Hubbry Logo
OximeOximeMain
Open search
Oxime
Community hub
Oxime
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Contribute something
Oxime
Oxime
Oxime
View on Wikipedia
from Wikipedia

In organic chemistry, an oxime is an organic compound belonging to the imines, with the general formula RR’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

[edit]

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

[edit]

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.

Certain metal salts reduce nitro compounds to oximes.

Oximes can also be obtained from rearrangement of unstable nitroso compounds. Thus alkyl nitrites react with carbon acids to give oximes: methyl ethyl ketone with ethyl nitrite,[4] propiophenone with methyl nitrite,[5] and phenacyl chloride with butyl nitrite, all in ethereal hydrochloric acid.[6] Alternatively, sodium nitrite in glacial acetic acid nitrosates ethyl acetoacetate[7][8] and malononitrile.[9]

A conceptually related reaction is the Japp–Klingemann reaction.

Reactions

[edit]

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). 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]

Ponzio reaction
Ponzio reaction

Gentler oxidants give mono-nitro compounds.[16]

In the Neber rearrangement certain oximes are converted to the corresponding alpha-amino ketones.

Oximes can be dehydrated using acid anhydrides to yield corresponding nitriles.

Certain amidoximes react with benzenesulfonyl chloride to make substituted ureas in the Tiemann rearrangement:[17][18]

Tiemann rearragement

Uses

[edit]

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 acid catalyst, the oxime undergoes the Beckmann rearrangement to give the cyclic amide caprolactam:[19]

Metal extractant

[edit]
Structure of Nickel bis(dimethylglyoximate).

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.[20]

Amidoximes such as polyacrylamidoxime can be used to capture trace amounts of uranium from sea water.[21][22] In 2017 researchers announced a configuration that absorbed up to nine times as much uranyl as previous fibers without saturating.[23]

Other applications

[edit]
  • 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.[24] The effectiveness of the oxime treatment depends on the particular nerve agent used.[25]
  • Perillartine, the oxime of perillaldehyde, is used as an artificial sweetener in Japan. It is 2000 times sweeter than sucrose.
  • Diaminoglyoxime is a key precursor to various compounds containing the highly reactive furazan ring.
  • Methyl ethyl ketoxime is a skin-preventing additive in many oil-based paints.
  • Buccoxime and 5-methyl-3-heptanone oxime ("Stemone") are perfume ingredients.[26]
  • Fluvoxamine is used as an antidepressant.

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Oxime

View on Grokipedia
from Grokipedia
An oxime is a class of organic compounds belonging to the imines, characterized by the C=NOH and the general formula RR′C=NOH, where R and R′ are organic side chains, atoms, or other substituents, with oximes derived from aldehydes termed aldoximes and those from ketones termed ketoximes. Oximes are typically synthesized through the of aldehydes or ketones with (NH₂OH) under mildly acidic or basic conditions, a process that involves to the followed by . This reaction is reversible and widely employed in laboratories for the identification and characterization of carbonyl compounds due to the distinct physical properties of oximes, such as their and melting points. Structurally, oximes exhibit E/Z geometric isomerism around the C=N bond, and they can tautomerize to forms under certain conditions, contributing to their reactivity. In , oximes play a crucial role as versatile intermediates and protecting groups for carbonyl functionalities, enabling selective transformations. Notable reactions include the , where oximes are converted to amides using acid catalysts or metal complexes, a process essential for producing ε-caprolactam, the monomer for nylon-6. They also undergo dehydration to nitriles and reduction to hydroxylamines, facilitating the construction of nitrogen-containing heterocycles and other complex molecules. Beyond synthesis, oximes find applications in ; for instance, compounds like act as antidotes for poisoning by reactivating inhibited through nucleophilic attack on the . Additionally, some oximes serve as inhibitors or in the formulation of artificial sweeteners.

Structure and Properties

Molecular Structure and Nomenclature

Oximes are organic compounds with the general molecular RR′C=NOHRR'C=NOH, where RR and R′R' represent atoms or organic substituents. When R′R' is , the compounds are classified as aldoximes, typically derived from aldehydes, while cases where both RR and R′R' are organic groups are known as ketoximes, derived from ketones. The defining of oximes is the C=N−OHC=N-OH unit, which constitutes an derivative in which the atom bears a hydroxyl substituent, resulting from the addition of to a carbonyl compound. In IUPAC , oximes are named by appending the term "oxime" to the name of the parent or , such as ethanal oxime for CH3CH=NOHCH_3CH=NOH. This approach reflects their origin as derivatives of carbonyl compounds, with stereochemical descriptors like (E)(E) or (Z)(Z) incorporated when specifying geometric isomers. The term "oxime" was coined in the 19th century as a portmanteau of "oxygen" and "imine," highlighting the compound's incorporation of an oxygen-containing imine-like structure.

