Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate

Product Name Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate
Alias ETMPC
Einecs 402-620-6
Mininmum Order 1g
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
Price Inquiry sales9@bouling-chem.com
Manufacturer Bouling Chemical Co., Limited
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In terms of specification, Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate is supplied with ≥98% purity (HPLC) and confirmed structure by ¹H NMR, making it suitable for pharmaceutical intermediate synthesis.

Specifications

HS Code	324715
Chemical Formula	C10H15NO2
Molecular Weight	181.23 g/mol
Appearance	Typically a liquid or solid (depending on conditions)
Boiling Point	Data may vary, specific value needs experimental determination
Melting Point	Data may vary, specific value needs experimental determination
Solubility In Water	Low solubility, organic - soluble
Density	Data may vary, specific value needs experimental determination
Flash Point	Data may vary, specific value needs experimental determination
Vapor Pressure	Data may vary, specific value needs experimental determination
Stability	Stable under normal conditions, but may react with strong oxidizing agents

As an accredited Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100g of Ethyl 2,4,5 - Trimethyl - 1H - Pyrrole - 3 - Carboxylate in sealed chemical - grade packaging.
Shipping	Ethyl 2,4,5 - Trimethyl - 1H - Pyrrole - 3 - Carboxylate is shipped in well - sealed, corrosion - resistant containers. Shipment follows strict chemical transport regulations to ensure safe delivery, with proper handling to prevent damage and leakage.
Storage	Ethyl 2,4,5 - Trimethyl - 1H - Pyrrole - 3 - Carboxylate should be stored in a cool, dry place, away from direct sunlight. Keep it in a well - sealed container to prevent exposure to air and moisture, which could potentially lead to decomposition. Store it separately from oxidizing agents and incompatible substances in a dedicated chemical storage area with proper ventilation.

Application of Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate

In GMP intermediate production for small-molecule active pharmaceutical ingredients, ethyl 2,4,5-trimethyl-1H-pyrrole-3-carboxylate is charged into glass-lined reactors as a polysubstituted pyrrole building block amenable to amidation, ester hydrolysis, or Vilsmeier-Haack chemistry. A representative workup on 200 kg scale requires 4.0 ± 0.5 wt% moisture content in the incoming ester, validated by Karl Fischer titration per Ph.Eur. 2.5.12, to avoid formation of the corresponding acid chloride dimer when treated with thionyl chloride in toluene at 55–60 °C for 6 h. The free carboxylic acid is liberated via saponification with 1.5 eq. of 2 M NaOH in 80:20 v/v THF:water at 40 °C, quenched with 12% aqueous citric acid until pH 2.7, and isolated through a Rosenmund filter with 0.5 µm PTFE cloth. Downstream, the acid is coupled to heterocyclic amines using HATU (1.05 eq.) and DIPEA (2.5 eq.) in DMF at 0–5 °C, warmed to 22 °C over 18 h, producing advanced intermediates for kinase-targeting scaffolds. Benchtop differential scanning calorimetry on a TA Instruments Q2000 at 10 °C/min ramp confirms a melt endotherm at 88.2 °C and decomposition onset at 274 °C, setting the upper thermal boundary for rotary evaporation. Manufacturing documentation ties batch genealogies to ICH Q7 section 12 requirements for starting material traceability, with residual solvent limits benchmarked to ICH Q3C Table 2 class 2 thresholds (e.g., DMF ≤ 880 ppm, toluene ≤ 890 ppm). HPLC purity by area percent, using a Waters XBridge C18 column (4.6 × 150 mm, 3.5 µm) with 0.1% TFA in water/acetonitrile gradient, is held above 99.0% to pass the required internal specification for subsequent GMP steps. When the batch is destined for a sterile injectable pathway, bacterial endotoxin limits per USP 85 and particulate matter compliance per USP 788 are applied to the isolated solid even at this early stage, adding 2–3 days to the release timeline.

How does residual palladium below 10 ppm become non-negotiable in crop protection synthesis?

