Piperidine-2-carbaldehyde - ≥95% , CAS No.144876-20-0

CAS: 144876-20-0 Cat. No.: P1072405 Formula: C₆H₁₁NO Peso molecolare: 113.160

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

C1CCNC(C1)C=O

IUPAC Name

piperidine-2-carbaldehyde

InChIKey

XHLCYFVJQKWNRH-UHFFFAOYSA-N

INCHI

1S/C6H11NO/c8-5-6-3-1-2-4-7-6/h5-7H,1-4H2

Peso molecolare

113.160

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Piperidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Piperidines
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Piperidines
• Alternative Parents: Dialkylamines Azacyclic compounds Organic oxides Hydrocarbon derivatives Aldehydes
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: Piperidine - Azacycle - Secondary amine - Secondary aliphatic amine - Organic nitrogen compound - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Carbonyl group - Amine - Aldehyde - Aliphatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with 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: 113.160 g/mol
• XLogP3: 0.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 113.084 Da
• Monoisotopic Mass: 113.084 Da
• Topological Polar Surface Area: 29.100 Ų
• Heavy Atom Count: 8
• Formal Charge: 0
• Complexity: 82.600
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 immunoassay, staining, or bioanalytical protocols are defined for this small-molecule reagent. For synthetic applications, see the Reaction Conditions and Synthetic Utility sections.

Biological Roles

This product is a synthetic small-molecule building block and does not have an established endogenous biological role.

• General context (literature):
  • The piperidine ring is a ubiquitous motif in natural products and bioactive small molecules; however, piperidine-2-carbaldehyde itself is not a known metabolite.
  • Its bifunctional nature (amine + aldehyde) makes it useful for generating libraries of 2-substituted piperidines for biochemical screening and SAR studies.
  • Protonated piperidines (ammonium salts) are more water-soluble and may be used in bioconjugation strategies after derivatization (e.g., oxime/hydrazone formation at the aldehyde), but such applications depend on subsequent functionalization and are outside the scope of inherent biological function.

Research Use Note: For research use only. Not for human or animal therapeutic or diagnostic use.

Buffer Applications

Piperidine-2-carbaldehyde is not a buffering agent and is not typically used to prepare laboratory buffers. The aldehyde functionality also makes it incompatible with many buffer components (e.g., primary amines) due to imine/Schiff base formation.

• Practical note:
  • If aqueous handling is required, consider converting the aldehyde to a more stable derivative (acetal or oxime) and/or forming a water-soluble ammonium salt for transient operations. Otherwise, select anhydrous organic media.

For buffer-making guidance, refer instead to dedicated buffering systems (phosphate, HEPES, Tris, acetate, etc.).

Green Alternatives

For processes employing piperidine-2-carbaldehyde as a substrate, greener choices relate primarily to solvent and reagent selection rather than replacement of the substrate itself.

• Greener solvent swaps (literature guidance):

  • Replace DCM with EtOAc, 2-MeTHF, or CPME for protection, reductive amination, and many carbonyl transformations.
  • Substitute THF with 2-MeTHF (bio-derived, higher boiling, improved safety) where compatible.
  • Favor alcohols (EtOH, iPrOH) over MeOH where feasible due to lower toxicity.

• Greener reductants/oxidants:

  • Use NaBH(OAc)3 or H2/Pd for reductive amination in ethanol, minimizing cyanide-containing reagents.
  • Oxidize aldehyde to acid with Pinnick (NaClO2) or catalytic TEMPO/bleach in buffered aqueous/EtOAc biphasic media, reducing heavy-metal use.

• Comparison snapshot (general):

  • DCM vs EtOAc: EtOAc offers lower toxicity and better environmental profile, but may change reaction rates/selectivity.
  • THF vs 2-MeTHF: 2-MeTHF is less prone to peroxide issues and often enables easier phase separations; note different Lewis basicity and solvation.

Tradeoffs should be evaluated on a case-by-case basis (yield, selectivity, EHS). Implement in-process controls (IPC) to ensure greener substitutions do not compromise product quality.

Pharmaceutical Uses

No excipient or formulation roles are specified for this item. Piperidine-2-carbaldehyde is primarily used as a synthetic intermediate in medicinal chemistry and process development.

• Typical roles in pharma R&D/manufacturing (literature):
  • Key intermediate to access 2-substituted piperidines via reductive amination, olefination/hydrogenation, or nucleophilic additions, enabling rapid exploration of structure–activity relationships (SAR).
  • Precursor to salt forms (after downstream derivatization), facilitating developability studies (solubility, stability, crystallinity) of candidate molecules containing the piperidine motif.
  • Building block for heterocycle annulation, furnishing bicyclic/bridged frameworks common in CNS and cardiovascular research compounds.