Stereoisomerism

Oximes exhibit geometric isomerism arising from the restricted rotation around the C=N double bond, similar to that in alkenes, due to the sp² hybridization of both the carbon and nitrogen atoms. This leads to E and Z isomers, where the configuration is determined by the Cahn-Ingold-Prelog priority rules: the E isomer (often termed anti) has the higher-priority substituents on opposite sides of the double bond, while the Z isomer (often termed syn) has them on the same side. For aldoximes specifically (R-CH=NOH), the traditional syn/anti nomenclature is commonly used, with the syn isomer defined as the one where the hydroxyl (OH) group and the aldehydic hydrogen (H) are on the same side of the C=N bond, corresponding to the E configuration, and the anti isomer having them on opposite sides, corresponding to the Z configuration. The Z isomers of oximes are generally less stable than the E isomers owing to steric hindrance between the OH group and the R substituent on the carbon atom. This destabilization arises from the closer proximity of these bulky groups in the Z configuration, leading to higher energy conformations, as confirmed by thermodynamic calculations showing the E isomers as the global minima for various oxime structures. Thermal interconversion between E and Z isomers is rare under ambient conditions due to the high energy barrier of the C=N rotation. Instead, isomerization typically requires , such as acid-promoted mechanisms in aqueous media involving of the oxime to form an iminoxy cation intermediate that facilitates , or photochemical conditions using visible .

Physical and Spectroscopic Properties

Oximes are typically colorless crystalline solids or viscous liquids at , depending on the specific and substituents. For example, acetone oxime is a white crystalline solid ( 60–63 °C) with a of 134.8 °C, significantly higher than that of acetone (56 °C), owing to intermolecular hydrogen bonding facilitated by the hydroxyl group. Similarly, cyclohexanone oxime is a white crystalline solid with a of 88–91 °C and a of 204–206 °C, compared to cyclohexanone's of 155 °C, again attributable to enhanced hydrogen bonding interactions. Solubility profiles of oximes vary: solubility in water depends on the substituents, with simple oximes often soluble while those with larger hydrophobic groups exhibit lower solubility, but they generally dissolve more readily in polar organic solvents such as and . Solubility in water tends to decrease with increasing aliphatic length, as longer hydrophobic tails reduce overall polarity, while solubility in non-polar organic solvents may increase accordingly. In (IR) , oximes display characteristic absorption bands that aid in their identification. The O-H stretching vibration appears as a broad band between 3115 and 3600 cm⁻¹, reflecting hydrogen bonding. The C=N stretch is observed around 1640–1665 cm⁻¹, while the N-O stretch occurs in the 900–1000 cm⁻¹ region, typically at 930–990 cm⁻¹ for simple oximes. Nuclear magnetic resonance (NMR) provides further diagnostic features. In ¹H NMR, the hydroxyl proton of oximes resonates as a broad singlet, often in the downfield region of 11–13 ppm, due to its acidic character and hydrogen bonding; this signal can shift or broaden further with or concentration changes. In ¹³C NMR, the carbon of the C=N group typically appears at 150–160 ppm, deshielded by the adjacent and oxygen atoms. Aliphatic oximes demonstrate notable hydrolytic stability under acidic conditions, with rate constants for approximately 10³ times lower than those for analogous hydrazones, making them more resistant to reversion to the parent carbonyl compounds. This enhanced stability arises from the structural reinforcement provided by the N-O bond, which slows the acid-catalyzed cleavage mechanism.

Preparation

Condensation with Hydroxylamine

The condensation of carbonyl compounds with represents the primary method for synthesizing oximes in both laboratory and industrial settings. This reaction involves the of hydroxylamine (NH₂OH) to the of an or , yielding the corresponding oxime after . The general equation for the process is: R2C=O+NH2OH→R2C=NOH+H2O\mathrm{R_2C=O + NH_2OH \rightarrow R_2C=NOH + H_2O} where R can be hydrogen, alkyl, or aryl groups. This method was first reported in 1882 by German chemist Victor Meyer and his student Alois Janny, who synthesized the first oximes, including acetone oxime and methylglyoxime, by treating carbonyl derivatives with . Their work established the foundational approach for oxime preparation and highlighted the utility of as a reagent. The reaction proceeds via a nucleophilic addition-elimination mechanism. acts as a , with its attacking the electrophilic carbonyl carbon to form a tetrahedral intermediate. This intermediate undergoes proton transfers, followed by to generate the C=N characteristic of the oxime. The process is reversible under certain conditions, but equilibrium can be driven toward product formation by removing or using excess . Acid or base facilitates the steps, with the often requiring mild acidification to protonate the hydroxyl group for elimination. Typical reaction conditions involve neutral or mildly basic pH to deprotonate and enhance its nucleophilicity, often achieved using buffers such as . is commonly generated from its hydrochloride salt (NH₂OH·) by addition of a base like or , in solvents such as , , or . Reactions are generally carried out at to , with yields exceeding 80% for most substrates under optimized conditions. For example, aromatic aldehydes react efficiently in ethanolic at 60–80°C. Aldehydes exhibit higher reactivity than ketones due to reduced steric hindrance and greater electrophilicity at the carbonyl carbon, with rate differences up to 44-fold (e.g., versus 2-butanone). This selectivity allows sequential oximation in molecules containing both functional groups. Dialdehydes, such as or , can form bis-oximes under stoichiometric conditions, provided the geometry permits double addition without steric interference.