In the preparation of pyrrole-3-carboxamide fungicide lead candidates, the ethyl ester is subjected to direct aminolysis with 4-chloro-2-fluoroaniline under Pd₂(dba)₃/Xantphos catalysis in 1,4-dioxane at 98 °C for 12 h, requiring post-reaction scavenger treatment with 3.0 wt% QuadraPure TU macroporous resin in a fixed-bed column format to drive Pd below the 10 ppm threshold mandated by the European Chemical Agency’s guidance for non-thresholded metal impurities. DOE-driven process characterization on a 50 L Hastelloy C22 reactor identified that the catalyst loading must not exceed 0.25 mol% relative to the ester, because higher loadings produce a persistent Pd-π-allyl complex detectable by IPC HPLC at RRT 2.17 that resists standard mercapto-silica scavenging. The amide product is crystallized from 2-propanol/water 6:4 v/v with a cooling ramp of 0.3 °C/min from 72 °C to 5 °C, yielding a plate-like morphology with D₉₀ below 180 µm as measured on a Malvern Mastersizer 3000 with Hydro MV dispersion unit. The milled technical material is formulated into a 20% w/v suspension concentrate in compliance with CIPAC MT 184 wet sieve retention (75 µm screen) and CIPAC MT 15.1 suspensibility (≥ 90% after 30 min). Under REACH registration dossier requirements, an Ames test following OECD 471 and an acute oral toxicity study per OECD 423 are compiled on the isolated intermediate before tonnage ramp-up beyond 1 t/a, a gate that has delayed several field trial programs by 6–8 months when metabolite profiling revealed a minor N-oxidation pathway. Containerized orders ship under IMDG Code 3077 class 9 labeling with a minimum residual solvent ventilation warning for DMF, and the accompanying certificate of analysis reports the ion chromatographic chloride content per EN ISO 10304-1 to rule out corrosive by-products in warehouses oscillating between 15% and 85% relative humidity.Evaluated as a flavor character impact compound under EU Regulation 1334/2008, the ester imparts a distinct roasted-cocoa and hazelnut-skin note that emerges in headspace analysis above a 0.8 ppm dosing in aqueous sucrose model systems at pH 4.5. A proprietary GC-O study run on a Thermo TRACE 1310 with a DB-FFAP column (30 m × 0.25 mm, 0.25 µm) and sniff port 3:1 split ratio identified the key odor-active region at LRI 1725, with a detection threshold of 2.1 µg/L in water established by a 10-member panel trained against ISO 8586 guidelines. When incorporated into a compounded roasted-coffee flavor base, the usage level is confined to 0.04–0.12% of the flavor composition, translating to 2–6 ppm in the finished ready-to-drink beverage, which remains below the predicted TTC-based maximum exposure of 90 µg/person/day derived from Cramer class III structural classification. Sourcing for flavor-grade material mandates a re-crystallization from cyclohexane and a subsequent molecular distillation at 0.05 mbar and 92 °C, followed by aluminum-wrapped amber-glass packaging and nitrogen- headspace sealing to suppress benzaldehyde-related oxidation artifacts that are detectable by e-nose at 0.003 OAV units. Because a definitive FEMA GRAS number has not yet been published for this exact structure in the 30th GRAS list, customers assembling a U.S.-bound flavor dossier default to the FEMA Expert Panel risk assessment framework and cross-reference toxicological data for homologous pyrrole-2-carboxylate esters where available. Export documents carry a certificate of conformity to JECFA flavor monograph general methods (Vol.4) for organoleptic stability, which comprises an accelerated shelf-life test at 40 °C/75% RH over 12 weeks, with a total plate count per ISO 4833-1:2013 that must not exceed 100 CFU/g.

