2-(3-Bromophenyl)azetidine - ≥97% , CAS No.1270556-17-6

CAS: 1270556-17-6 Cat. No.: B1010081 Summenformel: C9H10BrN EG-Nummer: 828-858-9 PubChem CID: 65804653

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: C1CNC1C2=CC(=CC=C2)Br
• IUPAC Name: 2-(3-bromophenyl)azetidine
• InChIKey: RBMKGJLVXVPZFJ-UHFFFAOYSA-N
• INCHI: 1S/C9H10BrN/c10-8-3-1-2-7(6-8)9-4-5-11-9/h1-3,6,9,11H,4-5H2
• Isomere SMILES: C1CNC1C2=CC(=CC=C2)Br
• PubChem CID: 65804653

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Azetidines
      • Subclass Phenylazetidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Azetidines
• Subclass: Phenylazetidines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylazetidines
• Alternative Parents: Bromobenzenes Aralkylamines Aryl bromides Dialkylamines Azacyclic compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-phenylazetidine - Bromobenzene - Halobenzene - Aralkylamine - Aryl bromide - Aryl halide - Monocyclic benzene moiety - Benzenoid - Secondary aliphatic amine - Azacycle - Secondary amine - Organobromide - Organohalogen compound - Hydrocarbon derivative - Organic nitrogen compound - Amine - Organonitrogen compound - Aromatic heteromonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as phenylazetidines. These are polycyclic aromatic compounds containing a phenyl ring substituted with an azetidine 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 212.090 g/mol
• XLogP3: 2.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 211 Da
• Monoisotopic Mass: 211 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 138.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 or immunoassay protocols are associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for general laboratory procedures and optimization strategies.

Biological Roles

This material is a synthetic small-molecule building block and is not intended for biological use as supplied. No endogenous biological role is expected.

• General medicinal chemistry context (non-clinical):
  • Azetidine motifs serve as conformationally restricted, basic amine fragments that can tune pKa, solubility, and permeability of leads (literature/general). The 3-bromophenyl handle enables rapid diversification via cross-couplings to explore structure–activity relationships.
  • Benzylic substitution at C2 influences amine basicity and can modulate hERG risk and CYP interactions compared to larger rings (general trend; substrate-dependent).

Any specific biological activity would arise from derivatives prepared from this scaffold rather than the starting material itself.

Buffer Applications

Not typically applicable. 2-(3-Bromophenyl)azetidine is a neutral/weakly basic organic building block, not a dedicated buffering agent. For aqueous work, the ammonium salt could be formed with a suitable acid, but conventional biological buffers (HEPES, PBS, acetate) are preferred and should be selected based on the biological assay requirements.

Green Alternatives

Sustainability can be improved primarily through solvent and catalyst choices when transforming the aryl bromide and the amine.

• Greener solvent swaps (literature/general):
  • Replace DCM with 2-MeTHF or CPME for extractions and couplings; both offer lower toxicity and favorable life-cycle metrics.
  • Employ water or water/ethanol with micellar catalysis (e.g., TPGS-750-M) for Suzuki/Buchwald couplings of aryl bromides.
  • Use EtOAc or IPA for workups and crystallizations instead of chlorinated solvents where feasible.

Comparison (general guidance):

• DCM: Excellent solvency; high VOC impact; potential worker exposure concerns.

• 2-MeTHF: Bio-based, good for organometallics and couplings; forms peroxides over time (manage accordingly).

• CPME: Broad liquid range, low peroxide formation compared to THF; hydrophobic.

• Water/micelles: Minimal VOCs; may need surfactants and careful degassing; substrate solubility can limit rates.

• Catalyst/energy considerations (general):

  • Use highly active Pd(NHC) or biaryl phosphine systems to reduce catalyst loadings; explore Ni-catalyzed couplings for lower Pd footprint.
  • Consider flow chemistry for exotherm control and reduced solvent inventory.

These strategies preserve the utility of the aryl bromide while reducing environmental burden; adapt to the required transformation.

Pharmaceutical Uses

No pharmacopeial excipient status or formulation use is specified for this item. It is supplied for research use as a synthetic intermediate.

