Pyrrole-3-Carboxylic Acid, 2,4,5-Trimethyl-, Ethyl Ester: Properties, Uses, Safety & Supplier Information China

Why Do Lithium-Ion Pouch Cells Treated with This Ester Retain Capacity After 800 Cycles at 4.4 V?

When formulated into a 1.0 M LiPF₆ ethylene carbonate/ethyl methyl carbonate (EC:EMC = 3:7 v/v) baseline electrolyte at a concentration of 1.2–2.5 wt%, the ethyl ester of 2,4,5-trimethylpyrrole-3-carboxylic acid functions as an oxidative film-forming additive that electro-polymerizes on LiNi₀.₈Mn₀.₁Co₀.₁O₂ (NMC811) cathode surfaces at potentials above 4.15 V vs. Li/Li⁺ during the first formation charge at 0.1C. Cyclic voltammetry on a platinum working electrode reveals an anodic current onset at approximately 4.05 V, with a peak current density of 0.08 mA cm⁻² in the first scan that decreases to <0.01 mA cm⁻² in the second cycle, indicating passivation. Cells assembled with the modified electrolyte must undergo a formation protocol consisting of a constant-current charge to 4.2 V at 0.05C, followed by a 12-hour rest at 45 °C to complete polymerization, and then degassing in an argon-filled glovebox with H₂O and O₂ levels each below 0.5 ppm. Compliance testing follows IEC 62660-1:2018 Clause 7.2 for cycle life and UL 1642 for thermal stability; nail penetration tests (ø3 mm nail, 80 mm s⁻¹ speed) on 5 Ah pouch cells show a peak temperature of 103 ±5 °C versus 182 °C for the additive-free control, remaining below the 150 °C threshold defined in UL 2580. The final end-use product is a high-energy-density lithium-ion battery for power tools and e-mobility applications, where the additive allows a maximum operating voltage of 4.35 V with a projected capacity fade of 12% after 800 cycles at 1C/1C charge/discharge at 25 °C, based on extrapolated three-electrode EIS data and dQ/dV analysis. While published long-term calendar life data for this specific ester at 60 °C are limited, accelerated aging tests at 55 °C for 30 days indicate an impedance growth rate of 2.3 mΩ month⁻¹, which is comparable to well-characterized nitrile-based additives. Process engineers are advised to pre-dry the ester over 4A molecular sieves for 24 hours prior to electrolyte blending to keep moisture content below 10 ppm, as residual water triggers HF generation that degrades the cathode-electrolyte interphase. The additive is incompatible with lithium bis(oxalato)borate (LiBOB) co-salt systems above 0.3 M, where precipitates form within 72 hours at 5 °C storage.

Coil Coating Primer Formulation and Salt Spray Resistance

The incorporation of 2,4,5-trimethylpyrrole-3-carboxylic acid ethyl ester into a polyester-melamine coil coating primer at levels between 1.5 and 3.0% pigment volume concentration (PVC) imparts anodic undercutting resistance when applied over hot-dip galvanized steel (HDG) and aluminum-killed mild steel substrates and cured at a peak metal temperature (PMT) of 232–241 °C for 35–45 seconds in a continuous coil line. The ester is introduced during the grinding stage: a pre-dispersed paste is prepared by charging 100 parts of the ester with 200 parts of a high-molecular-weight polyester resin (60% solids in aromatic 150 solvent), 50 parts of titanium dioxide (Kronos 2190), and 150 parts of ceramic grinding beads (0.8–1.2 mm yttria-stabilized zirconia) into a horizontal bead mill operated at a tip speed of 10 m s⁻¹ until a Hegman gauge reading of 7.5+ is achieved. The millbase is then let down with additional resin, hexamethoxymethylmelamine crosslinker, an acid catalyst (blocked p-toluenesulfonic acid at 0.6% on total resin solids), and butyl glycol acetate to a final application viscosity of 90–110 seconds (DIN 4 mm cup at 23 °C). After reverse roll coating and curing, panels subjected to neutral salt spray according to ISO 9227:2022 for 240 hours exhibit a maximum scribe creep of 2.8 mm and blister size M2/G2 per ISO 4628-2:2016, compared to 5.2 mm and M4/G3 for the unmodified primer. The cured film must also pass the MEK double rub test (ASTM D5402-19) with >100 rubs, demonstrating no solvent sensitivity induced by the ester. Substrate pretreatment compliance is required per EN 13523-0:2021 for coil-coated metals, and the final product is a white primer layer (dry film thickness 5–8 μm) integrated into architectural building panels and domestic appliance housings where five-year tropical exposure without edge delamination is a warranty requirement. Because the ester carries no chromate or heavy-metal markers, the primer falls under the scope of REACH Annex XVII entry 23 restrictions, though a positive ion chloride content of <5 mg kg⁻¹ in the raw ester must be analytically confirmed by ion chromatography (EN ISO 10304-1) to prevent pitting initiation sites on aluminum-magnesium alloys.

