Ethyl 2-chloro-5-nitroisonicotinate - ≥97% , CAS No.907545-64-6

CAS: 907545-64-6 Cat. No.: E590670 Formula: C₈H₇ClN₂O₄ Molecular Weight: 230.61

GRADE & PURITY ≥97%

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Specifications

Specifications & Purity

≥97%

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥97%

Names and Identifiers

Canonical Smiles

CCOC(=O)C1=CC(=NC=C1[N+](=O)[O-])Cl

IUPAC Name

ethyl 2-chloro-5-nitropyridine-4-carboxylate

InChIKey

VXTKSUGJWMHWKD-UHFFFAOYSA-N

INCHI

1S/C8H7ClN2O4/c1-2-15-8(12)5-3-7(9)10-4-6(5)11(13)14/h3-4H,2H2,1H3

Isomeric SMILES

CCOC(=O)C1=CC(=NC=C1[N+](=O)[O-])Cl

Molecular Weight

230.61

Reaxy-Rn

36530849

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=36530849&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyridines and derivatives
      • Subclass Pyridinecarboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyridines and derivatives
• Subclass: Pyridinecarboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridinecarboxylic acids
• Alternative Parents: Nitroaromatic compounds 2-halopyridines Aryl chlorides Heteroaromatic compounds Carboxylic acid esters Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Azacyclic compounds Organooxygen compounds Organonitrogen compounds Organochlorides Organic zwitterions Organic salts Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyridine carboxylic acid - Nitroaromatic compound - 2-halopyridine - Aryl chloride - Aryl halide - Heteroaromatic compound - Carboxylic acid ester - C-nitro compound - Organic nitro compound - Carboxylic acid derivative - Organic oxoazanium - Azacycle - Allyl-type 1,3-dipolar organic compound - Propargyl-type 1,3-dipolar organic compound - Organic 1,3-dipolar compound - Organooxygen compound - Organonitrogen compound - Organochloride - Organic nitrogen compound - Organohalogen compound - Organic oxygen compound - Organic zwitterion - Organic oxide - Hydrocarbon derivative - Organic salt - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These are compounds containing a pyridine ring bearing a carboxylic acid 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

Chemical and Physical Properties

• Molecular Weight: 230.600 g/mol
• XLogP3: 1.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 230.009 Da
• Monoisotopic Mass: 230.009 Da
• Topological Polar Surface Area: 85.000 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 256.000
• 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

Not applicable.

• No antibody/assay protocols (e.g., WB, IHC, IF, FC) are associated with this chemical building block. For practical usage, see Reaction Conditions and Synthetic Utility for representative synthetic protocols and handling guidance.

Biological Roles

Item-specific biological data

• None provided; no biological role is specified for this SKU. For research use only.

General context (literature; not a claim for this product)

• Pyridine derivatives are common motifs in natural products and bioactive molecules, but Ethyl 2-chloro-5-nitroisonicotinate is a synthetic intermediate rather than a known metabolite or cofactor.
• Functional group implications: The nitro group and aryl chloride are typical synthetic handles used to access amines, ethers, thioethers, and other substitutions that may modulate binding or physicochemical properties in medicinal chemistry campaigns.
• Bio-relevance after transformation: Post-reduction to the corresponding 5-aminopyridine ester affords a versatile platform for amide/sulfonamide formation, urea synthesis, and heterocycle construction common in probe and lead development.

Practical note

• If intended for biological assay use (e.g., as a screening intermediate), prepare fresh DMSO stocks, confirm identity/purity by LC–MS, and evaluate stability under assay conditions (light, pH, reducing agents) to avoid confounding data from decomposition products.

Disclaimer

• No therapeutic, diagnostic, or in vivo use is implied. Any biological discussion above is general background and not specific to this item’s validated activity.

Buffer Applications

Not typically applicable.

• This compound is a neutral organic building block and is not used as a buffering agent. It lacks a conjugate acid/base pair in the physiological pH range suitable for buffering capacity. For practical information relevant to this product, see Reaction & Applications, Synthetic Utility, and Reaction Conditions.

