Methylpyrrolecarboxylicacidethylester
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HS Code |
284223 |
| Chemical Formula | C8H11NO2 |
| Molar Mass | 153.18 g/mol |
| Appearance | Typically a colorless to pale yellow liquid |
| Boiling Point | Around 220 - 230 °C |
| Solubility In Water | Poorly soluble in water |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, dichloromethane |
| Density | Approximately 1.04 - 1.06 g/cm³ |
| Odor | May have a faint, characteristic organic odor |
| Flash Point | Relatively high, as it's an ester (approx. >90 °C) |
As an accredited Methylpyrrolecarboxylicacidethylester factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of Methylpyrrolecarboxylic acid ethyl ester packaged in a sealed, chemical - resistant bottle. |
| Shipping | Methylpyrrolecarboxylic acid ethylester is shipped in accordance with chemical transportation regulations. It's carefully packaged in suitable containers to prevent leakage, and transported by carriers licensed for handling such chemicals. |
| Storage | Methylpyrrolecarboxylic acid ethyl ester should be stored in a cool, dry, and well - ventilated area, away from heat sources and open flames. Keep it in a tightly sealed container to prevent moisture and air exposure, which could potentially lead to decomposition or reaction. Store it separately from oxidizing agents and incompatible substances to avoid dangerous chemical interactions. |
In multi-kilo scale cGMP manufacturing of pyrrole-bearing kinase inhibitors intended for Phases II–III clinical supply, ethyl 5-methyl‑1H‑pyrrole‑2‑carboxylate serves as the core heterocycle precursor introduced at the first convergent coupling stage. Batches are prepared under ICH Q7 §19.6 controlled environments in 500 L glass‑lined reactors equipped with retreat-curve impellers operating at 85–95 rpm, where the ester is dissolved in anhydrous tetrahydrofuran (KF ≤0.02% w/w) and added at 1.05 molar equivalents relative to the activated acyl chloride coupling partner. The addition is maintained at 2–8 °C with jacket brine circulation; deviation beyond this range results in dimeric by‑product formation exceeding 0.15 area% by HPLC‑UV at 254 nm (USP <621>). Following coupling, direct alkaline hydrolysis with 2.5 M NaOH in 3:1 methanol/water at 45 °C liberates the free carboxylic acid, which undergoes pH‑swing crystallization to deliver a polymorphically consistent intermediate with residual palladium controlled below 10 ppm (USP <233>). Every production campaign includes forced degradation studies under ICH Q1A(R2) conditions; the ester’s primary degradation pathway is oxidative ring opening accelerated by iron residuals, mandating pre‑passivation of all stainless‑steel transfer lines with 5% citric acid. The downstream API derived from this intermediate is typically a Type II ATP‑competitive inhibitor formulated as a mesylate or besylate salt, with final dosage forms including immediate‑release tablets and lyophilized powders for injection. Relevant compliance frameworks include 21 CFR 210/211, ICH Q3A(R2) for unspecified impurities (≤ 0.10% individual), ICH Q3C(R8) for residual THF (Class 2, ≤ 720 ppm), and the European Pharmacopoeia monograph for related substances (Ph. Eur. 10.0, 2.2.46). Process analytical technology employing in‑line ReactIR 15 probes tracks the disappearance of the ester carbonyl stretch at 1706 cm⁻¹, enabling real‑time endpoint determination and reducing off‑line sampling frequency.