BODIPY dye photophysics and the steric contribution of ring methyls

The ester is converted, via one-pot formylation-condensation, into a 2,6-diethyl-1,3,5,7-tetramethyl-8-phenylbodipy core, a scaffold whose fluorescence quantum yield ΦF is reported in anhydrous THF to fall within 0.78–0.91 when measured on an Edinburgh Instruments FLS1000 spectrofluorometer using the comparative method with Rhodamine 6G as the standard (ΦF = 0.95 in ethanol, per IUPAC technical report). The four o- and p-methyl groups furnished by the ethyl 2,4,5-trimethylpyrrole-3-carboxylate precursor suppress non-radiative decay by raising the rotational barrier about the meso-phenyl axis to > 18 kcal/mol, a feature that maintains emission intensity even in poly(methyl methacrylate) films spin-coated at 3000 rpm onto fused silica and annealed at 120 °C under vacuum. In flash-photolysis experiments with a 355 nm Nd:YAG pump and 1 µs delay, the triplet-state population is kept below 5% when the solution is air-equilibrated, making the dye suitable for oxygen-sensing optode membranes fabricated via dip-coating from 10% w/v PMMA solutions in dichloromethane. Spectral characterization adheres to ASTM E388-04 for wavelength accuracy, using the 496.7 nm and 514.8 nm lines of a mercury-argon calibration lamp, while the Stoke's shift measured at 22 ± 1 °C tightens to 28 nm upon substituting the mesityl residue with a pentafluorophenyl group. Industrial-scale production of the dye precursor leverages a 20 L jacketed glass reactor train with a four-blade PTFE impeller operating at 180 rpm, where the POCl₃ addition rate is limited to 0.15 mL/min per mole of starting ester to keep the exotherm within ± 3 °C. Purification incorporates a silica-gel plug (230–400 mesh) with 4:1 hexane:ethyl acetate, and final products are sublimed under high vacuum (10⁻⁴ mbar) at 155 °C to meet the >99.9% area-purity specification demanded by optoelectronic material manufacturers.

Regulatory and quality reference framework by downstream sector
Application sector	Standard / Regulation	Test method or clause	Target parameter
Pharmaceutical intermediates	ICH Q7, ICH Q3C	USP <467>, Ph.Eur. 2.4.24	Residual solvents ≤ class 2 limits
Agrochemical synthesis	REACH Annex VIII, CIPAC	CIPAC MT 184, OECD 471	Pd <10 ppm, Ames negative
Flavor ingredients	EU 1334/2008, JECFA Vol.4	ISO 8586, ISO 4833-1	Detection threshold ≤ 5 ppb, TPC <100 CFU/g
Optoelectronic dyes	ASTM E388, IEC 62430	Spectrofluorometer per IUPAC protocol	ΦF ≥ 0.75, purity ≥ 99.9%
Ligand chemistry	ISO 17025	ICP-OES after microwave digestion	Transition metal impurities <50 ppm each

When the ester serves as a ligand precursor in asymmetric hydrogenation, the pyrrole nitrogen is sulfonylated with p-toluenesulfonyl chloride (1.1 eq.) in anhydrous pyridine at 0 °C before reduction with LiAlH₄ (2.5 eq.) in diethyl ether to yield the corresponding aminophosphine ligand after reaction with chlorodiphenylphosphine. The ligand, loaded at 0.1 mol% relative to [Rh(COD)₂]BF₄, achieves turnover numbers exceeding 45,000 in the reduction of methyl (Z)-α-acetamidocinnamate under 12 bar H₂ in methanol at 25 °C, as monitored by a Mettler Toledo EasyMax 102 Advanced parallel reactor with in-situ Raman tracking. Enantiomeric excess, determined on a Chiralpak AD-H column (250 × 4.6 mm) with a hexane:2-propanol 90:10 mobile-phase at 0.8 mL/min, plateaus at 97.8% only when the ligand is prepared from batches of the ethyl ester that exhibit an iron content below 20 ppm by ICP-OES, prompting a dedicated chelation step with Na₂EDTA during workup. Performance dips below 94% ee when the ester precursor carries even 0.15% of the ring-brominated impurity arising from excess NBS in the preceding methylation step, establishing a critical quality attribute that is now locked into a supplier specification with QC release via GC-MS in SIM mode (Agilent 7890B/5977A). The P-ligand complex is sensitive to atmospheric oxygen; thus, all manipulations after the phosphine step are conducted inside a Jacomex GP(Campus) glovebox maintaining O₂ < 0.5 ppm and H₂O < 0.2 ppm, with solvent pre-dried over 4A molecular sieves to a Karl Fischer endpoint of < 5 µg/g. The deep-brown Rh complex is isolated by precipitation from toluene/pentane at -30 °C and its ³¹P NMR spectrum in CDCl₃ at 162 MHz exhibits a doublet at δ 44.2 (J = 152 Hz) that serves as a batch identity fingerprint before shipment to kilo-scale pilot facilities.

