Piperidine CAS 110-89-4

What is Piperidine?

Piperidine is a saturated six-membered ring with one nitrogen — the fully hydrogenated counterpart of pyridine, C₅H₁₁N. It is a cyclic secondary amine, and like cyclohexylamine against aniline, saturating the ring transforms the chemistry: pyridine is a weak aromatic base, piperidine is a strong aliphatic one.

It is a clear, colourless liquid boiling at about 106 °C, with a powerful and distinctive odour often described as peppery or ammoniacal. The flash point sits near 16 °C, so it is highly flammable with a flammable headspace at ordinary room temperature, and it is classified at the most stringent packing group for transport.

The piperidine ring is one of the most frequently occurring nitrogen heterocycles in medicinal chemistry. It appears across analgesic, antipsychotic, antihistamine and cardiovascular drug classes, which is why a disproportionate share of the world's piperidine goes into pharmaceutical synthesis rather than into bulk chemistry.

It also has a second life as a reagent. Being a strong, nucleophilic secondary amine with no steric hindrance, it is a standard base and catalyst for Knoevenagel condensation and related carbon-carbon bond-forming reactions, and a standard reagent for removing protecting groups in peptide synthesis. Buyers should be aware that piperidine is a controlled precursor chemical in several jurisdictions, so documentation requirements are heavier than for a comparable amine.

Why piperidine specifically

• A privileged pharmaceutical ring. The piperidine ring appears in an enormous number of drug molecules. Where a synthesis needs that ring, nothing else provides it.
• Strong, unhindered secondary amine. The ring holds the two alkyl groups back, so the nitrogen is both basic and genuinely nucleophilic — unlike an acyclic hindered amine such as diisopropylamine.
• Standard condensation catalyst. Its combination of basicity and nucleophilicity makes it the classical catalyst for Knoevenagel and related condensations.
• Completely different from pyridine. Saturating the ring moves the conjugate acid pK_a from around 5 to around 11. The two are not substitutes for one another in any application.

How Piperidine is Manufactured

Piperidine is made by hydrogenating pyridine. The route is straightforward in principle and demanding in practice, because the aromatic ring is stable and the conditions needed to saturate it also risk ring opening.

• Pyridine hydrogenation. Pyridine is hydrogenated over a nickel, cobalt or noble metal catalyst at elevated temperature and pressure. The aromatic ring is saturated to the piperidine ring in a single operation.
• Selectivity control. Conditions have to be firm enough to saturate the ring but controlled enough to avoid hydrogenolysis, which opens the ring to amylamine and related acyclic by-products. Catalyst choice is what manages that balance.
• Separation. The crude product is separated from unconverted pyridine and from ring-opened by-products by fractional distillation. Residual pyridine is the impurity most often reported, because it is both the starting material and easy to detect.
• Finishing. The product is dried to specification and filled into drums or IBCs, with nitrogen blanketing where colour and water matter. Pharmaceutical grades receive additional purification and tighter residual-solvent control.

Typical Commercial Specification

Figures below are representative of standard commercial grade. Pharmaceutical grades with tighter pyridine, water and metals limits are available — send us the specification you work to and we will quote against it.

Physical & Chemical Properties

Reactivity in practice

Piperidine is bought both as a building block and as a reagent. Four roles cover nearly all of its use:

• Ring incorporation. Alkylation, acylation and reductive amination attach the piperidine ring to a growing molecule — the single most common reason it is bought in pharmaceutical synthesis.
• Condensation catalysis. Catalyses Knoevenagel and related condensations between active methylene compounds and carbonyls, usually with a carboxylic acid co-catalyst.
• Protecting-group removal. The standard reagent for cleaving Fmoc protecting groups in solid-phase peptide synthesis, typically as a dilute solution in a polar aprotic solvent.
• Enamine formation. Condenses with ketones to give enamines, a classical route to selective alpha-functionalisation.

Piperidine vs Pyridine, Piperazine and Morpholine

Piperidine is most usefully understood against the three rings it is most often confused with or compared to. All four are six-membered nitrogen heterocycles, and the differences between them — aromaticity, a second nitrogen, an oxygen in the ring — change basicity and chemistry completely.

Stated plainly: saturating pyridine to piperidine moves the conjugate acid pK_a from around 5 to around 11, which is a factor of a million in basicity — they are not alternatives. Adding a second nitrogen gives piperazine, which is a difunctional solid rather than a monofunctional liquid. Replacing a ring carbon with oxygen gives morpholine, whose electron-withdrawing oxygen makes it a markedly weaker base. Each has its own market and they substitute for one another only rarely.

Industries We Supply Piperidine To

The same molecule leaves our warehouse for very different factories. What changes between them is not the CAS number but the grade, the precursor documentation and the expectations each sector brings.

