4-Fluorophenylmagnesium bromide solution - 2.0 M in diethyl ether , CAS No.352-13-6(diethyl ether)

CAS: 352-13-6(diethyl ether) Cat. No.: F432651 Numero EC: 627-087-3

GRADE & PURITY 2.0 M in diethyl ether

Synonyms

p-Fluorophenylmagnesium bromide solution | Bromo(4-fluorophenyl)magnesium solution

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Specifications

Sinonimi

p-Fluorophenylmagnesium bromide solution | Bromo(4-fluorophenyl)magnesium solution

Specifiche e purezza

2.0 M in diethyl ether

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.

Nomi e identificatori

• Sorrisi canonici: C1=CC(=CC=[C-]1)F.[Mg+2].[Br-]
• IUPAC Name: magnesium;fluorobenzene;bromide
• InChIKey: BRKADVNLTRCLOW-UHFFFAOYSA-M
• INCHI: 1S/C6H4F.BrH.Mg/c7-6-4-2-1-3-5-6;;/h2-5H;1H;/q-1;;+2/p-1
• Numero UN: 2924
• Gruppo di imballaggio: I

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Fluorobenzenes
• Alternative Parents: Aryl fluorides Organic metal halides Organic metal bromide salts Organofluorides Organic bromide salts Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Fluorobenzene - Aryl halide - Aryl fluoride - Organic metal halide - Organic metal bromide salt - Hydrocarbon derivative - Organic bromide salt - Organic salt - Organofluoride - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms 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: Heat sensitive；Moisture sensitive
• Peso molecolare: 199.300 g/mol
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 197.933 Da
• Monoisotopic Mass: 197.933 Da
• Topological Polar Surface Area: 0.000 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 133.000
• 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: 3

XLogP3

Riferimenti

1. Chunhui Luo, Bin Zhao, Zhibo Li.  (2012)  Dual stimuli-responsive polymers derived from α-amino acids: Effects of molecular structure, molecular weight and end-group.  POLYMER,      [PMID:] [10.1016/j.polymer.2012.02.032]

Application Protocols

• Not applicable. No immunoassay or bioanalytical application protocols (e.g., WB, IHC, IF, FC) are associated with this chemical reagent.
• For practical use, refer to the Reaction Conditions section for representative synthetic procedures and handling recommendations under inert atmosphere.

Biological Roles

• Not typically applicable. 4-Fluorophenylmagnesium bromide is a reactive organometallic reagent used in chemical synthesis and has no direct biological role under physiological conditions.
• Literature context:
  • Organomagnesium reagents hydrolyze rapidly in aqueous/physiological media to give the corresponding hydrocarbon (C–H) or, after electrophile capture, neutral organic products and Mg(OH)2/Mg salts.
  • Any discussion of metabolism or signaling pertains to downstream, neutral aryl products rather than the organomagnesium species itself.

Buffer Applications

• Not applicable. As a moisture-sensitive organometallic in an ethereal medium, this product is incompatible with aqueous buffers and is not used to prepare or adjust buffer systems.
• For relevant guidance, see the Reaction & Applications and Synthetic Utility sections for its role in anhydrous organic synthesis.

Green Alternatives

• Solvent considerations (literature):
  • Diethyl ether is effective but highly volatile and flammable. Greener ether alternatives like 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) can reduce VOC emissions and improve safety.
• Comparison (literature, general):
  • 2-MeTHF: biomass-derived, higher bp (~80 °C), better phase separation in aqueous workups, forms fewer peroxides vs Et2O; supports many Grignard reactions with comparable or improved yields.
  • CPME: hydrophobic ether with high oxidative stability, wide liquid range; often tolerates moisture better than Et2O, though strictly anhydrous conditions are still required for Grignards.
  • THF: widely used; not bio-based and forms peroxides; higher bp increases energy for solvent removal.
• Trade-offs:
  • Higher boiling ethers (2-MeTHF/CPME) may complicate solvent removal and can alter selectivity/aggregation states.
  • Catalyst compatibility in cross-couplings may differ; small-scale screening is recommended when switching solvents.
• Implementation tips:
  • When moving from Et2O to greener ethers, re-titrate the reagent and re-optimize temperature and addition rates.
  • Verify material compatibility (seals, tubing) and ensure appropriate drying/purification of the alternative solvent.

