5-Methyl-3-nitro-pyridine-2-thiol - ≥98% , CAS No.25391-74-6

CAS: 25391-74-6 Cat. No.: M930602 Formula: C₆H₆N₂O₂S Peso molecolare: 170.190

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=CNC(=S)C(=C1)[N+](=O)[O-]

IUPAC Name

5-methyl-3-nitro-1H-pyridine-2-thione

InChIKey

FHQQQGHOVLBHIU-UHFFFAOYSA-N

INCHI

1S/C6H6N2O2S/c1-4-2-5(8(9)10)6(11)7-3-4/h2-3H,1H3,(H,7,11)

Peso molecolare

170.190

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 Dihydropyridines Thiolactams Heteroaromatic compounds Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Azacyclic compounds Organosulfur compounds Organonitrogen compounds Organic salts Organic oxides Hydrocarbon derivatives Organic cations
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Nitroaromatic compound - Dihydropyridine - Methylpyridine - Hydropyridine - Pyridine - Heteroaromatic compound - Thiolactam - Organic oxoazanium - Azacycle - Organoheterocyclic compound - Propargyl-type 1,3-dipolar organic compound - Organic nitrogen compound - Organic oxygen compound - Organic salt - Hydrocarbon derivative - Organosulfur compound - Organonitrogen compound - 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: 170.190 g/mol
• XLogP3: 0.800
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 170.015 Da
• Monoisotopic Mass: 170.015 Da
• Topological Polar Surface Area: 89.900 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 275.000
• 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 validated bioassay or immunoassay protocols are associated with this small-molecule reagent in the product data. For synthetic procedures, see the Reaction Conditions and Synthetic Utility sections for general laboratory guidance.

Biological Roles

Applicability

• This product is a small heteroaromatic thiol intended for laboratory research. No biological role is assigned for this catalog item.

General biochemical considerations (literature; not product claims)

• Thiols can chelate soft metal ions and participate in redox chemistry; pyridine‑2‑thiols and their derivatives have been explored as metal-binding motifs and as ligands influencing bioinorganic models.
• Nitroaromatics are redox-active and, upon biotransformation, can yield reactive intermediates; such properties are studied in enzymology and toxicology models, but no specific biological function is attributed to this molecule.

Compliance note

• For research use only. Not for human or veterinary use, diagnostic procedures, or ingestion. No clinical or therapeutic claims are made.

Buffer Applications

Not typically applicable.

• 5‑Methyl‑3‑nitro‑pyridine‑2‑thiol is not used as a buffering agent. It lacks a conjugate acid/base pair with a practical, nontoxic window and adequate water solubility for standard buffer systems.
• For work in aqueous media, select conventional buffers (e.g., phosphate, tris, HEPES) and consider the compound’s limited aqueous solubility and thiol oxidation sensitivity.

Green Alternatives

Context

• This is a solid reagent rather than a solvent; “green alternatives” primarily concern solvent/catalyst choices and process design when using this compound.

Greener choices (literature guidance)

• Solvents: prefer ethyl acetate, 2‑MeTHF, CPME, or water/ethanol mixtures over chlorinated solvents for S‑alkylation and workup when feasible.
• Bases: carbonate bases (K2CO3, K3PO4) are milder and less hazardous than NaH or strong superbases, reducing hazard and waste neutralization load.
• Catalysis: for C–S cross-coupling, use ligand‑optimized Pd at low loadings or explore Ni catalysts to reduce precious metal usage.
• Process intensification: employ micellar catalysis (aqueous surfactant media) or solvent‑free mechanochemistry (ball milling) where compatible with reactivity and odor management.

Illustrative comparison (general; not product specs)

• Conventional: DMF or DMSO, NaH, Pd(PPh3)4, aryl bromide, 80–120 C.
• Greener: 2‑MeTHF or EtOAc, K2CO3, Pd/Ni at ≤1 mol%, aryl bromide/chloride, 50–90 C; or aqueous micellar medium with carbonate base at 40–70 C.

Trade-offs

• Lower‑boiling green solvents can increase odor emissions for thiols—ensure efficient hood capture.
• Micellar systems may require surfactant removal and thorough odor mitigation during workup.

