3-Propylpiperidine hydrochloride - ≥98% , CAS No.858443-89-7

CAS: 858443-89-7 Cat. No.: P972725 Summenformel: C₈H₁₈ClN Molekulargewicht: 163.690 EG-Nummer: 842-066-0

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Reinheit

≥98%

Namen und Kennungen

• Kanonisches Lächeln: CCCC1CCCNC1.Cl
• IUPAC Name: 3-propylpiperidine;hydrochloride
• InChIKey: JVSYZZXLFAPVAI-UHFFFAOYSA-N
• INCHI: 1S/C8H17N.ClH/c1-2-4-8-5-3-6-9-7-8;/h8-9H,2-7H2,1H3;1H
• Molekulargewicht: 163.690

Chemische und physikalische Eigenschaften

• Molekulargewicht: 163.690 g/mol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 2
• Exact Mass: 163.113 Da
• Monoisotopic Mass: 163.113 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 71.000
• 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: 2

XLogP3

Application Protocols

No assay or bioanalytical protocols are provided for this small-molecule building block in the Product Data. Typical use involves standard organic synthesis operations:

• Handling workflow (general)
  • Accurately weigh the HCl salt (assay basis per CoA). If needed, liberate the free base immediately before reaction. Execute coupling/alkylation/reductive amination under appropriate conditions (see Reaction Conditions tab). Upon completion, isolate as free base or convert back to HCl salt for purification and storage.

For any analytical methods (e.g., HPLC, NMR), develop project-specific protocols and refer to internal method validation requirements.

Biological Roles

This product is supplied for research use only and is intended as a synthetic building block, not as a biological reagent.

• General context (literature/knowledge)

  • Piperidine is a common motif in natural products and bioactive small molecules; it often serves as a basic, protonatable center that influences solubility and target binding.
  • N-alkylpiperidines are frequently used in medicinal chemistry to tune basicity (pKa), sterics, and lipophilicity (cLogP), thereby modulating ADME properties. The 3-propyl substituent increases hydrophobic surface area relative to unsubstituted piperidine.

• Not applicable to this item

  • No specific biological role, pathway involvement, or target interaction is assigned to 3-propylpiperidine hydrochloride in the Product Data. Any biological evaluations would be project-specific and should be designed and interpreted by the end user.

Note: No clinical or diagnostic use is intended or implied. For laboratory research only.

Buffer Applications

3-Propylpiperidine hydrochloride is not a standard buffering reagent. While protonated secondary amines can exhibit limited buffering capacity around their pKa, this salt is generally used as a synthetic intermediate rather than a buffer component.

• If a pH-stabilizing effect is desired (general guidance)

  • The conjugate acid of piperidine typically displays pKa ~10.5–11.2 (literature/typical). Thus, any incidental buffering would occur in alkaline ranges, which is uncommon for biochemical buffers.
  • Dedicated buffers (e.g., Tris, HEPES, MOPS) are recommended for reproducible pH control.

• Practical note

  • The hydrochloride form increases water solubility but does not make this compound a suitable buffer substitute. Use established buffer systems for analytical or biological workflows.

Green Alternatives

Greener practice considerations center on solvent and reagent choices rather than the amine salt itself.

• Solvent choices (typical greener swaps)

  • Replace chlorinated solvents (DCM, CHCl3) with ethyl acetate, 2-MeTHF, CPME, or MeCN when reaction scope permits.
  • Use bio-based/origin solvents where possible: 2-MeTHF (from hemicellulose), Cyrene (for some couplings) as alternatives to DMF/DMAc.
  • Favor water/EtOH/IPA for salt handling and crystallizations; the HCl salt is generally water/EtOH soluble.

• Reagents and conditions

  • Amide couplings: employ greener coupling protocols (e.g., CDI, T3P in EtOAc/2-MeTHF) rather than HATU/DMF when feasible.
  • Reductive amination: sodium triacetoxyborohydride in toluene/EtOAc or catalytic hydrogenation (H2/Pd) in ethanol as lower-toxicity options compared to cyanoborohydride in MeOH.
  • Base liberation: use aqueous carbonate/bicarbonate in biphasic systems to minimize strong-base waste and amine degradation.

• Illustrative comparison (general)

  • DMF vs. 2-MeTHF: 2-MeTHF is less toxic, from renewable feedstock, and facilitates easy workup; however, polarity may be insufficient for some salt solubilizations.
  • DCM vs. EtOAc: EtOAc is biodegradable and has a better environmental profile; note potentially higher boiling point and different extraction behavior.