Where Piperidine is Used

Piperidine is unusual in being both a high-value building block and a routine laboratory and plant reagent. These are the end uses our customers buy it for.

In pharmaceutical synthesis

The piperidine ring is one of the most frequently occurring nitrogen heterocycles in approved drugs, appearing across analgesics, antipsychotics, antihistamines, antiarrhythmics and many other classes. Medicinal chemists favour it because the saturated ring is conformationally well behaved, metabolically reasonably stable and easy to substitute. API producers run the tightest specifications in the market: residual pyridine, ring-opened by-products and metals all have to clear ICH limits, and traceability documentation matters as much as the assay.

As a peptide synthesis reagent

Fmoc solid-phase peptide synthesis depends on being able to remove the protecting group cleanly at every cycle without disturbing the growing chain, and piperidine in a polar aprotic solvent is the standard way to do it. Peptide manufacturers consume meaningful quantities and care about water content and colour, since both can affect a coupling sequence that has to run dozens of times in succession without a failure.

As a condensation catalyst

The Knoevenagel condensation — joining an active methylene compound to an aldehyde or ketone — is classically catalysed by piperidine, often with acetic acid as co-catalyst. The combination of strong basicity and genuine nucleophilicity is what makes it work, and it is why a hindered base such as diisopropylamine cannot simply be substituted. The reaction appears throughout fine chemical, dye and agrochemical manufacture.

In rubber and agrochemical chemistry

Reaction with carbon disulphide gives piperidinium dithiocarbamates and related accelerators, and the piperidinyl group appears in a range of crop protection actives. These applications are less demanding on purity than pharmaceutical work, but they are equally subject to the precursor documentation that follows this product everywhere.

Quality Control & Testing

Every lot is released against a batch-specific Certificate of Analysis. The methods behind the numbers are standard across the industry, and we are happy to share them or to work to your own in-house test protocol.

• Assay and impurity profile — gas chromatography, which quantifies residual pyridine, amylamine and other ring-opened by-products in a single run.
• Residual pyridine — reported explicitly rather than inferred. It is the unconverted starting material and the impurity most likely to matter downstream.
• Water content — Karl Fischer titration, which matters in acylation chemistry and in peptide coupling sequences.
• Colour — APHA / Hazen against a standard. Colour drift signals air ingress or metal contamination.
• Distillation range — a fast, revealing check for pyridine and by-product carry-over.
• Metals and residue — iron and evaporation residue, both of which matter in pharmaceutical service.

Common Process Problems & Likely Causes

When piperidine misbehaves in a plant, the cause is usually one of a short list of things. This table is the shortcut our technical desk works through before anyone opens a complaint file.

Packaging, Storage & Shipping

• Standard packing. 160 kg net in lined steel or HDPE drums, with 1000 L IBCs for larger users.
• Bulk packing. Tank movements arranged where volumes justify them and the destination's precursor controls permit.
• Inert blanketing. Nitrogen-blanketed at fill where the grade and end use call for it, to protect colour and limit carbon dioxide pickup.
• Storage. Cool, dry, well-ventilated and bunded area away from heat, ignition sources, oxidisers and acids, with containers kept tightly closed.
• Materials of construction. Stainless steel, carbon steel or suitable lined vessels. Avoid copper, brass, bronze, aluminium and mercury, all of which are attacked by amines.
• Shelf life. Typically 12 months in unopened original packing under those conditions. Beyond that, re-test rather than assume.
• Fire precautions. The flash point is near 16 °C, so the vapour space above the liquid is in the flammable range at ordinary room temperature. Bonding, earthing and explosion-proof fittings are not optional, and the storage area should be zoned accordingly.
• Transport classification. UN 2401, Piperidine, Class 8 corrosive with subsidiary risk 3 flammable, Packing Group I — the most stringent packing group, which restricts some transport options and requires more robust packaging.
• Security and records. As a controlled precursor in several jurisdictions, piperidine consignments may require secure storage, inventory records and reporting. Plan for that before the first delivery.

Hazards & Safe Handling

Piperidine is highly flammable, corrosive and acutely toxic, ships at the most stringent packing group and is a controlled precursor in several jurisdictions. It must be handled by trained personnel under a proper risk assessment. The classifications below are indicative — the current SDS supplied with your consignment is the governing document.

