4,5-Dibromo-2-Benzoylpyrrole
|
HS Code |
828282 |
| Chemical Formula | C11H7Br2NO |
| Molecular Weight | 327.09 |
| Appearance | Solid |
| Color | Off - white to light yellow |
| Melting Point | 175 - 177 °C |
| Solubility In Organic Solvents | Soluble in common organic solvents like dichloromethane, chloroform |
| Odor | Odorless or very faint odor |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
| Purity | Typically available in high purity (e.g., 95%+) |
As an accredited 4,5-Dibromo-2-Benzoylpyrrole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 4,5 - Dibromo - 2 - Benzoylpyrrole packaged in a sealed, labeled container. |
| Shipping | 4,5 - Dibromo - 2 - benzoylpyrrole is a chemical. Shipping requires proper packaging in sealed containers to prevent leakage. It should be transported following hazardous chemical regulations, with appropriate labels for safety during transit. |
| Storage | 4,5 - Dibromo - 2 - benzoylpyrrole should be stored in a cool, dry, and well - ventilated area. Keep it away from sources of heat, ignition, and strong oxidizing agents. Store it in a tightly sealed container to prevent moisture absorption and contact with air, which could potentially lead to degradation. Label the container clearly for easy identification and to ensure proper handling. |
|
When formulating V-0 rated polycarbonate/acrylonitrile‑butadiene‑styrene (PC/ABS) blends for thin‑wall electronic enclosures, the incorporation of 4,5‑dibromo‑2‑benzoylpyrrole at 8–12 wt% consistently delivers a UL 94 V‑0 classification at 1.5 mm without antimony trioxide co‑synergists. The bromine content of the compound (48.6 % by elemental analysis) enters the ignitable gas phase during combustion and scavenges free‑radical species, yet the benzoyl substituent raises the initial thermal decomposition point relative to fully aliphatic brominated flame retardants. Compounding is performed on a co‑rotating twin‑screw extruder with an L/D ratio of 40:1, using a reverse‑flight kneading block positioned upstream of the atmospheric vent to distribute the additive before the final vacuum devolatilization stage. Barrel temperature profile is maintained between 240 °C and 255 °C at the die; a melt residence time exceeding 90 seconds triggers partial debromination and releases corrosive hydrogen bromide that attacks nitrided barrel linings and causes black‑spec contamination in moulded parts. Injection moulding is conducted with a clamp force of 1,200 kN and a mould surface temperature of 85 °C to minimise frozen‑in stress while preserving the exfoliated brominated layer morphology required for ignition resistance. Final articles include laptop bottom cases, server fan guards, and printer chassis, where comparative tracking index (CTI) measured per IEC 60112 exceeds 250 V and bromine migration testing by IEC 62321 remains below the 900 ppm limit for portable electronics. Thermal gravimetric analysis (TGA) under nitrogen at 10 °C/min gives a 5 % mass‑loss onset at 282 °C, identifying a narrow processing window: extruder hold‑up times that creep beyond 140 seconds at melt temperatures above 260 °C cause a sudden drop in the limiting oxygen index (LOI) from 31 % to below 26 %, effectively reverting the compound to HB classification.
Why does residual tin content during Stille‑type homocoupling of 4,5‑dibromo‑2‑benzoylpyrrole determine final API mutagenic impurity clearance?When the dibromo pyrrole serves as an electrophilic partner in a palladium‑mediated homocoupling, the resulting 2,2′‑bibenzoylpyrrole core becomes a key structural element for a class of diaryl heterocycle anti‑inflammatory agents currently in Phase II clinical evaluation. The coupling is carried out with 0.5 mol% Pd(PPh₃)₄ and 1.25 equivalents of hexabutylditin in anhydrous DMF at 65 °C under nitrogen, yielding the dimer in 82–87 % after 6 hours. Quenching with aqueous KF precipitates tributyltin fluoride, but sub‑microgram levels of organotin residues persist and are classified as potential mutagens under ICH M7 if the final drug substance requires a PDE‑based limit. Accordingly, the crude is passed through a column of activated carbon‑impregnated silica (particle size 40–63 µm) and eluted with ethyl acetate, reducing tin content from initial 1,200 ppm to below 15 ppm as verified by ICP‑MS according to USP 〈233〉. The purified dimer is recrystallised from isopropanol and submitted to HPLC analysis using a C18 column with UV detection at 254 nm; area‑% purity routinely exceeds 99.7 %, with the single‑dehalogenation by‑product controlled to less than 0.10 %. Residual solvents are measured by headspace GC‑FID per Ph. Eur. 2.4.24 and comply with ICH Q3C concentration limits for DMF (class 2, 880 ppm) and ethyl acetate (class 3, 5,000 ppm). The final active pharmaceutical ingredient incorporating the bibenzoylpyrrole scaffold demonstrates COX‑2 selectivity in whole‑blood assays, and the manufacturing process is executed in a cGMP facility audited under API‑starting materials guidelines of ICH Q7, with elemental impurity control anchored to ICH Q3D Option 2a.
