Pyridine, 3-((methylthio)methyl)- - ≥95% , CAS No.69966-44-5

CAS: 69966-44-5 Cat. No.: P1027078 Formula: C₇H₉NS Peso molecolare: 139.220 Numero EC: 817-078-4

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CSCC1=CN=CC=C1

IUPAC Name

3-(methylsulfanylmethyl)pyridine

InChIKey

DMBKVOYJOGETRJ-UHFFFAOYSA-N

INCHI

1S/C7H9NS/c1-9-6-7-3-2-4-8-5-7/h2-5H,6H2,1H3

Peso molecolare

139.220

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridines and derivatives
• Alternative Parents: Heteroaromatic compounds Sulfenyl compounds Dialkylthioethers Azacyclic compounds Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyridine - Heteroaromatic compound - Azacycle - Dialkylthioether - Sulfenyl compound - Thioether - Organic nitrogen compound - Hydrocarbon derivative - Organosulfur compound - Organonitrogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as pyridines and derivatives. These are compounds containing a pyridine ring, which is a six-member aromatic heterocycle which consists of one nitrogen atom and five carbon atoms.
• 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: 139.220 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 139.046 Da
• Monoisotopic Mass: 139.046 Da
• Topological Polar Surface Area: 38.200 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 75.300
• 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 standardized bioassay or immunoassay protocols apply to this small-molecule building block. Typical laboratory uses involve organic synthesis. As starting points for chemical workflows:

• Handling/purification (general):

  • If odor or volatility is a concern, perform transfers with gas-tight syringes or positive-displacement pipettes in a fume hood.
  • For silica chromatography, pre-equilibrate the column with 0.5–1% triethylamine in the eluent to suppress tailing from pyridine adsorption.

• Example workflow snippets (non-binding guidance):

  • Oxidation screen: dissolve substrate (0.1–0.2 M) in DCM at 0 °C, add mCPBA (1.1 equiv) portionwise, stir to RT while monitoring by TLC. Quench with aq. Na2S2O3, wash, dry, and concentrate.
  • Benzylic functionalization: convert to sulfone, then displace with sodium alkoxide (1.5–2.0 equiv) in DMF at 60–80 °C, monitoring by LC-MS.

• Analytical methods:

  • LC-UV at 254 nm typically provides robust detection for pyridyl compounds.
  • GC may be feasible if thermal stability allows; otherwise use LC-MS for mass confirmation.

These are illustrative research procedures only. Always adapt to your scale/equipment and consult primary literature and the SDS before experimentation.

Biological Roles

Item context: This product is offered strictly for research use and is intended as a synthetic building block. No biological function is assigned for this specific compound in vivo.

General considerations for related motifs (non-clinical, literature context):

• Pyridine rings are common in enzyme cofactors (e.g., NAD+/NADH) and as pharmacophore elements; however, 3-((methylthio)methyl)pyridine itself is a synthetic molecule without known endogenous roles.
• Thioethers occur in biology (e.g., methionine, S-adenosylmethionine) and can influence lipophilicity and binding in probe design. The –CH2–S–CH3 unit can serve as a hydrophobic, polarizable handle in structure–activity exploration.
• The basic pyridine nitrogen can be protonated under physiological conditions (depending on pKa), affecting membrane partitioning and target engagement of derivatives built from this scaffold.

Practical implication for researchers:

• If incorporated into probe molecules, consider potential off-target binding via metal chelation or π–π interactions due to the pyridyl ring.
• Evaluate metabolic liabilities of thioethers (S-oxidation to sulfoxide/sulfone) in microsomal stability assays when designing analogs.

No claims are made regarding biological activity, safety, or efficacy. For any biological testing, ensure appropriate institutional approvals and risk assessments.

Buffer Applications

Not typically applicable. This product is a heteroaromatic organic building block and is not used as a buffering agent or pH standard. While pyridine and its salts can participate in acid–base equilibria, 3-((methylthio)methyl)pyridine is not a standard buffer component.

Guidance:

• For aqueous handling (e.g., extractions), the pyridine nitrogen can be protonated with mineral acids to form water-soluble pyridinium salts; this is a workup technique rather than a buffering application.
• Choose established buffer systems (e.g., phosphate, acetate, Tris, HEPES) for pH control in biochemical assays.