• Research/process chemistry context (general, non-clinical):
  • Serves as a versatile intermediate for preparing azetidine-containing APIs or probes during preclinical discovery.
  • Salt formation (e.g., HCl, TsOH) may improve handling, crystallinity, and purification in process development.
  • The aryl bromide facilitates late-stage diversification via cross-couplings to optimize properties of candidate molecules.

Do not use in human or veterinary applications. For regulatory or GMP needs, request batch documentation and suitability assessments separately.

Physical Properties

Item-specific specifications were not provided; values below are literature/general estimates to aid method development. Do not treat as CoA specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (literature): ~212.09 g/mol (C9H10BrN)
• Basicity: Secondary aliphatic amine; expected pKaH of conjugate acid in the ~9–11 range (literature, typical for azetidines). Exact value for this substitution not specified.
• Solubility (general):
  • Organic: Expected to be soluble in common organic solvents (e.g., DCM, THF, EtOAc, MeOH, acetonitrile) due to mixed polarity; salt formation increases solubility in alcohols and water–alcohol mixtures (literature/general behavior of secondary amines).
  • Aqueous: Free base has limited solubility in water; water solubility increases markedly as an ammonium salt (general).
• Boiling/melting points: Not specified for this item; refer to CoA/Spec Sheet. Small-ring amines may be low-melting solids or liquids at ambient (general note).
• Density, refractive index, UV cutoff, residual water/metals: Not specified for this item; refer to CoA/Spec Sheet.
• LogP (qualitative): Benzylic aryl bromide increases lipophilicity relative to azetidine; overall moderate lipophilicity is expected (literature/general).

Always confirm operational properties experimentally under your conditions.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Typical expectations for small-molecule research-grade building blocks (general):
  • Purity reported by HPLC/GC or qNMR; identity by 1H NMR/13C NMR and HRMS/ESI-MS.
  • Water content by Karl Fischer and residual metal content by ICP-MS may be provided for coupling-sensitive workflows; if critical, request a current CoA.
• Stabilizers: None specified for this item; refer to CoA/Spec Sheet. Secondary amines are generally stable without stabilizers but may slowly discolor on prolonged air exposure due to trace oxidation.
• Implications of aryl bromide functionality (general):
  • Residual palladium/nickel is typically low for catalog items but can impact subsequent cross-couplings; pre-washing over silica or metal scavengers (e.g., QuadraPure TU) can be used if necessary.
• Documentation: Batch-specific CoA/Spec Sheet should be consulted for exact purity, analytical methods, and any noted impurities or stereochemical composition (racemate vs. enantioenriched).

Reaction and Applications

This scaffold merges a strained, conformationally restricted amine (azetidine) with a cross-coupling-ready aryl bromide, making it a versatile intermediate for discovery and process chemistry.

• Diversification at the aryl bromide (literature/general):
  • Suzuki–Miyaura coupling to install (hetero)aryl or vinyl groups; broad ligand choices (e.g., SPhos, XPhos) enable mild conditions.
  • Buchwald–Hartwig amination to form anilines, carbazoles, or N-arylated systems.
  • Carbonylative couplings (CO insertions) to give benzamides/esters.
  • Lithiation/magnesiation of the aryl bromide (under carefully controlled, cryogenic conditions) followed by electrophile trapping; amine protection advised to avoid acid–base quenching.
• Functionalization at the azetidine nitrogen (general):
  • N-acylation, N-sulfonylation, or carbamate protection (Boc/CBz) to modulate basicity and improve handling/crystallinity.
  • Reductive amination or alkylation for tertiary amine libraries.
• C2 stereochemistry (general):
  • The benzylic C2 center is stereogenic; enantioenriched variants can be accessed by chiral auxiliary/catalyst strategies or by resolution of salts. Racemic material is appropriate for SAR exploration.
• Medicinal chemistry relevance (general, non-clinical):
  • Azetidines impart increased basicity vs. pyrrolidines and can improve metabolic stability and polarity balance; the aryl handle permits rapid SAR via cross-couplings.
• Practical notes:
  • Protect the amine when performing strong-base metalations or under Pd/Ni catalysis if it poisons the catalyst; alternatively, employ dialkylbiaryl phosphine ligands tolerant of free amines.
  • Monitor for debromination byproducts in hydrogenative or radical conditions.