Alternative Synthetic Routes

Oximes can be synthesized through the partial , particularly primary nitroalkanes, which are converted to the corresponding aldoximes using metal salts such as stannous chloride (SnCl₂) or chromous chloride (CrCl₂) in aqueous media. This method selectively stops at the oxime stage for aliphatic nitro compounds bearing an α-, avoiding over-reduction to amines; for example, 1-nitropropane yields propionaldoxime in moderate yields under these conditions. Catalytic represents another reduction pathway, where nitro compounds are treated with gas and a homogeneous catalyst like chlorotris()rhodium(I) to produce oximes directly, as demonstrated in early studies on both aromatic and aliphatic substrates. An alternative route involves the rearrangement of s with active methylene compounds, which generates oximes via nitroso tautomerism and subsequent . In this process, the acts as a nitrosating agent; for instance, the reaction of (CH₃CH₂ONO) with acetone (CH₃COCH₃) proceeds through rearrangement to yield acetone oxime ((CH₃)₂C=NOH) alongside other byproducts. This method is particularly useful for preparing ketoximes from simple ketones and is metal-free, though it requires careful control to minimize side reactions like O-alkylation. Recent advancements in the have introduced sustainable electrosynthetic routes, exemplified by anode-cathode cascade of hydroxyl compounds and ions. In one such approach, and are co-upgraded in a flow electrolyzer using a CoOOH/Ni foam and Cu-substituted Fe₃C , producing pyruvatoxime at a rate of 2.61 mmol cm⁻² h⁻¹ with 87 mM outlet concentration under ambient conditions (2.8 V cell voltage). This paired avoids hazardous intermediates like , leverages abundant feedstocks from , and demonstrates versatility for other oximes such as acetone oxime. A related method employs a Zn-Cu catalyst for reduction coupled with to form cyclohexanone oxime in a one-pot process under mild aqueous conditions. While these routes provide valuable alternatives to the conventional condensation of carbonyls with hydroxylamine, they are less frequently used owing to challenges in achieving high yields and regioselectivity, particularly for complex substrates.

Reactions

Hydrolysis and Reduction

Oximes undergo acid-catalyzed hydrolysis to regenerate the parent carbonyl compound and hydroxylamine, reversing the condensation reaction used in their preparation. This transformation typically employs dilute hydrochloric acid under heating conditions, with the reaction proceeding via protonation of the oxime oxygen, followed by nucleophilic attack of water on the resulting iminium-like intermediate. The general equation for this process is: R2C=NOH+H2O+H+→R2C=O+NH2OH\mathrm{R_2C=NOH + H_2O + H^+ \rightarrow R_2C=O + NH_2OH} Such hydrolytic cleavage is valuable for deprotecting carbonyl groups in synthetic sequences where oximes serve as temporary protecting groups. Reduction of oximes provides a direct route to primary amines by cleaving the N–O bond and hydrogenating the C=N double bond, yielding compounds of the form R₂CH–NH₂. Traditional methods include treatment with lithium aluminum hydride (LiAlH₄) in ether solvents at reflux, which delivers hydride to both the nitrogen-oxygen linkage and the carbon-nitrogen π-bond. Catalytic hydrogenation using palladium on carbon (Pd/C) under atmospheric or elevated hydrogen pressure, often in protic solvents like methanol or ethanol, achieves similar results with high efficiency and milder conditions. Another classical approach employs sodium amalgam (Na/Hg) in aqueous alcoholic media, facilitating electron transfer and protonation steps to form the amine product. These reductions are broadly applicable to both aldoximes and ketoximes, though yields may vary with steric hindrance around the C=N unit. The of oxime reductions is significantly influenced by the E/Z of the oxime, which can lead to diastereoselective or enantioselective formation of stereoisomers, particularly in catalytic hydrogenations using chiral catalysts. For example, E- and Z-oximes often produce opposite stereoisomers due to differences in substrate-catalyst interactions and the rigid of the oxime influencing the facial bias in or delivery. This selectivity enables access to enantioenriched amines when chiral catalysts are employed. In , oxime reduction serves as a key strategy for converting ketones or aldehydes to primary amines, bypassing limitations of direct such as instability or over-alkylation. For instance, this sequence has been utilized in the preparation of bioactive amines and derivatives, offering high and compatibility with sensitive functional groups.

