| HS Code | 228028 |
| Product | Piperidine |
| Chemical Formula | C5H11N |
| Cas Number | 110-89-4 |
| Molecular Weight | 85.15 g/mol |
| Appearance | Colorless liquid |
| Odor | Fishy, amine-like |
| Density | 0.862 g/cm³ at 20°C |
| Melting Point | -7°C |
| Boiling Point | 106°C |
| Flash Point | 16°C (closed cup) |
| Refractive Index | 1.4530 at 20°C |
| Solubility | Miscible with water |
| Vapor Density | 2.94 (air = 1) |
| Pka | 11.22 (conjugate acid) |
As an accredited Piperidine factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 25 L HDPE drum, UN-approved, sealed with corrosion-resistant closure, labeled with flammability and corrosivity hazard pictograms. |
| Container Loading (20′ FCL) | 20′ FCL: load securely labeled, compatible drums/containers of Piperidine, upright, blocked, with ventilation and hazard placards per regulations. |
| Shipping | Piperidine ships as UN 2401, Hazard Class 3 (flammable liquid) with corrosive subsidiary risk, Packing Group I. It requires approved drums or IBCs, ground/sea transport only unless specially permitted, and must be labeled flammable and corrosive. Keep away from oxidizers, acids, and heat sources. |
| Storage | Store Piperidine in tightly sealed containers in a cool, dry, well-ventilated area, away from heat, sparks, and open flames. Keep separate from oxidizing agents, acids, and reactive metals. Use explosion-proof equipment and bond/ground containers. Protect containers from physical damage. Always follow manufacturer’s guidelines and relevant safety data sheets. |
| Shelf Life | Piperidine should be stored tightly sealed, away from light and air; shelf life is typically 12 months. |
In automated solid-phase peptide synthesis, piperidine functions as a deprotection reagent rather than a chain-extension building block. A working solution of 20% v/v piperidine in N,N-dimethylformamide is prepared under nitrogen and held at 2–8°C when not in use. The solution is delivered to a packed-bed column of 50–100 mm internal diameter at 2–5 mL/min, corresponding to contact times of 3–10 min per Fmoc-removal cycle. The reaction proceeds by β-elimination of the Nα-9-fluorenylmethoxycarbonyl group, yielding dibenzofulvene and a piperidine–dibenzofulvene adduct; the adduct absorbs at 301 nm, which allows inline UV detection with a path-length-calibrated flow cell. Resin loading is typically maintained between 0.3 mmol/g and 0.8 mmol/g to avoid incomplete deprotection in sterically hindered sequences. For production-scale cGMP peptide synthesis, the deprotection step is repeated 10–100 times depending on target peptide length. Karl Fischer moisture in the DMF–piperidine reagent is controlled below 0.05% w/w because water competes with aminolysis and reduces cleavage efficiency. The spent deprotection stream is monitored for dibenzofulvene carryover, and the resin is washed with DMF until the UV trace returns to baseline. After chain assembly, the peptide is cleaved from the resin with trifluoroacetic acid, and residual piperidine is removed by cold diethyl ether precipitation and repeated filtration. Published deprotection half-life data for sequence-specific hindrance is limited, so pilot runs with the actual sequence are required before scale-up.
The conversion of piperidine to piperidinium pentamethylenedithiocarbamate is carried out by reacting piperidine with carbon disulfide at a molar ratio of 2:1 in aqueous ethanol at 0–5°C. The product precipitates as a pale solid and is isolated by filtration. In natural rubber latex compounding, this dithiocarbamate salt functions as an ultra-accelerator in sulfur vulcanisation. Formulation levels are typically 0.25–1.0 phr based on dry rubber content, with zinc oxide at 3–5 phr and sulfur at 1–2 phr. The accelerator is dispersed as a 50% aqueous paste before addition to the latex to prevent localised scorch. Vulcanisation progress is measured with an oscillating disc rheometer in accordance with ASTM D2084-19a; scorch safety and optimum cure are formulation-dependent, and published values for t_s2 and t_90 vary with ammonia content, zinc oxide particle size, and maturation temperature. Latex maturation is typically controlled at 35 ± 2°C in jacketed tanks with slow agitation, and Brookfield viscosity is recorded every 2 h to detect colloidal destabilisation. The cured films are evaluated for tensile strength and elongation at break according to ISO 37:2017. The dithiocarbamate accelerator is known to shorten scorch time significantly above 35°C and should not be stored in direct contact with oxidising agents or strong acids. End products include natural rubber latex dipped goods such as examination gloves, balloons, and catheters, where the fast cure rate reduces oven residence time and improves production throughput.