Reaction Conditions

Guidance below reflects typical literature conditions for aryl bromides and secondary amines; adjust based on scale and substrate response.

• Suzuki–Miyaura coupling (aryl bromide):
  • Catalyst: Pd2(dba)3 (1–2 mol%) + SPhos/XPhos (2–4 mol%) or Pd(PPh3)4 (3–5 mol%).
  • Base: K3PO4, K2CO3, or Cs2CO3 (2–3 equiv).
  • Solvent: 2-MeTHF, dioxane, toluene/H2O, or EtOH/H2O; 60–90 °C; 2–16 h.
  • Notes: Free amines can coordinate Pd; consider Boc protection or use amine-tolerant ligands; degas thoroughly.
• Buchwald–Hartwig amination (Ar–Br):
  • Catalyst: Pd-precatalyst (e.g., Pd-PEPPSI, Pd-Precatalyst with BrettPhos/RuPhos, 1–3 mol%).
  • Base: NaOtBu, KOtBu, or Cs2CO3.
  • Solvent: Toluene, 1,4-dioxane, or CPME; 80–110 °C.
• Sonogashira coupling (if alkyne installation desired):
  • Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%); DIPEA/Et3N; THF or MeCN; rt–60 °C.
  • Copper-free systems with Pd/NHC minimize Glaser byproducts.
• N-acylation/protection:
  • Boc2O (1.1–1.5 equiv), base (NEt3/NaHCO3), DCM or MeCN, 0 °C to rt, 1–4 h. For acyl chlorides: pyridine or DIPEA, 0 °C control.
• Halogen–metal exchange (advanced):
  • t-BuLi (1.0–1.2 equiv) in THF at −78 °C, then electrophile; requires pre-protection of the amine; strictly anhydrous.

Yields are substrate- and condition-dependent; consult primary literature and perform small-scale scouting to optimize.

Safety and Handling

Authoritative safety data must be taken from the product SDS. The following are general considerations for aryl-brominated secondary amines.

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general for amines/aryl bromides): Skin/eye irritation; harmful if swallowed; may cause respiratory irritation; sensitization is uncommon but possible with amines. Avoid aerosol formation.
• PPE: Lab coat, nitrile gloves, splash goggles; handle in a fume hood to avoid inhalation of vapors/mists.
• Incompatibilities: Strong oxidizers; acylating/alkylating agents (uncontrolled exotherm); acid chlorides/anhydrides without temperature control; avoid contact with strong bases in presence of halogenated solvents (risk of dehydrohalogenation byproducts). Aryl bromides are generally stable but can undergo metal-catalyzed reactions with residual Pd/Ni.
• Peroxide formation: Not applicable to this amine (no ether functionality), but commonly used solvents (e.g., THF, dioxane) may form peroxides.
• First aid (general):
  • Skin/eye: Rinse with water for 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention if symptoms develop.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire: Use CO2, dry chemical, or foam. Combustion may produce HBr, NOx; firefighters should wear SCBA.

Always consult the current SDS for definitive hazard classifications and response measures.

Solvent Selection

As a moderately lipophilic secondary amine with an aryl bromide, 2-(3-bromophenyl)azetidine dissolves in a range of organic solvents; salt formation can tailor polarity.

• Polarity/miscibility (general):
  • Good solubility expected in chlorinated solvents (DCM, CHCl3), ethers (THF, MTBE), esters (EtOAc), and polar aprotics (MeCN, DMF, DMSO). Limited solubility in nonpolar hydrocarbons; improves on acidification to the ammonium salt in alcohols/water.
• Selection guidance by task (general):
  • N-acylation/alkylation: Use dry DCM, THF, or acetonitrile; amine base may require tertiary amine scavengers.
  • Cross-coupling on aryl bromide: 2-MeTHF, CPME, dioxane, toluene, or water–ethanol with micellar catalysis; add polar co-solvent (DMF/MeCN) if needed.
  • Salt formation/purification: IPA/Et2O for crystallization of amine salts; MeOH for rapid dissolution.
• Small comparison (general):
  • DCM: rapid dissolution, easy removal; environmental concerns.
  • 2-MeTHF/CPME: greener, broader temperature window; slightly reduced polarity vs DCM.
  • MeCN: polar aprotic, good for SNAr and acylations; higher bp aids reactions.

