5-Chloro-3-methylpicolinaldehyde - ≥97% , CAS No.780801-55-0

CAS: 780801-55-0 Cat. No.: C972825 Numero EC: 196-141-1 PubChem CID: 72214055

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

CC1=CC(=CN=C1C=O)Cl

IUPAC Name

5-chloro-3-methylpyridine-2-carbaldehyde

InChIKey

ICESYAJTVYWHJW-UHFFFAOYSA-N

INCHI

1S/C7H6ClNO/c1-5-2-6(8)3-9-7(5)4-10/h2-4H,1H3

Isomeri SMILES

CC1=CC(=CN=C1C=O)Cl

PubChem CID

72214055

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives
      • Subclass Pyridine carboxaldehydes

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Pyridine carboxaldehydes
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridine carboxaldehydes
• Alternative Parents: Methylpyridines Aryl-aldehydes Aryl chlorides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-pyridine carboxaldehyde - Methylpyridine - Aryl-aldehyde - Aryl chloride - Aryl halide - Heteroaromatic compound - Azacycle - Aldehyde - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Organic oxygen compound - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as pyridine carboxaldehydes. These are aromatic compounds containing a pyridine ring which bears a carboxaldehyde 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: 155.580 g/mol
• XLogP3: 1.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 155.014 Da
• Monoisotopic Mass: 155.014 Da
• Topological Polar Surface Area: 30.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 129.000
• 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 assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic use, refer to the Reaction & Applications and Reaction Conditions tabs for general laboratory guidance.

Biological Roles

This compound is a synthetic heteroaromatic building block and is not known as a natural metabolite or cofactor.

• General context (literature; not specific to this item)

  • Pyridine derivatives are prevalent motifs in pharmaceuticals and coordination complexes due to the Lewis-basic ring nitrogen that can participate in metal binding or hydrogen bonding.
  • Aldehyde-bearing pyridines readily form Schiff bases with amines, a principle exploited in creating pyridyl-imine ligands for metal complexes and sensors.

• Relevance to biochemistry

  • The electrophilic aldehyde can react with nucleophilic biomolecules (e.g., amines of lysine) in vitro; this underpins its use in probe/ligand synthesis but does not imply any biological role or therapeutic utility.

• Safety reminder

  • For research use only (per Product Data). No medical or clinical applications are intended or implied.

Buffer Applications

Not typically applicable. As a neutral heteroaromatic aldehyde, this compound is not used to formulate laboratory buffers. If aqueous handling is required (e.g., workups or analytical dilutions), use organic cosolvents (MeCN, DMSO, EtOH) and appropriate pH control only to facilitate processing, bearing in mind that acidic conditions will protonate the pyridine nitrogen and basic conditions can promote side reactions of the aldehyde.

Green Alternatives

While the molecule itself is a building block, greener choices are relevant mainly in solvent and reagent selection for its common transformations.

• Greener solvent swaps (general guidance)

  • Replace DCM with EtOAc or 2-MeTHF for extractions and many condensations.
  • Use 2-MeTHF or CPME instead of THF/Et2O for Grignard-type additions (better safety profile, lower peroxide formation for CPME, biorenewable for 2-MeTHF).
  • Favor toluene/EtOAc over chlorinated solvents in imine/Knoevenagel condensations, using Dean–Stark or molecular sieves to remove water.
  • For Suzuki couplings, consider water/EtOH mixtures with phase-transfer/base systems when compatible, or propyl/iso-propyl acetates instead of DMF/NMP.

• Base and reagent choices

  • Prefer carbonate/bicarbonate bases in cross-coupling over strong inorganic bases when feasible to reduce waste and hazards.
  • For reductions in reductive amination, H2 (Pd/C) under mild pressure can replace cyanoborohydride, eliminating cyanide waste (ensure aldehyde selectivity and safety review).

