4-Chloro-2-methyl-5-nitropyridine - ≥98% , CAS No.856834-65-6

CAS: 856834-65-6 Cat. No.: C1031663 Formula: C₆H₅ClN₂O₂ Peso molecolare: 172.570 Numero EC: 980-452-1

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥98%

Nomi e identificatori

• Sorrisi canonici: CC1=CC(=C(C=N1)[N+](=O)[O-])Cl
• IUPAC Name: 4-chloro-2-methyl-5-nitropyridine
• InChIKey: JIDYHMKFZYTPEA-UHFFFAOYSA-N
• INCHI: 1S/C6H5ClN2O2/c1-4-2-5(7)6(3-8-4)9(10)11/h2-3H,1H3
• Peso molecolare: 172.570

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic 1,3-dipolar compounds
    • Classe Allyl-type 1,3-dipolar organic compounds
      • Subclass Organic nitro compounds
        • Level5 C-nitro compounds
          • Level6 Nitroaromatic compounds

• Kingdom: Organic compounds
• Superclass: Organic 1,3-dipolar compounds
• Classe: Allyl-type 1,3-dipolar organic compounds
• Subclass: Organic nitro compounds
• Intermediate Tree Nodes: C-nitro compounds
• Direct Parent: Nitroaromatic compounds
• Alternative Parents: Methylpyridines Aryl chlorides Heteroaromatic compounds Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Azacyclic compounds Organonitrogen compounds Organochlorides Organic salts Organic oxides Hydrocarbon derivatives Organic cations
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Nitroaromatic compound - Methylpyridine - Aryl chloride - Aryl halide - Pyridine - Heteroaromatic compound - Organic oxoazanium - Azacycle - Organoheterocyclic compound - Propargyl-type 1,3-dipolar organic compound - Organic nitrogen compound - Organic oxygen compound - Organic salt - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organic oxide - Organohalogen compound - Organic cation - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as nitroaromatic compounds. These are c-nitro compounds where the nitro group is C-substituted with an aromatic group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Peso molecolare: 172.570 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 172.004 Da
• Monoisotopic Mass: 172.004 Da
• Topological Polar Surface Area: 58.700 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 159.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No assay or bioanalytical application protocols are specified for this item. Typical laboratory use involves standard organic synthesis workflows. For guidance, see the Reaction & Applications and Reaction Conditions sections for representative synthetic procedures, and adjust to your substrate and scale. Always validate conditions by small-scale trials and analytical monitoring.

Biological Roles

This compound is a synthetic heteroaromatic building block and is not known to have intrinsic biological roles.

• General considerations (literature)

  • Nitro- and chloro-substituted pyridines are common intermediates in the synthesis of bioactive molecules, but the reagent itself is not a metabolite or biological cofactor.
  • The pyridine ring is prevalent in medicinal chemistry scaffolds due to tunable basicity and hydrogen-bonding capacity; derivatization of this substrate can yield analogs for SAR campaigns.

• Lab safety note

  • Handle exclusively for research use; avoid biological exposure. Follow institutional biosafety and chemical hygiene practices.

Buffer Applications

Not typically applicable. 4-Chloro-2-methyl-5-nitropyridine is a hydrophobic heteroaromatic reagent, not used as a buffering agent. For aqueous work, focus instead on its limited solubility and on extraction/partition behavior after reactions. Choose buffer systems based on downstream biological assays rather than this reagent’s properties.

Green Alternatives

This item is a solid reagent. Greener choices focus on solvent/catalyst selection and waste minimization during its use.

• Prefer greener solvents where feasible (literature guidance)

  • 2-MeTHF or CPME in place of THF/diethyl ether for hydrogenations or organometallics.
  • MeCN, propylene carbonate, or bio-based esters over DMF/NMP where catalysis allows.
  • Water or water–organic biphasic systems with phase-transfer catalysis for robust SNAr.

• Catalysis and bases

  • Employ Pd at low loadings with modern biaryl phosphines or use Ni-catalysis to reduce precious metal usage for cross-coupling of heteroaryl chlorides.
  • Use inorganic carbonates or phosphates rather than strong bases when compatible to reduce hazard and side reactions.

• Process intensification

  • Flow hydrogenation for safer nitro reductions with improved mass transfer and reduced solvent volume.
  • Micellar catalysis for couplings under aqueous conditions when substrate solubility permits.

• Comparison snapshot (general)

  • DMF vs MeCN: DMF offers higher rates but poor EHS profile and difficult removal; MeCN is more volatile and greener but may require higher temperatures.
  • THF vs 2-MeTHF: 2-MeTHF has better safety/renewability and forms fewer peroxides; solubility must be checked.

