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| | Piperidine Basic information |
| | Piperidine Chemical Properties |
| Melting point | -11 °C | | Boiling point | 106 °C(lit.) | | density | 0.930 g/mL at 20 °C | | vapor density | 3 (vs air) | | vapor pressure | 23 mm Hg ( 20 °C) | | FEMA | 2908 | PIPERIDINE | | refractive index | n20/D 1.452(lit.) | | Fp | 16 °C(lit.) | | storage temp. | Store in dark! | | solubility | miscible in water and alcohol; soluble in ether, acetone, benzene and
chloroform
maximum allowable concentration: not established; more toxic, irritating and
volatile than pyridine (Reinhardt and Brittelli 1981). | | pka | 11.123(at 25℃) | | PH | 12.6 (100g/l, H2O, 20°C) | | Odor | at 1.00 % in propylene glycol. heavy sweet floral animal | | Odor Type | animal | | explosive limit | 1.5-10.3%(V) | | Water Solubility | Miscible | | Sensitive | Air Sensitive | | Merck | 14,7468 | | JECFA Number | 1607 | | BRN | 102438 | | Stability: | Stable. Highly flammable. Incompatible with strong oxidizing agents, strong acids, organic acids, water. Vapours may flow along surfaces to a distant source of ignition. | | LogP | 0.61 | | CAS DataBase Reference | 110-89-4(CAS DataBase Reference) | | NIST Chemistry Reference | Piperidine(110-89-4) | | EPA Substance Registry System | Piperidine (110-89-4) |
| | Piperidine Usage And Synthesis |
| Chemical Properties | Clear or slightly yellow liquid | | Chemical Properties | Piperidine has a heavy, sweet, floral, animal odor and a burning peppery taste. | | Chemical Properties | Piperidine is a strong base (pKb = 2.88) that reacts vigorously with oxidizing
materials, is easily ignited, and forms explosive vapor concentrations at room
temperature. When heated to decomposition it gives off toxic fumes of NOx (Sax
1984). It behaves like an aliphatic secondary amine and can form complexes with
salts of heavy metals (HSDB 1988). | | Chemical Properties | Piperidine is a clear, colorless liquid. Pepper, ammonia or amine odor. | | Occurrence | Piperidine occurs at low levels in a variety of food products (Neurath et al 1977),
including baked ham (0.2 p.p.m.), milk (0.11 p.p.m.) coffee (1 p.p.m. dry) (Singer
and Lijinsky 1976) and canned fish (Tanikawa and Motohiro 1960). It is also
found in black pepper (Windholz 1983), hemp (Obata and Ishikawa 1960),
hemlock (Cromwell 1956) and tobacco (Furia and Bellanca 1975). Piperidine is a
natural constituent of skin (Sax and Lewis 1987), human urine (Von Euler 1944),
brain (Honegger and Honegger 1960) and cerebrospinal fluid (Perry et al 1964).
Humans excrete about 3-20 mg/d in the urine (Reinhardt and Britelli 1981). | | Uses | It is used in organic synthesis, especially inthe preparation of many crystalline derivativesof aromatic nitro compounds. | | Uses | Fits Applied Biosystems 431 and 433A peptide synthesizers. | | Uses | Piperidine is an organic heterocyclic amine widely used as building block and reagent in the synthesis of organic compounds including pharmaceuticals. | | Production Methods | Piperidine is usually prepared by the electrolytic reduction of pyridine. It may also
be obtained by heating piperidine with alcoholic KOH or by the cyclization of
1,5-diaminopentane hydrochloride (Windholz 1983). U.S. production in 1983 was
approximately 606,000 pounds (HSDB 1988). Commercial piperidine is supplied
in two grades, 95 and 98 percent pure (Sax and Lewis 1987). | | Definition | ChEBI: An azacycloalkane that is cyclohexane in which one of the carbons is replaced by a nitrogen. It is a metabolite of cadaverine, a polyamine found in the human intestine. | | Preparation | Usually prepared by electrolytic reduction of pyridine. | | Definition | piperidine: A saturated heterocycliccompound having a nitrogen atom ina six-membered ring, C5H11N; r.d.0.86; m.p. –7°C; b.p. 106°C. The structureis present in many alkaloids | | Brand name | Cypentil (Abbott). | | Aroma threshold values | Detection: 65.8 to 70.6 ppm | | General Description | A clear colorless liquid with a pepper-like odor. Less dense than water, but miscible in water. Will float on water. Flash point 37°F. Melting point -15.8°F (-9°C). Boiling point 222.8°F (106°C). May severely irritate skin and eyes. May be toxic by ingestion and inhalation. Vapors heavier than air. Used to make rubber and as a solvent. | | Air & Water Reactions | Highly flammable. Miscible in water. | | Reactivity Profile | 1-Oxa-4-azacyclohexane neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides. | | Health Hazard | Piperidine is a highly toxic compound. Theacute oral toxicity is high in many species oftest animals. The oral LD50 values in miceand rabbits are 30 and 145 mg/kg, respectively(NIOSH 1986). The liquid is moderatelytoxic by skin absorption. Inhalationtoxicity in experimental animals was low,however. A 4-hour exposure to 4000 ppmwas lethal to rats. Piperidine is corrosive toskin. Contact with eyes can produce severeirritation. | | Health Hazard | Strong local irritant and may cause permanent injury after short exposure to small amounts. Ingestion may involve both irreversible and reversible changes. 30 to 60 mg/kg may cause symptoms in humans. | | Health Hazard | An irritation threshold of 26 p.p.m. has been reported from studies on human
