1H-Pyrrole-3-Carboxylic Acid
|
HS Code |
204289 |
| Name | 1H-Pyrrole-3-Carboxylic Acid |
| Molecular Formula | C5H5NO2 |
| Molar Mass | 111.1 g/mol |
| Appearance | Solid |
| Color | Typically white to off - white |
| Odor | May have a faint, characteristic odor |
| Solubility In Water | Slightly soluble |
| Melting Point | 167 - 172 °C |
| Pka | Around 3.8 (estimated for carboxylic acid group) |
| Boiling Point | Decomposes before boiling |
As an accredited 1H-Pyrrole-3-Carboxylic Acid factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 1H - Pyrrole - 3 - Carboxylic Acid packaged in a sealed plastic bag. |
| Shipping | 1H - Pyrrole - 3 - Carboxylic Acid is shipped in well - sealed, corrosion - resistant containers. Shipment follows strict chemical transport regulations, ensuring proper handling to prevent spills and maintain product integrity during transit. |
| Storage | 1H - Pyrrole - 3 - Carboxylic Acid should be stored in a cool, dry place. Keep it in a well - sealed container to prevent moisture absorption and contact with air, which could potentially lead to degradation. Store away from heat sources and incompatible substances, such as strong oxidizing agents. Ideal storage temperatures are around 2 - 8 °C if long - term stability is required. |
|
Manufacture of torsemide, a loop diuretic with a pyridine-sulfonylurea pharmacophore, places 1H-pyrrole-3-carboxylic acid (PCA) on a critical-path synthesis node where the exothermic profile of acid chloride formation dictates batch homogeneity. In a 2500 L glass-lined reactor operated under a nitrogen blanket, PCA is suspended in dichloromethane at a moisture content strictly regulated below 0.05% Karl Fischer. Dropwise addition of thionyl chloride at a jacket temperature set to -5 °C generates 1H-pyrrole-3-carbonyl chloride; the instantaneous heat release measured via reaction calorimetry typically reaches −220 kJ/mol. Failure to maintain the internal temperature below 8 °C results in a runaway decarboxylation side-reaction producing nitrogenous tars that irreversibly foul the 50-micron Hastelloy C-276 dip-tube filter. Subsequent coupling with 4-chloro-3-sulfamoylaniline in ethyl acetate/water biphasic medium yields the penultimate intermediate N-(4-chloro-3-sulfamoylphenyl)-1H-pyrrole-3-carboxamide. Recrystallization from ethanol/water (70:30 v/v) at a cooling rate of 0.3 °C/min reduces the dimeric impurity to below the ICH Q3A reporting threshold of 0.05%; the impurity, assigned as a pyrrole-pyrrole oxidative coupling adduct, exhibits a relative retention time of RRT 1.42 on a Phenomenex Luna C18 column ( 150 × 4.6 mm, 5 µm ) with a mobile phase of acetonitrile/0.1% phosphoric acid gradient at 1.2 mL/min. For sunitinib synthesis, the same acid intermediate undergoes HATU-mediated amidation with 5-fluoroindolin-2-one in dimethylacetamide to install the 3-carboxamide linkage critical for vascular endothelial growth factor receptor-2 (VEGFR-2) inhibition. Residual palladium from upstream catalytic steps is controlled below 10 ppm via treatment with SiliaMetS Thiol resin, quantified by inductively coupled plasma mass spectrometry per USP <232>. At What Concentration Does 1H-Pyrrole-3-Carboxylate Exhibit a Transition from Physisorption to Chemisorption on Mild Steel in Aerated 1 N HCl?Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements confirm that the adsorption mechanism of 1H-pyrrole-3-carboxylate on AISI 1018 mild steel transitions sharply at a bulk concentration of 0.8 mM. Below this threshold, the inhibitor obeys a Temkin isotherm (ΔG°ads = −22.4 kJ mol⁻¹), indicative of charge-transfer-mediated physisorption. At concentrations exceeding 0.8 mM, the Langmuir isotherm prevails with a free energy of adsorption of −39.8 kJ mol⁻¹, consistent with covalent bond formation between the nitrogen lone pair and vacant d-orbitals of iron. The critical micelle concentration of PCA in 1 N HCl at 25 °C is 2.1 mM, above which inhibitor precipitation causes localized pitting. The table below compiles Tafel-extrapolated corrosion parameters derived from a standard three-electrode flat cell (ASTM G5-14, specimen surface area 1.0 cm², scan rate 0.166 mV/s). Oxygen saturation of the electrolyte consistently elevates the corrosion current density (icorr) by 12–15% across all inhibitor loadings, a factor often ignored in gravimetric immersion tests (ASTM G31-21).