• Acute toxicity. Piperidine is acutely toxic by oral, dermal and inhalation routes — a step above most of the aliphatic amines of comparable size. Exposure control should reflect that rather than treating it as a routine corrosive.
• Exposure control. Handle in a closed system or under local exhaust ventilation. All three exposure routes matter here, so controls need to address vapour and skin contact together.
• PPE. Chemical-resistant gloves, chemical goggles and face shield, chemical-resistant clothing, and respiratory protection suited to the task.
• Ignition control. With a flash point near 16 °C the headspace is flammable at room temperature. Vapours are heavier than air and can travel to a distant ignition source and flash back. Bonded, earthed and explosion-proof equipment throughout.
• Incompatibilities. Strong oxidising agents, strong acids, acid chlorides, nitrites, mercury, and copper, brass, bronze and aluminium equipment.
• Spill response. Evacuate, eliminate ignition sources and ventilate. Contain, absorb with inert non-combustible material and collect in a labelled closed container. Do not wash to drain.
• Fire. Highly flammable. Use alcohol-resistant foam, dry chemical or carbon dioxide; cool exposed containers with water spray from a protected position. Decomposition releases nitrogen oxides — use self-contained breathing apparatus.
• First aid. Move to fresh air, remove contaminated clothing immediately, wash skin with plenty of water, flush eyes for at least 15 minutes, and seek medical attention urgently with the SDS to hand.

Regulatory & Compliance Notes

Piperidine carries more regulatory weight than almost any other amine of its size. It is a listed precursor chemical in a number of jurisdictions, which means licensing, record-keeping and reporting obligations on top of ordinary chemical control. The notes below are orientation rather than legal advice — confirm your own position with your regulatory adviser well before importing.

• Precursor controls. Piperidine is a scheduled or listed precursor chemical under drug-precursor legislation in a number of countries, including under United States legislation and comparable controls elsewhere. Expect licence requirements, end-use declarations, secure storage, inventory records and in some territories transaction reporting as a normal part of the purchase.
• Inventory status. Listed on the principal chemical inventories in the major importing regions. Ask us for the inventory confirmation relevant to your destination country.
• Import registration and prior notification. Several territories require prior notification of individual shipments in addition to a standing importer registration. These are the clearances most often missed, and they are the most common reason a piperidine consignment is held.
• Hazard communication. Supplied with an SDS compliant with the format applicable to your region, and labelled in line with the GHS classification for the product.
• Dangerous goods. UN 2401, Piperidine, Class 8 with subsidiary risk 3, Packing Group I. The stringent packing group restricts some transport options, particularly by air — plan the routing early.
• Workplace exposure. Occupational exposure limits apply in most jurisdictions. Given the acute toxicity classification, set controls against the limit rather than against the odour, which is detectable far below it.

We Supply Piperidine Worldwide

Chelora Chemicals is a supplier and export partner, not a single-plant trader. We ship Piperidine from India to customers across Asia, Europe, the Middle East, Africa, and North and South America, handling the export documentation, dangerous-goods paperwork and freight so the material arrives ready to use.

• Incoterms. EXW, FOB, CIF, CFR and DAP quoted to suit your purchasing terms and freight arrangements.
• Ports. Regular shipments through Nhava Sheva (JNPT) and Mundra, with other Indian ports arranged where it suits the routing.
• Documentation. Commercial invoice, packing list, certificate of origin, COA, SDS and dangerous-goods declaration issued as a complete set.
• Flexible volumes. A single drum for laboratory qualification, through LCL consolidations, up to repeat full loads on a supply contract.
• Supply continuity. Because we are independent of any one producer, a plant turnaround or a shipping disruption at one source does not have to become your stock-out.

Buying Piperidine from Chelora

We are an independent sourcing and supply partner. For piperidine that means the regulatory work comes first: establishing what your destination requires, confirming your licence position and preparing the documentation, before the commercial terms are even useful.

• Documentation on every lot. Batch-specific COA including residual pyridine, current SDS and TDS with the consignment.
• Precursor compliance support. Help assembling the end-use declarations and clearances your destination requires.
• Samples before commitment. Trial quantities for process qualification ahead of a commercial order, subject to the same controls.
• Quantities. From a single 160 kg drum through to IBC and contract supply.
• Export experience. Packing Group I dangerous-goods documentation, packing and labelling for sea and road freight.
• Related intermediates. Piperazine, morpholine, N-methylmorpholine, cyclohexylamine and the wider heterocyclic amine range from one supplier.

How ordering works

• Send the enquiry. Product, grade or specification, quantity, destination port and the Incoterm you buy on. If you have a spec sheet, attach it — it saves a round trip.
• We quote. Price, lead time, packing and a sample COA, normally within one working day.
• Sample and qualify. For first orders or critical applications, we send a trial quantity so your lab can sign off before you commit.
• Confirm the order. Proforma invoice issued; payment terms agreed against the volume and the relationship.
• Production and QC. Material allocated and released against a batch-specific COA, with a pre-shipment sample where the application calls for it.
• Ship and document. Packed, labelled and loaded with the full export and dangerous-goods document set, and tracked through to arrival.

Related Heterocyclic Amines & Intermediates

Buyers of piperidine usually source several of these alongside it. Consolidating them on one order cuts freight cost and gives you a single point of contact for documentation.