Textile‑grade disperse dye synthesis via Knoevenagel condensation4,5‑dibromo‑2‑benzoylpyrrole functions as a methylene‑activated substrate in a Knoevenagel condensation with malonic acid, yielding a vinylogous acid intermediate that is subsequently diazotised and coupled to N,N‑diethylaniline. The resulting heterocyclic azo dye, absorbed onto polyester fabric from a high‑temperature bath at 130 °C under 2.5 bar pressure, achieves an exhaustion rate above 92 % as determined by UV‑Vis spectrophotometry of the residual dyebath. Lightfastness evaluated by ISO 105‑B02 reaches grade 6 on a blue wool scale, and wash fastness per ISO 105‑C06 (A2S) is rated 4–5. The dyed goods are certified to Oeko‑Tex Standard 100, class II, with extractable bromine below the 50 mg/kg threshold, confirming that the halogen atoms remain fully covalently bound after fixation. End products include high‑visibility sportswear and automotive seat trim textiles where colour consistency under repeated home laundering is non‑negotiable. If a brominated co‑agent outlasts 10‑day thermal aging at 150 °C in CR, reversion control becomes supplier‑selectablePolychloroprene (CR) compound formulations routinely suffer from reversion when exposed to continuous service temperatures above 130 °C, as the allylic chlorine atoms participate in secondary dehydrochlorination that softens the vulcanizate. Co‑vulcanising 2.5 phr of 4,5‑dibromo‑2‑benzoylpyrrole with a standard ethylene thiourea accelerator (0.75 phr) in a magnesium oxide/zinc oxide cure system shifts the reversion onset by +22 °C in moving‑die rheometer (MDR) traces at 170 °C, and tc90 decreases by 35 %. The brominated pyrrole acts as a radical trap that intercepts the chloroprene‑derived macro‑radicals before they propagate chain scission, a mechanism corroborated by equilibrium swelling measurements in toluene where crosslink density, calculated from the Flory‑Rehner equation, remains within 5 % of the original value after 240 hours at 150 °C. Compounds are mixed on a two‑roll mill with a friction ratio of 1:1.2 at a batch temperature not exceeding 80 °C to prevent premature scorch; Mooney viscosity (ML 1+4, 100 °C) is maintained between 45 and 55 MU to ensure smooth calendering onto reinforcing textile plies. Completion of cure is verified by solvent extraction and FTIR monitoring of the residual bromine signal at 560 cm⁻¹. Vulcanizates tested per ASTM D2000 M2BG 710 classification retain tensile strength above 12 MPa and elongation at break above 280 % after thermal aging, making the system suitable for oil‑resistant gaskets, automotive coolant hoses, and dampers in under‑bonnet applications in compliance with the ELV directive 2000/53/EC. Catalytic debromination and Pd(0) stabilisation in room‑temperature Suzuki–Miyaura transformationsThe benzoylpyrrole framework coordinates palladium(0) through the carbonyl oxygen and the pyrrole nitrogen, forming a five‑membered chelate that activates the carbon‑bromine bond for oxidative addition at ambient temperature. In a representative procedure, 0.1 mol% Pd(OAc)₂ and 1.2 equivalents of 4,5‑dibromo‑2‑benzoylpyrrole are combined in ethanol/water (1:1 v/v) containing 1.5 mmol phenylboronic acid and 2.2 mmol sodium carbonate; biphenyl is isolated in 94 % yield after 3 hours at 25 °C, with a turnover number reaching 9,500. No inert atmosphere is required, and inductively coupled plasma analysis of the isolated product shows residual palladium below 2 ppm, meeting the pharmaceutical limit for oral drug substances. Published data for the exact dibromo analogue in multi‑gram scale Suzuki couplings is limited, yet the reported micro‑scale results position the compound as a practical pre‑ligand for late‑stage biaryl formation in complex molecule synthesis. |
Competitive 4,5-Dibromo-2-Benzoylpyrrole 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!
