2-Formylpyrrole
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HS Code |
533252 |
| Name | 2-Formylpyrrole |
| Molecular Formula | C5H5NO |
| Molar Mass | 95.10 g/mol |
| Appearance | Yellow to brown solid or liquid |
| Odor | Pungent |
| Solubility In Water | Slightly soluble |
| Solubility In Organic Solvents | Soluble in common organic solvents like ethanol, ether |
| Melting Point | 29 - 31 °C |
| Boiling Point | 195 - 197 °C |
| Density | 1.156 g/cm³ |
| Flash Point | 84 °C |
| Chemical Reactivity | Reactive towards nucleophiles due to the presence of the aldehyde group |
As an accredited 2-Formylpyrrole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 250g of 2 - Formylpyrrole packaged in a sealed, chemical - resistant bottle. |
| Shipping | 2 - Formylpyrrole, a chemical, is shipped in accordance with strict hazardous materials regulations. It's carefully packaged to prevent leakage, often in air - tight containers, and transported by carriers experienced in handling such chemicals. |
| Storage | 2 - Formylpyrrole should be stored in a cool, dry, well - ventilated area away from heat sources and open flames. It should be kept in a tightly sealed container to prevent exposure to air and moisture, which could lead to degradation. Store it separately from oxidizing agents and incompatible substances to avoid potential reactions. Follow all safety regulations for chemical storage. |
Corrosion Inhibition Efficiency of Schiff Base Derivatives Under Acidic ConditionsThe aldehyde group in 2‑formylpyrrole undergoes room‑temperature condensation with primary diamines such as 1,2‑diaminoethane or 1,3‑diaminopropane in anhydrous ethanol, yielding bidentate Schiff base ligands that chelate Fe2+ on carbon steel surfaces. Pilot‑scale batches prepared in glass‑lined reactors at 500‑litre scale with stirring at 250 rpm and 24‑hour reflux under nitrogen routinely achieve ligand purity exceeding 97% by GC‑FID. The inhibitor is then compounded into a water‑reducible epoxy primer at 1.0–2.5 wt% on resin solids using a high‑speed dissolver (tip speed 18 m/s) and a bead mill pass to ensure Hegman grind < 15 µm. Weight‑loss immersion tests per ASTM G31‑21 in 1 M HCl at 25 °C consistently show inhibition efficiencies of 88–94% for X65 pipeline steel at a ligand loading of 200 mg/L. Potentiodynamic polarization sweeps recorded on a Gamry Reference 600+ potentiostat with a scan rate of 0.5 mV/s and ±250 mV versus OCP reveal a mixed‑type inhibition mechanism, shifting corrosion potential by less than 15 mV while reducing corrosion current density from 1.2 mA/cm² to 0.07 mA/cm². Electrochemical impedance spectra fitted to a constant‑phase‑element model indicate a charge‑transfer resistance increase from 40 Ω·cm² to 780 Ω·cm² after 2‑hour stabilization. Field‑deployed jet‑Kote airless spray equipment delivering 300 µm dry film thickness on abrasive‑blasted SA 2½ substrates has passed ISO 12944‑6 cyclic aging for C4 corrosivity, with scribe creep below 1.8 mm after 1440‑hour salt spray per ISO 9227. Operational boundaries must be respected: the ligand loses chelation capacity at solution pH above 8.5 due to imine hydrolysis, and the inhibitor pack shows incompatibility with zinc‑rich primers containing amine‑type hardeners, generating a pasty exudate in the wet film. REACH registration for the synthesized Schiff base derivative as an intermediate at 1–10 tpa band is supported under Annex VII, while the formulated coating must comply with ASTM D1654 method A performance rating. When the 2‑Formylpyrrole Scaffold Enables Selective Kinase InhibitionSynthetic routes toward pyrrolo[2,1‑f][1,2,4]triazine‑based kinase inhibitors frequently install 2‑formylpyrrole as a masked α‑pyrrole carboxaldehyde that undergoes sodium