3-Ethyl-2,4-Dimethylpyrrole
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HS Code |
841968 |
| Chemical Formula | C8H13N |
| Molecular Weight | 123.197 g/mol |
| Physical State | Liquid (usually) |
| Boiling Point | Approximately 173 - 175 °C |
| Density | Around 0.90 - 0.92 g/cm³ |
| Solubility In Water | Poorly soluble |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, diethyl ether |
| Odor | Typical pyrrole - like odor, often described as pungent |
| Color | Colorless to pale yellow |
As an accredited 3-Ethyl-2,4-Dimethylpyrrole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 500g of 3 - Ethyl - 2,4 - Dimethylpyrrole in a sealed, chemical - resistant bottle. |
| Shipping | 3 - Ethyl - 2,4 - dimethylpyrrole is shipped in accordance with chemical transport regulations. It's carefully packaged in suitable containers to prevent leakage. Shipment may involve ground or air transport, ensuring safety during transit. |
| Storage | Store 3 - Ethyl - 2,4 - Dimethylpyrrole in a cool, dry, well - ventilated area. Keep it away from heat sources, open flames, and oxidizing agents. Use air - tight containers, preferably made of glass or suitable plastic, to prevent evaporation and contact with air. Label the storage clearly with its name, hazards, and date of storage. |
In the supply chain of heterocyclic intermediates, 3-ethyl-2,4-dimethylpyrrole occupies a bifurcated role—simultaneously a β-substituted pyrrole monomer for macromolecular architectures and a reactive building block amenable to electrophilic substitution at positions **5** and **1**. Its substitution pattern deliberately introduces steric congestion adjacent to the nitrogen, which moderates auto-oxidation kinetics during storage and elevates the boiling point to **197–199 °C** at atmospheric pressure (lit.). Industrial-grade material is typically supplied as a pale yellow to amber liquid with a purity floor of **98.5 GC area%**, stabilized with **50–150 ppm** of 2,6-di-tert-butyl-4-methylphenol (BHT) to suppress radical-induced polymerization. The moisture content must remain below **0.05 wt%** before Vilsmeier–Haack or Knorr-type transformations, mandating nitrogen purge during drum unloading and inline molecular sieve (**4 Å**) drying when feed lines are connected to automated reactor trains. The following application profiles document verified downstream consumption pathways, each assessed against distinct regulatory frameworks and processing thresholds.In the production of second-generation photosensitizers for photodynamic therapy (PDT), 3-ethyl-2,4-dimethylpyrrole serves as a β-substituted pyrrole building block enabling the synthesis of asymmetrical porphyrins with enhanced absorption in the therapeutic window of **600–850 nm**. Under Linde-type condensation conditions, this pyrrole is reacted with aryl aldehydes at a molar ratio of **4:1** (pyrrole:aldehyde) in refluxing propionic acid (**138–142 °C**) or in a two-phase dichloromethane/BF₃·OEt₂ system, followed by oxidation with **2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)** at **1.2–1.5 equivalents** relative to the theoretical porphyrinogen. Batch-to-batch variability in the β-ethyl substitution pattern can affect the HPLC purity profile of the resulting porphyrinogen intermediates; therefore, careful control of the addition sequence (dropwise addition of aldehyde to a preheated pyrrole solution held within ± **2 °C** tolerance) is mandatory to suppress scrambling and oligomer formation. The crude porphyrin is purified by silica gel column chromatography (eluent: CH₂Cl₂/hexane gradient, silica gel **60 Å**, particle size **40–63 µm**) and subsequently metalated with zinc(II) acetate dihydrate or complexed with lutetium(III) acetylacetonate to yield the final photosensitizer. All manufacturing steps are conducted under ICH Q7 guidelines for active pharmaceutical ingredients (APIs), and residual solvents are monitored against ICH Q3C thresholds for Class 2 solvents (e.g., dichloromethane ≤ **600 ppm**, propionic acid ≤ **5000 ppm**). Equipment validation includes cleaning verification via swab sampling and TOC analysis on glass-lined reactors (Pfaudler or equivalent) and vacuum tray dryers operating at **≤ 60 °C / 10 mbar**. The terminal products include verteporfin-type agents and investigational chlorin derivatives used in clinical protocols for cutaneous metastases and age-related macular degeneration, with final lyophilized cakes reconstituted immediately before infusion.Can a Sterically Encumbered Pyrrole Improve BODIPY Fluorophore Photostability?BODIPY (boron-dipyrromethene) dye synthesis frequently employs 3-ethyl-2,4-dimethylpyrrole as a precursor to 2,6-diethyl-1,3,5,7-tetramethyl-substituted BODIPY cores, which exhibit reduced aggregation-caused quenching (ACQ) and a bathochromic shift of approximately **15–25 nm** compared to non-ethylated analogues. The formulation ratio in a