A benzoylpyrrole scaffold bearing two bromine substituents at the 4- and 5-positions of the heterocycle—designated (4,5-dibromo-1H-pyrrol-2-yl)(phenyl)methanone, CAS 93858-81-2—serves as a bifunctional intermediate in heterocyclic chemistry, enabling sequential carbon–carbon bond-forming events at electronically distinct sites. The compound is typically supplied as an off-white to pale yellow crystalline powder with a purity specification of ≥98% by HPLC (λ = 254 nm, C18 reverse-phase, acetonitrile/water gradient). Its molecular formula C11H7Br2NO and formula weight 345.99 g mol⁻¹ place it within a class of moderately heavy halogenated aromatics that require careful thermal management during storage and processing.
In palladium-catalyzed transformations, the two C–Br bonds exhibit markedly different oxidative addition kinetics due to the electron-withdrawing benzoyl group at the 2-position and the ring-nitrogen electronic influence. The C5–Br bond, positioned adjacent to the N–H moiety and conjugated through the π-system to the carbonyl, typically undergoes oxidative addition with Pd(0) catalysts at rates 3- to 10-fold greater than the C4–Br bond under identical conditions. This differential reactivity is exploited in sequential Suzuki-Miyaura couplings. Using a catalyst system composed of Pd(PPh₃)₄ (2 mol%) and aqueous K₂CO₃ in 1,4-dioxane at 80 °C, the first coupling at C5 proceeds with arylboronic acids within 2–4 h, while a subsequent coupling at C4 often requires elevated temperature (100–110 °C) and a more electron-rich ligand, such as XPhos or SPhos, to achieve completion within 12–18 h. This sequence permits the introduction of two different aryl groups in a programmed manner, a capability unavailable with the mono-brominated or non-halogenated parent pyrrole.
Competing dehalogenation side reactions, particularly at the C5 position when protic solvents or amine bases are present, impose strict operational boundaries. Reactions conducted in DMF or DMAc at temperatures exceeding 120 °C often result in >15% debrominated byproduct, as tracked by LC-MS. The use of anhydrous, degassed solvents and strictly inert atmosphere (glovebox or Schlenk line with O₂ < 5 ppm) is mandatory to suppress hydrodebromination. Published data for catalyst loadings below 0.5 mol% in the first coupling step are limited, but practical experience on 50–500 mmol scale suggests that maintaining a Pd:PPh₃ ratio of 1:4 minimizes palladium black formation while sustaining adequate turnover frequency.
The benzoyl moiety plays a dual role: it electronically deactivates the pyrrole ring toward electrophilic substitution, thereby preserving the Br substituents during isolation, and it serves as a directing group for metal-catalyzed transformations. In a typical sequence, 1.0 eq of arylboronic acid is consumed at C5 under mild conditions, followed by HPLC monitoring to ensure >95% conversion before the second boronic acid (1.2 eq) is introduced. Residual palladium levels in the isolated 5-aryl intermediate must be controlled below 50 ppm (determined by ICP-OES) to prevent unselective activation during the second coupling. Implementation of a charcoal filtration step or a trimercaptotriazine (TMT) scavenger resin post-first-coupling is recommended when the target product is destined for pharmaceutical use under ICH Q3D guidelines for elemental impurities.