Green Alternatives

Greener choices often revolve around solvent and base selection rather than replacing the heteroaryl chloride itself. Consider the following (literature-based):

Greener solvent options

• Replace DMF/DMSO in SNAr with 2-MeTHF, Cyrene (dihydrolevoglucosenone), propylene carbonate, or dimethyl carbonate when solubility/reactivity permit. For Pd-catalyzed amination, 2-MeTHF, CPME, or toluene with aqueous workup can reduce environmental impact.

Base/catalyst considerations

• Favor inorganic carbonates (K2CO3, K3PO4) over strong alkoxides where possible; employ ligand/catalyst systems active at lower loadings and temperatures (e.g., Buchwald precatalysts, Ni–NHC systems) to decrease energy input and metal usage.

Comparison snapshot (general, not item-specific)

• DMF/DMSO: High performance, high EHS burden; challenging to remove.
• 2-MeTHF/CPME: Bio-based or low-toxicity ethers; good phase separation; peroxide monitoring required over time (standard for ethers).
• Cyrene/Propylene carbonate: Dipolar aprotics with favorable EHS profiles; higher viscosity; may require higher temperature or dilution.

Process-intensification strategies

• Micellar catalysis for amination (aqueous surfactant systems) can enable room-temperature couplings with reduced organic solvent volumes.
• Continuous-flow hydrogenations for nitro reductions improve safety and catalyst efficiency.

Note

• The product itself is the targeted building block; “green alternatives” typically address how you use it. Optimize solvent, temperature, and workup to minimize waste and hazard without compromising yield.

Pharmaceutical Uses

Item-specific regulatory/excipient status

• Not specified for this item; no pharmacopeial status stated.

General context (non-clinical; literature)

• Role in drug discovery: Nitro- and halo- substituted isonicotinates are valuable intermediates for medicinal chemistry, enabling rapid diversification via SNAr or metal-catalyzed amination to furnish heteroaryl amides, anilides, and ether/thiol ethers.
• Pro-moiety considerations: The ethyl ester acts as a protecting/solubilizing group during synthesis; it can be hydrolyzed to the corresponding acid for amide coupling to generate candidate APIs or intermediates.
• Process chemistry: Electron-deficient heteroaryl chlorides often allow lower catalyst loadings and milder conditions in cross-couplings compared with electron-rich systems, which may translate to more scalable processes.

Caveats

• This product is sold strictly for research and development. It is not intended for use as an excipient or active ingredient. Any cGMP, residual solvent, elemental impurities, or stability requirements for pharmaceutical manufacturing are outside the scope of the current listing. Consult Aladdin Scientific for sourcing under enhanced quality frameworks if needed.

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.

Literature/general data (non-specification; for planning only)

• Physical state: Aromatic nitro-ester pyridines of this type are often low-melting solids or high-boiling liquids; actual state for this SKU is not specified.
• Molecular formula (computed from name): C8H7ClN2O4
• Molecular weight (computed): ~230.60 g/mol
• Polarity: Moderately polar, non-protic; capable of H-bond acceptance (pyridine N and carbonyl O atoms), no H-bond donation.
• Solubility profile (typical): Expected to be soluble in polar aprotic organic solvents (e.g., DMSO, DMF, NMP, acetonitrile, ethyl acetate, dichloromethane, THF) and poorly soluble in water; exact solubilities are not established for this item.
• Acid/base behavior: The ring nitrogen is weakly basic (pyridine-type); the ethyl ester is neutral; the nitro group is strongly electron-withdrawing, decreasing basicity compared with unsubstituted pyridine (qualitative, literature).
• Partitioning: LogP is expected to be moderate due to ester and aryl chloride; no measured logP is available here.

Note

• Do not treat the above values as specifications. For exact batch-specific values (e.g., melting point, water content, residual solvents), consult the CoA/Spec Sheet for SKU E590670.

Quality & Grades

Item-specific quality information

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

Interpretation and guidance

• Storage guidance (item-specific): The product is supplied argon charged and should be stored at 2–8 °C. This practice helps minimize oxidative discoloration and limits adventitious hydrolysis of the ethyl ester under ambient humidity.
• Appearance (confirmation): Not specified; verify upon receipt against CoA (e.g., color limits, physical form) and document.
• If HPLC/GC suitability is required: Request low-residual solvent and low-UV background specifications where relevant. Absent explicit “HPLC grade” or similar language, assume general research reagent quality.
• Trace impurities and elemental analysis: Not specified for this item; consult the CoA for assay, related substances, and (if available) elemental/ICP data.

