4-Azidoaniline , CAS No.14860-64-1

CAS: 14860-64-1 Cat. No.: A1069357 Formula: C₆H₆N₄ Molecular Weight: 134.140 EC Number: 238-929-0

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

Canonical Smiles

C1=CC(=CC=C1N)N=[N+]=[N-]

IUPAC Name

4-azidoaniline

InChIKey

SSMVDPYHLFEAJE-UHFFFAOYSA-N

INCHI

1S/C6H6N4/c7-5-1-3-6(4-2-5)9-10-8/h1-4H,7H2

Molecular Weight

134.140

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Phenylazides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Phenylazides
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylazides
• Alternative Parents: Aniline and substituted anilines Azo imides Azo compounds Primary amines Organopnictogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Aniline or substituted anilines - Phenylazide - Azo imide - Azo compound - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Primary amine - Organonitrogen compound - Amine - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylazides. These are compounds containing a phenylazide moiety, which consists of a linear azide substituent attached to a phenyl group.
• 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: 134.140 g/mol
• XLogP3: 2.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 134.059 Da
• Monoisotopic Mass: 134.059 Da
• Topological Polar Surface Area: 40.400 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 142.000
• 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

No item-specific, validated protocols are provided for this catalog entry. Refer to literature procedures and adapt to your system.

General starting points (literature; adjust as needed)

• CuAAC labeling: Dissolve 4-azidoaniline (or its derivative) and alkyne partner (1.0–1.5 equiv) in tBuOH/H2O (1:1). Add CuSO4·5H2O (1–2 mol%), sodium ascorbate (5–10 mol%), and a ligand such as THPTA (5–10 mol%). Stir at rt 2–6 h; monitor by LC–MS. Extract or precipitate product; remove copper with chelators (EDTA) if needed.
• Staudinger reduction: Stir 4-azidoaniline (1.0 equiv) with PPh3 (1.2 equiv) in THF (0.1–0.2 M) at rt under N2, then add water and continue stirring until azide band (IR ~2100 cm−1) disappears. Work up to obtain para-phenylenediamine derivative.
• Photolabeling: Prepare dilute solution in MeCN (e.g., 0.5–2 mM) with target substrate; irradiate at 365 nm with cooling and stirring for 5–30 min. Quench light, analyze by LC–MS. Optimize wavelength/intensity to minimize overreaction.

Note

• These are general literature-style outlines and are not validated for this specific item. Consult primary literature and perform small-scale trials. For research use only.

Biological Roles

Scope of applicability

• 4-Azidoaniline is a synthetic organic reagent, not a native metabolite. No inherent biological role is attributed to this specific compound.

Literature context (general)

• Photoaffinity probe precursor: Aryl azides are classical photo-crosslinking groups used to map ligand–protein interactions. 4-Azidoaniline can serve as a scaffold for generating photoaffinity labels after appropriate functionalization (e.g., installing a reporter through the aniline).
• Bioorthogonal reactivity: The azide group participates in bioorthogonal cycloadditions (CuAAC, SPAAC) with alkyne handles on biomolecules, enabling conjugation in biochemical research. Note that copper-catalyzed conditions may be incompatible with some living systems; SPAAC avoids copper but requires strained alkynes.

Cautions

• No claims are made regarding biological activity, safety, or suitability for clinical use. For research use only.
• If deploying in biochemical systems, thoroughly remove residual copper (if used), and evaluate cytotoxicity/biocompatibility of the full construct rather than the starting reagent.

Buffer Applications

Not typically applicable.

• 4-Azidoaniline is an organic reagent used primarily in synthetic and photochemical applications and is not used to prepare aqueous buffer systems.
• For aqueous-phase conjugation (e.g., CuAAC), buffers may be used to control pH and copper speciation (e.g., phosphate, HEPES), but those are chosen based on the reaction system, not on this reagent. Consult Reaction & Applications and Reaction Conditions for practical solvent/buffer choices in click chemistry.

Green Alternatives

Greener handling and media (general guidance)

• Solvent choices have the largest EHS impact when working with 4-azidoaniline. Favor low-toxicity, bio-based, or recyclable solvents when compatible with your transformation.