volunteers (Bazarova and Migukina 1975). Levels of 2 to 5 p.p.m. in air have been
recorded during the transfer of piperidine from drums in a semi-closed system. At
this level, the vapors were intolerable but no irritation was observed (ANON
1982). In an accidental case of skin exposure, third-degree burns developed after
only 3 min of skin contact (Linch 1965). Piperidine has a pronounced emetic effect
in humans. When administered to schizophrenic patients at doses of 1 to 6 g/d, it
was shown to cause nausea and a subjective sense of well being (Giacobini 1976;
Tasher et al 1960). The primary, but low-level, means of human exposure,
however, is from the natural piperidine content of foods (HSDB 1988). | | Fire Hazard | 1-Oxa-4-azacyclohexane evolves explosive concentrations of vapor at normal room temperatures. When heated to decomposition, 1-Oxa-4-azacyclohexane emits highly toxic fumes of nitrogen oxides. Dangerous, when exposed to heat, flame, or oxidizers. Avoid 1-Perchloryl1-Oxa-4-azacyclohexane and oxidizing materials. 1-Oxa-4-azacyclohexane is a reactive compound and forms complexes with the salts of heavy metals. 1-Oxa-4-azacyclohexane evolves explosive concentrations of vapor at normal room temperatures. Keep away from igniting sources and heat. | | Flammability and Explosibility | Highlyflammable | | Industrial uses | Piperidine is used as a solvent, a curing agent for rubber and epoxy resins, a
catalyst in silicone esters, an intermediate in organic synthesis and as a complexing
agent (HSDB 1988; Reinhardt and Britelli 1981). It is a trace constituent in oils
and fuels (Sax and Lewis 1987). It is used in the manufacture of local anesthetics,
analgesics and other pharmaceuticals, and also for wetting agents and germicides
(Gehring 1983). It is also used as a flavor additive in soups, meats, condiments,
baked goods, candy and non-alcoholic beverages at 0.05-5.0 p.p.m. (Furia and
Bellanca 1975). | | Safety Profile | Poison by ingestion,
skin contact, and intraperitoneal routes.
Moderately toxic by subcutaneous route.
Mildly toxic by inhalation. An experimental
teratogen. Experimental reproductive effects
by inhalation. A skin irritant. Mutation data
reported. A very dangerous fire hazard when
exposed to heat, flame, or oxidizers. Can
react vigorously with oxidzing materials. To
fight fire, use alcohol foam, CO2, dry
chemical. Explodes on contact with 1-
perchloryl-piperidme, dqanofurazan, N-
nitrosoacetadde. When heated to
decomposition it emits highly toxic fumes of
NOx. Used in agriculture and
pharmaceuticals, and as an intermediate for
rubber accelerators. Used in production of
drugs of abuse. | | Potential Exposure | Piperidine is used in agriculture and pharmaceuticals; intermediate for rubber accelerators; as a solvent; as a curing agent for rubber and epoxy resins; catalyst for condensation reactions; as an ingredient in oils and fuels; complexing agent; manufacture of local anesthetics; in analgesics; pharmaceuticals, wetting agents; and germicides; synthetic flavoring. Not registered as a pesticide in the Unied States. | | Carcinogenicity | No tumors were produced in
rats given piperidine (0.09%) in drinking water for
1 year. Mice receiving 19 doses of 50 mg/kg by intraperitoneal
injection within 61 weeks followed by an 18-week
observation period showed no increase in cancer incidences
(251). Piperidine and sodium nitrite given together
also failed to produce tumors. The failure of this treatment was surprising because nitrosopiperidine induced a high
incidence of lung and esophageal tumors. The authors
suggest that the relative strong basicity of piperidine
reduced the rate of reaction with nitrite to such an extent
that an ineffective amount of nitrosopiperidine was
formed. In mice that had cholesterol pellets containing
piperidine implanted in their bladders and were given
sodium nitrite in their drinking water, an increase in bladder
cancers was produced. Piperidine given as a series of
24 injections in groups of mice failed to produce lung
tumors in the strain A mouse cancer screen. When
piperidine and sodium nitrite were incubated in the isolated
rat urinary bladder, nitrosopiperidine was detected in the
bladder contents. No studies designed to evaluate the carcinogenic
potential of piperidine alone following lifetime
exposures have been reported. | | Metabolism | Piperidine is readily absorbed through the gastrointestinal tract, skin and lungs
(HSDB 1988). In hens, 35 to 70% of an injected dose is rapidly excreted
unchanged in the urine (Williams 1959; Sperber 1949). Rabbits also excrete
piperidine unchanged (Hildebrandt 1900). When injected intraventricularly into
rats, piperidine disappeared exponentially with a half-life of 20 min (Meek 1973).
