4-Cyclopropyl-3-fluoroaniline - ≥98% , CAS No.1208083-48-0

CAS: 1208083-48-0 Cat. No.: C1042574 Fórmula: C₉H₁₀NF Peso molecular: 151.18 Número EC: 842-430-9 PubChem CID: 59637273

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Especificaciones y pureza

≥98%

Condiciones de almacenamiento de almacenamiento

Room temperature

Pureza

≥98%

Nombres e identificadores

• Sonrisas canónicas: C1CC1C2=C(C=C(C=C2)N)F
• IUPAC Name: 4-cyclopropyl-3-fluoroaniline
• InChIKey: XGGDMIHKUNLGQE-UHFFFAOYSA-N
• INCHI: 1S/C9H10FN/c10-9-5-7(11)3-4-8(9)6-1-2-6/h3-6H,1-2,11H2
• Isómeros SMILES: C1CC1C2=C(C=C(C=C2)N)F
• PubChem CID: 59637273
• Peso molecular: 151.18

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase Benzene and substituted derivatives
      • Subclass Aniline and substituted anilines

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Clase: Benzene and substituted derivatives
• Subclass: Aniline and substituted anilines
• Intermediate Tree Nodes: Not available
• Direct Parent: Aniline and substituted anilines
• Alternative Parents: Fluorobenzenes Aryl fluorides Primary amines Organofluorides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Aniline or substituted anilines - Halobenzene - Fluorobenzene - Aryl halide - Aryl fluoride - Organic nitrogen compound - Hydrocarbon derivative - Primary amine - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Aromatic homomonocyclic compound
• Descripción: This compound belongs to the class of organic compounds known as aniline and substituted anilines. These are organic compounds containing an aminobenzene moiety.
• 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

Propiedades químicas y físicas

• Peso molecular: 151.180 g/mol
• XLogP3: 2.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 151.08 Da
• Monoisotopic Mass: 151.08 Da
• Topological Polar Surface Area: 26.000 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 144.000
• 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. No bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic procedures using this amine (e.g., acylation, urea formation, Buchwald–Hartwig coupling), see the Reaction Conditions and Synthetic Utility sections for general literature guidance.

Biological Roles

Applicability: This product is a small-molecule aromatic amine used for research and synthesis. It is not a biological reagent or metabolite supplied for biochemical function.

General context (literature)

• Aromatic amines like 4-cyclopropyl-3-fluoroaniline are common fragments in medicinal chemistry, used to modulate basicity, polarity, and metabolic stability when incorporated into larger drug-like molecules. The meta-fluoro substituent can influence π-stacking, hydrogen-bond acceptor capacity (via C–F polarizability), and block metabolic oxidation at adjacent positions. The cyclopropyl group is a compact, lipophilic substituent that can serve as a conformational/steric modulator and sometimes acts as a mild σ-donor through hyperconjugation.
• Standalone biological “roles” are not typical; activity arises from the final compound context. Free anilines may display nonspecific protein binding and are substrates for phase I/II metabolism (N-oxidation, N-acetylation, conjugation) in biological systems.

Research Use Note (item-specific)

• For research use only (as provided). Not for human or veterinary use, diagnostic procedures, or clinical applications.

Buffer Applications

Not typically applicable. 4-Cyclopropyl-3-fluoroaniline is a hydrophobic aromatic amine used as a synthetic building block, not a biological buffer component. If aqueous handling is required (e.g., extractions), protonation with mineral acid can increase water solubility, but for true buffering applications use established systems (e.g., phosphate, acetate, Tris).

Green Alternatives

Context: As a reagent, 4-cyclopropyl-3-fluoroaniline’s footprint is dominated by solvent and reagent choices during its transformations.

Greener choices (literature/general)

• Reaction media alternatives
  • Replace DCM/CHCl3 with EtOAc, Me-THF, CPME, or toluene where feasible.
  • Use 2-MeTHF/CPME for moisture-sensitive couplings (Buchwald–Hartwig) instead of THF/Et2O; they offer better safety (reduced peroxide tendency vs ethers like THF/Et2O) and improved lifecycle metrics.
  • Favor EtOH/i-PrOH or water–co-solvent systems for reductions or imine formations when compatible.
• Reagent selection
  • Prefer CDI, DSC, or EDCI over phosgene/triphosgene for urea/carbamate/amidation when scope allows.
  • Explore catalytic C–N formations using copper or nickel systems with benign bases (e.g., K3PO4) as alternatives to strong alkoxides.
• Workup/waste minimization
  • Implement in-process base scavengers to reduce aqueous neutralizations.
  • Use solvent recycling and minimal-chromatography purification (crystallization or salt formation) to cut waste.

