3-(4-Bromophenyl)-3-hydroxypropanenitrile - ≥96% , CAS No.65984-59-0

CAS: 65984-59-0 Cat. No.: B978315 PubChem CID: 10857133

GRADE & PURITY ≥96%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥96%

Storage

Room temperature

Reinheit

≥96%

Namen und Kennungen

• Kanonisches Lächeln: C1=CC(=CC=C1C(CC#N)O)Br
• IUPAC Name: 3-(4-bromophenyl)-3-hydroxypropanenitrile
• InChIKey: QBIXYALEBZJFSR-UHFFFAOYSA-N
• INCHI: 1S/C9H8BrNO/c10-8-3-1-7(2-4-8)9(12)5-6-11/h1-4,9,12H,5H2
• Isomere SMILES: C1=CC(=CC=C1C(CC#N)O)Br
• PubChem CID: 10857133

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Halobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Bromobenzenes
• Alternative Parents: Aryl bromides Secondary alcohols Nitriles Organobromides Hydrocarbon derivatives Aromatic alcohols
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Bromobenzene - Aryl bromide - Aryl halide - Secondary alcohol - Carbonitrile - Nitrile - Alcohol - Organooxygen compound - Organonitrogen compound - Organobromide - Organohalogen compound - Aromatic alcohol - Hydrocarbon derivative - Cyanide - Organic oxygen compound - Organic nitrogen compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as bromobenzenes. These are organic compounds containing a bromine atom attached to a 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 226.070 g/mol
• XLogP3: 1.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 224.979 Da
• Monoisotopic Mass: 224.979 Da
• Topological Polar Surface Area: 44.000 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 178.000
• 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 tested bioassay or analytical application protocols (e.g., WB, IHC, IF, FC) are provided for this item. For synthetic use, follow standard organic chemistry protocols appropriate to the chosen transformation (cross-coupling, oxidation, substitution). Consult primary literature and your institution’s SOPs for detailed conditions.

Biological Roles

This product is a synthetic small-molecule building block. It is not a biochemical reagent with defined physiological function.

General context (literature-based, not specific to this item)

• Structural motifs: aryl bromides and benzylic alcohols are common intermediates in medicinal chemistry campaigns for SAR exploration. The nitrile group is often employed as a metabolically stable, polar, and H-bond-accepting handle that can modulate potency through dipolar interactions.
• In living systems, benzylic alcohols can be oxidized by hepatic enzymes to ketones/acids; however, this compound is intended strictly for research and synthesis, not for biological use.
• No endogenous role is known or expected.

Research note

• Per Product Data: For research use only. Not for human or veterinary use, diagnostic procedures, or consumption.

Buffer Applications

Not typically applicable. This compound is an organic building block and is not used as a buffering agent. If dissolution in assay media is required for screening, prepare stock solutions in DMSO or MeCN and dilute into the assay buffer with attention to solvent limits (e.g., ≤1–2% organic cosolvent), but this is outside the usual scope for this material.

Green Alternatives

While this is a solid building block rather than a process solvent, greener choices can be made in its use and downstream chemistry.

Greener solvent/catalyst choices (literature-based)

• Replace chlorinated solvents (DCM) with EtOAc, CPME, 2-MeTHF, or toluene where feasible.
• Use aqueous micellar catalysis (e.g., surfactant media) for some Pd-catalyzed couplings of aryl bromides.
• Ligand/catalyst economy: modern ligand systems (e.g., Buchwald biaryl phosphines, NHCs) can lower Pd loading to <0.1 mol%, reducing metal footprint.
• Oxidations: prefer TEMPO/bleach or O2-mediated systems over Cr(VI) reagents; electrochemical oxidations can avoid stoichiometric oxidants.
• Reductions: catalytic hydrogenation or transfer hydrogenation (e.g., HCO2H/Et3N) instead of metal hydrides when compatible.

Comparison highlights (typical literature guidance)

• DCM vs EtOAc: EtOAc offers lower toxicity and better biodegradability; may require adjusted temperature to match solubility.
• THF vs 2-MeTHF/CPME: 2-MeTHF and CPME can reduce peroxide issues and enable biphasic workups; they have higher boiling points.
• DMF/DMSO vs MeCN/green amide solvents (e.g., NEP/Cyrene): MeCN often easier to remove; emerging bio-derived solvents can replace DMF in some couplings.

Waste minimization

• Sequence orthogonal transformations to reduce protection steps.
• Implement telescoped coupling–oxidation sequences under one-pot conditions where validated to minimize solvent exchanges.

