1-Ethyl-2-Pyrrolecarboxaldehyde
|
HS Code |
662789 |
| Chemical Formula | C7H9NO |
| Molecular Weight | 123.15 g/mol |
| Appearance | Liquid (usually) |
| Boiling Point | Around 202 - 204 °C |
| Solubility In Water | Low solubility |
| Solubility In Organic Solvents | Soluble in many organic solvents like ethanol, dichloromethane |
| Odor | Characteristic odor |
As an accredited 1-Ethyl-2-Pyrrolecarboxaldehyde factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 1 - Ethyl - 2 - Pyrrolecarboxaldehyde packaged in a sealed glass bottle. |
| Shipping | 1 - Ethyl - 2 - Pyrrolecarboxaldehyde is shipped in well - sealed, corrosion - resistant containers. It adheres to strict chemical shipping regulations, ensuring proper handling and storage to prevent spills and maintain product integrity during transit. |
| Storage | 1 - Ethyl - 2 - Pyrrolecarboxaldehyde should be stored in a cool, dry place away from direct sunlight. Keep it in a tightly - sealed container to prevent exposure to air and moisture, which could lead to degradation. Store it separately from oxidizing agents and incompatible substances. It is advisable to store it in a dedicated chemical storage area following safety regulations. |
In cGMP intermediate manufacturing, 1-ethyl-2-pyrrolecarboxaldehyde functions as the key electrophilic component for constructing pyrrolo[2,3-d]pyrimidine scaffolds that populate kinase inhibitor pipelines. The formyl group undergoes Knoevenagel condensation with active methylene compounds—most commonly cyanoacetamide or ethyl cyanoacetate—under mildly basic conditions. A representative charge specification for a 500 L glass-lined reactor includes 1.0 molar equivalent of the aldehyde, 1.05 eq of cyanoacetamide, 0.03 eq of piperidine catalyst, and ethanol (8 volumes). The mixture is heated to reflux (78 °C) for 4 hours, after which the Knoevenagel adduct crystallizes upon cooling to 5 °C. Filtration through a centrifuge and washing with chilled ethanol yields a pale-yellow solid with an isolated purity > 98.5% by HPLC. Critical process parameters include the exotherm during piperidine addition; batch-to-batch purity variance of ± 1.8% has been traced to inadequate agitator tip speed (< 2.5 m/s) leading to localized pH spikes. Residual aldehyde must be monitored by a dedicated HPLC method (C18, 250 × 4.6 mm, isocratic acetonitrile/water 60:40 v/v, detection at 280 nm) and controlled to 0.10% per ICH Q3A guidelines for unspecified impurities. Genotoxic impurity risk assessment according to ICH M7 is mandatory: the aldehyde itself exhibits structural alerts for potential DNA reactivity, requiring purge factor calculations or spiking studies to demonstrate clearance below the threshold of toxicological concern (TTC) of 1.5 µg/day. The dried intermediate complies with residual solvent limits under USP <467> (ethanol 5000 ppm, piperidine 290 ppm). The downstream synthetic sequence converts this intermediate into active pharmaceutical ingredients (APIs) that target tyrosine kinase domains, where the 1-ethyl substitution on the pyrrole ring enhances metabolic stability compared to N-methyl analogues. Storage of the aldehyde intermediate is recommended at 2–8 °C under nitrogen headspace; prolonged exposure to ambient air leads to a slow increase in peroxide value beyond 10 meq/kg, detectable by iodometric titration, which interferes with the subsequent cyclization step.What Practical Utility Does 1-Ethyl-2-formylpyrrole Offer in Modern Acaricide and Insecticide Scaffold Synthesis?Conversion of the aldehyde to the corresponding nitrile, 1-ethylpyrrole-2-carbonitrile, opens access to a class of halogenated pyrrole insecticides structurally related to chlorfenapyr and tralopyril. The formyl group is first transformed to the oxime: 1.0 mol of 1-ethyl-2-pyrrolecarboxaldehyde is dissolved in 2.5 L dimethylformamide, and 1.2 mol hydroxylamine hydrochloride is added together with 1.25 mol anhydrous sodium acetate as a buffering agent. The slurry is agitated at 80 °C for 3 hours, during which the pH is maintained between 4.5 and 5.5 to avoid oxime hydrolysis. Phase monitoring by TLC (silica gel, ethyl acetate/hexane 1:2) verifies complete consumption of the aldehyde. After quenching into ice water, the oxime is filtered and air-dried to ≤ 0.3% moisture. Subsequent