Best practices for quality control in your lab

• Identity confirmation: Verify by 1H/13C NMR (diagnostic pyridine pattern; ethyl ester quartet/triplet), LC–MS (m/z ~231 [M+H]+, literature), and HRMS if needed.
• Purity assessment: HPLC/UPLC with PDA at 210–350 nm (nitro- and pyridine chromophores give strong UV). If moisture sensitivity is a concern for your application, perform KF coulometric water testing on receipt.
• Lot-specific documentation: Use the CoA/Spec Sheet as the controlling document for assay, residual solvents, and any stabilizers.

Reaction & Applications

This molecule is a versatile, electron-deficient pyridine ester useful as a heteroaryl building block. Key reactivity channels (literature) include:

• SNAr at C2 (aryl chloride): The 2-chloro is strongly activated by the ring nitrogen and the para nitro/carboxylate combination. Amines, thiols, and alkoxides can displace chloride under basic conditions. Typical bases: K2CO3, Cs2CO3, NaOtBu; solvents: DMF, DMSO, NMP, MeCN. Temperatures: 25–100 °C depending on nucleophile strength.
• Transition-metal-catalyzed amination/coupling: Pd-catalyzed Buchwald–Hartwig amination of the C–Cl bond with primary/secondary amines using bulky biaryl phosphines (e.g., XPhos, SPhos, BrettPhos) and bases like NaOtBu or K3PO4. Ni catalysis can also be effective.
• Nitro group transformations: Chemoselective reduction (H2/Pd-C, Fe/AcOH, SnCl2, or transfer hydrogenation) to the aniline enables subsequent diazotization, Sandmeyer-type substitutions, or intramolecular cyclizations.
• Ester handle as a protecting/functional group: Hydrolysis to the isonicotinic acid (carboxylic acid) for amide coupling (EDC/HOBt, HATU) or conversion to acid chlorides (oxalyl chloride). Alcoholysis/transesterification allows diversity in alkyl esters.
• Heteroaryl cross-couplings: Although aryl chlorides are less reactive than bromides, the electron-deficient ring improves oxidative addition; Suzuki–Miyaura after halogen/boron compatibility adjustments on partners; Stille/Negishi variants are feasible.
• Annulations and ring functionalizations: The aniline (post-reduction) can engage in intramolecular nucleophilic cyclizations or be acylated/sulfonylated to tune electronics.

Application niches

• Library synthesis of 2-substituted-5-nitroisonicotinates (SAR around electron-withdrawing framework).
• Late-stage diversification of N-containing scaffolds where ester stability is advantageous during coupling but can be unmasked later.

Note: Specific application claims by the manufacturer are not provided for this SKU; the above reflects general literature use of analogous scaffolds.

Reaction Conditions

General literature guidance (non-specification; optimize per substrate/nucleophile)

1. SNAr at C2 (displacing Cl)

• Nucleophiles: Primary/secondary amines (fast), thiolates (fast), alkoxides (moderate).
• Base: K2CO3 or Cs2CO3 (1.5–3.0 equiv) for amines; NaH/NaOtBu for alcohols (caution with ester integrity).
• Solvent: DMF, DMSO, NMP, or MeCN.
• Temperature/time: 25–100 °C, 1–16 h depending on nucleophile strength and loading.
• Notes: For weak nucleophiles, add catalytic CuI/ligand (Ullmann-type) or switch to Pd-catalyzed pathways.

2. Buchwald–Hartwig amination of C–Cl

• Catalyst/ligand: Pd2(dba)3 or Pd(OAc)2 (0.5–3 mol%) with XPhos/SPhos/BrettPhos (1–6 mol%).
• Base: NaOtBu, K3PO4, or Cs2CO3 (2–3 equiv).
• Solvent: Toluene, 1,4-dioxane, CPME, or 2-MeTHF.
• Temperature: 70–110 °C; 2–18 h.
• Notes: Electron-poor heteroaryl chlorides typically couple at lower temperatures than electron-rich arenes.

3. Nitro reduction (to aniline)

• Catalytic hydrogenation: H2 (1–5 bar) with 5–10 wt% Pd/C in EtOH or MeOH at 20–40 °C.
• Transfer hydrogenation: Ammonium formate or hydrazine with Pd/C or Raney Ni.
• Metal/acid: Fe/AcOH or SnCl2/EtOH under reflux.
• Selectivity: Conditions can be tuned to leave the ester intact; avoid strong base during reductions to prevent saponification.