Pharmaceutical Uses

• No excipient or formulation role. This reagent is intended for synthetic steps in research and process development, not for direct inclusion in dosage forms.
• Literature/process context (no therapeutic claims):
  • Aryl Grignard reagents are commonly used to introduce para-fluorophenyl motifs into intermediates for APIs and agrochemicals via carbon–carbon bond formation (e.g., addition to carbonyls or acylation to give aryl ketones).
  • For GMP or pharmacopeial compliance, specifications (assay, residual solvents, metals) must be defined at the intermediate or API stage; this catalog item provides no such pharmacopeial designation. Verify all critical quality attributes via internal specifications.

Physical Properties

• Item-specific specs: Not specified for this item; refer to CoA/Spec Sheet.
• Literature (solution context):
  • Physical state: Ethereal solution of an arylmagnesium bromide; typically colorless to pale yellow, moisture sensitive.
  • Solubility/reactivity: Reactive with water/alcohols/CO2; not stable in protic or strongly electrophilic media. Compatible with coordinating ethers (diethyl ether, THF).
  • Concentration: Common commercial concentrations for Grignard solutions are 0.5–2.0 M (literature, not item-specific). Actual concentration for this SKU is not specified; refer to CoA/Spec Sheet.
• Solvent (diethyl ether) properties for planning purposes (literature):
  • Boiling point (Et2O): ~34.6 °C
  • Density (Et2O, 20 °C): ~0.713 g/mL
  • Dielectric constant (Et2O, 20 °C): ~4.3
  • Refractive index nD20 (Et2O): ~1.352
  • Peroxide formation: Ethers can form peroxides on storage; test before concentration/evaporation (literature caution).
• Notes:
  • Exact assay, water content, residual metals, stabilizers, and UV cutoffs: Not specified for this item; refer to CoA/Spec Sheet.
  • Measured pKa/logP are not applicable to reactive organometallic solutions; the reagent is consumed upon contact with water.

Quality and Grades

• Item-specific grade/purity, stabilizer, and assay: Not specified for this item; refer to CoA/Spec Sheet.
• General expectations for Grignard solutions (literature/practice):
  • Concentration is typically reported in molarity with an assay tolerance (e.g., ±0.05–0.1 M) based on titration.
  • Trace water and inhibitors (if any) are usually controlled to maintain reactivity; diethyl ether may be stabilized against peroxides at manufacture, but stabilizer presence varies by supplier. If low-ppm inhibitor content matters for your application, verify on the CoA.
  • Metals and halides: Background MgX2 from Schlenk equilibria is common; this can influence selectivity in acylations and cross-couplings.
• Practical guidance:
  • Verify active base by titration before sensitive transformations.
  • If low-UV background is needed (e.g., for online monitoring), confirm solvent grade (HPLC/GC grade) on the CoA.
  • For air/moisture critical work, consider transferring via cannula or positive-pressure air-free techniques to minimize assay drift.

Reaction and Applications

• Typical transformations with 4-fluorophenylmagnesium bromide (literature):
  • Nucleophilic addition to carbonyls (aldehydes/ketones) to form secondary/tertiary alcohols bearing a para-fluorophenyl group.
  • Acylation with acid chlorides/anhydrides to afford aryl ketones; use conditions that minimize over-addition to tertiary alcohols (e.g., low temperature, copper salts, or inverse addition).
  • Electrophilic substitution with CO2 to furnish 4-fluorobenzoic acid derivatives (carboxylation).
  • Transmetalation to Ni/Pd for Kumada cross-coupling with aryl/vinyl halides to construct biaryl or aryl–vinyl bonds.
  • Reaction with epoxides (regioselective ring opening at the less substituted carbon) to yield p-fluorophenethyl alcohols.
• Mechanistic notes:
  • Reactivity reflects a polarized C(sp2)–Mg bond; coordination of ether enhances nucleophilicity.
  • Schlenk equilibria and MgX2 content can influence chemoselectivity; additives (LiCl) may modulate aggregation/reactivity in cross-couplings.
• Practical tips:
  • Ensure rigorously anhydrous conditions; dry glassware and inert atmosphere are essential.
  • Titrate active base (e.g., with diphenylacetic acid/1,10-phenanthroline in the Gilman double titration) before use.
  • For sensitive electrophiles, perform inverse addition (add Grignard to electrophile) at low temperature to control exotherm and selectivity.
  • Quench cautiously with cold, dilute NH4Cl or saturated NH4Cl/ice under inert gas; allow controlled warming.