dehydration uses acetic anhydride (2.5 eq) and catalytic pyridine (0.1 eq) at 110 °C, delivering the nitrile in 82–87% isolated yield after fractional distillation under reduced pressure (8 mbar, 92–94 °C vapor temperature). The nitrile intermediate then undergoes regioselective bromination or iodination using N-bromosuccinimide in acetonitrile, ultimately yielding 4-halo derivatives that match the substitution pattern required for mitochondrial uncoupler activity. Process safety demands strict exclusion of water from the dehydration step because residual moisture (above 0.15% Karl Fischer) leads to exothermic acetic anhydride hydrolysis and temperature excursions beyond 130 °C, which degrade the nitrile to tarry by-products. Production-scale runs in a 1000 L glass-lined reactor equipped with a condenser and scrubber system have demonstrated steady-state output, provided the agitator maintains a Reynolds number > 10,000 to guarantee homogeneous heat transfer. Compliance with FAO specifications for technical-grade pesticide intermediates is verified by identity (GC-MS matching NIST library), purity (≥ 96% w/w by qNMR), and water content (0.2% max., CIPAC MT 30.5). The final formulated acaricide product, after further synthetic elaboration, falls under the registration framework of EC Regulation 1107/2009 and requires batch-specific toxicological studies per OECD 402 (acute dermal toxicity). Controlled Maillard-Driven Pyrazine and Pyrrole Generation for Roasted Aroma ComplexesIn the flavor industry, 1-ethyl-2-pyrrolecarboxaldehyde acts not as a direct flavorant but as a precursor that undergoes Strecker degradation and subsequent condensation with dicarbonyls to produce volatile heterocycles central to roasted, nutty, and coffee-like profiles. A typical thermal process formulation combines the aldehyde at 0.4–0.6% w/w, L-cysteine (0.8% w/w), D-glucose (2.0% w/w), and a phosphate buffer (0.1 M, pH 6.0) in a propylene glycol vehicle. The mixture is sealed in a pressure-rated stainless steel reactor and heated to 125 °C for 90 minutes. Under these conditions, cysteine liberates hydrogen sulfide and ammonia, which react with the aldehyde and fragmented sugars to form 2-ethyl-3,5-dimethylpyrazine, 1-ethyl-2-acetylpyrrole, and thiazole derivatives. Aroma character is assessed by gas chromatography-olfactometry (GC-O): the roasted note appears at a retention index of approximately 1080 on a DB-Wax column, with an odor threshold of 0.2 ng/L in air. The finished process flavor is standardized to 1 part per thousand usage level in finished consumer products and must comply with EU Regulation 1334/2008 for flavorings, meaning the aldehyde precursor must originate from a listed source material and not introduce any toxicologically significant reaction by-products. A hazard assessment per the European Food Safety Authority (EFSA) approach screens for ethyl carbamate formation; maintaining process pH ≥ 4.5 and temperature ≤ 130 °C keeps ethyl carbamate below the detection limit of 10 µg/kg. The final flavor concentrate is typically diluted onto a maltodextrin carrier and spray-dried to yield a free-flowing powder with a moisture content of 3.5–4.5%. Electrogenerated films of poly(1-ethyl-2-formylpyrrole) combine the electronic conductivity of polypyrrole with pendant aldehyde functionality for covalent bioconjugation, enabling label-free impedimetric immunosensors. The electropolymerization electrolyte is prepared in a nitrogen-atmosphere glovebox (O₂ < 5 ppm, H₂O < 1 ppm) by dissolving the monomer at 0.1 M in anhydrous propylene carbonate containing 0.05 M tetrabutylammonium hexafluorophosphate. A three-electrode cell with a platinum disk working electrode (2 mm diameter), platinum foil counter, and Ag/Ag⁺ non-aqueous reference is cycled between 0.0 V and +1.15 V at 50 mV/s for 15 cycles. Electrochemical quartz crystal microbalance (EQCM) data reveal a mass uptake corresponding to 0.28 µg per cycle, yielding a film thickness of 180–220 nm when measured by spectroscopic ellipsometry at 632.8 nm. The aldehyde groups on the polymer surface retain sufficient reactivity to react with protein amine moieties via reductive amination: after transfer to aqueous phosphate-buffered saline (PBS, pH 7.4), the film is exposed to anti-human IgG (50 