Pharmaceutical Uses

No pharmacopeial or excipient status is specified for this item; refer to CoA/Spec Sheet if such designation exists. This compound is primarily a synthetic intermediate/building block.

Formulation/manufacturing context (general)

• Aryl bromide motif: useful for rapid parallel synthesis via cross-coupling to generate analog libraries.
• Nitrile handle: can be transformed into amides, acids, amines—valuable for convergent routes.
• Benzylic alcohol: offers a handle for late-stage derivatization (oxidation to ketone, esterification to pro-moieties in research).

Compliance note

• For research use only. No clinical or therapeutic claims are made or implied. Any use in GMP or clinical supply chains would require independent qualification, full specification, and change control.

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. (Computed/literature formula: C9H8BrNO)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Computed/literature MW: ~226.07 g/mol)
• Water content, residual solvents, metals, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed properties (non-spec values; for planning/reference only)

• Acid/base: secondary alcohol (weakly acidic OH), neutral nitrile; no ionizable center in neutral water.
• Polarity: moderately polar due to OH and CN; aryl bromide imparts hydrophobic character.
• Solubility expectations: soluble in common organic solvents (EtOAc, DCM, acetone, MeOH/EtOH) and poorly soluble in water; exact values not established here.
• LogP/logS: not available here; consult databases or measure experimentally for method development.

General guidance for characterization

• Identity can be confirmed by 1H/13C NMR: benzylic CH (typically 4.8–5.2 ppm), CH2 adjacent to nitrile (2.6–3.0 ppm), aromatic protons (7.1–7.7 ppm), OH (broad, solvent-dependent). CN carbon appears ~118 ppm (13C). Strong IR band for C≡N ~2230 cm−1 and O–H ~3300 cm−1.
• HRMS: [M+H]+ expected at m/z ~227.07 with characteristic Br isotopic pattern (M/M+2 ≈ 1:1).

Quality and Grades

Item-specific grade/purity

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

General guidance on quality for this class of building blocks

• For synthesis and medicinal chemistry, typical quality attributes include: assay by quantitative NMR or HPLC, identity by NMR/HRMS, residual solvents by GC, and halogen content confirmation by isotopic pattern in MS.
• Aryl bromides with benzylic alcohols may undergo slow oxidation or dehydration; low-peroxide and low-water specifications improve reproducibility in sensitive transformations (e.g., Mitsunobu, Swern, or SN1/SN2-type reactions). Where critical, request recent CoA and, if needed, perform Karl Fischer and peroxide testing in-house.
• Chromatography-grade material (if offered) emphasizes low UV-absorbing impurities for photometric detection. “Synthesis grade” focuses on chemical purity and low inorganic residue.
• Trace metals: if using in cross-couplings, low ppm of transition metals (Pd, Ni, Cu) can matter for catalysis outcomes in pharmaceutical contexts; verify by ICP if required.
• Batch homogeneity: racemic mixtures are typical unless enantioenriched material is specified; enantiomeric excess should be confirmed when chirality matters to your route.

Reaction and Applications

This molecule is a versatile bifunctional building block featuring an aryl bromide, a benzylic secondary alcohol, and a terminal nitrile. Typical applications (literature-based) include:

• Cross-coupling elaboration of the aryl bromide:
  • Suzuki–Miyaura (to install diverse aryl/alkenyl groups). Use Pd(PPh3)4/Pd2(dba)3 with phosphine ligands in toluene/dioxane/MeCN, base K3PO4/K2CO3.
  • Buchwald–Hartwig amination to replace bromide with amines using Pd/XPhos or BrettPhos catalysts under mild conditions.
  • Sonogashira coupling for alkyne appendage (with terminal alkyne, Pd/Cu cocatalysis), monitoring for potential OH/CN compatibility.
• Benzylic alcohol transformations:
  • Oxidation to the corresponding ketone using Dess–Martin periodinane, PCC, TEMPO/bleach, or Swern—enables further condensations or reductive aminations.
  • Mitsunobu substitution to access benzylic ethers/esters (consider stereochemical inversion if using enantioenriched substrate; material here is unspecified for ee).
  • Protection as benzyl ether/benzoate or silyl ether if cross-coupling conditions risk competitive reactions.
• Nitrile chemistry:
  • Hydrolysis to amide or acid (acidic or basic conditions; control for benzylic dehydration).
  • Reduction (DIBAL-H to aldehyde; LiAlH4 or catalytic hydrogenation to amine) yielding β-amino alcohol motifs.
• Tandem strategies:
  • Cross-coupling first, then chemoselective oxidation/reduction to introduce diversity while maintaining the benzylic center.