Comparison (literature-based; choose per reaction)

• Acetonitrile vs 2-MeTHF
  • Pros (2-MeTHF): Bio-based, lower toxicity, recyclable, good for many coupling steps and some CuAAC variants.
  • Pros (MeCN): Excellent UV transparency for photolysis; strong polarity; easy removal; broad catalyst compatibility.
  • Tradeoff: 2-MeTHF is less UV-transparent and may be less suitable for photochemistry.
• DCM vs Ethyl acetate
  • Ethyl acetate offers lower environmental impact, is readily biodegradable, and often replaces DCM in extractions and some acylations.
• DMF/DMSO vs Cyrene/propylene carbonate
  • Emerging greener dipolar aprotics (e.g., Cyrene) can sometimes substitute DMF; validate solubility and reaction rates.

Process intensification ideas

• Use aqueous tBuOH/H2O or MeOH/H2O for CuAAC to reduce organic solvent load; implement ligand-accelerated systems (e.g., THPTA) to run at ambient temperature.
• LED photochemistry: If performing nitrene insertions, employ narrow-band LEDs (e.g., 365 nm) to minimize energy use and over-irradiation.
• Catalyst management: Employ supported copper catalysts for CuAAC to simplify recovery and reduce metal discharge; consider copper-free strain-promoted azide–alkyne cycloaddition (SPAAC) when feasible to avoid copper entirely (requires strained alkyne partners).

Safety–environment link

• Avoid chlorinated solvents and excessive heating to mitigate both hazards and energy consumption. Implement light shielding to prevent uncontrolled azide decomposition and waste generation.

Pharmaceutical Uses

Formulation/excipient status

• No pharmacopeial excipient status is known for 4-azidoaniline. It is a research chemical and synthetic intermediate rather than a formulation aid.

Manufacturing/research context (general)

• Intermediate for medicinal chemistry: Serves as a building block to access para-functionalized anilines, triazole-linked analogs (via CuAAC), or photoaffinity probes used in target identification workflows.
• Conjugation handle: The azide moiety can be retained in intermediates to allow late-stage attachment of solubilizing groups, fluorophores, or affinity tags during lead optimization and assay development.

Compliance note

• This product is supplied strictly for research and laboratory use. It is not intended for diagnostic, therapeutic, or human/animal consumption applications.

Physical Properties

Item-specific specs (this catalog item)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index, UV cutoff, trace metals: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties (for reference only; not specifications)

• Physical state: Typically a crystalline solid (literature, aryl azide/aniline class).
• Molecular weight: ~134.14 g/mol (C6H6N4, literature calculation).
• Solubility profile: Moderately soluble in polar organic solvents (e.g., ethyl acetate, acetone, acetonitrile, alcohols, DMSO, DMF); low solubility in water (general for aryl azides/anilines).
• Acidity/basicity: Aniline –NH2 is weakly basic (pKa of anilinium conjugate acid typically ~4.6–5.5 in water, literature range for anilines). Para azido substituent is weakly electron-withdrawing, further lowering basicity versus aniline (qualitative literature trend).
• Partitioning: Aromatic amines/aryl azides are generally moderately lipophilic (qualitative; logP expected positive, literature class behavior).
• Thermal behavior: Aryl azides can undergo exothermic decomposition to nitrenes on heating or photolysis; melting points for specific aryl azides vary and should be checked on the item CoA.

Practical notes

• Avoid prolonged exposure to elevated temperatures and intense light due to potential azide decomposition (general property). Verify exact numeric values (mp, bp) for your lot on the CoA before process design.