When Chlorfenapyr Intermediates Demand Regioselective Pyrrole HalogenationThe synthesis of the broad‑spectrum acaricide/insecticide chlorfenapyr (ISO common name) relies on ethyl 4‑methyl‑1H‑pyrrole‑2‑carboxylate as a starting unit that undergoes N‑ethoxymethylation followed by sequential bromination at the 4‑position. In campaign‑scale agrochemical production, the ester (1.00 molar equivalent) is dissolved in N,N‑dimethylformamide and treated with potassium carbonate (1.3 eq) and chloromethyl ethyl ether, with the reactor jacket held at 35 ±2 °C; deviation above 40 °C triggers exothermic runaway, generating quaternary ammonium tar that fouls the condenser. After phase separation into toluene and brine washing to ≤1 μS/cm conductivity, the resulting N‑substituted intermediate is subjected to bromination using bromine (1.02 eq) in glacial acetic acid containing sodium acetate buffer (pH 4.5–5.0). Real‑time monitoring of the dibromo over‑bromination impurity (critical threshold <2.0 area%) via GC‑FID (ASTM D6142‑21) dictates bromine feed rate; typical addition spans 5–7 h on a 2000 L glass‑lined vessel. The downstream transformation to chlorfenapyr 95% TC involves condensation with 4‑chlorophenyl‑trifluoromethyl ketone and subsequent ring closure, all steps governed by the FAO specification 362/TC (2020 revision) and U.S. EPA 40 CFR §180.500 tolerance levels. Process effluent is quenched with sodium metabisulfite to reduce residual bromine below 5 ppm before wastewater treatment; failure to maintain this threshold leads to bromate formation that exceeds EU 98/83/EC drinking‑water parameter values for intake water reused in the site loop. Thermally generated savoury flavour compositions incorporating ethyl 1‑methyl‑1H‑pyrrole‑2‑carboxylate demonstrate nutty, roasted depth and baked‑bread top notes at inclusion levels well below conventional aroma‑chemical detection thresholds. In model reaction‑flavour systems designed to mimic meat‑juice processing conditions, the ester is added at 0.5–5 ppm (w/w final food matrix) and participates in Maillard cascades with reducing sugars (0.2–0.5% glucose) and L‑cysteine at 110 °C for 60 min in a closed jacketed vessel with headspace pressure maintained at 1.2 bar absolute. Under these conditions, retro‑aldol degradation liberates trace pyrrole‑2‑carbaldehyde that immediately condenses with Strecker aldehydes to form roasted‑meat character impact compounds. All flavour formulations are assessed against Regulation (EC) No 1334/2008; the ester itself is evaluated through the EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) when used as a flavour precursor, with toxicological bridges drawn to structurally related pyrrole carboxylates listed in the FEMA GRAS™ inventory. Final consumer goods include liquid smoke condensates, yeast‑extract‑based bouillons, and retort‑stable beef‑tallow process flavours. A critical processing boundary exists: if the reaction pH drifts above 6.5 during thermal treatment, pyrrole ring‑opening yields off‑flavour alkyl‑amines detectable at ppb levels by GC‑olfactometry, requiring buffered conditions with 0.1 M phosphate. Storage stability tests per ISO 13301:2018 confirm that the ester‑containing flavour premix retains potency for 18 months at 25 °C/60% RH in aluminium‑lined triple‑layer packaging.If Hole Transport Layer Mobility Exceeds 10⁻⁴ cm²/V·s in Solution‑Processed OLEDsWhen fabricating phosphorescent organic light‑emitting diode stacks by slot‑die coating, ethyl 3‑methyl‑1H‑pyrrole‑2‑carboxylate is employed as a solubilizing monomer precursor that is copolymerized with 9,9‑dioctylfluorene‑2,7‑diboronic acid via Suzuki coupling to yield a non‑conjugated backbone bearing hole‑transporting pyrrole‑rich pendant groups. The copolymer composition is controlled at 35–50 mol% pyrrole