Pharmaceutical Uses

Not typically applicable as a formulated excipient.

• This compound is offered for research use as a synthetic/analytical reagent. It is not a recognized pharmacopeial excipient.

Process-related context (general)

• Heteroaromatic thiols may appear as intermediates or ligands during API process development (e.g., metal-catalyzed steps), but they are not intended to be present in finished products. Any such use must be supported by appropriate impurity controls and purge studies.

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 physicochemical properties (reference only; not product specifications)

• Expected state: solid heteroaromatic thiol at ambient conditions (literature/analogy to 2-mercaptopyridines)
• Molecular formula: C6H6N2O2S (literature)
• Molecular weight: ~170.19 g/mol (literature)
• Acidity/basicity: weak thiol (pKaS–H typically ~5–7 for 2-mercaptopyridines; literature, compound-class); pyridine N is basic (pKa of conjugate acid typically ~1–2; literature, class value).
• Tautomerism: mercapto–thione tautomerization can influence NMR/IR signatures and reactivity (literature for 2-mercaptopyridines).
• Solubility trend: generally sparingly soluble in water; soluble in polar aprotic organics (DMSO, DMF, NMP) and moderately in EtOAc/MeCN; low solubility in alkanes (literature, class behavior).
• Volatility: low (aromatic thiol solid). Melting/boiling points, density, refractive index, logP: Not specified for this item; consult literature databases and confirm against CoA for the supplied lot.

Practical notes

• Odor: thiol-like odor typical of mercaptans; manage in fume hood.
• Peroxide formation: not applicable (non-ether), but sulfhydryl groups can oxidize to disulfides under air.

Quality and Grades

Item-specific quality

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

Guidance for chemists (general)

• Analytical/Reagent grade typically indicates low inorganic/organic impurities and suitability for routine synthesis and analysis. For spectroscopic or synthetic applications sensitive to UV background or trace metals (e.g., photoredox, cross-coupling), verify UV cutoffs and metal content on the CoA.
• For heteroaromatic thiols, trace oxidation to disulfide is a common impurity; CoA may list assay by HPLC/GC and peroxide/oxidation levels. If your application is air-sensitive, consider purging headspace with inert gas on receipt.
• If LC/MS or HPLC method development is intended, low-UV/LC grade materials minimize baseline drift; confirm if such grading applies to this lot.
• Batch-specific data: Always rely on the CoA/Spec Sheet for assay, residual solvents, water (Karl Fischer), and any stabilizer presence. Where critical, perform inbound QC (1H/13C NMR, LC/MS, and sulfhydryl titration) to confirm lot suitability.

Reaction and Applications

General research uses (literature; not exhaustive)

• S‑Alkylation/arylation: The thiol can be deprotonated (e.g., K2CO3, NaH) to give the pyridine‑2‑thiolate, a potent nucleophile for forming thioethers via SN2 with alkyl halides or via cross-coupling (e.g., Buchwald-type C–S couplings with aryl halides under Pd catalysis).
• Disulfide formation: Air or mild oxidants (I2, ferricyanide, DMSO/O2) dimerize thiols to disulfides; reversible reduction enables redox-switchable ligands.
• Metal coordination: The N,S-bidentate motif (pyridyl N + thiol/thiolate S) forms chelating ligands for transition metals (Cu, Zn, Pd, Ni), useful in coordination chemistry and catalysis development.
• Functional group interconversions on the ring: The 3‑nitro group activates the ring for nucleophilic aromatic substitution at adjacent positions and can be reduced to the amine (3‑NH2), enabling further derivatization (diazotization, coupling) while retaining the 2‑thio handle.
• Protective/activating roles: As a leaving group precursor, the thiol can be transformed to thioesters or xanthates for radical or substitution chemistry.

Practical tips

• Base choice controls chemoselectivity: weak bases (K2CO3) favor S‑alkylation; strong bases (NaH) increase risk of side reactions (e.g., over-alkylation).
• Tautomer control: polar aprotic media tend to favor thiolate formation; monitor by 1H NMR (S–H ~1–3 ppm broad) and IR (C=S vs S–H stretches) if relevant.
• Odor/oxidation: work under inert gas; add small amounts of antioxidant (e.g., BHT) only if compatible with the intended chemistry and after verifying no interference.