Note: Select alternatives based on performance, regulatory, and EHS assessments for your process window.

Pharmaceutical Uses

No direct excipient or formulation role is typical for 4-chloro-2-methyl-5-nitropyridine. It is used, if at all, as a synthetic intermediate in API or agrochemical development.

• Possible roles (general/industry practice)

  • Intermediate for heteroaryl amines, ethers, and thioethers following SNAr or coupling.
  • Precursor to amino-substituted pyridines after nitro reduction, enabling salt formation or further derivatization.

• Regulatory

  • Not a pharmacopeial excipient. Any use in GMP manufacture would require full impurity profiling and process validation. Residual levels as a starting material/intermediate must be controlled per ICH Q3A/B.

For therapeutic claims or clinical use, none are made. Research use only.

Physical Properties

Item-specific specifications

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point (BP): Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility profile: Not specified for this item; refer to CoA/Spec Sheet.
• UV cutoff/refractive index: Not specified for this item; refer to CoA/Spec Sheet.

General/literature values and expectations (for context only)

• Empirical formula (literature): C6H5ClN2O2
• Formula weight (literature): ~172.58 g/mol
• Physical state: Typically a pale yellow to off-white crystalline solid for comparable halonitropyridines (literature).
• Solubility (literature/expected): Moderately soluble in polar aprotic organic solvents (e.g., DMF, DMSO, MeCN, dichloromethane); limited aqueous solubility due to heteroaromatic base with deactivating nitro and chloro.
• Acid-base: Weakly basic ring nitrogen; pKa of conjugate acid for similar nitro-substituted pyridines is often ~1–3 (literature), indicating low basicity.
• LogP: Halonitro pyridines commonly exhibit moderate lipophilicity; exact value not established here (literature trend only).

Notes

• Reported literature values are provided for planning purposes; always confirm item-specific specs on the CoA/Spec Sheet for your lot prior to process design or QC setting.

Quality and Grades

Item-specific grade/purity

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades (general information for planning)

• Research grade: Suitable for discovery and development work. For sensitive transformations (e.g., catalytic cross-couplings, SNAr at low catalyst loadings), users often prefer material with low water/metal/halide impurities and confirm identity by NMR/HRMS.
• HPLC grade/low UV absorbance: Typically applies to solvents rather than solids; for aromatic reagents, low UV background is less relevant than chemical purity and residual solvent content.
• Stabilizers/inhibitors: This compound is not typically stabilized; absence/presence of stabilizers should be checked on the CoA if critical to your process.

Quality control best practices

• Verify identity and purity by 1H/13C NMR, HRMS/LC–MS, and HPLC/GC as applicable.
• Check water content for moisture-sensitive applications (e.g., air/moisture-sensitive couplings). If Karl Fischer or loss on drying is critical, consult the CoA.
• Metals and halide content: If using in catalytic transformations with ppb–ppm metal sensitivity, pre-screen or purify as needed.

Documentation

• For exact acceptance criteria (assay, single-impurity limits, residual solvents), refer to the item-specific CoA/Spec Sheet.

Reaction and Applications

As a 4-chloro- and 5-nitro-substituted pyridine bearing a 2-methyl group, this reagent is highly versatile in heteroarene functionalization.

• Nucleophilic aromatic substitution (SNAr)

  • The 4-chloro is activated by both the ring nitrogen and the 5-nitro group, enabling displacement by O-, N-, S-, and C-nucleophiles.
  • Bases/solvents: K2CO3/Cs2CO3 in DMF, DMSO, MeCN; alkoxides in alcohols; thiolates in polar aprotics.
  • Applications: Synthesis of 4-amino-, 4-alkoxy-, 4-thio-, and 4-arylated 2-methyl-5-nitropyridines.

• Cross-coupling of the aryl chloride

  • Pd-catalyzed Suzuki–Miyaura, Buchwald–Hartwig (after amination), Negishi, or Stille couplings on the 4-position.
  • Catalyst systems: Buchwald-type ligands (e.g., XPhos, SPhos) with Pd2(dba)3 or Pd(OAc)2; bases such as K3PO4, Cs2CO3; solvents MeCN, dioxane, toluene/DMF.
  • Stereoelectronics: Heteroaryl chlorides typically couple at moderate temperatures (60–110 °C) with optimized ligands.

• Nitro-group transformations

  • Reductive conversion to the 5-amine (e.g., catalytic hydrogenation over Pd/C, or transfer hydrogenation/Fe–acid systems) affords 5-aminopyridines for subsequent acylation, sulfonylation, or cyclization.
  • Partial reduction to hydroxylamine or rearrangements are possible under tailored conditions.