ester units, with the ester subsequently hydrolyzed to the carboxylate and decarboxylated in situ to improve film morphology. Before integration into the active stack, the monomer must meet stringent electronic‑grade specifications: purity ≥ 99.95% by HPLC‑ELSD, single metal ion content ≤ 1 ppb each for Fe, Ni, Pd by ICP‑MS, and halide residuals ≤ 0.5 ppm. The purified material is dissolved in chlorobenzene at 8–12 mg/mL and blade‑coated onto ITO‑glass pre‑treated with UV‑ozone for 15 min, forming a 30–50 nm layer after drying at 120 °C in an inert glovebox (O₂, H₂O <1 ppm). Hole mobility is measured by the time‑of‑flight technique at an electric field of 2.5×10⁵ V/cm; only films achieving mobility ≥ 1.2×10⁻⁴ cm²/V·s proceed to device integration, as lower values cause charge accumulation at the emission‑layer interface that reduces external quantum efficiency by more than 15%. Performance validation follows IEC 62341‑1‑1:2015 for OLED endurance testing, with the target LT95 lifetime exceeding 5000 h at 1000 cd/m². Downstream finished components include bottom‑emission flexible displays and automotive interior lighting panels where the layer is combined with a phosphorescent Ir(III) emitter. Constructing Pyridine‑Enhanced MOFs via In Situ Ester HydrolysisEthyl 5‑methyl‑1H‑pyrrole‑2‑carboxylate is quantitatively hydrolyzed with 3 M aqueous NaOH at 80 °C to yield 5‑methyl‑1H‑pyrrole‑2‑carboxylic acid, which then serves as a ditopic pro‑ligand for assembling zinc‑based metal‑organic frameworks structurally analogous to MOF‑5. The secondary building unit formation combines Zn(NO₃)₂·6H₂O (1.60 mmol) with the pyrrole acid (0.80 mmol) and 4,4′‑bipyridine (0.40 mmol) in 40 mL of DMF, solvothermally treated at 120 °C for 24 h in a Parr 45 mL PTFE‑lined autoclave. Framework activation involves solvent exchange with anhydrous acetone over 72 h and degassing at 150 °C under dynamic vacuum (10⁻⁵ mbar) for 12 h. BET surface areas determined by nitrogen adsorption at 77 K in accordance with ISO 9277:2010 typically fall between 800–1450 m²/g, with the methyl substituent on the pyrrole ring sterically suppressing interpenetration relative to the parent unsubstituted framework. The resulting MOF exhibits selective CO₂ uptake of 2.8–3.5 mmol/g at 1 bar 298 K, measured by gravimetric sorption analyzer. Real‑scale production of shaped adsorbent monoliths by extrusion with kaolin binder (15 wt%) and methylcellulose temporary binder addresses the inherent powder‑handling risks; crush strength per ASTM D4179‑22 is maintained above 3.0 MPa after calcination at 300 °C. Application fields include biogas upgrading swing‑adsorption units and indoor‑air CO₂ scrubbers. A critical incompatibility must be noted: the framework collapses irreversibly upon exposure to relative humidity exceeding 70% at 25 °C unless pre‑coordinated with a hydrophobic post‑synthetic coating, limiting its deployment in unconditioned ambient environments.
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Methylpyrrolecarboxylicacidethylester — systematically indexed under CAS 61463-78-1 and commonly filed as 1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester — functions as a sterically anisotropic C₈H₁₁NO₂ building block within pharmaceutical and crop-protection chemistries. Its molecular mass of 153.18 g·mol⁻¹, combined with an ethoxycarbonyl group flanked by an N-methyl heterocycle, imparts a distinctive hydrolysis resistance and regioselectivity that deviates meaningfully from non-methylated or methyl-ester variants. The substance is isolated as a water-white to straw-colored liquid with a boiling point of 98–102 °C at 14 mmHg. Production campaigns typically release the ester at ≥ 99.0% purity (GC-FID, DIN 51405 internal normalization), accompanied by the specification envelope below.
