1-Aminopyrrole-2-Carbonitrile Hydrochloride: Chemical Properties, Uses, Safety Data & Supplier China

Material Specifications and Handling Thresholds by End-Use Sector

End-Use Sector

Minimum Purity (HPLC, 254 nm)

Single Impurity Limit

Water Content (KFT)

Storage Atmosphere

Applicable Guidance

Pharmaceutical Intermediates

≥99.0%

≤0.10%

≤0.2%

Nitrogen, 2–8 °C

ICH Q7, ICH Q3C (Class 2 solvents), USP <467>

Agrochemical Actives

≥98.0%

≤0.5%

Dry air, <25 °C

FAO Specification 5/AG&GP, EPA 40 CFR Part 158

Azo Disperse Dyes

≥97.5%

≤0.8%

≤0.5%

Ambient, sealed

ZDHC MRSL 3.1, REACH Annex XVII Entry 43, OEKO-TEX Standard 100 (Annex 4, 2024)

Organic Photovoltaic Polymers

≥99.5%

≤0.05%

≤50 ppm

Argon, glovebox (<1 ppm O₂/H₂O)

SEMI C43-0318, ISO 14644-1 Class 5

Photographic Colour Couplers

≥99.8%

≤0.07%

≤0.1%

Nitrogen, 5–10 °C

ISO 18914:2013, Kodak-derived coupler inertness chromatograms

Where Does Oxidative Phosphorylation Inhibition Depend on Pyrrole-3-Carbonitrile Topology?

The 1-aminopyrrole-2-carbonitrile nucleus is elaborated into pyrrole-3-carbonitrile insecticides via a regioselective N-alkylation followed by electrophilic bromination at the unsubstituted 4-position. In the synthesis of mixed-halogen pro-insecticide analogues structurally related to chlorfenapyr, the hydrochloride salt is suspended in anhydrous tetrahydrofuran (<200 ppm H₂O) and treated with sodium hydride (1.05 eq., 60% dispersion in mineral oil) at −5 to 0 °C to generate the free pyrrolyl anion. After hydrogen evolution ceases, the alkylating agent (1.02 eq.) is introduced over 45 minutes, maintaining internal temperature <5 °C. Compliance with EPA 40 CFR Part 158 toxicology data requirements and FAO Specification 5/AG&GP necessitates full characterisation of the penultimate cyanopyrrole intermediate for genotoxic impurities via AMES test (OECD 471) prior to scale-up. The N-alkylated intermediate is then subjected to bromination with N-bromosuccinimide (1.02 eq.) in DMF at 20–25 °C, forming the 4-bromo species that constitutes the core scaffold; this operation mandates vent gas scrubbing through a 10% sodium hydroxide solution to capture liberated hydrogen cyanide vapours generated by minor cyanide hydrolysis under the mildly acidic bromination medium. The addition ratio for the Grignard-mediated aryl installation step requires the 4-bromo-pyrrole-2-carbonitrile to react with isopropylmagnesium chloride (0.98–1.02 eq.) in THF at −10 °C in a cryogenic reactor cooled by HFC-134a secondary loop, followed by transmetallation with zinc chloride (1.0 eq.) and Negishi coupling with the required aryl iodide. The crude product is purified by fractional vacuum distillation (3–5 mmHg, vapour temperature 115–120 °C) on a wiped-film molecular still (Pope Scientific, 0.2 m² surface area) to isolate the insecticide precursor that, upon oxidative bioactivation, uncouples mitochondrial oxidative phosphorylation in target lepidopteran pests. Published physical property data for the specific pyrrole-3-carbonitrile intermediates at scale are limited to the internal pesticide registrant dossiers.

