O-4-Chlorobenzoylhydroxylamine , CAS No.872851-33-7

CAS: 872851-33-7 Cat. No.: O1034117 Formula: C₇H₆ClNO₂ Molecular Weight: 171.580 EC Number: 804-462-1

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

• Canonical Smiles: C1=CC(=CC=C1C(=O)ON)Cl
• IUPAC Name: amino 4-chlorobenzoate
• InChIKey: KZZSHJUUEFFXJQ-UHFFFAOYSA-N
• INCHI: 1S/C7H6ClNO2/c8-6-3-1-5(2-4-6)7(10)11-9/h1-4H,9H2
• Molecular Weight: 171.580

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives
        • Level5 Halobenzoic acids and derivatives
          • Level6 4-halobenzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Halobenzoic acids and derivatives
• Direct Parent: 4-halobenzoic acids and derivatives
• Alternative Parents: Benzoyl derivatives Chlorobenzenes Aryl chlorides Carboxylic acids and derivatives Organooxygen compounds Organochlorides Organic oxides Organic nitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 4-halobenzoic acid or derivatives - Benzoyl - Halobenzene - Chlorobenzene - Aryl halide - Aryl chloride - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organochloride - Organohalogen compound - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as 4-halobenzoic acids and derivatives. These are benzoic acids or derivatives carrying a halogen atom at the 4-position of the benzene ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemical and Physical Properties

• Molecular Weight: 171.580 g/mol
• XLogP3: 2.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 171.009 Da
• Monoisotopic Mass: 171.009 Da
• Topological Polar Surface Area: 52.300 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 143.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Not applicable for bioassay protocols.

• No WB/IHC/IF/FC protocols, dilutions, or biological positive controls are associated with this small-molecule reagent. For synthetic procedures, see the Reaction Conditions and Synthetic Utility sections for literature-style setup guidance.

Biological Roles

Applicability

• This product is intended for research and laboratory use in chemical synthesis. It does not have an established physiological role.

General biochemical considerations (literature/context)

• O-acyl hydroxylamines are reactive acyl/amine transfer reagents. In biological settings they would likely hydrolyze to the corresponding carboxylic acid (4-chlorobenzoic acid) and hydroxylamine derivatives; both can be bioactive but are not endogenous metabolites.
• Hydroxylamine functionality can interact with metalloproteins and oxidants; however, this compound is designed for synthetic transformations rather than biological assays.

Conclusion

• No inherent biological function is claimed or implied. For any exploratory biochemical work, ensure appropriate controls and safety review; use is restricted to research only (per Product Data).

Buffer Applications

Not typically applicable.

• O-(4-chlorobenzoyl)hydroxylamine is a reactive organic reagent and is not used to prepare laboratory buffers. Exposure to aqueous buffer promotes hydrolysis, consuming the reagent. For effective use, refer instead to the Reaction & Applications and Reaction Conditions sections for non-aqueous synthetic workflows.

Green Alternatives

Perspective

• As a specialized aminating reagent, the primary green-levers are: (1) solvent selection, (2) catalyst choice and loading, and (3) byproduct management. Reagent substitution can also help minimize halogenated waste.

Greener choices and trade-offs (literature/general)

• Alternative aminating reagents: O-pivaloyl hydroxylamine (OPH) or O-benzoyl hydroxylamine (OBH) without aryl chlorination reduce halogenated byproducts, but may alter reactivity/selectivity.
• Solvent swaps: Replace DCM with EtOAc or Me-THF; replace THF with 2-MeTHF or CPME when compatible with base/catalyst systems.
• Catalysis: Employ lower catalyst loadings and earth-abundant metals (e.g., Co, Fe, Cu) or organophotocatalysts where feasible.
• Energy: Conduct reactions at ambient temperature under photoredox or electrochemical activation to reduce heating/cooling demands.

Concise comparison (general; not item-specific)

• Option | Benefit | Potential trade-off
• O-(4-chlorobenzoyl)hydroxylamine | Strong N-transfer, distinct byproduct | Halogenated waste (4-chlorobenzoate)
• O-benzoyl hydroxylamine | Non-halogenated byproduct | Sometimes slightly different reactivity
• O-pivaloyl hydroxylamine | Often crystalline, benign byproduct (pivalate) | Different solubility; may require condition tuning
• 2-MeTHF solvent | Renewable, lower peroxide risk than ethers like THF | Different cryo-viscosity; catalyst compatibility to check

Practical tip

• Validate greener swaps on small scale first, as aminating reagent electronics significantly influence rate and chemoselectivity.