Rearrangement Reactions

Oximes undergo several important rearrangement reactions, with the Beckmann and Neber rearrangements being the most prominent examples involving carbon-nitrogen bond migrations. These transformations highlight the versatility of oximes as synthetic intermediates in organic chemistry. The Beckmann rearrangement is an acid-catalyzed conversion of oximes to amides, where the group anti to the hydroxyl functionality on the oxime migrates to the nitrogen atom. This reaction typically employs strong acids such as sulfuric acid or phosphorus pentachloride as catalysts, proceeding through an O-protonated or O-acylated intermediate that facilitates the stereospecific migration. The stereospecificity ensures that the anti substituent becomes the N-acyl group in the resulting amide, as illustrated by the general transformation: \ceR−(C=NOH)−R′−>[H2SO4orPCl5]R−C(=O)−NH−R′\ce{R-(C=NOH)-R' ->[H2SO4 or PCl5] R-C(=O)-NH-R'} where R migrates if it is anti to the OH group. This rearrangement is widely utilized due to its efficiency in synthesizing amides from ketones via oxime precursors. In contrast, the Neber rearrangement involves base-catalyzed conversion of ketoximes to α-aminoketones, typically through activation of the oxime hydroxyl with tosyl chloride followed by treatment with or another base. The mechanism proceeds via formation of an O-tosylated oxime intermediate, which undergoes intramolecular cyclization to a 2H-azirine, followed by ring-opening to yield the α-aminoketone product. This stereospecific process is valuable for introducing amino functionality adjacent to carbonyl groups in complex molecules. Industrially, the holds significant importance, particularly in the production of ε-caprolactam from oxime, which serves as the precursor to nylon-6. This process involves treating the oxime with or fuming at elevated temperatures to achieve high yields of caprolactam on a large scale. Recent developments in the have focused on milder conditions for the Beckmann rearrangement by activating the oxime hydroxyl group with non-harsh catalysts, such as iron-based systems under mechanochemical conditions, enabling efficient transformations without strong acids. These advancements improve and applicability to sensitive substrates.

Other Transformations

Oximes undergo oxidation in the Ponzio reaction, where aldoximes are converted to nitro compounds using oxidizing agents such as or . This transformation involves initial formation of a intermediate followed by tautomerization and oxidation, providing a direct route to primary nitro compounds or gem-dinitroalkanes from aldehydes via their oxime derivatives; for example, acetaldoxime can yield using peroxytrifluoroacetic acid in moderate yields under controlled conditions. The reaction is particularly useful for preparing aliphatic and aromatic nitro compounds, though it may require careful control to avoid over-oxidation. Recent advances in N-O bond cleavage of oximes have focused on radical and photocatalytic methods to generate iminyl radicals, enabling selective C-C bond formation. These approaches typically involve visible-light or single-electron transfer processes, where oximes are activated to cleave the N-O bond, producing amidyl or iminyl radicals that add to alkenes or participate in cascade cyclizations. For instance, in 2021, a copper-catalyzed radical relay mechanism using oxime esters allowed iminyl radical generation and subsequent C-C coupling with boronic acids, achieving high in the synthesis of diverse amines. Similarly, photocatalytic systems employing or organic dyes have enabled remote C-C functionalization via 1,5-hydrogen atom transfer from iminyl radicals, as demonstrated in 2023 protocols for constructing quaternary carbons from cyclic oximes. These methods, developed between 2020 and 2025, highlight the versatility of oxime-derived radicals in avoiding traditional multi-step sequences for C-C bond assembly. Oximes serve as precursors to nitrile oxides, which act as 1,3-dipoles in reactions with to form . The nitrile oxide is generated by of the oxime using reagents like or , followed by [3+2] dipolar addition that proceeds with high , typically favoring the 5-substituted isomer. This transformation, rooted in Huisgen's foundational work on 1,3-dipolar , is widely employed for synthesizing bioactive heterocycles; for example, the reaction of benzaldoxime-derived benzonitrile oxide with styrene yields 3,5-diphenyl in excellent yield under mild conditions. The process benefits from the dipole's concerted mechanism, minimizing side reactions and enabling stereocontrol in chiral substrates. O-Alkylation of oximes produces oxime ethers, typically achieved by treating the oxime with alkyl halides or tosylates in the presence of a base like or , favoring O-selectivity due to the nucleophilic oxygen. This ether formation is a key step in synthesizing compounds for agricultural applications, where oxime ethers function as pesticides or intermediates in ; notable examples include alkyloxyimino derivatives used in fungicides exhibiting broad-spectrum activity against crop pathogens. Additionally, certain oxime ethers serve as stabilizers in formulations, preventing oxidative degradation by scavenging free radicals, as seen in their incorporation into rubber compounds to enhance thermal stability. These derivatives maintain the oxime's reactivity for further transformations while imparting beneficial for biological applications.

