4-(Cyanoacetyl)benzonitrile - ≥95% , CAS No.71292-11-0

CAS: 71292-11-0 Cat. No.: C1069215 Fórmula: C₁₀H₆N₂O Peso molecular: 170.17 PubChem CID: 12540173

GRAU & PUREZA ≥95%

Storage

Room temperature

Especificações

Especificações e pureza

≥95%

Condições de armazenamento de armazenamento

Room temperature

Pureza

≥95%

Nomes e identificadores

Sorrisos canónicos

C1=CC(=CC=C1C#N)C(=O)CC#N

IUPAC Name

4-(2-cyanoacetyl)benzonitrile

InChIKey

HFABIHFBLNTOOW-UHFFFAOYSA-N

INCHI

1S/C10H6N2O/c11-6-5-10(13)9-3-1-8(7-12)2-4-9/h1-4H,5H2

SMILES isoméricas

C1=CC(=CC=C1C#N)C(=O)CC#N

PubChem CID

12540173

Peso molecular

170.17

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Ketones
          • Level6 Aryl ketones
            • Level7 Phenylketones
              • Level8 Alkyl-phenylketones

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Ketones - Aryl ketones - Phenylketones
• Direct Parent: Alkyl-phenylketones
• Alternative Parents: Benzoyl derivatives Benzonitriles Aryl alkyl ketones Nitriles Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Alkyl-phenylketone - Aryl alkyl ketone - Benzoyl - Benzonitrile - Benzenoid - Monocyclic benzene moiety - Nitrile - Carbonitrile - Organic nitrogen compound - Cyanide - Organic oxide - Hydrocarbon derivative - Organonitrogen compound - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and 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

Propriedades químicas e físicas

• Peso molecular: 170.170 g/mol
• XLogP3: 0.700
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 170.048 Da
• Monoisotopic Mass: 170.048 Da
• Topological Polar Surface Area: 64.700 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 283.000
• 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 application protocols are validated or provided for biological assays (e.g., WB, IHC, IF, FC) for this item. As a synthetic building block, usage is protocol-specific to the intended chemical transformation.

General handling protocol (chemistry focus):

• Weigh the solid quickly in a ventilated hood to minimize dust.
• Dissolve in a suitable dry solvent (e.g., DMSO, DMF, MeCN, EtOH, toluene) based on the transformation.
• For base-catalyzed condensations, add catalytic base (e.g., piperidine) and stir at RT or heat as required; monitor by TLC/LC-MS.
• Upon completion, quench appropriately (e.g., with aqueous ammonium chloride for basic reactions), extract, dry, and purify by recrystallization or chromatography.

For any biological screening use, prepare concentrated DMSO stocks (e.g., 10–100 mM), filter-sterilize if needed, and dilute into assay media keeping organic cosolvent low (≤1–2% v/v), subject to assay tolerance.

Biological Roles

This product is a synthetic organic building block and does not have a known intrinsic biological role. The following notes provide general context without implying bioactivity or clinical use.

• Structural class: Aromatic nitrile/ketone with an activated methylene. Such motifs are frequently explored in medicinal chemistry as precursors to heterocycles (e.g., pyrimidines, pyrazoles) or as intermediates to amides/acids via nitrile hydrolysis.
• Biotransformations (general): Nitriles can, in principle, be hydrolyzed by nitrilases/nitrile hydratases to corresponding amides/acids under biocatalytic conditions; applicability to this specific substrate depends on enzyme tolerance for aryl–dinitrile substrates.
• ADME-relevant features (conceptual): The presence of two nitriles and an aryl ketone increases polarity relative to simple arenes but typically maintains poor aqueous solubility; any pharmacokinetic inferences must be established experimentally for derivatives.

Research-only note: This product is provided for research use only and is not intended for diagnostic, therapeutic, or other clinical applications.

Buffer Applications

Not typically applicable. 4-(Cyanoacetyl)benzonitrile is a neutral organic building block and is not used as a buffering agent or pH control component.

