4-Ethoxy-2-methyl-1-nitrobenzene - ≥97% , CAS No.52177-06-7

CAS: 52177-06-7 Cat. No.: E1007803 Formula: C₉H₁₁NO₃ Molecular Weight: 181.190 EC Number: 610-793-0

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifications & Purity

≥97%

Storage

Room temperature

Purity

≥97%

Names and Identifiers

• Canonical Smiles: CCOC1=CC(=C(C=C1)[N+](=O)[O-])C
• IUPAC Name: 4-ethoxy-2-methyl-1-nitrobenzene
• InChIKey: BXMRWUIRVNVUBM-UHFFFAOYSA-N
• INCHI: 1S/C9H11NO3/c1-3-13-8-4-5-9(10(11)12)7(2)6-8/h4-6H,3H2,1-2H3
• Molecular Weight: 181.190

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Nitrobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrophenyl ethers
• Alternative Parents: Nitrotoluenes Phenoxy compounds Phenol ethers Nitroaromatic compounds Alkyl aryl ethers Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Organonitrogen compounds Organic salts Organic oxides Hydrocarbon derivatives Organic cations
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Nitrophenyl ether - Nitrotoluene - Phenoxy compound - Nitroaromatic compound - Phenol ether - Alkyl aryl ether - Toluene - C-nitro compound - Organic nitro compound - Ether - Organic oxoazanium - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Organic nitrogen compound - Organic oxygen compound - Organic salt - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Organic oxide - Organic cation - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as nitrophenyl ethers. These are aromatic compounds containing a nitrobenzene moiety that carries an ether group on the 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

Chemical and Physical Properties

• Molecular Weight: 181.190 g/mol
• XLogP3: 3.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 181.074 Da
• Monoisotopic Mass: 181.074 Da
• Topological Polar Surface Area: 55.100 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 178.000
• 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 assay/application protocols are specified for this item. As a research chemical building block, typical laboratory operations include dissolution in suitable organic solvents, inert-atmosphere handling for air/moisture-sensitive reagents used alongside it, and standard purification (chromatography/crystallization) of downstream products. For reaction examples and conditions, see Reaction Conditions and Reaction & Applications.

Biological Roles

This product is supplied strictly for research use as a synthetic building block.

• Item-specific biological roles: None stated. No biological function or role is claimed for this compound in living systems.
• General chemistry context (not a claim):
  • Small nitroaryl ethers are common synthetic intermediates and probes in physical organic chemistry but typically lack defined physiological roles.
  • The nitro group is a strong electron-withdrawing functionality often used to modulate binding or physicochemical properties in discovery chemistry; however, any biological activity would be highly context-dependent and is outside the scope of this catalog entry.

Research use only: Per Product Data, this material is for research use only and not for diagnostic, therapeutic, or clinical applications.

Buffer Applications

Not typically applicable. 4-Ethoxy-2-methyl-1-nitrobenzene is a neutral, hydrophobic organic building block and is not used to prepare aqueous buffers or as a buffering agent. For practical use information, see Reaction & Applications and Synthetic Utility.

Green Alternatives

Because this SKU is a building block rather than a solvent or reagent consumed stoichiometrically, green considerations focus on solvent and reducing agent choices during its use.

• Greener solvent choices (literature guidance):

  • Prefer 2-MeTHF over THF when feasible: similar polarity, higher boiling point, bio-based, and improved safety profile.
  • Replace DCM/chloroform with EtOAc, Me-THF, or toluene where solubility and reaction rates permit.
  • For extractions, cyclopentyl methyl ether (CPME) or EtOAc often substitute for DCM with comparable partitioning for nitroaryl ethers.

• Greener reductions of nitro groups (comparative overview): | Approach | Greenness | Notes | | --- | --- | --- | | H2 with Pd/C in EtOH or iPrOH | High | Atom-efficient, benign solvent; filterable catalyst. | | Fe/AcOH or Fe/NH4Cl in water/EtOH | Moderate | Cheap, aqueous-compatible; generates iron salts. | | Transfer hydrogenation (HCO2H/Et3N, ammonium formate) | Moderate–High | Avoids H2 gas; simple setup. | | SnCl2/HCl | Low | Effective but produces hazardous tin waste.

