5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid

Product Name 5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid
Alias PYRROLE-2-CARBOXYLIC ACID, 5-FORMYL-2,4-DIMETHYL-
Einecs 'EINECS 638-488-5'
Mininmum Order 1g
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
Price Inquiry sales9@bouling-chem.com
Manufacturer Bouling Chemical Co., Limited
CONTACT NOW

In terms of specification, 5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid is supplied with HPLC purity and melting point, making it suitable for pharmaceutical intermediate synthesis.

Specifications

HS Code	400271
Name	5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid
Chemical Formula	C8H9NO3
Molar Mass	167.162 g/mol
Appearance	Solid (usually a powder)
Physical State At Room Temp	Solid
Boiling Point	N/A (decomposes before boiling)
Solubility In Water	Low solubility
Solubility In Organic Solvents	Soluble in some organic solvents like ethanol
Odor	Odorless (assumed as no distinct odor reported)
Color	Colorless to light - colored (usually white powder)

As an accredited 5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100g of 5 - Formyl - 2,4 - Dimethyl - 3 - Pyrrolecarboxylic Acid in sealed chemical - grade bag.
Shipping	5 - Formyl - 2,4 - Dimethyl - 3 - Pyrrolecarboxylic Acid is shipped in sealed, corrosion - resistant containers. Special care is taken to ensure proper labeling, following all safety regulations for chemical transport to avoid any spillage or damage.
Storage	Store 5 - Formyl - 2,4 - Dimethyl - 3 - Pyrrolecarboxylic Acid in a cool, dry place, away from direct sunlight. Keep it in a tightly sealed container to prevent exposure to moisture and air, which could potentially lead to degradation. Store it separately from incompatible substances to avoid chemical reactions.

Application of 5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid

Red-shifted BODIPY fluorophores bearing a carboxylic acid handle for direct bioconjugation are routinely constructed from 5-formyl-2,4-dimethyl-3-pyrrolecarboxylic acid through a modified Lindsey-type one-flask protocol, wherein the non-symmetric pyrrole aldehyde acid (1.00 equiv) is condensed with freshly distilled 2,4-dimethylpyrrole (1.05–1.10 equiv) in anhydrous dichloromethane under 0.5 mol% trifluoroacetic acid catalysis at 22 ± 1 °C for 45–60 min, followed by oxidation with 1.05 equiv 2,3-dichloro-5,6-dicyano-1,4-benzoquinone at –5 °C, complexation with 3.0–3.5 equiv boron trifluoride diethyl etherate in the presence of 3.5 equiv N,N-diisopropylethylamine at ambient temperature, and final precipitation from ice-cold methanol to deliver the crude 3-carboxy-BODIPY in yields of 38–52% after silica gel flash chromatography. The free carboxylic acid component eliminates the need for post-synthetic ester hydrolysis and permits immediate activation with 1.5–2.0 equiv N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 1.8 equiv N-hydroxysuccinimide in MES buffer at pH 6.0–6.5, enabling direct coupling to primary amine-terminated oligonucleotides, monoclonal antibodies, or streptavidin under controlled stoichiometry (typically 8–15 dye molecules per protein) monitored by size-exclusion HPLC using a TSKgel G3000SWXL column and 280/502 nm dual-wavelength detection. Production-scale equipment employed for the condensation step includes a 200 L jacketed glass-lined reactor with PTFE-coated mechanical agitation operating at 120–150 rpm under a nitrogen blanket (dew point ≤ –40 °C), while the activation and bioconjugation stages utilize a disposable tangential flow filtration system with a 10 kDa MWCO polyethersulfone membrane for buffer exchange and purification to a free dye content of <0.5 area% by HPLC. The terminal products comprise fluorescent antibody conjugates for use in 8-color flow cytometry panels for leukemia and lymphoma immunophenotyping, and lyophilized oligonucleotide probes employed in real-time qPCR diagnostic kits requiring reporter-quencher pairs with excitation maxima at 498 ± 2 nm and emission at 508 ± 3 nm. Industry compliance for these in vitro diagnostic intermediates references ISO 13485:2016 clauses 7.3.3–7.3.7 for design and development transfer, IVDR (EU) 2017/746 Annex I general safety and performance requirements, residual solvent analysis per USP <467> Procedure A with headspace GC-FID (limit of dichloromethane ≤ 600 ppm, methanol ≤ 3000 ppm), elemental impurity verification against USP <232>/<233> with an acceptance criterion of cadmium ≤ 2 µg/g, and spectrophotometric molar extinction coefficient determination according to ISO 20473:2007 Clause 4.2 utilizing a NIST-traceable spectrophotometer at 1 nm spectral bandwidth. Process limitations include the strict exclusion of moisture (raw material pre-dried under vacuum 5 mbar at 45 °C until water content ≤ 0.1% by Karl Fischer titrator Metrohm 870 KF Titrino plus); the formyl group is susceptible to aerobic oxidation during prolonged storage in solution, mandating preparation within 4 h of use when held in dichloromethane at 4 °C under argon; and incompatibility with primary or secondary amine additives prior to the boron complexation step must be observed, as premature Schiff base formation diverts > 15% of the precursor to non-fluorescent byproducts detectable as an additional peak at RRT 1.18 in the HPLC chromatogram.