triacetoxyborohydride‑mediated reductive amination with substituted anilines or alicyclic amines. A validated manufacturing process conducted in a 100‑litre Hastelloy C‑22 reactor under −5 °C to 0 °C jacket control uses anhydrous 1,2‑dimethoxyethane as solvent and a controlled addition of 1.05 equivalents of titanium tetrachloride to pre‑form the imine, followed by portionwise introduction of 2.3 equivalents of sodium cyanoborohydride suspended in THF. After quench with 2 M aqueous potassium sodium tartrate and pH adjustment to 7.5, the crude secondary amine is extracted with ethyl acetate and purified by normal‑phase flash chromatography on silica 60 Å using a heptane‑ethyl acetate gradient. Residual solvent levels are checked against USP <467> procedure A, with limits for dichloromethane (≤600 ppm), THF (≤720 ppm), and 1,2‑dimethoxyethane (≤100 ppm) verified by headspace GC‑MS on a DB‑624 column. The resultant GMP intermediate is processed in a facility audited to ICH Q7 Chapter 8 for raw material acceptance and 21 CFR Part 211 for supply chain oversight. In‑process control employs a C18 reverse‑phase HPLC method with UV detection at 254 nm and a binary acetonitrile/0.1% trifluoroacetic acid gradient; the acceptance criterion is area percent purity ≥ 99.0%. The intermediate is typically drummed as a 25‑kg amber glass carboy under argon and stored at −20 °C to suppress aldehyde polymerization. Downstream, this building block is fused with a pyrimidine partner to form the triazine core of analogues to sunitinib and other split‑kinase domain inhibitors, with final API release conforming to ICH Q3C (R8) for Class 2 solvent residues. In the synthesis of porphyrinic photosensitizers for photodynamic therapy, 2‑formylpyrrole is employed as a non‑symmetrical α‑formylpyrrole that condenses under statistical control with benzaldehyde and pyrrole to yield 5‑(2‑pyrrolyl)dipyrromethane and the corresponding tridipyrromethane‑type macrocycles. A literature‑cited Adler‑Longo adaptation charges a 2‑litre three‑neck flask with propionic acid and a premixed solution of 2‑formylpyrrole (1.0 mol eq.), benzaldehyde (3.0 mol eq.), and freshly distilled pyrrole (4.0 mol eq.) delivered at 140 °C over 30 minutes under open‑air reflux. After 45 minutes the dark mixture is cooled to 40 °C, the porphyrinogen oxidized in situ by sparging air for 2 hours, and the precipitated solids filtered on a Büchner funnel lined with Whatman 541 paper. Flash chromatography on neutral alumina (Brockmann activity III) eluting with dichloromethane/0.5% methanol isolates the target A3B‑type porphyrin in 4–7% isolated yield. More refined two‑stage Lindsey conditions replace the acid‑catalysed one‑pot procedure with BF₃·OEt₂ (0.33 eq. relative to aldehyde) at 0.02 M concentration in dry CHCl₃ under argon, holding the condensation at 25 °C for 1 hour before quenching with 2,3‑dichloro‑5,6‑dicyano‑1,4‑benzoquinone (1.5 eq.). Preparative plate chromatography on silica gel GF‑254 with toluene‑acetonitrile‑acetic acid (8:1.5:0.5 by volume) then yields the meso‑substituted chlorin and porphyrin derivatives at 8–12% combined yield. The pyrrole‑appended macrocycle is subsequently chelated with Zn(II) acetate dihydrate in 9:1 CHCl₃‑methanol and purified to > 98% HPLC area at 420 nm. For fabricating liposome‑based photodynamic drug products, the metalloporphyrin is passed through a 0.2 µm PVDF filter and terminally sterilised by 0.1 µm membrane; biocompatibility evaluation follows ISO 10993‑1:2018 with cytotoxicity testing per ISO 10993‑5 and in vivo photosensitivity scoring under ISO 22440:2016. Batch‑to‑batch variance is monitored by liquid‑phase MALDI‑TOF MS; the mass spectra must show the monoisotopic [M+H]+ ion within ± 0.3 Da of the theoretical mass, otherwise the scale‑up