Practical guidance:

• For aqueous or bioconjugation work involving this substrate or its derivatives, select an appropriate buffer based on the reaction/transformation being conducted (e.g., acetate, phosphate, carbonate). Ensure the organic cosolvent (e.g., DMSO, MeCN, EtOH) compatibility with the chosen buffer.
• If performing biocatalytic nitrile hydrolysis, buffers such as phosphate (pH 7–8) or Tris may be used per enzyme requirements; optimize ionic strength and cosolvent content empirically.

Green Alternatives

While 4-(Cyanoacetyl)benzonitrile itself is a substrate rather than a solvent, greener choices can be made for its processing and transformations.

Greener solvent options (general guidance):

• Replace chlorinated solvents with:
  • Ethyl acetate or methyl tert-butyl ether (MTBE) for extractions and crystallizations when feasible.
  • 2-Methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME) for nonpolar to moderately polar reaction media; they offer better safety/renewable sourcing vs THF/Et2O.
• Replace DMF/NMP in condensations with:
  • Green alcohols (ethanol, isopropanol) when base-catalyzed Knoevenagel reactions tolerate protic media.
  • Acetonitrile as a lower-toxicity polar aprotic alternative to DMF/NMP (tradeoff: sometimes lower solubility).

Small comparison (general, literature-based):

• DMF vs ethanol (for Knoevenagel):
  • DMF: higher substrate solubility; challenging removal; reproductive toxicity concerns.
  • Ethanol: renewable, low toxicity, easy removal; may need azeotrope or sieves to manage water.
• Dichloromethane vs 2-MeTHF (workup):
  • DCM: effective, but volatile chlorinated solvent with environmental concerns.
  • 2-MeTHF: bio-based, broader liquid range, water-immiscible; can simplify phase separations.

Catalyst/energy considerations:

• Employ organocatalysts (e.g., piperidine, amino acids) and run at ambient temperature when possible.
• Use solvent-free or mechanochemical conditions for condensations where feasible to reduce solvent usage.

Note: Evaluate green substitutions with small-scale trials to confirm solubility, selectivity, and crystallization behavior.

Pharmaceutical Uses

No pharmacopeial excipient role is defined for 4-(Cyanoacetyl)benzonitrile. It is used, if at all, as a synthetic intermediate in discovery and process chemistry.

• Typical roles in pharmaceutical R&D (general):

  • Intermediate for heterocycle formation (e.g., condensation/cyclization to pyrimidinones, pyrazoles) en route to candidate molecules.
  • Precursor to carboxamides/acids via nitrile hydrolysis for structure–property tuning (e.g., polarity, H-bonding) of lead series.
  • Building block for push–pull chromophores used in assay probes after Knoevenagel condensation with electron-rich aldehydes.

• Regulatory status: No monograph known (USP/EP/JP) for this specific fine chemical; any use in GMP manufacturing would require establishment of in-house specifications and appropriate quality controls.

• Formulation considerations: As a reactive intermediate, it is generally not formulated as a final excipient or API. If used in screening, stock solutions are commonly prepared in DMSO/DMF, then diluted into assay media, maintaining DMSO ≤1–2% v/v to limit vehicle effects.

Research-only disclaimer: For research use only; not for diagnostic or therapeutic applications.

Physical Properties

Item-specific physical property specifications are not provided in the Product Data. The following are general/literature-style considerations for this structural class; they are not Aladdin item specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet. (Compounds of this class are typically crystalline solids.)
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/practically decomposes before boiling at atmospheric pressure for many aromatic dinitrile ketones (literature trend); specific value: Not specified for this item.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable to solids; Not specified for this item.
• Solubility (qualitative, literature/general):
  • Poorly soluble in water due to dual nitriles and aryl core.
  • Readily soluble in polar aprotic organic solvents (e.g., DMSO, DMF, NMP, acetonitrile) and moderately soluble in chlorinated solvents and hot alcohols.
• Lipophilicity/logP: Not specified for this item; literature expectation is moderate aromatic polarity due to ketone and nitriles.
• pKa: The methylene flanked by carbonyl and nitrile is significantly acidified (active methylene); exact pKa depends on solvent and is not specified for this item.
• UV/Vis: Aryl ketone/nitrile chromophores absorb in the UV; exact cutoffs/extinction coefficients are not specified for this item.