Reaction Conditions

• General guidance (literature; adjust to substrate and confirm by experimentation):
  • Preparation/handling: Use oven-dried glassware; maintain argon blanket. Cool reactions (−78 to 0 °C) for sensitive electrophiles; 0 to room temperature for robust substrates.
  • Stoichiometry: 1.05–1.5 equiv for carbonyl additions; 1.1–2.0 equiv for acylations/carboxylation depending on substrate and desired selectivity.
  • Solvents: Supplied in diethyl ether; reactions are commonly run in Et2O, THF, or mixtures. For cross-coupling, THF/Et2O/toluene are typical.
  • Additions to carbonyls: Add reagent slowly to a cooled solution of electrophile (inverse addition) to manage exotherm; allow controlled warm-up after addition. Work up with cold, saturated NH4Cl.
  • Acylations: For ketone formation from acid chlorides, maintain −78 to −20 °C and add cuprous salts (e.g., CuI, catalytic) if over-addition is an issue.
  • Epoxide opening: 0 °C to room temp in ether or THF; quench after complete consumption by TLC/GC.
  • Carboxylation: Bubble dry CO2 at −78 to 0 °C; then warm and quench to isolate the acid after acidic workup.
  • Kumada cross-coupling: Ni or Pd catalysts (e.g., NiCl2(dppp), Pd(dppf)Cl2); 0–60 °C; anhydrous Et2O/THF; inert atmosphere. Typical times 0.5–6 h; yields substrate-dependent.
• Assay control:
  • Determine active concentration by titration (e.g., Gilman) prior to use; correct stoichiometry accordingly.
• Safety:
  • Control exotherms; ensure efficient stirring and cooling; have quench protocols and Class B fire control measures at hand.

Safety and Handling

• Item-specific hazard classification (GHS, signal word, pictograms, H-statements): Not specified for this item; consult the product SDS for authoritative information.
• General hazards (literature, Grignard in diethyl ether):
  • Highly flammable solvent (diethyl ether; low flash point, forms explosive vapors and peroxides).
  • Moisture sensitive; reacts violently with water, alcohols, acids, and CO2 with heat and flammable gas evolution.
  • Can cause severe skin/eye irritation and chemical burns due to strong basicity/nucleophilicity.
• PPE and engineering controls (good laboratory practice):
  • Use in a fume hood under inert atmosphere (argon) with air-free techniques.
  • Wear chemical-resistant gloves (e.g., nitrile; consider laminated gloves for extended contact), splash goggles/face shield, lab coat.
  • Keep away from ignition sources; use grounded metal canisters when handling larger volumes of ether.
• Handling tips:
  • Maintain argon blanket; use oven-dried glassware, dry needles/syringes or cannula.
  • Titrate active base (e.g., Gilman double titration) before critical use.
  • Never add water to the reagent. For quench: add reagent slowly into cold, well-stirred, dilute aqueous ammonium chloride or saturated NH4Cl/ice under inert gas.
  • Test ether for peroxides before concentrating; discard if peroxide-positive per institutional guidance.
• Incompatibilities: Air, moisture, oxidizers, protic solvents, CO2 (including carbonate-based drying tubes), halogenated solvents during handling.
• First aid (overview; defer to SDS):
  • Skin/eye contact: Immediate copious water rinse for ≥15 min; remove contaminated clothing; seek medical attention.
  • Inhalation: Move to fresh air; oxygen/supportive care as needed; seek medical attention.
  • Ingestion: Do not induce vomiting; rinse mouth; seek medical attention immediately.

Solvent Selection

• Item context: Supplied in diethyl ether.
• Polarity and coordination (literature):
  • Diethyl ether (Et2O): weakly polar, coordinating donor solvent; dielectric constant ~4.3; promotes formation and stability of Grignard reagents while moderating aggregation.
  • THF: more polar/stronger donor (ε ~7.6) that can enhance reactivity but may increase side reactions (e.g., β-hydride transfers with certain substrates).
• Miscibility profile:
  • Et2O is miscible with many organic solvents (pentane, toluene, THF) but immiscible with water; it extracts into organic phase during aqueous workups.
• Choosing the medium (literature guidance):
  • Prefer Et2O for sensitive electrophiles where milder coordination lowers over-addition or minimizes rearrangements.
  • Prefer THF for sluggish substrates or at lower temperatures when higher reactivity is needed.
• Small comparison (literature):
  • Et2O: bp 34.6 °C, low boiling for easy removal; higher flammability; lower solvating power.
  • THF: bp 66 °C, better solvating power; also peroxide-forming; may better solubilize magnesium salts formed during reaction.
• Practical notes:
  • Avoid protic and halogenated solvents during active handling.
  • For cross-couplings (Kumada), Et2O, THF, or mixtures are commonly used; catalyst system may dictate the optimal solvent.

