6-(2-Hydroxyethoxy)nicotinaldehyde - ≥97% , CAS No.1011487-86-7

CAS: 1011487-86-7 Cat. No.: H993433 Summenformel: C₈H₉NO₃ Molekulargewicht: 167.16 EG-Nummer: 116-042-9 PubChem CID: 59278605

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: C1=CC(=NC=C1C=O)OCCO
• IUPAC Name: 6-(2-hydroxyethoxy)pyridine-3-carbaldehyde
• InChIKey: JKVDEQIUVMTXNC-UHFFFAOYSA-N
• INCHI: 1S/C8H9NO3/c10-3-4-12-8-2-1-7(6-11)5-9-8/h1-2,5-6,10H,3-4H2
• Isomere SMILES: C1=CC(=NC=C1C=O)OCCO
• PubChem CID: 59278605
• Molekulargewicht: 167.16

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Pyridines and derivatives
• Subclass: Pyridine carboxaldehydes
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridine carboxaldehydes
• Alternative Parents: Aryl-aldehydes Alkyl aryl ethers Heteroaromatic compounds Azacyclic compounds Primary alcohols Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 3-pyridine carboxaldehyde - Alkyl aryl ether - Aryl-aldehyde - Heteroaromatic compound - Ether - Azacycle - Organic oxide - Organic oxygen compound - Primary alcohol - Organooxygen compound - Organonitrogen compound - Alcohol - Organic nitrogen compound - Aldehyde - Hydrocarbon derivative - Aromatic heteromonocyclic compound
• Beschreibung: 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 167.160 g/mol
• XLogP3: -0.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 167.058 Da
• Monoisotopic Mass: 167.058 Da
• Topological Polar Surface Area: 59.400 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 140.000
• 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

No assay-specific protocols (e.g., WB, IHC, IF, FC) are applicable to this small-molecule building block.

• General laboratory usage suggestions (non-specific)
  • For imine/oxime formation, combine the aldehyde (1.0 equiv) with amine/hydroxylamine (1.1–1.5 equiv) in MeOH or acetate buffer (pH ~5) with 3Å molecular sieves; stir at room temperature until completion by TLC/LC–MS.
  • For reductive amination, add NaBH3CN or STAB portionwise at 0–25 °C; quench with aqueous buffer and extract with EtOAc.
  • For alcohol activation, convert to mesylate (MsCl, Et3N, DCM, 0 °C→rt) and use in SN2 with desired nucleophile in MeCN/DMF.

These are general literature-style procedures to guide method development. Optimize stoichiometry, solvent, temperature, and workup for your specific application.

Biological Roles

• Item-specific biological/biochemical data: Not specified for this item; refer to primary literature if required.

• General considerations (no medical/clinical claims)

  • As a small heteroaromatic aldehyde, 6-(2-hydroxyethoxy)nicotinaldehyde has no established endogenous biological role. The pyridine motif is common in cofactors (e.g., nicotinamide derivatives) and ligands, but this specific compound is synthetic.
  • The aldehyde group readily forms reversible adducts (Schiff bases) with primary amine residues in biomolecules under suitable conditions; this property is used in conjugation chemistry and probe assembly, typically followed by stabilization (e.g., reduction to secondary amines or formation of oxime/hydrazone linkages).
  • The terminal hydroxyl enables installation of bio-orthogonal handles (azide/alkyne after activation), facilitating bioconjugation workflows. The pyridine nitrogen can engage in hydrogen bonding and metal coordination, potentially influencing binding in target screening campaigns.

• Research use framing

  • Suitable as a fragment or intermediate in medicinal chemistry programs, library synthesis, and as a linker-bearing aldehyde for generating imine/oxime/hydrazone libraries under mild conditions.

Note: Any biological testing, target engagement, or toxicity profiling is outside the scope of this catalog entry; use is restricted to research laboratory applications only.

Buffer Applications

This compound is not a buffering agent. It lacks the acid/base pairs and pKa spacing typical of dedicated buffer systems.