Adopt in-process controls to reduce solvent volumes (telescoping salt liberation into subsequent steps) and consider salt selection to optimize crystallization from green media.

Pharmaceutical Uses

• Item intent

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

• General formulation/CMC context (literature/knowledge)

  • 3-Substituted piperidines are prominent scaffolds in drug discovery. 3-Propylpiperidine hydrochloride is typically employed as a starting material or intermediate for API candidates rather than as an excipient.
  • Salt handling: the HCl salt provides improved stability, defined assay, and batch-to-batch consistency for medicinal chemistry campaigns and library synthesis.

• Not specified for this item

  • No pharmacopeial monograph (USP/Ph. Eur.) or excipient role is indicated in the Product Data. Any incorporation into GMP workflows would require qualification and full release testing according to the intended use.

Physical Properties

• Item-specific specs (from Product Data)

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

• Computed/literature values (general guidance; not item-specific)

  • Molecular formula (hydrochloride): C8H18NCl (computed)
  • Molecular weight (hydrochloride): ~163.69 g/mol (computed)
  • Physical state: hydrochloride salts of aliphatic amines are typically crystalline solids (literature/typical), but specific polymorph and habit are item-specific.
  • Solubility (literature/typical): high in water, methanol, ethanol; moderate in isopropanol; sparing in less polar solvents (e.g., EtOAc). Free base is miscible with many organics but far less soluble in water.
  • pKa (literature, analogous piperidinium conjugate acids): pKa of conjugate acid typically ~10.5–11.2 for piperidinium; exact value depends on substitution and ionic strength.
  • LogP (free base, literature/typical for N-alkylpiperidines): often in the 1–2 range; salt form exhibits very low effective logP due to charge.

• Not specified for this item; refer to CoA/Spec Sheet

  • Melting point, water content, residual solvents, inorganic impurities, UV cutoff, refractive index, density.

Always verify property requirements (e.g., solubility in an assay buffer) experimentally with the specific lot supplied.

Quality and Grades

• Item-specific quality information (from Product Data)

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

• Guidance on interpreting grades (general)

  • Research grade: suitable for most synthetic and discovery workflows; impurity profiles are controlled for lab use.
  • Purity reporting: for amine salts, purity may be reported on a salt basis or free-base basis—check CoA to interpret assay values correctly.
  • Residual solvents and volatiles: often controlled via loss on drying (LOD) for hygroscopic salts; confirm with CoA if critical.
  • Counterion content: chloride content and chloride-to-base stoichiometry may be verified by titration or ion chromatography; important when preparing stoichiometric solutions.

• Stabilizers/additives

  • Not specified for this item; refer to CoA/Spec Sheet. Many small-molecule amine salts are shipped without stabilizers; if anti-caking agents are used, they will be declared on the CoA.

• Lot-specific documentation

  • CoA will typically include appearance, assay, identity (e.g., 1H NMR, IR, MS), water (Karl Fischer), and residual solvents. Always consult the CoA for exact acceptance criteria that apply to your purchased lot.

Reaction and Applications

As a 3-substituted piperidine building block, 3-propylpiperidine hydrochloride is valuable in medicinal and agrochemical discovery for assembling saturated N-heterocycles with tailored lipophilicity.

• Common transformations (literature/typical)

  • Amide formation: convert to the free base and couple with acid chlorides, anhydrides, or via carbodiimide/HATU/HBTU-mediated couplings to give N-acyl piperidines.
  • N-alkylation: SN2 alkylation of the free base with primary halides/tosylates under basic conditions (e.g., K2CO3 in MeCN) to access tertiary amines; care to avoid over-alkylation where undesired.
  • Reductive amination: condense the free base with aldehydes/ketones followed by NaBH3CN/NaBH(OAc)3 or catalytic hydrogenation to elaborate N-substitution.
  • Quaternization: reaction with alkyl halides affords quaternary ammonium salts for phase-transfer or structure–activity studies.
  • Salt metathesis: exchange chloride for other counterions (e.g., p-toluenesulfonate) to alter crystallinity/solubility.

• Role of the propyl substituent

  • The 3-propyl group adjusts sterics and basicity relative to unsubstituted piperidine, often modulating receptor binding in SAR campaigns (general medicinal chemistry rationale).