Green Alternatives

As a reagent/building block, the compound itself is not readily replaced, but greener choices can be made for solvents, oxidants, and workups involving 3-((methylthio)methyl)pyridine.

• Solvent choices (comparative considerations):

  • Replace dichloromethane with ethyl acetate or 2-methyltetrahydrofuran (2-MeTHF) when feasible (lower halogenated solvent footprint).
  • Replace DMF/DMA with propylene carbonate or Cyrene for polar aprotic needs where reactivity tolerates it.
  • Aqueous ethanol or MeCN/water mixtures can often support oxidation steps while easing workup.

• Oxidant and reagent selection:

  • For S-oxidation, use hydrogen peroxide or urea–hydrogen peroxide adduct (UHP) with appropriate catalysts in place of peracids to reduce chlorinated waste.
  • Electrochemical or photoredox desulfurative couplings can reduce stoichiometric tin/silicon waste versus classical radical methods (literature-dependent).

• Workup/waste minimization:

  • Employ acid–base extraction to avoid extensive silica usage; if chromatography is required, use neutral/alumina or buffered silica to lower amine adsorption and reduce solvent volumes.
  • Recycle high-boiling polar solvents via distillation; use in-line drying (molecular sieves) to extend solvent life.

• Tradeoffs (balance performance vs. greenness):

  • Greener solvents may coordinate differently to catalysts (especially with pyridines), potentially altering rates/selectivities.
  • Aqueous peroxide systems can over-oxidize sulfur to sulfone; careful control of equivalents/temperature is needed.

Small comparison table (general):

• DCM vs EtOAc: EtOAc is biodegradable/low toxicity; DCM offers superior nonpolarity and easy evaporation but is halogenated.
• THF vs 2-MeTHF: 2-MeTHF is bio-based and less peroxide-prone; THF is more widely validated and often gives faster rates.

Pharmaceutical Uses

Formulation/excipient status: Not applicable. This compound is not specified as a pharmacopeial excipient, and no pharmaceutical grade is declared for this item.

Research/manufacturing context (non-clinical):

• Role as an intermediate: The 3-((methylthio)methyl) substituent can serve as a transformable handle to access 3-(hydroxymethyl), 3-(halomethyl), or 3-alkyl derivatives of pyridine, which may be explored in discovery programs.
• Salt formation: The basic pyridine nitrogen enables formation of non-API salts (e.g., HCl, p-toluenesulfonate) to modulate crystallinity/handling of intermediates during process development.
• Impurity/marker studies: Thioether-containing heteroaromatics are sometimes used to probe oxidative stress conditions in stability-indicating methods due to readily monitorable S-oxidation.

Compliance note:

• No therapeutic, diagnostic, or in vivo use is claimed or supported. For GMP or clinical supply chains, obtain appropriate grades/specifications and regulatory documentation. This catalog item is provided for research use only.

Physical Properties

Item-specific specifications: Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for 3-(methylthiomethyl)pyridine (for planning only; confirm with primary sources before process design):

• Physical state: typically a colorless to pale yellow liquid for benzylic thioether pyridine derivatives of this size.
• Volatility: moderate; benzylic thioethers often show mid-range boiling points relative to similarly sized oxygen analogs.
• Acid–base: the pyridine nitrogen is weakly basic (pKa of the conjugate acid for unsubstituted pyridine ≈ 5.2, literature). The benzylic substituent at C-3 can slightly modulate basicity; expect broadly similar behavior (literature/generic).
• Solubility profile: expected high solubility in polar aprotic organics (e.g., acetonitrile, DMF, DMSO, dichloromethane, ethyl acetate) and good solubility in many nonpolar organics (toluene, ethers). Water solubility likely low to moderate due to heteroatom content but dominated by hydrophobic ring/alkylthio chain (literature/generic for pyridine thioethers).
• Partitioning: thioethers tend to increase hydrophobicity versus alcohol/ether analogs; logP expected in the low-to-moderate range for C7–C8 heteroaromatics (literature/generic trend).
• Spectroscopic notes: pyridine ring shows diagnostic 1H NMR signals at δ ~8–9 ppm (aromatic), benzylic –CH2– adjacent to S typically δ ~3.5–4.0 ppm; –S–CH3 δ ~2.0–2.5 ppm (literature/generic). UV absorption shows π→π* of pyridine; for chromatographic detection, 254 nm is usually effective (literature/generic).