Always verify critical properties (e.g., solubility for assay prep, polymorph/mp) on the item CoA/SDS for your lot.

Quality and Grades

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

Guidance on interpreting grades (general):

• Research-grade organics are suitable for routine synthesis and screening. If your application is moisture- or UV-sensitive (e.g., base-promoted condensations, photochemical steps), consider verifying trace-water content and any stabilizers on the CoA.
• If HPLC/LC-MS analysis is critical, prefer lots with low UV background and minimal non-volatile residues; check chromatographic purity and residual solvent profiles on the CoA.

Batch-to-batch considerations for this compound class:

• Residual acidic/basic impurities can alter the reactivity of the activated methylene (e.g., in Knoevenagel condensations). If you observe rate variability, pre-wash with base-free solvent or recrystallize.
• Trace hydrolysis/oxidation of the ketone is uncommon under dry storage but can occur with moisture/heat; verify by NMR/LC as needed.

Documentation to consult before use:

• Certificate of Analysis (assay/purity method, chromatographic profile, residual solvents, water content if available).
• Specification sheet for any additional contaminant limits or stabilizers.

Note: Do not treat the above as item specifications; default to the lot-specific CoA/Spec Sheet for definitive quality attributes.

Reaction and Applications

4-(Cyanoacetyl)benzonitrile is a versatile bifunctional synthon combining an activated methylene (between a carbonyl and nitrile) with a para-aryl nitrile. This arrangement enables complementary bond-forming strategies.

Key reaction families (literature/general):

• Knoevenagel condensations: Deprotonation of the –CH2– between C=O and C≡N forms a stabilized carbanion that condenses with aldehydes/ketones to give aryl-substituted acrylonitriles or enones bearing a pendant nitrile. Bases such as piperidine, pyridine, ammonium acetate, or DBU are often effective.
• Heterocycle synthesis: Condensation/cyclization with binucleophiles (e.g., urea/thiourea/guanidine, hydrazines, amidines) can furnish pyrimidinones, thiazoles, pyrazoles, and related scaffolds. The aryl nitrile can remain as a diversification handle.
• Nitrile transformations: Hydrolysis (acidic/basic) to amides/acids, Pinner reactions to imidates/esters, and [3+2] cycloadditions with azide to tetrazoles (often catalyzed by Lewis acids like ZnCl2/AlCl3) provide polar bioisosteres.
• Reductions: Ketone reduction (NaBH4; stereochemistry not a concern here) or selective nitrile reductions (DIBAL-H for aldehydes, LiAlH4 for amines) unlock further elaboration. Chemoselectivity must be planned carefully given two nitriles and a ketone.
• Cross-coupling (indirect): While the substrate lacks a halide/boron handle, the aryl nitrile can be transformed (e.g., to an amide/acid/amine) to enable subsequent coupling.

Applications:

• Diversified library synthesis in medicinal chemistry (electron-poor aryl scaffolds with dual nitrile functionality).
• Precursors to push–pull chromophores after Knoevenagel condensation with electron-rich aldehydes.

Practical notes:

• Control base strength/equivalents to avoid over-condensation.
• Water removal (Dean–Stark or molecular sieves) often improves yields in condensations.

Reaction Conditions

General literature-style conditions for common transformations of 4-(Cyanoacetyl)benzonitrile (verify and optimize for your system):

• Knoevenagel condensation (with aromatic aldehydes):

  • Solvent: EtOH, i-PrOH, toluene, or MeCN.
  • Catalyst/base: piperidine (5–20 mol%), ammonium acetate (0.5–1.5 equiv), or weak inorganic base (K2CO3).
  • Temperature/time: RT to reflux, 1–12 h. Water removal (sieves or Dean–Stark) often enhances yields.
  • Notes: Avoid strong base excess to limit side reactions (self-condensation/polymerization).

• Alkylation at methylene:

  • Base: NaH (1.1–1.5 equiv, THF), K2CO3 (2–3 equiv, DMF/MeCN) depending on electrophile.
  • Temperature: 0 °C to RT (NaH) or RT to 60 °C (K2CO3); 1–6 h.
  • Notes: Use dry, oxygen-free conditions; quench cautiously.

