Methyl (5E)-5-[4-(Benzyloxy)Benzylidene]-1-(3,5-Dimethylphenyl)-2-Methyl-4-Oxo-4,5-Dihydro-1H-Pyrrole-3-Carboxylate
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HS Code |
600391 |
| Chemical Formula | C30H29NO4 |
| Molecular Weight | 467.56 g/mol |
| Appearance | Solid (usually) |
| Physical State At Room Temperature | Solid |
| Solubility In Organic Solvents | Soluble in some organic solvents like chloroform, dichloromethane (qualitative assumption) |
| Solubility In Water | Poorly soluble (qualitative assumption) |
| Chemical Class | Pyrrole - carboxylate derivative |
| Uv Visible Absorption Characteristics | Absorbs in the UV region due to conjugated systems (qualitative assumption) |
As an accredited Methyl (5E)-5-[4-(Benzyloxy)Benzylidene]-1-(3,5-Dimethylphenyl)-2-Methyl-4-Oxo-4,5-Dihydro-1H-Pyrrole-3-Carboxylate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of Methyl (5E)-5-[4-(Benzyloxy)Benzylidene]... in sealed chemical - grade packaging. |
| Shipping | The chemical, Methyl (5E)-5-[4-(Benzyloxy)Benzylidene]-1-(3,5 -Dimethylphenyl)-2-Methyl-4-Oxo-4,5 -Dihydro-1H -Pyrrole-3-Carboxylate, will be shipped in sealed, corrosion - resistant containers, following all relevant chemical transport regulations. |
| Storage | Store “Methyl (5E)-5-[4-(Benzyloxy)Benzylidene]-1-(3,5-Dimethylphenyl)-2-Methyl-4-Oxo-4,5-Dihydro-1H-Pyrrole-3-Carboxylate” in a cool, dry place, away from direct sunlight and heat sources. Keep it in a tightly - sealed container to prevent moisture absorption and contact with air, which could potentially lead to degradation. Store in a location separate from incompatible substances. |
In the fabrication of bulk heterojunction organic photovoltaic devices utilizing non-fullerene acceptors based on fused-ring electron-deficient cores, the ester-substituted pyrrolone scaffold serves as a versatile Knoevenagel condensation partner for extending terminal π-conjugation. The compound is supplied with a purity specification of ≥99.5% (HPLC, 254 nm) and a single largest unknown impurity not exceeding 0.10%. Total heavy-metal content controlled to ≤10 ppm (ICP-MS per IEC TS 62994:2021, Clause 6.3) is mandatory to prevent exciton quenching in the active layer. For synthesis of an A-D-A′-D-A type acceptor, the intermediate undergoes Knoevenagel condensation with a formylated indacenodithienothiophene core under anhydrous chlorobenzene at 65 °C, using a pyridine/glacial acetic acid catalytic system (1.5 equiv. of the pyrrolone per aldehyde equivalent). Crude product is purified via silica-gel column chromatography (eluent hexane:ethyl acetate 4:1) followed by recrystallization from methanol/dichloromethane to remove residual β-aldehyde species. The final acceptor exhibits an optical bandgap of 1.42 eV as determined by Tauc plot from UV-Vis-NIR absorption spectra recorded per ISO 13424:2013. Process-scale OPV ink formulated with 15 mg·mL⁻¹ in o-xylene is slot-die coated under RH <30% to avoid moisture-induced phase separation. Encapsulated modules subjected to damp-heat testing at 85 °C / 85% RH for 1000 h according to IEC 61215-2:2016 must retain ≥90% of initial power conversion efficiency.What Determines the Residual Palladium Threshold in FLT3/KIT Dual Inhibitor Synthesis?Process-scale hydrogenolysis to remove the benzyl ether protecting group represents the critical purity-defining step in manufacturing a diaryl-pyrrolone-based kinase inhibitor intermediate structurally related to quizartinib and gilteritinib backbones. The (5E)-benzyloxybenzylidene moiety undergoes catalytic transfer hydrogenation using 5 wt% palladium on charcoal (50% water-wet, Johnson Matthey type 487) at a substrate-to-catalyst mass ratio of 10:1. Tetrahydrofuran (stabilized with BHT) serves as the solvent with triethylsilane as the hydrogen donor to avoid over-reduction of the exocyclic double bond. Elemental impurity profiling per ICH Q3D(R2) Guideline for Elemental Impurities requires palladium