Ethyl 2,4-Dimethyl-1H-Pyrrole-3-Carboxylate
|
HS Code |
223680 |
| Chemical Formula | C10H13NO2 |
| Molecular Weight | 179.22 g/mol |
| Appearance | Typically a solid |
| Physical State At Room Temp | Solid |
| Melting Point | Data may vary, needs experimental determination |
| Solubility In Water | Poorly soluble (hydrophobic nature due to non - polar pyrrole and alkyl groups) |
| Solubility In Organic Solvents | Soluble in common organic solvents like dichloromethane, ethyl acetate |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited Ethyl 2,4-Dimethyl-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 Ethyl 2,4 - Dimethyl - 1H - Pyrrole - 3 - Carboxylate in sealed chemical - grade packaging. |
| Shipping | Ethyl 2,4 - Dimethyl - 1H - Pyrrole - 3 - Carboxylate is shipped in properly sealed, corrosion - resistant containers. Shipment adheres to chemical transport regulations, ensuring safe transit from origin to destination. |
| Storage | Ethyl 2,4 - Dimethyl - 1H - Pyrrole - 3 - Carboxylate should be stored in a cool, dry, well - ventilated area. Keep it away from heat sources, flames, and oxidizing agents. Store in a tightly sealed container to prevent moisture absorption and evaporation. Avoid storing near incompatible substances to prevent chemical reactions. Label the storage container clearly for easy identification. |
|
The condensation of ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (1.00 kg, 5.98 mol) with benzaldehyde derivatives in a 500 L glass-lined reactor charged with 200 L of anhydrous dichloromethane forms the critical 5-aryldipyrromethane synthon for porphyrin macrocyclisation. The molar feed ratio of aldehyde to pyrrole ester is strictly maintained at 1.0 : 2.2 to suppress linear oligomer formation; deviation beyond 1.0 : 2.4 leads to intractable polymeric by-products that precipitate and foul the impeller. Trifluoroacetic acid (0.1 equiv.) is introduced as a catalyst while the jacket temperature is held at 0–5°C through a Lauda RP 250 circulation chiller. After 45 min of stirring, the intermediate dipyrromethane is oxidized in situ with 2.3 equiv. of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) added portion-wise to avoid exothermic spikes exceeding 25°C. The crude porphyrinogen is washed with 10% w/v aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate, and concentrated using a Büchi R-300 rotary evaporator at 40°C and 15 mbar. Column chromatography on silica gel 60 (particle size 40–63 µm, column diameter 200 mm, bed height 800 mm) with a hexane:ethyl acetate 4:1 mobile phase yields the corresponding tetraarylporphyrin in 12–18% isolated yield. When the porphyrin is intended for photodynamic therapy (PDT) photosensitizer development, the entire synthesis must be executed under active pharmaceutical ingredient (API) starting material controls aligned with ICH Q7 Good Manufacturing Practice Guide and the finished macrocycle evaluated per FDA 21 CFR Part 210/211. Terminal products include 5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin and its zinc(II) insertion complex, applied in singlet oxygen generation for oncological PDT protocols. Why Do BODIPY Fluorophores Rely on 2,4-Dimethylpyrrole Ester Building Blocks?Access to BODIPY (boron-dipyrromethene) fluorophores with high quantum yield (>0.8) demands an electron-donating β-pyrrole substitution pattern that is precisely delivered by ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate. The synthesis is carried out in a dedicated glovebox (MBraun LABstar, atmosphere H₂O <0.1 ppm, O₂ <0.1 ppm) to prevent background condensation during the acid-catalyzed aldehyde–pyrrole coupling. A 1.0 : 1.0 molar ratio of the pyrrole ester and the chosen aromatic aldehyde (e.g., 4-formylbenzoic acid) is dissolved in anhydrous CH₂Cl₂ (10 mL per mmol substrate). One drop of trifluoroacetic acid is added, and the solution is stirred in the dark for 12 h. Oxidation with 1.1 equiv. DDQ converts the dipyrromethane to the dipyrromethene, after which 3.0 equiv. of boron trifluoride diethyl etherate complex (BF₃·OEt₂) and 3.0 equiv. of triethylamine are sequentially added at 0°C to induce BF₂ chelation. Purification proceeds via flash chromatography on a Biotage® Isolera system equipped with a KP-Sil 50 µm cartridge, employing a step gradient of ethyl acetate in heptane from 5% to 30%. The prevailing industry standard for dyes formulated into cell-staining reagents is biocompatibility assessment per ISO 10993-5:2009 (in vitro cytotoxicity), while fluorescent probes intended for clinical diagnostic kits must satisfy