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外観
無色～ほとんど無色, 澄明の液体
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種類
ピペリジンは、主に研究??開発用試薬として販売されています。通常、ガラス瓶で販売され、25mL , 100mL , 500mLなどの種類があります。
常温保存可能な試薬として取り扱われますが、人体への有害性があり、また引火性も高い液体です。取り扱いの際は注意が必要です。
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性質
ピペリジンは、引火性の高い液体です。蒸気は空気より重いため、遠距離発火することもあります。燃焼すると分解し、分解生成物は窒素酸化物などの有毒ガスを発します。そのため、消防法においては、第4類引火性液体、第一石油類水溶性液体に指定されている化合物です。
人体に対しては有毒で、特に目、皮膚、気道に対して腐食性を示します。高濃度の蒸気を吸入すると肺水腫を起こすことがあります。
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溶解性
水に混和, アルコール, エーテル, ベンゼン, クロロホルムに可溶。水に極めて溶けやすく、エタノールに溶ける。
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解説
ピペリジン．アザシクロヘキサンともいう．ピリジンを接触還元するか，ペンタメチレンジアミンの塩酸塩を蒸留してつくる．アンモニア臭のある無色の液体．融点－13 ℃，沸点106 ℃．d2040.8622．n20D1.4534．pKa 11.2(25 ℃)．水，有機溶媒に可溶．強塩基性があるので空気中の二酸化炭素を吸収する．引火性がある．皮膚や口からの吸入は有毒．溶剤，エポキシ樹脂の硬化剤，有機合成，医薬原料に用いられる．ピペリン(コショウの辛味成分であるアルカロイド)をアルコール中で水酸化カリウムと加熱分解すると得られることから，ピペリジンの名称が与えられた。ピリジンをニッケルまたはルテニウム触媒上で水素化して作る。塩基解離指数pKb＝2.88で，ジエチルアミン(C2H5)2NH(pKb＝3.07)よりも少し強い塩基性を示し，脂肪族第二アミンと同様の反応を行う。
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用途
染色、医薬原料、ゴム薬品
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用途
ペプチド合成用溶媒。
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用途
ゴムの加硫促進剤や血管拡張剤原料の製造、溶剤など、溶剤、エポキシ樹脂硬化剤など
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使用上の注意
不活性ガス封入
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化学的特性
Piperidine is a clear, colorless liquid. Pepper, ammonia or amine odor.
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天然物の起源
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).
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使用
Piperidine is an organic heterocyclic amine widely used as building block and reagent in the synthesis of organic compounds including pharmaceuticals.
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主な応用
The secondary amine piperidine is highly reactive and is therefore frequently employed as an intermediate for pharmaceuticals and for plant protection agents. It is also used as a vulcanization accelerator in rubber manufacture and as an oil or fuel additive. Piperidine and, in many cases, piperidine acetate are useful catalysts for condensation reactions, e.g., the Knoevenagel reaction, aldol condensation, and the condensation of a nitroparaffin with an aldehyde. However, for the last of these reactions, diethylamine is the preferred catalyst. The use of piperidine is particularly advisable where the reactants or products are unstable in the presence of stronger bases.
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調製方法
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).
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製造方法
Usually prepared by electrolytic reduction of pyridine.
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定義
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
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一般的な説明
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.
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空気と水の反応
Highly flammable. Miscible in water.
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反応プロフィール
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.
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健康ハザード
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).
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火災危険
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.
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化学反応
ピペリジンは、ケトンをエナミンに変換する反応に広く使用されています。生成するエナミンの代表的な利用方法として、Storkエナミン反応があります。
この反応は、生成したエナミンをアルキルハライド、アシルハライド、Michealアクセプターなどの求電子剤と反応させることにより、α置換を行うものです。置換基の挿入後、加水分解を行うことにより、エナミンを再びケトンへと変換することができます。また、有機合成化学では、溶媒や塩基として広く使用されています。
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使用用途
ピペリジンの主な用途は、ゴムの加硫促進剤や溶剤、エポキシ樹脂の硬化剤などです。非常に単純な分子構造を持つため、様々な医薬品の部分構造になっています。代表的なものとして、モルヒネ、ピチジン、フェンタニルが挙げられます。
また、実験室におけるピペリジンの重要な用途の一つが、ペプチド固相合成における脱保護反応です。
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工業用途
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).
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安全性プロファイル
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.
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職業ばく露
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.
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発がん性
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.
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製造方法
ピペリジンは、工業的にはピリジンの還元によって製造されます。代表的なものは、硫化モリブデン (IV) 触媒を用いた、水素化反応です。
また、、金属ナトリウム、液体アンモニアを用いた、Birch還元によってもピリジンをピペリジンに還元することができます。
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代謝
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).
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合成方法
ピリジンを酸化白金またはスポンジニッケルの触媒存在下で水素添加して得られる
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輸送方法
UN2401 Piperidine, Hazard Class: 8; Labels: 8-Corrosive material, 3-Flammable liquid.
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純化方法
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
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不和合性
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.