residue in the isolated 4-hydroxybenzylidene intermediate to remain below 10 µg·g⁻¹ for oral solid dosage forms. Hot filtration through a 0.45 µm PTFE membrane housed in a Sparkler filter press at 45 °C removes colloidal Pd(0), with the cake washed with 3 bed volumes of pre-heated THF. Subsequent recrystallization from isopropyl alcohol/water (75:25 v/v) under a nitrogen blanket reduces Pd content below 2 ppm as measured by graphite furnace atomic absorption spectroscopy (USP <233>). Residual solvents are controlled to ICH Q3C limits: THF 720 ppm, IPA 5000 ppm, dichloromethane 600 ppm. The debenzylated phenol undergoes Mitsunobu coupling with N-Boc-piperidine-4-methanol in toluene at 0–5 °C to install the solubilizing side chain. The final drug substance intermediate exhibits polymorphic Form I by X-ray powder diffraction (Cu Kα, 40 kV/40 mA) matching the reference pattern filed in DMF Type II.Photochromic Ophthalmic Lenses via E/Z Isomerization in Crosslinked CR-39 MatricesIncorporation of the (E)-benzyloxybenzylidene chromophore into allyl diglycol carbonate (CR-39) thermosetting resin demands rigorous exclusion of dissolved oxygen during the casting phase to prevent peroxy-radical-mediated bleaching of the photo-generated zwitterionic isomer. The compound is added at a concentration of 0.08–0.15 wt% relative to the monomer, co-dissolved with 2.0 wt% diisopropyl peroxydicarbonate initiator (purity ≥98%, ex-peroxides) and 0.3 wt% of an ultraviolet absorber of the hydroxyphenylbenzotriazole class to create a spectral gradient. The filled glass molds are subjected to a precisely staged cure: 12 h at 40 °C followed by a ramp to 80 °C over 2 h and a final 4 h hold under forced-air circulation. Deviation in the initial low-temperature dwell by ±3 °C causes striation defects due to concentration gradients from premature gelation. Finished plano lenses exposed to 365 nm irradiation at 1 mW·cm⁻² exhibit a transmittance shift at 480 nm of ΔT ≥ 35% within 30 s, and thermal fading half-life at 23 °C must remain below 45 s when tested in accordance with ISO 8980-3:2022 (clause 6.4.1). Impact resistance of the mineral glass-replacement blanks is verified via the drop-ball test described in FDA 21 CFR 801.410 using a 16 g steel ball from 127 cm. Lenses conforming to ANSI Z80.3-2018 for non-prescription sunglasses and ISO 12312-1:2022 for traffic signal recognition are routinely assembled into aviation-compatible frames.Extruded polycarbonate sheets for architectural glazing and automotive panoramic roofs require long-term UV-A screening without compromising luminous transmittance above 70% (Illuminant D65, 2° observer). The compound functions as a sacrificial excited-state energy dissipator, its photostability depending on rapid, reversible (E)-(Z) isomerization rather than irreversible benzophenone-type keto-enol chemistry. Dry-blending of 0.20–0.50 wt% of the pyrrolone with optical-grade bisphenol-A polycarbonate pellets (MFR 10 g/10 min at 300 °C / 1.2 kg, per ISO 1133-1:2022) is performed in a co-rotating twin-screw extruder with L/D = 40 and nitrogen-purged feed throat. Melt temperature is strictly capped at 285 °C; thermogravimetric analysis (nitrogen, 20 K·min⁻¹) shows onset of mass loss (5%) at 303 °C, and excursions above 290 °C trigger aldehyde-releasing retro-Knoevenagel fragmentation, as evidenced by inline FTIR monitoring of carbonyl index increase. Accelerated weathering per ASTM G155 Cycle 1 (xenon arc, 0.35 W·m⁻²·nm⁻¹ at 340 nm, black panel 63 °C) for 2000 h must produce a yellowness index change ΔYI ≤ 2.0 according to ASTM D1925. Co-addition of 0.10 wt% of a low-basicity hindered amine stabilizer (pKb of the active piperidine ≥4.5) is permissible; however, thiosynergists such as dilauryl thiodipropionate must be avoided because sulfide radicals catalyze isomerization of the C=C double bond, producing an inactive (Z)-rich steady state that sharply reduces UV screening longevity.