Pyrrolo[2,3-d]pyrimidine Scaffold Construction for Targeted Oncology APIs

In the synthesis of fedratinib and structurally related JAK2/FLT3 kinase inhibitors, 5-formyl-2,4-dimethyl-3-pyrrolecarboxylic acid is employed as the progenitor of the pyrrole C-5 substituent that ultimately becomes the hinge-binding heterocycle upon annulation with formamide. The documented kilolab procedure charges the pyrrole aldehyde acid (1.00 mol) into 3.0 volumes of methanol, adds 1.25 mol hydroxylamine hydrochloride and 1.30 mol sodium acetate, and stirs at 55 °C for 4 h to furnish the corresponding oxime, which is isolated in 94–97% yield after vacuum filtration and water wash; subsequent reduction with 5.0 equiv zinc dust in acetic acid/1.2 equiv water at 40 °C provides 5-amino-2,4-dimethyl-3-pyrrolecarboxylic acid at 78% yield following recrystallization from ethanol/water (3:1 v/v). The pyrimidine ring closure is executed in a Hastelloy C-276 clad pressure vessel (design pressure 0.8 MPa, tested to 1.2 MPa per ASME BPV Code Section VIII) by heating 1.00 kg of the amino-pyrrole acid with 1.35 kg formamide and 0.05 kg ammonium chloride at an internal temperature ramp of 80 °C for 2 h, then 115–120 °C for 12–14 h, during which ammonia generated is vented through a back-pressure regulator set to 0.15 MPa to maintain sufficient formamide reflux. After cooling to 25 °C, the slurry is drowned into 8 volumes deionized water, stirred for 3 h, filtered, washed, and dried under vacuum (50 °C, 10 mbar) to afford the key pyrrolo[2,3-d]pyrimidine-5-carboxylic acid intermediate in 82% yield with HPLC purity >99.0 area% and single impurity <0.15. This carboxylic acid is subsequently converted to the corresponding acid chloride via oxalyl chloride (1.15 equiv, DMF 0.01 equiv, toluene, 60 °C) and coupled with the requisite benzenesulfonamide-piperazine fragment at 0–5 °C in tetrahydrofuran/triethylamine to yield the penultimate amide, defining the fedratinib free base that is transformed into the dihydrochloride monohydrate API using 2.05 equiv HCl gas in isopropanol. The terminal product, fedratinib dihydrochloride monohydrate, is indicated for intermediate-2 or high-risk primary myelofibrosis and is formulated as 100 mg capsules requiring particle size control d90 ≤ 30 µm via jet milling under nitrogen. The entire intermediate and API manufacturing chain adheres to ICH Q7 GMP principles, with impurity control per ICH Q3A(R2) (reporting threshold 0.05%, identification 0.10%, qualification 0.15% relative to the drug substance), genotoxic impurity risk assessments conducted in accordance with ICH M7(R2) using two complementary in silico QSAR models (DEREK Nexus and Sarah Nexus) and purge factor calculations for the oxime intermediate (purge factor >1.5×10^4 for the hydroxylamine-related impurity), residual solvents monitored under ICH Q3C(R8) with a limit of methanol ≤ 3000 ppm and toluene ≤ 890 ppm, and elemental impurities fulfilling USP <232>/<233> using microwave-assisted acid digestion and ICP-MS determination. HPLC release testing for the pyrrolo[2,3-d]pyrimidine acid intermediate relies on USP <621> using a 4.6 × 150 mm, 3 µm octadecylsilane column maintained at 30 °C, gradient elution with 0.1% trifluoroacetic acid in water/acetonitrile at 1.0 mL/min, and UV detection at 254 nm; retention time of the target compound is 9.2 ± 0.3 min. A known processing bottleneck arises when the amino-pyrrole acid intermediate retains water above 0.20% w/w (determined by coulometric Karl Fischer ASTM E1064-16), which promotes hydrolysis of formamide to ammonium formate and reduces the cyclization yield by 8–12%, hence requiring a pre-drying step under vacuum with active nitrogen sweep for 6 h at 58 °C. Additionally, palladium-catalyzed reductive amination alternatives have been assessed for the oxime reduction but are disfavored due to pyrophoric catalyst handling concerns at scale and the need