• Directed metalation/functionalization

  • The 2-methyl substituent can be benzylicly deprotonated under strong base (e.g., LDA, LHMDS) to introduce side-chain functionality (alkylation, acylation) given appropriate protection of other sites.

• Heterocycle assembly

  • Acts as a synthon for constructing N-containing scaffolds used in agrochemical and materials discovery, leveraging orthogonal reactivity at positions 4 and 5.

All reaction notes are literature guidance; optimize conditions for your substrate and scale.

Reaction Conditions

General literature guidance (optimize per substrate and scale)

• SNAr displacement of Cl at C4

  • Nucleophiles: amines, alkoxides, thiolates, cyanide, enolates.
  • Bases: K2CO3, Cs2CO3, NaOtBu (for hindered systems).
  • Solvents: DMF, DMSO, MeCN, tBuOH (for alkoxides).
  • Temperature/time: 25–110 °C, 1–24 h depending on nucleophile/basicity.
  • Notes: Electron-deficient ring and ortho nitro enhance rate; monitor by LC–MS or HPLC.

• Suzuki–Miyaura at C4

  • Catalyst/ligand: Pd2(dba)3 (0.5–2 mol%) with SPhos/XPhos (1–4 mol%).
  • Base: K3PO4 or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O, toluene/DMF, or MeCN.
  • Temperature: 60–100 °C; 2–12 h.
  • Tip: Heteroaryl chlorides often require electron-rich bulky ligands; add water to enhance transmetalation.

• Buchwald–Hartwig amination

  • Pd(OAc)2 (1–3 mol%) + BrettPhos or RuPhos; NaOtBu or Cs2CO3; toluene, dioxane, or MeCN; 80–110 °C.

• Nitro reduction to aniline (C5)

  • H2 (1–5 bar) with Pd/C (5–10 wt% of substrate) in EtOH, MeOH, or 2-MeTHF; 20–50 °C; 1–6 h.
  • Alternative: Fe/AcOH or SnCl2/HCl in EtOH/H2O; manage workup to remove salts/metal residues.

• Benzylic functionalization at 2-methyl

  • Base-mediated deprotonation with LDA (−78 to 0 °C) in THF, followed by electrophile quench.
  • Radical bromination (NBS, AIBN) in CCl4/benign substitutes, then substitution/oxidation sequences.

All conditions are representative literature practices and should be adapted based on analytical monitoring and DoE.

Safety and Handling

Item-specific hazard information

• Signal Word: Not specified for this item; refer to SDS.
• GHS Classification: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.
• H-Statements: Not specified for this item; refer to SDS.

General safety guidance (literature/experience; not a substitute for SDS)

• Likely hazards: Irritation to skin/eyes/respiratory tract; harmful if swallowed/inhaled. Nitroaromatics can present toxicity upon prolonged exposure; handle with care. Avoid dust formation.
• PPE: Lab coat, safety glasses or splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or vapors from heated operations.
• Incompatibilities: Strong reducing agents (nitro group), strong bases under forcing conditions (can promote SNAr with release of chloride), strong oxidizers (general precaution). Avoid contact with reactive metals and strong acids that may lead to N-oxide formation or hydrolysis.
• Thermal/processing notes: Avoid excessive heating; nitroarenes can decompose at elevated temperatures. If performing reductions (e.g., to the aniline), control exotherms and manage hydrogenation hazards with proper ventilation and ignition control.
• First aid overview: Eye/skin contact—rinse with water for at least 15 minutes; remove contaminated clothing. Inhalation—move to fresh air. Ingestion—rinse mouth; do not induce vomiting. Seek medical attention in all cases.
• Waste: Treat as halogenated nitroaromatic organic waste; segregate and dispose of per institutional and local regulations.

Always consult the product’s SDS for definitive hazard and handling information.

Solvent Selection

Applicability: This is a solid heteroaromatic building block, not a solvent. The guidance below addresses solvent choice for its common reactions (SNAr, cross-coupling, reductions, nitration-derived transformations).

• Polarity and solubility considerations (general/literature)

  • Polar aprotic solvents such as DMF, DMAc, DMSO, NMP, and MeCN often provide good solubility and rates for SNAr and metal-catalyzed couplings.
  • Ethers (THF, 2-MeTHF, MTBE) can be used where solubility permits, especially for organometallic steps or hydrogenations.
  • Chlorinated solvents (DCM, DCE) may dissolve the substrate but are less preferred on green metrics.

• Base and nucleophile effects

  • For SNAr (Ar–Cl displacement), polar aprotics with inorganic bases (K2CO3, Cs2CO3) or alkoxides are common. Phase-transfer setups can enable reactions in less polar media.

