4-Ethoxybenzoyl Chloride - ≥98% , CAS No.16331-46-7

CAS: 16331-46-7 Cat. No.: E131914 Formula: C₉H₉ClO₂ Peso molecolare: 184.62 Beilstein Registry Number: 10(4)430 Numero EC: 605-323-6

GRADE & PURITY ≥98%

Synonyms

4-Ethoxybenzoyl chloride, 98% | 4-ethyloxybenzoyl chloride | p-ethoxy benzoyl chloride | 4-ethoxybenzoylchloride | BBL100049 | para-ethoxybenzoyl chloride | 4-Ethoxybenzoyl chloride | 4-Ethoxy-benzoyl chloride | A810467 | DTXSID40167565 | SCHEMBL275646 |

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Panoramica

4-Ethoxybenzoyl chloride may be used in chemical synthesis studies.

Specifications

Sinonimi

4-Ethoxybenzoyl chloride, 98% | 4-ethyloxybenzoyl chloride | p-ethoxy benzoyl chloride | 4-ethoxybenzoylchloride | BBL100049 | para-ethoxybenzoyl chloride | 4-Ethoxybenzoyl chloride | 4-Ethoxy-benzoyl chloride | A810467 | DTXSID40167565 | SCHEMBL275646 |

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Store at 2-8°C,Argon charged

Spedito in

Wet ice

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Purezza

≥98%

Nomi e identificatori

• Pubchem Sid: 488188063
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/488188063
• Sorrisi canonici: CCOC1=CC=C(C=C1)C(=O)Cl
• IUPAC Name: 4-ethoxybenzoyl chloride
• InChIKey: XLWQUESMILVIPR-UHFFFAOYSA-N
• INCHI: 1S/C9H9ClO2/c1-2-12-8-5-3-7(4-6-8)9(10)11/h3-6H,2H2,1H3
• Isomeri SMILES: CCOC1=CC=C(C=C1)C(=O)Cl
• WGK Germania: 3
• Peso molecolare: 184.62
• Beilstein: 10(4)430
• Reaxy-Rn: 2248154
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=2248154&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acids and derivatives
• Alternative Parents: Phenoxy compounds Phenol ethers Benzoyl derivatives Alkyl aryl ethers Acyl chlorides Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoic acid or derivatives - Phenoxy compound - Phenol ether - Benzoyl - Alkyl aryl ether - Ether - Acyl halide - Acyl chloride - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organochloride - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzoic acids and derivatives. These are organic compounds containing a carboxylic acid substituent 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

Proprietà chimiche e fisiche

• Sensibilità: Moisture Sensitive,Heat Sensitive
• Indice di rifrazione: 1.57
• Punto di infiammabilità (°F): 235.4 °F
• Punto di infiammabilità (°C): 113 °C
• Punto di ebollizione (°C): 145 °C/20 mmHg
• Punto di fusione (°C): 22 °C
• Peso molecolare: 184.620 g/mol
• XLogP3: 3.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 184.029 Da
• Monoisotopic Mass: 184.029 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 151.000
• 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 item‑specific tested application protocols are provided for this product.

General laboratory protocol outlines (for guidance only)

• Amide formation (typical): To a dry, stirred solution of amine (1.0 equiv) and TEA (2.0–3.0 equiv) in anhydrous DCM at 0 °C under argon, add 4‑ethoxybenzoyl chloride (1.05–1.20 equiv) dropwise. Stir 0–25 °C until complete (TLC/LC). Quench with cold saturated NaHCO3, separate, wash, dry, and purify.
• Esterification with alcohol: As above, optionally include DMAP (5–10 mol%) or use pyridine as solvent/base. Maintain temperature to control rate and minimize transacylation.
• Biphasic acylation: Combine organic solution of substrate with aqueous Na2CO3; add acid chloride portionwise at 0–10 °C under vigorous stirring; maintain basic pH to neutralize HCl; work up after completion.

Note: These are general literature practices. Optimize stoichiometry, temperature, and solvent for your substrate. Always consult the item’s CoA/SDS and perform appropriate risk assessment.

Biological Roles

This product is a synthetic aromatic acyl chloride intended for laboratory synthesis. It does not have a known natural biological role.