for dedicated hydrogenation infrastructure (Parr stirred reactor, 0.5 MPa H₂, 5% Pd/C, 10% w/w loading), which increases the overall process mass intensity by 1.4-fold compared to the zinc-acetic acid method.The dimerization reactivity of formyl-substituted pyrrolic monomers under MacDonald-type [2+2] condensation dictates the incorporation ratio of 5-formyl-2,4-dimethyl-3-pyrrolecarboxylic acid in the mixed-aldehyde synthesis of asymmetric 5,15-diarylporphyrins destined for photodynamic therapy (PDT). Operating a stirred jacketed reactor with a 1.6 L working volume, 0.20 mol of the formyl-pyrrole acid is dissolved together with 0.80 mol of 4-methoxybenzaldehyde and 1.00 mol of 2,4-dimethylpyrrole in 1.2 L propionic acid, and the mixture is heated at reflux (141 °C) for 90 min under exclusion of light; the propionic acid acts simultaneously as solvent and Brønsted acid catalyst. After air-oxidation for 12 h, the desired mono-carboxyl-substituted porphyrin is isolated via column chromatography on neutral alumina (activity grade III) with a gradient from dichloromethane to dichloromethane/5% methanol, yielding 6–9% of the target fraction relative to total pyrrole input, with the carboxylic acid-bearing porphyrin displaying an Rf = 0.35 on silica gel TLC (ethyl acetate/heptane 1:1 + 1% acetic acid). The product is subsequently converted to the zinc(II) complex by treatment with 1.2 equiv zinc acetate dihydrate in chloroform/methanol (4:1) at 60 °C for 4 h, reaching > 98% metallation confirmed by the disappearance of the Q-band at 620 nm and the appearance of a sharp Soret band at 423 nm. The carboxylic acid group is then activated to the N-hydroxysuccinimidyl ester, enabling attachment of targeting moieties such as folic acid or cyclic RGD peptides that mediate receptor-selective uptake by tumor cells overexpressing folate receptor-α or αvβ3 integrin. The formulated injectable photosensitizer is reconstituted as a sterile liposomal dispersion in phosphate-buffered saline (pH 7.4) with a drug-to-lipid ratio of 1:20 (w/w) using hydrogenated soy phosphatidylcholine and cholesterol, and sterilized by terminal 0.22 µm polyvinylidene fluoride filtration in accordance with ISO 22457:2023 Annex B for photoactive pharmaceutical sterility assurance. Photostability screening follows the ICH Q1B Option 2 confirmatory identification protocol, exposing the freeze-dried cake to a minimum of 1.2 million lux hours of visible light and 200 Wh/m² ultraviolet A radiation; the photobleaching quantum yield is determined to be 2.3×10^−5 by comparative actinometry using potassium ferrioxalate (ASTM E181-21), with an acceptance criterion of <5% loss of absorbance at the Soret maximum. The terminal product category encompasses verteporfin-type and redaporfin-analogue photosensitizers intended for the treatment of esophageal carcinoma (Palliative Photofrin-based PDT) and non-melanoma skin cancers, where irradiation at 690 ± 3 nm using a diode laser delivering a fluence of 150 J/cm² results in singlet oxygen generation sufficient to achieve a photodynamic threshold dose. Compliance for clinical-grade photosensitizer manufacture integrates ICH Q6A specification testing for new drug substances, ISO 10993-1:2018 biological evaluation of the drug-device combination product (where the light delivery system is a class IIb medical device), and trace-level impurity profiling by LC-MS/MS with detection limits of 0.01% for heme-related contaminant porphyrins. The significant limitation of the mixed-aldehyde route is the stochastic distribution of products, which constrains the usable yield and necessitates rigorous preparative chromatography infrastructure; attempts to shift selectivity by replacing propionic acid with 0.1 M boron trifluoride etherate in dichloromethane at 25 °C resulted in a 3-fold increase in the biladiene side-product, identified by its characteristic absorption at 450 nm.