• Practical notes

  • Start from the HCl salt for stable handling and precise assays; liberate the free base immediately before use by partitioning with aqueous base and extracting into dry solvent.
  • Control moisture and CO2 uptake when using the free base; re-salt to HCl for storage and purification if needed (e.g., gas-phase HCl in iPr2O/Et2O).

Reaction Conditions

General conditions below are literature/typical for secondary aliphatic amines and should be optimized for specific substrates.

• Liberation of free base

  • Partition the HCl salt between water and an immiscible organic solvent (e.g., DCM/EtOAc). Basify aqueous phase to pH ≥11 with NaOH or K2CO3. Extract organic layer, dry (Na2SO4/MgSO4), and use immediately.

• Amide coupling (to acylate nitrogen)

  • Solvent: DCM, DMF, or 2-MeTHF. Base: DIPEA or Et3N (2–3 equiv). Reagents: acid chloride or HATU/HBTU/EDC with carboxylic acid. Temp: 0 °C to rt. Time: 1–12 h. Typical yields: good to excellent for unhindered acids.

• Reductive amination

  • Solvent: MeOH, EtOH, or DCE. Add carbonyl (1.0 equiv), amine (1.2–2.0 equiv as free base), AcOH (0.5 equiv) optional. Reductant: NaBH(OAc)3 at rt, 2–16 h. Workup with basification and extraction; re-salt with HCl in iPr2O if desired.

• N-Alkylation (SN2)

  • Solvent: MeCN or acetone. Base: K2CO3/Cs2CO3 (2–3 equiv). Electrophile: primary alkyl bromide/iodide or mesylate. Temp: reflux 2–24 h. Monitor for over-alkylation; may require protection (Boc) then deprotection to ensure monoalkylation.

• Quaternization

  • Solvent: MeCN or MeOH. Electrophile: excess MeI/EtI or benzyl bromide. Temp: rt–reflux; 2–24 h.

Note: Conditions are general guidelines and not item-specific specifications. Verify compatibility with the 3-propyl substituent and desired selectivity.

Safety and Handling

• Item-specific hazard data (from Product Data)

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

• General safety information for aliphatic amine hydrochloride salts (literature/typical)

  • Likely hazards: irritant/corrosive to eyes, skin, and respiratory tract in concentrated forms; may be harmful if swallowed.
  • Incompatibilities: strong bases (liberates free base), strong oxidizers; avoid contact with nitrosating agents (general for secondary amines) to prevent N-nitrosamine formation.
  • Thermal behavior: organic salts can decompose on heating; avoid excessive temperatures.

• PPE and handling

  • Use in a chemical fume hood with appropriate PPE: lab coat, safety glasses/goggles, and nitrile gloves. Avoid dust formation and inhalation; handle solids gently.
  • First aid (general): rinse affected skin/eyes with water for ≥15 min; remove contaminated clothing; if inhaled, move to fresh air; if ingested, rinse mouth. Seek medical attention as per SDS guidance.

• Spill/leak response

  • Collect spills with inert absorbent, minimize dust, and place in compatible waste container. Neutralize aqueous residues appropriately.

• Storage compatibility

  • Store away from bases and oxidizers. Keep container tightly closed and dry at room temperature (per Product Data), protected from moisture to prevent caking.

Refer to the product SDS for authoritative, item-specific safety information.

Solvent Selection

3-Propylpiperidine hydrochloride is an ionic, water-soluble organic salt. Solvent choice often depends on whether you use the salt directly or first liberate the free base.

• Salt form (R2NH2+Cl−)

  • Aqueous media: readily soluble in water; ideal for aqueous-phase reactions (e.g., amide coupling with water-soluble activators) or for phase-transfer strategies.
  • Polar protic solvents: methanol, ethanol, and isopropanol typically dissolve amine hydrochlorides well (literature/typical).
  • Polar aprotic solvents: DMF/DMAc/DMSO accommodate high loadings of ammonium salts; useful for high-concentration couplings.

• Free base (after basification, e.g., NaOH, K2CO3)

  • Organic solvents: dichloromethane, THF, EtOAc, toluene, acetonitrile commonly used with the free base in SN2 alkylations, acylations, and reductive aminations.