General biochemical context (literature)

• Aroyl chlorides are not typical biomolecules; in aqueous/physiological media they hydrolyze rapidly to the corresponding carboxylic acids, releasing HCl. For 4‑ethoxybenzoyl chloride, the hydrolysis product is 4‑ethoxybenzoic acid, an aromatic carboxylate lacking specific endogenous metabolic roles.
• In chemical biology workflows, para‑ethoxybenzoyl moieties may be introduced as amide/ester linkers to modulate lipophilicity or spectroscopic properties of probes. Such uses are strictly for research and require careful control to avoid nonspecific acylation.

Compliance note

• For research use only. Not for use in diagnostic procedures, foods, drugs, or cosmetics.

Buffer Applications

Not typically applicable. 4‑Ethoxybenzoyl chloride is moisture‑sensitive and hydrolyzes in water, releasing HCl and forming 4‑ethoxybenzoic acid. It is therefore unsuitable as a buffering component.

Practical guidance

• If an aqueous acylation is intended (Schotten–Baumann conditions), use a biphasic system with controlled base (e.g., Na2CO3/NaOH) to neutralize HCl, but recognize this is a synthetic transformation rather than a buffering application.

Green Alternatives

Greener strategy overview (general guidance)

• While 4‑ethoxybenzoyl chloride is highly effective for acyl transfer, acid chlorides are corrosive and moisture sensitive. Consider greener acylation tactics that reduce hazards, improve atom economy, or use safer solvents.

Potential alternatives and trade‑offs

• In situ activation from 4‑ethoxybenzoic acid with CDI to form the imidazolide (CDI: milder, avoids HCl, byproduct CO2/imidazole; may require longer reaction times).
• Carbodiimide couplings (EDC/HOBt or EDC/DMAP) in green(er) solvents (EtOAc, 2‑MeTHF): Good for amide/ester formation without acid chlorides; watch for urea waste and potential sensitizers.
• Anhydride route (symmetric or mixed anhydrides): Less volatile/corrosive than acid chlorides; can be formed in situ and used for acylation with catalytic DMAP.
• Enzymatic esterifications (lipases) using 4‑ethoxybenzoic acid in organic/solvent‑free systems: High selectivity, mild conditions; limited substrate scope and slower kinetics.

Solvent selection improvements

• Replace DCM with EtOAc, 2‑MeTHF, CPME, or toluene where feasible.
• Use aqueous micellar catalysis for amide formation (surfactants like TPGS‑750‑M) with acid activation strategies—minimizes organic solvent use.

Mini comparison (general)

• Acid chloride: Fast, high reactivity; hazards—HCl release, corrosivity; requires dry conditions.
• CDI/EDC routes: Safer handling; often longer reaction times and additional reagents; easier waste management.

Note: Selection depends on substrate sensitivity, scale, and regulatory requirements; validate greener alternatives on small scale first.

Pharmaceutical Uses

Formulation/excipient status

• Not used as an excipient. Acid chlorides are generally too reactive/corrosive for formulation roles.

Role in pharmaceutical R&D (general; research use only)

• Intermediate for synthesis: Frequently employed to introduce the 4‑ethoxybenzoyl group into amines and alcohols, generating amide and ester libraries during medicinal chemistry SAR campaigns.
• Pro‑moiety exploration: The para‑ethoxybenzoyl group can modulate lipophilicity and metabolic stability of candidate molecules when incorporated as an amide or ester (conceptual medicinal chemistry use).

Regulatory note

• No pharmacopeial monograph is implied. All uses are limited to laboratory research and process development. No therapeutic or clinical claims are made.

Physical Properties

Item-specific specifications

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

Computed/literature properties (for reference; not item-specific specifications)

• Molecular formula: C9H9ClO2 (literature)
• Molecular weight: ~184.62 g/mol (literature)
• Qualitative solubility: Typical of aroyl chlorides—miscible with many aprotic organic solvents (e.g., dichloromethane, toluene, THF, acetonitrile); reacts with water and lower alcohols to form the corresponding acid or esters (general literature behavior).
• Volatility: Lower volatility than benzoyl chloride due to the para‑ethoxy substituent; nevertheless, vapors may be irritating/lachrymatory (general for acyl chlorides).
• Hydrolytic sensitivity: Hydrolyzes in the presence of moisture to 4‑ethoxybenzoic acid with HCl evolution (general behavior).