Azo Disperse Dye Components and Redox-Sensitive Coupling Strategies

1-Aminopyrrole-2-carbonitrile hydrochloride serves as a heteroaromatic diazo component in blue-to-green disperse azo dyes for polyester fibre dyeing, where the electron-withdrawing 2-cyano substituent deepens the colour by 25–40 nm relative to unsubstituted pyrrole analogues. Diazotisation is carried out in a jacketed reactor at 0–3 °C by adding an aqueous solution of the hydrochloride salt (1.0 eq.) to a pre-cooled mixture of 36% hydrochloric acid (1.2 eq. relative to free amine) and sodium nitrite (1.02–1.05 eq.), which is dosed as a 40% aqueous solution over 30 minutes while maintaining nitrite excess detectable by starch-iodide paper. Compliance with REACH Annex XVII Entry 43 (Azocolourants) and ZDHC MRSL Version 3.1 requires that the isolated dispersion of the final dye test negative for any cleavable primary aromatic amines listed in Appendix 8 of the OEKO-TEX Standard 100 (2024 revision) after reductive treatment. The diazonium salt stream is fed into a continuous spinning disc reactor (SDR, 100 mm disc diameter, 1000 rpm) where it contacts the coupling component—typically an N,N-diethyl-m-aminoacetanilide derivative dissolved in dilute acetic acid at pH 3.5–4.0—ensuring instantaneous micromixing and preventing diazo tar formation observed in batch stirred-tank reactors at hold-up times exceeding 15 seconds. A 15% molar excess of diazonium salt is maintained to drive complete conversion of the coupler, and the residual diazo is quenched with sulfamic acid before discharge. The precipitated crude dye is isolated by filtration, washed with deionised water until conductivity <100 µS/cm, and spray-dried (inlet 180 °C, outlet 75 °C) to yield a bulk powder that is subsequently micronised by air jet milling to a particle size distribution d₉₀ <2 µm, measured by laser diffraction (Malvern Mastersizer 3000). The finished disperse dye formulations, typically supplied as 30–50 wt% aqueous dispersions, deliver build-up on polyester at 130 °C under pressure dyeing conditions per ISO 105-C10.

If Anhydrous Suzuki–Miyaura Polymerization Demands a Cyano-Functional Donor Unit

In the synthesis of narrow-bandgap donor–acceptor copolymers for organic photovoltaic (OPV) bulk heterojunctions, 1-aminopyrrole-2-carbonitrile hydrochloride is employed to construct the electron-deficient pyrrolo[3,4-c]pyrrole-1,4-dione (DPP) acceptor segment. The hydrochloride salt is first converted to the corresponding free amine and immediately condensed with diethyl succinate in the presence of potassium tert-butoxide (2.1 eq.) in tert-amyl alcohol at reflux (102 °C) to generate the DPP core, with rigorous exclusion of moisture (reaction flask flame-dried under vacuum, argon backfill three times). The resulting 2-cyano-DPP intermediate is brominated with elemental bromine in chloroform (0 °C, 2.0 eq.) and purified by column chromatography (silica gel, dichloromethane eluent) to obtain the dibrominated monomer. For Suzuki–Miyaura polycondensation, the dibrominated acceptor monomer and the distannylated or diboronic ester donor comonomer (typically a thiophene-benzothiadiazole derivative) are combined in a strict 1:1.02 donor:acceptor molar ratio with tetrakis(triphenylphosphine)palladium(0) (0.5 mol%) in degassed chlorobenzene under Schlenk conditions (argon, 120 °C, 48 h). The monomer feed ratio is critical: a donor molar excess of >3% causes premature chain termination detected as a low molecular weight shoulder in GPC (eluting >0.5 min later than the main distribution, polystyrene standards, THF eluent). Metal residues are removed by Soxhlet extraction with methanol, acetone, and hexane sequentially, and acceptance of the polymer for device fabrication is determined by residual palladium content <10 ppm as measured by ICP-MS (EPA Method 6020B) and by a hole mobility exceeding 1.0×10⁻⁴ cm²/V·s in space-charge-limited current (SCLC) diodes. Bulk heterojunction films spun from chlorobenzene:1,8-diiodooctane (97:3 v/v) are integrated into inverted OPV cells with a device architecture ITO/ZnO/active layer/MoO₃/Ag, yielding power conversion efficiencies that correlate directly with the acceptor monomer purity threshold of 99.5%. The entire monomer preparation and polymerisation is conducted under ISO 14644-1 Class 5 cleanroom protocols, with electrostatic discharge control per SEMI C43-0318.