When a Chromoionophore Requires Covalent Immobilization on an Optical Fiber Surface, 5-Formyl-2,4-dimethyl-3-pyrrolecarboxylic Acid Provides a Dual-Anchoring Mechanism

For the fabrication of evanescent-wave fiber-optic heavy metal sensors, the pyrrole aldehyde acid is converted to the corresponding salen-type ligand through condensation with 1.05 equiv of hydrazine hydrate in ethanol at 78 °C for 3 h, yielding a bright yellow hydrazone that exhibits a bathochromic shift of 82 nm (from 338 nm to 420 nm) upon chelation of Cu²⁺ ions in aqueous solution at pH 5.8 (acetate buffer, 50 mM). The ligand is covalently tethered to the silica core of a 600 µm plastic-clad fiber via a 1.0 cm sensing region etched with 48% hydrofluoric acid to a final core diameter of 400 ± 5 µm, then silanized with 2% (v/v) 3-aminopropyltriethoxysilane in dry toluene at 110 °C under argon for 1 h, after which the hydrazone's pendant carboxylic acid is coupled to the terminal amine using 2.0 equiv N,N'-dicyclohexylcarbodiimide and 1.8 equiv N-hydroxysuccinimide in anhydrous dioxane at 20 °C for 18 h. The formulation addition ratio of the chemoactive compound in the sensing layer is optimized at 0.8 weight percent of the sol-gel matrix, where the sol is prepared from tetraethoxysilane and methyltriethoxysilane in a 70:30 molar ratio with 0.04 M hydrochloric acid catalyst and dip-coated onto the fiber at a withdrawal speed of 80 mm/min, followed by curing at 60 °C for 24 h. The finished fiber-optic probe is integrated into a flow cell (volume 0.5 mL) and interfaced to a tungsten-halogen light source and a CCD-array spectrophotometer covering 350–800 nm, with absorbance measurements performed at 425 nm referenced against a non-coated fiber leg. Instrument calibration for copper(II) nitrate standards in the range 5×10^−7 M to 1×10^−4 M follows ISO 11095:1996 linear calibration using ordinary least squares, yielding a limit of detection of 3.1×10^−7 M (calculated from 3σ/sensitivity) and a response time (t₉₀) of 45 s. The terminal product class, a wavelength-interrogated optode, is deployed for on-line monitoring of cupric ion breakthrough in electroplating rinse water at electroplating facilities operating under ISO 14001 environmental management, where the permissible discharge limit is 0.5 ppm Cu. Interference from Fe³⁺ is suppressed by addition of 0.01 M potassium fluoride to the sample stream, shifting the iron redox potential and rendering the fiber selective with a selectivity coefficient log K_Cu,Fe –2.8 as determined by the matched potential method. Critical operational boundaries stem from the hydrazone’s susceptibility to photoisomerization under continuous exposure to UV-rich light below 380 nm; hence, a long-pass optical filter (cut-on 395 nm) is mandatory in the source path, and the immobilized sensing layer must be stored in the dark at 4 °C when not in use to prevent a baseline drift exceeding 0.002 absorbance units per 24 h. Compliance for the sensor assembly references ISO 15839:2003 for performance testing of on-line water quality sensors, IEC 61326-1:2020 electromagnetic compatibility for measurement and laboratory equipment, and ISO/IEC 17025:2017 for calibration and competence of the performing testing laboratory.