No claims are made regarding therapeutic efficacy or clinical use. All applications are for research and laboratory synthesis only.

Physical Properties

Item-specific physico-chemical specifications are not provided in the Product Data. The following are literature/general values for the neat compound; verify against the CoA/SDS for this specific lot.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not widely tabulated; analogous 2-alkylpiperidine aldehydes typically distill under reduced pressure due to thermal lability (literature generalization).
• Melting point: Expected to be a liquid at ambient temperature (literature expectation for small aliphatic aldehydes/piperidines).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• LogP/logD: Estimated logP for C6H11NO aldehydes is modest (ca. 0.3–0.8, literature estimations); actual value depends on protonation state and medium.
• pKa: The conjugate acid of piperidine typically has pKaH ≈ 11.0 (literature, for piperidine). Substitution at C2 slightly lowers basicity; expect pKaH ~10–11 (literature trend).
• Solubility (qualitative, literature):
  • Miscible with many polar organic solvents (e.g., alcohols, ethers, esters, chlorinated solvents).
  • Limited solubility in water as the free base; increased aqueous solubility upon protonation to the ammonium salt.
• Vapor pressure/UV cutoff/trace impurities: Not specified for this item; refer to CoA/Spec Sheet.

Note: The aldehyde can hydrate in water and can polymerize/condense under basic or acidic conditions; handle and store accordingly.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade implies (general guidance):
  • For small-molecule building blocks like piperidine-2-carbaldehyde, grades may range from technical to ≥95–98% assay for synthetic use. Higher grades may control aldehyde hydration level, amine content (as ammonium salt), and low residual solvents.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet. In general, aldehydes are sometimes packaged with trace acid or antioxidant to discourage polymerization/oxidation; verify before use if such additives would interfere with your chemistry.
• Quality considerations for this structure:
  • Monitor for impurities arising from self-condensation (aldol/hemiaminal dimers), over-oxidation to the corresponding acid, and N-formylation byproducts.
  • Determine water content (Karl Fischer) and residual amine/imine ratio if your process is water- or speciation-sensitive.
  • For stereosensitive work, confirm whether any chiral induction or epimerization at C2 is relevant in your downstream steps (parent aldehyde itself is achiral, but may form chiral products).
• Recommended incoming QC (best practices):
  • 1H/13C NMR to assess aldehyde proton (~9–10 ppm), ring methylenes, and any hydrate/hemiaminal signals.
  • GC or HPLC assay for purity, and LC–MS for mass confirmation (m/z 114 [M+H]+ expected, literature).
  • Titrate basicity or determine pKaH by non-aqueous titration if relevant to isolation protocols.

Reaction and Applications

Piperidine-2-carbaldehyde is a versatile bifunctional building block enabling divergent access to 2-substituted piperidines and more complex nitrogen heterocycles.

• Key reaction manifolds (literature):
  • N-protection then aldehyde chemistry: Protect the ring nitrogen (Boc, Cbz, Fmoc) to suppress intramolecular iminium formation, then utilize the aldehyde in Wittig, Horner–Wadsworth–Emmons, Nozaki–Hiyama–Kishi, or organometallic additions (e.g., RMgX/RLi under controlled conditions) to forge C2–C(sp3) or C2–C(sp2) bonds.
  • Reductive amination at C2: Convert the aldehyde to a secondary/tertiary amine using external amines and NaBH3CN or NaBH(OAc)3. N-protection of the ring nitrogen is often necessary to avoid intramolecular iminium formation.
  • Mannich-type/aza-Friedel–Crafts: Under acidic catalysis, the alpha-aminated aldehyde can form iminium intermediates that participate in nucleophilic additions, enabling stereoinduction in chiral-catalyst settings.
  • Oxidation: Oxidize the aldehyde to the corresponding carboxylic acid (e.g., NaClO2, Pinnick; or TEMPO/bleach to the acid via aldehyde hydrate) to access 2-carboxypiperidine derivatives.
  • Cyanation/olefination: Cyanohydrin formation or C=C installation expands to nitriles or alkenes for further elaboration (hydrogenation/hydrofunctionalization).
• Application domains (general):
  • Synthesis of 2-substituted piperidines, privileged motifs in agrochemical and pharmaceutical research.
  • Assembly of bicyclic frameworks via intramolecular cyclizations (e.g., formation of bridged or fused systems after olefination and ring-closure).
• Practical tips:
  • Work under dry, oxygen-limited conditions to suppress over-oxidation and self-condensation.
  • Control pH: mildly acidic conditions promote iminium chemistry; basic conditions can cause aldol-type side reactions.
  • Quench and workup quickly; store intermediates as stable derivatives (oximes, acetals) when appropriate.