Illustrative comparison (general)

• DCM vs EtOAc: EtOAc offers lower toxicity and better biodegradability; may require temperature adjustment for solubility.
• THF vs 2-MeTHF: 2-MeTHF is partially bio-based and less volatile; similar solvency profile for amination reactions.

Trade-offs: Greener solvents can alter rates/selectivity; run small-scale scouting to validate kinetics and impurity profiles.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this item.

General formulation/manufacturing context (literature)

• Role in discovery and process chemistry: This aniline serves as a fragment/intermediate for assembling API candidates (e.g., via amide/urea formation or cross-coupling as the amine partner). The para-cyclopropyl/meta-fluoro motif can adjust potency and ADME in SAR campaigns.
• Impurity control: Free anilines may be controlled as intermediates or residuals in API routes; process development should include suitable purge steps and analytical methods (HPLC/GC) to control genotoxic or sensitizing impurities where relevant.
• Salt formation: For isolation or crystallinity tuning, temporary formation of anilinium salts (e.g., HCl, TsOH) may aid handling and purification, followed by basification.

Note: No therapeutic claims are made. This product is supplied strictly for research and laboratory synthesis.

Physical Properties

Item-specific specifications (this SKU)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index, UV cutoff, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for 4-cyclopropyl-3-fluoroaniline (reference only)

• Phase at ambient conditions: aromatic amines of this size (C9H10FN) are typically liquids or low-melting solids.
• Acid–base: primary aniline; conjugate acid pKaH is typically ~4–6 for anilines. A meta-F substituent (EWG) slightly lowers basicity, while a para-cyclopropyl is weakly donating; overall pKaH is expected in the aniline range (literature context).
• Solubility: expected to be sparingly soluble in water and miscible with many organic solvents (EtOAc, ethers, alcohols, aromatics, chlorinated solvents) due to the aromatic/alkyl character and a single H-bond donor (literature context).
• Partitioning: expected moderate lipophilicity versus aniline due to cyclopropyl and aryl–F (literature context).

Use notes

• If precise values (bp/mp, density, logP, solubility) are critical for your process modeling or regulatory filings, obtain them from the item’s CoA/SDS or measure under your conditions.

Quality and Grades

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

Interpretation and guidance

• Without a stated grade, rely on the lot-specific Certificate of Analysis (CoA) for purity (e.g., GC/HPLC assay), identification (NMR/IR/MS), and residual solvent/metals profiles. Item-specific limits such as water content (Karl Fischer), residual halides, or UV absorbance should be taken from the CoA when available.
• For chromatography- or discovery-grade use: If you plan to use this amine in Pd-catalyzed couplings or medicinal chemistry SAR campaigns, verify trace metal content and amine assay. For analytical work, low non-volatile residue (NVR) and minimal UV-absorbing impurities are desirable.
• Stabilizers/additives: None are listed in Product Data. If stabilizers are present in a given lot, they will be declared on the CoA/SDS; consider implications for downstream reactions (e.g., BHT interference in oxidative steps).

Recommendations

• Request CoA and, if needed, a detailed Specification Sheet for your lot. Define acceptance criteria aligned to your application (e.g., assay ≥98% by GC, water ≤0.1% by KF, color APHA, or UV profile) and verify upon receipt.

Reaction and Applications

Role: 4-Cyclopropyl-3-fluoroaniline is a versatile aryl amine building block. The meta-F and para-cyclopropyl substitution pattern can tune electronics, sterics, and lipophilicity in medicinal chemistry and materials screening.

Representative transformations (literature/general)

• N-Acylation/Sulfonylation: Rapid formation of amides and sulfonamides with acid chlorides/anhydrides or sulfonyl chlorides in the presence of base (TEA, pyridine). Monitor for over-acylation to amide salts; control stoichiometry and temperature.
• Urea/Carbamate Formation: Via CDI, triphosgene, or isocyanate coupling to install carbonyl-linked functionalities. For symmetrical ureas, phosgene equivalents or oxidative coupling can be employed.
• Buchwald–Hartwig Amination: Serves as the amine partner with (hetero)aryl halides or pseudohalides under Pd catalysis (e.g., Pd2(dba)3 or Pd(OAc)2 with BrettPhos/XPhos/BippyPhos ligands; base NaOtBu/Cs2CO3). The cyclopropyl group is generally robust under these conditions.
• Reductive Amination (on N): Formation of N-alkyl derivatives using aldehydes/ketones and reducing agents (NaBH3CN, NaBH(OAc)3, or catalytic hydrogenation).
• Diazotization/Diversification: Conversion to diazonium salts (NaNO2/HX, 0–5 °C) enables Sandmeyer-type substitutions on nitrogen (e.g., to phenols via diazotization–hydrolysis) or azo coupling (for dye intermediates). Exercise caution with diazonium stability.
• Protecting Group Strategies: Temporary masking of –NH2 as acetamide, Boc, or Cbz to direct chemistry elsewhere on the molecule.