Functional Dopants in Carboxylated Polypyrrole Coatings for Neural Electrode Arrays

Electrochemical co-polymerization of 5-formyl-2,4-dimethyl-3-pyrrolecarboxylic acid with pyrrole monomer onto lithographically defined gold microelectrode sites (geometric area 1963 µm², 50 µm diameter) generates a thin, ionically conducting polymer film with pendant –COOH groups that serve as anchor points for laminin-derived peptides. The deposition electrolyte consists of 0.1 M pyrrole, 0.012 M of the pyrrole-carboxylic acid comonomer (molar ratio pyrrole:comonomer 8.3:1), and 0.1 M sodium p-toluenesulfonate as supporting electrolyte, all dissolved in de-ionized water at pH 2.8 adjusted with hydrochloric acid; the solution is sparged with high-purity nitrogen for 20 min prior to use. Potentiostatic polymerization is carried out at 0.78 V versus a Ag/AgCl (3 M KCl) reference electrode using a Gamry Interface 1010E potentiostat, with the charge density limited to 25 mC/cm² to achieve a polymer thickness of approximately 120 ± 15 nm as confirmed by stylus profilometry (KLA Tencor P-7, tip radius 2 µm, force 1 mg). After deposition, the microelectrode array is rinsed and immersed in 50 mM MES buffer pH 5.5 containing 2 mM EDC and 4 mM sulfo-NHS for 30 min to activate surface carboxylic acid groups, then soaked overnight at 4 °C in a 20 µg/mL solution of the peptide sequence GGGYDCDPGYIGSR in phosphate-buffered saline. The covalently modified coating reduces the electrochemical impedance at 1 kHz from an initial 1.8 MΩ to 260 kΩ (measured in 0.01 M phosphate-buffered saline with a 10 mV RMS AC perturbation), meeting the ASTM F2129-19a recommended practice for cyclic potentiodynamic polarization screening of small implantable neural stimulating electrodes. The terminal medical device product, a flexible polyimide-based penetrating cortical microelectrode array, is utilized as a chronic neural interface for recording local field potentials and single-unit activity in motor cortex regions during brain–machine interface studies, and as a stimulation electrode for deep brain stimulation research in rodent models. Biological safety evaluation follows ISO 10993-6:2016 for local effects after implantation, with a 14-day intramuscular implantation in rabbit paravertebral muscle demonstrating a fibrous capsule thickness of 38 ± 9 µm, statistically equivalent to the smooth platinum control. Sterilization is achieved by ethylene oxide gas (preconditioning at 45 °C, 60% RH for 12 h; EO concentration 600 mg/L at 55 °C for 3 h) with residual ethylene oxide measured below 4 µg/cm² by headspace GC per ISO 10993-7:2008. The aldehyde group of the comonomer remains intact during polymerization at pH < 3.0, but exposure to alkaline conditions (pH > 9.0) during the peptide coupling step or post-implantation inflammation-induced alkaline environments triggers irreversible imine crosslinking within the matrix, documented rheologically by an increase in the storage modulus of the hydrated film from 1.2 MPa to 4.7 MPa and a corresponding decrease in charge storage capacity from 8.2 mC/cm² to 3.5 mC/cm²; therefore, all aqueous processing after polymerization must be buffered within the range pH 3.5–7.0 to preserve the electroactivity of the coating.

