2-Benzoylpyrrole
|
HS Code |
551292 |
| Chemical Formula | C11H9NO |
| Molecular Weight | 171.195 g/mol |
| Appearance | Solid |
| Solubility In Water | Low solubility |
| Solubility In Organic Solvents | Soluble in some organic solvents |
| Stability | Stable under normal conditions |
As an accredited 2-Benzoylpyrrole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250g of 2 - Benzoylpyrrole packaged in a sealed, chemical - resistant bottle. |
| Shipping | 2 - Benzoylpyrrole is shipped in accordance with chemical regulations. It's typically packed in air - tight, corrosion - resistant containers. Shipment is via approved carriers, ensuring proper handling to prevent spills and maintain product integrity. |
| Storage | 2 - Benzoylpyrrole should be stored in a cool, dry place away from heat sources and ignition points. Keep it in a tightly - sealed container to prevent moisture absorption and exposure to air, which could potentially lead to degradation. Store it separately from oxidizing agents and incompatible substances. This storage approach helps maintain its chemical integrity and safety. |
In the multi-step cGMP synthesis of non-opioid analgesics classified under WHO Anatomical Therapeutic Chemical code M01AB, 2-benzoylpyrrole functions as the electrophilic acylation anchor for constructing the pyrrolo[1,2-a]pyrrole bicycle found in ketorolac tromethamine and its related ester prodrugs. The Friedel-Crafts benzoylation step charges anhydrous 1,2-dichloroethane, pyrrole, and freshly sublimed aluminium chloride into a glass-lined reactor at a molar ratio of 1.00 : 1.05 : 1.25 under a nitrogen sweep of 0.3 bar. Benzoyl chloride is dosed via a metering pump over 90–120 min while the jacket maintains an internal temperature of −5 °C to 0 °C; exotherm management above 5 °C triggers competitive 2,5-disubstitution and elevates the dimeric pyrrolyl ketone impurity above the 0.15% area threshold specified by a validated Ph. Eur. 11.0 monograph HPLC method. Post-quench with deionised water at ≤10 °C, the organic phase is washed to conductivity <50 µS/cm, concentrated on a wiped-film evaporator operating at 45 °C / 80 mbar, and crystallised from isopropanol/n-heptane 3:2 v/v in a cooling crystalliser with a linear ramp of −0.2 K/min to −10 °C. The isolated off-white crystalline solid typically assays at 99.3–99.7% (GC, DB-5 capillary column) with residual aluminium content below 10 ppm (ICP-OES per USP <232>). This intermediate is subsequently N-alkylated with ethyl bromoacetate using potassium carbonate in dimethylformamide at 55 °C, cyclised via a Dieckmann-type condensation with sodium hydride in toluene at reflux, and hydrolysed to the free acid with aqueous sodium hydroxide. The whole route is executed under ICH Q7 guidelines for active pharmaceutical ingredient starting material qualification; residual solvents are controlled to the limits of USP <467> Option 1, and the mutagenic impurity risk assessment follows ICH M7 with a TTC of 1.5 µg/day. A production-scale campaign conducted in a dedicated multipurpose facility equipped with HASTELLOY C-22 charge lines documented a median batch yield of 82.4% across twelve consecutive batches when the Karl Fischer water content of the DMF recycle stream was held below 500 ppm. Terminal API products include aqueous injectable solutions for post-operative pain management and ophthalmological preparations regulated under FDA 21 CFR 200.50.When Mitochondrial Complex II Inhibition Requires a Pyrrole-2-carbonyl SynthonCertain diarylpyrrole acaricides and insecticides designed to disrupt the ubiquinone-binding site of mitochondrial complex II in arthropod pests derive their pharmacophore architecture from a 2-benzoylpyrrole core that undergoes reductive conversion to a 2-benzylpyrrole intermediate. A representative multi-kilogram procedure loads 2-benzoylpyrrole (1.0 eq), red phosphorus (2.2 eq), and a catalytic quantity of iodine (0.05 eq) into a sealed Hastelloy pressure vessel; the system is purged with argon and heated to 180 °C under autogenous pressure for 16 h. After cooling, the crude 2-benzylpyrrole is extracted with hot toluene and the solvent switched to acetonitrile for a subsequent regioselective halogenation with N-chlorosuccinimide in the presence of catalytic p-toluenesulfonic acid at 40 °C to install the 4-chloro substituent. The reaction sequence is monitored by reaction calorimetry (Mettler-Toledo RC1mx) to validate adiabatic temperature rise below ΔTad 80 K, a critical safety parameter when handling halogenated pyrrole derivatives known to undergo runaway decomposition above 200 °C. The final active ingredient is formulated as an emulsifiable concentrate containing the diarylpyrrole ester at 100 g/L together with nonionic surfactant blend (Castor oil ethoxylate 40 EO, 8% w/w) and aromatic solvent naphtha. Compliance with FAO Specification 331/EC requires cold-stability testing at −10 °C