4-Phenoxyquinazoline - ≥98% , CAS No.16347-97-0

CAS: 16347-97-0 Cat. No.: P1041009 Formula: C₁₄H₁₀N₂O Peso molecolare: 222.240

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥98%

Nomi e identificatori

• Sorrisi canonici: C1=CC=C(C=C1)OC2=NC=NC3=CC=CC=C32
• IUPAC Name: 4-phenoxyquinazoline
• InChIKey: DCFAIAIIVSJFJE-UHFFFAOYSA-N
• INCHI: 1S/C14H10N2O/c1-2-6-11(7-3-1)17-14-12-8-4-5-9-13(12)15-10-16-14/h1-10H
• Peso molecolare: 222.240

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diarylethers
• Alternative Parents: Quinazolines Phenoxy compounds Phenol ethers Pyrimidines and pyrimidine derivatives Heteroaromatic compounds Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Diaryl ether - Diazanaphthalene - Quinazoline - Phenoxy compound - Phenol ether - Monocyclic benzene moiety - Pyrimidine - Benzenoid - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Hydrocarbon derivative - Organonitrogen compound - Organopnictogen compound - Organic nitrogen compound - Aromatic heteropolycyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
• 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

• Peso molecolare: 222.240 g/mol
• XLogP3: 3.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 222.079 Da
• Monoisotopic Mass: 222.079 Da
• Topological Polar Surface Area: 35.000 Ų
• Heavy Atom Count: 17
• Formal Charge: 0
• Complexity: 240.000
• 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 biological application protocols (e.g., WB, IHC, IF, FC) or analytical methods are provided in the Product Data.

General guidance for handling in research workflows:

• Stock preparation: Prepare DMSO stocks at 10–50 mM; filter through 0.22 µm PTFE if particulate is observed.
• Assay dosing: Add to aqueous assay buffers via serial dilution to avoid precipitation; keep final DMSO ≤1–2% v/v unless assay-tolerant.
• Analytical QC: Verify identity and purity by LC–MS and 1H/13C NMR where appropriate before use in critical experiments.

For any validated method or detailed SOP, please consult your internal protocols or contact Aladdin Scientific for additional documentation if available.

Biological Roles

No item-specific biological data are provided. The following notes are general and for research context only (no medical or clinical claims):

• Quinazoline frameworks are frequent in chemical biology as π-rich, hydrogen-bond-accepting scaffolds. The two ring nitrogens can engage in electrostatic and π–stacking interactions in protein pockets (general literature observation).
• The 4-phenoxy substituent modulates the electron density of the quinazoline ring and can influence lipophilicity, membrane permeability, and binding mode in target-agnostic probe development (research use only). Phenoxy groups often act as shape/complementarity elements rather than H-bond donors.
• UV-active chromophore: Useful for tracking by HPLC/UV in biochemical sample handling and for estimating compound recovery across fractionation steps.

If a defined biochemical role, target, or binding profile is required for your application, please consult primary literature or generate assay-specific data; none are specified for this catalog item.

Buffer Applications

This compound is a neutral, sparingly water-soluble heteroaromatic and is not typically used as a buffering agent. It lacks the acid/base conjugate pair behavior and high water solubility required for practical buffer systems.

Practical notes:

• For preparing aqueous assay solutions, dissolve first in a water-miscible organic co-solvent (e.g., DMSO) and then perform staged dilutions into the desired biological buffer (e.g., PBS, HEPES), ensuring final organic content remains compatible with the assay.
• If pH-dependent solubility modulation is desired, limited protonation of ring nitrogens under strong acidic conditions may increase solubility, but this is application-specific and should be validated experimentally.

Green Alternatives

Process and discovery chemists can often replace traditional solvents or reagents around this scaffold with greener choices without sacrificing performance.

Greener solvent options (general guidance):

• Replace chlorinated solvents (DCM, chloroform) with ethyl acetate, 2-MeTHF, CPME, or toluene where solubility allows.
• For high-boiling polar aprotics (DMF, NMP), consider alternatives such as dimethyl carbonate (for extractions), propylene carbonate (for some substitutions), or Cyrene (dihydrolevoglucosenone) for suitable base-mediated reactions. Always assess stability of the aryl–O–aryl ether and quinazoline nitrogens in these media.