Compliance and Analytical Specification Cross-Reference by Application Segment
Application Segment	Key Purity / Performance Parameter	Limit / Specification	Reference Standard / Method
BODIPY Fluorophore Precursor	Assay (anhydrous, solvent-free basis)	≥ 98.0 % (HPLC area)	USP <621> (C18, gradient ACN/0.05 % TFA)
BODIPY Fluorophore Precursor	2,4-Dimethylpyrrole homodimer impurity	≤ 0.5 area%	In-house HPLC (RRT 1.32)
BODIPY Fluorophore Precursor	Residual Solvent, Dichloromethane	≤ 600 ppm	USP <467> Procedure A
Oncology API Intermediate	Purity (HPLC, 254 nm)	≥ 99.0 area%	USP <621> (C18, 3 µm, 4.6×150 mm)
Oncology API Intermediate	Any unspecified impurity	≤ 0.10%	ICH Q3A(R2)
Oncology API Intermediate	Water Content	≤ 0.15 % w/w	ASTM E1064-16 (Coulometric KF)
Oncology API Intermediate	Genotoxic Impurity (hydroxylamine)	≤ 1.5 µg/g	ICH M7(R2) LC-MS/MS
PDT Photosensitizer Precursor	Mono-carboxyl porphyrin content	≥ 95% of porphyrin fraction	Preparative HPLC, ISO 22457:2023 Annex C
PDT Photosensitizer Precursor	Photobleaching quantum yield	≤ 5×10⁻⁵	ASTM E181-21
Fiber-Optic Sensor Component	Copper(II) complex formation constant (log β)	4.8 ± 0.1 (at pH 5.8)	ISO 11095:1996 linearity check
Fiber-Optic Sensor Component	Fiber coating thickness uniformity	200 ± 30 nm (SEM)	ISO 21250:2019
Neural Electrode Co-Dopant	Charge Storage Capacity	≥ 7.5 mC/cm²	ASTM F2129-19a cyclic voltammetry
Neural Electrode Co-Dopant	Impedance at 1 kHz	≤ 300 kΩ (1963 µm² site)	ASTM F2129-19a EIS

Free Quote

Competitive 5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic 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

Get Free Quote of Bouling Chemical Co., Limited

Flexible payment, competitive price, premium service - Inquire now!

Get A Free Quote Now

Certification & Compliance

5-Formyl-2,4-Dimethyl-3-Pyrrolecarboxylic Acid 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

5-Formyl-2,4-dimethyl-3-pyrrolecarboxylic acid (FDMPCA) is typically supplied under product code FDMP-98 as a pale-yellow to light-brown crystalline powder. The material is characterised by a molecular formula C₈H₉NO₃ and a molecular weight of 167.16 g mol⁻¹. Commercial lots exhibit an assay of ≥97.0% (HPLC, λ = 254 nm, area normalisation), with loss on drying not exceeding 0.5% when determined at 50 °C under vacuum (20 mbar) for 4 h. The melting range, observed by differential scanning calorimetry in sealed aluminium pans at 5 K min⁻¹, lies between 208 °C and 213 °C (decomposition). Solubility in common organic solvents at 25 °C is ≤5 g L⁻¹ in dichloromethane, ≤12 g L⁻¹ in tetrahydrofuran, and ≤3 g L⁻¹ in acetonitrile; the compound is only sparingly soluble in water (<0.1 g L⁻¹). Storage under inert atmosphere at −20 °C is recommended because the aldehyde group is susceptible to air oxidation, which manifests as a colour shift toward amber and a concomitant drop in HPLC purity below 95% within 30 days at 25 °C and 60% RH in unopened polyethylene bags. This hygroscopic tendency mandates that containers be equilibrated to ambient temperature before opening to prevent localised moisture condensation.

What Differentiates the 5-Formyl-2,4-Dimethyl Substitution Pattern from the 4‑Formyl‑3,5‑Dimethyl Analogue?

Regioisomeric purity is critical because the relative positioning of the formyl and carboxylic acid groups determines the electronic environment of the pyrrole β‑positions, which in turn governs condensation kinetics. In the 5‑formyl‑2,4‑dimethyl‑3‑carboxy isomer, the electron‑withdrawing aldehyde moiety is situated para to the ring nitrogen and shares conjugation with the carboxylic acid through the C2–C3 bond, lowering the nucleophilicity of the free α‑position (C5 when unprotected). In the 4‑formyl‑3,5‑dimethyl‑2‑carboxy isomer—a common Knorr‑pyrrole derivative—the aldehyde is located ortho to the carboxylic acid, facilitating intramolecular hydrogen bonding that stabilises the enolic tautomer and alters the regioselectivity of dipyrromethane formation. These differences become operationally visible during acid‑catalysed condensations with aldehydes in dichloromethane at 23 °C: the 5‑formyl‑2,4‑dimethyl‑3‑carboxy isomer yields the expected 5‑(aryl) dipyrromethane‑1‑carboxylic acid as the predominant product (>80% selectivity by HPLC), whereas the 4‑formyl‑3,5‑dimethyl‑2‑carboxy isomer generates up to 25% of a rearranged β‑substituted byproduct under identical Lindsey‑type conditions (BF₃·OEt₂ at 3.0 mol%, 30 min). Table 1 contrasts the key physicochemical and reactivity parameters of the two isomers as received from typical commercial batches.