• Comparison snapshot (general)

  • THF vs 2-MeTHF: similar polarity; 2-MeTHF is partially renewable and easier to separate from water; may alter reaction rates/selectivity.
  • DCM vs EtOAc: EtOAc is less toxic and biodegradable; higher boiling point may require longer removal times.
  • DMF/NMP vs Cyrene/PolarClean: emerging bio-based dipolar aprotics can sometimes substitute, but catalyst/solubility compatibility must be verified.

• Process considerations

  • Minimize air/oxidant exposure to limit acid byproduct formation, reducing neutralization waste.
  • Implement solvent recovery and in-line drying (molecular sieves cartridges) to avoid single-use desiccants.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this item; refer to CoA/Spec Sheet. In practice, 5-chloro-3-methylpicolinaldehyde may serve as a medicinal chemistry intermediate for discovery-scale synthesis due to:

• The 2-formyl handle enabling rapid library generation via imine formation/reductive amination and olefination.
• The 5-chloro position serving as a modular coupling site (Suzuki/amide/amine installations) to diversify the scaffold.

This information is provided solely in the context of research and development/manufacturing of chemical intermediates; no therapeutic claims are made or implied.

Physical Properties

• Item-specific specs (this catalog item)

  • Appearance: 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.

• Literature/computed values for reference (not product specifications)

  • Empirical formula (derived from structure): C7H6ClNO (literature/computed)
  • Formula weight: ~155.58 g/mol (computed from C7H6ClNO)
  • Expected physical state: low–moderate melting solid or high-boiling liquid, typical for substituted picolinaldehydes of similar substitution (literature expectation; verify on CoA).
  • Polarity/functional profile: polar aprotic heteroaromatic with a protic-reactive aldehyde; typically soluble in common organic solvents (EtOAc, DCM, THF, MeCN) and sparingly soluble in water (literature-general).
  • UV absorption: aromatic chromophore and n→π* carbonyl transitions typically give absorbance in near-UV; exact cutoff/λmax not specified for this item; refer to CoA/Spec Sheet.
  • LogP/logD, density, refractive index, mp/bp: Not specified for this item; consult CoA/Spec Sheet or measure as needed.

• Practical notes (general chemistry)

  • Aldehydes may oxidize to carboxylic acids on air exposure, especially in basic media; monitor by NMR/HPLC.
  • The pyridine nitrogen can increase aqueous basicity of the ring but does not ionize as a functional group under neutral conditions; salt formation (e.g., with HCl) can alter solubility, if desired, for handling. These are general observations, not item specifications.

Quality and Grades

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

• How to interpret typical grades for small-molecule building blocks (general guidance)

  • Research or synthetic grade aldehydes are commonly supplied with purity suitable for organic synthesis (e.g., ≥95% by HPLC/GC/NMR). If high spectral purity or low UV background is required (e.g., for photophysics), request detailed impurity profiles.
  • Stabilizers are generally not used for heteroaromatic aldehydes; however, some vendors may control headspace oxygen or provide under inert atmosphere. For this item, no stabilizer is specified.

• What to check on the CoA for this compound class

  • Purity assay and method (HPLC/GC/NMR), residual solvents profile.
  • Identity confirmation (1H/13C NMR, MS, HRMS where applicable).
  • Water content (Karl Fischer) and acid content (carboxylic acid byproduct), if reported. If not listed: Not specified for this item; refer to CoA/Spec Sheet.
  • For cross-coupling applications: check for halide integrity (no hydrodehalogenation) and absence of protodechlorinated impurities.

• Lot-to-lot considerations (general)

  • Aldehyde headspace oxidation can generate trace acid over time; titration or HPLC area % may drift slightly. If sensitivity matters, consider fresh material or purify by short-path or column immediately prior to use.

Reaction and Applications

5-Chloro-3-methylpicolinaldehyde merges two orthogonal handles—an electrophilic 2-formyl group and a cross-coupling-capable 5-chloro substituent—on a directing pyridyl scaffold. This makes it a versatile intermediate for heteroarene diversification and synthesis of chelating ligands.