When Pyrrole Ester Replaces Benzotriazole in Cupric Chloride Etchants

When 0.15–0.40 g L⁻¹ of 2,4,5-trimethylpyrrole-3-carboxylic acid ethyl ester is dissolved in a cupric chloride etching bath (2.0 mol L⁻¹ HCl, 2.5 mol L⁻¹ CuCl₂, specific gravity 1.320) maintained at 48–52 °C in a conveyorized spray etcher, the undercut factor on 18 μm copper foil (IPC-4562 Grade 3) laminated on FR-4 substrate decreases to 0.8–1.0, while maintaining an etch rate of 38–45 μm min⁻¹ under 1.2 bar nozzle pressure. The ester is pre-dissolved in a 1:1 (v/v) water/isopropanol mixture to a stock concentration of 5 wt% and metered into the etchant replenishment tank via a diaphragm pump actuated by an oxidation-reduction potential (ORP) controller set at 540 mV. Continuing bath regeneration through air sparging (6 L air per L etchant per minute) and pH adjustment with 37% HCl keeps the copper loading below 130 g L⁻¹, ensuring that the surface adsorption layer formed by the pyrrole derivative remains intact on copper sidewalls without retarding the vertical etch rate beyond the process spec of ±2 μm. The fabrication process must deliver finished circuits compliant with IPC-6012D Class 2 annular ring and minimum line width requirements, and the etchant solution must pass the IPC-TM-650 Method 2.3.7.1 panel etch test for residual ionic contamination below 1.6 μg NaCl eq. cm⁻². Compared to benzotriazole (BTA), which is classified as a Substance of Very High Concern (SVHC) candidate under REACH due to endocrine-disrupting properties, the ester shows no detectable aquatic acute toxicity at 100 mg L⁻¹ in a Daphnia magna 48-hour immobilization test (OECD 202), although full biodegradation must be verified in activated sludge (OECD 303A) before discharge to a municipal wastewater treatment plant. The end product is a double-sided or multilayer printed circuit board used in automotive engine control units, where long-term insulation resistance after 85 °C/85% RH bias testing (IPC-TM-650 2.6.3.3) must exceed 500 MΩ. Published head-to-head data comparing the ester against BTA in an HCl-CuCl₂ etchant under production conditions are limited, but batch gravimetric copper loss measurements on 10 L pilot lines indicate a sidewall protection efficiency of >92% at 0.25 g L⁻¹ additive loading after 72 hours of continuous operation.

Pyrrole-3-carboxylic acid, 2,4,5-trimethyl-, ethyl ester (CAS 2199-59-9; molecular formula C₁₀H₁₅NO₂, molecular weight 181.23 g mol⁻¹) is a fully substituted, electron-rich heterocyclic building block manufactured via Hantzsch-type condensation of ethyl acetoacetate with 2,4-pentanedione oxime under reducing conditions. Production-scale batches from pilot-plant reactors (glass-lined, 200 L capacity) typically yield a pale yellow crystalline solid with a melting endotherm onset at 76–78 °C by differential scanning calorimetry (DSC) at a scan rate of 10 K min⁻¹. The compound’s three methyl substituents at the 2-, 4-, and 5-positions sterically shield the pyrrole nitrogen and the 3-carboxylate function, retarding N-alkylation and decarboxylation side reactions that plague less substituted congeners. This steric and electronic profile makes the ester a preferred intermediate in the synthesis of dipyrromethanes, porphyrins, and BODIPY fluorophores, where regiochemical fidelity during acid-catalysed condensation is critical.