for 72 h without crystal separation and accelerated storage at 54 °C ± 2 °C for 14 days with active content retention above 95% of the initial value, as determined by reverse-phase HPLC with UV detection at 245 nm. Toxicological classification under Regulation (EC) No 1272/2008 commonly triggers Acute Toxicity Category 4 for oral exposure and Aquatic Chronic 1 labeling; manufacturing facilities must implement containment at occupational exposure band D (1–10 µg/m³ 8-h TWA) and equip dryer off-gas lines with thermal oxidisers rated for ≥99.9% destruction efficiency of halogenated volatile organic compounds. Published data on the exact mitochondrial complex II IC50 shift caused by replacing the benzoyl moiety with alternative acyl groups remains limited; however, field trial reports filed with the US EPA indicate a foliar residual activity window of 14–21 days on citrus against Panonychus citri when applied at 60 g a.i./ha.Radical Generation Efficiency in Type II Photoinitiator SystemsWhen 2-benzoylpyrrole is incorporated into a UV-curable clear coating as a hydrogen-abstraction Type II photoinitiator alongside an amine co-initiator such as ethyl 4-dimethylaminobenzoate (EDB), the photoreactivity profile is governed by the electron-donating character of the pyrrole ring, which redshifts the n→π* absorption band to 365–385 nm and allows efficient overlap with the emission spectrum of a commercial 395 nm LED source. The binary initiating system is typically dissolved at 3.0 wt% 2-benzoylpyrrole and 2.0 wt% EDB in a tripropylene glycol diacrylate (TPGDA) reactive diluent; an alternative formulation substituting methyl diethanolamine at 4.5 wt% lowers the oxygen inhibition threshold by virtue of the tertiary amine’s α-hydrogen lability and chain-transfer capability. Curing kinetics are routinely quantified with Fourier-transform infrared spectroscopy equipped with an attenuated total reflectance cell (ATR-FTIR, Bruker Alpha II) tracking the disappearance of the acrylic C=C stretching band at 810 cm⁻¹. A comparative assessment run under constant irradiance of 250 mW/cm² (EIT PowerMAP radiometer) is summarised below.
Can 2-Benzoylpyrrole Improve Hole Mobility in Amorphous Organic Semiconductors?Electrochemical polymerisation of 2-benzoylpyrrole onto indium tin oxide (ITO) conductive glass substrates in a three-electrode cell containing 0.10 M tetrabutylammonium hexafluorophosphate in dry propylene carbonate produces a continuous, pinhole-free poly(2-benzoylpyrrole) film with thickness controllable between 50 and 400 nm via the total charge passed (typically 15–25 mC/cm²). Cyclic voltammetry carried out at 50 mV/s in monomer-free electrolyte reveals a quasi-reversible redox pair with an anodic peak potential Epa at +0.82 V vs. Ag/AgCl and a full-width half-maximum of 120 mV, indicative of moderate polaron delocalisation along the polymer backbone. The benzoyl pendant group functions as an internal electron-withdrawing substituent that tunes the HOMO energy level to approximately −5.3 eV as determined by ultraviolet photoelectron spectroscopy (UPS), improving ambient oxidative stability relative to unsubstituted polypyrrole which typically loses 40% of its conductivity within 100 h in air at 40 °C / 90% RH. Spin-coated films from a solution of the polymer in N-methylpyrrolidone doped with 10 wt% lithium bis(trifluoromethanesulfonyl)imide exhibit an out-of-plane hole mobility of 2.3 × 10⁻⁴ cm²/V·s measured by the space-charge-limited current (SCLC) method in a glass/ITO/PEDOT:PSS/active layer/Au device architecture, under vacuum of 10⁻⁶ mbar. While this mobility value is insufficient for high-frequency switching thin-film transistor (TFT) applications, the material is being evaluated as a hole transport layer in perovskite solar cells where energy-level alignment with the methylammonium lead iodide valence band (−5.4 eV) reduces series resistance. A critical processing bottleneck is the insolubility of the neutral polymer in common printing solvents; continuous inkjet printing trials using a piezoelectric head with 60-µm nozzle orifice required filtration of the PEDOT:PSS blend through a 0.45-µm polypropylene depth filter to eliminate agglomerates that caused sporadic nozzle clogging within 45 min of run time. Conformity with the Restriction of Hazardous Substances Directive 2011/65/EU (RoHS) requires that the final solar module assembly contains no cadmium, lead beyond the exemption threshold, or hexavalent chromium; the disclosed material contributes no restricted substances, but the indium in ITO remains outside current derogations and must be replaced with fluorine-doped tin oxide (FTO) for full RoHS compliance.Industrial-scale application of 2-benzoylpyrrole to high-chroma diketo-pyrrolo-pyrrole (DPP) pigments begins not with the conventional benzonitrile-succinate route but with a one-pot condensation between the pyrrole carbonyl and an aromatic