µg/mL) and sodium cyanoborohydride (5 mM) for 2 hours. Subsequent blocking with bovine serum albumin (1% w/v) reduces non-specific binding. Impedance spectroscopy (frequency range 0.1 Hz to 100 kHz, amplitude 10 mV) detects antigen binding as an increase in charge-transfer resistance Rct with a limit of detection of 8 ng/mL. From a quality assurance standpoint, the monomer batch intended for electrochemical sensor fabrication must satisfy semiconductor-grade purity specifications: total transition metal content ≤ 50 ppb by ICP-MS and water content ≤ 30 ppm by Karl Fischer coulometric titration, as metal impurities catalyze unwanted crosslinking and increase leakage current beyond 5 µA/cm² at +0.8 V. Storage stability tests under argon at −20 °C maintain monomer purity above 99.0% for 12 months. When 1-Ethyl-2-pyrrolecarboxaldehyde Reacts with Pyrrole Under Anhydrous Acid Catalysis—Access to Red-Shifted BODIPY FluorophoresThe two-step synthesis of meso-unsubstituted BODIPY dyes leverages the aldehyde as a diformyl equivalent surrogate after activation. In a rigorously dried Schlenk flask, 1.5 equivalents of 1-ethyl-2-pyrrolecarboxaldehyde are combined with 1.0 equivalent of pyrrole in anhydrous dichloromethane (freshly distilled over CaH₂) under argon. A catalytic amount of trifluoroacetic acid (0.05 eq) is added dropwise at 0 °C, and the mixture is allowed to warm to 25 °C over 30 minutes with magnetic stirring. The intermediate dipyrromethane is not isolated; instead, 1.1 eq of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is introduced as a single portion, causing an immediate color shift to deep maroon. Oxidation proceeds for 45 minutes before the addition of 3.0 eq diisopropylethylamine, followed by 1.5 eq BF₃·OEt₂, yielding the 8-(1-ethylpyrrol-2-yl)-BODIPY core after aqueous workup and column chromatography (silica gel, dichloromethane/hexane 3:2). The isolated fluorophore exhibits an absorption maximum at 508 nm and emission at 525 nm in toluene, with an absolute quantum yield of 0.82 determined by an integrating sphere method (ISO 21367:2007). Process sensitivity is acute at the oxidation stage: residual water above 20 ppm in the solvent attenuates the DDQ oxidation potential, lowering the conversion efficiency to the dipyrrin intermediate to below 45%. Furthermore, the exothermic BF₃ complexation must be controlled by maintaining the internal temperature below 35 °C; excursions above 40 °C promote demethylation of the ethyl group on the pyrrole, giving rise to a des-ethyl impurity that is separable only with preparative HPLC. For labeling applications requiring bioconjugation, the 8-(1-ethylpyrrol-2-yl) substituent can be converted to an active N-hydroxysuccinimidyl ester via oxidation with pyridinium dichromate to the corresponding carboxylic acid, followed by activation. The final fluorescent conjugate, intended for flow cytometry, is validated according to ISO 13485 under design controls that include lot-to-lot brightness consistency (coefficient of variation < 5% for the fluorescence intensity ratio at 488 nm excitation). The user must be aware that these BODIPYs are prone to photobleaching under continuous illumination above 5 mW/cm² without oxygen scavenger additives, limiting their use in time-lapse microscopy to 60 minutes under standard conditions. |
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1-Ethyl-2-pyrrolecarboxaldehyde (CAS 2167-14-8) is delivered as a clear, pale-yellow liquid with a molecular weight of 123.15 g mol⁻¹ and an assay specification of ≥98.0% (GC area%, DB‑5 column, 30 m × 0.25 mm). Typical residual water content, determined by Karl Fischer titration per ASTM E203, remains below 0.1% w/w; total acidity as 1‑ethyl‑2‑pyrrolecarboxylic acid is kept under 0.5 mg KOH g⁻¹. The density at 20 °C is 1.023 g cm⁻³ and the refractive index n²⁰D 1.541. During packaging, the material is blanketed with dry nitrogen and sealed in amber glass bottles or fluorinated HDPE drums to suppress photo‑oxidation. The isomer 1‑ethyl‑3‑pyrrolecarboxaldehyde is controlled to <0.5% because its presence interferes with regiospecific acylation steps downstream.
A side-by-side comparison with the N-methyl and N-H congeners highlights the impact of the N-alkyl substituent on physical properties and synthetic utility.