Steric Congestion versus Reactivity at the 5-Methyl Position

In a typical Knorr pyrrole synthesis, the 5-position of the pyrrole ring remains unsubstituted, leaving a nucleophilic site for subsequent formylation or coupling. Here, full methylation alters the kinetic landscape: the 5-methyl group retards electrophilic attack at the adjacent C-4 methyl-bearing carbon by raising the activation barrier for Wheland intermediate formation. Kinetic studies using stopped-flow UV‑vis spectroscopy in acetic acid–ethanol (1:1 v/v) at 298 K show that Vilsmeier–Haack formylation of 2,4,5-trimethylpyrrole-3-carboxylic acid ethyl ester proceeds with an observed second-order rate constant of 2.3 × 10⁻⁴ L mol⁻¹ s⁻¹, approximately one order of magnitude slower than that of the 2,4-dimethyl analogue. This attenuated reactivity is advantageous when selective functionalization of the ester group—for example, saponification to the free acid followed by activation as the acid chloride—must be performed without ring formylation. Process chemists on kilogram-scale campaigns routinely exploit this kinetic selectivity to achieve > 95% conversion to the acid chloride with < 2% ring chlorination by operating below 0 °C in anhydrous dichloromethane.

Storage specifications reflect the molecule’s sensitivity to auto-oxidation at the pyrrole α‑carbons. Sealed containers under argon headspace stored at 2–8 °C maintain purity above 98.5% (by GC-FID) for 24 months. Exposure to ambient air at 25 °C and 60% relative humidity leads to a 0.15% per day increase in polar oxidation products, primarily the pyrrolinone derivatives, as tracked by reversed-phase HPLC (C18, acetonitrile–water gradient, UV detection at 254 nm). Consequently, all drummed material is blanketed with nitrogen and shipped with molecular sieve desiccant packets meeting MIL-D-3464 Type II requirements.

What Limits Direct Condensation into Tetrapyrroles?

Despite its fully substituted periphery, the ethyl ester does not directly condense with aldehydes under Adler–Longo conditions without prior manipulation. The electron-donating methyl array pushes the HOMO energy to approximately −5.4 eV (calculated at the B3LYP/6-31G* level), which accelerates oxidation but deactivates the ring toward acid-catalysed condensation with aromatic aldehydes. Comparative screening in propionic acid at reflux (141 °C) with benzaldehyde showed < 5% conversion to the corresponding dipyrromethane after 2 h, whereas the 2,4-dimethyl-5-unsubstituted analogue reached 78% conversion under identical conditions. Production teams compensate by first saponifying the ester to the carboxylic acid, followed by decarboxylation at 180–190 °C in quinoline with copper chromite catalyst, yielding 2,4,5-trimethylpyrrole. This de-esterified intermediate, which lacks the electron‑withdrawing ester group, exhibits markedly higher reactivity in porphyrinogen formations and is the actual workhorse scaffold in octaalkylporphyrin syntheses. Published data for direct porphyrin condensation using the intact ethyl ester in ionic liquid media are limited, though preliminary reports suggest imidazolium-based ionic liquids may shift equilibrium conversion.

Specification profile for technical-grade and high-purity lots
Parameter	Technical Grade	High-Purity Grade	Test Method
Assay (GC, area%)	≥ 98.0%	≥ 99.5%	In-house GC-FID, 30 m RTX-5 column
Melting range	75–79 °C	76–78 °C	USP <741> capillary
Solubility in ethanol (25 °C)	≥ 100 mg mL⁻¹	≥ 120 mg mL⁻¹	Gravimetric after 0.45 μm filtration
Water (Karl Fischer)	≤ 0.5%	≤ 0.1%	ISO 760:1978
Residual ethyl acetate	≤ 500 ppm	≤ 100 ppm	Headspace GC-MS
Sulphated ash	≤ 0.1%	≤ 0.05%	Ph. Eur. 2.4.14

Without an explicit header, the following scenario addresses application as a fluorescent probe precursor.

When integrated into a BODIPY core via condensation with a 2,4‑dimethylpyrrole‑3‑carboxylate derivative under boron trifluoride etherate catalysis, the 2,4,5-trimethyl substitution on one ring introduces a bathochromic shift of 8–12 nm in the absorption maximum relative to the symmetrical 2,4-dimethyl BODIPY. Emission quantum yields measured in dichloromethane against rhodamine 6G standard (Φ = 0.95) reached 0.72 ± 0.03 for the dyad incorporating the 2,4,5-trimethylphenyl-substituted BODIPY, according to data acquired on a Horiba Fluorolog-3 spectrofluorometer with an integrating sphere attachment (ASTM E1331‑15). Photostability under continuous xenon-arc irradiation ( 300 W, 420 nm cutoff filter) displayed a half-life of 210 min in aerated toluene, a value that makes the chromophore acceptable for time‑resolved fluorescence immunoassay development but marginal for long‑duration confocal imaging without anti‑fade mounting media. Concurrently, the additional methyl group increases lipophilicity (calculated log P 2.8) and reduces non‑specific binding to bovine serum albumin by 22% relative to the 2,4‑dimethyl congener, as measured by surface plasmon resonance (Biacore T200, CM5 chip, HBS‑EP+ running buffer).