Coordination Architectures of Cu(II)-Pyrrole-3-Carboxylate FrameworksSolvothermal reaction of 1H-pyrrole-3-carboxylic acid with copper(II) nitrate trihydrate in a mixed solvent system of N,N-dimethylformamide and ethanol (1:3 v/v) at 85 °C for 48 h yields two distinct metal-organic framework topologies depending on the modulator stoichiometry. With 2.0 equivalents of glacial acetic acid as a competitive ligand, a three-dimensional pillared-layer structure (CCDC deposition number analogous to 2083742) crystallizes in the orthorhombic space group Pbca, featuring a bis-monodentate carboxylate bridging mode and a Cu···Cu paddlewheel node distance of 2.652 Å. Without modulator, a two-dimensional sql-net precipitates where the pyrrole N–H remains uncoordinated, providing a post-synthetic metalation site. Thermogravimetric analysis under flowing nitrogen at a ramp rate of 10 °C/min reveals framework stability up to 280 °C, followed by abrupt weight loss of 62% corresponding to ligand decarboxylation and pyrrole ring collapse. Activated at 150 °C under dynamic vacuum for 12 h, the three-dimensional framework exhibits a Brunauer–Emmett–Teller surface area of 680 m² g⁻¹ (determined by N₂ adsorption at 77 K). Published data for selective CO₂/CH₄ separation on this specific pyrrole-carboxylate motif is limited; however, the uncoordinated pyrrole N–H functionality is predicted by density functional theory calculations to engage in hydrogen-bonding interactions with CO₂ at a binding enthalpy of −32 kJ mol⁻¹. Seed treatment fungicide fludioxonil, registered under EPA 40 CFR 180.516, is synthesized through a multi-step route originating from 1H-pyrrole-3-carboxylic acid. The process sequence converts PCA via a Rosenmund reduction analogue to pyrrole-3-carbaldehyde, followed by a Knoevenagel condensation with 2,2-difluoro-1,3-benzodioxole-4-acetonitrile to generate the vinyl-nitrile bridge in an ethanol/piperidine reflux. A subsequent palladium-catalyzed N-formylation and cyclization under basic conditions yields the 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile core. The GMP production batch record specifies that the residual difluorobenzodioxole precursor, a potential genotoxic impurity, must be quantified below 1.5 µg/g using a dedicated gas chromatography-mass spectrometry (GC-MS) method in selected ion monitoring mode (m/z 201). In commercial seed treatment suspensions (e.g., Maxim XL), fludioxonil is co-formulated with mefenoxam at a loading of 2.5 g a.i. and 1.0 g a.i. per 100 kg of corn seed, respectively. Rheological compatibility tests using a Brookfield RVDV-II+ Pro viscometer with a #4 spindle at 20 rpm confirm that slurry viscosity must remain below 300 cP to ensure uniform film coating in a batch treater (e.g., Gustafson Accu-Treat) without bridging the seed dump gate. When 1H-Pyrrole-3-Carboxylic Acid Replaces Proline in a Solid-Phase Peptide Turn MimeticIncorporation of Fmoc-1H-pyrrole-3-carboxylic acid into a growing peptide chain on a Rink amide resin introduces a conformationally constrained heterocyclic scaffold that reduces backbone flexibility compared to L-proline. In a standard Fmoc solid-phase peptide synthesis (SPPS) cycle performed on an automated peptide synthesizer (e.g., CEM Liberty Blue, scale 0.1 mmol), the unnatural pyrrole acid requires an extended coupling protocol. Activation is achieved with 4.0 equivalents of PyClock and 8.0 equivalents of N,N-diisopropylethylamine in N-methyl-2-pyrrolidone at 50 °C for 15 min under microwave irradiation. The coupling efficiency, monitored by Kaiser test, falls below 98% after a single cycle, necessitating a double-coupling sequence. The electron-rich pyrrole ring renders the amide bond susceptible to acidolytic cleavage during the final global deprotection with trifluoroacetic acid (TFA)/triisopropylsilane/water (95:2.5:2.5 v/v), generating a hydrolytic des-acyl byproduct at 3–5% of the crude peptide peak area in reverse-phase HPLC at 214 nm. Purification via preparative HPLC on a Waters CSH C18 column using a 0.1% TFA-water/acetonitrile gradient isolates the target peptide at greater than 95% purity, though the isolated yield is typically 22–28%. The pyrrole-containing analogue exhibits a type-II β-turn propensity in circular dichroism spectroscopy with a characteristic positive band at 228 nm. Post-Functionalization of BODIPY Dyes Through a Pyrrole-3-Carboxylate Platform1H-Pyrrole-3-carboxylic acid provides a direct entry into unsymmetrical 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores through its condensation with a second pyrrole unit bearing a keto-ester functionality. In phosphorus oxychloride at −10 °C, PCA and ethyl 3,5-dimethylpyrrole-2-carboxylate condense to form a dipyrromethene intermediate, which is complexed in situ with boron trifluoride diethyl etherate in the presence of triethylamine to lock the emissive chelate. The resulting meso-unsubstituted BODIPY features a reactive carboxy handle at the C3 position, enabling bioconjugation via EDC/NHS esterification to primary amine-containing biomolecules. Fluorescence quantum yield (ΦF) determined by the comparative method using fluorescein in 0.1 N NaOH as a standard (ΦF = 0.92) is 0.81 in ethanol, with a Stokes shift of 16 nm that limits sensitivity in fluorescence resonance energy transfer (FRET) applications due to spectral overlap. Photodegradation under continuous xenon arc illumination ( 300 W, ICH Q1B Option 2) leads to a 22% decrease in emission intensity after 8 h, a performance deficit relative to meso-thienyl-substituted BODIPY analogues.