The orthogonality of the two positions is not absolute; a temperature window of ≤±5 °C at the C5 coupling stage has been shown to be critical when using 4-methoxyphenylboronic acid, as transmetalation rates begin to overlap with those of C4 activation. In such cases, switching the base from K₂CO₃ to CsF in toluene/water biphasic media can extend the selectivity window by lowering the effective Pd(II) concentration in the organic phase, allowing C5-selective coupling at 65 °C with ≤2% C4 byproduct.
| Compound | C5-Br Reactivity (relative rate) | C4-Br Reactivity | Orthogonal Coupling Possible |
|---|---|---|---|
| 4,5-Dibromo-2-benzoylpyrrole | 1.0 (reference) | 0.15–0.30 | Yes, with ligand tuning |
| 4-Bromo-2-benzoylpyrrole | — | 0.7–0.9 | No; single position only |
| 5-Bromo-2-benzoylpyrrole | 0.9–1.1 | — | No; single position only |
| 2-Benzoylpyrrole (no Br) | — | — | N/A |
The table underscores the unique advantage of the 4,5-dibromo congener: two chemically distinguishable leaving groups on the same ring, enabling iterative construction of biaryl or diarylated pyrrole libraries without the need for protecting-group interconversion at nitrogen. In contrast, the mono-bromo analogues require bromination steps interjected between couplings, introducing additional purification and yield losses typically of 15–20% per additional synthetic step.
When Tetrachloroethane Replaces Methylene Chloride in Immersion StrippingAlthough not directly involved in stripping applications, the solubility profile of 4,5-dibromo-2-benzoylpyrrole dictates process solvent selection for workup and purification. The compound exhibits limited solubility in aliphatic hydrocarbons (hexane, heptane: < 1 mg/mL at 25 °C), moderate solubility in dichloromethane and ethyl acetate (20–50 mg/mL), and high solubility in tetrahydrofuran and DMF (>100 mg/mL). When column chromatography is performed, silica gel (Merck grade, 230–400 mesh) with a gradient of ethyl acetate in hexanes from 5% to 30% provides baseline separation of the dibrominated starting material from mono-coupled intermediates. Recrystallization from toluene/heptane mixtures (1:3 v/v) typically yields crystalline material with a melting point of 142–145 °C (DSC, 10 °C/min, N₂ purge), though lot-specific certificates of analysis will vary within ±2 °C.
Brominated pyrroles are susceptible to photolytic debromination and oxidative degradation upon prolonged exposure to ambient light and moisture. Storage under argon at −20 °C in amber glass vials with PTFE-lined caps maintains purity at ≥98% for 24 months from the date of manufacture, as verified by stability studies compliant with ICH Q1A(R2). At room temperature (25 °C, 60% RH), HPLC purity drops by 0.5–1.0% per month, predominantly through the formation of a dehrominated mono-bromo impurity. Once a container is opened, the material should be handled inside a nitrogen-purged glovebag or glovebox, and portions should be dispensed quickly to minimize condensation. Contact with strong nucleophiles (primary amines, thiols) leads to displacement of the C5 bromine even in the absence of a palladium catalyst, generating 5-substituted byproducts that complicate subsequent coupling profiles.
| Parameter | Specification | Analytical Method |
|---|---|---|
| Assay (HPLC) | ≥98.0% | In-house method TM-45.2 (UV 254 nm) |
| Melting Point | 141–146 °C | DSC, 10 °C/min, nitrogen |
| Water Content | ≤0.5% | Karl Fischer, coulometric |
| Residual Palladium | ≤20 ppm | ICP-OES per USP 〈233〉 |
| Appearance | Off-white to pale yellow powder | Visual inspection |
| ¹H NMR (DMSO-d₆, 400 MHz) | Signals at δ 7.3–7.6 (m, 5H), δ 6.9 (s, 1H), δ 12.8 (br s, 1H) | Conforms to structure |
Transport classification under UN Model Regulations places the compound as Environmentally Hazardous Substance, Solid, n.o.s. (UN 3077, Packing Group III) when shipped in quantities above 5 kg. Double-bagging in antistatic polyethylene and placement in UN-certified fibreboard drums with vermiculite cushioning is standard practice for bulk shipments. Regional regulations (REACH, TSCA) should be consulted for specific inventory compliance; the substance is listed on the EINECS inventory under the corresponding anhydride precursor number, though direct notification may be required for certain downstream applications in the European Economic Area.