• Workup/waste minimization:

  • Use crystallization or trituration in lieu of chromatography when possible.
  • Plan telescoped sequences (e.g., reduction → coupling) to reduce solvent usage and intermediate isolation.

Pharmaceutical Uses

• Item-specific pharmacopeial status and excipient roles: Not specified for this item; refer to CoA/Spec Sheet.

General guidance:

• This compound is a research-grade intermediate. While aryl nitro ethers can appear as intermediates in medicinal chemistry routes, they are not typical pharmaceutical excipients.
• Process considerations (if used in route development): pay attention to purge of nitroaromatic impurities and control of residual solvents/metals according to ICH Q3 guidelines in later development stages.

Physical Properties

• Item-specific specifications: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance for the class (substituted nitroarenes with aryl ethyl ethers):

• Physical state: typically low-melting solids or high-boiling liquids depending on substitution; this substitution pattern often affords an oil at ambient temperature.
• Polarity: moderately polar aromatic due to the nitro and aryl ether groups; significantly less polar than nitrophenols but more polar than toluene.
• Solubility (qualitative, literature):
  • Water: very low solubility is expected for neutral nitroarenes with ether substituents.
  • Organic solvents: high solubility in ethers (THF, MTBE), chlorinated solvents (DCM, chloroform), esters (EtOAc), aromatics (toluene, xylene), and good solubility in alcohols (MeOH, EtOH) and polar aprotics (MeCN, DMF, DMSO).
• Partition behavior (qualitative, literature): logP likely in the moderate range characteristic of nitroaryl ethers; expect strong retention on nonpolar stationary phases and good extractability into organic phases.
• Spectroscopic notes (literature):
  • 1H NMR: distinct ethoxy quartet/triplet (–OCH2CH3), methyl singlet on ring (Ar–CH3), and three aromatic protons with substitution pattern (1,2,4-trisubstitution).
  • IR: strong asymmetric/symmetric NO2 stretches near ~1520 and ~1350 cm−1 (literature), aryl–O–C stretches near ~1200–1050 cm−1.
• Refractive index, density, mp/bp, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet or primary literature for this exact isomer.

Quality & Grades

• Grade/Purity for this specific SKU: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• UV cutoff, water/peroxide content, and elemental impurities: Not specified for this item; refer to CoA/Spec Sheet.

How to interpret grades (general guidance):

• Research-grade organics typically emphasize identity, purity by NMR/GC/HPLC, and limited residual solvents/metals. If HPLC grade or GC grade is offered for solvents, that indicates low UV background or low non-volatile residue; for solid/liquid building blocks like this, typical metrics include assay (%), isomeric purity, and residual solvent limits.
• Stabilizers: Not commonly required for nitroaryl ethers; if listed on the CoA, understand the impact on downstream synthesis (e.g., BHT traces in oxidative couplings) and plan purification accordingly.

Quality control suggestions (practical):

• Verify identity by 1H/13C NMR and HRMS; nitro stretches in IR provide supportive evidence. GC–MS or HPLC for purity. For moisture sensitivity assessments, Karl Fischer can be performed if needed, though aryl ethers are generally not hygroscopic.

Reaction & Applications

As a substituted nitrobenzene bearing an ether and a methyl group, 4-ethoxy-2-methyl-1-nitrobenzene is a versatile intermediate in aromatic chemistry.

• Representative transformations (literature):
  • Reduction of –NO2 to an aniline (–NH2) using catalytic hydrogenation (H2/Pd, H2/Pt) or stoichiometric methods (Fe/AcOH, SnCl2/HCl). The resulting aniline enables diazotization, Sandmeyer reactions, and coupling to form azo dyes.
  • Nucleophilic aromatic substitution (SNAr) at positions activated by the nitro group is generally limited here due to the absence of a halide leaving group; however, installation of a halogen ortho/para to NO2 greatly enhances SNAr potential.
  • Electrophilic aromatic substitution (EAS): directing effects are complex due to competing donors/acceptor; nitration/sulfonation are deactivated by –NO2 but can proceed under forcing conditions. The ethoxy and methyl groups can direct further substitution ortho/para relative to themselves.
  • Cross-coupling pathways: After halogenation (e.g., bromination) of an available ring position, Suzuki–Miyaura, Buchwald–Hartwig, or Ullmann-type couplings can elaborate the scaffold.
  • Ether transformations: O-dealkylation (e.g., BBr3, AlCl3) can convert the ethoxy to a phenol, enabling subsequent derivatization.
• Applications in synthesis (general):
  • Intermediate toward substituted anilines, nitroso derivatives, and heterocycles.
  • Useful as an electron-deficient/electron-rich mixed arene probe in mechanistic studies assessing substituent effects.
• Practical notes:
  • Preserve the nitro group by avoiding strong nucleophiles at elevated temperatures unless desired to reduce or denitrate.
  • Reductions should be monitored to avoid over-reduction (e.g., to hydroxylamine or anilines followed by dealkylation under harsh acidic conditions).