Illustrative comparison (general; optimize case-by-case):

• DMF vs 2-MeTHF/EtOAc
  • Pros (green): lower toxicity/biopersistence, easier workup, better environmental profile.
  • Trade-offs: reduced solvency for highly aromatic heterocycles; may require higher temperature or co-solvent DMSO spike (1–5%).
• DCM vs CPME
  • Pros (green): CPME has lower peroxide formation than ethers like THF, better safety profile, and broad utility in extractions and reactions.
  • Trade-offs: Higher boiling point and different polarity; evaporation time increases.

Waste minimization:

• Concentrate libraries via high-solubility DMSO stocks to reduce solvent volumes.
• Favor telescoped sequences and crystallization-based purifications (EtOAc/hexane) over silica-intensive chromatography when feasible.

Pharmaceutical Uses

No item-specific pharmacopeial status, excipient role, or formulation grade information is provided for this product. The compound is offered for research use only.

General R&D formulation context (non-clinical):

• As a hydrophobic, UV-active heteroaromatic, 4-phenoxyquinazoline can be formulated into discovery screening libraries using DMSO stock solutions (commonly 10–50 mM) and dispensed into assay plates with appropriate controls for solvent percentage.
• For preformulation research, solubility enhancement strategies may include co-solvents (DMSO, PEG 400), surfactants (Tween 80, Pluronic), or solid-state approaches (amorphous dispersions) strictly within non-clinical research.

No medical or clinical claims are made or implied. For any use beyond research, appropriate regulatory and quality pathways would be required and are outside the scope of this listing.

Physical Properties

Item-specific properties (specifications) not provided in Product Data:

• Melting point, boiling point, density, refractive index, water content, metals, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties for context (not product specifications):

• Molecular formula: C14H10N2O (literature)
• Molecular weight: ~222.24 g/mol (literature)
• Physical state: typically a crystalline solid for analogous 4-aryloxyquinazolines (literature trend); exact appearance for this item is not specified.
• Solubility profile (qualitative, literature):
  • Sparingly soluble in water due to extended aromaticity and lack of ionizable groups under neutral conditions.
  • Soluble in common organic solvents such as DMSO, DMF, NMP, chlorinated solvents, and moderately soluble in ethyl acetate and acetonitrile; solubility in alcohols varies with temperature.
• Ionization: The quinazoline nitrogens are weakly basic; protonation under strong acid is possible, but no practical pKa values are provided here.
• UV–vis: Quinazoline chromophores typically show π–π* absorptions in the near-UV (literature), useful for monitoring by HPLC/UV; specific λmax for this compound is not provided.

Practical notes (general): For weighing and solution prep, use dry glassware and anhydrous solvents when moisture-sensitive transformations follow. Verify solubility empirically at intended concentration and temperature.

Quality and Grades

• Item-specific grade/purity, appearance, stabilizers, metal content, and chromatographic suitability: Not specified for this item; refer to CoA/Spec Sheet.

General guidance on quality considerations for heteroaromatic building blocks:

• Purity context: For use in synthesis (e.g., C–N/C–O couplings or late-stage diversification), a high assay by HPLC/GC and low inorganic/metal content help minimize side reactions and catalyst poisoning. If used in discovery workflows, LC–MS purity trace is often preferred.
• Residual solvents/water: Karl Fischer water and residual solvent limits may be relevant for moisture-sensitive reactions; verify in the CoA when planning moisture-intolerant steps (e.g., strong base-mediated SNAr).
• Particle size/appearance: Impacts dissolution and filtration; finely crystalline solids dissolve more readily but can dust more easily. If appearance is critical (e.g., for formulation screening), confirm with the batch CoA.
• Documentation: Request batch-specific CoA including assay method, impurity profile, and, where applicable, NMR/LC–MS traces for structure confirmation.

If a chromatography-grade or screening-grade variant is required (e.g., low UV background for analytical work), contact Aladdin Scientific for availability and specifications.

Reaction and Applications

As a 4-aryloxy-substituted quinazoline, this compound functions primarily as a heteroaromatic scaffold and as a reference/control in SAR programs involving quinazoline cores.

Representative applications (general literature context):

• Scaffold in heteroaromatic libraries: The 4-phenoxy group modulates electronics of the quinazoline ring (deactivating at C4, tuning basicity at N1/N3), useful for probing binding in discovery chemistry (research use only).
• Cross-coupling diversification: Remaining positions on the quinazoline ring (e.g., halogenated derivatives) can undergo C–N, C–C, or C–O couplings (Buchwald–Hartwig, Suzuki–Miyaura) to generate analogs. 4-Phenoxyquinazoline can serve as a starting point or reference for such series.
• Electrophilic/nucleophilic aromatic substitution: While the 4-position is blocked by phenoxy, other activated positions can participate in EAS (nitration, sulfonylation) or, when suitably substituted, SNAr.
• O-aryl ether stability studies: The aryl–O–aryl linkage provides a platform to examine ether cleavage or stability under acidic/basic/transition-metal conditions.