• Practical guidance

  • Preparing anhydrous solutions: dissolve the salt in minimal MeOH/EtOH, neutralize with base, and extract the free base into anhydrous organic solvent.
  • pH control: in mixed aqueous–organic systems, maintain pH >11 to keep the amine deprotonated for nucleophilic reactivity; for isolation as the salt, acidify aqueous layers to pH 2–3 with HCl.

• Quick comparison (typical)

  • Water/MeOH: best for handling the HCl salt, extractions back to salt form.
  • DCM/THF/MeCN: preferred once converted to the free base for many organic reactions.

Storage and Reconstitution

• Storage (from Product Data)

  • Store at room temperature. Keep container tightly closed in a dry, well-ventilated place. Protect from excessive moisture to prevent caking/hygroscopic uptake.

• Shipping

  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet. Room-temperature shipment is generally suitable for stable amine salts.

• Reconstitution/Preparation

  • For aqueous stock solutions: dissolve the weighed HCl salt in deionized water to the desired concentration; filter if necessary. Adjust pH only if required for your application, noting the salt’s inherent acidity.
  • For organic-phase reactions: if the free base is required, basify an aqueous solution/suspension of the HCl salt (e.g., 1–2 M NaOH) and extract the liberated amine into dry organic solvent. Use immediately or convert to a protected derivative.

• Stability considerations

  • Avoid prolonged exposure of the free base to air/CO2 (can form carbamates) and moisture. For long-term storage, maintain as the hydrochloride salt.

• Additional item-specific conditions

  • Appearance, purity, water content, and assay basis: Not specified for this item; refer to CoA/Spec Sheet.

Structure and Identity

Overview: 3-Propylpiperidine hydrochloride is an aliphatic secondary amine presented as its protonated hydrochloride salt. It features a saturated six-membered piperidine ring bearing a linear n-propyl substituent at the 3-position.

• Item-specific identifiers (from Product Data)

  • CAS: 858443-89-7
  • PubChem CID: 69039931
  • InChIKey: 171398 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature structural details (general; not item-specific specs)

  • Core scaffold: piperidine (cyclohexane analog with one ring nitrogen)
  • Substitution pattern: n-propyl at C-3 (relative to ring nitrogen)
  • Salt form: protonated amine (ammonium) paired with chloride anion
  • Typical protonation state: R2NH2+ Cl− in neutral aqueous media
  • Molecular formula (neutral base → salt; computed): base C8H17N; hydrochloride C8H18NCl (computed)
  • Molecular weight (computed, hydrochloride): ~163.69 g/mol

• 2D structural description (general)

  • Six-membered saturated ring with one tertiary amine lone pair in the free base; in the hydrochloride, nitrogen is protonated (ammonium). The 3-position carbon (beta to nitrogen) carries a straight-chain propyl (–CH2–CH2–CH3). Counterion is chloride.

Note: Where exact identifiers (e.g., canonical SMILES, full 27-character InChIKey) are required for regulatory documentation, consult the item’s CoA/Spec Sheet.

Synthetic Utility

• Functional group features

  • Secondary amine (as hydrochloride salt) on a saturated six-membered ring; 3-propyl substituent modulates steric profile and basicity.

• Transformations and retrosynthetic value (literature/typical)

  • N-Acylation → secondary amides and ureas/carbamates (with phosgene substitutes: triphosgene, CDI) to generate masked amines or adjust pKa/lipophilicity.
  • N-Alkylation/quaternization → tertiary and quaternary ammonium derivatives for structure–activity exploration or phase-transfer agents.
  • Reductive amination on the nitrogen (via iminium) or on appended aldehydes/ketones to build complexity efficiently.
  • Ring-functionalization: alpha to nitrogen deprotonation is challenging under strong base due to ring stability, but directed lithiation on protected derivatives can enable C–C bond formation (advanced use).
  • Salt interconversion: exchange chloride for other counterions (e.g., fumarate, citrate, mesylate, tosylate) to modulate crystallinity and processability for isolation and purification.

• Protecting group strategies

  • Transient protection of nitrogen (Boc, Cbz) after free-base liberation allows selective manipulation at carbon without N-alkylation; subsequent deprotection regenerates the amine for final salt formation.

• Practical outcomes

  • The scaffold provides a balance of basicity and hydrophobicity, enabling rapid synthesis of analog series by acylation/alkylation while maintaining favorable solubility profiles during SAR campaigns.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information is associated with this item in the Product Data.