2-(Bromomethyl)-5-nitropyridine - ≥97% , CAS No.887588-20-7

CAS: 887588-20-7 Cat. No.: B1335474 PubChem CID: 29922174

QUALITÀ & PUREZZA ≥97%

Storage

Room temperature

Shipped In

Normal

Specifiche

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

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

IUPAC Name

2-(bromomethyl)-5-nitropyridine

InChIKey

IODCATCUKODATB-UHFFFAOYSA-N

INCHI

1S/C6H5BrN2O2/c7-3-5-1-2-6(4-8-5)9(10)11/h1-2,4H,3H2

Isomeri SMILES

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

CAS alternativo

887588-20-7

PubChem CID

29922174

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: Pyridines and derivatives Heteroaromatic compounds Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Azacyclic compounds Organonitrogen compounds Organobromides Organic salts Organic oxides Hydrocarbon derivatives Alkyl bromides Organic cations
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Nitroaromatic compound - Pyridine - Heteroaromatic compound - Organic oxoazanium - Propargyl-type 1,3-dipolar organic compound - Organoheterocyclic compound - Azacycle - Organic salt - Alkyl halide - Organic nitrogen compound - Organonitrogen compound - Organobromide - Alkyl bromide - Organohalogen compound - Organic oxygen compound - Hydrocarbon derivative - Organic oxide - 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: 217.020 g/mol
• XLogP3: 1.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 215.953 Da
• Monoisotopic Mass: 215.953 Da
• Topological Polar Surface Area: 58.700 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 148.000
• 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 bioassay or immunoassay protocols (WB, IHC, IF, FC) are associated with this small-molecule reagent. For chemical synthesis, see Reaction Conditions and Synthetic Utility sections for representative setups.

Biological Roles

This compound is a synthetic heteroaromatic building block and is not known to have a natural biological role.

General context (literature/general; not item-specific and not a medical claim):

• Nitro-substituted pyridines are frequently used as intermediates in medicinal chemistry campaigns to modulate electronics, polarity, and H-bonding of lead series. The nitro group can serve as a synthetic handle (e.g., for reduction to an amine) rather than as a final functional group in bioactive molecules.
• The benzylic bromide function enables rapid library diversification by SN2 introduction of amines, alcohols/phenols, thiols, or carbon nucleophiles, facilitating structure–activity relationship exploration on a fixed heteroaromatic core.
• No specific metabolic pathway or endogenous interaction is associated with 2-(bromomethyl)-5-nitropyridine itself; any biological activity would be context-dependent on derivatives prepared from it.

Research use only: This material is offered solely for research and laboratory use. It is not intended for human or veterinary applications.

Buffer Applications

Not typically applicable. 2-(Bromomethyl)-5-nitropyridine is a reactive synthetic intermediate and is not used as a buffering agent. For experimental work, select a buffer compatible with your planned reaction or assay, ensuring it does not contain nucleophiles (e.g., primary amines) that could react with the benzylic bromide.

Green Alternatives

Consider greener choices from both solvent and leaving-group perspectives, balancing reactivity with safety and environmental impact.

Greener solvent options (literature/general):

• Replace DMF/DMSO where possible with:
  • Acetonitrile (readily recoverable, lower toxicity vs DMF; still polar aprotic)
  • 2-MeTHF or CPME for reactions with strong nucleophiles under phase-transfer or with soluble bases (better EHS profiles; immiscible with water for easier workups)
  • Propylene carbonate for some SN2 processes (high polarity; non-volatile), though viscosity/workup can be challenging

Alternative leaving groups/building blocks (tradeoffs):

• 2-(Mesyloxymethyl)- or 2-(tosyloxymethyl)-5-nitropyridine
  • Pros: Avoids alkyl bromide handling; often crystalline; reduced volatility/odor
  • Cons: May require stronger bases or higher temperatures for comparable rates; generates sulfonate waste
• 2-(Chloromethyl)-5-nitropyridine
  • Pros: Less hazardous than bromide in some contexts
  • Cons: Lower SN2 reactivity; longer reaction times or higher temperatures

Process intensification (general):

• Phase-transfer catalysis to run in greener media (e.g., toluene/water or 2-MeTHF/water) at lower temperatures
• Micellar catalysis (surfactant-water systems) for certain nucleophiles, reducing organic solvent volumes
• Continuous flow for improved heat/mass transfer and reduced inventory of reactive alkyl halides

Note: Verify performance and impurity profiles when switching solvents or leaving groups; kinetics and selectivity can change substantially.

Pharmaceutical Uses

Formulation/excipient use: None. This compound is a reactive small-molecule intermediate and is not used as a pharmaceutical excipient.