• Nitrile hydrolysis (to amide/acid):

  • Acidic: 6 M HCl or H2SO4(aq), 80–120 °C, 4–24 h → amide/acid depending on time; water co-solvent with MeOH/EtOH can improve wetting.
  • Basic: NaOH/KOH (2–5 equiv) in EtOH/H2O, reflux, 4–24 h. Work up under acidic conditions.

• Tetrazole formation (from nitrile):

  • Reagents: NaN3 (1.2–2.0 equiv) + Lewis acid (ZnCl2/AlCl3), DMF or MeCN, 80–120 °C, 6–24 h. Observe azide safety protocols.

• Reductions:

  • Ketone → alcohol: NaBH4 (1.1–1.5 equiv) in MeOH/EtOH, 0–25 °C, 0.5–2 h.
  • Nitrile → aldehyde: DIBAL-H (1.2–2.0 equiv), toluene/THF, −78 to −20 °C, 0.5–2 h; strict temperature control to avoid over-reduction.
  • Nitrile → amine: LiAlH4 or catalytic hydrogenation (Raney Ni/Pd), THF/EtOH, 0–25 °C to reflux.

All conditions above are general literature guidance and not product specifications. Run small-scale trials and monitor by TLC/LC-MS/NMR.

Safety and Handling

The Product Data do not include GHS classification details for this item. Treat as a laboratory chemical of unknown hazards and consult the SDS for authoritative guidance.

• GHS/CLP

  • Signal word: Not specified for this item; refer to SDS.
  • Hazard statements (H-phrases): Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

• Likely hazards (general for aromatic nitrile/ketone building blocks; not product-specific):

  • May cause irritation to skin, eyes, and respiratory tract.
  • Avoid dust formation and inhalation of particulates.

• Handling/PPE

  • Use in a fume hood; avoid inhalation/ingestion.
  • Wear appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves (e.g., nitrile). For weighing fine powders, consider a dust mask or respirator per risk assessment.

• Incompatibilities (general):

  • Strong bases may promote self-condensation/Knoevenagel-type reactions; handle base-mediated operations with temperature control.
  • Strong oxidizers and strong reducing agents (e.g., hydrides) can react vigorously with the ketone/nitrile functions.

• First aid (overview; see SDS):

  • Skin/eye contact: Rinse with water for ≥15 min; remove contaminated clothing; seek medical evaluation.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.

• Fire safety: Combustible organic solid; use CO2, dry chemical, or foam. Avoid water jets on dust fires.

• Stability: Typically stable at room temperature in sealed containers. Avoid prolonged exposure to moisture and strong UV.

Solvent Selection

Solubility and solvent choice for 4-(Cyanoacetyl)benzonitrile follow general patterns for aromatic ketone–dinitriles.

• Polarity/miscibility (general):

  • Poor water solubility; expect better solubility in polar aprotic solvents (DMSO, DMF, NMP, acetonitrile). Moderate solubility in ethyl acetate, acetone, and chlorinated solvents; limited in hexane/heptane.

• Common preparation solvents:

  • Stock solutions for screening: DMSO or DMF (10–100 mM typical in medicinal chemistry libraries).
  • Reaction media: ethanol or isopropanol (for base-catalyzed condensations), toluene or xylene (with Dean–Stark), acetonitrile (for polar reactions), or DMF/DMSO for difficult solubility substrates.

• When to choose which solvent (practical tips):

  • Knoevenagel condensations: ethanol, isopropanol, or toluene with catalytic piperidine/ammonium acetate; remove water azeotropically if necessary.
  • Nucleophilic additions to the carbonyl or Michael acceptors derived from this substrate: use polar aprotics (DMF, DMSO, MeCN) to stabilize anions and enhance rates.
  • Nitrile transformations (hydrolysis, amidoxime/tetrazole formation): protic media (aq. acid/base, alcohols) or mixed MeCN/H2O with Lewis/Brønsted acids.

• Brief comparison (general):

  • DMSO vs DMF: DMSO often affords higher solubility; DMF is easier to remove and lower odor. MeCN provides cleaner workups but may limit solubility.