Notes: The three functional handles enable orthogonal diversifications; sequence planning should consider chemoselectivity (e.g., protect OH prior to strong base, or use ligand choices that suppress benzylic C–O activation).

Reaction Conditions

General literature guidance for this scaffold class (non-binding; optimize per route):

• Suzuki–Miyaura coupling (on aryl Br):
  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd2(dba)3 (0.5 mol%) + XPhos/SPhos (1–4 mol%)
  • Base: K3PO4 (2–3 equiv) or K2CO3
  • Solvent: toluene/dioxane, MeCN, 2-MeTHF, or aqueous micellar media
  • Temp/time: 60–100 °C, 2–16 h
• Buchwald–Hartwig amination:
  • Catalyst: Pd2(dba)3 (0.5–1 mol%) + BrettPhos/RuPhos (1–3 mol%)
  • Base: NaOtBu or Cs2CO3
  • Solvent: toluene, dioxane, or CPME
  • Temp: 60–110 °C
• Sonogashira coupling:
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%)
  • Base: Et3N, DIPEA, or K2CO3
  • Solvent: THF, MeCN, or toluene; 25–70 °C
• Benzylic alcohol oxidation:
  • DMP (1.3 equiv) in DCM, 0–25 °C, 0.5–2 h; or TEMPO/NaOCl (pH ~9), 0–10 °C
• Nitrile modifications:
  • Hydrolysis to amide: H2SO4(aq) or HCl(aq), reflux; or basic NaOH(aq)/ETOH, reflux
  • Reduction to amine: H2/Pd-C (1–5 bar) or LiAlH4 in THF/ether, 0–25 °C

Compatibility tips

• Protect the benzylic OH (e.g., TBS) before strong base or high-temperature couplings to prevent dehydration.
• Nitrile generally tolerates Pd-catalyzed conditions but can coordinate; ligand choice and base strength can mitigate rate suppression.
• Monitor for protodebromination under forcing conditions; adjust temperature or catalyst to minimize.

Safety and Handling

Item-specific hazard information

• Signal word: Not specified for this item; refer to SDS.
• H-statements/GHS classification/pictograms: Not specified for this item; refer to SDS.
• Research use only (per Product Data).

General safety considerations for aryl bromide/benzylic alcohol/nitrile compounds (literature-based; not a substitute for SDS)

• Potential hazards: irritant to skin/eyes/respiratory tract. Nitriles can release toxic gases under combustion (e.g., HCN, NOx). Avoid inhalation of dust or aerosols.
• PPE: lab coat, safety glasses or goggles, nitrile gloves (change regularly). Use in a fume hood when weighing, transferring, or heating.
• Incompatibilities: strong oxidizers (may oxidize benzylic alcohol), strong bases/acids (can promote elimination or hydrolysis), reducing metals/reactive organometallics (aryl bromide may undergo oxidative addition).
• Thermal decomposition: may emit HBr, HCN, CO/CO2; avoid overheating and open flames.
• First aid (overview; consult SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: wash with soap and water; remove contaminated clothing.
  • Eye contact: rinse cautiously with water for several minutes; remove contact lenses if present and easy; seek medical attention.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Spill response: absorb with inert material, avoid dust generation, collect for disposal in accordance with institutional and local regulations.
• Waste: halogenated organic waste stream is typically appropriate; follow local regulations.

Solvent Selection

Applicability

• This product is a small-molecule building block, not a solvent. However, solvent choice is important for its handling and reactions.

General solvent behavior (literature-based)

• Polarity class: moderately polar organic compound; dissolves well in ethyl acetate, dichloromethane, acetone, THF, acetonitrile, and alcohols; limited aqueous solubility.
• Hydrogen bonding: acts as H-bond donor (OH) and acceptor (OH, CN); exhibits enhanced solubility in protic and dipolar aprotic media.
• Dielectric considerations: dipolar aprotic solvents (DMF, DMSO, MeCN) stabilize the nitrile and may shift equilibria in reactions involving ion pairs.

Practical selection tips

• Workups: for extractions, ethyl acetate/MTBE often give good phase separation vs brine; avoid highly water-miscible solvents during quench when product is polar.
• Drying: if water-sensitive chemistry is planned, dry solvents thoroughly (e.g., molecular sieves for EtOAc/MeCN; solvent stills or alumina columns for THF/Et2O).
• Crystallization: mixtures such as EtOAc/hexanes or toluene/EtOAc can be explored for solid isolation, leveraging aromaticity and moderate polarity.
• Analytical: MeCN or MeOH mobile phases with 0.1% formic acid/base modifiers typically provide sharp peaks by LC; DMSO-d6 or CDCl3/CD3OD for NMR depending on solubility and OH exchange.