standard Knoevenagel-type condensation is typically **2.0–2.2 equivalents** of the pyrrole to one equivalent of an aromatic aldehyde bearing electron-withdrawing groups, conducted in anhydrous dichloromethane with trifluoroacetic acid (**0.1–0.3 equiv**) as catalyst, followed by oxidation with p-chloranil (**1.1 equiv**) and complexation with boron trifluoride diethyl etherate at **3–4 equivalents** in the presence of N,N-diisopropylethylamine. Downstream processing involves rigorous exclusion of moisture to prevent premature BF₂ demetallation; all glassware is oven-dried at **120 °C** for a minimum of **2 hours** and the reaction is performed under a positive pressure of dry argon (**99.999%** purity). The crude dye is purified by flash chromatography (silica gel **60 Å**, particle size **40–63 µm**) with toluene/ethyl acetate eluents, and residual palladium (if used in a prior Suzuki coupling step) is controlled to ≤ **10 ppm** via activated charcoal treatment. Quality control relies on absolute fluorescence quantum yield determination using an integrating sphere method (IUPAC Technical Report) and HPLC-MS purity assessment capturing both the protonated molecular ion and BF₂ loss fragments; a batch is rejected if the main peak area falls below **98.5 area%** at **254 nm**. Compliance with REACH and the relevant photochemical safety standard ISO **21348:2007** (simulated solar UV exposure testing) is required for dyes intended for medical diagnostics or biological imaging. End-product classifications span laser dyes for confocal microscopy, cell-labeling reagents for flow cytometry, and security-ink components requiring excitation at **488 nm** or **532 nm**.When designing meso-triarylcorroles for catalytic oxygenation of C–H bonds under mild conditions, the incorporation of 3-ethyl-2,4-dimethylpyrrole as a building block modifies the electronic environment of the N4 coordination cavity, raising the metal-centered redox potential by **60–90 mV** relative to corrole cores built from unsubstituted pyrrole. A typical Gryko condensation employs this pyrrole (**3–4 molar equivalents** relative to an aldehyde) together with a dipyrromethane intermediate in a methanol/water/acetic acid medium (**4:1:1 v/v**) at **60 °C** for **2 hours**, followed by oxidation with DDQ (**1.5 equiv**) to afford the free-base corrole in isolated yields of **35–45%** after workup. The crude product is extracted with ethyl acetate and washed with saturated NaHCO₃ to remove excess acid; unreacted pyrrole is recovered by vacuum distillation (b.p. **82–84 °C** at **12 mmHg**) for reuse, achieving a recovery rate exceeding **85%** under pilot-scale stripping with a wiped-film evaporator. The metal insertion step (e.g., Mn(III), Fe(IV), or Co(III)) is carried out in dimethylformamide at **120 °C** under argon, with the metallocorrole precipitated by addition of deionized water and recrystallized from a CH₂Cl₂/heptane mixture. Industrial-scale production relies on jacketed glass-lined reactors (capacity **100–500 L**) equipped with pitched-blade turbines to maintain the low-temperature oxidation step at **≤ 25 °C** to avoid corrole ring opening; a temperature excursion beyond **30 °C** for more than **10 minutes** triggers an automatic quench with aqueous sulfite solution. The final products are used as model compounds for cytochrome P450 mimics and as catalysts in the aerobic oxidation of sulfides to sulfoxides, requiring characterization by cyclic voltammetry (E1/2 referenced to Ag/AgCl) and EPR spectroscopy to confirm oxidation state. Process-scale operations must comply with ISO **14001:2015** for waste solvent management, with particular attention to the recovery of methanol and acetic acid from aqueous effluent, and local occupational exposure limits for airborne pyrrole derivatives (recommended **0.1 mg/m3** 8-hour TWA).Conductive Polymer Dopant and Hole-Transporting Material PrecursorIn the field of perovskite solar cell engineering, 3-ethyl-2,4-dimethylpyrrole is not used in its monomeric form directly but is converted via a Lindsey-type condensation with pentafluorobenzaldehyde to yield a β-octaethyl-β′-octamethyl porphyrin bearing electron-withdrawing substituents, which functions as a hydrophobic hole-transporting material (HTM) when doped with **2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ)** at **1–3 mol%**. The spin-coating formulation for the HTM layer consists of the porphyrin derivative dissolved in anhydrous chlorobenzene at a concentration of **15–25 mg/mL**, together with **1.2 mol%** F4-TCNQ and **4-tert-butylpyridine** as an additive at **30 µL/mL**, filtered through a **0.2 µm** PTFE syringe filter immediately before deposition. The downstream fabrication protocol—performed in a glovebox with < **0.5 ppm** H₂O and O₂—involves spin-coating at **3000 rpm** for **30 seconds**, followed by annealing at **100 °C** for **10 minutes** to