• Aldehyde-centered transformations (general/literature)

  • Imine/Schiff base formation with primary amines; subsequent reductive amination (NaBH3CN, H2/Pd, or BH3·THF) affords 2-(aminomethyl) derivatives.
  • Wittig/HWE olefination to introduce vinyl groups ortho to N, enabling access to 2-vinyl-5-chloro-3-methylpyridines.
  • Knoevenagel condensations with active methylenes (malononitrile, barbiturates) for electron-poor alkenes.
  • Oxime/hydrazone formation as protecting groups or as ligands; E/Z control can be solvent/temperature dependent.
  • Nucleophilic additions (RMgX, RLi) to afford secondary alcohols; the ring N may chelate and influence diastereoselectivity with chelating nucleophiles.

• Aryl chloride transformations (general/literature)

  • Suzuki–Miyaura coupling to append (hetero)aryl boron partners at C-5; aldehyde generally tolerated with mild bases (K2CO3, Na2CO3) in mixed aqueous/organic media.
  • Buchwald–Hartwig amination to install anilines or amides; aldehyde can be protected as imine/oxime if necessary to avoid side reactions under strong base.
  • Negishi/Kumada/Stille to introduce alkyl/aryl substituents where Suzuki is suboptimal.

• Heterocycle/ligand assembly

  • Condensation with 1,2-diamines or amino alcohols gives pyridine-based chelating ligands (e.g., salen-like imines) useful in coordination chemistry and catalysis.

• Applications context

  • Suitable as a diversifiable fragment in SAR campaigns and as a building block for luminescent/coordination materials, leveraging the pyridyl nitrogen for metal binding (general research use; no clinical claims).

Reaction Conditions

The following are general literature-guidance ranges for transformations typical of pyridyl aldehydes and aryl chlorides. They are not item-specific specifications.

• Imine formation / Reductive amination

  • Solvent: toluene (Dean–Stark), MeOH, or i-PrOH; add 3Å molecular sieves when using aprotics.
  • Conditions: 20–110 °C (reflux for azeotropic removal); catalytic acid (0.1–1 equiv AcOH or p-TsOH) may accelerate; reduction with NaBH3CN (rt, 1–6 h) or H2/Pd (1–3 bar, rt–40 °C).

• Wittig / HWE olefination

  • Solvent: THF or DCM; base: NaHMDS, KOtBu, or DBU (for HWE) at −78 to 25 °C; typical times 1–12 h.

• Nucleophilic additions (Grignard)

  • Solvent: anhydrous THF or Et2O; temperature −78 to 0 °C; quench at low temperature to minimize over-reduction; 1.1–1.5 equiv nucleophile, 0.5–3 h.

• Suzuki–Miyaura coupling at C–Cl

  • Catalyst/ligand: Pd2(dba)3 or Pd(OAc)2 with dialkylbiaryl phosphines (SPhos, XPhos, RuPhos, etc.).
  • Base: K2CO3, Cs2CO3, or Na2CO3 (1.5–3 equiv); Solvent: toluene/H2O, dioxane/H2O, or DMF; 60–110 °C; 2–16 h.
  • Note: Aldehyde often tolerated; if side reactions occur, protect as acetal/imine.

• Buchwald–Hartwig amination

  • Catalyst: Pd2(dba)3 or Pd(OAc)2 with BrettPhos/XPhos; Base: NaOtBu or K3PO4; Solvent: toluene, dioxane, or t-AmylOH; 80–120 °C; 4–18 h.

• Oxime/hydrazone formation

  • Solvent: MeOH, EtOH, or MeCN; Reagents: hydroxylamine HCl or hydrazines with base (pH 4.5–6.5); rt–60 °C; 0.5–6 h.