Comparative Properties of Pyrrole‑Formyl‑Carboxylic Acid Regioisomers (Commercial Batches)
Parameter	5‑Formyl‑2,4‑dimethyl‑3‑carboxy (FDMPCA)	4‑Formyl‑3,5‑dimethyl‑2‑carboxy (Knorr-type)
CAS RN	14369-86-5	2386-25-6
Appearance	Pale‑yellow crystalline powder	Off‑white to beige crystalline powder
Melting range (onset, DSC)	208–213 °C (dec.)	235–240 °C (dec.)
HPLC purity (λ = 254 nm)	≥97.0%	≥98.0%
Dominant tautomer in CDCl₃	Fully covalent aldehyde; free acid	Enol‑acid equilibrium (ca. 15% enol)
Reactivity in dipyrromethane condensation (BF₃·OEt₂, CH₂Cl₂)	Linear product > 80%; minimal scrambling	β‑scrambled byproduct 20–25%

The enhanced regiochemical fidelity of FDMPCA makes it the preferred building block when the 3‑carboxy group must remain intact for downstream macrocycle closure, as the meta‑relationship between the reactive α‑site and the acid avoids the β‑attack pathway that plagues the ortho‑analogue. When this compound is employed as a precursor for meso‑substituted dipyrromethanes, the presence of the 3‑carboxylic acid moiety necessitates ester protection strategies to avoid unwanted decarboxylation during acid‑catalysed condensation. For kilogram‑scale campaigns run in a 50 L glass‑lined reactor equipped with a retreat‑curve impeller, the acid is first converted to its methyl or benzyl ester by treatment with thionyl chloride (1.1 eq) in methanol at 0 °C followed by precipitation from ice‑water; isolated yields of the 3‑methoxycarbonyl derivative routinely exceed 88% after drying at 40 °C for 12 h. Unprotected FDMPCA can be condensed directly with aryl aldehydes under modified Adler‑Longo conditions in propionic acid at 130 °C, but the concomitant decarboxylation leads to a statistical mixture of di‑ and tri‑pyrrolic species, reducing the yield of the desired dipyrromethane to <35%. Consequently, the fully protected route is universally adopted for multi‑gram porphyrin precursor synthesis. Pre‑drying of the monomer at 50 °C under 10 mbar oil‑free vacuum for 6 h is mandatory when the subsequent reaction uses moisture‑sensitive Lewis acids; residual water levels above 200 ppm (determined by Karl Fischer titration of the reaction solvent after monomer addition) depress the catalytic activity of BF₃·OEt₂ and increase the induction period to >45 min.

Utilisation in BODIPY Dye Core Construction Demands Strict Anhydrous Conditions

The 5‑formyl‑2,4‑dimethyl‑3‑carboxy architecture can be integrated directly into 4,4‑difluoro‑4‑bora‑3a,4a‑diaza‑s‑indacene (BODIPY) chromophores by exploiting the formyl group as a Knoevenagel‑active centre while retaining the carboxylic acid for water‑solubilisation or bioconjugation. A representative procedure involves the initial formation of the BODIPY core from a dipyrromethene intermediate generated by condensation of FDMPCA with pyrrole‑2‑carboxaldehyde, followed by complexation with BF₃·OEt₂ in dry CH₂Cl₂ containing 2.5 eq of triethylamine. The entire operation must be executed on a Schlenk line maintaining an internal argon atmosphere with <3 ppm O₂ and <5 ppm H₂O, because even trace moisture hydrolyses the boron‑fluorine bonds, leading to the formation of the non‑fluorescent 4‑hydroxy‑4‑bora derivative. After complexation, the residual 3‑carboxy group is activated in situ with N‑(3‑dimethylaminopropyl)‑N′‑ethylcarbodiimide hydrochloride (EDC·HCl, 1.2 eq) and coupled with 1.0 eq of a primary amine NHS ester; typical conversions reach 70–85% as judged by LC‑MS. In a pilot‑plant setting using a 20 L jacketed glass reactor, exotherms of ΔT = 8–12 °C were observed upon addition of the BF₃·OEt₂ complex, necessitating jacket cooling to maintain the bulk temperature below −5 °C during the first 15 min of dosing to suppress a thermally induced demethylation side reaction that generates a 2‑desmethyl impurity at 2–4% area.