Medicinal chemistry/manufacturing context (general, not a therapeutic claim):

• Useful as a building block for the synthesis of nitropyridine-containing scaffolds. The benzylic bromide allows rapid installation of side chains; the nitro group can be converted to an aniline to access diverse heteroaryl amide/urea/sulfonamide motifs.
• In route design, benzylic displacement can be leveraged late stage to append linkers or solubilizing groups under mild conditions, often avoiding transition metals.
• Quality considerations for GMP-adjacent research: control of residual inorganic bromide, alkyl bromide carryover, and nitrosation risks (avoid nitrosating conditions) during API intermediate campaigns.

Regulatory: No pharmacopeial monograph known for this specific intermediate. Any use in manufacturing requires appropriate impurity assessment and process validation.

Physical Properties

Item-specific specifications (this lot):

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

General/literature or computed information (for context only; not item specs):

• Molecular formula: C6H5BrN2O2 (computed from structure)
• Molecular weight: ~217.02 g/mol (computed)
• Physical state/volatility: Small heteroaryl benzylic bromides of this type are typically low-volatility crystalline solids or low-melting solids; exact MP/BP for this item are not specified.
• Solubility profile (qualitative, literature): Commonly soluble in polar aprotic organic solvents (DMSO, DMF, acetonitrile, dichloromethane, THF); limited solubility in water. Actual solubility should be verified experimentally for your system.
• Acid/base behavior: The ring nitrogen reduces basicity due to the nitro substituent; salt formation is possible under strong acid, but the benzylic bromide is sensitive to nucleophilic media.
• Partitioning: Expect moderate lipophilicity vs. pyridine due to benzylic bromide and nitro group; no logP measured here.

Not provided for this specific item; consult CoA/Spec Sheet for: melting/boiling points, density, refractive index, peroxide level, residual metals/UV cutoff, water content, and detailed solubility.

Quality and Grades

Item-specific quality details:

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

Guidance for this compound class (general):

• For electrophile-driven transformations (SN2 on –CH2Br), trace moisture and adventitious amines can cause side reactions. Practical quality attributes to consider include:
  • Purity by NMR/GC/LC (to suppress polysubstitution/over-alkylation from impurities)
  • Residual halide acids (HBr) and water content (can promote hydrolysis to alcohol)
  • Inorganics (Br−/Na+/K+) if the material has been crystallized or neutralized
• Analytical grade vs. synthetic grade:
  • Analytical grade emphasizes low UV background and tight impurity profiles suited for trace analysis.
  • Synthetic grade prioritizes assay and low moisture for reproducible coupling/substitution yields.
• Chromatographic suitability: For kinetic/assay studies, low-UV-absorbing solvent residuals and clean baseline around 200–300 nm are beneficial given the nitro-pyridine UV profile.

Recommendation: Review the CoA for assay, residual solvents, and moisture; if using for medicinal chemistry or scale-up, consider verifying:

• Karl Fischer moisture (if moisture-sensitive nucleophiles are planned)
• Halide quantitation (ion chromatography)
• Identity/purity by 1H/13C NMR and LC–MS.

Reaction and Applications

This benzylic bromide is a versatile electrophile for constructing 2-(substituted-methyl)-5-nitropyridine derivatives and for further diversification of the nitro-pyridine core.

Representative application families (literature/general):

• SN2 Benzylic substitution:
  • Nucleophiles: amines, azide, thiols/thiolates, alkoxides/phenoxides, cyanide, malonates, enolates.
  • Outcomes: 2-(R-CH2)-5-nitropyridines, where R = NR2, OR, SR, CN, etc.
  • Tips: Use polar aprotic solvents; control temperature to suppress elimination; employ excess nucleophile or base scavengers to avoid bis-alkylation of amines.
• Azide installation and traceless reduction:
  • Displace Br with N3−, then reduce to primary amine to access aminomethyl analogs useful for SAR libraries.
• Kornblum oxidation / Swern-like variants:
  • Oxidize –CH2Br to aldehyde (2-formyl-5-nitropyridine) under DMSO/base or sulfoxide-activating conditions; avoids metal reagents.
• Thioether/ether synthesis:
  • Phenoxides/thiolates couple cleanly at the benzylic position, enabling linker installation to the nitropyridine scaffold.
• Radical chemistry:
  • Photoredox or AIBN/initiated radical pathways from the benzylic bromide can forge C–C bonds (Giese-type additions) with electron-poor alkenes.
• Downstream nitro group edits:
  • Reduction to 5-aminopyridine derivatives (Fe/AcOH, catalytic hydrogenation, or SnCl2 systems), enabling further acylation/sulfonylation/urea formation. Protect the benzylic substituent as needed.