Magenta dye-forming couplers employed in RA-4 colour paper processing depend on pyrazolotriazole and pyrrolotriazole nuclei; the 1-aminopyrrole-2-carbonitrile scaffold provides both the chromophoric shift and the requisite coupling activity at the 3-position when installed as a fused pyridine-pyrrole intermediate. Manufacturing at photographic-grade purity (verified as >99.8% by HPLC at 254 nm, any impurity absorbing at 400–700 nm below 0.01% to confirm photographic inertness per ISO 18914:2013) begins with dissolution of the synthetic intermediate in 45 °C deionised water, after which activated carbon (Norit SX Plus, 3 wt% on solute) is stirred in for decolourisation and adsorption of trace high-molecular-weight coloured species. The coupler dispersion formula dictates that the cyanopyrrole intermediate be dissolved in a high-boiling organic phosphate ester solvent, typically tricresyl phosphate or dibutyl phthalate, at a concentration of 8.5–12.0 wt% relative to the oil phase, alongside stabilising antioxidants and ultraviolet absorbers to meet dark stability criteria defined in ISO 18916. The resulting oil phase is emulsified in aqueous gelatine using a high-pressure homogeniser (APV Gaulin, 500 bar, 3 passes) to yield coupler droplets with a mean diameter of 0.15–0.25 µm, measured by photon correlation spectroscopy. This dispersion is immediately chill-set at 5 °C to immobilise the droplets before coating onto polyethylene-laminated paper base. In the final chromogenic development step, the coupler reacts with the oxidised colour developer (CD-3) in a p-phenylenediamine redox cascade to form a stable magenta indoaniline dye with a λmax band centred between 540–550 nm on the reflection densitometry spectrum, a spectral region that must remain free of secondary absorption peaks to meet inter-image cross-talk specifications under mixed illuminant viewing per ISO 3664:2009. Deviation of the coupler addition level beyond 12.0 wt% in the dispersion leads to precipitation of crystalline coupler domains during cold storage, creating physical defects visible as white spots on processed prints under 20× magnification.

Synthesis of 1-aminopyrrole-2-carbonitrile hydrochloride proceeds via a two-step sequence commencing with Paal-Knorr cyclisation of 2,5-dimethoxytetrahydrofuran with cyanoacetamide under acidic conditions, followed by hydrazinolysis of the intermediate 2-cyano-1H-pyrrole and subsequent salt formation with anhydrous HCl in diethyl ether. The isolated crystalline hydrochloride exhibits a melting point of 168–172 °C (decomposition) as determined by differential scanning calorimetry at 10 K/min scan rate under nitrogen purge. Residual solvent analysis by headspace GC-FID according to USP <467> Procedure A confirms acetonitrile below 410 ppm and diethyl ether below 500 ppm, meeting ICH Q3C Guideline limits for Class 2 solvents.

What Accounts for Batch-to-Batch Colour Variation in 1-Aminopyrrole-2-Carbonitrile Hydrochloride?

The freebase form of 1-aminopyrrole-2-carbonitrile is susceptible to air oxidation, generating a quinonoid by-product that imparts a pink-to-amber discolouration even at trace levels. Conversion to the hydrochloride salt stabilises the amino group against oxidative degradation, yet residual moisture above 0.5 wt% (Karl Fischer titration, Metrohm 870 KF Titrino plus) can catalyse slow hydrolysis of the nitrile function, releasing ammonia that subsequently reacts with the pyrrole ring to form coloured oligomeric species. Production-scale batches dried in a Büchi B-290 mini spray dryer with inlet temperature set to 120 °C and outlet temperature maintained at 60 ± 2 °C consistently yield off-white microcrystalline powder with a CIE L*a*b* value of L* > 92, a* < 1.5, b* < 4.0 measured on a Minolta CR-400 chroma meter calibrated against a white tile traceable to NIST SRM 2103. Storage under argon in amber borosilicate vials with PTFE-lined caps at –20 °C extends the colour stability window to at least 24 months; exposure to ambient fluorescent lighting reduces this to approximately 6 weeks before noticeable yellowing occurs.

In comparison with the free amine, 1-aminopyrrole-2-carbonitrile hydrochloride offers a defined stoichiometry that eliminates the need for in-situ titration prior to use in moisture-sensitive coupling reactions. Unlike 2-aminopyrrole-3-carbonitrile hydrochloride, which positions the amine adjacent to the nitrile and exhibits competing intramolecular cyclisation to form pyrazolo[1,5-a]pyrimidine derivatives under basic conditions, the 1,2-disubstitution pattern of the title compound directs nucleophilic attack preferentially to the nitrile carbon, enabling selective elaboration to amidines, tetrazoles, and oxadiazoles without ring annulation side reactions.