Quality & Grades

Item-specific quality data

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

Context and guidance (general)

• Research grade aryl azides: Typically provided for synthetic and labeling applications. Purity is commonly expressed as GC/HPLC area % or NMR assay. Impurities of concern include aniline-derived byproducts, reduction products (e.g., corresponding amines), or partial decomposition products (e.g., triazene/tetrazole traces under certain conditions).
• UV/Chromatography considerations: If using for photochemistry or photoaffinity labeling, low background UV absorbance from stabilizers is desired. If HPLC-grade specifications or stabilizers are critical for your workflow, request full specification details.
• Residual metals/peroxides/water: Unless explicitly stated, these are not controlled to specialized levels. For moisture- or metal-sensitive transformations (e.g., catalytic couplings, click chemistry), consider in-house pre-treatment (drying, filtration through silica/alumina) and verify by KF or ICP if necessary.
• Lot release: For sensitive workflows, request CoA detailing analytical method (GC/HPLC), residual solvents, and spectral verification (1H/13C NMR, IR with azide stretch ~2100 cm−1, literature) to corroborate identity and purity.

Recommendation

• For photochemical or bio-conjugation applications, confirm stabilizer-free status and photopurity requirements with our technical team prior to scale-up. Always rely on the item’s CoA for binding specifications.

Reaction & Applications

Overview

• 4-Azidoaniline is a versatile bifunctional building block combining an aniline nucleophile with an aryl azide handle. Its reactivity underpins both classic aniline chemistry and azide-specific transformations.

Key application families (literature)

• Click chemistry (CuAAC): The aryl azide reacts with terminal alkynes under Cu(I) catalysis to form 1,2,3-triazoles. The pendant aniline can be orthogonally protected (e.g., Boc, sulfonyl) to direct selectivity. Use CuSO4/sodium ascorbate or preformed Cu(I) with stabilizing ligands (e.g., TBTA, THPTA) to mitigate amine–Cu coordination.
• Photoaffinity labeling: Aryl azides generate nitrenes upon UV irradiation (typically 250–365 nm), enabling insertion into C–H, N–H, or π-bonds to form covalent adducts. The aniline allows further conjugation (e.g., acylation to reporter tags) post-photolysis.
• Staudinger chemistry: Reduction of the azide with PPh3 affords the corresponding aniline (para-diamine) via an iminophosphorane intermediate, providing a protected amine handle for downstream coupling.
• Diazotization/Sandmeyer on the aniline: Conversion of the –NH2 to a diazonium salt enables further substitutions (e.g., –F via Balz–Schiemann, –CN, –H via hypophosphorous acid), while retaining or transforming the para azide depending on conditions. Careful condition choice is required to avoid azide decomposition.
• Urea/amide/sulfonamide formation: The aniline is readily derivatized with acyl chlorides, anhydrides, sulfonyl chlorides, and isocyanates, providing functional triazole–anilide hybrids after CuAAC.

Practical considerations

• Protect from strong light during handling to avoid premature azide activation.
• For CuAAC with an aniline-bearing azide, use chelating ligands and pH/solvent control to sustain catalyst activity and minimize amine oxidation.

Reaction Conditions

General guidance (literature; adjust to your system and verify by small-scale trials)

CuAAC (azide + terminal alkyne → 1,2,3-triazole)

• Catalyst: CuSO4 (0.5–5 mol%) + sodium ascorbate (reducing agent) or preformed CuI/CuBr with ligands (e.g., TBTA 5–10 mol%, THPTA for aqueous media).
• Solvent: tBuOH/H2O (1:1), MeOH/H2O, DMF, DMSO, or MeCN; 0.05–0.2 M substrate concentration typical.
• Temperature/time: rt to 60 °C; 1–16 h depending on substrate and catalyst/ligand.
• Notes: Aniline can coordinate copper; use excess ligand to maintain active Cu(I). Degas if oxidation is problematic.

Staudinger reduction (azide → amine)

• Reagents: PPh3 (1.1–1.5 equiv) in THF or THF/H2O; then hydrolysis under aqueous conditions.
• Conditions: 0–25 °C, 1–6 h. Monitor by disappearance of azide IR band (~2100 cm−1; literature).

Photolysis/nitrene insertion (photoaffinity work)

• Light source: 300–365 nm (UV-A) LEDs or mercury lamps with filters.
• Solvent: UV-transparent, non-nucleophilic (MeCN, cyclohexane, DCM). Concentration 0.1–5 mM typical for labeling.
• Temperature: 0–25 °C. Protect from oxygen and use inert atmosphere when needed to control nitrene pathways.