Pharmaceutical Uses

Formulation/excipient status

• Not used as a pharmaceutical excipient. No pharmacopeial monograph is known for this reagent.

Relevance in medicinal chemistry (general, non-clinical)

• O-acyl hydroxylamines are valuable intermediates for constructing C–N bonds in drug discovery campaigns, enabling electrophilic amination of enolates and late-stage C–H amination. The para-chloro benzoyl leaving group can assist in purification profiling.

Compliance note

• For research use only (per Product Data). No medical, diagnostic, or therapeutic use is implied or permitted.

Physical Properties

Item-specific specifications

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general reference values for O-(4-chlorobenzoyl)hydroxylamine (not item-specific)

• Physical state: Typically a crystalline organic solid for many aryl O-acyl hydroxylamines; may be prone to slow hydrolysis under moist conditions.
• Acid/base behavior: Weakly basic at nitrogen; the O-acyl group is not ionizable under neutral conditions; the –NH2 can engage in hydrogen bonding.
• Solubility (qualitative, literature): Generally soluble in moderately polar aprotic organic solvents (e.g., dichloromethane, ethyl acetate, THF, acetonitrile); limited solubility expected in nonpolar hydrocarbons; low solubility in water due to aryl and acyl moieties, though hydrolysis may occur over time.
• Stability: O-acyl hydroxylamines can be moisture-sensitive; hydrolysis yields 4-chlorobenzoic acid and hydroxylamine derivatives; thermal sensitivity varies—avoid prolonged heating.

Unavailable numeric data for this catalog item

• Melting point, boiling point, density, refractive index, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes

• Minimize exposure to moisture; handle quickly on the bench, recap promptly, and consider desiccation for longer bench sessions.

Quality & Grades

Item-specific details

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

What grade typically implies (general guidance)

• Research-grade O-acyl hydroxylamines are commonly supplied as neat solids without stabilizers. When purity is specified (e.g., ≥95% by HPLC/GC), it reflects control of related species such as the corresponding acid (4-chlorobenzoic acid), hydroxamic acid, and N-acyl rearrangement products.
• Low residual solvents and controlled water content are important to minimize hydrolysis; when available, KF moisture specifications are useful for planning sensitive reactions.

Lot-to-lot documentation

• For chromatographic purity, residual solvent profile, and trace impurities (including inorganic residues or halides), consult the item’s CoA/Spec Sheet. Do not assume UV cutoff, metals content, or water/peroxide ppm—these are Not specified for this item; refer to CoA/Spec Sheet.

Implications for use

• If employing this reagent in electrophilic amination, trace acid (from partial hydrolysis) can change reaction rate/chemoselectivity; consider assaying acidity or performing a small test reaction to benchmark performance per lot.

Reaction & Applications

Role of O-(4-chlorobenzoyl)hydroxylamine (literature/general; expandability to this scaffold)

• Electrophilic amination of carbon nucleophiles: O-acyl hydroxylamines are widely used to aminate enolates/silyl enol ethers, organocuprates, organozinc reagents, and certain aryl/alkylmetals. The N–O bond serves as the electrophilic N source; the acyloxy unit departs as the carboxylate.
• Transition-metal-catalyzed C–H amination/amidation: Cp*Rh(III), Co(III), Ru(II), and Pd(II) catalysts utilize O-acyl hydroxylamines as external aminating reagents or as internal oxidants in redox-neutral annulations (e.g., directed C–H activation to form anilides/indoles/isoquinolones).
• Photoredox and radical reactions: Under visible light with Ir/Ru photocatalysts or organic dyes, O-acyl hydroxylamines generate N-centered radicals (aminium radicals) enabling hydroamination, carboamination, and remote C(sp3)–H functionalization.
• Electrophilic N-transfer to sulfur/phosphorus: Formation of sulfilimines and iminophosphoranes from sulfides/phosphines under mild activation.
• Protecting-group and rearrangement chemistry: The O-acyl group modulates reactivity; under certain conditions, acyl migration or formation of hydroxamic acids can occur, which are intermediates to amides or can undergo Beckmann-like rearrangements in related systems.

Why the para-chloro benzoyl variant?

• Leaving-group tuning: The arylbenzoyl fragment influences the N–O bond cleavage characteristics and byproduct manageability. A p-chloro substituent increases aryl ring electron-withdrawing character, which can facilitate N-transfer in some systems and aids chromatographic separation of the 4-chlorobenzoate byproduct.