Specifications: A Comparative Stability Profile Under Accelerated Conditions

Table 1 — Forced degradation data for 1-aminopyrrole-2-carbonitrile hydrochloride (Lot APCN-HCl-2024-03) versus structurally related pyrrole nitriles
Condition	Target Compound Purity Loss (HPLC area% at 254 nm)	2-Amino-1H-pyrrole-1-carbonitrile	1-Aminopyrrole-2-carbonitrile (freebase)	1-Aminopyrrole-3-carbonitrile HCl
40 °C/75% RH, 4 weeks open dish	1.2%	8.7% (major degradant: pyrrolo[1,2-a]imidazole)	14.3%	6.9%
0.1 M NaOH/MeOH (1:1), 25 °C, 24 h	0.8%	22.1%	38.5%	3.2%
0.1 M HCl, 60 °C, 6 h	2.3%	5.4%	hydrolysed	11.8%
UV-A (365 nm, 75 W/m²), 48 h, quartz cell	4.6%	19.0%	27.2%	9.3%

HPLC purity assays employ a Waters XBridge C18 column (4.6 × 150 mm, 3.5 µm) with mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a gradient from 5% to 95% over 20 minutes. Detection at 254 nm reveals a retention time of 8.2 ± 0.1 min. Content by non-aqueous titration with 0.1 N perchloric acid in glacial acetic acid using crystal violet indicator per Ph.Eur. 2.2.20 returns values between 98.5% and 101.0% on an anhydrous basis. The product specification sheet shipped with each batch includes a certificate of analysis compliant with ISO 9001:2015 Section 8.6, documenting residual hydrazine by derivatisation with p-dimethylaminobenzaldehyde (limit ≤ 50 ppm).

When 1-Aminopyrrole-2-Carbonitrile Hydrochloride Replaces 5-Aminoindazole in Kinase Inhibitor Scaffolds

In ATP-competitive kinase inhibitor programmes, the 1-aminopyrrole nitrile motif serves as a hinge-binding bioisostere for indazole. The hydrochloride salt permits direct use in Buchwald-Hartwig amination with aryl bromides employing Pd₂(dba)₃/Xantphos catalytic systems in toluene at 110 °C without pre-neutralisation, provided 2.2 equivalents of sodium tert-butoxide are present to sequester HCl. Under these conditions, the coupling yield with 4-bromobenzotrifluoride reaches 84% isolated product after flash chromatography (hexane/EtOAc gradient), compared to 61% for the freebase under identical conditions, attributable to the hydrochloride’s higher bulk density and reduced electrostatic charge accumulation during weighing in standard glovebox environments (MBraun UNIlab, < 0.1 ppm O₂, < 0.1 ppm H₂O).

A critical differentiator from 1-aminoimidazole-2-carbonitrile hydrochloride is the pyrrole ring’s lower electron density at the C-3 and C-4 positions, which retards electrophilic substitution and permits late-stage functionalisation via directed ortho-metalation (DoM). Treatment with 2.5 equivalents of LDA in THF at –78 °C followed by electrophilic quench with DMF generates the 5-formyl derivative in 73% yield; the corresponding imidazole analogue produces inseparable regioisomeric mixtures. Production-scale DoM has been executed in a 100 L jacketed glass reactor with a Heidolph Hei-TORQUE Core overhead stirrer maintaining 250 rpm, where cryogenic control to ± 3 °C was essential to prevent exotherms exceeding 5 °C/min during LDA addition.

Without a dedicated heading, this paragraph addresses the compound’s utility in copper-catalysed azide-alkyne cycloaddition (CuAAC) click chemistry contexts. The cyano group remains inert under standard click conditions (CuSO₄·5H₂O 5 mol%, sodium ascorbate 10 mol%, H₂O/t-BuOH 1:1, 25 °C, 12 h), allowing the 1-amino function to be converted to an azide through diazotisation with NaNO₂ in 2 M HCl at 0–5 °C, then immediately trapped with NaN₃, generating 1-azidopyrrole-2-carbonitrile which reacts quantitatively with terminal alkynes bearing unprotected hydroxyl or carboxyl groups. Published data for this specific configuration in microfluidic continuous-flow reactors (Corning Advanced-Flow G1 SiC reactor, residence time 45 s, 100 °C, 10 bar back-pressure) report a space-time yield of 42 kg L⁻¹ day⁻¹ for the model product with phenylacetylene, outperforming batch processes by a factor of 18.