Because acidizing fluids contact N80 steel at bottomhole temperatures above 90°C, piperidine-derived Mannich bases are introduced into 15% w/w hydrochloric acid at 0.1–0.5 vol% to control uniform and pitting corrosion. The Mannich base is prepared by condensation of piperidine, formaldehyde, and a ketone such as acetophenone or cyclohexanone; the resulting tertiary amino ketone adsorbs onto the steel surface through the amine and carbonyl groups. Corrosion performance is measured by weight-loss coupons according to NACE TM0169-2012, using N80 coupons with a surface area of 4.8 cm² and an immersion period of 6 h at 90°C. The acceptance criterion for inhibited acid is commonly set at a mass loss not exceeding 0.05 lb/ft² over the test period. In field blending, the inhibitor is pre-diluted in an alcohol or glycol ether before injection into the acid stream to avoid phase separation at temperatures below 5°C. A production-scale acid blending skid typically uses a static mixer and positive-displacement dosing pump; the injection rate is tied to acid flow and verified by refractometric or conductivity monitoring. Piperidine-derived inhibitors are often combined with a propargyl alcohol synergist and a quaternary ammonium salt to extend protection to vapour-phase zones. Published data for piperidine-specific Mannich bases in high-pressure, high-temperature gas wells is limited; therefore, autoclave testing with the actual produced water composition is required before field deployment. The use of these inhibitors allows matrix acidizing of carbonate reservoirs without exceeding pitting limits specified in NACE RP0775.
Piperidine is used as a nucleophilic secondary amine in the manufacture of 1-substituted piperidine intermediates that feed into CNS-active APIs. A typical 2,000 L glass-lined reactor is charged with piperidine, potassium carbonate, and a substituted benzyl chloride in acetonitrile at 25 ± 5°C; the exothermic N-alkylation is controlled by jacket cooling. Reaction progress is monitored by gas chromatography on a 30 m × 0.25 mm 5% phenyl methyl siloxane capillary column with flame ionisation detection; the endpoint specification requires residual piperidine below 0.1% by area. The product is isolated by vacuum distillation at 20–30 mbar after aqueous extraction to remove inorganic salts. For reductive amination routes, piperidine is condensed with a substituted benzaldehyde and then reduced with sodium triacetoxyborohydride; this route requires strict water control because the reducing agent decomposes in wet media. Cleaning validation for piperidine residues follows ICH Q7, and analytical methods are qualified under ICH Q2(R2). Residual piperidine in the isolated intermediate is controlled because it can form impurities of concern in downstream coupling steps; batch release often uses gas chromatography with a limit of quantitation not higher than 50 ppm. Operational boundaries include incompatibility with acid chlorides and sulfonyl chlorides, which react rapidly with secondary amines and generate dimeric impurities if the piperidine feed is not quenched before work-up. The 1-substituted piperidine intermediates are subsequently converted to 4-arylpiperidine and 4-aryl-4-piperidinol scaffolds used in antipsychotic and antihistamine drug synthesis. Published data for piperidine-specific process yields in proprietary CNS routes is limited; route-specific development reports and ICH Q7 process validation override generic assumptions.
Piperidine is evaluated as a Lewis base accelerator in anhydride-cured diglycidyl ether of bisphenol A (DGEBA) formulations for cast electrical components. In a methylhexahydrophthalic anhydride system, piperidine is added at 0.1–0.5 parts per hundred resin by mass, where its secondary amine nitrogen opens the anhydride ring and generates carboxylate propagating species. The gel time is measured by hot plate stroke cure according to ASTM D2471; differential scanning calorimetry at heating rates of 5, 10, and 20 K/min is used to determine the exotherm peak and specific heat of reaction. Published piperidine-specific kinetic constants for filled DGEBA–anhydride systems are limited, so production-scale cure schedules must be validated by dynamic mechanical analysis and dielectric analysis on the actual filled formulation. Because piperidine contains one active amine hydrogen, its use alters the stoichiometric ratio between epoxide and anhydride; the anhydride loading must be corrected for the epoxide consumption by the secondary amine. Vacuum degassing of the loaded formulation should be completed immediately after addition, as the pot life at 25°C falls below 45 min for a 200 g mass in many unfilled systems. Residual piperidine can discolour cured castings when the cure schedule includes a post-cure above 130°C; therefore, lower post-cure temperatures or alternative accelerators are used for optically clear parts. The cured DGEBA–anhydride network is used in indoor electrical insulators and potting compounds where high glass transition temperature and low moisture uptake are required.
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Piperidine, CAS 110-89-4, EINECS 203-813-0, is a saturated six-membered secondary amine supplied as a clear, colorless to pale-yellow fuming liquid. The molecule has the formula C5H11N, a molar mass of 85.15 g/mol, a boiling point of 106 °C at 101.3 kPa, a melting point of −9 °C, and a density of 0.861–0.863 g/cm³ at 20 °C. The compound is miscible with water, ethanol, and diethyl ether. Its conjugate acid exhibits a pKa of 11.22 at 25 °C, which contrasts with the lower basicity of aromatic pyridine. Industrial production is dominated by catalytic hydrogenation of pyridine over nickel or cobalt fixed-bed catalysts followed by distillation in stainless steel columns. The commercial product is distributed in three broad model grades—anhydrous, technical, and chemically pure—distinguished by water content, residual pyridine, color, and non-volatile residue rather than by a single supplier brand.