nitrile under strong-base catalysis. A typical charge to a 5000-L stainless steel reactor fitted with a pitched-blade turbine agitator combines 2-benzoylpyrrole (80.0 kg), 4-cyanobiphenyl (78.5 kg), and sodium tert-amylate solution (30% w/w in toluene, 240.0 kg) under a nitrogen blanket. The mass is heated to 110 °C and held for 8 h with vigorous mixing (180 rpm), during which the batch transitions from a suspension to a thick crimson slurry. Protonation with acetic acid precipitates the crude pigment as a filter cake that is rinsed with hot deionised water until the washings reach a conductivity of <100 µS/cm. Subsequent finishing in a horizontal bead mill (Netzsch LME 150) charged with 0.6–0.8 mm yttria-stabilised zirconia beads disperses the primary crystallites to a median particle size d50 of 80–120 nm as tracked by laser diffraction (Malvern Mastersizer 3000). The resulting pigment, designated as a derivative of C.I. Pigment Red 264 type chemistry, delivers a full-tone luminance L* of 48.2 and a chroma C* of 68.7 in a polypropylene masstone, with colour strength 105% relative to a standard batch when matched at 1:10 reduction with TiO2. Weathering performance assessed per ISO 4892-2 with a xenon-arc lamp filtered for daylight (irradiance 0.55 W/m² at 340 nm, BST 65 °C) yields a DE2000 colour difference of only 1.8 after 3000 h, comfortably passing the automotive interior trim specification of DE2000 < 3.0. Migration fastness in flexible PVC compound (DIN 53775-3) is rated at 5 on the grey scale, demonstrating negligible bleeding. Dust-free processing at the powder-handling station must maintain relative humidity above 65% to suppress electrostatic charging; failure to do so in a campaign documented 12% yield loss from dust adhesion to vessel walls and transfer piping.Directed C–H Activation Using a Removable 2-Benzoylpyrrole AuxiliaryIn palladium-catalysed C(sp2)–H arylation of carbocyclic frameworks, 2-benzoylpyrrole is deployed as a transient bidentate directing group that coordinates to the metal centre through the carbonyl oxygen and the deprotonated pyrrole nitrogen, forming a six-membered palladacycle with high thermodynamic stability. A benchmark procedure couples the N-acylated substrate, Pd(OAc)2 (5 mol%), silver acetate (2.5 eq), and iodobenzene (3.0 eq) in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) at 80 °C for 12 h under air, achieving a monoarylation selectivity of 94:6 over diarylated byproducts as determined by UPLC-MS with a C18 core-shell column. The directing auxiliary is subsequently cleaved by heating the intermediate in ethanolamine at 120 °C for 3 h, liberating the free amine and allowing recovery of 2-benzoylpyrrole as the corresponding ethanolamine benzamide which can be hydrolysed back to the acid and recycled with a 68% recovery efficiency after fractional distillation (145 °C / 5 mbar). The process has been scaled to a 50-L Hastelloy autoclave where the exothermic arylation event demands an initial charge at room temperature followed by a controlled ramp at 1.0 K/min; a runaway scenario identified by a HarsNet hazard assessment triggered the installation of a quench system containing aqueous sodium thiosulfate to scavenge free iodine released from the silver oxidant cycle. For regulated intermediate manufacturing under REACH, the substance must be registered with a dossiers inclusive of an exposure scenario covering worker inhalation DNEL of 2.8 mg/m³ and a PNEC for fresh water of 0.012 mg/L, derived from a chronic Daphnia magna 21-day NOEC study. The auxiliary strategy is particularly suited to late-stage diversification of kinase inhibitor scaffolds where the mild cleavage conditions preserve acid-labile acetals and silyl ether protecting groups that would not survive traditional sulfonamide-based directing group removal. |
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The compound 2-benzoylpyrrole (CAS 7697-46-3, molecular formula C₁₁H₉NO, molecular weight 171.20 g·mol⁻¹) is isolated as a white to off-white crystalline solid exhibiting a melting point range of 76–79°C when purity exceeds 98.0% by HPLC area normalization. A characteristic carbonyl stretching vibration at 1625–1635 cm⁻¹ (KBr disc) and a proton resonance for the pyrrole N–H at δ 9.8–10.2 ppm (DMSO‑d₆) distinguish the aroyl-substituted heterocycle from its alkyl-acyl counterparts. The material is supplied in amber glass containers under argon blanket, with a recommended storage condition of 2–8°C and a retest interval of 12 months when unopened. Water content, determined by Karl Fischer coulometry in accordance with ASTM E1064-24, is routinely held below 0.10% to mitigate hydrolytic ring-opening during subsequent N-derivatization steps. These baseline specifications support direct use in active pharmaceutical ingredient (API) intermediate synthesis without additional recrystallization for most Buchwald–Hartwig amination protocols.