If the Compound is Intended for Pharmaceutical Intermediate Synthesis, Trace Metal Specifications Become Paramount

For customers operating under ICH Q3D guidelines, FDMPCA is offered in a controlled Low‑Metals grade that meets the limits for Class 1, 2A, and 2B elements. Table 2 provides the test panel of a representative lot.

Trace Elements and Residual Solvent Profile – FDMPCA Low‑Metals Grade (Lot FM24‑087)
Test	Method	Result	Specification
Cadmium (Cd)	ICP‑OES after microwave digestion (USP<233>)	0.8 µg g⁻¹	≤ 2 µg g⁻¹
Lead (Pb)	ICP‑OES (USP<233>)	<0.5 µg g⁻¹	≤ 5 µg g⁻¹
Arsenic (As)	Hydride generation‑AAS (USP<211>)	<0.3 µg g⁻¹	≤ 1.5 µg g⁻¹
Mercury (Hg)	Cold vapour‑AAS (USP<261>)	<0.1 µg g⁻¹	≤ 3 µg g⁻¹
Palladium (Pd)	ICP‑MS	1.2 µg g⁻¹	≤ 10 µg g⁻¹
Residual solvents	HS‑GC (USP<467> Procedure A)	Methanol: 120 ppm; DCM: 35 ppm	Methanol ≤ 3000 ppm; DCM ≤ 600 ppm

The unformylated parent compound, 2,4‑dimethyl‑3‑pyrrolecarboxylic acid (CAS 17140-86-6), is sometimes considered as an alternative entry point for porphyrin chemistries, yet its lack of an aldehyde handle restricts late‑stage diversification to N‑alkylation or decarboxylative coupling. Under Vilsmeier‑Haack formylation attempts on the parent acid, the 5‑position is attacked preferentially, but competing formylation at the free α‑carbon often produces the 5‑formyl derivative in only 55–60% isolated yield with significant co‑eluting diformyl side products; the direct purchase of FDMPCA eliminates this purification bottleneck. Corrosion inhibition in acid pickling baths has been explored with certain pyrrolecarboxylic acid derivatives; however, published data for this specific 5‑formyl variant is limited. In a single‑study evaluation using low‑carbon steel coupons immersed in 1 M HCl at 30 °C with 5 × 10⁻³ M FDMPCA, a weight‑loss‑derived inhibition efficiency of 62% was reported, which falls below the 90% benchmark achievable with imidazoline‑based inhibitors under identical conditions. Therefore, this application class does not drive product demand. For academic laboratories employing automated parallel synthesis platforms, FDMPCA is compatible with solid‑phase resins bearing Wang or Rink amide linkers provided the 3‑carboxy group is pre‑activated with HBTU/DIEA in DMF. Loading efficiencies of 0.45–0.60 mmol g⁻¹ are typical on aminomethyl polystyrene ( 100–200 mesh, 1% DVB) after a 2 h coupling at 25 °C. Monitoring by chloranil test confirms the absence of free amino groups, and the resin‑bound formyl group can subsequently be condensed with α‑free pyrroles in a 1:1 (v/v) mixture of glacial acetic acid and dichloromethane containing 0.1 M pyrrole, enabling the generation of combinatorial libraries of 5‑aryl‑dipyrromethane‑1‑carboxylic acids without solution‑phase work‑up. The space‑time yield advantage over traditional solution‑phase approaches is material only for library sizes exceeding 48 compounds; below that threshold, labour‑intensive column chromatography on the free acid intermediates often proves more cost‑effective. Incompatibility with amine‑based bases such as triethylamine in protic solvents is noteworthy: prolonged exposure (> 6 h) at 25 °C leads to Schiff‑base formation at the aldehyde moiety, generating a coloured imine that co‑crystallises with the desired product and necessitates recrystallisation from hot toluene/hexane (1:3). For this reason, all final‑stage purifications utilise non‑nucleophilic hindered bases such as N,N‑diisopropylethylamine or inorganic carbonates.