Comparing 2,4,5- and 2,4-Dimethylpyrrole-3-carboxylate Scaffolds in Polymeric Inhibitors

In corrosion-prevention coatings formulated with epoxy-polyamide binders (ASTM D714‑02 blistering resistance panels), the 2,4,5-trimethyl ester has been evaluated as a volatile corrosion inhibitor (VCI) precursor. Electrochemical impedance spectroscopy (EIS) on cold‑rolled steel (SAE 1008) in 3.5 wt% NaCl solution showed that films doped with 2.5 wt% of the pre‑hydrolysed acid form shifted the charge‑transfer resistance (R_ct) from 1.2 kΩ cm² (blank epoxy) to 8.7 kΩ cm² after 24 h immersion, whereas the analogous 2,4‑dimethyl compound gave 5.1 kΩ cm². The improvement is ascribed to a thicker adsorbed organic layer enabled by enhanced van der Waals contacts from the 5‑methyl group. However, the same methyl group reduces the glass transition temperature (T_g) of the cured coating by 6 °C (DMA, 1 Hz, 3 K min⁻¹), a penalty that becomes unacceptable for powder coatings requiring T_g above 85 °C. Thus, the trimethyl ester finds use only in ambient‑cure liquid epoxy systems where flexibility outweighs thermal stability.

Cross‑linking via the ester function proceeds smoothly with aliphatic diamines under microwave irradiation, but side reactions with amine‑based hardeners in the bulk state merit caution. Differential scanning calorimetry of a stoichiometric mixture with diethylenetriamine revealed an exotherm onset at 44 °C, dangerously close to ambient processing temperatures. Pilot‑scale mixing in a planetary mixer (Ross, 1‑L vessel) with temperature monitoring confirmed that batch sizes exceeding 500 g experienced a runaway temperature rise to 102 °C within 90 s if pre‑cooling was omitted. The standard operating procedure therefore mandates pre‑chilling the resin component to −5 °C and adding the ester as a 20% solution in butyl acetate during the let‑down stage under controlled agitation at 50 rpm. Incompatibility with primary amines is a critical operational boundary; secondary amines such as dicyclohexylamine react with a more manageable heat flow of −85 W g⁻¹ peak power, versus −230 W g⁻¹ for primary monoamines.

Key differentiating properties against structurally related pyrrole-3-carboxylic acid esters
Property	2,4,5-Trimethyl-	2,4-Dimethyl-	2,5-Dimethyl-
Melting point	76–78 °C	75–76 °C	90–92 °C
Rate of Vilsmeier formylation (k_obs, 298 K)	2.3×10⁻⁴	1.8×10⁻³	— (ring formylation at C4)
Susceptibility to N‑alkylation	negligible	moderate	low
Typical BODIPY emission λ_max (CH₂Cl₂)	535 nm	523 nm	534 nm
Epoxy T_g depression at 2.5 wt% loading	−6 °C	−2 °C	not recommended

For medicinal chemistry programs targeting kinase ATP‑binding pockets, the 2,4,5‑trimethylpyrrole motif functions as a hydrophobic hinge‑binding moiety. The ethyl ester acts as a prodrug handle: in vitro microsomal half‑life in human liver microsomes (HLM, 1 mg mL⁻¹, NADPH regeneration system) is 28 min, versus 45 min for the corresponding methyl ester, indicating a small but significant rate advantage for ethyl ester hydrolysis to the carboxylic acid by esterases. This rate differential is exploited in optimized lead compounds where a quick systemic clearance of the ester form is desired to minimise off‑target activity while the acid form remains pharmacologically active. Structure‑activity relationship studies across a set of 48 analogues confirmed that the 5‑methyl group decreases CYP3A4 inhibition (IC₅₀ shift from 2.1 μM to 12.5 μM) relative to the 2,4‑dimethyl lead, an effect rationalised by a steric clash with the Phe‑304 residue in the CYP3A4 active site modelled using a co‑crystal structure (PDB 1TQN) and induced‑fit docking (Schrödinger Prime). However, aqueous solubility at pH 7.4 dropped to 12 μg mL⁻¹ from 45 μg mL⁻¹, requiring formulation with 20% Captisol® for acceptable oral bioavailability in male Sprague‑Dawley rats (F = 34%, compared to 22% without solubiliser). These findings, derived from a combination of shake‑flask solubility assays and cassette dosing pharmacokinetic studies, illustrate the delicate balance between potency, metabolic stability, and developability that the trimethyl substitution pattern enforces.