Always optimize on small scale; monitor by LC/MS or NMR. Employ inert atmosphere for moisture/air-sensitive steps.

Safety and Handling

• GHS classification, signal word, H/P statements, and pictograms: Not specified for this item; refer to the product SDS for authoritative hazard information.

• General hazards for heteroaromatic aldehydes (literature/general guidance)

  • May cause irritation to skin, eyes, and respiratory tract. Avoid inhalation and contact.
  • Aldehydes are electrophilic and can form Schiff bases with amines and proteins; handle with appropriate containment.

• Recommended PPE and engineering controls

  • Use in a fume hood with local exhaust.
  • Wear lab coat, chemical-resistant gloves (e.g., nitrile), and splash goggles or face shield.

• Incompatibilities and reactivity (general)

  • Avoid strong bases (risk of self-condensation/aldol-type side reactions) and strong oxidizers (oxidation to the corresponding acid).
  • Reacts readily with nucleophiles (amines, hydrazines, hydroxylamine) to form imines/schiff bases, hydrazones, and oximes.
  • Aryl chlorides are stable under ambient conditions but can undergo cross-coupling in the presence of Pd/Ni catalysts and base.

• First-aid overview (general)

  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

• Storage and handling notes

  • Follow the item-specific storage guidance: Room temperature (per Product Data). Store tightly closed, away from moisture and bases. Protect from prolonged air exposure to minimize oxidation. Always defer to the SDS/CoA for the specific lot.

Solvent Selection

This compound is a polar, aprotic heteroaromatic aldehyde with an aryl chloride. Solvent choice should accommodate both the electrophilic aldehyde chemistry and, where relevant, cross-coupling of the aryl chloride.

• Miscibility and polarity (general/literature)

  • Typically soluble in common organic solvents: DCM, ethyl acetate, THF, toluene, MeCN, DMF, DMSO.
  • Sparingly soluble in water as a neutral species; solubility can increase upon protonation of the pyridine N (e.g., in acidic aqueous media), but that will deactivate the aldehyde toward nucleophiles.

• Choosing solvents by transformation

  • Imine formation/Reductive amination: MeOH, EtOH, i-PrOH, or toluene with Dean–Stark; add molecular sieves or azeotropic water removal to drive equilibrium.
  • Wittig/Horner–Wadsworth–Emmons: THF, toluene, or DCM under anhydrous conditions.
  • Nucleophilic additions (Grignard/organolithium): Ether solvents (THF, Et2O) strictly anhydrous and oxygen-free.
  • Cross-coupling at C–Cl (Suzuki/Negishi/Kumada): Polar aprotic (DMF, DMAc, NMP) or mixed toluene/tert-BuOH systems; for Buchwald–Hartwig amination, toluene, dioxane, or t-AmylOH with suitable ligands.

• Small comparison (general)

  • THF: excellent for nucleophilic additions; forms peroxides over time – test before distillation/use.
  • MeCN: good for condensation chemistry; higher polarity aids solubility but can slow imine formation unless dehydrated.
  • Toluene: lower polarity; beneficial for water removal via Dean–Stark in imine/Knoevenagel reactions.

• Practical tips

  • Use 3Å molecular sieves for imine/oxime/hydrazone formation.
  • Avoid strongly basic alcoholates in protic solvents if aldol/self-condensation is a concern.

Storage and Reconstitution

• Item-specific storage

  • Storage Conditions: Room temperature (per Product Data). Store tightly closed in a dry place. Keep away from strong bases and oxidants.

• General handling best practices for aldehydes (not item-specific specs)

  • Minimize headspace oxygen and moisture exposure to limit gradual oxidation to the corresponding acid. If feasible for your workflow, blanket with inert gas after each use.
  • For extended storage, keep in amber glass to reduce UV exposure; the compound is aromatic and may absorb near-UV.