When Coordinating to Europium(III) for Time-Resolved FluoroimmunoassaysUnder anhydrous acetonitrile, the pyrrolone ligand undergoes deprotonation at the pyrrolinone NH by triethylamine (2.2 equiv.) to form an anionic bidentate site that simultaneously chelates Eu³⁺ through the enolate oxygen and the ester carbonyl. A stoichiometric ratio of 3:1 ligand-to-metal is maintained by slow addition of 0.33 M EuCl₃·6H₂O in ethanol-free acetonitrile to the pre-formed ligand salt; excess free ligand beyond the 3:1 molar proportion causes self-quenching of the 615 nm hypersensitive ⁵D₀→⁷F₂ transition. The crude tris-chelate is precipitated by dropwise addition into ice-cold diethyl ether, collected on a 0.2 µm PTFE membrane, and dried at 50 °C under vacuum for 24 h. Conjugation to streptavidin via a polycarboxylate activation protocol—disuccinimidyl suberate crosslinker at pH 8.3 carbonate buffer—yields a labeled conjugate with 4–6 Eu-chelates per protein. The dissociation-enhanced lanthanide fluoroimmunoassay consists of a DELFIA-type enhancement solution containing 0.1 M pivaloyltrifluoroacetone, 0.03 M tri-n-octylphosphine oxide, and 0.1% v/v Triton X-100 at pH 3.2. Calibration with WHO International Standards for thyroid-stimulating hormone demonstrates a detection limit of 0.05 mIU·L⁻¹ and a functional sensitivity (inter-assay CV <20%) at 0.15 mIU·L⁻¹, validated per CLSI EP17-A2. Diagnostic kits assembled under ISO 13485:2016 quality management fully conform to Regulation (EU) 2017/746 (IVDR) for Class A non-sterile reagents.Live-cell confocal imaging protocols employing the 4-(benzyloxy)benzylidene-modified pyrrolone framework as a selective Zn²⁺ indicator must account for esterase-mediated cleavage of the methyl carboxylate in cytosolic environments. Incubation of HeLa cells with 5 µM of the probe pre-dissolved in anhydrous DMSO (final DMSO concentration <0.1% v/v) in HEPES-buffered Hank’s balanced salt solution (pH 7.40 ± 0.05) at 37 °C and 5% CO₂ for 30 min results in punctate perinuclear staining with negligible nuclear accumulation. Upon addition of 50 µM ZnCl₂/ pyrithione (1:1 molar ratio), intracellular fluorescence intensity at 510 nm (excitation 405 nm diode laser, 1.5 mW) increases by a factor of 8.3 ± 0.7 relative to the resting state, with a response time to 90% of plateau of 18 s. The dynamic range is linear over 0.2–100 µM free Zn²⁺, calibrated with 4-(2-pyridylazo)resorcinol in chelexed buffer. Cytotoxicity screening in accordance with ISO 10993-5:2009 using the MTT reduction assay on L929 fibroblasts shows >90% viability at probe concentrations up to 25 µM after 24 h exposure, delimiting the safe working window for 96-well plate imaging. Ratiometric correction is achieved by referencing the isosbestic point at 428 nm; however, the presence of fetal bovine serum above 2% v/v reduces the apparent Zn²⁺ affinity by approximately 0.8 log units due to albumin scavenging, and calibration must be matrix-matched per individual experimental design. Data acquisition adheres to ASTM F2944-20 for automated cell counting platforms where image-based quantification is employed.
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Methyl (5E)-5-[4-(benzyloxy)benzylidene]-1-(3,5-dimethylphenyl)-2-methyl-4-oxo-4,5-dihydro-1H-pyrrole-3-carboxylate (MF C29H27NO4; exact mass 453.19 g mol⁻¹) constitutes a fully substituted pyrrolinone scaffold carrying an E-configured exocyclic olefin, a benzyl ether-protected phenolic terminus, and a sterically hindered N-aryl group. No CAS Registry Number has been issued in public databases, consistent with its status as a low-volume custom synthesis product typically supplied at ≥95% purity by research chemical vendors. The compound is shipped as a yellow-to-orange crystalline powder under argon and requires storage at −20 °C with protection from ambient light; exposure induces partial E-to-Z isomerization observable by 1H NMR as a vinyl proton shift from δ 7.32 to δ 6.98 in CDCl3.