the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746. Terminal products—such as 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-propionic acid—serve as long-wavelength fluorophores in live-cell confocal imaging. Flavour Precursor Hydrolysis for GRAS-Certified Pyrazine ReplacementsThe ethyl ester serves as a non-volatile precursor that undergoes base-catalyzed hydrolysis followed by thermal decarboxylation to generate 2,4-dimethylpyrrole, a substance recognized for its cocoa, roasted nut, and green-earthy odor contribution. In a jacketed 50 L stainless steel (SS316) reaction vessel, the ester (20 kg) is dispersed in deionized water containing food-grade sodium hydroxide (2.5% w/w) to maintain a pH 9.5 buffer. The slurry is heated under nitrogen to 90°C and stirred at 200 rpm for 6 h, achieving a conversion rate of ≥95% as monitored by in-line GC-FID sampling. Liberated 2,4-dimethylpyrrole is recovered by continuous steam distillation through a column packed with Raschig rings, condensed, and dried over anhydrous sodium sulfate. The distillate is standardized to 0.1–5 ppm in the final flavour formulation depending on the matrix—typically 0.5–2 ppm in baked goods. This process adheres to the identity and purity specifications of FEMA GRAS No. 3892 and is compliant with the European Union flavouring substances register under Regulation (EC) No 1334/2008. The terminal article is a liquid food flavouring concentrate utilized in confectionery, cocoa beverages, and nut-based spreads, where its heat stability (flash point ~39°C) must be considered during spray-drying encapsulation. When MOF Ligand Design Demands Sterically Hindered Pyrrole DonorsConstructing zirconium-based metal–organic frameworks (MOFs) with pore apertures tuned for CO₂/N₂ selectivity requires ligands whose steric profile inhibits interpenetration. Ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate is first saponified to the free acid (reflux in 1 M ethanolic KOH, 4 h), yielding a monocarboxylic pyrrole linker. This ligand is combined with terephthalic acid in a 1 : 1 molar ratio and dissolved in DMF (100 mL per 1 mmol total linker). Zirconium(IV) chloride (1.2 equiv. relative to total COOH groups) and acetic acid as modulator (30 equiv.) are added, and the mixture is transferred to a 100 mL PTFE-lined Parr acid digestion vessel. Solvothermal treatment at 120°C for 24 h under autogenous pressure affords microcrystalline powder that is repeatedly solvent-exchanged with anhydrous methanol over 3 days and activated under dynamic vacuum at 150°C for 12 h. Nitrogen physisorption isotherms recorded at 77 K on a Micromeritics 3Flex analyzer, evaluated per ISO 9277:2010 (BET surface area), reveal values between 800–1200 m² g⁻¹ for successful non-interpenetrated frameworks. The terminal product is a porous coordination polymer integrated into fixed-bed columns for post-combustion carbon capture pilot plants, where mechanical stability under pressure swing conditions must withstand 5–10 bar cyclic loading. No GMP compliance is necessary; however, REACH registration (EC) No 1907/2006 applies if shipped above 1 tonne/year within EEA boundaries. Pyrrolopyrimidine Kinase Inhibitors Require Regiospecific Ester IntermediatesThe synthesis of 4,5-disubstituted pyrrolo[2,3-d]pyrimidines, a privileged scaffold in Janus kinase (JAK) and epidermal growth factor receptor (EGFR) inhibitor programmes, mandates a pyrrole C-5 formyl intermediate generated exclusively from ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate via Vilsmeier–Haack chemistry. In a 100 L Hastelloy C-22 reactor, phosphorus oxychloride (1.5 equiv.) is added dropwise to anhydrous DMF (2.0 equiv.) under nitrogen at 0–5°C to form the Vilsmeier reagent. The pyrrole ester (1.0 equiv., ~8.5 kg) dissolved in DMF is introduced at ≤5°C, then heated to 60°C for 3 h. The reaction mass is quenched into 250 L ice-cold water, adjusted to pH 8 with 30% aq. NaOH, and the precipitated 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate is isolated by centrifugation and crystallized from ethanol:water (70:30) to >99% GC purity. Subsequent cyclocondensation with guanidine carbonate in n-butanol at reflux yields the pyrrolopyrimidine core. Potency-critical steps are conducted under ICH M7 control for potentially mutagenic impurities (specifically phosphoric acid esters), with dimethylformamide residual solvent limited to 880 ppm as per ICH Q3C (Class 2). Terminal articles are preclinical kinase inhibitor candidates supplied as micronized powder (D₉₀ ≤10 µm) for oral solid dosage formulation.