Applications

Industrial Applications

One of the primary industrial applications of oximes is in the production of ε-caprolactam, a key for nylon-6 synthesis. oxime undergoes the , typically catalyzed by strong acids such as fuming , to yield ε-caprolactam on a massive scale. This process is central to the global polyamide industry, with worldwide ε-caprolactam production exceeding 6.8 million metric tons annually as of 2023, driven largely by demand for textiles, engineering plastics, and films. The rearrangement involves migration of the anti-alkyl group to the nitrogen atom, forming the lactam ring essential for into nylon-6. Methyl ethyl ketoxime () finds widespread use as an anti-skinning additive in alkyd-based s and coatings. In these formulations, MEKO complexes with metal driers like or salts, inhibiting oxidative drying on the paint surface while allowing normal curing upon application. This prevents the formation of a surface during storage, extending for air-drying systems used in architectural and industrial coatings. MEKO's volatility ensures it evaporates during film formation, avoiding interference with the final paint properties. Perillartine, the oxime derivative of perillaldehyde, serves as a high-intensity artificial in and products. Synthesized via of perillaldehyde with , perillartine exhibits sweetness approximately 2,000 times that of , activating sweet taste receptors in a species-dependent manner. It is particularly employed in to enhance flavors in low-calorie beverages and to reduce irritation in smoke, providing a minty aftertaste without significant caloric contribution. Oximes also act as versatile intermediates in the synthesis of fragrance compounds for perfumes. For instance, certain oximes, such as 2-methyl-3-hexanone oxime, are transformed into carbamoyloxime derivatives or other odorants through reactions like oximation and reduction, contributing to woody, floral, or musky notes in commercial scents. These transformations leverage the oxime's nitrogen-oxygen functionality for selective functionalization, enabling the creation of stable, long-lasting aroma chemicals used in fine fragrances and .

Analytical and Extractive Uses

Oximes play a significant role in analytical chemistry, particularly in gravimetric methods for metal ion detection and quantification. Dimethylglyoxime (DMG), a common oxime derivative, is widely used to detect and determine nickel(II) ions by forming a bright red, insoluble chelate complex, nickel dimethylglyoximate (Ni(DMG)2), which precipitates quantitatively from ammoniacal solutions. This reaction allows for precise gravimetric analysis, where the precipitate is filtered, dried, and weighed to calculate nickel content with high accuracy, often achieving results within 0.1% error in standard laboratory conditions. In extractive applications, oximes facilitate the selective recovery of metals from aqueous solutions through solvent extraction processes in . Commercial oxime-based reagents, such as the LIX series (e.g., LIX 84 and LIX 984), are employed to extract (II) ions from acidic leach solutions by forming stable, lipophilic complexes that partition into an organic phase, typically or similar diluents. These reagents enable high selectivity over iron and other impurities, with extraction efficiencies exceeding 95% in multi-stage counter-current operations, supporting large-scale purification in operations. Amidoximes, a subclass of oximes, have been immobilized on polymeric supports for the adsorption and extraction of as from , addressing the low concentration (approximately 3.3 ppb) challenge through via the amidoxime functional group. These adsorbents bind selectively amid competing ions like and calcium, with capacities reaching up to 1.5 g U/kg adsorbent after prolonged exposure. A 2017 advancement introduced amidoxime-functionalized carbon hybrid fibers integrated with half-wave rectified , achieving extraction nine times more efficiently than passive adsorption methods by enhancing migration and release, reducing processing time from weeks to hours. Recent developments in the have focused on bifunctional oxime reagents that incorporate additional coordinating groups to improve selectivity in metal recovery from complex matrices. For instance, novel oxime derivatives paired with β-diketones or isoxazolones enable synergistic solvent extraction of rare earth elements (e.g., ) with distribution coefficients over 103 under optimized pH conditions, facilitating sustainable recovery from leachates while minimizing co-extraction of base metals. These bifunctional systems enhance kinetic rates and stripping efficiencies, promoting greener hydrometallurgical processes.