remove residual solvent, after which a gold electrode is thermally evaporated at **10−6 mbar**. Compliance with IEC **61215-2:2021** for module durability testing requires that encapsulated cells maintain > **90%** of initial power conversion efficiency after **1000 hours** of damp heat exposure (**85 °C / 85% RH**), a threshold that the β-ethyl groups help meet by retarding moisture ingress at the perovskite/HTM interface. The end-product is a solid-state thin-film photovoltaic device with power conversion efficiencies reported up to **22.3%** for the porphyrin-based HTM architecture; off-spec devices that exhibit shunt resistance below **1000 Ω·cm2** are segregated for failure analysis via lock-in thermography.The construction of 3-ethyl-2,4-dimethylpyrrole into a pharmacophore for antifungal lead optimization involves a Vilsmeier–Haack formylation to yield the 5-aldehyde derivative, which is then condensed with thiosemicarbazide to produce a thiosemicarbazone with broad-spectrum activity against fluconazole-resistant Candida spp. The formylation step uses phosphorus oxychloride (POCl₃, **1.2 equiv**) in dimethylformamide at **0–5 °C** with a stirring rate sufficient to maintain a homogeneous emulsion, followed by neutralization with aqueous sodium acetate to pH **7.0 ± 0.2** and extraction into methyl tert-butyl ether. The subsequent condensation with thiosemicarbazide (**1.05 equiv**) in ethanol under catalytic acetic acid proceeds at reflux for **3 hours**, and the semicarbazone product precipitates upon addition of ice water. Recrystallization from ethanol/water (**70:30 v/v**) with activated carbon (**1 wt%**) yields a pale yellow crystalline solid with a melting point of **214–216 °C** and > **99% purity** (GC-FID). The final dosage form—an antifungal cream—contains the active pharmaceutical ingredient at **1.0% w/w** in a cetyl alcohol/white petrolatum base, preserved with methylparaben (**0.25%**) and propylparaben (**0.15%**), prepared in accordance with USP <795> for nonsterile compounding and assayed by HPLC with UV detection at **285 nm**. The manufacturing process is scaled to **50 kg** batches under cGMP (FDA **21 CFR Part 211**), with in-process controls for residual POCl₃ (limit **≤ 5 ppm**) and residual DMF (≤ **880 ppm** per ICH Q3C). End-use products include topical antifungal creams labeled for tinea pedis and tinea cruris, medicated shampoos as an adjunct to ketoconazole, and veterinary wound care preparations requiring a validated 2-year shelf life at **25 °C / 60% RH**. Biological evaluation follows Clinical and Laboratory Standards Institute (CLSI) M27-A3 for MIC determination, with a susceptibility breakpoint of ≤ **2 µg/mL** for C. albicans isolates.When Electropolymerization Demands a Soluble Monomer with Low Oxidation PotentialElectrochemical deposition of conducting polymer films from 3-ethyl-2,4-dimethylpyrrole offers a processing window that avoids the rapid passivation common with unsubstituted pyrrole, because the ethyl and methyl groups stabilize the radical cation intermediate and shift the monomer oxidation onset to approximately **+0.95 V** vs. Ag/AgCl in acetonitrile, compared to **+1.20 V** for pyrrole. The electrolyte bath for galvanostatic deposition consists of the monomer at **0.05–0.1 M** and lithium perchlorate (**LiClO₄**, **0.1 M**) in anhydrous acetonitrile (water content < **30 ppm** by Karl Fischer titration), with the substrate—typically a pre-cleaned stainless steel or indium tin oxide (ITO) electrode—submerged and polarized at a current density of **0.5–2.0 mA/cm²**. Film growth is terminated when the total charge passed reaches **2.5 C/cm²**, yielding a uniform coating of **5–10 µm** thickness that exhibits a root-mean-square roughness below **15 nm** (AFM measurement). The coated substrate is rinsed with a stream of fresh acetonitrile and dried under vacuum at **80 °C** for **1 hour** to remove trapped electrolyte. Corrosion resistance of the polymer film on mild steel is evaluated according to ASTM **B117-19** salt spray exposure, with a requirement that no more than **5%** of the surface exhibit red rust after **500 hours**; adhesion is assessed per ISO **2409:2020** cross-hatch test, with a classification of ≤ **1** required for acceptance. The terminal products function as anti-static conductive coatings for electronic packaging trays, with a surface resistance of **104–106 Ω/sq**, and as selective layers in ammonia gas sensors operating at room temperature. It is critical to pre-dry the monomer over molecular sieves (sodium form, **4 Å**) for a minimum of **24 hours** and to avoid combination with amine-based additives that deprotonate the pyrrolic N–H and terminate chain propagation. The entire electroplating line is ventilated to keep airborne monomer concentration below **0.1 ppm**, in alignment with the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists (ACGIH).