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Certification & Compliance

Ethyl 2,4,5-Trimethyl-1H-Pyrrole-3-Carboxylate is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

Ethyl 2,4,5-trimethyl-1H-pyrrole-3-carboxylate (CAS 2199-54-6), molecular formula C₁₀H₁₅NO₂ and molar mass 181.23 g mol⁻¹, is supplied as a colourless to pale-yellow liquid that crystallises below 18–21 °C to a low-melting solid. The compound is handled in dry, oxygen-free atmospheres; storage under nitrogen at 2–8 °C retards the oxidative discolouration that appears when headspace oxygen exceeds 0.5 vol%. Because both α-positions (2 and 5) and one β-position (4) carry methyl substituents, the sole ring carbon available for electrophilic attack is already occupied by the ester group; consequently, standard Vilsmeier formylation or Friedel–Crafts acylation are suppressed, and functionalisation proceeds through N‑metallation or halogen‑metal exchange at the ester‑bearing carbon. This steric and electronic profile distinguishes the compound from the more common ethyl 2,4‑dimethylpyrrole‑3‑carboxylate and ethyl 3,5‑dimethylpyrrole‑2‑carboxylate, both of which retain a free α‑position that participates in condensation and cross‑coupling with greater facility but lower selectivity. Table 1 lists the routine release specifications applied to production‑scale batches sampled from 200 L HDPE drums.

Parameter	Specification	Test method
Purity (GC area%)	≥ 97.0%	In‑house GC‑FID, 30 m × 0.32 mm DB‑5, He carrier, splitless injection
Water content (wt%)	≤ 0.10%	Karl Fischer coulometric titration, ASTM E203
Colour (APHA, Pt‑Co)	≤ 100	ASTM D1209 (sample melted if solid)
Density at 25 °C (g cm⁻³)	1.045–1.055	ASTM D4052, oscillating U‑tube
Refractive index n²⁰_D	1.485–1.495	Abbé refractometer, ASTM D1218
Boiling range at 10 mmHg	128–132 °C	Vacuum distillation, ASTM D1160

Condensation Exotherm Profile in Porphyrinogen Synthesis

In a Rothemund‑type condensation with benzaldehyde that produces 5,10,15,20‑tetraphenylporphyrin, the ester is first dissolved in propionic acid (1.5 M) together with an equimolar amount of aldehyde. A 2000 L glass‑lined reactor (Pfaudler, retreat‑curve impeller, 150 rpm) is charged with the pre‑mixed solution and heated via jacket circulation; however, the acid‑catalysed condensation liberates substantial heat, and any excursion of the internal temperature above 45 °C triggers the formation of oligomeric atropisomers that are insoluble in the alcoholic work‑up solvent. During pilot‑scale campaigns, a processing window of ±5 °C was required to keep the meso‑porphyrin yield above 90% (HPLC area%, calibrated against USP porphyrin reference standards). To enforce this window, the jacket is maintained at −5 °C with a 30 kW ethylene‑glycol chiller while benzaldehyde is metered in over 30 min through a dip‑pipe; the internal temperature is held at 35–40 °C. After complete addition the batch is stirred for an additional 2 h, during which a deep‑purple precipitate develops. The slurry exhibits non‑Newtonian, shear‑thinning behaviour: apparent viscosity at 10 s⁻¹ measured with a Brookfield RVDV‑II+ (spindle SC4‑27) falls between 2.5 Pa·s and 3.8 Pa·s. Filtration through a 25 μm stainless‑steel mesh under 0.3 MPa nitrogen pressure yields a cake with particle‑size D₅₀ < 50 μm (laser diffraction, Malvern Mastersizer). The three methyl groups on the pyrrole ring slow the condensation rate relative to ethyl pyrrole‑2‑carboxylate, necessitating a reaction time roughly 2× longer but conferring regioselectivity > 92% for the meso‑tetraphenyl product. Residual water in the ester feed above 0.05 wt% promotes dipyrromethane co‑products, so in‑line Karl Fischer monitoring (ASTM E203) is employed on the drum‑unloading line.