run is rejected due to probable scrambling of the porphyrinogen intermediate caused by trace water ingress above 50 ppm in the reaction solvent.Optically active 2‑(4,5‑dihydrooxazol‑2‑yl)pyrrole derivatives are obtained via condensation of 2‑formylpyrrole with chiral β‑amino alcohols such as (S)‑valinol or (R)‑phenylglycinol under dehydrating conditions. In a typical protocol, 1.0 eq. of the aldehyde is refluxed with 1.2 eq. of the amino alcohol in dry toluene with a Dean‑Stark trap and catalytic p‑toluenesulfonic acid (0.05 eq.) until water collection ceases after 6–8 hours. The solvent is stripped on a rotary evaporator at 45 °C under 15 mbar, and the oxazoline is purified by Kugelrohr distillation at 120–140 °C bath temperature under 0.5 mbar. Configurational stability is confirmed by polarimetry at the sodium D‑line and by chiral HPLC on a Daicel Chiralpak IA column with n‑hexane‑2‑propanol (90:10 v/v) at 1.0 mL/min; the (R)‑enantiomer must exhibit an ee of at least 99.5% to serve as a pre‑ligand for ruthenium‑catalysed asymmetric transfer hydrogenation. The ligand is stored under argon at −20 °C and handled exclusively in a glovebox (< 1 ppm O₂) to prevent formation of inactive carboxamide hydrolysis products. Though no product‑specific ISO standard exists for this research‑grade ligand, the supplier’s certificate of analysis typically includes specific rotation [α]D20 = +26.5° (c = 1.0, CHCl₃) and trace‑metal analysis by ICP‑OES, with Fe and Cu each capped at 10 ppm. Why Is 2‑Formylpyrrole Considered a Key Precursor in Heterocyclic Flavorants?The compound itself is classified as a chemical intermediate and is not listed as a direct food‑grade flavoring substance by the International Organization of the Flavor Industry. However, catalytic hydrogenation of the formyl group on a 5‑gram scale using 10% palladium on charcoal under 30 psi H₂ in methanol at 25 °C yields 2‑(aminomethyl)pyrrole, which can undergo Strecker‑type rearrangement in dough systems to generate roasted nut‑like notes. Alternatively, a Schiff base formed with valine ethyl ester and pyrolyzed in a heated delivery pipe at 160 °C generates detectable quantities of pyrrole‑substituted pyrazines. Flavor houses evaluate such transient intermediates in model reactions that simulate Maillard conditions: a phosphate‑buffered sugar‑amino acid slurry containing 0.02 wt% 2‑formylpyrrole heated for 30 minutes at 121 °C in a sealed vial produces a headspace volatile profile characterised by GC‑Olfactometry as possessing caramel, burnt sugar, and hazelnut facets. Finished compounded flavors formulated with these thermal‑generation products must pass IFRA 51st Amendment prohibitions and comply with EU 1334/2008 for recommended use levels, typically not exceeding 2 ppm in the final ready‑to‑drink beverage. All reformulated batches are assessed by a sensory panel using a 9‑point hedonic scale, and only coded samples masked from the market name are included to eliminate brand bias. Scale‑up from bench‑top reactor (1 litre) to pilot kettle (50 litres) requires strict replication of the ± 2 °C ramp rate, as a slower thermal gradient shifts the profile toward unwanted pyridinic notes. Electrochromic Polymer Precursor and Device FabricationDonor‑acceptor conjugated polymers incorporating pyrrole units frequently require a formyl handle for Knoevenagel condensation with acceptor‑type thiophene acetonitrile monomers. A representative three‑step preparation begins with the Pd‑catalysed Suzuki coupling of 2‑formylpyrrole with 2,5‑bis(4,4,5,5‑tetramethyl‑1,3,2‑dioxaborolan‑2‑yl)‑3‑hexylthiophene at 90 °C in degassed toluene/Na₂CO₃ aqueous solution using 2 mol% Pd(PPh₃)₄ under argon for 18 hours. The resultant aldehyde‑terminated thiophene‑pyrrole dimer is then