Reaction Conditions

General literature guidance for common transformations of nitroaryl ethers (not item-specific specifications):

• Catalytic hydrogenation of –NO2 to –NH2:
  • Typical catalysts: 5–10% Pd/C (0.5–5 mol% Pd), Pt/C, or Raney Ni.
  • Solvents: EtOH, iPrOH, EtOAc, or mixtures; pressures 1–5 bar H2 (balloon to Parr), 20–50 °C.
  • Workup: filter catalyst through celite, concentrate, and, if necessary, basify and extract.
• Iron-mediated reductions:
  • Reagents: Fe powder (3–6 equiv) with AcOH or NH4Cl/H2O; solvents EtOH/H2O.
  • Temperatures: 50–90 °C; monitor by TLC/LC-MS; typical times 1–6 h (literature).
• O-dealkylation (to phenol):
  • BBr3 in DCM at −78 to 0 °C (1–3 equiv per O-alkyl); quench with MeOH then aqueous workup.
  • Alternatively, AlCl3/thiophenol or HBr/AcOH under reflux (harsher).
• Electrophilic halogenation for subsequent coupling:
  • NBS/NCS under radical or electrophilic conditions; solvent choices include MeCN, DCM, or AcOH; temperatures 0–25 °C.
• Cross-coupling after halogenation:
  • Suzuki–Miyaura: Pd(dppf)Cl2 (1–3 mol%), K2CO3 or K3PO4, dioxane/H2O or toluene/H2O, 60–100 °C.
  • Buchwald–Hartwig amination: Pd2(dba)3 or Pd(OAc)2 with dialkylbiaryl phosphine ligands, NaOtBu or Cs2CO3, toluene/dioxane, 80–110 °C.

Notes:

• Protect the ether if using strong Lewis acids elsewhere in the sequence.
• The nitro group can suppress some metal-catalyzed steps; ensure ligand/catalyst choices tolerate electron-poor arenes.

Safety & Handling

• GHS classification, pictograms, and H-statements: Not specified for this item; refer to the SDS for authoritative safety information.
• General hazards for nitroarenes and aryl ethers (literature-based):
  • May cause skin and eye irritation; harmful if swallowed or inhaled. Nitroaromatics can present methemoglobinemia risk upon significant exposure—avoid ingestion and inhalation.
  • Combustible organic; avoid ignition sources. Not known as a peroxide former (unlike dialkyl ethers), but standard good practice is to store away from strong oxidizers and strong reducing agents.
• Incompatibilities (general): strong bases (can promote nucleophilic aromatic substitution at activated positions), strong acids (can lead to cleavage of aryl ethers under harsh conditions), powerful oxidants/reductants.
• PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to control vapor and dust/aerosol.
• First aid (general guidance; defer to SDS):
  • Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing.
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Handling tips: Minimize aerosol formation; use sealed containers and proper waste labeling. For weighing liquids, use tared vials or syringes to prevent spills.
• Fire response: Use CO2, dry chemical, or foam. Cool containers with water spray if safe. Consult SDS for specifics.

Solvent Selection

This substance is an aromatic nitro ether—neutral, moderately polar, and hydrophobic.