Use cases:

• Scaffolding in medicinal chemistry to probe benzylic vectors on a nitro-pyridine ring
• Installation of handles (–CH2–X) for subsequent conjugation or cyclization strategies.

Reaction Conditions

The following conditions are representative literature-style guidance for benzylic bromides on heteroaromatics; optimize for your substrate/nucleophile. These are not item specifications.

• Amination (secondary/tertiary amines):
  • Solvent: MeCN or DMF; Base: DIPEA or K2CO3; Temp: 20–60 C; Time: 2–16 h.
  • Notes: Use slight excess amine; monitor for over-alkylation. For primary amines, run colder and use base scavengers.
• Azide displacement → amine:
  • Reagents: NaN3 (1.2–1.5 eq); Solvent: DMF; Temp: 25–80 C; Time: 2–8 h.
  • Workup: Quench with water; extract; subsequent Staudinger or catalytic hydrogenation to convert N3 → NH2.
• Thioether formation:
  • Reagents: RSH (1.1–1.5 eq), base (K2CO3/NaH); Solvent: MeCN/acetone/DMF; Temp: 0–25 C; Time: 1–6 h.
  • Notes: Thiolates are highly reactive; control odor and oxidation.
• Ether formation (phenoxides/alkoxides):
  • Reagents: ArOH/ROH + base (K2CO3/NaH); Solvent: MeCN/acetone; Temp: 20–60 C.
  • Notes: Limit elimination by avoiding strong heating with bulky bases.
• Cyanation (to nitrile):
  • Reagents: NaCN/KCN (caution); Solvent: DMF; Temp: 20–50 C; Phase-transfer variants in toluene/H2O.
• Kornblum oxidation (to aldehyde):
  • Reagents: DMSO (solvent), base (Et3N/K2CO3) or DMSO/Ac2O; Temp: 20–60 C.

General tips:

• Dry solvents and glassware to prevent hydrolysis to alcohol.
• Add bromide last to minimize exposure of nucleophiles to alkylating agent.
• Monitor by LC–MS/GC–MS; nitro-pyridines absorb strongly 254–320 nm.
• For scale-up, consider flow to control exotherm of SN2 and manage HBr traces.

Safety and Handling

Authoritative safety data must be taken from the SDS. The following are general precautions for benzylic bromides and nitro-heteroarenes and are not item-specific GHS classifications.

• GHS/SDS: Signal word, H/P statements, pictograms: Not specified for this item; refer to SDS.
• Likely hazards (general):
  • Benzylic bromides are potent alkylating agents; may cause skin/eye irritation and respiratory irritation; may be harmful if swallowed or inhaled.
  • Nitroaromatics may present toxicity concerns and can be irritants; avoid dust/aerosol formation.
• PPE: Lab coat, nitrile gloves (change frequently), splash goggles. Use in a chemical fume hood.
• Handling: Minimize exposure to moisture and strong nucleophiles to prevent premature substitution/hydrolysis. Avoid strong bases if undesired elimination is a concern.
• Incompatibilities (general): Strong nucleophiles/bases (may substitute/eliminate); strong reducing agents (may reduce –NO2); strong oxidants (combustibility). Avoid prolonged contact with amines unless intended.
• First aid (summary):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Immediate decontamination with water for ≥15 minutes; remove contaminated clothing; seek medical attention for irritation.
  • Ingestion: Rinse mouth; do NOT induce vomiting; seek medical attention.
• Spill/leak: Absorb with inert material; avoid generating dust; dispose per local regulations.
• Fire: Use CO2, dry chemical, or foam; combustion may release HBr/NOx.

Always consult the SDS for definitive hazard classification and emergency measures.

Solvent Selection

This substrate is a heteroaryl benzylic bromide; substitution reactions benefit from polar aprotic media that enhance nucleophilicity without solvolysis.

General solvent behavior (literature/general):

• Polarity class: Polar aprotic preferred for SN2 (e.g., DMF, DMSO, acetonitrile). THF/toluene can be used with phase-transfer or stronger nucleophiles.
• Water miscibility: DMSO/DMF/MeCN are fully miscible with water; dichloromethane/THF/toluene are not. Aqueous-organic biphasic systems with PTCs often work well for thiolations and azidations.
• Solubility expectation: Good in DMSO/DMF/MeCN/CH2Cl2; modest in THF/EtOAc; poor in water (verify experimentally).