Reaction Conditions

General literature conditions (guidance only; not product specifications)

• S‑Alkylation (thioether synthesis): 1.0 equiv substrate, 1.1–1.5 equiv alkyl bromide/iodide, 1.5–2.5 equiv K2CO3 or Cs2CO3; solvent DMF or MeCN (0.1–0.5 M); 20–60 C; 1–12 h. Typical isolated yields 70–95% reported for unhindered substrates.
• C–S cross-coupling (aryl thioethers): 1.0 equiv substrate, 1.2 equiv aryl bromide/chloride, 1–2 mol% Pd catalyst with bulky monophosphine (e.g., XPhos–Pd G3), 2.0 equiv K3PO4, toluene/2‑MeTHF or dioxane; 60–100 C; 4–16 h. Ni catalysts (NiCl2(dppp)) can be effective for aryl chlorides.
• Disulfide formation: 0.5 equiv I2, MeOH or MeCN, rt; or air oxidation in base (NaHCO3, aq/EtOH) over several hours; quench excess oxidant with thiosulfate.
• Nitro reduction to amine: H2 (1–3 bar), 5–10 wt% Pd/C (5–10 mol% relative to substrate) in EtOH/EtOAc with a base additive (Et3N) at 25–50 C; or Fe powder (3–5 equiv) in HOAc/EtOH reflux. Protect thiol if needed to prevent catalyst poisoning.
• Metal complexation: generate thiolate in situ (NaOMe/MeOH or NaHCO3/H2O–EtOH), then add metal salt (Cu2+, Zn2+, Pd2+); monitor by UV‑vis/ESI‑MS.

Tips

• Pre-dry solvents and maintain inert atmosphere to suppress oxidation and odor.
• If the thiol poisons catalysts, protect as thioacetate prior to cross-coupling, then deprotect (hydrolysis) post‑step.

Safety and Handling

Item-specific hazard data

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

General safety considerations for heteroaromatic thiols (literature/class guidance; defer to SDS for authority)

• Likely hazards: skin/eye irritation, respiratory irritation; strong odor typical of thiols. Nitroaromatic functionality may present additional toxicity concerns; avoid inhalation/ingestion.
• PPE: lab coat, nitrile gloves (consider double-gloving for extended contact), splash goggles. Work in a certified fume hood.
• Handling: minimize exposure to air and light to limit oxidation to disulfides; keep containers tightly closed. Avoid bases/acids that could generate volatile species. Prevent release to the environment.
• Incompatibilities: strong oxidizers (risk of rapid oxidation), strong bases (formation of thiolate salts), strong reducing agents in combination with nitro groups (possible exotherms/gas evolution), and soft metal salts (complexation/precipitation).
• First aid (overview): eye/skin contact—rinse with water for 15 minutes; remove contaminated clothing. Inhalation—move to fresh air, monitor breathing. Ingestion—rinse mouth; seek medical attention. Always follow site SOPs and consult the SDS.
• Spill response: contain and absorb with inert material; avoid creation of dust; ventilate area. For odor control, seal waste promptly.
• Waste: dispose according to local regulations for organic sulfides/nitroaromatics; segregate from oxidizers.

Solvent Selection

Applicability

• This product is a solid heteroaromatic thiol; solvent selection is relevant for dissolution, handling, and reactions.

Literature-based solubility/miscibility guidance (not product specifications)

• Polar aprotic solvents: DMSO, DMF, and NMP generally dissolve 2-mercaptopyridines well; useful for S-alkylations and NMR sample prep.
• Moderately polar organics: acetonitrile and ethyl acetate can be suitable for workups, recrystallizations, and some reactions.
• Alcohols: methanol/ethanol may dissolve the thiolate salt formed under basic conditions; neutral form may have limited solubility.
• Nonpolar solvents: hexanes/toluene often show low solubility at room temperature; toluene or xylene may be serviceable at reflux for certain transformations.