• Practical note
  • If used in aqueous bioconjugation (e.g., oxime/hydrazone formation), select compatible buffers (literature examples):
    • Acetate buffer (pH 4–5.5) for oxime formation with hydroxylamine.
    • Phosphate or citrate buffers (pH 5–7) for hydrazone formation; aniline catalysts may accelerate imine chemistry at near-neutral pH.
  • Avoid high-pH buffers that can trigger side reactions (Cannizzaro-type pathways are rare for aromatic aldehydes but strong base can induce undesired condensations) and avoid nucleophilic amine buffers during imine formation unless they serve as reactants/catalysts.

For any buffer recipes, ionic strengths, or compatibility limits specific to this item: Not specified for this item; consult procedural literature for your chosen transformation.

Green Alternatives

Although this product is a substrate, greener choices mainly concern solvent and reagent selection for its transformations.

• Greener solvent options (literature guidance)

  • Replace DCM/DMF when possible with 2-MeTHF, CPME, MeCN, EtOAc, or bio-ethanol; these often provide comparable outcomes in imine formation, Wittig/HWE, and carbonate/urethane couplings.
  • Employ water or water/EtOH mixtures for oxime/hydrazone formations using surfactant catalysis or micellar conditions (e.g., TPGS-750-M), where compatible.

• Oxidation/reduction choices

  • Oxidation of the aldehyde to acid: prefer Pinnick (NaClO2 with scavenger) over chromium(VI) reagents; catalytic TEMPO/bleach for alcohol oxidations (if reducing then re-oxidizing) avoids heavy metals.
  • Reductive amination: select sodium triacetoxyborohydride or picoline borane in green solvents (EtOH, 2-MeTHF) instead of cyanoborohydride in DCE.

• Workup and purification

  • Favor brine-free minimal-aqueous workups; use solid-supported scavengers and crystallization over extensive silica chromatography.

• Comparison snapshot (general)

  • 2-MeTHF vs THF: similar polarity, higher boiling point, renewable feedstock, better phase separation; may improve E-factor by enabling solvent recycle.
  • CPME vs DCM: reduced toxicity, wider liquid range, low peroxide tendency; ensure removal of hydroperoxides where formed.

Balance green choices with chemoselectivity needs (aldehyde can be sensitive to aqueous/basic conditions). Validate on small scale before scale-up.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; refer to CoA/Spec Sheet.

• General context (no therapeutic claims)

  • This molecule is a research-grade synthetic intermediate. In pharmaceutical R&D, heteroaromatic aldehydes with pendant hydroxyl groups are often leveraged as:
    • Intermediates in API route scouting (e.g., building substituted pyridines via aldehyde-centric C–C coupling, then derivatizing the –CH2CH2OH side chain).
    • Linker-equipped fragments for structure–activity relationship (SAR) exploration and for covalent/reversible imine probes in screening campaigns.
    • Precursors to more complex ligands or heterocycles (oxazoles, pyridines elaborated via annulations) used in process or discovery chemistry.
  • Any use in GMP manufacturing would require full qualification, impurity profiling, and pharmacopeial compliance, none of which are specified for this catalog item.

• Formulation notes

  • Not intended as an excipient. If handled in pre-formulation research, typical solvents include EtOH, PEGs, or buffered aqueous/organic mixtures; ensure compatibility with aldehyde reactivity.

Research Use Only: not for human or veterinary use; not for diagnostic or therapeutic applications.

Physical Properties

• Item-specific values

  • 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 expectations for 6-(2-hydroxyethoxy)nicotinaldehyde (reference only; not item specifications)

  • Estimated MW: ~167.16 g/mol (based on C8H9NO3 computed formula)
  • Physical state: typically a low-melting solid or high-boiling liquid for comparable heteroaromatic aldehydes with short hydroxyalkoxy chains.
  • Polarity: moderately polar due to aldehyde, ether, and terminal alcohol; capable of H-bond donation and acceptance.
  • Solubility profile: expected to be soluble in polar organic solvents (MeOH, EtOH, acetonitrile, acetone, DMSO, DMF) and sparingly to moderately soluble in water owing to the terminal –OH; actual aqueous solubility depends on temperature and ionic strength.
  • Volatility: significantly lower than unsubstituted nicotinaldehyde; aldehyde odor possible.

• General properties of related pyridinecarboxaldehydes (literature)

  • Refractive indices for liquid analogues often nD20 ≈ 1.50–1.55; densities ~1.1–1.2 g/mL.
  • UV absorbance: aromatic π→π* band in near-UV; n→π* aldehyde band in ~280–320 nm region (solvent-dependent).