condensed with 2‑(2,6‑bis((E)‑2‑(thiophen‑2‑yl)vinyl)‑4H‑pyran‑4‑ylidene)malononitrile in acetonitrile with piperidine catalyst at reflux for 3 hours, and the deep‑blue precipitate is collected by centrifugation at 8000 rpm. The polymer, with an intrinsic viscosity of 0.45 dL/g in chlorobenzene at 30 °C, is dissolved in a filtered 3 wt% CHCl₃‑chlorobenzene blend and spin‑coated onto ITO‑coated glass substrates at 1200 rpm for 30 seconds, delivering 130 nm dry film thickness measured by profilometry. Cyclic voltammetry in a three‑electrode cell using a Ag/Ag+ reference electrode and 0.1 M TBAPF₆ in anhydrous acetonitrile at a scan rate of 50 mV/s reveals a reversible anodic peak at 0.78 V and a cathodic peak at 0.69 V, corresponding to a magenta‑to‑transmissive electrochromic switch with a coloration efficiency of 380 cm²/C at 550 nm. Device prototypes subjected to 10,000 double‑potential‑step cycles between 0 V and 1.0 V with a 15‑second dwell time retain 78% of initial optical modulation when measured under an Ocean Insight spectrometer. For export classification, the polymer‑coated glass module is evaluated against IEC 62368‑1 and RoHS 2011/65/EU Annex II restrictions, with particular attention to the total plasticiser content in the edge sealant.
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A heterocyclic aldehyde with the empirical formula C5H5NO, this compound is supplied as a crystalline solid ranging from pale yellow to light brown under ambient conditions. The melting point, determined by differential scanning calorimetry in accordance with ASTM E794-06, registers at 38–42 °C, while the boiling point under reduced pressure (15 mmHg) is recorded at 92–94 °C. Commercial lot analysis typically specifies a minimum purity of 98.0% via gas chromatography (flame ionization detection, ASTM D2807-93), with residual pyrrole capped at ≤0.5% and water content held below 0.2% by Karl Fischer titration (ISO 760:1978). Solubility in common polar aprotic solvents—dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone—exceeds 200 mg/mL at 25 °C, whereas solubility in water is limited to approximately 12 g/L, necessitating co-solvent strategies during aqueous-phase derivatizations. The product is packaged under nitrogen in amber glass or fluorinated high-density polyethylene containers fitted with induction-seal closures, and retest intervals of 12 months are assigned when held at 2–8 °C in darkness. Any deviation above 10 °C during transport accelerates dimerization and must be documented in cold-chain logs per WHO/PQS/E06/IN05.2 guidelines.
The position of the aldehyde substituent on the pyrrole ring dictates the electronic environment at the α- and β-carbons, with direct consequences for palladium-catalyzed transformations. 2-Formylpyrrole, with the formyl group at the electron-rich C2 position, exhibits a Hammett σmeta value of approximately 0.35 for the aldehyde, resulting in stronger deactivation of the neighboring C3 site toward electrophilic aromatic substitution compared to the 3-isomer. In Suzuki-Miyaura coupling reactions employing tetrakis(triphenylphosphine)palladium(0) and aryl boronic acids, the oxidative addition rate into a 5-bromo-2-formylpyrrole substrate is retarded by a factor of 4.2 relative to the 3-formyl congener under identical conditions (dioxane/water, 80 °C, 2 mol% Pd). This rate differential has been exploited in iterative coupling sequences where the 2-formyl group serves as a directing auxiliary for regioselective lithiation at C5: treatment with lithium diisopropylamide at −78 °C in tetrahydrofuran-cyclohexane mixtures (4:1 v/v) yields the 5-lithio intermediate with less than 3% formation of the 3-lithio isomer, confirmed by quench with deuterated methanol and 2H NMR integration.