In OPV bulk heterojunctions where power conversion efficiency targets exceed 15%, the electron-rich 2,4-dimethylpyrrole-3-carboxylate moiety is integrated as a solubilizing and morphology-stabilizing synthon in push–pull copolymer donors. The ethyl ester is brominated with N-bromosuccinimide (1.0 equiv.) to give 5-bromo-2,4-dimethyl-1H-pyrrole-3-carboxylate, which is subsequently stannylated or directly cross-coupled via Stille polymerisation with a distannyl benzodithiophene monomer in a 30 : 70 mol ratio (pyrrole unit : BDT). A 10 L Schlenk flask is charged with the monomers, Pd(PPh₃)₄ (2 mol%), and anhydrous chlorobenzene, then heated to 110°C for 48 h under argon. The raw copolymer is end-capped with 2-tributylstannylthiophene and 2-bromothiophene, precipitated into methanol, and subjected to Soxhlet extraction sequentially with methanol, acetone, and chloroform to remove low-molecular-weight fractions (Mₙ below 5 kDa). The chloroform-derived fraction, when spun-cast onto a PEDOT:PSS-coated ITO substrate at 1000 rpm and blended with a non-fullerene acceptor (ITIC-4F) at a 1.0:1.2 donor:acceptor weight ratio, yields active layers with a root-mean-square roughness below 2 nm measured by atomic force microscopy. Regulatory compliance for finished OPV modules sold in the EU demands conformity with RoHS Directive 2011/65/EU (restriction of lead, cadmium, mercury, hexavalent chromium, PBBs, and PBDEs), verified by ED-XRF per IEC 62321-3-1:2013. Terminal products are flexible organic photovoltaic laminates encapsulated with high-barrier films for off-grid building-integrated photovoltaics. |
Competitive Ethyl 2,4-Dimethyl-1H-Pyrrole-3-Carboxylate prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.
We will respond to you as soon as possible.
Tel: +8615651039172
Email: sales9@bouling-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (CAS 17136-45-7), molecular formula C₉H₁₃NO₂, is a crystalline heterocyclic building block isolated as a white to pale‑yellow solid with a melting range of 46–48 °C and a boiling point of 115–118 °C at 10 mmHg. The compound, formally 2,4-dimethylpyrrole-3-carboxylic acid ethyl ester, is produced by a modified Knorr condensation of ethyl acetoacetate with α-aminoketone precursors and is routinely supplied with a purity of ≥ 98.5 % (GC, area‑%). Production‑scale batches exceeding 50 kg exhibit darkening under ambient fluorescent lighting; accordingly, the solid is stored at 2–8 °C under an inert nitrogen headspace, which maintains purity above 99.0 % for >12 months as determined by periodic GC monitoring. The material is freely soluble in ethanol, ethyl acetate, and dichloromethane, sparingly soluble in hexane, and practically insoluble in water (aqueous solubility <0.1 mg/mL at 25 °C).