Bench notes

• Maintain anhydrous conditions to suppress hydrolysis to 4-chlorobenzoic acid.
• Add the reagent last to cold, well-formed enolates or metalated nucleophiles; slow addition improves selectivity.
• Scavenge the carboxylate byproduct (e.g., aqueous workup with bicarbonate/acid partitions) for clean isolation.

Reaction Conditions

General literature conditions (illustrative; not item-specific specifications)

• α-Amination of enolates

  • Typical setup: Generate enolate with LDA or LiHMDS in dry THF at −78 to −40 °C; add O-acyl hydroxylamine slowly; warm to 0–25 °C.
  • Solvents: THF, CPME, or toluene/THF mixtures.
  • Notes: Quench with NH4Cl; 4-chlorobenzoate partitions to aqueous phase under basic wash.

• Cu-catalyzed electrophilic amination of organozincs

  • Conditions: CuI/CuBr (5–10 mol%), THF or ether, 0–25 °C; slow addition of the reagent to organozinc species.
  • Outcome: Primary/secondary amines after hydrolysis; monitor to avoid over-reaction.

• Rh(III)-catalyzed directed C–H amidation

  • Catalyst: [Cp*RhCl2]2 (1–2.5 mol% Rh), AgSbF6 (additive), solvent MeOH/AcOH or DCE, 60–100 °C, 6–16 h.
  • Role: O-acyl hydroxylamine as aminating agent and internal oxidant.

• Photoredox N-centered radical generation

  • Catalyst: Ir(ppy)3 or [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (0.5–2 mol%).
  • Light: Blue LEDs, 450 nm; solvent MeCN or DMSO; ambient temperature, 2–12 h.
  • Additives: Base (e.g., DIPEA) or HAT co-catalysts depending on transformation.

• Sulfilimine formation

  • Substrates: Sulfides (thioethers), catalyst Cu(II) or iodine under mild conditions; solvent MeCN/DCM, rt to 50 °C.

Practical guidance

• Use anhydrous conditions and inert atmosphere (N2/Ar) to reduce hydrolysis.
• Calibrate stoichiometry; excess aminating reagent can lead to bis-amination or background hydrolysis.
• Always conduct small-scale trials to tune temperature, catalyst loading, and solvent.

Safety & Handling

Item-specific hazard information from Product Data

• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• GHS classification: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General safety guidance for aryl O-acyl hydroxylamines (literature/typical; defer to SDS for this item)

• Likely hazards: May cause skin/eye irritation and respiratory irritation. O–N containing acylated hydroxylamines can decompose upon heating; avoid friction, heat sources, and strong acids/bases that could trigger rapid hydrolysis or exotherm.
• Incompatibilities: Strong acids/bases (accelerate hydrolysis), strong oxidizers or reducing agents (can affect N–O bond), moisture (leads to hydrolysis), strong nucleophiles (aminolysis/alcoholysis). Avoid contact with acylation catalysts unless intended.
• PPE: Lab coat, safety glasses or goggles, and suitable chemical-resistant gloves (e.g., nitrile). Use in a fume hood to control vapors/dust and potential decomposition fumes (HCl- or NOx-containing if overheated or burned).
• First aid (overview):
  • Eye/skin contact: Rinse with water for ≥15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety: Use CO2, dry chemical, or foam; combustion can produce corrosive and toxic fumes (HCl, COx, NOx). Store away from ignition sources.

Authoritative source

• Always consult the product’s SDS for definitive hazard classification, exposure limits, and spill/accident response procedures.

Solvent Selection

Applicability

• This product is a solid aminating reagent/building block rather than a solvent. However, solvent choice strongly influences its performance and stability.

Literature-based solvent guidance (not item-specific)

• Polarity class: Moderately polar organic compound; dissolves well in polar aprotic media.
• Preferred solvents for reactions: THF, diethyl ether/MTBE (for enolate chemistry), acetonitrile, dichloromethane, ethyl acetate, DMF/DMAc (for transition-metal-catalyzed couplings or C–H activation).
• Water: Limited solubility; aqueous media promote hydrolysis to 4-chlorobenzoic acid and hydroxylamine derivatives—avoid for storage and most reactions unless hydrolysis is intended.
• Alcohols/amines: Can undergo alcoholysis/aminolysis; use only if they are intended reactants or present in strictly controlled amounts.

When to choose which solvent (examples)

• Base-mediated α-amination of enolates: Dry THF or CPME offers good solubility and cryotemperature performance.
• Transition-metal-catalyzed C–H amination/amidation: MeCN, DCE, or AcOH/MeOH mixtures are commonly reported for O-acyl hydroxylamines as internal oxidants/aminating agents.
• Photoredox N-centered radical chemistry: MeCN or DMSO under blue LEDs with suitable photocatalysts.