For exact BP/MP, density, refractive index, water/peroxide/metal limits, and UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Item-specific quality information

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

• How to interpret grades (general guidance)

  • Research/analytical grades typically indicate low levels of non-volatile residue and tight control of organic/metallic impurities; aldehydes may be reported with GC purity and aldehyde content (titrimetric or NMR).
  • HPLC grade designation (when applicable) emphasizes low UV background and particulate control for chromatography applications.
  • Water and peroxide specifications, when present, directly impact storage stability and performance in moisture/air-sensitive steps (e.g., imine formation, Wittig-type olefinations).

• Practical quality considerations for this compound class

  • Aldehyde integrity: confirm by 1H NMR (distinct formyl singlet ~9.5–10.2 ppm) prior to critical steps; inspect for carboxylic acid byproducts.
  • Residual solvents: check by GC-HS if your synthesis is solvent-sensitive.
  • Trace metals: typically low for small-molecule organics; if used in catalysis-ligand development, ICP-MS screening may be warranted.

For the definitive specifications (purity assay, residual solvents, water content, stabilizers, UV cutoff, metal limits): Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

6-(2-Hydroxyethoxy)nicotinaldehyde is a versatile building block combining an electrophilic aldehyde, a coordinating pyridine nitrogen, and a terminal alcohol for linker chemistry.

• Key transformation families (literature/generic)

  • Imine/oxime/hydrazone formation with amines, hydroxylamine, or hydrazines; downstream reduction to secondary amines (NaBH3CN, BH3·THF, or catalytic hydrogenation).
  • Carbon–carbon bond formation from the aldehyde: Wittig, Horner–Wadsworth–Emmons, Julia–Kocienski, and Knoevenagel condensations to access alkenyl-pyridines.
  • Oxidation to the corresponding carboxylic acid (e.g., NaClO2, Pinnick), or to acyl chlorides/esters for further coupling.
  • Reduction to benzyl-type alcohols (NaBH4, DIBAL-H) or to methylene (Wolff–Kishner/Clemmensen equivalents, or catalytic hydrogenation after oxime formation).

• Linker and derivatization chemistry via –CH2CH2OH

  • Activation to tosylate/mesylate then SN2 substitution to install azides, halides, or amines; useful for click chemistry (azide→triazole via CuAAC after alkyne coupling).
  • Carbonate/urethane formation to tether to polymers, resins, or surfaces for immobilized ligand preparation.

• Role of the pyridine nitrogen

  • Acts as a directing/coordination site in metal-mediated processes (e.g., chelation during reductions or in catalytic C–C/C–N couplings of suitably functionalized derivatives).

• Practical tips

  • Maintain anhydrous conditions for water-sensitive steps (HWE, Wittig).
  • Use mild bases (DIPEA, K2CO3) to limit side reactions (self-condensation/over-oxidation).
  • Monitor by 1H NMR/LC–MS; the formyl proton (δ ~9.8–10.1 ppm) is a convenient handle.

Reaction Conditions

The following are general literature conditions for common transformations of aromatic aldehydes bearing pendant alcohols; adapt to your substrate and scale.

• Imine/oxime/hydrazone formation

  • Solvent: MeOH, EtOH, or MeCN; for bioconjugation, acetate buffer pH 4.5–5.5.
  • Catalyst: aniline (5–20 mol%) can accelerate at neutral pH; molecular sieves (3Å) aid water removal.
  • Temperature/time: 20–50 °C, 1–16 h. Reduction (NaBH3CN or STAB) at 0–25 °C, 1–4 h.

• Wittig/Horner–Wadsworth–Emmons olefination

  • Solvent: dry THF or toluene; base (NaH, KOtBu, or K2CO3 for stabilized ylides/HWE phosphonates).
  • Temperature: −78 to 25 °C (Wittig) or 0 to 25 °C (HWE) depending on ylide stability; 1–6 h.

• Reduction of aldehyde

  • NaBH4 (MeOH, 0–25 °C, 0.5–2 h) to alcohol; DIBAL-H (THF, −78 to 0 °C) for chemoselective reductions when other groups are present.