Pharmaceutical and Biological Applications

Oximes play a critical role in , particularly as antidotes for (OP) poisoning. , also known as 2-PAM, is a prototypical oxime that reactivates (AChE) inhibited by OP compounds, such as nerve agents like or pesticides. By binding to the anionic site of the phosphorylated AChE, pralidoxime displaces the OP moiety, forming a hydrolyzable complex that restores the enzyme's and alleviates symptoms. This mechanism is most effective when administered early, ideally within 48 hours, before irreversible "aging" of the enzyme occurs. Developed in the 1950s through rational design to counter agents, was among the first oximes approved by the FDA for treating OP toxicity, often in combination with atropine. In plant biology, oximes serve as versatile signaling molecules derived from via enzymes, influencing growth regulation, pathogen defense, and ecological interactions. For instance, indole-3-acetaldoxime (IAOx) acts as a precursor in biosynthesis, modulating root and shoot development, while phenylacetaldoxime contributes to defense pathways against herbivores and microbes by integrating with signaling. Oximes also facilitate attraction through volatile emissions, such as in floral scents where they enhance benzoxazinoid-derived compounds that deter antagonists while luring beneficial . The E-isomers of these oximes often exhibit higher bioactivity, owing to their stability and preferential recognition by enzymatic systems in stress responses.30384-2.pdf) Beyond and , oxime derivatives demonstrate diverse therapeutic potential, including anticancer, , and antiviral effects. In , compounds like indirubin-3'-oxime induce in cancer cells by inhibiting kinases such as CDK2 and GSK-3β, leading to arrest and caspase-3 activation, as observed in pancreatic and models with IC50 values in the low micromolar range. properties arise from suppression of and JNK pathways, reducing production (e.g., TNF-α, IL-6) in LPS-stimulated models, exemplified by 6-bromoindirubin-3'-oxime in fibroblasts. Antiviral activity is evident in derivatives like penta-1,4-diene-3-one oxime ethers, which inhibit replication, and indirubin oximes that delay A (H5N1) propagation by modulating proinflammatory responses. , an oxime ether antidepressant, inspires derivatives with enhanced and potential antiviral profiles through agonism. Efficacy of oximes in OP poisoning treatment varies significantly across species, complicating . For example, reactivates AChE more effectively in s and rabbits than in rats or mice, where rapid enzyme aging and differing limit reactivation rates. In dogs, obidoxime shows promise but induces hepatic toxicity absent in , attributed to variations in serum paraoxonase levels and AChE kinetics. These differences underscore the need for species-specific dosing and highlight challenges in extrapolating animal data to therapy.

History and Developments

Discovery and Early History

The discovery of oximes is attributed to German , who in 1882 synthesized the first examples by reacting with aldehydes and ketones, such as the preparation of acetone oxime from acetone and hydrochloride. This reaction demonstrated the general formation of the >C=NOH , establishing oximes as a new class of organic nitrogen compounds and laying the groundwork for their structural elucidation. In the early , oximes gained recognition in for their utility in protecting carbonyl groups and as intermediates in structural determinations, while Meyer's earlier work also introduced a diagnostic test for primary nitroalkanes involving nitrosation to form α-nitro oximes (nitrolic acids), which produce a characteristic red color upon treatment with . This test, developed in , highlighted oximes' role in for distinguishing nitro group types and contributed to broader applications in synthetic methodologies during the period. Following , the development of (OP) pesticides and nerve agents spurred research into oximes as therapeutic antidotes, with a significant medicinal push in the 1950s. (2-PAM), synthesized as an reactivator, was introduced in 1958 through studies demonstrating its efficacy in reversing OP-induced enzyme inhibition in human subjects. By the 1960s, five key oximes—, obidoxime, HI-6, TMB-4 (trimedoxime), and MMB-4 (methoxime)—had been synthesized and entered clinical and military use for treating OP poisoning, marking a pivotal milestone in their therapeutic application.