| Parameter | Method | Limit |
|---|---|---|
| Assay (GC area%) | DIN 51405 | ≥ 99.0% |
| Water content | ISO 760 (Karl Fischer coulometry) | ≤ 0.10% |
| Residual ethanol | USP ⟨467⟩ headspace GC | ≤ 0.5% |
| Heavy metals (as Pb) | USP ⟨231⟩ ICP-MS | ≤ 10 ppm |
| Refractive index nD20 | ISO 489 | 1.495–1.500 |
| Density at 20 °C | ASTM D4052 | 1.055–1.065 g·cm⁻³ |
When the ester is converted to the corresponding amide via direct reaction with primary amines — a key transformation in the assembly of 1-methylpyrrole-2-carboxamide pharmacophores — the thermal profile demands close attention. Reaction calorimetry conducted in a 1-L Mettler Toledo RC1e under semi-batch mode (amine addition at 0.5 mol·min⁻¹ to a 2 M ester solution in THF at 55 °C) registers an instantaneous heat release of −180 ± 15 kJ·mol⁻¹. The adiabatic temperature rise extrapolates to 48 K, placing the system within the threshold where a runaway scenario becomes credible if cooling is interrupted. A MTSR (maximum temperature of the synthesis reaction) of 103 °C exceeds the solvent boiling point, imposing a vent-sizing requirement evaluated under VDI 2263-2 dust and vapor explosion guidelines. Plant-scale batches executed in a 1600-L glass-lined reactor with jacket temperature offset of −10 K versus the setpoint maintain the reaction mass within the safe envelope, provided the amine feed is dispersed through a dip pipe with an orifice velocity above 2 m·s⁻¹ to avoid localized accumulation.
Hydrolysis of the ester during workup represents the competing pathway that erodes yield. Comparative kinetic data generated under OECD TG 111 conditions (pH 7, 25 °C) show a half-life of 120 ± 10 h for the ethyl ester, a figure that drops to 45 ± 5 h for the methyl ester analog. This 2.7-fold advantage allows a six-hour aqueous quench window without product losses exceeding 2%, a practical margin that manufacturing suites with automated phase-separation sequences routinely exploit. The steric bulk of the ethoxy group also retards base-catalyzed saponification; processing with 0.5 M NaOH at 20 °C results in 12% conversion after 30 min, whereas the methyl ester reports 33% conversion under identical conditions.
In the synthesis of pyrrole-based GABA-gated chloride channel antagonists — the structural backbone of several commercial insecticidal agents — the crystalline intermediates derived from methylpyrrolecarboxylicacidethylester consistently exhibit superior filtration characteristics when contrasted with those prepared from the methyl ester. On a 500-L Rosenmund filter-dryer operating at 0.4 bar pressure differential, the ethyl-ester-derived wet cake registers a specific cake resistance α of 1.2 × 10⁹ m·kg⁻¹, compared to 1.8 × 10⁹ m·kg⁻¹ for the methyl homolog. The consequence is a filtration cycle shortened by roughly 30%, from 48 min to 34 min, and a corresponding reduction in heel volume from 8% to 5% of the batch mass. Granulometry data (Malvern Mastersizer 3000, dry dispersion at 2 bar) further confirm a D₅₀ shift from 85 µm to 120 µm, consistent with the more drainable crystal habit. This difference becomes operationally decisive in multi-ton campaigns where filtration is the rate-limiting unit operation.Unlike the parent pyrrole-2-carboxylic acid ethyl ester, which directs electrophiles predominantly to the C-4 position, the N-methylated analog reroutes the regioselectivity toward C-5. Nitration with acetyl nitrate at −10 °C in acetic anhydride yields the 5-nitro derivative in a 9:1 ratio over the 4-nitro isomer, as quantified by ¹H NMR integration of the H-4 singlet at δ 7.45 versus the residual H-3 doublet at δ 6.72 (J = 4.2 Hz). This reversal, corroborated by DFT calculations at the B3LYP/6-311+G(d,p) level, arises from the steric shielding of the C-4 position by the N-methyl group combined with the electronic push of the ester carbonyl reinforcing charge density at C-5. For the synthetic chemist, the upshot is that the ethyl ester tolerates a Vilsmeier-Haack formylation at 0–5 °C to install a formyl group at C-5 with 83% isolated yield after 18 h, without requiring the cryogenic conditions or directing-metal strategies that the unmethylated pyrrole ester would demand to achieve a comparable isomer ratio.