• Oxidation to acid (Pinnick)

  • NaClO2 (1.5–2.0 equiv), NaH2PO4 buffer, 2-methyl-2-butene scavenger, tBuOH/H2O or MeCN/H2O; 0–25 °C, 1–3 h.

• Alcohol derivatization

  • Tosylation: TsCl, pyridine or DMAP/Et3N, DCM (0–25 °C, 1–3 h); subsequent SN2 in MeCN/DMF with nucleophiles.
  • Mitsunobu: DEAD/DIAD with PPh3 in THF/THF alternatives; 0–25 °C, 1–4 h (ensure aldehyde is protected as acetal to avoid side reactions).

Yields vary with substrate and conditions; consult primary literature and run small-scale trials. Always maintain anhydrous/inert conditions when base- or moisture-sensitive steps are involved.

Safety and Handling

• Item-specific hazard data

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

• General safety considerations for heteroaromatic aldehydes (literature/good practice)

  • Irritation/sensitization: aldehydes may cause skin/eye irritation and respiratory irritation; avoid inhalation and contact.
  • Reactivity: aldehydes can oxidize to acids and form acetals/hemiacetals with alcohols; the terminal –OH may form internal/external hydrogen bonds and esters/ethers upon derivatization.
  • Peroxide formation: not typically prone like dialkyl ethers, but always check long-stored materials; avoid unnecessary air/UV exposure.

• Handling

  • Use in a chemical fume hood; wear appropriate PPE: lab coat, nitrile gloves, splash goggles.
  • Avoid strong oxidizers (risk of over-oxidation), strong bases (aldol/self-condensation in basic media), and strong acids (acetalization/polymerization in alcohol-rich, acid-catalyzed conditions).
  • Keep containers tightly closed to minimize oxidation or moisture uptake; purge headspace with inert gas after opening for long-term stability.

• First aid (overview; defer to SDS)

  • Skin/eye contact: rinse with water for ≥15 min; remove contaminated clothing; seek medical evaluation.
  • Inhalation: move to fresh air; monitor breathing; seek medical attention if symptoms persist.
  • Ingestion: rinse mouth; do not induce vomiting; seek immediate medical attention.

Always consult the product’s SDS for authoritative hazard, exposure limits, and spill/fire-fighting guidance.

Solvent Selection

This product is a polar, multifunctional heteroaromatic building block rather than a solvent. Selection focuses on dissolving and reacting it efficiently.

• Polarity and miscibility (general expectations)

  • Good solubility in polar organics: MeOH, EtOH, i-PrOH, MeCN, acetone, THF, DMSO, DMF.
  • Limited to moderate solubility in water; cosolvents or pH adjustment may be required for aqueous work.

• Choosing media by reaction type

  • Imine formation/reductive amination: MeOH, EtOH, i-PrOH, or toluene with molecular sieves; DCM with 3Å sieves for water removal; DMSO/DMF for poorly soluble amines (then reduce with NaBH3CN or picoline borane).
  • Wittig/Horner–Wadsworth–Emmons: dry THF, toluene, or MeCN under inert atmosphere.
  • Knoevenagel condensations: MeOH, EtOH, or acetonitrile; catalytic piperidine/secondary amines; sometimes green solvents (2-MeTHF) perform well.
  • Nucleophilic substitutions on the terminal –OH (after activation): polar aprotic (MeCN, DMF, DMSO) to facilitate SN2.

• Practical notes

  • Remove dissolved oxygen/moisture when required (degassing, sieves, or azeotropic drying).
  • The pyridine nitrogen may coordinate metals; in transition-metal catalysis this can be beneficial or inhibitory—adjust ligand/solvent accordingly.

For chromatography, start with EtOAc/hexanes or MeOH/DCM gradients; the compound’s polarity may require 1–5% MeOH with 0.1% Et3N to prevent tailing.

Storage and Reconstitution

• Item-specific storage/shipping

  • Storage conditions: Room temperature (per Product Data).
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• General storage guidance for aldehyde-bearing heteroaromatics

  • Keep tightly sealed under dry, inert atmosphere (nitrogen or argon) to minimize oxidation to the corresponding acid and prevent moisture-induced acetal/hemiacetal formation.
  • Protect from prolonged light and heat; store in amber glass where practical. If long-term storage is anticipated, consider refrigeration (2–8 °C) as a precaution, unless otherwise contraindicated by the CoA.
  • Avoid contact with strong oxidizers and strong acids/bases in storage areas.