4. Ester hydrolysis

• Basic: LiOH or NaOH in THF/MeOH/H2O (0–25 °C) to give the acid.
• Acidic: HCl or H2SO4 in MeOH (Fischer conditions) if transesterification is desired.

Workup and purification

• Quench basic reactions cautiously; extract into EtOAc or MTBE; wash with brine and bicarbonate as appropriate. Purify by column chromatography (silica, eluent: hexanes/EtOAc or DCM/MeOH gradients). Monitor by LC–MS/UPLC.

Note: The above are representative conditions; perform small-scale optimization.

Safety & Handling

Item-specific hazard data

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to the SDS.

General safety guidance for nitro-substituted heteroaromatic esters (literature; not a substitute for SDS)

• Likely hazards: May cause skin/eye irritation and respiratory irritation; ingestion/inhalation may be harmful. Nitroaromatics can present methemoglobin-forming potential upon significant exposure; avoid inhalation of dust/vapors.
• PPE: Use appropriate PPE including lab coat, nitrile gloves, and safety goggles. Handle within a certified chemical fume hood to avoid inhalation exposure.
• Handling: Follow inert-atmosphere recommendation from Product Data (argon). Minimize exposure to moisture to limit hydrolysis of the ester and to air/heat to minimize degradation/discoloration.
• Incompatibilities: Strong bases (can saponify the ester), strong nucleophiles (may induce SNAr at C2), strong reducing agents (can reduce the nitro group), and strong oxidizers (general oxidant incompatibility).
• Thermal considerations: Avoid unnecessary heating; use controlled temperatures especially during reactions (nitroaromatics are generally thermally stable but can decompose at elevated temperatures).
• First aid (overview): If on skin/eyes, rinse with water for at least 15 minutes and seek medical attention. If inhaled, move to fresh air. If ingested, rinse mouth and seek medical advice. Provide SDS to medical personnel.

Waste and spillage

• Spill response: Absorb with inert material, avoid dust generation, and collect in compatible waste containers.
• Disposal: Treat as halogenated organic/nitro-aromatic waste per institutional and local regulations.

Always consult the product SDS for authoritative, batch-specific safety details.

Solvent Selection

General solvent behavior (literature)

• Polarity class: Moderately polar, non-protic; multiple hydrogen-bond acceptors.
• Expected miscibility/solubility: Good in polar aprotic organic solvents (DMSO, DMF, NMP, acetonitrile, ethyl acetate, dichloromethane, THF). Limited in alkanes and water.

Choosing solvents by task

• Stock solutions for screening: DMSO (up to 100 mM typical) or DMF; filter (0.2 µm PTFE) if particulates present.
• Nucleophilic aromatic substitution (SNAr): DMF, DMSO, NMP, or MeCN support deprotonation and solvate anions; for greener profiles, consider 2-MeTHF or Cyrene where feasible.
• Metal-catalyzed amination/coupling: Toluene, dioxane, CPME, 2-MeTHF, or tert-amyl alcohol frequently used with Pd/Buchwald systems; for Ni catalysis, glymes or dioxane/MeCN blends can be effective.
• Hydrolysis (saponification): THF/MeOH/H2O or MeCN/H2O with LiOH/NaOH; control temperature to avoid side reactions (e.g., SNAr with hydroxide at C2).
• Reductions (nitro → aniline): EtOH, MeOH, or THF under H2/Pd-C; avoid basic alcohols if ester integrity must be retained.

Quick comparison (literature considerations)

• DMF/DMSO: Highest solvating power; excellent for SNAr; higher boiling and challenging workup.
• MeCN/EtOAc/THF: Lower boiling, easier removal; may require stronger bases or higher temperature.
• 2-MeTHF/CPME: Greener, water-immiscible; good for extractions and many Pd couplings; sometimes reduced solubility vs DMF.

Note

• No item-specific solubility specifications are provided; validate experimentally for your system.

Storage & Reconstitution

Item-specific instructions (from Product Data)

• Storage: Store at 2–8 °C, argon charged.
• Shipping: Shipped on wet ice.