Aniline acylation/sulfonylation

• Reagents: Acyl chloride or sulfonyl chloride (1.05–1.5 equiv), base (Et3N, DIPEA, pyridine), DCM/THF/EtOAc.
• Temperature: 0 °C to rt; 0.5–4 h. Workup by aqueous quench and extraction.

Cautions

• Avoid strong heat/UV unless intentionally activating the azide. Conduct small-scale DoE to define optimal conditions for your substrate pair.

Safety & Handling

Item-specific hazard information

• 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 azides and aromatic amines (literature/industry practice)

• Principal hazards: Aryl azides can decompose exothermically to nitrenes under heat or UV; avoid heating and protect from strong light. Aromatic amines may be harmful by inhalation, ingestion, or skin contact and can cause skin/eye irritation and sensitization in some cases.
• PPE: Use lab coat, safety goggles, and suitable chemical-resistant gloves (e.g., nitrile). Handle in a fume hood to minimize inhalation exposure.
• Incompatibilities: Avoid strong acids or strong oxidizers without control. Prevent contact with strong reducing agents that could generate anilide radicals. Avoid heavy metal salts/contaminants that can form sensitive metal azides (general azide caution), although aryl azides are less prone than inorganic azides.
• Handling: Minimize friction, impact, and grinding of dry azide powders. Use amber glassware or foil-wrap when practical to limit photolysis. Scale-up should be subject to calorimetric assessment.
• First aid (overview; defer to SDS): Remove to fresh air if inhaled; rinse skin/eyes with water for at least 15 minutes on contact; seek medical attention if symptoms persist. If ingested, do not induce vomiting; seek immediate medical attention.
• Fire response: Use CO2, dry chemical, or foam. Avoid excessive heat; decomposition may release nitrogen and reactive intermediates. Evacuate area if significant heating occurs.

Always consult the product-specific SDS for authoritative hazard and response information.

Solvent Selection

Applicability

• 4-Azidoaniline is a small, bifunctional aromatic compound (aniline + aryl azide). It is typically handled and reacted in organic media rather than aqueous buffers.

General solvent guidance (literature/experience)

• Polarity/miscibility: Soluble in polar aprotic solvents (DMF, DMSO, acetonitrile), polar protic solvents (methanol, ethanol), and moderately in less polar solvents (ethyl acetate, dichloromethane). Poorly soluble in water.
• Reaction media:
  • CuAAC/“click” derivatizations (with an alkyne partner): DMF, DMSO, tBuOH/H2O mixtures, or MeOH/H2O are commonly used; amine may coordinate copper—use ligand (e.g., TBTA, THPTA) to maintain catalyst performance (literature practice).
  • Photolysis/nitrene insertions: Non-nucleophilic, UV-transparent solvents (acetonitrile, cyclohexane, dichloromethane) minimize side reactions and facilitate monitoring.
  • Electrophilic acylation/sulfonylation on the aniline: Use base-scavenging or biphasic conditions (e.g., Et3N in DCM/THF) to control protonation.

Comparison notes (general)

• DMF vs acetonitrile: DMF dissolves substrates and catalysts well but is higher boiling and harder to remove; MeCN is lower boiling and more UV-transparent, preferred for photolysis.
• Alcohol/water mixtures: Useful for CuAAC; enhance catalyst solubility but can increase side hydrolysis for some acylations.
• EHS considerations: Prefer greener solvents like 2-MeTHF or ethyl acetate when compatible; avoid chlorinated solvents for scale-up if an alternative works.

Practical tips

• Dry solvents when moisture-sensitive steps are involved (e.g., acyl chloride couplings). Protect solutions from strong light to limit azide photolysis.