• Handling on receipt

  • Allow to equilibrate to room temperature before opening to avoid condensation.
  • If necessary for water-sensitive reactions, dry briefly under high vacuum or co-evaporate with dry toluene/THF; verify aldehyde integrity by 1H NMR (formyl proton ~9.8–10.1 ppm).

• Reconstitution/solution preparation

  • Readily dissolves in common polar organics (MeOH, EtOH, MeCN, DMSO, DMF). Prepare stock solutions under dry, inert gas and store aliquots at −20 °C for extended periods to limit repeated freeze–thaw and air exposure.

For any item-specific shelf life, stabilizers, or solution stability data: Not specified for this item; refer to CoA/Spec Sheet.

Structure and Identity

Brief overview: 6-(2-Hydroxyethoxy)nicotinaldehyde is a heteroaromatic aldehyde based on a nicotinaldehyde (pyridine-3-carbaldehyde) core bearing a 2-hydroxyethoxy substituent at the 6-position.

• Item-specific (from Product Data)

  • SKU: H993433
  • Product name: 6-(2-Hydroxyethoxy)nicotinaldehyde
  • CAS: 1011487-86-7
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers and features (for reference; not item specifications)

  • Likely molecular formula: ~C8H9NO3 (literature/computed for a 3-formyl-6-alkoxypyridine with –O–CH2–CH2–OH)
  • Approx. molecular weight: ~167.16 g/mol (literature/computed)
  • Core scaffold: pyridine ring (one ring N, sp2), with an aldehyde at C3 (nicotinaldehyde) and an alkoxy substituent at C6 bearing a terminal hydroxyl.
  • Functional groups: aromatic heterocycle (pyridine), aldehyde (–CHO), ether (Ar–O–CH2–), primary alcohol (–CH2–OH).
  • 2D description: a six-membered aromatic ring with N at position 1; formyl at position 3; an O-alkyl chain (–O–CH2–CH2–OH) at position 6 oriented para to the ring N through one carbon.

• Stereochemistry: none (no stereocenters; all substituents on an sp2 ring).

Note: Exact structural strings (SMILES/InChI/InChIKey) and any definitive elemental analysis should be taken from the item’s CoA/Spec Sheet.

Synthetic Utility

• Functional group leverage

  • Aldehyde (–CHO): gateway to imines/oximes/hydrazones; reductive amination to secondary amines; Wittig/HWE/JKO olefinations; cyanohydrin formation; selective oxidations to acid/esters; reductions to alcohol or methylene.
  • Terminal alcohol (–CH2CH2OH): convert to sulfonates (Ms/Ts) for SN2 substitutions; install azides/halides; form carbonates/urethanes; perform Mitsunobu to invert and couple nucleophiles (mind pyridine N basicity).
  • Pyridine nitrogen: modulates electronics; facilitates metal coordination; can be quaternized for phase-transfer or for directing effects in further functionalizations.

• Retrosynthetic value

  • Disconnection at the aldehyde allows tracing back to 6-(2-hydroxyethoxy)pyridine with formylation at C3 (e.g., directed metalation/formylation or Vilsmeier–Haack on the appropriately protected/activated ring).
  • The –O–CH2–CH2–OH arm can arise from ethylene glycol derivatives via Williamson ether synthesis on 6-hydroxynicotinaldehyde or via O-alkylation of 6-hydroxynicotinaldehyde with 2-haloethanol/ethylene carbonate.

• Protecting group strategies

  • Protect the alcohol as TBDMS/TBS, THP, or carbonate during aldehyde-sensitive steps; protect the aldehyde as acetal (ethylene glycol dimethyl acetal) for base/metalation or strong nucleophile conditions.

• Purification/analysis tips

  • Aldehyde proton at δ ~9.8–10.1 ppm (1H NMR) and characteristic carbonyl at ~190–195 ppm (13C NMR); IR C=O ~1685–1705 cm−1 (ring-conjugated).
  • Silica chromatography may show tailing due to pyridine/basicity—add 0.1–1% Et3N to eluents.

Target Specificity

Not applicable. This product is a small-molecule research reagent, not an antibody, enzyme, or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity data apply to this item.