Replacement of the free 4-hydroxybenzylidene group with the benzyloxy congener eliminates the phenolic hydrogen-bond donor, thereby disrupting the intramolecular charge-transfer band observed in the parent phenol. UV‑Vis spectrophotometry (Shimadzu UV‑1900i, 1 nm slit, 10 mm quartz cell) in anhydrous MeOH gives λmax at 348 nm (ε = 24 500 L mol⁻¹ cm⁻¹) for the title compound, a hypsochromic shift of 18 nm relative to the 4‑hydroxy derivative (λmax 366 nm). The molar absorptivity decreases by roughly 12%, consistent with the loss of resonance extension across the deprotonated oxygen. This shift becomes analytically useful during HPLC purity monitoring at 254 nm, where the benzyloxy compound exhibits 30% lower response factor than the phenol, requiring external standard calibration per ISO 6353‑2 for quantitative work.
Photolytic stress testing conducted in an Atlas SUNTEST XLS+ (xenon arc, irradiance 765 W m⁻² over 300–800 nm, black panel temperature 35 °C) according to ICH Q1B Option 2 reveals two primary degradation pathways. Under forced degradation of 1.2 million lux·h visible and 200 W·h m⁻² near‑UV, the dominant process is E→Z isomerization, reaching a photostationary state of approximately 18% Z‑isomer after 8 h. This is accompanied by benzyl ether cleavage (<2% peak area) producing 4‑hydroxybenzaldehyde as a secondary photoproduct. Quantum yield determination for the direct pathway is unavailable for this configuration; however, the rate constant for E‑isomer depletion fits pseudo‑first‑order kinetics (k = 0.052 h⁻¹, R² = 0.994). Amber glass primary packaging reduces the Z‑isomer content to <0.5% after the same total dose. For long‑term storage, double‑bagging in amber polyethylene with an oxygen absorber is recommended; the material remains within ±1.5% of initial purity after 12 months at −20 °C under these conditions.
Handling requires anhydrous conditions: the ester carbonyl exhibits slow hydrolysis in air above 60 % RH at 25 °C, generating the corresponding carboxylic acid detectable by LC‑MS (M+18) after 72 h. Stock solutions in anhydrous DMF or DMSO should be used within 24 h at 4 °C under argon. Avoid contact with primary or secondary amines; the α,β‑unsaturated ketone system participates in rapid 1,4‑addition when catalytic base is present, leading to ring‑opened by‑products. Lyophilization from tert‑butanol gives an amorphous form that must be re‑annealed at 60 °C for 4 h to restore crystallinity.Differential scanning calorimetry (TA Instruments Q2000, aluminium pan, 10 K min⁻¹ under 50 mL min⁻¹ N2) yields a single sharp endotherm with onset at 178 °C (peak 182 °C) and ΔHfus 96 J g⁻¹, indicative of high crystallinity and the absence of significant polymorphic contamination. Single‑crystal X‑ray diffraction of platelets grown from ethyl acetate/heptane (1:4 v/v) confirms the E‑configuration with a C=C torsion angle of 178.4° and a dihedral angle of 67.2° between the pyrrolinone ring and the benzyloxybenzylidene plane. Powder X‑ray diffraction (Cu Kα, 1.5406 Å) of the bulk material matches the calculated pattern from the single‑crystal structure, verifying batch‑to‑batch phase consistency. No glass transition is observed prior to melting, and dynamic vapor sorption (DVS Intrinsic, 25 °C, 0–95 % RH) shows <0.2 % mass uptake, confirming the anhydrous nature and low hygroscopicity of the crystalline solid.