Optical/refractive and thermophysical data

• Boiling point, melting point, density, refractive index, logP, pKa: Not specified for this item; consult literature or the CoA/SDS for authoritative values.

Practical notes

• Handle under dry, inert atmosphere to preserve material quality.
• Use anhydrous solvents and glassware; exclude adventitious water to avoid hydrolysis during measurement or handling.

Quality and Grades

Item-specific quality information

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet for assay, related substances, and any stabilizers.

General guidance on quality expectations for acid chlorides

• Typical contaminants: Hydrolysis product (4‑ethoxybenzoic acid), residual solvents, and trace HCl. Moisture content and acid content are commonly monitored to ensure performance in moisture‑sensitive transformations.
• Stabilizers: Some acid chlorides are supplied inhibitor‑free; others may include trace acid or phosgene surrogates from manufacturing. If a stabilizer is present, it will be listed on the CoA—confirm compatibility with planned reactions (e.g., amide couplings, Friedel–Crafts).
• Analytical assurance: Common release tests include identity (IR: strong C=O ~1800 cm−1; 4‑ethoxy aryl ether bands), NMR, GC/HPLC for purity/assay, and hydrolyzable chloride. Karl Fischer moisture may be reported for moisture‑sensitive materials.

Practical notes for users

• If extremely low acid content is critical (e.g., base‑sensitive substrates), consider brief pre‑distillation under dry inert atmosphere where permitted, or convert in situ to a less volatile acylating intermediate.
• Upon opening, record the date and minimize exposure cycles; consider aliquoting under dry argon to preserve grade between uses.

Reaction and Applications

Use domains (general/literature for para‑ethoxy aroyl chlorides)

• Amide synthesis: Efficient acylation of primary/secondary amines to afford 4‑ethoxybenzamides. Bases such as triethylamine (TEA), DIPEA, or pyridine act as HCl scavengers. Low‑temperature addition (0–5 °C) limits over‑acylation and side reactions.
• Ester formation: Reaction with alcohols (ROH) under base (pyridine, DMAP catalysis) yields 4‑ethoxybenzoate esters. Schotten–Baumann conditions allow biphasic aqueous Na2CO3/NaOH with vigorous stirring.
• Anilide and carbamate elaboration: Useful for preparing substituted anilides and carbamates via stepwise acylation of amines or alcohols, leveraging the electron‑donating ethoxy’s effect on aryl electronics.
• Friedel–Crafts acylation: As an acyl donor (RCOCl) in the presence of Lewis acids (e.g., AlCl3), forming aryl ketones. Choice of solvent (DCM, CS2, nitrobenzene, or toluene) and temperature controls regioselectivity and reduce polyacylation.
• Intermediates in pharmaceutical/agrochemical research: Serves as a building block for para‑ethoxybenzoyl‑containing motifs in SAR series, pro‑moieties, and protecting group strategies (context: research use only).

Practical guidance

• Rigorous exclusion of water is essential; pre‑dry substrates and apparatus.
• Add the acid chloride slowly to the nucleophile/base mixture to manage exotherm and suppress HCl‑mediated side reactions.
• For hindered or weak nucleophiles, catalytic DMAP (0.05–0.10 equiv) can accelerate acylation at 0–25 °C in DCM or toluene.
• Monitor by TLC/GC/HPLC; quench with aqueous base at 0–5 °C to control HCl release; anticipate formation of 4‑ethoxybenzoic acid if hydrolysis occurs.

Reaction Conditions

General literature guidance (representative, not item-specific specifications)