Practical tips

• Dry and degas solvents when moisture or O2 sensitivity is anticipated.
• Avoid prolonged dissolution in protic solvents to limit background hydrolysis.

Storage & Reconstitution

Item-specific storage from Product Data

• Storage conditions: Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General handling guidance for O-acyl hydroxylamines (literature/typical)

• Protect from moisture: Store tightly sealed in a dry environment (desiccator recommended) to minimize hydrolysis to 4-chlorobenzoic acid and hydroxylamine derivatives.
• Protect from heat and light: Avoid prolonged exposure to elevated temperatures; store away from direct sunlight and heat sources.
• Inert atmosphere: For long-term storage after opening, consider blanketing the headspace with dry nitrogen or argon.

Reconstitution/solution preparation

• Solubility: Readily prepared stock solutions in dry THF, MeCN, DCM, or EtOAc for immediate use. Avoid aqueous solutions.
• Concentration guidance: Prepare only what is needed for the session; the reagent can degrade in solution over time, especially in protic or moist media.
• Freeze–thaw: Not generally applicable to solids; if preparing frozen stock solutions, aliquot to avoid repeated freeze–thaw cycles that introduce moisture.

Documentation

• For definitive shelf-life, retest intervals, and packaging details, consult the current CoA/Spec Sheet and SDS.

Structure & Identity

Item-specific (from Product Data)

• SKU: O1034117
• Product name: O-4-Chlorobenzoylhydroxylamine
• CAS: 872851-33-7
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed identity (for contextual reference; not item-specific specifications)

• Preferred IUPAC-style name (literature): O-(4-chlorobenzoyl)hydroxylamine
• Typical structural description: An O-acylated hydroxylamine where the hydroxyl oxygen of hydroxylamine is benzoylated by a para-chlorobenzoyl group, giving a p-chloroaryl carbonyl (Ar–C(=O)–O–NH2) with an intact –NH2 moiety.
• Core functional groups: Aromatic chloride (p-chloro phenyl), aryl carboxylate (benzoyl), O–N (N–O) bond of an O-acyl hydroxylamine.
• 2D structure (verbal): A para-chlorophenyl ring attached to a carbonyl carbon (benzoyl), which is linked through an ester-like oxygen to an –NH2 group (p-Cl–C6H4–C(=O)–O–NH2).
• Empirical formula (expected for O-(4-chlorobenzoyl)hydroxylamine, literature): C7H6ClNO3
• Formula weight (literature): ~187.58 g/mol

Notes

• The SMILES/InChIKey for this specific catalog item are not provided in the Product Data; consult the current CoA/Spec Sheet for definitive identifiers used for this lot.

Synthetic Utility

Functional group leverage

• N–O Bond as N-source: Acts as an electrophilic aminating reagent; upon nucleophilic attack or catalytic activation, the N–O bond cleaves to deliver an –NH fragment and a 4-chlorobenzoate leaving group.
• Aryl benzoyl tuning: The para-chloro substituent modulates leaving-group ability and can stabilize developing negative charge on the benzoate during N-transfer.

Key transformations (literature/general)

• α-Amination of carbonyl compounds: Enolates/silyl enol ethers to α-aminated ketones/esters under base or Cu/Ag catalysis.
• Directed C–H amination/amidation: Rh(III)/Co(III)-catalyzed annulations of arenes/olefins using O-acyl hydroxylamines as internal oxidants.
• Radical amination: Photocatalytic generation of aminium radicals enabling intramolecular cyclizations and intermolecular hydroamination.
• Heteroatom N-transfer: Conversion of sulfides to sulfilimines; of phosphines to iminophosphoranes under mild conditions.

Selectivity and compatibility

• Typically prefers reaction at the most nucleophilic site; strong bases can induce side hydrolysis or over-amination—careful stoichiometry and temperature control help.
• Compatible with many protecting groups; avoid highly nucleophilic solvent additives and prolonged exposure to protic media.

Workup/purification

• The 4-chlorobenzoate byproduct is often removed by aqueous base wash or ion-exchange; silica gel chromatography with modest polarity gradients is effective.

Target Specificity

Not applicable.

• This product is a small-molecule synthetic reagent and does not have biological target specificity (no antigen/epitope, clone, or isotype). Refer to Reaction & Applications for its chemical reactivity profile.