Crude reaction mixtures from the Knoevenagel condensation of N‑(3,5‑dimethylphenyl)‑2‑methyl‑4‑oxo‑4,5‑dihydro‑1H‑pyrrole‑3‑carboxylate precursor with 4‑benzyloxybenzaldehyde typically contain 8–12% of the Z‑isomer. Automated flash chromatography on a Teledyne ISCO RediSep Rf Gold 330 g silica cartridge (column dimensions 110 mm × 57 mm) using isocratic ethyl acetate/hexane (30:70 v/v) at 85 mL min⁻¹ achieves baseline resolution (Rs = 2.1) between the Z‑isomer (retention volume 2 625 mL) and the target E‑isomer (retention volume 2 340 mL). Fraction analysis at 310 nm permits pooling of heart cuts with >99.5 % diastereomeric purity. Scale‑up to 5 kg crude has been demonstrated on a NovaSep LC150 preparative HPLC system using a 20 μm irregular silica packed bed (500 mm × 100 mm) with heptane/ethyl acetate (75:25) at 1.2 L min⁻¹, delivering 2.8 kg of purified E‑isomer per run with residual Z‑isomer below the 0.05 % HPLC quantitation limit.
| Parameter | Title compound (benzyloxy) | 4‑Hydroxybenzylidene analog | N‑Phenyl analog (no 3,5‑dimethyl) |
|---|---|---|---|
| Calculated LogD (pH 7.4, ChemAxon) | 5.2 | 3.8 | 4.6 |
| HPLC retention time (C18, 250 mm × 4.6 mm, MeCN/H2O 70:30) | 8.7 min | 5.1 min | 7.2 min |
| λmax (MeOH) | 348 nm | 366 nm | 342 nm |
| Melting onset (DSC) | 178 °C | 201 °C | 163 °C |
| E→Z photoisomerization rate (k, h⁻¹, ICH Q1B) | 0.052 | 0.11 | 0.045 |
| Solubility in DMSO (mg mL⁻¹, 25 °C) | >50 | >50 | 42 |
The benzyl ether imparts a substantial increase in lipophilicity compared to the free phenol, which translates into longer reversed‑phase retention and reduced aqueous solubility (calculated intrinsic solubility <0.1 µg mL⁻¹ from fragment‑based methods). This difference must be factored into biological assay design; the hydroxy analog is often preferred for targets requiring hydrogen‑bond donor interactions, while the benzyloxy variant offers superior cell‑membrane permeability in Caco‑2 monolayer models (apparent Papp > 20 × 10⁻⁶ cm s⁻¹ predicted). The 3,5‑dimethylphenyl substitution on nitrogen restricts rotational freedom of the N‑aryl ring, a feature that has been correlated with improved metabolic stability in microsomal incubations of related pyrrolinone libraries.
Exposure to aqueous sodium hydroxide (0.1 M, THF/H2O 1:1, 25 °C) leads to rapid ester saponification with a half‑life of 12 min as monitored by LC‑UV at 254 nm. The resulting carboxylic acid precipitates upon neutralization and can be isolated at 87 % yield. More critically, primary amines such as n‑butylamine (1.2 eq, MeOH, 40 °C) attack the exocyclic double bond via conjugate addition, giving a ring‑opened enaminone product within 2 h. This reactivity contrasts with the 4‑hydroxybenzylidene analogue, where the phenol deprotonation suppresses the electrophilicity of the benzylidene carbon under identical conditions. Consequently, synthetic protocols for further derivatization of the title compound avoid amine bases; K2CO3 in anhydrous DMF is the preferred heterogeneous base for N‑alkylation or O‑alkylation steps, yielding <5% ring‑opening side products. The compound should not be stored in solution with stabilizers such as BHT, which can generate radical species that accelerate benzyl ether hydrogen abstraction under thermal stress above 60 °C.
| Test | Acceptance Criterion | Reference Method |
|---|---|---|
| Appearance | Yellow crystalline powder | Visual (Ph.Eur. 2.2.1) |
| Identity (1H NMR, 400 MHz, CDCl3) | Conforms to structure | ASTM E386‑90 (re‑approved 1999) |
| Purity (HPLC, 254 nm) | ≥98.0% area | ISO 6353‑2 R.32 |
| Z‑isomer content | ≤0.5% | Internal method (C18, MeCN/H2O) |
| Residual solvents (GC‑FID) | Meets ICH Q3C Option 1 limits | USP <467> |
| Water content (KF) | ≤0.5% | ASTM E203‑16 |
| Heavy metals (ICP‑MS) | ≤20 ppm total | USP <233> |