| Parameter | 1‑Ethyl‑2‑pyrrolecarboxaldehyde | 1‑Methyl‑2‑pyrrolecarboxaldehyde | Pyrrole‑2‑carboxaldehyde |
|---|---|---|---|
| CAS RN | 2167‑14‑8 | 1192‑58‑1 | 1003‑29‑8 |
| Molecular formula | C₇H₉NO | C₆H₇NO | C₅H₅NO |
| Boiling point | 80–82 °C at 8 mmHg | 88–90 °C at 22 mmHg | 217–219 °C (decomposition) |
| Density (20 °C) | 1.023 g/cm³ | 1.015 g/cm³ | 1.149 g/cm³ |
| Refractive index n²⁰D | 1.541 | 1.542 | 1.559 |
| Water solubility (25 °C) | ~2.5 g/L | ~6.8 g/L | ~15 g/L |
| Commercial purity (GC) | ≥98.0% | ≥97.0% | ≥98.0% |
| Critical differentiating factor | Ethyl chain mandated in ketorolac synthesis; elevated lipophilicity aids phase‑transfer processes. | Methyl analog; not a direct substitute in regulated APIs. | Free N–H allows N‑deprotonation and competing alkylation; higher water solubility complicates extractive work‑up. |
Vilsmeier–Haack formylation of pyrrole itself yields a mixture of 2‑ and 3‑carboxaldehydes; selective introduction of the formyl group at the 2‑position is instead achieved by starting from the appropriate N‑alkylpyrrole. When 1‑ethyl‑2‑pyrrolecarboxaldehyde is used as an electrophile for further Friedel–Crafts acylation, the ethyl substituent exerts a distinct steric and electronic effect. In a typical ketorolac intermediate step, acylation with benzoyl chloride in the presence of anhydrous aluminium chloride in dichloromethane at −5 to 0 °C proceeds with a regioselectivity exceeding 95% for the 5‑position. By contrast, the N‑H analog pyrrole‑2‑carboxaldehyde under the same conditions generates substantial N‑acylation by‑products because the acidic N–H proton is abstracted by AlCl₃, leading to a drop in desired product yield to below 40%. The methyl congener, 1‑methyl‑2‑pyrrolecarboxaldehyde, does not suffer from N‑acylation but exhibits a slower reaction rate: the required reaction time to reach 85% conversion is approximately 1.8‑fold longer than for the ethyl derivative, as measured by in‑process HPLC monitoring. This kinetic advantage of the ethyl chain has been attributed to reduced aggregation of the acylating complex, facilitating the rate‑determining electrophilic attack at the ring. Additionally, the slightly higher lipophilicity (logP increase of ~0.5 units) of the ethyl compound improves partitioning into organic phases during aqueous quenching, reducing emulsion formation in pilot‑plant batches performed in 500 L glass‑lined reactors equipped with pitched‑blade agitators.
In the multistep synthesis of ketorolac tromethamine (USP), the alkyl appendage at the pyrrole nitrogen is structurally fixed; it must be ethyl. Any attempt to substitute 1‑methyl‑2‑pyrrolecarboxaldehyde leads to a final product that fails the compendial identity test due to different chromatographic retention. The process commences with a Friedel–Crafts acylation of 1‑ethyl‑2‑pyrrolecarboxaldehyde using benzoyl chloride and AlCl₃, producing 5‑benzoyl‑1‑ethyl‑2‑pyrrolecarboxaldehyde. That intermediate is subjected to a Darzens glycidic ester condensation with ethyl chloroacetate, followed by hydrolysis and decarboxylation to yield the ketorolac free acid. Pilot‑scale campaigns at 50 kg input of the aldehyde have documented that when the 3‑isomer content of the starting aldehyde exceeds 0.8%, the crystallinity of the isolated 5‑benzoyl intermediate deteriorates, and the final API requires a supplementary recrystallization to meet the ≤0.10% individual impurity threshold mandated by ICH Q3A. Therefore, the specification for the 3‑isomer is tightened to <0.5% in technical‑grade material. Residual benzoyl chloride in the aldehyde is also detrimental, as it prematurely consumes the pyrrole ring and generates dimeric species detected by HPLC–MS at m/z 463.2. Suppliers routinely provide a certificate of analysis that reports benzoyl chloride content below 10 ppm.
1‑Ethyl‑2‑pyrrolecarboxaldehyde has been evaluated as a corrosion inhibitor for mild steel in 1 M hydrochloric acid pickling baths, employing weight‑loss coupons according to ASTM G31‑72 and potentiodynamic polarisation per ASTM G5‑14. At a concentration of 5 × 10⁻³ M, the compound reduces the corrosion rate from 4.2 mm y⁻¹ to 0.15 mm y⁻¹, giving an inhibition efficiency of 96.4%. The protection arises from adsorption of the aldehyde through the π‑electron system of the pyrrole ring and the lone pair of the carbonyl oxygen, forming a compact film that obeys the Langmuir adsorption isotherm. In contrast, 1‑methyl‑2‑pyrrolecarboxaldehyde under identical conditions achieves an efficiency of 91.7%; its lower hydrophobicity caused by the shorter alkyl chain results in a thinner, less coherent barrier, as evidenced by scanning electron micrographs showing localised pitting on the metal surface. Pyrrole‑2‑carboxaldehyde, with an unprotected N–H, partially dehydrogenates in the acidic medium, generating oligomeric species that precipitate and foul the pickling bath—an operational drawback not observed with the N‑ethyl derivative. For formulating inhibitors intended for continuous pickling lines where bath life exceeds 72 h, the ethyl analogue is preferred because its film persists after multiple withdrawal–immersion cycles, whereas the methyl version requires replenishment every 8–10 h to maintain 90% efficiency. The addition of 0.1 wt% of potassium iodide synergistically boosts the efficiency of the ethyl derivative to 98.8%, a level matching commercial inhibitor packages.