In a more recent study, Okano et al (1978) found that in rats most of an i.p. dose of
[3H]-piperidine was excreted unchanged. Two major metabolites were identified
as 3- and 4-hydroxypiperidine. Both compounds were also found in untreated
animals and thus are probably metabolites of piperidine of exogenous or endogenous
origin. These metabolites represent a detoxification mechanism, since they
lack the potent pharmacological activities of the parent compound. Two unidentified
metabolites were assumed to be conjugates. In a much earlier study, Novello
et al (1926) claimed that piperidine was excreted as the ethereal sulfate. Metabolic
studies of analgesics and anesthetics containing the piperidine ring have demonstrated
the occurrence of N-hydroxylation, formation of a 6-oxo-derivative, and
C-oxidative ring cleavage (Oelschlager and Al Shaik 1985). N-nitrosopiperidine
has been synthesized from piperidine and sodium nitrite in the gastric contents,R.L. Reed
isolated stomach and isolated small intestine of rats (Alam et al 1971; Epstein
1972). | | Shipping | UN2401 Piperidine, Hazard Class: 8; Labels: 8-Corrosive material, 3-Flammable liquid. | | Purification Methods | Dry piperidine with BaO, KOH, CaH2, or sodium, and fractionally distil (optionally from sodium, CaH2, or P2O5). Purify from pyridine by zone melting. [Beilstein 22 H 6, 22 | | Incompatibilities | Piperidine is a highly flammable liquid. Vapor may form explosive mixture with air (at room temperature). A medium-strong base. Reacts violently with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides. Piperidine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides. |
| | Piperidine Preparation Products And Raw materials |
| Raw materials | Sodium-->Hydrogen-->Piperidine hydrochloride | | Preparation Products | 3-CYANO-7-METHOXYCOUMARIN-->3-(4-AMINO-PHENYL)-CHROMEN-2-ONE-->7-HYDROXY-2-OXO-2H-CHROMENE-3-CARBOXYLIC ACID METHYL ESTER-->2-Chloro-6-methyl-3-pyridinecarbonitrile-->6-BROMO-3-BUTYRYL-2H-CHROMEN-2-ONE-->3-(3-AMINOPHENYL)-2H-CHROMEN-2-ONE-->5-METHYL-4-ISOXAZOLESULFONYL CHLORIDE-->2-Amino-5-nitropyrimidine-->Minoxidil-->Bis(pentamethylene)thiuram tetrasulfide-->CLOPERASTINE-->3-ACETAMIDOCOUMARIN-->5,6,7,8-TETRAHYDRO-3H-BENZO[4,5]THIENO[2,3-D]-PYRIMIDIN-4-ONE-->RARECHEM AL BI 0736-->3-PYRIDIN-2-YL-PROPIONIC ACID H2SO4-->6-CHLORO-2-OXO-2H-CHROMENE-3-CARBOXYLIC ACID-->4-Hydroxy-3,5-dimethoxycinnamic acid-->3-ACETYL-7-HYDROXY-2H-CHROMEN-2-ONE-->trans-2,4,5-Trimethoxycinnamic acid-->Difenidol hydrochloride-->5-BROMO-2-FLUOROCINNAMIC ACID-->4-ETHOXYCINNAMIC ACID-->1-PIPERIDINEPENTANOL-->1,2,3,5-TETRAHYDRO-8-THIA-5,7-DIAZA-CYCLOPENTA[A]INDENE-4-ONE-->7-HYDROXY-2-OXO-2H-CHROMENE-3-CARBOXYLIC ACID METHYL ESTER-->3-(TRIFLUOROMETHOXY)CINNAMIC ACID-->4-Fluorocinnamic acid-->3,5-DIMETHOXYCINNAMIC ACID-->3,4-(Methylenedioxy)cinnamic acid-->2-AMINO-4-ETHYL-5-METHYL-THIOPHENE-3-CARBOXYLIC ACID METHYL ESTER-->2-AMINO-5,6-DIHYDRO-4H-CYCLOPENTA[B]THIOPHENE-3-CARBOXYLIC ACID ETHYL ESTER-->Syringaldehyde-->N-(2-Aminoethyl)piperidine-->NAPHTHALENE-2,3-DICARBOXALDEHYDE-->2-AMINO-6-METHYL-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE-->3-(3-METHYL-2-THIENYL)ACRYLIC ACID-->ETHYL 2-AMINO-4,5,6,7-TETRAHYDROBENZO[B]THIOPHENE-3-CARBOXYLATE-->2-AMINO-5,6-DIHYDRO-4H-CYCLOPENTA[B]THIOPHENE-3-CARBOXYLIC ACID METHYL ESTER-->Tolperisone hydrochloride |
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