Recent Advances

In recent years, innovations in oxime synthesis have emphasized through electrochemical methods. A notable 2025 advancement involves an -cathode cascade electrolyzer that co-upgrades biomass-derived hydroxyl compounds, such as , with ions to produce oximes like pyruvatoxime. This process operates at 2.8 V with a flow rate of 0.5 mL cm⁻² min⁻¹, using a CoOOH/Ni foam and Cu substrate/Fe₃C , achieving a production rate of 2.61 mmol cm⁻² h⁻¹ and an outlet concentration of 87 mM, while maintaining stability over 72 hours. Unlike traditional routes that rely on explosive or unstable carbonyl intermediates, this method integrates oxidation and reduction in a single step, minimizing , hazardous byproducts, and , thereby enhancing for industrial applications. Progress in asymmetric synthesis has enabled efficient production of chiral amines from oximes. A 2024 review highlights recent developments in catalytic of oximes and oxime ethers to chiral hydroxylamines, employing catalysts such as , , and under mild conditions, achieving up to 99% enantiomeric excess for various aryl and alkyl substrates. These approaches address the challenges of the labile N-O bond and inert C=N bond, providing hydroxylamines as versatile precursors for chiral amines used in pharmaceuticals like sabcomeline. The review also covers expansions to oxime ethers using and complexes, streamlining access to enantiopure building blocks. Radical chemistry leveraging oxime derivatives has emerged as a powerful tool for carbon-carbon bond formation in the . Oxime esters serve as bifunctional reagents in the radical difunctionalization of alkynes, where visible-light triggers C-centered radical addition followed by N-centered radical migration via N-O bond cleavage, enabling alkylamination with yields up to 85% for diverse terminal alkynes. This strategy facilitates the synthesis of functionalized enamines useful in . Complementing this, N-O bond cleavage of oximes generates iminyl radicals that participate in C-C couplings, such as the coupling of oxime ethers with boronic acids under copper , producing ketones with moderate to high efficiency (50-90% yields) while avoiding harsh oxidants. These methods underscore the versatility of oxime-derived radicals in constructing complex scaffolds. In therapeutic applications, oxime-based compounds have advanced nerve agent detoxification. A 2025 library of 100 click-chemistry-derived oximes identified potent reactivators for (BChE) inhibited by s like , , VX, and tabun. Notably, mono-pyridinium oxime 5B achieved a reactivation rate of 34,120 M⁻¹ min⁻¹ for cyclosarin-inhibited BChE, surpassing standards like 2-PAM (525-fold) and HI-6 (44-fold), with reactivation exceeding 90% in within 6 minutes. These oximes enhance binding affinity and maximal reactivation rates, enabling pseudo-catalytic bioscavenging for improved antidotal efficacy. Efforts toward environmental include greener variants of oxime transformations and less toxic derivatives. A 2025 catalytic using a Hg(II)-perimidine-2-thione complex promotes ketoxime conversion to amides and lactams under mild conditions (80°C in ), accommodating aryl, alkyl, and cyclic substrates with yields of 71-99%, such as 95% for oxime and 92% for oxime, while improving and reducing formation compared to conventional acid-mediated processes. Additionally, oxime ethers have been explored as biodegradable alternatives to parent aldehydes and ketones in fragrances, exhibiting reduced aquatic toxicity—for instance, oxime O-ethyl ether shows EC₅₀ values up to 154 mg/L in versus higher sensitivity for carbonyls—offering greater chemical stability and lower environmental persistence.