The grade designation has operational consequences. Anhydrous piperidine is specified when downstream chemistry uses water-sensitive organometallic reagents or acyl chlorides, while technical piperidine is selected for bulk derivatization where a small water carry-over can be tolerated. The analytical release values below are representative of publicly available commercial data sheets and certificate-of-analysis templates; each producer reports the actual batch data against its own validated methods.
| Parameter | Analytical method | Anhydrous model | Technical model |
|---|---|---|---|
| Assay | Capillary GC-FID, internal normalisation | ≥99.0% | ≥98.5% |
| Water content | ASTM E203 Karl Fischer coulometric | ≤0.1% | ≤0.2% |
| Color | ASTM D1209 | ≤10 APHA | ≤20 APHA |
| Distillation range | ASTM D1078 | 105–107 °C | 104–107 °C |
| Non-volatile residue | ASTM D1353 | ≤0.005% | ≤0.010% |
| Refractive index n20/D | Digital refractometer, 20 °C | 1.4520–1.4540 | 1.4510–1.4545 |
During production-scale distillation, residual pyridine is removed in a light-ends column; high-boiling impurities such as piperidine oligomers and oxidation products are rejected in the bottoms. The technical grade may retain water content up to 0.2% because a final drying stage is omitted to reduce throughput cost. For anhydrous service, molecular sieve or azeotropic drying is used before packaging under nitrogen. Batch-to-batch color variation in stored material is usually traced to dissolved iron from carbon steel piping, which is why 316L or fluoropolymer-lined transfer lines are specified in pharmaceutical intermediates plants. These grade descriptors function as product models in procurement: the anhydrous model is selected for water-sensitive chemistry, the technical model for bulk derivatization, and the chemically pure model for analytical standardization.
In pharmaceutical synthesis, anhydrous piperidine functions as both a ring precursor and a condensation catalyst. The piperidine pharmacophore appears in local anaesthetics such as bupivacaine and ropivacaine and in central nervous system actives such as paroxetine and haloperidol; the free base is used to construct the secondary or tertiary amine ring during the sequence rather than as a terminal residual solvent. For water-sensitive amide coupling or lithiation stages, water content above 0.1% reduces conversion and can generate process impurities that fail subsequent purity testing. Residual pyridine above approximately 0.1% in anhydrous grades is similarly controlled because it may poison chiral hydrogenation catalysts in downstream steps. In Knoevenagel condensations, a piperidine acetate buffer in toluene is operated at 110–120 °C with Dean-Stark water removal; catalyst loadings of 0.05–0.20 molar equivalents are typical for aromatic aldehydes. The stage is temperature-sensitive: below 100 °C, water removal from toluene is slow, while above 120 °C, decarboxylation of malonic acid can reduce selectivity. The bench-scale procedure transfers to pilot-plant stirred reactors with glass-lined vessels and triple-wall condensers. Published data for continuous-flow Knoevenagel applications using piperidine as the base are more limited; scale-up therefore requires retention-time validation with process analytical technology.
The reaction of piperidine with carbon disulfide in aqueous sodium hydroxide at 0–15 °C yields piperidinium pentamethylenedithiocarbamate, a fast dithiocarbamate accelerator used in natural rubber latex and dry rubber compounds. In dry rubber formulations, the derivative is dispersed at 0.5–2.0 phr and evaluated in a moving die rheometer according to ASTM D5289 at 150 °C. The piperidine-based dithiocarbamate shortens the induction period relative to sulfenamide-only systems and increases the maximum torque slope; because of this, delayed-action sulfenamides such as N-cyclohexyl-2-benzothiazolesulfenamide are added to move the cure curve toward a stable plateau. Open-mill handling of the free amine above 70 °C produces vapour losses and amine odour, so closed mixing lines with local exhaust are required. The molecular basis for the fast cure is the high basicity of piperidine; the protonated amine forms a labile zinc dithiocarbamate complex in the presence of ZnO, accelerating sulfur insertion. This behaviour differs from morpholine-derived accelerators, which typically exhibit lower basicity and a slower cure onset. In latex dipping operations, the accelerator is used at 0.3–1.0 phr in pre-vulcanized natural latex at 60–70 °C; residence time is adjusted with ammonia content and pH rather than by increasing free piperidine concentration.