• Solution preparation and short-term storage (general)

  • Prepare stock solutions in dry solvents (e.g., anhydrous DCM, THF, toluene, MeCN, or DMSO) immediately before use.
  • Working solutions can be aliquoted and stored at −20 °C to reduce degradation; allow to warm to ambient before opening to avoid moisture ingress. Avoid repeated freeze–thaw of the same aliquot.

• Stability notes

  • Aldehyde functionality may slowly hydrate or oxidize in moist air; monitor by NMR/HPLC if stored for long periods.

• Research Use Note

  • For research use only (per Product Data). Refer to the CoA/SDS for lot-specific handling and stability information.

Structure and Identity

A heteroaromatic aldehyde bearing a chloro substituent on a picoline (methylpyridine) core, useful as both an electrophilic formyl handle and an aryl chloride coupling substrate.

• Item-specific identifiers (from Product Data)

  • SKU: C972825
  • CAS: 780801-55-0
  • Product Name: 5-Chloro-3-methylpicolinaldehyde
  • Storage conditions: Room temperature
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

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

  • Preferred IUPAC name (literature): 5-chloro-3-methylpyridine-2-carbaldehyde
  • Molecular formula (derived from name): C7H6ClNO (literature/computed)
  • Key functional groups: pyridine ring (aza-aromatic), aldehyde at the 2-position, aryl chloride at the 5-position, methyl at the 3-position.
  • 2D structure description: A six-membered aromatic ring containing one nitrogen (pyridine). Adjacent (ortho) to the ring nitrogen is a formyl substituent (–CHO). The carbon para to the ring nitrogen bears chlorine, and the carbon meta to both the nitrogen and the formyl bears a methyl group.

• Stereochemistry: None (achiral, no stereocenters).

• Structural features of interest

  • The aldehyde is strongly electrophilic and enables imine formation, Wittig/HWE olefinations, and nucleophilic additions.
  • The C–Cl bond on an electron-deficient aza-arene is a competent handle for Pd-catalyzed cross-couplings (e.g., Suzuki, Buchwald–Hartwig after amination pathways), often more reactive than on simple benzenes due to N-directed activation.
  • The ring nitrogen can coordinate to metals and influence regioselectivity/reactivity in directed metallations.

Synthetic Utility

• Functional group portfolio

  • Aldehyde (2-position): engages in condensations (imine, oxime, hydrazone), olefinations (Wittig/HWE), and nucleophilic additions (Grignard, organolithium), and can be oxidized (to acid) or reduced (to alcohol) selectively.
  • Aryl chloride (5-position): platform for Pd/Ni-catalyzed cross-coupling (Suzuki, Negishi, Kumada, Stille) or nucleophilic aromatic substitution under activating conditions.
  • Pyridine nitrogen: directs metalation (e.g., lithiation at C-6 under strong base/low temperature) and acts as a ligand site in product assemblies.

• Retrosynthetic leverage

  • Late-stage diversification at C-5 through coupling allows rapid access to aryl/hetaryl analogs while retaining the 2-formyl for convergent elaboration.
  • Temporarily mask the aldehyde as an acetal or imine to protect during strong-base couplings or metalations; deprotect under mild acidic or hydrolytic conditions.

• Named reaction context (literature)

  • Bredereck/Knöevenagel-type condensations for push–pull alkenes.
  • Povarov (after imine formation with anilines) to assemble N-heterotricycles.
  • Buchwald–Hartwig amination at C-5 followed by intramolecular cyclizations to generate bicyclic N-heterocycles.

• Practical tips

  • For cross-coupling, modest bases (K2CO3, Cs2CO3) and ligands that activate aryl chlorides (e.g., dialkylbiaryl phosphines) are typically effective; consider aldehyde protection if strong nucleophiles/bases are used.
  • Monitor aldehyde integrity by 1H NMR (formyl ~δ 9.7–10.2 ppm) and HPLC; trace acid formation may occur on storage.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent. No target, epitope, isotype, or species-reactivity information applies.