Storage and Reconstitution

• Item-specific (Product Data):
  • Store at 2–8 °C, Argon charged. Shipped on wet ice.
• General guidance for this reagent class (literature/practice):
  • Keep tightly sealed under inert gas; do not store with CO2-containing drying tubes. Use air-free techniques (syringe or cannula transfer). Avoid exposure to moisture and ignition sources.
  • Do not freeze to concentrate; diethyl ether is low-boiling and will evaporate readily—maintain cap integrity to prevent concentration drift.
  • Inspect before use: solution should be homogeneous; absence of heavy precipitate is preferred. If solids are present, gentle mixing may re-dissolve Mg salts; if not, re-titrate active base.
  • No reconstitution required; supplied as a ready-to-use solution. If dilution is needed, use anhydrous, oxygen-free ether (Et2O or THF) and maintain inert atmosphere.
  • Shelf life/assay: Activity can change over time due to slow decomposition or solvent loss; verify concentration by titration prior to critical reactions.
  • Disposal/quench: Destroy excess carefully by slow addition to cold, stirred, dilute ammonium chloride solution under inert atmosphere. Collect organic/aqueous wastes separately per institutional and regulatory requirements.

Structure and Identity

• Item-specific (Product Data):
  • Product name: 4-Fluorophenylmagnesium bromide solution (in diethyl ether)
  • CAS: 352-13-6 (diethyl ether solution)
  • Storage: Store at 2–8 °C, Argon charged; shipped on wet ice
  • Research use: For research use only
  • InChIKey (as provided): 32370 (note: not a standard InChIKey string)
• Literature/Computed (general identity for the organomagnesium species):
  • Common formula (anhydrous reagent): C6H4FMgBr (para-fluoroarylmagnesium bromide)
  • Approx. molecular weight (C6H4FMgBr): ~199.30 g/mol (literature)
  • Synonyms: p-Fluorophenylmagnesium bromide; 1-bromo-magnesium-4-fluorobenzene; p-F–Ph–MgBr
  • Structural features: An arylmagnesium bromide (Grignard reagent) derived from 4-fluorobromobenzene; the magnesium is bonded to the ipso carbon of a para-fluorinated phenyl ring with a counter bromide.
  • 2D description: Benzene ring bearing a para-fluoro substituent; the ipso carbon bears a polar covalent C–Mg bond (carbanion character), with Br− coordinated to Mg2+.
  • SMILES/InChI: These are not uniquely standardized for Grignard reagents due to ionic/aggregate structures; refer to supplier SDS/CoA for a specific line notation if required.
• Notes on structure: In ethereal solution, Grignard reagents often exist as solvent-separated ion pairs or Schlenk equilibria (RMgX ⇌ R2Mg + MgX2), and aggregation state depends on solvent and concentration (literature).

Synthetic Utility

• Functional group and retrosynthetic value (literature):
  • Provides a nucleophilic para-fluorophenyl synthon for C–C bond construction. Strategic for late-stage installation of a p-F–aryl moiety to tune lipophilicity and metabolic stability in discovery chemistry.
• Key transformations:
  • Carbonyl additions: to aldehydes/ketones forming secondary/tertiary alcohols (p-F–aryl carbinols).
  • Acylations: reaction with acid chlorides to give p-fluoroaryl ketones; control chemoselectivity to suppress over-addition.
  • Carboxylation: CO2 capture furnishing 4-fluorobenzoic acid derivatives.
  • Epoxide openings: affords p-fluorophenethyl alcohols with predictable regiochemistry.
  • Cross-coupling precursor: serves as transmetalating partner in Kumada couplings to assemble biaryls/aryl–vinyl architectures.
• Chemoselectivity notes:
  • Competes as a strong base; may deprotonate acidic C–H (α to carbonyls, heteroaryl N–H, phenols) before nucleophilic addition.
  • Halogen–magnesium exchange with aryl iodides/bromides can occur; consider temperature and halide order for directed metalation strategies.
• Practical value:
  • Complementary to lithium reagents: generally milder, better functional-group tolerance with optimized conditions; compatible with Cu/Ni/Pd catalysis.

Target Specificity

• Not applicable. This product is a small-molecule organometallic reagent and does not have antigen/epitope targets, species reactivity, clones, or isotypes.