Note: Solubility and solvent choices can vary with substitution pattern on reaction partners. Confirm with a small-scale solubility test before scale-up.

Storage and Reconstitution

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

General storage guidance (for aromatic nitrile/ketone solids):

• Keep tightly closed in the original container. Store in a cool, dry, and well-ventilated place away from strong bases, oxidizers, and reducing agents.
• Protect from prolonged exposure to moisture and strong light to minimize potential degradation or discoloration.
• If frequent access leads to humidity ingress, consider secondary containment with desiccant.

Reconstitution/solution preparation (general):

• Prepare stock solutions in dry organic solvents such as DMSO, DMF, MeCN, ethanol, or toluene, depending on downstream use.
• Typical screening stock concentrations: 10–100 mM in DMSO; filter through 0.22 µm PTFE for particulate removal if needed.
• For water-containing systems, use cosolvent strategies (e.g., DMSO 5–20% v/v) or surfactants if appropriate for your application.

Shelf life: Not specified for this item; refer to CoA/Spec Sheet. Inspect periodically by NMR/LC for long-term projects.

Research Use Note: For research use only.

Structure and Identity

Brief description: 4-(Cyanoacetyl)benzonitrile is an aromatic bifunctional building block bearing an aryl nitrile and a cyanoacetyl moiety (aryl ketone conjugated to a terminal nitrile through a methylene).

• SKU: C1069215
• Product name: 4-(Cyanoacetyl)benzonitrile
• CAS: 71292-11-0
• PubChem CID: 12540173
• InChIKey (as provided): 119779
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (Literature inference for this structure: C10H6N2O)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Literature calculation for C10H6N2O: ~170.17 g/mol)

Structural features (general, based on chemical name/literature):

• Aromatic ring bearing two para-substituents: one is a nitrile (–C≡N), the other is a cyanoacetyl group (–CO–CH2–C≡N).
• Functional groups: one aryl ketone (benzoyl), two nitriles (one aryl nitrile attached directly to the ring; one aliphatic nitrile beta to the carbonyl), and an activated methylene between carbonyl and nitrile.
• 2D description: A para-disubstituted benzene core; at C1, a –C≡N substituent; at C4, an acyl chain –C(=O)–CH2–C≡N. No stereocenters.

Notes

• Item-specific identifiers (SMILES, exact formula/MW) are not specified in the Product Data and should be confirmed on the item CoA/Spec Sheet prior to critical use.

Synthetic Utility

The combination of an activated methylene (–CO–CH2–C≡N) and a para-aryl nitrile renders 4-(Cyanoacetyl)benzonitrile a highly versatile synthon.

Transformations centered on the active methylene (literature):

• Knoevenagel condensations with aldehydes/ketones → α,β-unsaturated nitriles/enones. Subsequent Michael additions, cycloadditions, or reductions extend diversity.
• Alkylation: Soft-base deprotonation (e.g., K2CO3/EtOH, NaH/THF, DBU/MeCN) followed by alkyl halide trapping to install substituents alpha to the carbonyl.
• Condensation with nucleophiles: Hydrazines → pyrazoles; urea/thiourea/guanidine → (thio)pyrimidinones; malononitrile-like reactivity under basic conditions.

Transformations of the nitriles/ketone:

• Nitrile → amide/acid via hydrolysis (acidic or basic); → amidine via Pinner chemistry; → tetrazole via [3+2] azide cycloaddition (often ZnCl2-catalyzed); → aldehyde (DIBAL-H, low temperature) or amine (LiAlH4, catalytic hydrogenation).
• Ketone → oxime/hydrazone (derivatization); → secondary alcohol (NaBH4, catalytic hydrogenation); → enamine formation with secondary amines.

Orthogonal reactivity strategy:

• Use chemoselective conditions to functionalize the methylene first (mild base, polar protic/MeCN), then engage nitriles under stronger conditions. Alternatively, protect the carbonyl as an acetal/imine to manipulate nitriles selectively.

Retrosynthetic value:

• Accessible from 4-cyanobenzoyl chloride and acetonitrile equivalents (e.g., via acylation/cyanomethylation), making it a logical branch point for SAR libraries.

Target Specificity

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