Condensation of 1‑ethyl‑2‑pyrrolecarboxaldehyde with pyrrole or 2,4‑dimethylpyrrole under acid‑catalysed conditions followed by oxidation with 2,3‑dichloro‑5,6‑dicyano‑1,4‑benzoquinone (DDQ) and complexation with BF₃·OEt₂ yields a BODIPY fluorophore exhibiting an absorption maximum at 502 nm and emission at 513 nm in dichloromethane. The ethyl substituent on the meso‑pyrrole ring does not alter the spectral profile dramatically compared to the methyl congener (λabs 500 nm, λem 511 nm), yet it provides enhanced solubility in toluene and methyl tert‑butyl ether, facilitating purification by silica gel chromatography and enabling higher loading in polymer matrix doping for luminescent solar concentrators. When the N‑H pyrrole‑2‑carboxaldehyde is used as starting material, the acidic proton quenches the DDQ oxidation step, and the final boron complex shows broadened emission with a quantum yield drop from 0.88 to 0.52 (measured by the relative method using fluorescein in 0.1 M NaOH as standard). Therefore, the N‑alkylated aldehydes, particularly the ethyl variant, are preferred in photophysical research for constructing standard‑quality BODIPY cores.
Aldimine formation between 1‑ethyl‑2‑pyrrolecarboxaldehyde and (S)‑valinol in refluxing ethanol provides a bidentate Schiff base that, upon complexation with copper(II) acetate, catalyses the enantioselective Henry reaction of nitromethane with 4‑nitrobenzaldehyde. The ethyl substituent on the pyrrole ring improves the solubility of the copper complex in toluene, enabling a homogeneous catalytic run at −20 °C with a catalyst loading of 5 mol%. Under these conditions, the product β‑nitro alcohol is obtained in 92% ee and 85% isolated yield. The methyl congener, under identical conditions, yields only 78% ee, attributed to subtle differences in the steric environment around the metal centre as analysed by DFT calculations. Moreover, the N–H pyrrole‑2‑carboxaldehyde‑derived Schiff base undergoes competing imine‑enamine tautomerisation during the reaction, leading to racemisation. Thus, in asymmetric catalysis applications, the N‑ethyl group emerges not merely as a solubilising handle but as a stereochemical modulator.
Like most aryl and heteroaryl aldehydes, 1‑ethyl‑2‑pyrrolecarboxaldehyde is susceptible to autoxidation. Accelerated aging studies at 40 °C and 75% relative humidity over 6 months show an increase in total acidity from 0.2 mg KOH g⁻¹ to 1.8 mg KOH g⁻¹ when the container headspace is air, corresponding to the formation of 1‑ethyl‑2‑pyrrolecarboxylic acid at approximately 2.1%. When the material is stored under a nitrogen blanket at 2–8 °C, acidity remains below 0.5 mg KOH g⁻¹ for 18 months. Photochemical degradation is also significant: exposure to ambient laboratory light (fluorescent, 800 lux) for 48 h generates a yellow‑brown discoloration and an increase in high‑molecular‑weight oligomers detectable by GPC. The flash point, determined by ASTM D93 Pensky‑Martens closed cup, is 96 °C, classifying the liquid as combustible rather than flammable under UN GHS criteria; nonetheless, storage away from ignition sources is mandated. Contact with strong aqueous alkalis (pH > 12) at temperatures above 40 °C induces rapid Cannizzaro‑type disproportionation, necessitating immediate quenching. Consequently, the recommended packaging is amber glass, and the retest date is set at 12 months from the date of manufacture when stored continuously at ≤8 °C and protected from light. Containers partially used in production must be re‑blanketed with nitrogen before resealing, and any material showing a colour greater than Gardner 4 should be rejected for GMP synthesis. The oxidation sensitivity also imposes constraints on drying methods: molecular sieves (3 Å) can be used to reduce water, but anhydrous sodium sulfate should be avoided because its slight acidity catalyses aldehyde disproportionation, as evidenced by a 2–3% loss in assay after 24 h of contact.