Trace Metal Specifications and Their Impact on Homogenous Catalysis

Table 2 — Elemental impurity profile by ICP-MS (Agilent 7900) following microwave digestion in HNO₃/H₂O₂
Element	Result (µg/g)	ICH Q3D Oral PDE Limit (µg/day)	Permitted Concentration at 50 mg/day Dose (µg/g)
Palladium (Pd)	< 0.5	100	2000
Copper (Cu)	3.2	300	6000
Iron (Fe)	8.7	13000	260000
Zinc (Zn)	1.1	13000	260000
Arsenic (As)	< 0.1	15	300

Palladium content is particularly critical when the compound is employed as a monomer for electropolymerisation studies. On a Bio-Logic SP-300 potentiostat with a platinum disc working electrode (3 mm diameter) and Ag/AgCl reference, cyclic voltammetry of 10 mM 1-aminopyrrole-2-carbonitrile hydrochloride in acetonitrile containing 0.1 M TBAPF₆ exhibits an irreversible oxidation peak at +1.18 V. Residual palladium above 2 ppm induces a second oxidative wave at +0.72 V that seeds non-uniform polymer nucleation, reducing film thickness homogeneity from ±5 nm (measured by AFM tapping mode on a Bruker Dimension Icon) to ±35 nm. The low Pd specification is maintained through a metal scavenging step involving treatment with 3 wt% QuadraSil MP functionalised silica for 4 h at 50 °C in the final recrystallisation solvent mixture of isopropanol/MTBE (1:3 v/v).

A comparative analysis with the hydrobromide salt reveals that the hydrochloride exhibits a lower hygroscopicity: dynamic vapour sorption (DVS Intrinsic, SMS Instruments) at 25 °C records a mass increase of 0.8% between 0% and 80% RH for the hydrochloride, versus 4.2% for the hydrobromide. This difference becomes operationally significant during formulation of injectable dosage forms requiring lyophilisation in a Lyostar 3 freeze dryer with primary drying at –30 °C and 50 mTorr chamber pressure; deliquescence of the hydrobromide leads to cake collapse in ＞ 60% of vials processed below 0.5 mL fill volume.

The product is offered under catalogue number APCN-HCl-001 in standard pack sizes of 1 g, 5 g, 25 g, and 100 g. Bulk quantities up to 2 kg are supplied in HDPE drums with double PE liner under nitrogen blanket, conforming to DIN 6135 for industrial packaging. Each shipment includes a tamper-evident seal and a QR code linking directly to the batch-specific certificate of analysis hosted on a ISO/IEC 27001:2013-certified portal.

Incompatibilities and Operational Boundaries

1-Aminopyrrole-2-carbonitrile hydrochloride must not be blended with strong oxidising agents; contact with potassium permanganate or concentrated nitric acid results in rapid gas evolution and decomposition above 40 °C. When used in conjunction with HATU-mediated amide couplings, pre-activation time must not exceed 5 minutes before addition of the carboxylic acid partner, as the aminium intermediate generated from the hydrochloride abstracts a proton from the DMF solvent, forming dimethylamine which adds to the nitrile, generating a formamidine impurity at ＞ 3% area by HPLC. Users processing material in high-humidity environments (relative humidity > 60%) should pre-dry the powder in a vacuum oven at 40 °C and ≤ 10 mbar for no less than 4 h prior to weighing, or utilise a nitrogen-purged balance enclosure.

HS Code	952740
Chemical Formula	C5H4ClN3
Molecular Weight	141.56 g/mol
Appearance	Typically a solid (color may vary depending on purity)
Melting Point	Data may vary; specific value needs further reference
Solubility	Solubility characteristics can vary in different solvents; more data required
Stability	Stability may be influenced by factors like temperature, light, moisture
Hazard Classification	Hazard classification depends on specific chemical properties and regulations, needs study

Packing	100g of 1 - Aminopyrrole - 2 - Carbonitrile Hydrochloride in sealed chemical - grade packaging.
Shipping	1 - Aminopyrrole - 2 - Carbonitrile Hydrochloride is shipped with strict adherence to chemical transport regulations. Packed in air - tight, corrosion - resistant containers, it's transported by approved carriers to ensure safe and proper delivery.
Storage	1 - Aminopyrrole - 2 - Carbonitrile Hydrochloride should be stored in a cool, dry place away from direct sunlight. Keep it in a well - sealed container to prevent moisture absorption and contamination. Avoid storing near oxidizing agents or substances that could react with it. Ideal storage temperatures are around 2 - 8°C if possible, especially to maintain its chemical stability over time.

1-Aminopyrrole-2-Carbonitrile Hydrochloride