Important: Do not treat the above as specifications. For exact BP, MP, density, refractive index, or purity cutoffs, consult the product’s CoA/SDS.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• Interpreting grades (general guidance):

  • Research grade: suitable for most synthetic and analytical R&D; impurity profiles are controlled but not pharmacopeial.
  • ≥95–99% (if specified): indicates organic purity by NMR/GC/HPLC; trace metals, water, and residual solvents may not be tightly controlled unless stated.
  • HPLC/GC grade (solvents): optimized UV background/volatility—typically not applicable to this heteroaromatic building block unless explicitly labeled.

• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet. Note that thioethers generally do not require polymerization inhibitors, but low-level antioxidants may be used in some catalogs—verify on the label/CoA.

• What to check on receipt:

  • Appearance and odor consistency; thioethers often have characteristic sulfurous odors.
  • Purity certificate (GC/HPLC/NMR) and water content (Karl Fischer) if your process is moisture-sensitive; item-specific values are not provided here.
  • Residual solvent profile and identity confirmation (1H/13C NMR, MS) for regulated workflows.

• Fit for purpose:

  • For air/moisture-sensitive transformations (e.g., polar organometallics), consider additional in-lab purification/drying even when catalog purity is high.
  • For photochemical/electrochemical uses, low UV background and trace metal content may be critical; request expanded CoA if needed.

Reaction and Applications

Use profile: 3-((Methylthio)methyl)pyridine is a versatile heteroaromatic building block. The juxtaposition of a Lewis-basic pyridine nitrogen and a benzylic thioether enables diverse synthetic manipulations.

• Transformations at sulfur and benzylic carbon:

  • Oxidation: chemoselective oxidation to the sulfoxide or sulfone (e.g., mCPBA, Oxone, peracids). Sulfone formation can activate the benzylic carbon toward substitution/elimination.
  • Pummerer-related chemistry: from the sulfoxide, Pummerer rearrangement can introduce electrophiles at the benzylic position, enabling C–C or C–heteroatom bond formation (literature).
  • Benzylic functionalization: radical or cationic conditions can convert –CH2–SMe into alcohols, halides, or carbon–carbon extensions (e.g., via desulfurative cross-couplings).

• Transformations on the pyridine ring:

  • N-oxidation (mCPBA) to pyridine N-oxide as a handle for directed metalation or rearrangements.
  • Electrophilic substitution is limited on pyridines, but metal-catalyzed C–H activation (directed by the ring N) enables alkenylation/arylation under Pd/Rh/Ir catalysis (literature, method dependent).
  • N-alkylation/acylation to pyridinium salts for phase-switching or subsequent transformations.

• Coordination and ligand effects:

  • The pyridine nitrogen can coordinate to transition metals (Pd, Ni, Cu, Ir), occasionally acting as a hemilabile donor when sulfur is oxidized or under specific conditions. This can be leveraged in catalysis or complex synthesis.

• Application contexts:

  • Intermediate toward 3-(hydroxymethyl)pyridines or 3-alkylpyridines via oxidation/substitution sequences.
  • Precursor to sulfone-based leaving groups for SN2 at the benzylic position.
  • Useful handle for introducing sulfur-containing motifs into heteroaromatic scaffolds for materials or medicinal chemistry discovery (research use only).

Reaction Conditions

The following are general literature-style conditions for common transformations of benzylic thioethers on pyridine rings. They are guidance only and must be optimized for each lab and scale.

• S-oxidation:

  • Sulfoxide: mCPBA (1.0–1.2 equiv) in DCM or EtOAc at 0–25 °C, 0.5–3 h; monitor by TLC/LC. Alternatively, H2O2 (30%, 1–2 equiv) with AcOH or catalytic tungstate in MeOH/H2O at 0–25 °C.
  • Sulfone: mCPBA (2.0–2.5 equiv) or Oxone (excess) in MeCN/H2O, 0–25 °C; typical isolated yields in the good–excellent range in literature reports.

• Benzylic substitution via sulfone activation:

  • Form sulfone, then treat with base (e.g., NaH, K2CO3) and a nucleophile (ROH, RSH, halides) in DMF/MeCN at 25–80 °C; SN2 at the benzylic carbon affords substituted products.