• Polarity/miscibility (general expectations):
  • Miscible with many organic solvents; insoluble/very slightly soluble in water.
  • Performs well in aprotic media (toluene, DCM, EtOAc, THF, MeCN). DMSO/DMF are excellent for SNAr or reduction chemistry but complicate workup.
• When to choose solvents:
  • Electrophilic/aromatic transformations: toluene or chlorobenzene allow higher temperatures and preserve ether integrity.
  • Reductions of nitro to aniline: EtOH, iPrOH, or EtOAc under catalytic hydrogenation; or EtOH/THF with iron or SnCl2 reductions (literature).
  • Metal-catalyzed cross-couplings after further functionalization (e.g., halogenation): use polar aprotics (dioxane, THF, MeCN) with bases.
• Small comparison (general):
  • Toluene: good for high-temp EAS; easy workup.
  • THF/2-MeTHF: better for nucleophilic processes; 2-MeTHF offers greener profile.
  • EtOAc: balanced polarity; easy removal; greener than chlorinated solvents.
  • DCM: strong solvency and fast evaporation; consider environmental and safety drawbacks.
• Practical tip: For chromatography, start with hexanes/EtOAc gradients. Nitroaryl ethers typically elute at moderate EtOAc content due to their polarity relative to simple aromatics.

Storage & Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; supplied neat. If received as a solid (lot-dependent), warm gently to room temperature to ensure homogeneity before use.
• Handling/storage tips (general):
  • Keep container tightly closed in a dry, well-ventilated place; protect from strong light and heat sources.
  • Segregate from strong oxidizers and strong reducing agents. Avoid prolonged exposure to strong acids/bases if integrity of the ether is critical.
  • If long-term storage is planned, consider aliquoting to minimize headspace exposure during repeated use.
• Stability notes: Nitroaryl ethers are generally stable at ambient conditions. Consult the CoA for any lot-specific observations (appearance, assay) before use.

Structure & Identity

Brief description: 4-Ethoxy-2-methyl-1-nitrobenzene is a substituted nitrobenzene bearing an ethoxy substituent para to the nitro group and a methyl ortho to the nitro group. The molecule presents three key functionalities on an aromatic ring: a strongly electron-withdrawing nitro group, an electron-donating ethoxy group, and a weakly donating methyl group.

• Item-specific identifiers (from Product Data):
  • CAS: 52177-06-7
  • PubChem CID: 11564566
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature identity (for reference; not item specifications):
  • Empirical formula (literature/structure-derived): C9H11NO3
  • Molecular weight (literature/computed): ~181.19 g/mol
• Structural features (general description):
  • Aromatic ring with three substituents: nitro (–NO2) at C1, ethoxy (–O–CH2CH3) at C4, methyl (–CH3) at C2.
  • Functional groups: nitroarene (–NO2 on Ar), aryl ether (Ar–O–Et), alkyl substituent (Ar–CH3).
  • Resonance/electronics: nitro group is a strong –M/–I director; ethoxy is +M/–I; methyl is weakly +I. This substitution pattern creates an anisotropic electron density distribution across the ring, relevant to regioselectivity in further electrophilic substitutions.
  • 2D description: a benzene ring bearing, clockwise, nitro at position 1, methyl at 2, hydrogen at 3, ethoxy at 4, hydrogens at 5 and 6.

Synthetic Utility

Key functional elements and reactivity leverage:

• Nitro group (–NO2):
  • Reductive handle to access anilines, which unlock diazotization, Sandmeyer, azo coupling, and acylation to anilides.
  • Strongly deactivates the ring toward EAS but activates ortho/para positions for SNAr when a leaving group is present (not the case here unless further functionalized).
• Aryl ether (–OEt):
  • Orthogonal protecting/directing element. Can be demethylated/deethylated with Lewis/Brønsted acids (e.g., BBr3, AlCl3, HBr) to yield phenols for diversification (sulfonates, carbonates, etherification).
  • Donating by resonance; influences regioselectivity of any subsequent EAS.
• Aryl methyl (–Me):
  • Oxidizable to aldehyde or acid (e.g., benzylic oxidation with KMnO4 or SeO2 under specific conditions), enabling further elaboration.

Retrosynthetic value:

• Serves as a convergent node where the nitro group can be reduced late-stage to reveal amine functionality while the ether can be retained to modulate solubility and electronics.
• Precursor to heterocycles: anilines derived from reduction can enter cyclizations (e.g., forming benzoxazoles or benzimidazoles after appropriate functionalization).

Practical considerations:

• Choose conditions that tolerate both nitro and ether groups; avoid strong bases at high temperature that may cleave the ether or promote unwanted side reactions.
• If halogenation is planned to enable cross-coupling, use selective methods (e.g., NBS for benzylic or directed electrophilic bromination) accounting for directing effects of –OEt and –NO2.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biologic. No target, epitope, clone, or isotype information applies.