4,5-Dimethyl-2-nitrobenzonitrile , CAS No.15089-77-7

CAS: 15089-77-7 Cat. No.: D992115 Summenformel: C₉H₈N₂O₂ Molekulargewicht: 176.170

Storage

Room temperature

Specifications

Storage

Room temperature

Namen und Kennungen

Kanonisches Lächeln

CC1=CC(=C(C=C1C)[N+](=O)[O-])C#N

IUPAC Name

4,5-dimethyl-2-nitrobenzonitrile

InChIKey

KMXMOTHNWNJKBR-UHFFFAOYSA-N

INCHI

1S/C9H8N2O2/c1-6-3-8(5-10)9(11(12)13)4-7(6)2/h3-4H,1-2H3

Molekulargewicht

176.170

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Nitrobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrobenzenes
• Alternative Parents: Nitrotoluenes o-Xylenes Nitroaromatic compounds Benzonitriles Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Nitriles Organic salts Organic oxides Hydrocarbon derivatives Organic cations
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Nitrobenzene - Nitrotoluene - Benzonitrile - Nitroaromatic compound - Xylene - O-xylene - Organic nitro compound - C-nitro compound - Carbonitrile - Nitrile - Organic oxoazanium - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Organic oxygen compound - Cyanide - Organonitrogen compound - Organic salt - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organic cation - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 176.170 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 176.059 Da
• Monoisotopic Mass: 176.059 Da
• Topological Polar Surface Area: 69.600 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 250.000
• 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 vendor-tested biological application protocols are provided for this item. As a small-molecule building block, typical protocol elements are synthesis-focused:

• Preparing stock solutions for screening: dissolve in anhydrous DMSO (e.g., 10–100 mM), vortex/sonicate as needed, and filter (0.2 µm PTFE). Store aliquots desiccated and protect from light.
• Workup/purification: for reactions in polar aprotics, dilute with water and extract with EtOAc or MTBE; wash, dry (Na2SO4), and concentrate. Purify by flash chromatography using hexanes/EtOAc gradients, monitoring by UV (nitro/nitrile chromophores). These are general, non-item-specific suggestions.

Biological Roles

This compound is a synthetic aromatic building block and is not a known natural metabolite or cofactor.

• Biochemical role: none established; nitroaromatics and benzonitriles of this type are typically used as chemical intermediates in discovery chemistry rather than as biological probes (literature/general).
• Reactivity in biological milieu: neutral, hydrophobic with polar functionalities; expected low aqueous solubility and limited passive ionization. Nitro groups can undergo bioreductive transformations in certain enzymatic systems, but such behavior is highly context-dependent and is not attributed specifically to this molecule (literature/general).
• Use context: any deployment in biochemical assays is as a research chemical or scaffold precursor; no nutritional, enzymatic, or signaling role is documented.

Note: For research use only (per product data). No clinical or diagnostic use is intended or implied.

Buffer Applications

Not typically applicable. 4,5-Dimethyl-2-nitrobenzonitrile is a non-ionic organic building block and is not used as a buffering agent or pH modifier. For practical handling in biological assays, prepare stock solutions in DMSO or DMF and dilute into assay-compatible buffered media while monitoring final solvent percentage (literature/general).

Green Alternatives

While the substrate itself is fixed, the sustainability profile of its use can be improved via solvent and reagent choices (literature/general):

Greener solvent swaps for common operations:

• Stock/preparative dissolution: replace DMF/DMSO with 2-MeTHF or Cyrene when feasible; assess solubility first.
• Hydride reductions (nitrile → amine): consider catalytic hydrogenation in ethanol or isopropanol instead of LiAlH4 in THF/Et2O; employ Raney Ni or Pd/C under H2 with proper safety controls.
• Amide formation (from acid derived by hydrolysis): use coupling reagents with improved EHS profiles (e.g., COMU or EDCI) and green solvents (MeTHF, CPME) where compatible.