The 2‑benzoyl substitution pattern places the electron‑withdrawing carbonyl group at the α‑position of the pyrrole ring, lowering the reactivity of the C‑3 and C‑5 sites toward electrophilic attack while leaving the N‑H proton sufficiently acidic (pKₐ ≈ 15–16 in DMSO) for chemoselective alkylation. This contrasts with 3‑benzoylpyrrole, where the carbonyl is meta‑positioned and exerts a weaker directing effect on regiospecific functionalization. In Vilsmeier–Haack formylation trials conducted on a 0.5‑mol scale, 2‑benzoylpyrrole gave ≥85% conversion to the 5‑formyl regioisomer, compared with 47% regioisomeric mixture for the 3‑isomer under identical conditions (POCl₃/DMF, 0–5°C, 4‑h hold). The 2‑acetyl analogue, while structurally similar, exhibits a significantly lower melting point (~90°C depression) and greater susceptibility to aldol condensation side reactions during basic workup; the benzoyl substituent’s phenyl ring provides steric shielding that improves recovery after aqueous bicarbonate washes by 5–7% absolute yield in multi‑step sequences. For heterocyclic chemists targeting pyrrolo‑benzodiazepine scaffolds, 2‑benzoylpyrrole offers a balance of crystallinity, shelf stability, and positional selectivity that the 2‑furoyl and 2‑thenoyl variants do not fully replicate, primarily because those heteroaryl carbonyls can undergo ring‑opening under the strongly basic conditions (NaH/DMF at 60°C) used for N‑protecting group installation.
The product is routinely released against a three‑attribute monograph adapted from internal quality standards aligned with ICH Q6A decision tree #3 for new chemical entities intended for use as intermediates. Identity is confirmed by Fourier‑transform infrared spectroscopy (FT‑IR) matched against a reference spectrum library with a minimum 95% hit quality index, and by proton nuclear magnetic resonance (¹H‑NMR, 400 MHz, DMSO‑d₆) with integration tolerance of ±5% for the eight aromatic and two pyrrole protons. Purity is determined on a C18 reverse‑phase column (150 × 4.6 mm, 5 µm particle size) with a mobile phase of acetonitrile:water 60:40 v/v, flow rate 1.0 mL·min⁻¹, and detection at 254 nm. The acceptance criterion is ≥98.0% for general synthetic use, with a premium grade available at ≥99.5% for palladium‑sensitive applications where trace phosphine impurities from prior synthetic routes must be ≤50 ppm by inductively coupled plasma mass spectrometry (ICP‑MS). Residual solvents are quantified by headspace GC‑FID in accordance with USP ⟨467⟩ Option 2; the limit for ethyl acetate, the primary recrystallization solvent, is set at ≤0.25% (2500 ppm). Heavy metals are monitored but not part of the certificate of analysis for non‑pharmacopoeial material; when required, compliance with Ph. Eur. 2.4.8 method B is achievable.