¹H NMR assignments for the parent ester (400 MHz, CDCl₃) serve as a primary forensic fingerprint: δ 6.82 (d, J = 4.0 Hz, 1H, H-3), 6.18 (d, J = 4.0 Hz, 1H, H-4), 4.29 (q, J = 7.1 Hz, 2H, OCH₂CH₃), 3.92 (s, 3H, N-CH₃), 1.35 (t, J = 7.1 Hz, 3H, OCH₂CH₃). Lot-to-lot consistency of these shifts within ± 0.02 ppm is monitored as a release quality gate to exclude N-methyl migration or ring-alkylation by-products.
Differential scanning calorimetry at a ramp rate of 10 K·min⁻¹ under 30 mL·min⁻¹ nitrogen flow detects a pronounced exotherm with onset at 228 °C and a total energy release of 450 ± 20 J·g⁻¹. Thermogravimetric analysis (TGA, heating rate 20 K·min⁻¹) shows a 5% mass loss at 185 °C, accelerating sharply beyond 220 °C. Headspace GC-MS of the degraded mass identifies ethanol, 1-methylpyrrole, and traces of N-ethyl-2-methylpyrrole — a signature consistent with competitive decarboxylation, transesterification, and N-methyl → N-ethyl rearrangement pathways. In practice, this translates to an upper storage limit of 40 °C for bulk containers, with headspace ullage purged to 0.5% oxygen using nitrogen blanketing. Drum quantities held in uninsulated warehouses during summer months in tropical climates have generated discolored product with assay losses exceeding 2% within 90 days; accelerated stability testing at 50 °C/75% RH as per ICH Q1A thus forms a mandatory part of the supplier’s annual revalidation protocol.
Oxidative degradation follows a separate trajectory. Excluding oxygen from the headspace is essential because the electron-rich pyrrole ring undergoes slow autoxidation at ambient temperature, forming a peroxide-linked oligomer that manifests as a faint yellow hue detectable at 10 APHA units and escalating to 50 APHA within four weeks of uncontrolled exposure. The addition of 50 ppm butylated hydroxytoluene is permissible for grades destined for non-pharmaceutical applications where a free-radical scavenger does not interfere, though the pharmaceutical-grade material is supplied additive-free to meet ICH M7 mutagenic impurity control requirements.
| Property | 1-Methyl-1H-pyrrole-2-carboxylic acid ethyl ester (target) | 1H-Pyrrole-2-carboxylic acid ethyl ester | 1-Methyl-1H-pyrrole-2-carboxylic acid methyl ester |
|---|---|---|---|
| CAS | 61463-78-1 | 2199-43-3 | 61463-76-9 |
| Molecular weight (g·mol⁻¹) | 153.18 | 139.15 | 139.15 |
| Boiling point | 98–102 °C (14 mmHg) | 70–72 °C (0.5 mmHg) | 88–92 °C (14 mmHg) |
| Hydrolysis t½ (pH 7, 25 °C) | 120 ± 10 h | 98 ± 8 h | 45 ± 5 h |
| Electrophilic substitution preference | C-5 (nitration selectivity 9:1) | C-4 (12:1 for 5-nitro:4-nitro) | C-5 (8.5:1) |
| Filtration α (10⁹ m·kg⁻¹) | 1.2 | 1.4 | 1.8 |
| Flash point (closed cup) | 108 °C | 101 °C | 98 °C |
Isocyanates and strongly nucleophilic secondary amines present an incompatibility boundary; the ethyl ester undergoes electrophilic attack at the carbonyl carbon when exposed to benzylamine at concentrations exceeding 0.2 eq in aprotic media without temperature control, generating symmetrical urea by-products identifiable at m/z 297 (LC-MS, ESI+). This side reaction is suppressed effectively by maintaining a slight ester excess of 1.05 eq and dosing the amine below the liquid surface with a mass flow controller set to a feed ratio of 0.02 eq·min⁻¹. Published data for high-pressure hydrogenation of the ester to the corresponding alcohol over Ru/C catalysts at 80 bar and 100 °C are limited; however, batch-screening experiments on a 50-mL Parr reactor indicate partial ring hydrogenation (12% conversion to pyrrolidine after 6 h) unless the catalyst loading is kept below 2 wt%.