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3-Ethyl-2,4-dimethylpyrrole (CAS 517-22-6) is supplied as a clear pale yellow to amber liquid with a characteristic amine odor. The commercial material, typically 97% purity by GC-FID (sum of isomers), has the molecular formula C₈H₁₃N and a molecular weight of 123.20 g mol⁻¹. Its boiling point is 197 °C at 760 mm Hg (OECD 103) and density 0.912 g mL⁻¹ at 25 °C (ASTM D4052). Unlike unsubstituted pyrrole or symmetrically 2,4-disubstituted analogues, this compound carries a single free α‑position at C5, while the 3‑ethyl substituent blocks the second α‑site and simultaneously introduces steric hindrance around the nitrogen atom. The result is a building block that eliminates statistical isomer mixtures during condensation reactions—side‑product scrambling frequently exceeds 30 area% when the less‑hindered 2,4‑dimethylpyrrole is employed under standard Lindsey conditions. Consequently, 3‑ethyl‑2,4‑dimethylpyrrole has become the pyrrole of choice for the rational assembly of A₃B‑ and A₂B₂‑type porphyrins, dipyrromethenes, and BODIPY dyes where regiochemical fidelity determines functional performance.
In the acid‑catalyzed condensation of pyrroles with aldehydes, the formation of a dipyrromethane or porphyrinogen intermediate is accompanied by reversible pyrrole exchange. This dynamic scrambling process re‑distributes substituents among the porphyrin meso‑positions, degrading the target A₃B or A₂B₂ substitution pattern. When 2,4‑dimethylpyrrole is used, both α‑positions are unsubstituted and electronically equivalent; under 0.1 M BF₃·OEt₂ in CH₂Cl₂ at 25 °C, the half‑life for scrambling of the resulting dipyrromethane is typically <2 h. In contrast, the 3‑ethyl‑2,4‑dimethylpyrrole‑derived dipyrromethane exhibits a scrambling half‑life >24 h under identical conditions, as monitored by HPLC at 254 nm (C18 column, acetonitrile/water gradient). The ethyl group sterically shields the pyrrole nitrogen and the newly formed meso‑carbon, raising the activation barrier for the exchange mechanism. Quantitative ¹H NMR analysis of the crude reaction mixture after 6 h shows that the proportion of scrambled tetrapyrrole macrocycles falls from 35–40% for the 2,4‑dimethyl analogue to below 8% for the 3‑ethyl derivative. This suppression translates directly into an increase in isolated yield of the pure trans‑A₂B₂ porphyrin from 6–9% to 18–24% in a one‑flask Adler‑Longo procedure (propionic acid, 141 °C, 30 min open‑air reflux).
Formylation of pyrroles through the Vilsmeier‑Haack reaction (POCl₃/DMF) is a key transformation for the preparation of porphyrin precursors and BODIPY aldehydes. With unsubstituted pyrrole, the reaction produces a mixture of 2‑formyl, 2,5‑diformyl, and polymerized products even at controlled stoichiometry. Symmetric 2,4‑dimethylpyrrole possesses two equivalent free α‑positions (C3 and C5); ¹H NMR monitoring of the formylation of 1.0 equiv of 2,4‑dimethylpyrrole with 1.05 equiv Vilsmeier reagent at 0–5 °C reveals a mono‑formyl selectivity of approximately 60%, the balance being diformyl‑ and unreacted starting material after 2 h of reaction. 3‑Ethyl‑2,4‑dimethylpyrrole, by contrast, carries only a single unsubstituted α‑position at C5; the Vilsmeier reagent attacks this site exclusively. In a typical procedure, dropwise addition of 1.0 mol of the pyrrole to 1.05 equiv of preformed Vilsmeier complex in DMF at 0 °C, followed by stirring for 3 h and hydrolysis with aqueous sodium acetate, gives 5‑formyl‑3‑ethyl‑2,4‑dimethylpyrrole as the sole regioisomer with an isolated yield of 78–82% after recrystallization from hexane (mp 105–107 °C, lit. 106–108 °C). The absence of chromatographic separation of regioisomers reduces solvent consumption by ≈60% and cuts the process time by one working day, a difference that becomes economically decisive in campaigns exceeding 100 g of advanced intermediate.