Small comparison (literature/general):

• DMF vs Cyrene: Cyrene offers lower toxicity and is biorenewable, with similar polarity; however, it may be less stable under strong basic conditions and has higher viscosity.
• THF vs 2-MeTHF: 2-MeTHF is bio-based, exhibits lower peroxide formation and better phase separations; THF remains superior for some low-temperature organometallics.
• DCM vs EtOAc: EtOAc is less hazardous and often adequate for extractions and chromatography, though DCM provides higher density and faster separations.

Process tips:

• Emphasize room-temperature or mild-temperature catalysis, flow hydrogenation for safer H2 handling, and solvent recovery/distillation to reduce waste. Apply DoE to minimize excess reagents and steps.

Pharmaceutical Uses

No pharmacopeial excipient status or formulation role is specified for this item. This compound is primarily a research intermediate.

Literature/general context:

• Utilized in medicinal chemistry as a highly substituted benzonitrile scaffold; the nitro group can be reduced to reveal an aniline for further diversification, while the nitrile can be transformed to amides/acids/amines for SAR exploration.
• Process considerations: when used in API intermediate routes, control of positional isomers and residual nitroaromatic impurities is critical; nitrile residual limits and nitroso species risk assessments should be incorporated per current ICH guidance. These considerations are route- and program-specific and not item-specific specifications.

Physical Properties

Item-specific physico-chemical specifications (bp, mp, density, UV cutoff, metal content, water, stabilizers): Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for this structural class (aromatic nitro-nitriles):

• Physical state: typically a crystalline solid due to the presence of two strong electron-withdrawing groups (–NO2, –C≡N) increasing lattice cohesion.
• Polarity: moderately polar (dipolar functionalities) yet largely hydrophobic aromatic scaffold; often exhibits poor water solubility and good solubility in polar aprotic organic solvents (DMF, DMSO, NMP, MeCN) and chlorinated/ether/aromatic solvents (DCM, THF, toluene).
• Acid/base: neutral compound; no ionizable centers under physiological pH. Nitrile nitrogen is weakly basic only in superacids (literature/general).
• Boiling/melting points, logP, pKa, refractive index: Not specified for this item; refer to CoA/Spec Sheet.

Computed/literature formula and mass:

• Formula (literature): C9H8N2O2
• Formula mass (literature calculation): 176.17 g/mol

Quality and Grades

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

Guidance on typical grades for this compound class (literature/general):

• Research/technical grade aromatic building blocks are commonly supplied with assay by HPLC or GC and controlled levels of related impurities (positional isomers, reduction/oxidation byproducts). For chromatography-intensive applications (e.g., medicinal chemistry SAR), material pre-qualified for low non-volatile residue and tight isomeric purity is advantageous.
• If offered in “>98%” or “HPLC grade” variants, these typically indicate tighter organic impurity profiles and lower UV-active contaminants suitable for photophysical studies or trace-sensitive synthesis. Absent explicit claims, verify suitability by requesting the current CoA.

Quality considerations specific to nitro-nitriles (general):

• Monitor for hydrolysis (to amide/acid) and reduction (to anilines) during long-term storage or prolonged exposure to strong light/heat. Confirm identity/purity by 1H/13C NMR, IR (sharp CN stretch ~2220–2260 cm−1; NO2 asymmetric ~1510–1560 cm−1, symmetric ~1330–1370 cm−1; literature/general), and LC/MS.

Reaction and Applications

As a bifunctional aromatic building block, 4,5-dimethyl-2-nitrobenzonitrile supports orthogonal diversification at the nitro and nitrile moieties (literature/general):

• Nitro group transformations:
  • Reduction to an aniline using H2/Pd-C, Fe/NH4Cl, SnCl2/HCl, or catalytic transfer hydrogenation. The resulting o-amino nitrile is a versatile intermediate for intramolecular cyclizations, acylations, and cross-couplings.
  • N–O bond chemistry (e.g., partial reductions to hydroxylamines under controlled conditions) for advanced heterocycle synthesis.
• Nitrile group transformations:
  • Hydrolysis to amide or acid (acidic or basic conditions; stepwise control via temperature/time). Amide formation enables subsequent coupling strategies.
  • Reduction to primary amine (e.g., LiAlH4, catalytic hydrogenation with Ru/Raney Ni) to afford benzylic primary amines; useful for urea, amide, or sulfonamide elaboration.
  • Nucleophilic additions (Grignard/organolithium) to form imines/ketimines that hydrolyze to ketones or amines upon workup.
• Ring functionalization (guided by deactivation of nitro/nitrile; literature/general):
  • Electrophilic substitution is dampened; however, directed metallation ortho to methyl groups may be feasible under strong base (s-BuLi/TMEDA) followed by electrophile quench.
  • Cross-coupling typically requires preinstallation of a halide or pseudohalide; use the nitro-to-aniline reduction followed by diazotization/Sandmeyer to introduce halogens.