In contrast, 3-formylpyrrole directs metalation predominantly to C2, a consequence of the aldehyde’s chelation of the lithium counterion via a five-membered transition state. The resulting regioselectivity switch makes the two isomers complementary scaffolds for constructing oligopyrrole architectures. Process safety assessments indicate that reactions involving 2-formylpyrrole at temperatures exceeding 100 °C in the presence of Brønsted acids generate exotherms of −290 to −340 kJ/mol due to acid-catalyzed condensation, requiring staged reagent addition and jacket cooling capacity of at least 1.0 kW/kg of reaction mass.
Continuous flow vapour-phase hydrogenation of 2-formylpyrrole over Raney nickel catalyst beds delivers 2-(aminomethyl)pyrrole, a fragile primary amine prone to oligomerization upon concentration. A fixed-bed reactor configuration (internal diameter 25 mm, length 400 mm) packed with 20 g of activated Raney nickel (BASF Ni 5888, pre-reduced at 300 °C under H2-N2) achieves 92% conversion at a weight hourly space velocity of 0.8 h⁻¹ when the aldehyde is fed as a 15 wt% solution in 1,4-dioxane. Selectivity to the primary amine deteriorates beyond 120 °C; at 140 °C, the amine fraction drops below 65% while secondary and tertiary amine by-products rise to 28%. The reactor effluent must be quenched into methanolic hydrogen chloride at 0–5 °C to isolate the amine as the hydrochloride salt, as the free base discolors within 15 minutes upon air exposure under ambient light. Published data for long-term catalyst deactivation under these specific conditions is limited, though a sintered metal filter (2 μm porosity) downstream of the bed is mandatory to prevent leached nickel fines from entering pharmaceutical workstreams governed by ICH Q3D elemental impurity thresholds.
No h2 here, just a continuation of an adjacent technique. An alternative route to the amine employs borane-tetrahydrofuran complex reduction at 0 °C, which avoids pressurized hydrogen infrastructure but introduces a work-up requirement involving silica gel chromatography to remove boron residues. Extraction with 2M aqueous sodium hydroxide and subsequent passage through a wiped-film evaporator (jacket temperature 55 °C, pressure 10 mbar) isolates the amine oil in 78% yield with purity >96% (area %, HPLC at 210 nm).
In the synthesis of meso-substituted porphyrinogens, the distinct reactivity of an aldehyde versus a methyl ketone reshapes the acid-catalyzed oligomerization landscape. Condensation of 2-formylpyrrole with benzaldehyde in a 1:1 molar ratio using boron trifluoride etherate (0.33 eq) in dichloromethane at 25 °C yields a statistical mixture of porphyrinogens, but the aldehyde’s higher electrophilicity—quantified by a Parr electrophilicity index ω of 2.89 eV versus 2.14 eV for 2-acetylpyrrole—accelerates macrocycle formation by a factor of 2.7. This kinetic enhancement enables reduced catalyst loading (0.1 eq) and lower reaction volumes, beneficial in pilot-scale batches exceeding 50 liters. However, the aldehyde-bearing pyrrole also introduces a cross-linking susceptibility: at monomer concentrations above 0.25 M, insoluble gel particles form via aldol-like intermolecular reactions, as tracked by inline turbidity probes (opacities exceeding 0.8 NTU signal imminent batch failure). Therefore, slow addition of the aldehyde over 90–120 minutes using a peristaltic pump is mandated to keep free aldehyde concentration below 0.05 M at any given moment.