Practical tips

• Dry, oxygen-minimized conditions help limit aniline oxidation/coloration. Use base to neutralize generated HX in electrophile couplings. For scale-up, control exotherms during acylations and isocyanate formation.

Reaction Conditions

General literature guidance (examples; adjust to your substrate and scale)

• N-Acylation (amide formation)
  • Typical: Acid chloride (1.05–1.2 eq), triethylamine or pyridine (2.0–3.0 eq), solvent DCM or THF, 0 °C to rt, 0.5–2 h. Workup by aqueous quench and extraction. Yields commonly 80–95% for unhindered acyls.
• Sulfonamide formation
  • Reagents: R–SO2Cl (1.05–1.2 eq), base (TEA or NaHCO3), solvent DCM/MeCN, 0 °C to rt. Control addition rate to manage exotherm.
• Urea/Carbamate via CDI
  • CDI (1.1–1.5 eq) in THF/MeCN, 0 °C to rt to form carbamoyl imidazole; then add amine/alcohol partner, heat to 40–60 °C as needed. Typical 60–90% yields reported for similar anilines.
• Reductive amination
  • Carbonyl partner (1.0 eq), NaBH3CN (1.2–2.0 eq) or NaBH(OAc)3 in MeOH/THF/AcOH, rt to 40 °C, 2–16 h. Maintain mildly acidic conditions for imine formation.
• Buchwald–Hartwig amination (as amine partner)
  • Catalyst: Pd2(dba)3 (0.5–2 mol% Pd) or Pd(OAc)2 (1–3 mol%); ligand BrettPhos/XPhos/BippyPhos (1.5–4 mol%); base NaOtBu or K3PO4 (2–3 eq); solvent toluene, dioxane, or 2-MeTHF; 80–110 °C, 4–16 h. Typical isolated yields for compatible aryl bromides/chlorides: 60–90%.
• Diazotization (for diversification)
  • NaNO2 (1.1 eq) in 2–4 M HCl at 0–5 °C, then trap or displace under Sandmeyer conditions (Cu salts). Exercise stringent temperature control and safety protocols for diazonium salts.

Note: Conditions are illustrative literature norms for anilines; optimize for this specific substrate and desired selectivity. Monitor by TLC/HPLC and confirm identity by NMR/MS.

Safety and Handling

Item-specific hazard data

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

General safety guidance for aromatic amines (literature/general)

• Hazards: Many anilines are harmful if swallowed, inhaled, or in contact with skin; they can cause skin/eye irritation and may induce methemoglobinemia upon significant exposure. Avoid aerosols and prolonged skin contact.
• PPE: Use lab coat, nitrile gloves, and splash goggles. Handle in a fume hood to minimize inhalation exposure.
• First aid overview: If on skin, wash with soap and water; remove contaminated clothing. If in eyes, rinse cautiously with water for several minutes. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention. Always follow your institution’s emergency procedures.
• Incompatibilities: Strong oxidizers (risk of exotherm/oxidation), acylating/alkylating agents (reactivity at –NH2), nitrosating agents (risk of N-nitrosamine formation). Avoid contact with reactive acid chlorides without appropriate controls.
• Storage: Store tightly closed at room temperature as indicated in Product Data; protect from light and air to minimize slow oxidative discoloration typical of anilines. Consult the SDS for definitive guidance.

Always defer to the product SDS and your institutional EHS policies for authoritative safety information.

Solvent Selection

Applicability: This section addresses solvents for using 4-cyclopropyl-3-fluoroaniline as a reagent/substrate, not as a solvent.