Practical tips:

• Analytical monitoring: Strong UV chromophore facilitates HPLC/UV methods.
• Protection/compatibility: Phenoxy ether is generally robust to mild base and many catalysts but may cleave under strong nucleophilic or Lewis-acidic conditions; test conditions on small scale.
• Solubility management: Use polar aprotic solvents (DMSO/DMF) for high-concentration stock solutions; filter through PTFE to remove particulates before dosing into reactions or assays.

Reaction Conditions

The following are general, literature-style conditions relevant to the synthesis and modification of 4-aryloxyquinazoline scaffolds; they are provided as guidance and are not product specifications.

• SNAr formation of 4-aryloxyquinazolines

  • Typical approach: 4-chloroquinazoline + phenol (1.1–1.5 eq) + base (K2CO3, Cs2CO3, or NaH)
  • Solvent: DMF, DMSO, NMP, or dioxane
  • Temperature: 60–120 °C depending on base/solvent
  • Time: 2–16 h; monitor by TLC/HPLC
  • Workup: Aqueous quench, extraction (EtOAc), and crystallization or column purification

• Pd-catalyzed C–O coupling (alternative to SNAr)

  • Aryl halide (4-haloquinazoline) + phenol, Pd2(dba)3 or Pd(OAc)2 (1–5 mol%), bulky phosphine ligand (e.g., XPhos), base (K3PO4)
  • Solvent: toluene, dioxane, or CPME; 80–110 °C
  • Pros: Broader scope with deactivated partners; milder bases

• Downstream functionalization of the quinazoline core

  • Electrophilic halogenation: NBS/NCS under controlled conditions to install handles for cross-coupling.
  • N-oxidation: mCPBA to form N-oxide, enabling regioselective subsequent substitution, then reduction back (e.g., PCl3) after functionalization.

Yields are substrate- and condition-dependent; representative literature reports for forming 4-aryloxyquinazolines often range from moderate to high isolated yields after optimization. Always confirm compatibility of the aryl–O–aryl ether under the chosen conditions.

Safety and Handling

Item-specific hazard statements, pictograms, or GHS classification are not provided in the Product Data. Always consult the product’s SDS for authoritative information.

General laboratory safety guidance for aromatic heteroaromatics/aryl ethers:

• Likely hazards (general): May cause irritation to skin, eyes, or respiratory tract if dust is generated. Dust management and good hygiene practices are recommended.
• Personal protective equipment (PPE):
  • Safety glasses or chemical splash goggles; lab coat; appropriate chemically resistant gloves (e.g., nitrile). Use a dust mask or work in a fume hood to avoid inhalation of particulates and solvent vapors during handling and dissolution.
• Handling: Avoid generating dust. Use in a well-ventilated area or fume hood. Prevent contact with strong oxidizers and strong acids/bases unless intended for reaction.
• Storage incompatibilities (general): Keep away from strong oxidizing agents. Strong acids can protonate the diazine nitrogens; strong bases can induce nucleophilic attack at activated positions—store accordingly.
• First aid overview (general):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with plenty of water for at least 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Note: This product is for research use only. Defer to the SDS and institutional protocols for spill response, waste disposal, and fire-fighting measures.

Solvent Selection

4-Phenoxyquinazoline is a neutral, π-rich heteroaromatic with limited aqueous solubility and good solubility in polar aprotic organics.

• Polarity/miscibility (general literature trends):

  • Highly soluble: DMSO, DMF, NMP.
  • Good solubility: dichloromethane, chloroform, THF, acetonitrile, ethyl acetate.
  • Variable: alcohols (MeOH, EtOH; improve with warming or sonication).
  • Poor: water and very nonpolar alkanes (hexanes).

• Selection guidance by task:

  • Stock solutions for screening/biology interfaces: DMSO is typically preferred due to high solvency and compatibility with assay dilution (avoid precipitation upon aqueous dilution by pre-warming/serial dilution).
  • Synthetic transformations (e.g., SNAr, Buchwald–Hartwig/Chan–Lam variants for analog generation): DMF, DMSO, NMP, dioxane, or toluene with phase-transfer or base; chlorinated solvents for electrophilic substitutions or purification.
  • Crystallization/recrystallization: Ethyl acetate/hexane or toluene/EtOAc mixtures are common starting points; adjust polarity empirically.