• Amide formation
  • Typical setup: Dry DCM, 0–25 °C, 1.0–1.2 equiv 4‑ethoxybenzoyl chloride, 2.0–3.0 equiv base (TEA or DIPEA).
  • Catalyst: Optional 5–10 mol% DMAP for hindered amines at 0–25 °C.
  • Time/yield: 0.5–4 h to completion by TLC/LC; good to excellent isolated yields when water is rigorously excluded.
• Esterification (aliphatic alcohols/phenols)
  • Solvent: DCM, toluene, or pyridine; 0–40 °C.
  • Base/catalyst: Pyridine or 1.1–2.0 equiv base; 2–10 mol% DMAP accelerates phenol acylation.
  • Notes: Slow addition controls exotherm; for phenols, mild heating (30–50 °C) may be beneficial.
• Schotten–Baumann (biphasic)
  • Conditions: Organic phase (DCM or toluene) with substrate; aqueous 5–10% Na2CO3 or NaOH; 0–10 °C initially, then allow to warm; vigorous stirring to disperse HCl.
  • Caveat: Competes with hydrolysis; charge slight excess of acid chloride to compensate.
• Friedel–Crafts acylation
  • Catalyst: AlCl3 (1.1–2.0 equiv) in DCM or nitrobenzene; −10 to 25 °C.
  • Considerations: Control stoichiometry to limit polyacylation; quench carefully into ice/wet ether then aqueous acid.

Monitoring and controls

• Use anhydrous conditions and inert atmosphere. Track by IR (loss of acid chloride band ~1800 cm−1; literature), TLC/LC‑MS. Maintain temperature control to manage HCl evolution and avoid side reactions.

Safety and Handling

Authoritative safety classification

• GHS classification, pictograms, signal word, and H‑statements: Not specified for this item; refer to SDS for definitive hazard information.

General safety guidance for aroyl chlorides (literature/industry practice)

• Hazard profile: Corrosive, moisture‑sensitive acylating agent; contact with moisture liberates HCl. Vapors may be strongly irritating/lachrymatory. Avoid inhalation and skin/eye contact.
• PPE: Use chemical splash goggles, lab coat, and appropriate chemically resistant gloves (e.g., nitrile). Employ a face shield for scale‑up and a fume hood at all times.
• Incompatibilities: Water, alcohols (uncontrolled exothermic acylation), strong bases (rapid reaction), strong oxidizers, amines without temperature control. Avoid contact with metals that can corrode in HCl.
• First aid (overview; follow SDS): Eye/skin exposure—immediate 15+ min water rinse, remove contaminated clothing, seek medical attention. Inhalation—move to fresh air, monitor breathing, obtain medical attention. Ingestion—do not induce vomiting; seek urgent medical care.
• Handling: Use dry, inert atmosphere (argon or nitrogen). Add slowly to nucleophiles with external cooling to manage exotherm. Keep containers tightly closed; minimize headspace humidity.
• Spill/neutralization: Quench small residues cautiously with ice‑cold, dilute aqueous base in a well‑ventilated hood after adsorbing on inert material. Avoid direct water addition to bulk reagent due to vigorous HCl release.

Storage & transport (from Product Data)

• Store at 2–8 °C, argon charged. Shipped on wet ice.

Solvent Selection

Solvent class and polarity (general guidance)

• Suitable media: Dry, aprotic solvents are preferred to suppress hydrolysis and enable controlled acylation—e.g., dichloromethane (DCM), chloroform, toluene, acetonitrile, THF, CPME, 2‑MeTHF, and ethyl acetate (anhydrous). Avoid protic solvents unless intentionally performing alcohol acylation under controlled conditions.

Miscibility and choice considerations (literature/general)

• DCM/CHCl3: Excellent for amide/ester formation with organic bases (TEA, DIPEA); easy temperature control from −78 to 25 °C.
• Toluene: Higher boiling for sluggish acylations or when substrates need elevated temperatures; compatible with Lewis acid catalysis (e.g., AlCl3 for Friedel–Crafts).
• Acetonitrile: Polar aprotic; beneficial for reactions with ionic bases or catalysts; good for monitoring by HPLC.
• THF/2‑MeTHF/CPME: Ether solvents facilitate solubility of organometallic bases and permit low‑temperature control; note peroxide management for ethers (see SDS) and strictly exclude moisture.
• Pyridine/collidine: Serve as both solvent and HCl scavenger for Schotten–Baumann‑type acylations; facilitates in situ acid neutralization but can complicate workup.

Practical tips

• Dry solvents over molecular sieves (3 Å or 4 Å) and verify dryness before use.
• For aqueous biphasic acylations (esters/amides), employ vigorous phase transfer with base (e.g., Na2CO3/NaOH) and control temperature to manage exotherm and HCl evolution.
• Avoid DMSO for acyl chloride handling due to potential side reactions (e.g., formation of acylated sulfoxide species).