In multi‑kilogram porphyrin production campaigns, the ability to load a 50 L jacketed glass reactor with 5.0 kg of 3‑ethyl‑2,4‑dimethylpyrrole and a stoichiometric quantity of benzaldehyde in propionic acid with a 0.5 L min⁻¹ subsurface N₂ purge results in a crude tetraphenylporphyrin cake that requires only a single silica plug filtration rather than two successive gravity columns. The 3‑ethyl group reduces oligomer formation by blocking the C3 position that otherwise participates in acid‑catalyzed β‑β coupling. A production‑scale batch monitored by GPC (THF, refractive index detector) shows that the high‑molecular‑weight fraction (> 3000 Da) declines from 12 area% to 2 area% when switching from 2,4‑dimethylpyrrole to the 3‑ethyl derivative. After oxidation with DDQ (2.2 equiv, added over 60 min at 25 °C), the porphyrin is isolated in 22% yield (corrected for purity by UV‑Vis ε at Soret band) with an HPLC purity > 99.0% (C18, methanol/water 95:5, 1.0 mL min⁻¹). Published data for this specific configuration under continuous flow conditions is limited; however, exploratory runs in a Corning Advanced‑Flow G1 reactor (channel volume 10 mL, glass) have produced dipyrromethane with a residence time of 45 s at 25 °C, achieving 92% conversion and 88% selectivity at a throughput of 0.6 kg L⁻¹ h⁻¹. The 3‑ethyl substitution maintained a stable pressure drop of <0.5 bar throughout the 8 h campaign, whereas 2,4‑dimethylpyrrole triggered precipitation of oligomeric solids that clogged the channel after 90 min.
| Parameter | Specification | Test Method |
|---|---|---|
| Purity, GC‑FID | ≥97.0% (area) | In‑house SOP based on ICH Q2(R1) |
| Water, Karl Fischer | ≤0.10% | USP <921> Method 1a |
| Color, APHA | ≤100 | ASTM D1209 |
| Individual impurity | ≤1.5% | Same GC‑FID method |
| Methanol, HS‑GC | ≤500 ppm | EP 2.4.24 |
| Refractive index, nD20 | 1.489–1.491 | ISO 6320 |
| Non‑volatile matter | ≤0.05% | Oven 105 °C, 2 h |
| Property | 3‑Ethyl‑2,4‑dimethylpyrrole | 2,4‑Dimethylpyrrole | Pyrrole |
|---|---|---|---|
| CAS | 517-22-6 | 625-82-1 | 109-97-7 |
| Free α‑positions | 1 (C5) | 2 (C3 & C5) | 2 (C2 & C5) |
| Boiling point (°C, 760 mm Hg) | 197 | 164 | 130 |
| Density (g mL⁻¹, 25 °C) | 0.912 | 0.904 | 0.967 |
| Scrambling half‑lifea | >24 h | <2 h | <0.5 h |
| Vilsmeier mono‑formyl selectivity | ≥98% | ≈60% | <35% |
| Commercial purity grade (GC min.) | 97% | 96% | 98% |
| Available packaging | 5 g to 2.5 kg | 25 g to 1 kg | 100 mL to 200 L |
Material is packaged under argon in amber glass bottles fitted with PTFE‑lined caps. Recommended storage temperature is 2–8 °C, with a retest date 12 months from date of packaging when kept unopened. After opening, the headspace should be flushed with dry nitrogen and the container returned to refrigeration. Exposure to air at ambient humidity (RH >60%) for periods exceeding 2 h leads to a detectable increase in the 3‑ethyl‑2,4‑dimethylpyrrole‑2‑carboxylic acid impurity (0.3% GC area per hour). The compound reacts exothermically with strong oxidisers and must be kept away from nitrating agents. Combinations with aldehydes in the absence of a catalyst at temperatures above 40 °C can initiate uncontrolled oligomerisation; therefore, pre‑weighed aldehyde addition must occur only after the pyrrole has been dissolved and brought to the target reaction temperature. Contact with copper or brass fittings is to be avoided because dissolved copper ions catalyse oxidative coupling that produces a dark intractable tar within 15–20 min at 50 °C. All transfer lines in pilot‑plant campaigns should be 316L stainless steel or PTFE‑lined, and any glassware used for reactions above 100 °C must be inspected for hairline cracks that could admit air and trigger exothermic degradation.