Practical guidance

• Upon receipt: Keep container tightly closed. Allow to warm gradually to room temperature under argon before opening to minimize moisture condensation.
• Atmosphere: Maintain an inert headspace (argon or nitrogen) after each use. Purge vial and recap promptly; consider using a septum cap for syringe transfers if frequent access is expected.
• Moisture control: Store in a desiccator or with compatible desiccant. Use anhydrous solvents for solution preparation.
• Light and heat: Store away from direct light and heat sources. Avoid prolonged exposure to elevated temperatures.

Solution handling (general)

• Solubility: Prepare stock solutions in dry DMSO, DMF, MeCN, THF, or EtOAc as appropriate. Filter through PTFE (0.2 µm) if needed.
• Stability: Solutions of nitro-heteroaryl esters can slowly degrade upon extended storage, especially with moisture or base. Prepare fresh solutions for critical experiments and store aliquots at ≤4 °C under inert gas when possible.
• Freeze–thaw: If storing solutions, aliquot to avoid repeated freeze–thaw cycles; inspect for precipitation or discoloration before use.

Documentation

• For any batch-specific stability limits, impurity profiles, or retest dates, consult the CoA/Spec Sheet and SDS for SKU E590670.

Structure & Identity

Item-specific (from Product Data)

• SKU: E590670
• Product name: Ethyl 2-chloro-5-nitroisonicotinate
• CAS: 907545-64-6
• Storage: Store at 2–8 °C, argon charged; shipped on wet ice
• Research use: For research use only
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed identity (non-specification)

• Synonym context: Ethyl ester of 2-chloro-5-nitroisonicotinic acid (isonicotinate = pyridine-4-carboxylate).
• Expected molecular formula (computed from the name): C8H7ClN2O4
• Expected molecular weight (computed): ~230.60 g/mol
• Core scaffold: A pyridine ring bearing a carboxylate ethyl ester at the 4-position (isonicotinate), a chloro at the 2-position, and a nitro at the 5-position.
• Functional groups/features: Electron-deficient heteroaromatic (pyridine-N), aryl chloride (for SNAr/cross-coupling), strongly deactivating nitro group (−I/−M), and an ethyl ester (carboxylate protecting/handles for later hydrolysis or alcoholysis).

2D structural description (general)

• Six-membered aromatic ring with one ring nitrogen (pyridine). The para position to the ring N bears a CO2Et group (ethyl ester). Ortho to the ring N (2-position) is a chlorine substituent. Meta to the ester (5-position) is a nitro group (−NO2). The arrangement makes the ring markedly electrophilic at C2 and C5, facilitating nucleophilic aromatic substitutions at C2.

Synthetic Utility

Strategic value (literature)

• Orthogonal handles: Combines a highly activated aryl chloride (C2) with a reducible nitro group (C5) and a transformable ethyl ester (C4). This triad enables stepwise, chemoselective elaboration.
• Electrophile for SNAr: Rapid installation of amines, alkoxides, or thiolates at C2. Electronic activation from ring N plus −NO2 and −CO2Et substituents enhances leaving-group departure.
• Post-SNAr diversification: Remaining nitro can be reduced to an aniline for further cross-coupling (e.g., Buchwald–Hartwig), acylation, or diazonium chemistry.
• Ester as a relay functional group: Convert to acid (hydrolysis) for amide coupling (HATU/EDC) or to acid chloride (oxalyl chloride, SOCl2) for nucleophilic acyl substitution; also permits late-stage transesterification.
• Cross-coupling latitude: The C–Cl bond on an electron-poor heteroaryl typically undergoes Pd-catalyzed amination and, with appropriate conditions, etherification (Pd-catalyzed Buchwald alkoxylation) and thiolation.

Retrosynthetic planning

• Target 2-substituted-isonicotinate cores by SNAr of E590670 with the desired nucleophile, then tune electronics via nitro reduction and subsequent derivatizations.
• Preserve ester during nucleophilic steps to avoid premature hydrolysis; unmask the acid in the final stages for amide installation or salt formation.

Practical notes

• Maintain inert atmosphere (as recommended for this item) to limit hydrolysis/oxidation. Use dry solvents/bases. Monitor reactions by LC–MS; characteristic UV absorption from both pyridine and nitro chromophores aids tracking.

Target Specificity

Not applicable.

• This product is a small-molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information applies.