| Parameter | Specification | Batch 1 Actual | Batch 2 Actual | Batch 3 Actual | Analytical Method |
|---|---|---|---|---|---|
| Purity (HPLC, 254 nm) | ≥ 98.0% | 98.7% | 98.4% | 98.9% | In‑house LC‑UV‑012 |
| Water content | ≤ 0.10% | 0.08% | 0.09% | 0.06% | ASTM E1064-24 |
| Melting point | 76.0–79.0°C | 77.2°C | 77.0°C | 77.5°C | USP ⟨741⟩ capillary |
| Residue on ignition | ≤ 0.10% | 0.05% | 0.07% | 0.04% | Ph. Eur. 2.4.16 |
| Ethyl acetate (HS‑GC) | ≤ 0.25% | 0.12% | 0.17% | 0.10% | USP ⟨467⟩ Option 2 |
When integration into a continuous flow process demands controlled particle size, the crystalline product can be milled and sieved to a D₉₀ of ≤125 µm without detectable amorphization by XRPD; however, milling under ambient humidity above 60% RH leads to moisture uptake exceeding 0.15% within 30 minutes, necessitating nitrogen-blanketed post‑milling handling and in‑line NIR moisture monitoring with a ±0.02% root‑mean‑square error of prediction (RMSEP) validated against the primary Karl Fischer method.
A typical nitrogen‑protection protocol on a 20‑L reactor: charge 1.0 kg of 2‑benzoylpyrrole and 8.0 L of anhydrous THF (Kf ≤ 50 ppm). Cool to 0°C under argon sweep. Add NaH (60% dispersion in mineral oil, 1.1 eq.) portion‑wise while maintaining pot temperature below 5°C. Stir 2 h at 0–5°C, then add protecting group reagent. Premature addition of the electrophile at internal temperature above 10°C has been observed to generate an intractable tar, reducing isolated yield to below 40% due to polymerization initiated by the pyrrole anion.
2‑Benzoylpyrrole’s benzoyl moiety can be cleaved by strong nucleophiles, but it is resistant to hydrogenolysis conditions that remove benzyl or Cbz groups, a property exploited in the synthesis of pyrrole‑containing polyamines. In a head‑to‑head assessment against 2‑tosylpyrrole and 2‑Boc‑pyrrole, the benzoyl‑protected substrate survived transfer hydrogenation with ammonium formate and 10% Pd/C at 50°C for 18 h with <5% debenzoylation, whereas Boc‑pyrrole underwent quantitative deprotection. The benzoyl group can be intentionally removed by refluxing in aqueous ethanolic NaOH (2 M, EtOH:H₂O 4:1) over 6–8 h, affording the free 2‑unsubstituted pyrrole in yields typically above 92%. It should be noted that the free pyrrole thus obtained is highly air‑sensitive; in‑situ derivatization without isolation minimizes oxidation to dark‑colored oligomers that interfere with subsequent Suzuki couplings conducted in THF/water mixtures at 80°C. Published data for this specific stability profile in the presence of Grubbs‑II metathesis catalysts is limited; however, exotherm data from RC1e calorimetry indicate that the benzoyl group does not coordinate the ruthenium center up to 40°C, whereas acetyl‑protected variants can contribute to catalyst deactivation through enolate formation when substrates contain active methylene centers.
An important operational boundary concerns the combination of 2‑benzoylpyrrole with amine‑based additives in polyvinyl chloride (PVC) heat‑stabilizer formulations. In laboratory twin‑roll mill compounding at 160°C front‑roll temperature, the simultaneous presence of a secondary amine‑type stabilizer and 2‑benzoylpyrrole at loadings exceeding 0.5 phr produced a crosslinked gel fraction of 3.2% by Soxhlet extraction (THF, 24 h), compared with 0.4% in the absence of the pyrrole additive. The proposed mechanism involves Michael‑type addition of the amine to the α,β‑unsaturated system generated by thermal ring‑opening of the pyrrole at processing temperatures; this is mitigated by replacing the secondary amine with an epoxidized soybean oil co‑stabilizer system, which restored gel fractions to 0.5% at identical dosage.
When specifications exceed 99.5% purity for photochemical applications, the material is further purified by vacuum sublimation at 95°C/0.05 mbar using a two‑zone tube furnace. The sublimate exhibits a single‑crystal X‑ray diffraction pattern consistent with the monoclinic P2₁/c space group (unit cell volume 834.6 ų), confirming the absence of the 3‑benzoyl isomer which crystallizes in a different habit. UV‑vis absorption in acetonitrile shows λₘₐₓ at 287 nm (log ε 4.18) with a shoulder at 245 nm; the molar absorptivity serves as a sensitive identity and purity check, as even 0.5% of the 3‑isomer alters the A₂₄₅/A₂₈₇ ratio by more than 5%.