When the condensation catalyst is upgraded from pyridine to piperidine, the reaction medium changes from a weak aromatic base to a more nucleophilic secondary amine. The pKa shift from 5.23 to 11.22 allows enolization of malonic ester donors at lower catalyst loadings and accelerates Knoevenagel and Michael additions. However, the processing window narrows because piperidine has a closed-cup flash point of 4 °C, compared with 20 °C for pyridine, and the free amine is corrosive to skin and eyes under Regulation (EC) No 1272/2008. The saturated ring also consumes electrophiles differently: piperidine can form amides with acid chlorides more readily than pyridine, so it must be added after the electrophile is quenched in certain one-pot sequences. For Mannich reactions, piperidine hydrochloride or acetate is preferred in aqueous ethanol at 25–50 °C to buffer pH between 4.5 and 5.5. Pyrrolidine offers comparable basicity but a lower boiling point, making piperidine preferable when reflux temperature above 90 °C is required. Morpholine is a weaker base and gives a higher boiling reflux medium, but its ether oxygen alters solvation and can slow crystallization of the desired enamine intermediate.
| Property | Piperidine | Pyridine | Pyrrolidine | Morpholine | Piperazine |
|---|---|---|---|---|---|
| Ring type | Six-membered secondary amine | Six-membered heteroaromatic tertiary amine | Five-membered secondary amine | Six-membered secondary amine ether | Six-membered diamine |
| Molar mass | 85.15 g/mol | 79.10 g/mol | 71.12 g/mol | 87.12 g/mol | 86.14 g/mol |
| Boiling point at 101.3 kPa | 106 °C | 115.2 °C | 86–87 °C | 128.9 °C | 146 °C |
| Melting point | −9 °C | −41.6 °C | −63 °C | −4.9 °C | 106 °C |
| pKa of conjugate acid at 25 °C | 11.22 | 5.23 | 11.31 | 8.36 | 9.8 first, 5.6 second |
| Water miscibility | Miscible | Miscible | Miscible | Miscible | Soluble solid |
| Primary downstream role | Pharmaceutical and accelerator synthon | Solvent and reagent | Enamine catalysis | Corrosion control and waxes | Polyamide and anthelmintic synthon |
Manufacturing routes also differ. Pyridine is recovered from coal tar or synthesized by the Chichibabin route, pyrrolidine is made by hydrogenation of pyrrole or cyclization of tetrahydrofurfurylamine, morpholine is produced by dehydration of diethanolamine, and piperazine is produced from ethylenediamine and ethylene glycol. These routes leave different residual catalyst and solvent fingerprints, which influence the selection of the amine for regulated pharmaceutical routes. Piperidine is selected when a liquid secondary amine with a six-membered ring is required for medicinal chemistry; piperazine is chosen when dual amine functionality or solid handling is preferred. Pyridine is less aggressive in acylation but insufficiently basic for many enolate-driven routes. Morpholine is used in steam-volatile boiler treatment because its boiling point and basicity are balanced, whereas piperidine is generally not recommended for open condensate systems because of its lower flash point and higher acute dermal toxicity. Pyrrolidine remains an alternative for low-temperature enamine formation, but its lower boiling point reduces the attainable reflux ceiling in non-pressurized vessels.
Storage of uninhibited piperidine at ambient relative humidity above 60% reduces assay through water and carbon dioxide uptake; the resulting carbamate/carbonate can increase viscosity and precipitate in feed lines. Bulk tanks are therefore kept under 5–10 kPa nitrogen pad pressure, and transfer pumps are specified as magnetically coupled or sealless because the flash point is 4 °C. Explosive vapour-air mixtures form between 1.1 vol% and 10.3 vol%, and autoignition occurs at 320 °C. Product-wetted equipment in 316L stainless steel or fluoropolymer-lined carbon steel avoids iron-induced color drift; copper alloys are avoided because amine-copper complexes can create blue discoloration and accelerate localized corrosion. Small packaging is often in 200 L epoxy-lined steel drums under a nitrogen headspace. For anhydrous synthesis, each drum is sampled through a dip-leg using a manual vacuum assembly without opening the lid; this reduces moisture ingress. If a drum is opened in ambient relative humidity above 60%, the remaining contents should be verified by Karl Fischer titration before use in organometallic stages. In addition, piperidine reacts with nitrosating agents to form N-nitrosopiperidine, so nitrite-bearing process streams and acidified nitrous acid wash systems must be segregated from the amine storage and reactor area.
Corrosion inhibition is a secondary industrial use. Piperidine has been evaluated in acid-pickling and vapour-phase inhibition packages for carbon steel; electrochemical impedance spectroscopy in 1 mol/L HCl at 25 °C shows an increase in charge-transfer resistance after amine addition, but published inhibition efficiency values vary with surface roughness, acid concentration, and flow velocity. Product-specific validation under the intended field electrolyte is therefore required before deployment. This limitation is particularly restrictive for open pickling tanks because the product’s flash point of 4 °C may conflict with local fire code.