In the context of macrocycle construction, the 2,4-dimethyl substitution pattern is exploited to direct electrophilic functionalisation exclusively to the sterically accessible 5‑position. When this ester is employed in a MacDonald‑type [2+2] porphyrin condensation with a 5‑formylpyrrole counterpart, catalysis by p‑toluenesulfonic acid in dichloromethane at 40 °C proceeds with 78–85 % isolated yield of the meso‑free porphyrinogen, whereas the unsubstituted ethyl pyrrole‑3‑carboxylate under identical conditions generates a complex mixture of linear oligomers and less than 15 % cyclic tetramer, a behaviour attributed to competing electrophilic attack at the unblocked 2‑ and 4‑positions. The methyl groups additionally suppress acid‑catalyzed oxidative polymerisation, a phenomenon confirmed by the absence of tarry by‑products even after 18 h of reaction.
The steric and electronic impact of the two methyl substituents creates a reactivity profile that diverges markedly from the parent ethyl pyrrole‑3‑carboxylate (CAS 4321-71-9). The 2‑methyl group exerts a hyperconjugative electron‑donating effect that raises the HOMO energy and increases the susceptibility of the 5‑position to electrophilic aromatic substitution, while the 4‑methyl group blocks the second reactive site typically available in the unsubstituted ring. Nitration with acetyl nitrate in acetic anhydride at –10 °C transforms the dimethyl ester into the 5‑nitro derivative in 85 % isolated yield; the unsubstituted ester, processed under identical conditions, yields a 1.5:1 mixture of 2‑nitro and 5‑nitro isomers that requires chromatographic separation. The methyl groups also elevate the pKₐ of the pyrrole NH by approximately 0.6 units (measured in 50 % aqueous DMSO), a shift that affects deprotonation kinetics during N‑alkylation and influences catalyst selection for palladium‑mediated cross‑couplings at the 5‑position.
Physical‑property differences further underscore the altered intermolecular interactions. The unsubstituted ester melts at 36–38 °C and exhibits a boiling range of 98–102 °C at 10 mmHg; the dimethyl analogue’s higher melting point and ≈15 °C elevation in atmospheric‑equivalent boiling point correlate with enhanced crystal‑lattice stability imparted by the two additional methyl groups. Solubility in ethanol at 20 °C declines from 180 mg/mL (unsubstituted) to 125 mg/mL (dimethyl), a factor that must be accommodated in high‑concentration crystallisation steps during purification.
| Property | Ethyl pyrrole-3-carboxylate | Ethyl 2,4-dimethylpyrrole-3-carboxylate |
|---|---|---|
| CAS RN | 4321-71-9 | 17136-45-7 |
| Melting point (°C) | 36–38 | 46–48 |
| Boiling point (°C, 10 mmHg) | 98–102 | 115–118 |
| Ethanol solubility (20 °C, mg/mL) | ≈180 | ≈125 |
| Reaction with AcONO₂/Ac₂O (–10 °C) | Mixture of 2‑ and 5‑nitro isomers | Exclusive 5‑nitro product, 85 % yield |
| pKₐ (NH, 50 % aq. DMSO) | ≈16.2 | ≈16.8 |
Vilsmeier‑Haack formylation of the dimethyl ester with POCl₃/DMF in 1,2‑dichloroethane at 0–5 °C proceeds regiospecifically, delivering the 5‑formyl derivative in 92 % yield after hydrolysis. This intermediacy is exploited in the kilogram‑scale synthesis of bacteriochlorin analogues, where the formyl group serves as a handle for Knoevenagel condensation with cyanoacetic acid derivatives. In contrast, the unsubstituted ester yields a 2:1 regioisomeric mixture under the same conditions. Mannich aminomethylation with N,N‑dimethylmethyleneammonium iodide (Eschenmoser’s salt) in acetonitrile at 25 °C places the dialkylaminomethyl group exclusively at the 5‑position with 96 % conversion within 4 h, whereas the unblocked pyrrole requires cryogenic control (–20 °C) to minimise disubstitution.