• Desulfurative C–C coupling (literature examples):

  • Photoredox/Ni dual catalysis: Ir(ppy)3 (1–2 mol%), NiCl2(dme) (5–10 mol%), ligand (bipyridine), aryl bromide (1.2 equiv), base (K2HPO4), MeCN, blue LEDs, 25–40 °C, 6–24 h.
  • Radical bromination (NBS, AIBN) to benzylic bromide in CCl4 or greener alternatives (MeCN), then cross-couple under Pd/Ni catalysis.

• Ring functionalization strategies:

  • Directed C–H activation using pyridine coordination under Pd/Rh with oxidant (Ag salts) in polar solvents at 60–120 °C (method-specific conditions).
  • N-oxide pathways: peracid N-oxidation, then rearrangements (e.g., to install acyloxy at ortho positions) under acylating conditions.

• Workup/purification:

  • Acid–base toggling of pyridine improves separations. Add 0.1–1% NEt3 to silica eluents to minimize tailing. For volatile/smelly sulfur species, use cold traps and good ventilation.

Note: Parameters above are literature-style guidance, not product specifications. Verify compatibility with your substrate, scale, and EHS requirements.

Safety and Handling

Authoritative safety data for this specific item are Not specified for this item; refer to SDS. The following are general considerations for pyridine thioethers:

• Likely hazards (general):

  • Irritation: pyridine derivatives may cause eye/skin/respiratory irritation; thioethers can have strong odors and may be irritating.
  • Flammability: many low–mid molecular weight pyridine derivatives are combustible liquids; handle away from ignition sources (general guidance; check SDS for flash point/GHS codes).
  • Environmental: sulfur-containing organics may be harmful to aquatic life; prevent release to the environment.

• GHS classification, H/P statements, pictograms: Not specified for this item; refer to SDS for definitive classification.

• PPE and engineering controls:

  • Use in a chemical fume hood to control vapors/odors.
  • Wear safety glasses, lab coat, and appropriate chemical-resistant gloves (e.g., nitrile). Consider double-gloving for extended contact.
  • Avoid skin contact; promptly remove contaminated clothing.

• Incompatibilities and reactive hazards:

  • Strong oxidizers (may oxidize thioether to sulfoxide/sulfone exothermically).
  • Strong acids can protonate the pyridine N and generate heat; strong bases can deprotonate acidic impurities; avoid reactive metals.
  • Avoid prolonged air/UV exposure if purity-sensitive work is planned; thioethers can slowly oxidize on storage.

• First aid (overview; defer to SDS):

  • Inhalation: move to fresh air, monitor breathing; seek medical attention if symptoms persist.
  • Skin/eyes: rinse with water for ≥15 minutes; remove contact lenses; seek medical advice.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

• Spill/response:

  • Contain with inert absorbent, ventilate area, collect for disposal per local regulations. Prevent entry to drains.

Always consult the product SDS for item-specific hazards, flash point, exposure limits, and disposal guidance.

Solvent Selection

Applicability: This product is a heteroaromatic liquid building block rather than a solvent. However, choosing suitable media for its use or purification is important.

• Polarity and miscibility (general behavior of pyridine thioethers):

  • Polar aprotic character due to the pyridine nitrogen; good solubility in acetonitrile, DMF, DMSO, dichloromethane, THF, and ethyl acetate.
  • Generally soluble in aromatic/aliphatic hydrocarbons (toluene, heptane) but with reduced polarity; solubility may vary—perform a small test.
  • Limited water solubility is typical; protonation with mineral acids affords water-soluble pyridinium salts (useful for extractions).

• Workup and purification:

  • Acid–base extraction: protonate the pyridine N with dilute HCl to drive the compound into the aqueous layer; basify to recover the free base.
  • Chromatography: thioethers can tail on silica; adding a small percentage of triethylamine to eluents can sharpen bands. Mixed eluents (hexanes/EtOAc or DCM/MeOH with base) are typical.

• Choosing reaction media:

  • For nucleophilic substitutions or oxidations at sulfur/benzylic positions, polar aprotic solvents (MeCN, DCM, DMF) often perform well.
  • For metal-mediated couplings (on the ring or benzylic position), etheric (THF/2-MeTHF) or amide solvents (DMA/DMF) are commonly used, balancing solubility and coordination effects.

• Comparison notes:

  • Versus oxygen analogs (benzylic ethers), thioethers are more polarizable and may dissolve better in less polar solvents, but can coordinate more strongly to metals, sometimes affecting catalyst speciation.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.

