-4.[23] The effectiveness of the oxime treatment depends on the particular nerve agent used.[24]
^The name "oxime" is derived from "oximide" (i.e., oxy- + amide). According to the German organic chemist
Victor Meyer (1848–1897) – who, with Alois Janny, synthesized the first oximes – an "oximide" was an organic compound containing the group (=N−OH) attached to a carbon atom. The existence of oximides was questioned at the time (ca. 1882). (See page 1164 of: Victor Meyer und Alois Janny (1882a)
"Ueber stickstoffhaltige Acetonderivate" (On nitrogenous derivatives of acetone), Berichte der Deutschen chemischen Gesellschaft, 15: 1164–1167.) However, in 1882, Meyer and Janny succeeded in synthesizing methylglyoxime (CH3C(=NOH)CH(=NOH)), which they named "Acetoximsäure" (acetoximic acid) (Meyer & Janny, 1882a, p. 1166). Subsequently, they synthesized 2-propanone, oxime ((CH3)2C=NOH), which they named "Acetoxim" (acetoxime), in analogy with Acetoximsäure. From Victor Meyer and Alois Janny (1882b)
"Ueber die Einwirkung von Hydroxylamin auf Aceton" (On the effect of hydroxylamine on acetone), Berichte der Deutschen chemischen Gesellschaft, 15: 1324–1326, page 1324: "Die Substanz, welche wir, wegen ihrer nahen Beziehungen zur Acetoximsäure, und da sie keine sauren Eigenschaften besitzt, vorläufig Acetoxim nennen wollen, …" (The substance, which we – on account of its close relations to acetoximic acid, and since it possesses no acid properties – will, for the present, name "acetoxime," … )
^Suter, C. M.; Moffett, Eugene W. (1934). "The Reduction of Aliphatic Cyanides and Oximes with Sodium and n-Butyl Alcohol". Journal of the American Chemical Society. 56 (2): 487.
doi:
10.1021/ja01317a502.
^Plapinger, Robert; Owens, Omer (1956). "Notes – The Reaction of Phosphorus-Containing Enzyme Inhibitors with Some Hydroxylamine Derivatives". J. Org. Chem.21 (10): 1186.
doi:
10.1021/jo01116a610.
^Smith, Andrew G.; Tasker, Peter A.; White, David J. (2003). "The structures of phenolic oximes and their complexes". Coordination Chemistry Reviews. 241 (1–2): 61–85.
doi:
10.1016/S0010-8545(02)00310-7.
^Kassa, J. (2002). "Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents". Journal of Toxicology: Clinical Toxicology. 40 (6): 803–16.
doi:
10.1081/CLT-120015840.
PMID12475193.
S2CID20536869.
^Johannes Panten and Horst Surburg "Flavors and Fragrances, 2. Aliphatic Compounds" in Ullmann's Encyclopedia of Industrial Chemistry, 2015, Wiley-VCH, Weinheim.
doi:
10.1002/14356007.t11_t01