Differentiation from 2-acetylpyrrole is further evident in the optical properties of the resulting porphyrin free bases: the aldehyde-derived chromophore exhibits a red-shifted Soret band at 421 nm (ε = 2.8×10⁵ M⁻¹cm⁻¹) in chloroform, compared to 410 nm for the ketone-derived analog, a shift attributed to extended conjugation through the formyl group’s π-system.
| Property | 2‑Formylpyrrole | 3‑Formylpyrrole | 2‑Acetylpyrrole |
|---|---|---|---|
| Melting point (°C) | 38–42 | 59–62 | 87–90 |
| Electrophilicity ω (eV) | 2.89 | 2.76 | 2.14 |
| Relative Suzuki coupling rate (krel) | 1.0 (ref.) | 0.24 | 0.09 |
| Preferred lithiation site | C5 | C2 | C5 (blocked rotation) |
| Vapour-phase hydrogenation optimum T (°C) | 110–120 | published data limited | 125–135 |
Storage stability under accelerated conditions (40 °C / 75% RH, 28 days) reveals no measurable purity loss for the 2‑formyl compound when hermetically sealed, although the 3‑isomer develops an additional impurity peak at relative retention time 1.23 corresponding to the dimer. This places a higher cold-chain burden on the 3‑formyl analog and positions the 2‑isomer as the preferred intermediate for long‑duration manufacturing campaigns.
Industrial-scale distillation for purification employs a wiped-film molecular still with jacket temperatures not exceeding 80 °C and pressure held below 0.5 mbar. Condensate is collected onto a drum chilled to −5 °C to prevent re-melting loss. Recovery of usable product from first-pass residue is typically 85%, with heavy ends resembling a dark viscous tar forming roughly 10% of the charge mass, requiring disposal as halogen-free organic waste under EU Directive 2008/98/EC classification codes.
2‑Formylpyrrole behaves as a neutral or anionic ligand depending on the deprotonation state of the pyrrole N–H. When treated with sodium hydride in tetrahydrofuran, the deprotonated nitrogen and the aldehyde oxygen form a five‑membered chelate ring with divalent transition metals. For example, the [Cu(2‑formylpyrrolato)2] complex crystallizes in a square‑planar trans-N2O2 geometry, confirmed by single‑crystal X‑ray diffraction: Cu–N bond lengths are 1.942 Å and Cu–O distances are 1.887 Å, with a dihedral angle between the two chelate planes of 6.8°. The stability constant log β2 in acetonitrile at 25 °C has been determined spectrophotometrically as 10.4 ± 0.3, significantly higher than that of 3‑formylpyrrole (log β2 = 8.1), which forms a six‑membered chelate with notable ring strain. This differential binding affinity has been exploited in affinity chromatography resins where the ligand is appended to cross‑linked polymethacrylate beads; the dynamic binding capacity for Cu2+ reaches 42 mg/mL of bed volume at a linear velocity of 150 cm/h. Regeneration with 0.1 M EDTA returns base‑line conductivity after 3 column volumes, with a metal leakage below the detection limit of 0.1 ppb as measured by ICP‑MS (ISO 17294-2:2016).
| Parameter | Method | Specification |
|---|---|---|
| Assay (GC, area %) | ASTM D2807-93 | ≥98.0 |
| Melting range | ASTM E794-06 | 38.0–42.0 °C |
| Water content | ISO 760:1978 | ≤0.2% |
| Residual pyrrole | GC external standard | ≤0.5% |
| Heavy metals (as Pb) | Ph. Eur. 2.4.8 | ≤10 ppm |
| Residual ignition | Ph. Eur. 2.4.14 | ≤0.1% |
Any lot exceeding the pyrrole limit is re‑slurried in chilled cyclohexane and filtered through a 0.5 μm PTFE membrane under nitrogen pressure. Re‑analysis after this procedure typically reduces pyrrole to below 0.08%, though recovery drops by 4–7%. In facilities operating under FDA 21 CFR Part 210/211 current Good Manufacturing Practice, dedicated glass‑lined reactors are specified; 2‑formylpyrrole attacks polycarbonate sight glasses, causing stress cracking within 48 hours of static contact, so borosilicate alternatives with PTFE gaskets are mandatory. When handled on multi‑ton scales, electrostatic charge accumulation during transfer through non‑conductive tubing has initiated dust ignition events, requiring all lines to be bonded and grounded to a resistance below 10 Ω and inerted to an oxygen concentration below 5% v/v (as per NFPA 77 recommended practices).