• General storage guidance for pyridine thioethers:

  • Keep container tightly closed in a dry, well-ventilated place. Minimize headspace oxygen if long-term storage is anticipated.
  • Protect from strong light and heat sources. Store away from oxidizing agents and acids/bases that could cause unwanted reactions.
  • If purity is critical, consider storing under inert gas (nitrogen/argon) and adding a desiccant in the outer container. Periodically check by NMR/LC for signs of S-oxidation.

• Packaging/handling:

  • Use septum-sealed amber bottles when possible to limit light and vapor exposure. Given potential odor, ensure secondary containment in shared cold/room storage.

• Reconstitution: Not applicable; this item is expected to be supplied neat. If solidification occurs at low ambient temperatures (rare for such structures), warm gently to room temperature and mix thoroughly before use.

• Freeze–thaw guidance: Not typically relevant. If stored cold to extend shelf life, avoid repeated temperature cycling—aliquot into smaller vials to minimize exposure.

• Shipping: Not specified for this item; refer to CoA/Spec Sheet. Under standard conditions, shipment at ambient temperature is usually compatible with storage at room temperature.

Always consult the product label and SDS for definitive handling and storage instructions.

Structure and Identity

Brief overview: Pyridine, 3-((methylthio)methyl)- is a heteroaromatic building block featuring a pyridine ring bearing a benzylic thioether side chain.

• Item-specific identifiers (from Product Data):

  • CAS: 69966-44-5
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: 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.

• Structural features (general chemistry description):

  • Core ring: a six-membered aromatic pyridine (one ring nitrogen at position 1).
  • Substitution pattern: the 3-position (meta to ring nitrogen) bears a benzylic methylene group (–CH2–) that is connected to a methyl thioether (–S–CH3), giving a –CH2–S–CH3 side chain.
  • Functional groups: basic heteroaromatic nitrogen (pyridine N) and a thioether (sulfide). The thioether is susceptible to oxidation to sulfoxide/sulfone; the pyridine nitrogen can be protonated or metal-coordinated.
  • 2D description in words: a pyridine ring with the ring nitrogen at the top (position 1). Counting clockwise, at position 3 there is a –CH2–S–CH3 substituent; other ring positions are unsubstituted carbons.

• Literature identifiers (for reference only; verify before use):

  • Common name: 3-(Methylthiomethyl)pyridine; pyridin-3-ylmethyl methyl sulfide.
  • Typical tautomerism: not expected (aromatic heterocycle). No stereocenters present.

Synthetic Utility

Key reactivity handles:

• Pyridine nitrogen (Lewis basic):
  • Salt formation (quaternization or protonation) for phase switching or activation toward nucleophilic substitution at the benzylic position (via benzylic cation stabilization under some conditions).
  • N-oxide formation enabling directed ortho metalation or rearrangements (e.g., Boekelheide).
• Benzylic thioether (–CH2–SMe):
  • Oxidation to sulfoxide/sulfone to enhance leaving-group ability; sulfone can undergo SN2 or elimination transforming the side chain.
  • Desulfurative couplings (radical or photoredox) to forge C–C bonds from the benzylic position using nickel or copper catalysis (literature examples).
  • Halogenation/hydroxylation of the benzylic carbon after activation (e.g., NBS in wet solvents or via sulfone pathways) to generate 3-(halomethyl/hydroxymethyl)pyridines.

Retrosynthetic value:

• Serves as a masked 3-(hydroxymethyl) or 3-(carbonyl) equivalent: oxidation or oxidative cleavage strategies can reveal alcohols or carbonyls at C-3.
• Sulfur as a traceless handle: after facilitating C–C bond formation, sulfur can be removed by reductive or eliminative steps to yield purely carbon frameworks.

Practical notes:

• Thioethers can poison some catalysts (Pd, Pt) via coordination; block or oxidize sulfur (to sulfone) prior to cross-coupling on the ring, or employ catalyst systems tolerant to soft donors.
• For chromatographic purification, add base to suppress pyridinium formation on silica, which causes tailing.
• Monitor S-oxidation state carefully by 13C/1H NMR and HRMS; sulfoxide formation changes benzylic chemical shifts and polarity.

Target Specificity

Not applicable. This product is a small-molecule heteroaromatic building block and is not an antibody, enzyme, or biological reagent with defined target specificity. No antigen/epitope, species reactivity, clone, or isotype information applies.