Storage and Reconstitution

Storage (from Product Data)

• Store at 2–8 °C, argon charged (inert atmosphere). Shipments are on wet ice.

Handling after receipt

• Allow container to reach room temperature before opening to avoid moisture condensation. Open only in a dry glovebox or under a positive flow of dry inert gas.
• Reseal tightly, back‑fill with argon, and minimize headspace. Consider aliquoting into dry, inert vials to reduce repeated air exposure.

Stability considerations (general)

• Sensitive to moisture; gradual hydrolysis to 4‑ethoxybenzoic acid occurs upon exposure to humid air.
• Avoid protic contaminants and acidic/basic impurities that may catalyze decomposition.

Reconstitution

• Not applicable; supplied neat. If a solution is required, prepare immediately before use in anhydrous solvent (e.g., DCM, toluene, THF, acetonitrile) under inert atmosphere.

Shelf‑life notes

• For item‑specific expiry/retest dates and quality attributes (assay, moisture, inhibitor content), consult the CoA/Spec Sheet.

Use restrictions

• For research use only.

Structure and Identity

Brief description: 4-Ethoxybenzoyl chloride is a para-ethoxy–substituted aroyl chloride, a moisture‑sensitive electrophile commonly used to prepare para‑ethoxybenzamides and esters.

Item-specific identifiers (from Product Data)

• SKU: E131914
• Product Name: 4-Ethoxybenzoyl Chloride
• CAS: 16331-46-7
• PubChem CID: 140059
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Computed/literature structural data (for reference; not item-specific specifications)

• Molecular formula (literature): C9H9ClO2
• Molecular weight (literature): ~184.62 g/mol
• Example SMILES (literature): CCOc1ccc(cc1)C(=O)Cl
• Core functional groups: aroyl chloride (–C(=O)Cl), para‑ethoxy aryl ether (–O–CH2–CH3)
• Structural features (2D description): A benzene ring bearing two para‑disposed substituents: an acyl chloride carbonyl (–C(=O)Cl) and an ethoxy group (–OCH2CH3). The carbonyl carbon is sp2‑hybridized and electrophilic; the ethoxy oxygen donates electron density into the ring (p‑directing, activating).

Notes

• No stereocenters; planar aromatic system with conjugation between the aryl ring and acyl chloride carbonyl.
• Literature identifiers are provided for chemical context; confirm identity against the item’s CoA/SDS prior to use.

Synthetic Utility

Reactivity profile (general)

• Electrophilicity: The acyl chloride carbonyl reacts readily with nucleophiles (amines > alcohols > water). The para‑ethoxy substituent is electron‑donating, which slightly reduces acyl chloride electrophilicity versus unsubstituted benzoyl chloride but does not impede typical acylations.
• Chemoselectivity: Preferential acylation of amines over alcohols in mixed nucleophile systems; DMAP catalysis levels rates for less reactive alcohols/phenols.

Key transformations

• Amide formation: With amines and a base (TEA/DIPEA/pyridine). Useful for constructing 4‑ethoxybenzamide derivatives and peptidic fragments via acyl chloride coupling.
• Esterification: With alcohols/phenols under base or DMAP catalysis; enables protecting group strategies or pro‑ester synthesis.
• Friedel–Crafts acylation: Formation of aryl ketones from activated aromatics with AlCl3 or FeCl3.
• Acyl transfer cascades: In presence of nucleophilic catalysts (DMAP/NMI), enables rapid acyl migration and mixed anhydride strategies.

Practical tactics

• Order of addition: Add the acyl chloride to a cooled solution of nucleophile + base to moderate exotherm and suppress HCl‑promoted side reactions.
• Workup: Quench at 0–5 °C with aqueous bicarbonate/carbonate; extract into organic solvent; wash to remove amine salts/pyridinium species.
• Troubleshooting: For sluggish alcohol acylation, add 5–10 mol% DMAP and warm to 25–40 °C in DCM or toluene; for sensitive amines, keep ≤0 °C initially to prevent over‑acylation.

Target Specificity

Not applicable. This product is a small‑molecule reagent (aromatic acyl chloride) and does not have biological target specificity, antigen reactivity, clone, or isotype. No antibody/protein target information is associated with this item.