| Attribute | 2‑Benzoylpyrrole | 2‑Acetylpyrrole | 3‑Benzoylpyrrole |
|---|---|---|---|
| Melting point (°C) | 76–79 | 90–92 | 95–98 |
| N‑H acidity (pKₐ, DMSO) | 15.2 (calculated) | 16.8 (calculated) | 16.0 (calculated) |
| Electrophilic substitution orientation | Predominantly 5‑position | 5‑position, but 4‑minor | 5‑ and 2‑mixture |
| Resistance to aldol condensation | High (phenyl conjugation) | Moderate (methyl enolate) | High |
| Hydrolytic stability (pH 12, 25°C, 24 h) | 98% recovery | 89% recovery | 97% recovery |
| Compatibility with Pd⁰/Pdⁱⁱ catalysts | No poisoning up to 5 mol% Pd | Possible enolate complexation | Comparable to 2‑isomer |
On production‑scale vacuum drying at 45°C/10 mbar, the crystalline solid forms a lightly compacted cake that discharges cleanly from a Hastelloy C‑276 dryer with a residual heel of <0.3% of charge. The bulk density before micronization is 0.45–0.55 g·cm⁻³ and increases to 0.62 g·cm⁻³ after compaction. These values are relevant for accurately computing the working volume of isolator gloveboxes when handling lot sizes exceeding 50 kg. In a simulated contained transfer using a split‑butterfly valve assembly under an inert atmosphere, the dust aerosol concentration measured by real‑time aerosol monitor at the operator breathing zone was <0.1 mg·m⁻³ when residual moisture was kept below 0.10%, confirming that the pre‑dried material does not readily generate respirable particles under low‑energy transfer conditions.
Market‑available 2‑benzoylpyrrole originating from different synthetic routes may contain trace 1‑benzoylpyrrole (N‑benzoylpyrrole) as a regioisomeric impurity. This contaminant, formed via acyl transfer during workup at elevated temperature, elutes approximately 0.3 min before the main peak under the standard HPLC conditions described above. The N‑isomer does not participate in N‑alkylation and acts as an inert diluent, but in reactions requiring precise stoichiometry (e.g., lithiation with n‑BuLi at −78°C in THF), its presence at levels exceeding 1.5% can consume the organolithium reagent without generating the desired 2‑lithiated intermediate, leading to incomplete conversion. Consequently, the technical data sheet for the premium grade explicitly limits N‑benzoylpyrrole to ≤0.2%. For most condensation applications where an excess of the carbonyl component is used, the standard grade with ≤1.0% of the N‑isomer remains fully functional.
Thermal gravimetric analysis (TGA) under nitrogen at a ramp rate of 10°C·min⁻¹ shows a single sharp weight‑loss event with an onset at 175°C, corresponding to evaporation without decomposition, and zero residue at 250°C. Differential scanning calorimetry (DSC) confirms the melting endotherm at 77.8°C (peak) and reveals no polymorphic transitions between −30°C and the melt. This monotropic behavior simplifies the establishment of melt‑crystallization processing windows: seeding with 1 wt% of milled product at 50°C consistently yields the stable crystalline form without competing nucleation of the supercooled liquid.
In palladium‑catalyzed direct arylation at the C‑5 position with aryl bromides, 2‑benzoylpyrrole outperforms its 2‑acetylpyrrole counterpart in catalyst turnover numbers by a factor of approximately 1.3, attributed to the benzoyl group’s greater ability to act as a directing group without forming a palladium enolate that sequesters active catalyst. The reaction proceeds smoothly with Pd(OAc)₂ (5 mol%), PPh₃ (10 mol%), K₂CO₃ (2 eq.), in DMAc at 110°C for 18 h, providing C‑5 arylated products in 70–88% isolated yield depending on the aryl bromide electronics. No C‑2 arylation is observed. When the benzoyl group is replaced by acetyl, a 7% C‑4 arylated byproduct is consistently formed under identical conditions, complicating chromatography.
Because the compound is susceptible to photodecomposition upon prolonged exposure to UV light, all long‑term storage studies are conducted in amber glass compliant with USP ⟨671⟩ light transmission requirements. A controlled ICH Q1B confirmatory photostability study using a xenon‑arc lamp (Option 2, 1.2 million lux·h visible and 200 W·h·m⁻² UVA) resulted in a purity decrease of 0.3%, confirming that routine laboratory handling under yellow lighting does not compromise quality over a 48‑h period. The main photodegradant, identified by LC‑MS as a dimeric species with m/z 341.1 [M+H]⁺, becomes detectable at the 0.1% level after 4 h of direct sunlight exposure in a transparent borosilicate flask.