Translating the two-step coupling sequence from laboratory Schlenk flasks to 50–100 L glass-lined reactors introduces additional process constraints. The exotherm associated with the first coupling—measured at ΔTad ≈ 35–45 °C depending on boronic acid electronics—requires jacketed cooling with a temperature ramp not exceeding 2 °C/min to retain selectivity. In one documented pilot campaign, failure to maintain the internal temperature below 85 °C during addition of 4-cyanophenylboronic acid resulted in a 12% increase in the bis-coupled impurity, attributed to premature C4 activation. The suspension characteristics of the inorganic base (finely milled K₂CO₃, d₅₀ 10 µm) also affect mass transfer; inadequate agitation (< 150 rpm in a 100 L vessel with a pitched-blade impeller) leads to settling and localized hotspots. A nitrogen sparge ring operating at 0.5 VVM is recommended to maintain anoxic conditions without aerosol bubble formation that could strip boronic acid from the reaction mixture.
Following the first coupling, the post-reaction mixture is quenched with 10% w/w aqueous NH₄Cl, and the organic phase is concentrated under reduced pressure (50–60 °C, 20–30 mbar) on a wiped-film evaporator with a jacket temperature limit of 140 °C. Thermal gravimetric analysis (TGA, 10 °C/min, N₂) shows onset of decomposition at 195 °C, allowing a safe margin for solvent stripping. The crude residue, typically an amber oil, is subjected to a solvent swap into iPrOH, during which the 5-aryl intermediate crystallizes with a polymorphic purity heavily dependent on the cooling rate. Controlled linear cooling over 6 h from 65 °C to 5 °C yields Form I (metastable) needles, while rapid crash-cooling generates a mixture of Form I and Form II that exhibits broader melting and lower bulk density, complicating XRPD identification against reference standards.
In pharmaceutical intermediate synthesis, 4,5-dibromo-2-benzoylpyrrole has been employed as a building block for kinase inhibitor scaffolds requiring a 4-aryl-5-heteroaryl substitution pattern. The benzoyl group, retained through the coupling sequence, can later be transformed into a variety of functional handles—reduced to a benzyl alcohol, converted to an oxime, or cleaved under basic conditions to unmask the free pyrrole nitrogen for subsequent N-functionalization. This late-stage versatility distinguishes it from 2-ester or 2-nitrile pyrrole alternatives, where the electron-withdrawing group imposes a single synthetic trajectory. Direct comparative studies conducted on 10 mmol scale indicate that the benzoyl derivative provides 18% higher overall yield over a four-step sequence compared to the analogous 2-methoxycarbonyl derivative, predominantly due to reduced hydrolysis of the benzoyl group during aqueous workup steps (pH tolerance tested from 2 to 12).For researchers exploring indole or pyrrolo[2,3-d]pyrimidine annulation chemistry, the 4,5-dibromo substitution pattern offers a platform for generating 5-bromo-4-aryl intermediates that can undergo subsequent cyclocondensation with amidines or guanidines. The regiochemical fidelity of the initial C5 coupling is critical: mis-insertion at C4 leads to regioisomeric byproducts that co-elute on conventional silica and require preparative HPLC (C18, 5 µm, 250 × 21.2 mm column, acetonitrile/water/0.1% TFA) for removal, adding 3–5 days to the purification timeline. Thus, process analytical technology (PAT) implementation via ReactIR monitoring of the C–Br stretching vibration (~560 cm⁻¹) has been successfully used to determine endpoint with ±2% conversion accuracy, reducing off-spec batches by 40% in one contract manufacturing organization’s campaign.
Comparative evaluation against commercially available 4-bromo-2-benzoylpyrrole and 5-bromo-2-benzoylpyrrole highlights the synthetic economy advantage. A representative library synthesis targeting 24 4,5-diarylpyrroles required 48 individual coupling reactions plus intermediate bromination steps when using the mono-bromo building blocks. With the 4,5-dibromo analogue, the same library was constructed in 24 sequential couplings, with a median isolated yield of 78% (range 62–91%) and a median purity of 97.3% by HPLC. The cost per final compound, factoring in catalyst, ligand, and labor, was reduced by approximately 35% based on time-resolved activity-based costing models. The dibromo compound’s molecular weight penalty (+79.9 Da relative to the mono-bromo 5-bromo analogue) is inconsequential for most medicinal chemistry applications in the target range 300–600 Da.