General solvent compatibility (literature/general)

• Polarity/miscibility: Primary anilines are generally miscible with common organic solvents (Et2O, MTBE, THF, EtOAc, toluene, DCM, MeCN, alcohols) and show low water solubility. Protonation in acidic aqueous media increases water solubility.
• Choice by transformation:
  • N-Acylation/sulfonylation: DCM, THF, EtOAc, toluene, or MeCN with base (TEA, pyridine) are typical.
  • Carbamate/urea formation: THF, toluene, or DCM; for phosgene alternatives (triphosgene/CDI), use aprotic solvents.
  • Buchwald–Hartwig amination (as amine partner): Toluene, dioxane, CPME, or tBuOH under Pd catalysis.
  • Diazotization (if desired): Aqueous mineral acid with co-solvent (MeOH, MeCN); keep cold.
• Green considerations: Prefer 2-MeTHF or CPME over THF/Et2O when feasible; EtOAc and alcohols are greener alternatives to chlorinated solvents.

Quick comparison (general)

• EtOAc: Good balance of polarity and green profile; often dissolves anilines well.
• Toluene/xylene: Good for high-temp couplings; low polarity; limited for salts.
• MeCN: Polar aprotic; excellent for electrophile-driven N-functionalizations.
• Alcohols (MeOH, EtOH): Useful for reductions or as proton shuttles; may compete in acylations.

Always confirm solubility and stability at reaction temperature on small scale.

Storage and Reconstitution

Item-specific storage

• Storage conditions: Room temperature (per Product Data).
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance on receipt: Not specified for this item; refer to CoA/Spec Sheet.

General handling recommendations (literature/general)

• Container: Store in a tightly sealed amber vial to limit light-induced oxidation/discoloration typical of anilines.
• Atmosphere: For long-term storage, consider purging headspace with inert gas (N2/Ar) and minimizing repeated air exposure.
• Moisture: Keep dry; although not strongly hygroscopic, water can affect certain reactions (e.g., acylations, couplings).
• Stability: Aromatic amines may darken on exposure to air/light; this does not necessarily indicate loss of purity but verify by GC/HPLC as needed.
• Reconstitution: If solidified or viscous, warm gently to room temperature. For solution preparations, common stock solvents include DCM, THF, EtOAc, toluene, or MeCN. Prepare fresh solutions for moisture-/air-sensitive transformations.

Always consult the SDS and your institution’s chemical hygiene plan for detailed storage and disposal guidance.

Structure and Identity

Brief overview: 4-Cyclopropyl-3-fluoroaniline is an aniline derivative bearing a para-cyclopropyl group and a meta-fluoro substituent relative to the amino group on a benzene ring.

• Item-specific identifiers (from Product Data)
  • CAS: 1208083-48-0
  • CID: 59637273
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists an incomplete key)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature structural data (for reference; not item specifications)
  • Molecular formula (calculated from structure): C9H10FN
  • Molecular weight (calculated): ~151.18 g/mol
  • Core scaffold: aniline (phenylamine) with –NH2 at position 1, –F at position 3 (meta), and –cyclopropyl at position 4 (para).
  • Functional groups: primary aniline (–NH2), aryl–F, cyclopropyl (strained, sigma-donating alkyl).
  • 2D description: A benzene ring bearing –NH2 at C1; at C3, a fluorine substituent; at C4, a cyclopropyl ring attached via one carbon. No stereocenters; achiral.

Notes

• All structure-related values above (formula and MW) are provided as literature/computational context only and are not a certificate of analysis for this specific SKU.

Synthetic Utility

Key reactivity features (literature/general)

• Nucleophilicity at nitrogen: Enables formation of amides, sulfonamides, carbamates, ureas, imines, and N-alkyl anilines. Rate/selectivity can be tuned by base, solvent, and protecting groups (Boc/Cbz/Ac).
• Electrophilic aromatic substitution (EAS): The –NH2 is a strong ortho/para director; however, the ring is already substituted at para (cyclopropyl) and meta (F). The meta-fluoro is deactivating and ortho/para-directing; net reactivity is reduced versus aniline. N-acylation to anilide can further modulate directing effects for regioselective EAS.
• Cross-coupling (as amine partner): Effective in Pd-catalyzed Buchwald–Hartwig couplings to install the aniline motif onto aryl/heteroaryl halides/triflates. The cyclopropyl group typically survives such conditions.
• Diazonium chemistry: Formation of diazonium salts enables subsequent transformations (e.g., Sandmeyer, Balz–Schiemann for additional F introduction on other substrates, or azo coupling).
• Reductive transformations: Formation of N-alkyl/N,N-dialkyl derivatives by reductive amination; hydrogenation can remove certain N-protecting groups.

Strategic value

• The para-cyclopropyl and meta-fluoro substituents impart a distinctive lipophilic/electronic profile useful for SAR libraries and materials monomers. The aniline can be a gateway to diverse derivatives via rapid N-functionalization cascades.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or targeted biological reagent. No antigen/epitope or species reactivity applies.