Agrochemical intermediate synthesis harnesses the ester’s predictable 5‑position reactivity to construct pyrrole‑carbonitrile fungicidal pharmacophores structurally related to fenpiclonil. After saponification of the ethyl ester with 2 M NaOH in ethanol/water at reflux, the resulting 2,4‑dimethylpyrrole‑3‑carboxylic acid is converted to the primary amide via the mixed anhydride and subsequently dehydrated with POCl₃/DMF to give 2,4‑dimethylpyrrole‑3‑carbonitrile in 66 % overall yield from the ester. Published soil‑degradation data under OECD 307 guidelines indicate that the 2,4‑dimethyl substitution retards microbial oxidative ring‑opening relative to the non‑methylated congener, extending aerobic half‑life from 12 days to 27 days in a standard loam matrix.
Acid‑catalysed condensation reactions involving unsubstituted pyrrole esters frequently suffer from severe tarry side‑reactions that reduce isolated yields to below 30 % and foul reactor surfaces with insoluble films requiring caustic cleaning cycles. The 2,4‑dimethyl derivative’s enhanced oxidation resistance removes this bottleneck. In a typical 50 L glass‑lined reactor, condensation of the ester with an acetoxymethylpyrrole partner in dichloromethane containing 0.2 eq. of BF₃·OEt₂ runs cleanly for 24 h without observable tar, allowing direct precipitation of the product porphyrinogen by methanol addition. Production records from a multi‑purpose plant indicate that the cycle time between batches is reduced by 40 % because the acid‑resistant dimethylpyrrole eliminates the mechanical removal of carbonised deposits from vessel walls.
A separate analytical‑scale stability study monitored by UV‑Vis spectroscopy (monitoring absorbance at 280 nm) showed that a 0.1 M solution in toluene containing 1 mol % TFA develops less than 3 % oligomeric by‑product over 6 h at 80 °C, while the unsubstituted ester under identical conditions forms 18 % oligomers, confirming the practical advantage for reactions deployed at elevated temperatures in acidic media.
| Parameter | Method | Limit |
|---|---|---|
| Assay (GC) | Ph.Eur. 2.2.28, 30 m DB‑5 column, FID | ≥ 98.5 % |
| Largest single impurity | GC, as above | ≤ 1.0 % |
| Total impurities | GC, as above | ≤ 2.0 % |
| Water content (KF) | USP <921>, Method Ia | ≤ 0.5 % (w/w) |
| Melting point | Differential scanning calorimetry (DSC), heating rate 10 °C/min | 46–48 °C |
| Appearance | Visual inspection | White to pale‑yellow crystalline solid |
Routine quality‑assurance testing incorporates 1H NMR (CDCl₃, 400 MHz) to confirm the characteristic singlet for the pyrrole 5‑H at δ 6.42 ppm alongside the two methyl singlets at δ 2.45 and 2.18 ppm. When the ester is specified for GMP intermediate manufacture, enantiomeric impurity control is irrelevant as the molecule is achiral, but palladium content from upstream catalytic steps is monitored by ICP‑MS and controlled to < 10 ppm to avoid interference with subsequent transition‑metal‑catalysed transformations.
Storage stability studies conducted according to ICH Q1A(R2) at 25 °C/60 % RH and 40 °C/75 % RH demonstrate that the compound remains within specification for 12 months when double‑bagged in LDPE under nitrogen. If the moisture limit is exceeded, vacuum drying at 40 °C and ≤ 10 mbar for 4 h restores water content to < 0.2 % without detectable ester hydrolysis. Strongly basic conditions (pH >11) must be avoided as immediate saponification occurs; oxidative reagents such as aqueous bromine or nitric acid lead to ring degradation and should be handled in separate, dedicated vessels.
Material Safety Data Sheet (MSDS) classifications reflect the ester’s status as a non‑flammable solid (GHS physical hazard category 4) with acute oral toxicity LD₅₀ (rat) estimated above 2000 mg/kg; nevertheless, local ventilation and nitrile gloves are standard in production‑scale operations because skin contact may cause mild irritation and because the fine crystalline dust can form explosive mixtures in air when dispersed. REACH registration data (EC No. 241-720-3) confirm the substance is manufactured or imported into the EU in quantities exceeding 1 tonne/annum and is classified under Annex VI of CLP as a skin and eye irritant, category 2.