Selection tips

• For S-alkylation: DMF/MeCN with mild base (K2CO3/Cs2CO3) balance solubility and selectivity.
• For metal complexation studies: ethanol/MeOH or buffered aqueous-organic mixtures may be used after deprotonation to thiolate.
• Purification/crystallization: ethyl acetate/hexanes or toluene/hexanes systems are commonly effective for heteroaromatic thiols; test small-scale.
• Odor management: choose low-volatility solvents (DMSO/DMF) for weighing/dissolution steps to minimize odor release; conduct operations in a hood.

Storage and Reconstitution

Item-specific instructions from Product Data

• Storage Conditions: Room temperature.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General handling guidance (literature/class-based)

• Protect from air and light to limit oxidation to disulfides. Store tightly sealed under inert gas (argon/nitrogen) if long-term storage is anticipated.
• Keep in a cool, dry, well-ventilated area. Avoid proximity to oxidizers.
• If preparing stock solutions, use anhydrous solvents (e.g., DMSO, DMF, MeCN). Store solutions in amber vials, under inert headspace, at ≤4 C when compatible, and use within a few days to minimize oxidation.
• Do not freeze/thaw solid repeatedly in humid environments to avoid caking or moisture uptake.

Reconstitution

• Solubility will depend on solvent choice; DMSO or DMF typically provide rapid dissolution for analytical/synthetic use. Filter through PTFE syringe filters (0.2 µm) for analytical applications if particulates are present.

Research use note

• For research use only.

Structure and Identity

Item-specific data from Product Data

• SKU: M930602
• Product Name: 5-Methyl-3-nitro-pyridine-2-thiol
• CAS: 25391-74-6
• PubChem CID: 19378732
• 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 details (for reference only; not product specifications)

• Common synonyms: 2-mercapto-5-methyl-3-nitropyridine; 5-methyl-3-nitro-2-mercaptopyridine
• Molecular formula (literature): C6H6N2O2S
• Molecular weight (literature): ~170.19 g/mol
• Structural features: aromatic pyridine ring (N at position 1) bearing three substituents: thiol (–SH) at C2, nitro (–NO2) at C3, and methyl (–CH3) at C5. The –SH/–thione tautomerism (2-mercapto vs 2-thione) is common for 2-mercaptopyridines and can be solvent/pH dependent.
• 2D description: a six-membered aromatic ring with one ring nitrogen; adjacent to N (ortho) is a thiol group; meta to N is a nitro group; para to N is unsubstituted; meta to N on the other side carries a methyl group. No stereocenters.

Notes

• Any definitive identifiers (SMILES, InChI, exact formula/weight) for this catalog item should be confirmed from the CoA/Spec Sheet for the supplied lot.

Synthetic Utility

Functional-group leverage

• S‑H (thiol): readily deprotonated to nucleophilic thiolate (N,S‑chelating) for thioether formation, thioesterification, and metal binding.
• 3‑NO2 (nitro): versatile handle—reduction to aniline (then acylation, diazotization), nucleophilic aromatic substitution activation, or Sandmeyer-type downstream chemistry after reduction to 3‑amino.
• 5‑Me (methyl): provides steric/electronic tuning; benzylic functionalization is not applicable, but methyl subtly modulates ring electronics and directs regioselectivity in metalation.

Named/representative transformations (literature)

• S‑alkylation: R–X (primary halides) + K2CO3 or Cs2CO3 in DMF/MeCN.
• C–S cross-coupling: Pd or Ni catalysis with aryl/vinyl halides; ligands such as BrettPhos/XPhos or bidentate phosphines can enhance turnover.
• Nitro reduction: H2/Pd‑C, Fe/AcOH, SnCl2, or transfer hydrogenation to afford 3‑aminopyridine‑2‑thiol derivatives.
• Oxidation: controlled formation of disulfides; over‑oxidation to sulfenic/sulfinic/sulfonic acids is possible under strong oxidants.
• Metalation: directed ortho‑lithiation is less relevant due to ring N; however, temporary protection or metal–ligand cooperation may enable selective functionalization.

Retrosynthetic value

• Serves as a bifunctional building block enabling orthogonal diversification at sulfur and the 3‑position (post‑NO2 manipulation), facilitating library synthesis of N,S‑donor ligands and heteroaryl thioethers.

Target Specificity

Not applicable.

• This product is a small-molecule reagent, not a biological targeting agent or antibody. No antigen/epitope, species reactivity, clone, or isotype information applies.