Storage & Reconstitution

Item-specific storage/shipping

• Storage Conditions: Room temperature (per Product Data). Protect from strong light to preserve azide integrity (general azide handling).
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General guidance

• Container: Store in tightly closed, amber glass container with desiccant if possible. Keep away from heat sources and direct sunlight.
• Stability: Aryl azides are generally stable at ambient conditions when protected from light; avoid prolonged storage at elevated temperature.
• Solution handling: Prepare stock solutions in dry, oxygen-free solvents (e.g., acetonitrile, DMF, DMSO) as needed. Store solutions in amber vials at 2–8 °C or −20 °C for short periods, minimizing headspace and light exposure. Discard if discoloration or gas evolution is observed.
• Freeze–thaw: Not typically applicable to solids; if storing solutions frozen, avoid repeated freeze–thaw by aliquoting.

Verification

• Prior to critical applications, confirm identity/purity by IR (azide stretch ~2100 cm−1, literature), LC–MS, or NMR. Always consult the item-specific CoA and SDS for definitive guidance.

Structure & Identity

Item-specific (from Product Data)

• SKU: A1069357
• Product Name: 4-Azidoaniline
• CAS: 14860-64-1
• InChIKey: 344207 (as provided)
• Storage Conditions: Room temperature
• Research Use Note: For research use only

Literature/general identity (for reference; not item specifications)

• Synonyms: p-Azidoaniline; 4-azidobenzenamine; p-azidobenzenamine
• Molecular formula: C6H6N4 (literature)
• Molecular weight: ~134.14 g/mol (literature)
• Structural features: An aniline ring (para-aminobenzene) bearing a para aryl azide (–N3) substituent relative to the –NH2 group. The ring is para-disubstituted, giving a 1,4-arrangement: –NH2 at C1 and –N3 at C4.
• Functional groups: Primary aniline (–NH2); aryl azide (–N3). No stereocenters.
• 2D description in words: A benzene ring with an amino group at position 1 and an azido group at position 4, creating a strongly conjugated, para-disubstituted aryl system. The azide is linear (Nα=Nβ+=Nγ− resonance) attached through Nα to the ring.

Notes

• The azide functionality enables nitrene generation under photolysis/thermolysis and participates in CuAAC after appropriate derivatization on the complementary partner (alkyne). The aniline offers nucleophilic reactivity (acylation, sulfonylation, diazotization to diazonium). Always verify exact identifiers on the CoA/Spec Sheet for this item.

Synthetic Utility

Functional handles and strategies

• Orthogonal bifunctionality: The molecule offers an aniline nucleophile and an aryl azide electrophile/1,3-dipole.

Transformations (literature)

• 1,3-Dipolar cycloaddition (CuAAC/SPAAC): Forms 1,4-disubstituted 1,2,3-triazoles with terminal alkynes (CuAAC) or with strained alkynes (SPAAC). The aniline can be derivatized before or after cycloaddition to modulate electronics and solubility.
• Protection/derivatization of –NH2: Boc, Cbz, sulfonyl (e.g., tosyl, nosyl), or acyl protections increase chemoselectivity during azide transformations.
• Staudinger reduction: Azide → amine using PPh3 (then hydrolysis), giving p-phenylenediamine derivatives. Iminophosphorane intermediates can be trapped (e.g., Staudinger ligation) to linkers/carbonyl partners.
• Photochemical nitrene chemistry: Upon UV irradiation, aryl azides form singlet/triplet nitrenes that rearrange (e.g., to dehydroazepines) or insert into C–H/N–H bonds—useful for covalent capture in materials and chemical biology after proper derivatization.
• Diazonium chemistry on the aniline: –NH2 → Ar–N2+ for Sandmeyer-type substitutions (Cl, Br, CN), Balz–Schiemann (F), or reductive deamination (H), enabling diversification while retaining/transforming the azide as required by conditions.
• Electrophilic coupling: Formation of amides, ureas, carbamates, and sulfonamides from the aniline expands into libraries of functional conjugates.

Retrosynthetic value

• Provides a convergent node: assemble aryl core with para azide, then append diversity via either aniline derivatization or azide cycloadditions. Useful in late-stage diversification of aromatic scaffolds.

Target Specificity

Not applicable to this product type.

• 4-Azidoaniline is a small-molecule reagent, not an antibody, enzyme, or affinity reagent with defined biological target specificity.
• For photoaffinity or bioconjugation experiments, specificity arises from the attached recognition motif you design, not from 4-azidoaniline itself.