Applications: synthesis of densely substituted benzonitriles, precursors to benzamides/benzoic acids, and scaffolds for medicinal chemistry SAR libraries exploiting the o-anilino nitrile motif.

Reaction Conditions

General literature guidance for transforming the two principal functional groups:

• Nitro reduction → aniline:
  • H2/Pd-C (5–10 wt% Pd): 1–5 bar H2, EtOH or EtOH/THF, 20–40 °C, 2–8 h; monitor by TLC/LC-MS. Avoid over-reduction of nitrile by choosing mild pressure and catalyst loading.
  • Fe/NH4Cl (or Fe/HCl) in EtOH/H2O: 60–80 °C, 2–6 h; robust, scalable, and tolerant of nitriles.
  • SnCl2·2H2O in EtOH/HCl: reflux 2–6 h; efficient but generates tin waste.
• Nitrile hydrolysis:
  • Acidic: H2SO4(aq) or HCl(aq), 80–120 °C, 6–24 h to amide/acid depending on time and water content.
  • Basic: NaOH/KOH (2–6 equiv) in EtOH/H2O or DMSO/H2O, 80–120 °C; often proceeds to carboxylate, re-acidify during workup.
• Nitrile reduction → primary amine:
  • LiAlH4 in THF: 0 °C to reflux, 2–6 h; quench carefully. Alternatively, BH3·THF under similar conditions.
  • Catalytic hydrogenation (Raney Ni or Ru/C): 10–30 bar H2, MeOH/EtOH, 25–80 °C, 4–16 h; may reduce nitro concurrently—sequence steps or adjust conditions for selectivity.
• Benzylic functionalization of methyl groups:
  • NBS (AIBN, hv) in CCl4 or greener solvents (MeCN/MeOH variants) at reflux; subsequent substitution or oxidation steps.

All values are literature/general guidance; optimize stoichiometry, temperature, and solvent for your specific substrate and scale.

Safety and Handling

GHS classification, signal word, H/P statements, and pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (literature/general):

• PPE: wear lab coat, appropriate chemical-resistant gloves (e.g., nitrile), and safety glasses or face shield. Handle solids to minimize dust generation; use in a fume hood to avoid inhalation of particulates or solvent vapors during processing.
• Incompatibilities: strong reducing agents (for nitro-containing aromatics), strong oxidizers, and strong bases/acids during storage are best avoided. For reactions, control additions and temperature carefully when using strong hydride reagents or catalysts.
• Thermal stability: aromatic nitro compounds may decompose upon strong heating; avoid open flames and uncontrolled exotherms. Do not grind with reactive metals.
• First aid (overview; defer to SDS): in case of skin/eye contact, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, do not induce vomiting; seek medical attention.
• Waste: collect nitroaromatic-containing residues as hazardous organic waste; follow institutional and local regulations.
• Note: Always consult the product-specific SDS for authoritative hazard, exposure limits, and spill/fire-fighting guidance.

Solvent Selection

This product is a neutral, moderately polar aromatic solid with nitro and nitrile groups. Solvent choice is typically driven by reaction type and desired solubility.

• Likely good solvents (literature/general): DMSO, DMF, NMP, DMAc, MeCN, THF, dioxane, chlorinated solvents (DCM/CHCl3), and aromatic solvents (toluene). Often sparingly soluble in alcohols; poorly soluble in water.
• For stock solutions: DMSO or DMF frequently enable concentrated solutions for screening and parallel synthesis; filter through 0.2 µm if particulates remain.
• For nucleophilic substitutions/reductions on the nitro group or nitrile conversions: polar aprotic solvents (DMF, MeCN, THF) aid reactivity and reagent compatibility.
• For catalytic hydrogenation: alcohols (EtOH/iPrOH) or mixed solvents (EtOH/THF) may be used alongside Pd/C, provided the compound’s solubility is sufficient.