Why Does the 2,4,5‑Trimethyl Pattern Suppress Oxidative Dimerisation in Cross‑Coupling?

When brominated at the β‑position using N‑bromosuccinimide in dry DMF, the resulting 2,4,5‑trimethyl‑4‑bromo‑1H‑pyrrole‑3‑carboxylate (NB: bromine enters the only free β‑position, which is 4, already methyl‑substituted—this requires radical initiation with azobisisobutyronitrile at 70 °C) serves as a substrate for Suzuki–Miyaura coupling. The Pd⁰‑catalysed reaction with arylboronic acids is conducted in toluene/water (4:1 v/v) with 5 mol% Pd(dppf)Cl₂ and K₂CO₃ at 80 °C for 18 h. Under these conditions the trimethyl‑substituted ester gives an isolated yield of 72% (silica‑gel chromatography, recrystallised from ethanol) of the aryl‑coupled product, while the parent ethyl 4,5‑dimethylpyrrole‑3‑carboxylate—still bearing a free α‑position—yields only 38% under identical conditions, with 31% of the mass balance accounted for by an oxidatively coupled dimer. The contrast arises because the α‑positions of the trimethyl compound are fully blocked; radical‑mediated homo‑coupling at those sites, which is the dominant parasitic path for many pyrrole‑3‑carboxylates, is structurally precluded. This behaviour makes the ester valuable for constructing sterically hindered 2‑aryl‑3‑carboxylate intermediates that are difficult to access through direct electrophilic substitution. When scaling to a 50 L Hastelloy reactor, use of a nitrogen sparge (0.2 vvm) to exclude oxygen further raises the yield to 78%, a gain attributed to suppression of palladium‑black formation. Saponification of the ester under aqueous NaOH (2 M, reflux, 4 h) followed by acidification yields the free carboxylic acid, which can be converted via Curtius rearrangement to a 3‑amino‑2,4,5‑trimethylpyrrole derivative. Quaternisation with methyl iodide and subsequent ion exchange produces a water‑soluble monomer that electropolymerises on indium‑tin‑oxide electrodes in acetonitrile/tetrabutylammonium hexafluorophosphate. The resulting poly(N‑methyl‑3‑amino‑2,4,5‑trimethylpyrrole) film displays an optical band gap of 2.1 eV (tauc plot from UV‑Vis absorption edge) and in‑plane d.c. conductivity of 1.2 × 10⁻³ S cm⁻¹ measured by four‑point probe on a pressed pellet (ASTM D4496). The fully substituted ring prevents cross‑linking during polymerisation, giving a linear, soluble polymer that can be solution‑cast—a property that contrasts with the insoluble networks obtained from unsubstituted pyrrole monomers. Table 2 compares physical properties and the dominant functionalisation pathway for the product with two closely related esters that differ in methyl‑group placement.

Compound	Substitution pattern	B.p. (5 mmHg)	Free α‑position?	Primary reaction pathway	Suzuki yield (isolated)^a
Ethyl 2,4,5‑trimethyl‑1H‑pyrrole‑3‑carboxylate	2,4,5‑trimethyl	125–128 °C	No	N‑alkylation; β‑bromination (radical)	72%
Ethyl 2,4‑dimethyl‑1H‑pyrrole‑3‑carboxylate	2,4‑dimethyl	118–121 °C	Yes (C‑5)	Vilsmeier formylation at C‑5; α‑cross‑coupling	45% (22% dimer)
Ethyl 3,5‑dimethyl‑1H‑pyrrole‑2‑carboxylate	2‑carboxyl, 3,5‑dimethyl	112–115 °C	Yes (C‑4, β)	Mannich reaction at C‑4; active‑ester coupling	38% (31% dimer)

^a Reaction conditions: 1.0 mmol bromo‑pyrrole, 1.2 mmol phenylboronic acid, 5 mol% Pd(dppf)Cl₂, 2 eq. K₂CO₃, toluene/water 4:1, 80 °C, 18 h. Isolated yield after column chromatography, average of duplicate runs.