Validate solubility and stability experimentally for your specific application.

Storage and Reconstitution

• Storage (from Product Data): Store at room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Container: Store tightly closed under inert gas if long-term storage is anticipated to minimize oxidation or discoloration (general good practice for amines).
• Stability: Secondary amines and aryl bromides are generally stable; avoid prolonged exposure to air, light, and moisture to maintain assay purity (general guidance).
• Reconstitution/handling (general):
  • Dissolution: Typical solvents include DCM, THF, EtOAc, MeOH, and MeCN; select based on application. If needed, convert to an ammonium salt (e.g., HCl) to improve crystallinity/handling.
  • Drying: If water-sensitive steps are planned, dry solutions over molecular sieves (3Å/4Å) and use anhydrous solvents.
• Freeze–thaw: Not typically required; if storing solutions, keep at 2–8 °C, protected from moisture, and avoid repeated freeze–thaw cycles.

Always refer to the batch CoA/SDS for any additional, item-specific storage or stability notes.

Structure and Identity

Briefly: 2-(3-Bromophenyl)azetidine is a small-ring secondary amine (azetidine) bearing a 3-bromophenyl substituent at the ring C2 position, combining a strained saturated nitrogen heterocycle with an aryl bromide handle for cross-coupling.

• Product identifiers (from Product Data):
  • CAS: 1270556-17-6
  • PubChem CID: 65804653
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Structure (described):
  • Core: Four-membered azetidine ring (one tertiary amine nitrogen and three sp3 carbons).
  • Substitution: A 3-bromophenyl group is attached at the C2 (α to nitrogen) position of the azetidine ring; the aryl bromide is meta-brominated relative to the ring–carbon bond.
  • Functional groups: Secondary amine (basic), aryl bromide (cross-coupling handle), aromatic ring.
  • Stereochemistry: The C2 center is tetrahedral and may be chiral; unless specified as enantioenriched, commercial material is typically racemic (literature/general note).
• Composition (literature/computed):
  • Molecular formula (literature): C9H10BrN
  • Molecular weight (literature): ~212.09 g/mol

2D description in words: An azetidine ring (N–CH–CH2–CH2) where the CH at C2 is bonded directly to a brominated benzene ring (bromine in the meta position relative to the benzylic attachment).

Synthetic Utility

Key reactive elements drive broad synthetic value:

• Aryl bromide (meta to attachment):
  • Cross-coupling platform (Suzuki, Sonogashira, Heck, Negishi, Kumada, Buchwald–Hartwig) enabling rapid installation of diverse fragments (aryl, heteroaryl, alkenyl, alkynyl, amido via carbonylation) under Pd/Ni catalysis (literature/general).
  • Metal–halogen exchange under t-BuLi or i-PrMgCl•LiCl at low temperature for electrophile trapping (requires amine protection and careful quench).
• Secondary azetidine nitrogen:
  • Protection as Boc/CBz to control reactivity and improve compatibility with bases/catalysts; deprotection under standard conditions.
  • N-alkylation/arylation to access tertiary azetidines; N-acyl/sulfonyl derivatization for ureas, amides, and sulfonamides.
• Benzylic C2 center:
  • Potential for stereocontrolled transformations; chiral pool or catalytic asymmetric methods can access enantioenriched variants (general literature note).
• Retrosynthetic value:
  • Acts as a convergent node: ring-retentive diversification on the aryl side combined with orthogonal N-functionalization simplifies library synthesis.

Overall, this building block enables efficient, orthogonal derivatization to generate chemotype diversity around an azetidine core.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or ligand with defined biological target specificity. Any target engagement would pertain to derivatives synthesized from this scaffold.