References

  1. https://goldbook.iupac.org/terms/view/O04372
  2. https://pubs.acs.org/doi/10.1021/acs.chemrev.7b00264
  3. https://www.chemistrylearner.com/oxime.html
  4. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/oxime
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC8779982/
  6. https://byjus.com/chemistry/oximes/
  7. https://www.ebi.ac.uk/chebi/CHEBI:25750
  8. https://www.chem.ucla.edu/~harding/IGOC/O/oxime.html
  9. https://www.acdlabs.com/iupac/nomenclature/79/r79_583.htm
  10. https://www.collinsdictionary.com/us/dictionary/english/oxime
  11. https://www.dalalinstitute.com/wp-content/uploads/Books/A-Textbook-of-Organic-Chemistry-Volume-1/ATOOCV1-2-15-Geometrical-Isomerism-in-Alkenes-and-Oximes.pdf
  12. https://www.sciencedirect.com/science/article/abs/pii/S0166128006000716
  13. https://pubchem.ncbi.nlm.nih.gov/compound/Acetone_-oxime
  14. https://www.vedantu.com/chemistry/oximes
  15. https://cdnsciencepub.com/doi/pdf/10.1139/v62-310
  16. https://www.sciencedirect.com/science/article/pii/B978012523475750173X
  17. https://www.sciencedirect.com/science/article/abs/pii/S0040403911014341
  18. https://wissen.science-and-fun.de/chemistry/spectroscopy/13c-chemical-shifts/
  19. https://pmc.ncbi.nlm.nih.gov/articles/PMC2743602/
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC5580355/
  21. https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cber.188201501257
  22. https://doi.org/10.1021/ja01544a017
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC3339398/
  24. https://doi.org/10.1002/anie.200602877
  25. https://www.sciencedirect.com/science/article/pii/S001085459800215X
  26. https://pubs.acs.org/doi/10.1021/jo00959a011
  27. https://www.thieme-connect.de/products/ebooks/pdf/10.1055/sos-SD-127-00117.pdf
  28. https://www.nature.com/articles/s41467-025-61186-2
  29. https://pubs.acs.org/doi/10.1021/acscatal.3c05388
  30. https://www.sciencedirect.com/science/article/abs/pii/S0003267001936128
  31. https://pubs.acs.org/doi/10.1021/jo01258a062
  32. https://www.organic-chemistry.org/synthesis/N1H/reductionsoximes.shtm
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC9306632/
  34. https://par.nsf.gov/servlets/purl/10342408
  35. https://www.chemistrysteps.com/beckmann-rearrangement/
  36. https://www.sciencedirect.com/topics/chemistry/beckmann-reaction
  37. https://www.masterorganicchemistry.com/reaction-guide/beckmann-rearrangement/
  38. https://www.sciencedirect.com/topics/chemistry/neber-rearrangement
  39. https://pubs.acs.org/doi/10.1021/acssuschemeng.2c04409
  40. https://www.sciencedirect.com/science/article/abs/pii/B9780444532022500178
  41. https://pubs.acs.org/doi/10.1021/acssuschemeng.0c07254
  42. https://pubs.rsc.org/en/content/articlehtml/2025/ra/d5ra02843d
  43. https://onlinelibrary.wiley.com/doi/full/10.1002/prep.202100277
  44. https://www.mdpi.com/1420-3049/28/4/1775
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC10058904/
  46. https://pubs.rsc.org/en/content/articlelanding/2002/p1/b200549m
  47. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/celc.202300434
  48. https://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra15299b
  49. https://www.science.org/doi/10.1126/science.abl4822
  50. https://prismaneconsulting.com/report-details/caprolactam-market-size-share-analysis-and-industry-forecast
  51. https://research.tue.nl/files/3051284/693616.pdf
  52. https://pubs.rsc.org/en/content/articlelanding/2003/nj/b211236a
  53. https://borchers.com/meko-free/
  54. https://foreverest.net/products/aroma-chemicals/perillartine.html
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC2969981/
  56. https://patents.google.com/patent/US20030069167A1/en
  57. https://data.epo.org/publication-server/rest/v1.0/publication-dates/20070103/patents/EP1291409NWB1/document.pdf
  58. https://chemlab.truman.edu/files/2015/07/nickelgrav.pdf
  59. https://vlab.amrita.edu/index.php?sub=2&brch=193&sim=348&cnt=1
  60. https://www.sciencedirect.com/science/article/pii/0304386X75900110
  61. https://energy-resources.basf.com/global/en/mining_solutions/BASF_Hydrometallurgy
  62. https://www.mdpi.com/1420-3049/28/22/7467
  63. https://www.ncbi.nlm.nih.gov/books/NBK558908/
  64. https://www.cambridge.org/core/journals/disaster-medicine-and-public-health-preparedness/article/pralidoxime-is-no-longer-fit-for-purpose-as-an-antidote-to-organophosphate-poisoning-in-the-united-kingdom/8421AF115463EBD96D000B33EA24DE08
  65. https://www.sciencedirect.com/science/article/pii/S1674205217303842
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC8224626/
  67. https://pmc.ncbi.nlm.nih.gov/articles/PMC7457954/
  68. https://link.springer.com/article/10.2165/00139709-200322030-00004
  69. https://pubmed.ncbi.nlm.nih.gov/12242610/
  70. https://riviste.fupress.net/index.php/subs/article/download/3439/2279/23888
  71. https://www.sciencedirect.com/topics/chemistry/nitronic
  72. https://jamanetwork.com/journals/jama/article-abstract/299833
  73. https://pmc.ncbi.nlm.nih.gov/articles/PMC7367912/
  74. https://www.sciencedirect.com/science/article/abs/pii/S004040392400008X
  75. https://www.researchgate.net/publication/394859968_Oxime_ester_as_bifunctional_reagent_for_the_alkylamination_of_alkynes_via_C-centered_radical_addition_and_N-centered_radical_migration
  76. https://pmc.ncbi.nlm.nih.gov/articles/PMC9964420/
  77. https://www.mdpi.com/1420-3049/28/6/2667
  78. https://pmc.ncbi.nlm.nih.gov/articles/PMC12085358/
  79. https://pmc.ncbi.nlm.nih.gov/articles/PMC12247047/
  80. https://www.sciencedirect.com/science/article/abs/pii/S1642359325000394
Add your contribution
Related Hubs
Contribute something
User Avatar
No comments yet.