Reaction Conditions

Representative literature-style conditions are provided as general guidance; optimize for your system and consult original references.

• Reductive amination at C2 (after N-protection):
  • Aldehyde (1.0 eq), amine nucleophile (1.1–2.0 eq), NaBH(OAc)3 (1.5–3.0 eq), HOAc (0.2–0.5 eq), solvent: DCE or MeCN or MeOH; 0–25 °C, 2–16 h. Typical isolated yields: 60–90% depending on sterics/electronics (literature ranges).
• Wittig olefination (on N-Boc derivative):
  • Phosphonium ylide (1.5–2.0 eq) in THF or toluene, 0–25 °C, 2–12 h. For stabilized ylides (E-selective), use reflux in toluene or THF; for non-stabilized, run cold to room temperature. Work under inert atmosphere, dry solvents.
• Organometallic additions:
  • RMgX or RLi (1.1–1.5 eq) in dry THF/Et2O, −78 to 0 °C, then quench. Protect N (e.g., Boc) to avoid deprotonation/side reactions. Yields highly substrate-dependent (often 50–85%).
• Oxidation to acid (Pinnick):
  • NaClO2 (1.5 eq), NaH2PO4 buffer (pH ~6.5), 2-methyl-2-butene scavenger, tBuOH/H2O (or MeCN/H2O), 0–25 °C. Typically clean conversion with minimal over-oxidation.
• Formation of oximes/hydrazones:
  • Hydroxylamine·HCl (1.2–1.5 eq) or hydrazine derivative, pyridine or EtOH as solvent, catalytic acid, 0–25 °C, 1–4 h.
• Workup/purification tips:
  • Avoid strong base during chromatography; use slightly acidic eluents (0.1–1% Et3N or 0.1% AcOH in hexanes/EtOAc or DCM/MeOH) judiciously to manage tailing while not decomposing sensitive carbonyl adducts.

Note: Exact conditions depend on the choice of N-protecting group and desired C2 substitution pattern.

Safety and Handling

• GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to the SDS for authoritative hazard information.
• General hazard profile (literature/structural inference for amine–aldehydes):
  • Likely to be corrosive/irritant to skin, eyes, and respiratory tract due to basic amine and reactive aldehyde functionalities.
  • Aldehyde may cause sensitization in susceptible individuals; avoid skin contact and inhalation of vapors/mists.
• PPE and engineering controls:
  • Use in a certified chemical fume hood.
  • Wear lab coat, chemical-resistant gloves (e.g., nitrile), and splash goggles. Consider face shield for bulk transfers.
• Handling precautions:
  • Avoid contact with oxidizers and strong acids/bases that may induce condensation, iminium formation, or polymerization.
  • Minimize exposure to moisture/air to limit self-condensation or oxidation; keep containers tightly closed.
  • Ground/bond if transferring flammable solvents alongside.
• First-aid overview (general):
  • Skin/eye contact: Immediate decontamination with copious water for ≥15 min; remove contaminated clothing; seek medical attention.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety:
  • Combustible organic; use CO2, dry chemical, or foam. Thermal decomposition may release NOx/CO.
• Spill response:
  • Absorb with inert material (vermiculite), avoid neutralizing with strong acids/bases that could trigger side reactions. Dispose per local regulations.

Always defer to the product-specific SDS for definitive safety, toxicity, and regulatory guidance.

Solvent Selection

This product is a reactive building block, not a solvent. Solvent choice should be guided by the intended transformation and the dual amine–aldehyde functionality.

• Polarity/miscibility (literature expectations):
  • Freely soluble in polar aprotic organics (THF, acetonitrile, DMF, DCM, EtOAc) and polar protics (MeOH, EtOH). Limited solubility in nonpolar hydrocarbons unless co-solvent is used.
• Selection tips by transformation (general):
  • Reductive amination (after N-protection): Alcoholic solvents (MeOH, EtOH) or DCE/MeCN work well with NaBH(OAc)3 or H2/Pd; avoid strongly basic media that trigger self-condensation.
  • Wittig/HWE on the aldehyde (N-protected substrate): Conduct in THF, toluene, or DCM with base control; rigorously dry solvents.
  • Acylation/protection of the amine (Boc, Cbz): DCM or THF commonly used with base (TEA/DIPEA); then proceed to aldehyde chemistry in the same or swapped solvent system.
• Comparisons and alternatives:
  • If hydrolytic sensitivity is an issue, choose dry, aprotic solvents (THF, DCM) and exclude water.
  • For greener profiles, consider 2-MeTHF or CPME in place of THF/DCM (see Green Alternatives).