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/physical form: Not specified for this item; refer to CoA/Spec Sheet.

General handling and stability guidance (literature-based)

• Store tightly closed in a dry, inert atmosphere (desiccator or with desiccant) to minimize moisture uptake and potential benzylic oxidation.
• Protect from prolonged light and heat. Avoid contact with strong acids/bases and oxidizers.
• If preparing solutions, use anhydrous solvents and store stock solutions at 2–8 °C or −20 °C in amber vials when feasible; allow to warm to room temperature before opening to avoid condensation.
• Freeze–thaw: for solutions, aliquot to avoid repeated freeze–thaw cycles.

Reconstitution

• No reconstitution protocol is required for neat material. For solution preparation, dissolve to the desired concentration in a compatible dry organic solvent (e.g., DMSO, MeCN, THF, EtOAc) with brief sonication if needed.

Documentation

• Always refer to the lot-specific CoA and SDS for authoritative guidance on storage limits, stability, and handling.

Structure and Identity

Item-specific (from Product Data)

• SKU: B978315
• Product name: 3-(4-Bromophenyl)-3-hydroxypropanenitrile
• CAS: 65984-59-0
• PubChem CID: 10857133
• InChIKey: 292498 (as provided; note: this is not in standard 27-character InChIKey format—consult CoA/Spec Sheet for the definitive identifier)
• Storage conditions: Room temperature

Literature/computed identity details (for reference)

• Synonym (descriptive): p-bromophenyl-substituted 3-hydroxypropanenitrile; 3-hydroxy-3-(4-bromophenyl)propanenitrile
• Structural features: aromatic ring bearing para-bromine; benzylic secondary alcohol at the benzylic position; terminal nitrile (–C≡N) two carbons away from the ring.
• Functional groups: aryl bromide, secondary alcohol, nitrile
• 2D structure (verbal): a para-bromobenzene ring bonded at the para position to a –CH(OH)–CH2–C≡N side chain; the hydroxyl resides on the benzylic carbon adjacent to the ring.
• Likely SMILES (literature/notation): N#CCC(O)c1ccc(Br)cc1 (reference notation only; verify against CoA)
• Empirical formula (computed from structure): C9H8BrNO (literature)
• Molecular weight (computed): ~226.07 g/mol (literature)

Notes

• Stereochemistry: the benzylic alcohol carbon is stereogenic; commercial material is typically racemic unless otherwise specified (not specified for this item; refer to CoA/Spec Sheet).

Synthetic Utility

Key reactive elements and strategies (literature-based)

• Aryl bromide (para):
  • Platform for Pd/Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Sonogashira, Negishi, Kumada). Para-bromo position typically couples efficiently under standard conditions.
  • Nucleophilic aromatic substitution is not expected on a simple para-bromobenzene; rely on cross-coupling.
• Benzylic secondary alcohol:
  • Oxidation to ketone enables aldol, reductive amination, or Wittig/HWE elaborations.
  • Activation (e.g., tosylate/mesylate) or Mitsunobu reaction to introduce O-, N-, or S-nucleophiles at the benzylic center.
  • Protection as silyl ether/benzyl or acyl derivatives to survive strong bases used in couplings.
• Nitrile terminus:
  • Hydrolysis to amide/acid (control chemoselectivity with catalysts or stepwise conditions).
  • Reduction to primary amine or aldehyde (DIBAL-H). The combination with benzylic OH can furnish β-amino alcohol scaffolds after reduction.

Retrosynthetic value

• Disconnection via benzylic alcohol formation: accessible from p-bromobenzaldehyde and acetonitrile equivalents (e.g., cyanomethyl anion addition then protonation/oxidation state adjustment) or by cyanohydrin-type strategies applied to a p-bromophenyl ketone.
• Orthogonality: sequence cross-coupling first, then manipulate OH/CN, or vice versa, to maximize compatibility.

Selectivity notes

• Protect OH for base- or metal-intensive couplings to mitigate competitive β-elimination or coordination issues. Choose ligands/catalysts tolerant of nitriles (e.g., SPhos, XPhos).

Target Specificity

Not applicable. This product is a small-molecule building block and does not possess biological target specificity data (no antigen/epitope/clone/isotype). No item-specific selectivity information is provided in the Product Data.