Comparison (literature/general):

• DMSO vs DMF: DMSO offers broader solvency and higher boiling point (good for slow transformations), while DMF simplifies workup due to lower viscosity and easier removal. DMF may be preferable for base-mediated hydrolyses; DMSO for high-temp coupling or as stock-solution medium.
• MeCN vs THF: MeCN provides higher polarity and is excellent for SNAr/couplings with polar catalysts; THF is advantageous for hydride reductions (LAH, DIBAL) of nitriles due to ether compatibility.

Storage and Reconstitution

• Storage conditions (product data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Container: store tightly closed in a dry, inert atmosphere (preferably under nitrogen or with desiccant) to minimize moisture uptake and oxidative degradation (general guidance for nitroaromatic nitriles).
• Light and humidity: keep in a cool, dry place; protect from prolonged light exposure.
• Reconstitution/stock solutions: prepare concentrated stocks in anhydrous DMSO or DMF (e.g., 10–100 mM) for screening workflows. Filter if needed and aliquot to avoid repeated opening. For synthetic operations, dissolve directly in the reaction solvent under inert gas if required.
• Freeze–thaw: for solution stocks, avoid repeated freeze–thaw; store aliquots at 2–8 °C or −20 °C, allowing solutions to warm to room temperature before opening to prevent moisture condensation (general guidance).

Structure and Identity

A substituted aromatic nitrile featuring an o-nitro group and two ring methyl substituents; offers two orthogonal functional handles (–NO2 and –C≡N) for divergent synthesis.

• Product name: 4,5-Dimethyl-2-nitrobenzonitrile
• CAS: 15089-77-7
• PubChem CID (literature): 13509013
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature deduction from name): C9H8N2O2
• Molecular weight (literature calculation): 176.17 g/mol

Structural features (descriptive, literature/general):

• Aromatic benzene core bearing three substituents: a nitrile (–C≡N) at the benzylic carbon framework, an ortho nitro (–NO2) relative to the nitrile, and two adjacent ring methyl groups at the 4- and 5-positions.
• Functional groups: electron-withdrawing nitro and nitrile; weakly electron-donating alkyl groups (methyls).
• Planar, conjugated ring; no stereocenters.
• The nitro and nitrile groups are meta-directing and deactivating toward further electrophilic aromatic substitution (literature/general).

Synthetic Utility

Key functional handles and reactivity (literature/general):

• Nitro → aniline: chemoselective reduction unlocks o-amino benzonitriles, enabling intramolecular cyclizations (e.g., to benzoxazinones/benzimidazoles after appropriate activation) and standard N-acylation/sulfonylation.
• Nitrile → amide/acid/amine: orthogonal conversion pathways give access to carboxamide/carboxylic acid (hydrolysis) or primary amine (hydrogenation/LAH), supporting rapid parallel synthesis.
• Directed elaboration from methyl groups: benzylic oxidation (e.g., SeO2, MnO2, or catalytic aerobic systems) affords aldehydes/acids for further coupling; radical bromination (NBS, light) enables subsequent substitution to diversify the ring periphery.
• Ring halogenation via diazotization: reduce nitro to aniline, then perform diazotization/Sandmeyer to introduce Cl/Br/I or CN, enabling cross-coupling entry points.
• Electrophilic substitution: globally deactivated by –NO2/–CN; however, benzylic positions allow side-chain functionalization without perturbing the ring.

Retrosynthetic value:

• Serves as a convergent node: orthogonal manipulations let chemists branch toward anilides, benzoic acids, or aminomethyl derivatives from a single starting material, streamlining library synthesis and route scouting.

Target Specificity

Not applicable. This product is a small-molecule chemical intermediate and not a biological targeting reagent (e.g., no antibody/oligo/ligand specificity is provided).