|
Competitive 1H-Pyrrole-3-Carboxylic Acid 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!
1H-Pyrrole-3-carboxylic acid (CAS 931-03-3, molecular formula C5H5NO2, molecular weight 111.10 g·mol⁻¹) is a β‑substituted heterocyclic aromatic carboxylic acid that is isolated as a white to off‑white crystalline powder. The product is manufactured under an ISO 9001:2015‑certified quality management system, with traceability from raw pyrrole feedstocks to final packaging. Typical batch purity determined by reversed‑phase HPLC at 254 nm (C18 column, acetonitrile/phosphate buffer mobile phase, method compliant with USP <621>) exceeds 98.0% (area percent). The material is packaged in amber borosilicate glass vials under a nitrogen overlay and sealed with PTFE‑faced septa to exclude atmospheric moisture and oxygen during shipping and storage.
Batch‑to‑batch consistency is verified against the release specifications shown in the following table. Two standard grades are routinely supplied: a research‑grade intermediate and a cGMP‑compliant intermediate that meets the requirements of ICH Q3C (R8) for residual solvents and USP <231> for elemental impurities.
| Parameter | Research Grade | cGMP Intermediate |
|---|---|---|
| Appearance | White to pale cream powder | White crystalline powder |
| Purity (HPLC, area %) | ≥98.0 | ≥99.0 |
| Melting point | 144–146 °C | 144–146 °C |
| Loss on drying (105 °C, ISO 6353‑1) | ≤0.5 % | ≤0.3 % |
| Residue on ignition | ≤0.1 % | ≤0.05 % |
| Heavy metals (as Pb) | <10 ppm | <5 ppm |
| Residual dichloromethane | — | <600 ppm (ICH Q3C Class 2) |
| Residual toluene | — | <890 ppm (ICH Q3C Class 2) |
The β‑carboxylic acid group of 1H‑pyrrole‑3‑carboxylic acid lacks the resonance stabilization that moderates the electrophilicity of the α‑isomer; consequently, its activated esters react rapidly with amine nucleophiles but are also susceptible to competing hydrolysis and acylurea formation. In a representative coupling protocol executed on a 10 mmol scale in a 250 mL jacketed glass reactor (PTFE paddle stirrer, 250 rpm) under argon, the carboxylic acid (1.0 equiv) was pre‑dissolved in anhydrous DMF that had been dried over activated 4Å molecular sieves (water content <50 ppm by Karl Fischer). Addition of HATU (1.05 equiv) and DIPEA (3.0 equiv) at 0 °C generated the 1‑hydroxy‑7‑azabenzotriazole ester within 5 min, after which benzylamine (1.1 equiv) was introduced. After 4 h at 0–5 °C, the amide product was isolated in 89% yield (off‑white solid, purity 97.8% by HPLC). When DCC (1.1 equiv) and HOBt (1.1 equiv) were substituted in dichloromethane at 0–25 °C over 12 h, the yield rose to 91%, whereas omission of the auxiliary nucleophile HOBt caused yield to collapse to 67% and generated 18% of the corresponding N‑acylurea impurity (identified by LC‑MS). Ambient relative humidity above 50% during reagent weighing consistently reduces yield by 7–10% owing to premature hydrolysis of the activated ester; all manipulations are therefore conducted inside a glovebox or under a positive argon flow.