• Small comparison (literature trends)

  • DMF/DMSO: Excellent for SNAr and strong nucleophiles; high bp aids conversion but complicates workup.
  • MeCN: Balanced polarity; good for Pd-catalyzed couplings at reflux with appropriate bases.
  • 2-MeTHF: Greener alternative to THF; suits hydrogenation and some couplings if solubility is adequate.

• Practical tips

  • Perform small-scale solubility screening at intended temperature.
  • Include water scavengers/dry conditions for air-/moisture-sensitive catalysts.
  • Consider cosolvent systems (e.g., toluene/DMF) to tune solubility and remove heat effectively.

Storage and Reconstitution

Item-specific storage

• Storage Conditions: Room temperature (as provided in Product Data). Store in a tightly closed container in a dry, well-ventilated place.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General handling

• Protect from moisture and prolonged light exposure. Although the compound is typically stable, nitroaromatics can discolor upon long storage; assess purity before critical use.
• If hygroscopicity is a concern for your application, store under inert gas or with desiccant.

Reconstitution/solution preparation

• Not supplied as a lyophilized biological; no reconstitution is required.
• To prepare stock solutions, dissolve in a suitable dry organic solvent (e.g., DMSO, DMF, MeCN, THF) based on your intended reaction. Filter if particulates are present.
• For long-term solution storage, keep under inert atmosphere at low temperature where compatible, and verify stability by LC–MS/HPLC prior to use.

Shelf-life and QA

• Check the CoA for retest/expiry dates. Reassay material after extended storage or if containers have been opened multiple times.

Research Use Note: For research use only.

Structure and Identity

Brief description: 4-Chloro-2-methyl-5-nitropyridine is a chlorinated, nitrated pyridine bearing a methyl substituent; it is a versatile heteroaromatic building block for cross-coupling and nucleophilic aromatic substitution chemistry.

• Item-specific identifiers (from Product Data)

  • SKU: C1031663
  • Product Name: 4-Chloro-2-methyl-5-nitropyridine
  • CAS: 856834-65-6
  • InChIKey: 161085 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identity (for reference; not item-specific specs)

  • Common structural formula (literature): C6H5ClN2O2
  • Approx. molecular weight (literature): ~172.58 g/mol
  • Core scaffold: pyridine ring (one ring nitrogen) with three ring substituents
    • 2-position: methyl (–CH3)
    • 4-position: chloro (–Cl)
    • 5-position: nitro (–NO2)
  • Functional groups: heteroaromatic pyridine, aryl chloride (activated by ring N and para nitro), nitro group (reducible), benzylic methyl equivalent on ring.

• 2D structure (described in words)

  • A six-membered aromatic ring containing one ring nitrogen (pyridine). Clockwise from the ring nitrogen: the adjacent carbon (2-position) bears a methyl group; two carbons further (4-position) bears chlorine; the 5-position (meta to N, ortho to Cl) bears a nitro group; remaining ring positions are unsubstituted carbons with aromatic hydrogens.

• Stereochemistry: None (achiral, planar aromatic).

Synthetic Utility

Key functional handles and their strategic use

• Aryl chloride at C4: Acts as a versatile leaving group. Options include SNAr with hard nucleophiles or Pd/Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Negishi, Kumada). The electron-withdrawing nitro and ring N increase the aryl chloride’s reactivity relative to simple chlorobenzenes.
• Nitro at C5: Can be reduced to an aniline (orthogonal to C4 chemistry), enabling two-stage diversification: first functionalize C4, then reduce and elaborate C5.
• Benzylic-like 2-methyl: Under strong base, deprotonation enables side-chain functionalization (e.g., alkylation or oxidation to an aldehyde/acid following benzylic halogenation/oxidation protocols).

Retrosynthetic considerations

• The scaffold provides orthogonal reactivity: C4 electrophilicity (Cl) vs. C5 redox handle (NO2), facilitating divergent library synthesis from a single substrate.
• The heteroaryl chloride can serve as a masked pseudo-halide for C–C and C–X bond constructions, while the nitro can be converted to diazonium surrogates after reduction.

Practical notes

• Protect sensitive nucleophiles when performing SNAr to avoid overreaction.
• For couplings, use heteroaryl-optimized ligands; halide exchange (to bromide/triflate) is often unnecessary due to sufficient activity of the chloride in this activated system.
• Sequence planning: Execute C4 substitution/coupling first, then nitro reduction to maintain chemoselectivity.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biological probe with defined biomolecular targets. No target or epitope specificity data are provided for this item.