When to choose what:

• N-, O-, S-alkylation via SN2: DMF or MeCN at 0–60 C for balanced rate/control.
• Azide displacement (to amine after reduction): DMF/DMSO, 25–80 C.
• Ether/thioether formation with alkoxides/thiolates: MeCN or acetone to limit elimination.
• Kornblum-type oxidation to aldehyde: DMSO with base or DMSO/Ac2O (literature), avoiding nucleophilic solvents that cause substitution.

Comparison (general):

• MeCN: Low viscosity, easy workup, good rates; lower solubility for some salts.
• DMF/DMSO: Excellent rates/solubility; harder removal; consider high-vacuum or co-evaporation.
• THF: Useful with strong nucleophiles/crowded bases; may need heating or catalysts.

Storage and Reconstitution

Item-specific storage/shipping:

• Storage conditions: Room temperature (from product data). Keep container tightly closed.
• Shipped: Normal (from product data).
• Research use only (from product data).

General handling guidance for this class of compounds (non-contradictory, not a specification):

• Store in a dry, well-ventilated area away from strong bases, strong nucleophiles, and reducing agents.
• Protect from prolonged exposure to moisture to prevent hydrolysis/substitution. Amber glass is recommended to limit light-excited reactions, though light sensitivity is not specifically established for this item.
• If preparing solutions: Use anhydrous solvents (e.g., DMSO, DMF, MeCN). Prepare fresh just before use; benzylic bromide solutions may slowly degrade via substitution or elimination.
• Long-term: If extended storage is anticipated, consider an inert atmosphere (argon/nitrogen) and desiccant. Periodically check purity by NMR/LC–MS before critical experiments.

No reconstitution is required for this neat reagent. For any lot-specific stability or assay data, consult the CoA/Spec Sheet and the SDS.

Structure and Identity

A heteroaromatic benzyl bromide bearing a nitro substituent on a pyridine ring; a versatile benzylic electrophile for N/O/S/C-alkylations.

• Product name: 2-(Bromomethyl)-5-nitropyridine (B1335474)
• CAS: 887588-20-7; PubChem CID: 29922174
• InChIKey (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• SMILES (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (computed/literature): C6H5BrN2O2
• Molecular weight (computed/literature): ~217.02 g/mol

Structural features (descriptive, literature/general):

• Core ring: pyridine (six-membered aromatic ring containing one ring nitrogen at position 1)
• Substituents: bromomethyl group at C2 (benzylic-type –CH2Br) and nitro group (–NO2) at C5
• Functional groups: benzylic bromide (excellent SN2 electrophile), nitro (strong –I/–M withdrawing), heteroaromatic N (basic, directs electronics and coordination)
• 2D description: The ring nitrogen (N1) is adjacent to a –CH2Br substituent at the 2-position; the 5-position bears –NO2 meta to N1. The –CH2Br is sp3, capable of substitution and radical chemistry; the –NO2 is conjugated to the ring, deactivating it toward electrophilic substitution and modulating basicity.

Identity notes:

• Isomerism: no stereocenters; single constitutional isomer implied by name/positioning.
• Synonyms (literature): 5-nitro-2-(bromomethyl)pyridine; 2-(bromomethyl)pyridine-5-nitro.

Synthetic Utility

Key reactive elements and their strategic value (literature/general):

• Benzylic bromide (–CH2Br):
  • High SN2 reactivity with a broad nucleophile set (N, O, S, C). Enables late-stage introduction of side chains under mild conditions.
  • Compatible with phase-transfer catalysis; allows biphasic processing and greener solvent choices.
  • Can be converted to aldehyde (Kornblum oxidation) or to nitrile (via cyanide displacement) to modulate oxidation state and polarity.
• Nitro group (–NO2):
  • Strongly electron withdrawing; tunes pyridine basicity and can influence neighboring benzylic reactivity.
  • Convertible into an aniline (5-aminopyridine) enabling subsequent urea, amide, sulfonamide, and diazonium chemistry.
• Pyridine nitrogen:
  • Coordinates metals and can direct or inhibit certain transformations; may require protection/quaternization in sensitive metal-catalyzed steps.

Retrosynthetic leverage:

• The –CH2–X vector provides a handle for modular diversification: R–Nu + 2-(bromomethyl)-5-nitropyridine → 2-(Nu-CH2)-5-nitropyridine.
• Sequential edits: SN2 substitution → nitro reduction → further functionalization (e.g., acylation), enabling rapid scaffold hopping.

Compatibility notes:

• Avoid strongly basic, hot conditions that promote E1/E2 or ring N-alkylation of nucleophiles unless desired.
• Protect sensitive nucleophiles or use non-nucleophilic bases (e.g., DIPEA) to manage selectivity.

Target Specificity

Not applicable. This product is a small-molecule synthetic reagent, not a biological targeting agent (no antigen/epitope/clone/isotype information).