• Comparison note:

  • Versus more polar heteroaromatics, 4-phenoxyquinazoline requires less polar protic co-solvent but benefits from polar aprotics for high concentration stocks.
  • If greener choices are desired, consider 2-MeTHF or CPME instead of THF/DCM, balancing solubility and process safety.

Storage and Reconstitution

• Storage (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 heteroaromatic solids:

• Keep container tightly closed in a dry, well-ventilated place. Protect from prolonged light exposure if long-term storage is anticipated.
• For extended storage, consider desiccation with a drying agent to prevent moisture uptake that may affect weighability or reactivity in moisture-sensitive steps.

Reconstitution/preparation notes (general):

• For stock solutions, dissolve in anhydrous DMSO, DMF, or another suitable organic solvent. Typical discovery stocks: 10–50 mM in DMSO.
• Filter sterilization (0.22 µm PTFE) may be used for biological assay stocks if required by protocol.
• Avoid repeated freeze–thaw of DMSO stocks; aliquot into single-use vials and store according to the solvent’s stability recommendations (e.g., 2–8 °C for DMSO stocks if desired). Verify solution clarity and absence of precipitate before use.

Research Use Note: For research use only.

Structure and Identity

4-Phenoxyquinazoline is a fused diaza-aromatic (quinazoline) bearing a phenoxy substituent at the C4 position, giving a rigid, planar, π-rich scaffold with two ring nitrogens (N1, N3) and an aryl–O–aryl ether linkage.

• Item-specific identifiers (from Product Data)

  • CAS: 16347-97-0
  • InChIKey: 59676 (as provided)
  • SKU: P1041009

• Literature/computed identifiers and descriptors (general reference; not item specifications)

  • Molecular formula (literature): C14H10N2O
  • Molecular weight (literature): ~222.24 g/mol
  • Canonical SMILES (literature): O(c1ccccc1)c2ncnc3ccccc23
  • Core features: quinazoline (1,3-diazanaphthalene) ring; phenoxy substituent at C4; no stereocenters; fully aromatic.

• Verbal 2D structure description (general)

  • A bicyclic quinazoline ring (benzannulated pyrimidine) with nitrogens at positions 1 and 3. At C4 (para to N1 and ortho to N3 within the pyrimidine portion), an ether oxygen connects to an unsubstituted phenyl ring (phenoxy). The framework is flat and conjugated, enabling strong UV absorption and π–π interactions.

Note: Any structure depictions and the literature identifiers above are provided for general reference. For item-specific identifiers beyond those listed in Product Data, refer to the Certificate of Analysis (CoA) or specification sheet.

Synthetic Utility

4-Phenoxyquinazoline is a versatile heteroaromatic building block featuring:

• Functional elements

  • Diazine ring (quinazoline) with two ring nitrogens (H-bond acceptors) that influence directing effects and reactivity.
  • Aryl–O–aryl ether at C4 providing a handle for further derivatization (e.g., demethylation/ether manipulation strategies in related systems).

• Typical transformations (literature context)

  • Electrophilic substitution on the benzannulated ring (e.g., nitration, halogenation) under controlled conditions, enabling subsequent cross-couplings.
  • Directed metalation or lithiation at activated positions (with caution due to ring nitrogens), followed by quench with electrophiles.
  • Formation of N-oxides (on ring nitrogens) to modulate reactivity, followed by regioselective functionalization.
  • Cross-coupling on pre-halogenated analogs (Suzuki–Miyaura, Buchwald–Hartwig) to build focused libraries around the quinazoline core using 4-phenoxyquinazoline as a reference scaffold.

• Retrosynthetic value

  • Often accessed via SNAr of 4-chloroquinazoline with phenol under basic conditions or via Pd-catalyzed C–O coupling (Ullmann-type or Buchwald conditions), making the phenoxy group a modular substituent interchangeable with varied phenols.

Practical considerations

• The phenoxy substituent is relatively robust, tolerating many cross-coupling conditions. Avoid strongly nucleophilic cleavage conditions (e.g., molten alkali) if preservation of the ether is required.

Target Specificity

Not applicable for this catalog item. No antibody, enzyme, or biologic target specificity is provided in the Product Data. 4-Phenoxyquinazoline is a small-molecule chemical compound intended for general research and synthetic use.