Long‑term stability data generated on production batches indicate that 1H‑pyrrole‑3‑carboxylic acid undergoes autocatalytic oxidative polymerization when stored above 8 °C in the presence of adventitious moisture. Accelerated ageing studies at 25 °C in sealed amber vials under air revealed a purity loss of approximately 3% per month by HPLC, accompanied by the formation of a dark brown insoluble film. The degradation pathway is consistent with acid‑catalysed pyrrole ring coupling and is suppressed when the solid is kept at 2–8 °C under argon. For storage periods exceeding 6 months, the manufacturer advises transferring the product immediately after opening into a septum‑sealed vial, flushing with argon, and holding at –20 °C. When removing vials from cold storage, a dwell time of 60–90 min at ambient temperature must be allowed before opening; failure to do so causes condensation of ambient moisture onto the cold powder, reducing the effective purity by as much as 1.5% within a single weighing operation. Pre‑drying of the solid at 40 °C under vacuum (10 mbar) for 4 h is recommended before any water‑sensitive transformation.
The carboxylate anion of 1H‑pyrrole‑3‑carboxylic acid exerts a strong ortho‑directing effect on lithiation, enabling selective deprotonation at the C‑2 position with organolithium reagents. Treatment of the sodium salt of the acid with lithium 2,2,6,6‑tetramethylpiperidide (LiTMP, 1.2 equiv) in THF at –78 °C generates the 2‑lithio species, which can be trapped with electrophiles such as trimethylsilyl chloride to give 2‑trimethylsilyl‑1H‑pyrrole‑3‑carboxylic acid in 76% yield after acidification. In contrast, the 2‑carboxy isomer directs lithiation to the C‑5 position, leading to a different substitution pattern. The dichotomy arises because the carboxylate group in the β‑position withdraws electron density inductively from C‑2 without the participating resonance that stabilizes the α‑carboxylate conjugate base, resulting in a higher kinetic acidity at C‑2 (estimated pKa ~35 on the Streitwieser scale). This difference is exploited in the synthesis of 2‑arylated pyrrole‑3‑carboxylates via directed metallation, a route inaccessible with the 2‑carboxy isomer under the same conditions.
The substitution position of the carboxyl group profoundly alters the physical and spectroscopic properties of the two isomeric pyrrolecarboxylic acids, and these variations directly influence their handling and reactivity in synthesis. The table below summarizes the key discriminators. Because the pyrrole ring possesses a plane of symmetry, the 3‑ and 4‑positions are equivalent, and 1H‑pyrrole‑3‑carboxylic acid is sometimes catalogued as 4‑pyrrolecarboxylic acid; the material supplied is the energetically identical β‑substituted isomer.
| Property | 1H‑Pyrrole‑3‑carboxylic acid | 1H‑Pyrrole‑2‑carboxylic acid |
|---|---|---|
| CAS registry number | 931‑03‑3 | 69881‑14‑3 |
| Melting point (lit.) | 144–146 °C | 206–208 °C (dec.) |
| IR C=O stretch (KBr) | 1685 cm⁻¹ | 1655 cm⁻¹ |
| Aqueous solubility profile | Low; sparingly soluble in cold water | Moderate; ~5 g·L⁻¹ at 25 °C |
| Preferred synthetic utility | Decarboxylative cross‑coupling, 2‑aryl derivatives | Vilsmeier‑Haack formylation to 2‑formyl‑pyrrole |
In decarboxylative coupling processes, 1H‑pyrrole‑3‑carboxylic acid serves as a masked 3‑pyrrolyl nucleophile. Under palladium catalysis (Pd(PPh3)4, 5 mol%, K2CO3 base, DMF, 120 °C, 16 h), reaction with iodobenzene delivers 3‑phenyl‑1H‑pyrrole in yields up to 85% without requiring pre‑functionalization of the heterocycle. The corresponding 2‑carboxy isomer decarbonylates much more sluggishly under these conditions, owing to stronger conjugation between the carboxyl group and the ring.
Personnel handling airborne particulates during weighing or transfer must wear NIOSH‑approved particulate respirators (N95 or equivalent). The product is not classified as a hazardous substance under 29 CFR 1910.1200 (OSHA HCS) or under EU Regulation (EC) No 1272/2008 (CLP) in its solid form, but as a fine organic powder it can form combustible dust clouds; area grounding and inert‑gas blanketing are required when working with quantities above 50 g. Contact with strong oxidizing agents — notably chromic acid or concentrated nitric acid — causes rapid exothermic decomposition with evolution of CO2 and charring, and must be strictly avoided. Waste disposal complies with US EPA 40 CFR Part 261; the material is not a listed hazardous waste, but spent containers should be triple‑rinsed and incinerated by a licensed waste contractor.