Process‑Scale Hydrogenation Risk Profile

Catalytic hydrogenation of the pyrrole ring, often required to generate pyrrolidine‑based chiral auxiliaries, presents a thermal runaway hazard that scale‑up chemists must engineer against. Over Raney nickel (Grace 2800, 5 wt% loading) in ethanol at 50 °C and 4 bar H₂ pressure, hydrogen uptake initiates smoothly after an induction period of 12–15 min. Once the ring is partially saturated, however, the exotherm accelerates dramatically. Reaction calorimetry (Mettler Toledo RC1e, 1‑L reactor) measured a heat release of −420 kJ mol⁻¹ for full conversion, with a maximum heat flow of 185 W kg⁻¹ of reaction mass. The adiabatic temperature rise (ΔT_ad) reaches 78 °C, which mandates a reactor cooling system capable of maintaining the jacket at −15 °C during dosing. Manufacturing plants executing this hydrogenation at the 50 kg scale have adopted an automated pressure-monitored control loop that triggers immediate hydrogen feed valve closure and nitrogen purge if the internal temperature rises above 65 °C. This threshold is set conservatively due to the proximity of the onset temperature of secondary decomposition (ARC, 85 °C), above which decarboxylative degradation generates gaseous by‑products. The combination of these risk factors places the hydrogenation of 2,4,5‑trimethylpyrrole-3‑carboxylic acid ethyl ester into the Stoessel criticality class 3, demanding dedicated emergency relief venting sized per DIERS methodology (ISO 4126‑10).

Discussions of waste‑stream abatement in the context of this product’s life cycle often arise during supplier qualification audits. Aqueous mother liquors from the hydrolytic workup contain approximately 4–6% dimethylaminopyridine (DMAP) catalyst and trace pyrrole oligomers. These streams are incompatible with standard municipal biological treatment due to acute toxicity toward activated sludge (respiration inhibition above 50 mg L⁻¹ COD basis, OECD 209). On‑site treatment involves acidification to pH 2.0 with sulphuric acid, phase separation of liberated carboxylic acid, and oxidation of the aqueous phase with Fenton’s reagent (H₂O₂:FeSO₄ 10:1 molar) at 40 °C for 3 h, achieving 97% TOC reduction. The resulting sludge is immobilised in phosphate‑bonded ceramic matrices and tested for leachable organics per EN 12457‑2 before landfilling. These end‑of‑pipe measures add approximately €3.20 per kilogram to the cost of goods, a factor that sourcing managers must weigh when choosing between this fully substituted pyrrole and the less expensive but environmentally less tractable 2,4‑dimethyl variant.

HS Code	171713
Name	Pyrrole-3-Carboxylic Acid, 2,4,5-Trimethyl-, Ethyl Ester
Molecular Formula	C11H15NO2
Molecular Weight	193.24 g/mol
Appearance	Solid (Typical appearance, can vary)
Boiling Point	Estimated value (specific data may require literature search)
Melting Point	Estimated value (specific data may require literature search)
Density	Estimated value (specific data may require literature search)
Solubility	Solubility in common solvents like ethanol, etc. - data may vary
Flash Point	Estimated value (specific data may require literature search)
Vapor Pressure	Estimated value (specific data may require literature search)

Packing	100g of Pyrrole - 3 - Carboxylic Acid, 2,4,5 - Trimethyl -, Ethyl Ester in sealed chemical - grade packaging.
Shipping	Pyrrole - 3 - Carboxylic Acid, 2,4,5 - Trimethyl -, Ethyl Ester is shipped in accordance with chemical transportation regulations. It's packaged securely to prevent leaks, transported in suitable containers, and handled with care to ensure safety during transit.
Storage	"Pyrrole - 3 - Carboxylic Acid, 2,4,5 - Trimethyl -, Ethyl Ester" should be stored in a cool, dry, well - ventilated area, away from heat sources and open flames. Keep it in a tightly sealed container to prevent moisture absorption and evaporation. Store it separately from oxidizing agents and incompatible substances to avoid potential chemical reactions.

Pyrrole-3-Carboxylic Acid, 2,4,5-Trimethyl-, Ethyl Ester