Always verify solvent and additive compatibility with both the aldehyde and amine functionalities to prevent undesired intramolecular iminium/hemiaminal formation.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Container/atmosphere (best practices for aldehydes):
  • Store tightly closed under inert gas (N2/Ar) if possible, in amber glass to reduce oxidative and photochemical degradation.
  • Minimize headspace and exposure to moisture to limit hydrate formation and self-condensation.
• Stability notes (general):
  • Aldehydes may slowly oxidize to acids or form dimers/hemiaminals, especially in the presence of acids/bases or moisture. Conduct regular QC (NMR/LC) if stored long-term.
• Preparative handling:
  • If necessary for aqueous operations, consider forming a transient ammonium salt with a non-nucleophilic acid (e.g., HCl in Et2O) and/or protect the aldehyde as an acetal or oxime; deprotect immediately before use.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Supplied as a neat liquid/solid depending on grade (appearance not specified). If solidified on cold storage, warm gently to ambient and mix thoroughly before dispensing. For solution preparations, use dry, oxygen-free solvents and label with preparation date; for long-term stock solutions, store refrigerated/inert and monitor for degradation.

Always consult the product CoA and SDS for lot-specific guidance on storage, stability, and handling.

Structure and Identity

Piperidine-2-carbaldehyde (2-formylpiperidine) is a saturated six-membered nitrogen heterocycle bearing an aldehyde at the carbon alpha to nitrogen.

• Item identifiers (from Product Data):
  • CAS: 144876-20-0
  • PubChem CID: 10996990
  • InChIKey: 418059 (as provided; appears incomplete — verify against CoA/SDS)
• Structure (literature/computed identifiers):
  • Preferred IUPAC name (literature): piperidine-2-carbaldehyde
  • Molecular formula (literature): C6H11NO
  • Molecular weight (literature): 113.16 g/mol
  • Canonical SMILES (literature): Not specified for this item; refer to CoA/Spec Sheet.
• Functional groups and features (general structural description):
  • Contains a secondary amine (piperidine) and an aldehyde at the 2-position (alpha to N).
  • The ring is conformationally flexible (chair conformers), and the aldehyde can adopt axial/equatorial orientations relative to N.
  • The proximity of the amine and aldehyde enables transient intramolecular interactions (e.g., hemiaminal/iminium under acidic conditions), influencing reactivity.
• 2D description in words:
  • A six-membered ring with one nitrogen atom (piperidine). The carbon adjacent to nitrogen (C2) bears a formyl substituent (–CHO). The remaining ring atoms are methylenes. No stereogenic centers in the parent compound.

Synthetic Utility

The juxtaposition of a secondary amine and an aldehyde at C2 provides orthogonal handles for stepwise diversification, with strategic protection to control chemoselectivity.

• Functional group tactics (literature):
  • Amine protection first (Boc, Cbz, sulfonyl): Stabilizes the substrate and unveils the aldehyde for carbonyl chemistry (Wittig/HWE, addition of RMgX/RLi, cyanation, Prins-like reactions). Deprotection then reveals the piperidine nitrogen for further elaboration or salt formation.
  • Aldehyde derivatization first: Convert to oxime, hydrazone, or acetal to mask the carbonyl, enabling selective N-functionalization (alkylation, acylation, sulfonylation). Subsequent unveiling of the aldehyde allows installation of C2 substituents with controlled stereochemistry.
  • Iminium catalysis: Under Brønsted/Lewis acid, intramolecular iminium formation can direct nucleophilic additions at C2, useful for asymmetric induction when chiral catalysts or auxiliaries are used.
• Retrosynthetic value:
  • Serves as a convergent node for routes to 2-alkyl, 2-aryl, and 2-alkenyl piperidines, with the aldehyde as the linchpin for C–C bond formation.
  • Oxidation to the acid or homologation to the nitrile expands access to carboxamide or amide-bearing derivatives.
• Practical considerations:
  • Maintain anhydrous, oxygen-controlled conditions for sensitive steps; aldehydes can hydrate/oxidize.
  • Use mild bases (DIPEA, 2,6-lutidine) for protection steps to avoid self-condensation.
  • Monitor for hemiaminal impurities by NMR; brief acid washes can shift equilibria but must be optimized to avoid degradation.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biologic. No antigen/epitope or species reactivity data apply.

Domande frequenti

What is the purity of this product?

This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 144876-20-0, the molecular formula is C6H11NO, and the molecular weight is 113.160 g/mol. InChIKey XHLCYFVJQKWNRH-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.