ニコチン 化学特性,用途語,生産方法
発見
ニコチン，ピリミジンアルカロイドの一つで、1809年にタバコの煙より初めて単離され、ポルトガル大使で、喫煙の風習をフランスに導入し流行させたニコJean Nicot（1530？―1600）にちなんで命名された。純粋なニコチンは無色・無臭・揮発性の油状液体で、水、アルコール、エーテルなどによく溶ける。沸点247℃。空気中では速やかに褐変する。この場合のタバコ臭は分解生成物による。
溶解性
水, エタノール, エーテルに可溶。アルコール, クロロホルム, エーテルに可溶、水に易溶。
解説
(S)-3-(1-methylpyrrolidin-2-yl)pyridine．C10H14N2(162.24)．ナス科タバコNicotiana tabacumにリンゴ酸塩またはクエン酸塩として含有されるピリジンアルカロイドの代表．タバコ葉に石灰乳を加えて塩基を遊離させ，水蒸気蒸留して，留出液をエーテルで抽出する．また，合成のDL-ニコチンをD-酒石酸塩として分割し，天然品と同一のL-ニコチンを得ることができる．特異臭のある無色の液体．沸点247 ℃．d204 1.0097．n20D 1.5282．[α]20D－169°(水)．pK1 6.16，pK2 10.96．吸湿性が強く，空気中で褐色にかわる．水，エタノールに可溶．中枢および末梢神経を興奮させ，腸および血管の収縮により血圧を上昇させる．さらに，おう吐，精神錯乱，けいれんを起こし，ヒトに対しては40 mg で死に至らしめる．気化ニコチンは毒性が強いので，硫酸ニコチンを石灰乳とまぜて殺虫用農薬や家畜用駆虫剤として用いる．LD50 50 mg/kg(ラット，経口)．森北出版「化学辞典（第2版）
用途
殺虫剤、殺菌剤
毒性
ニコチンは，猛烈な神経毒で、交感神経および副交感神経の神経節を刺激し、のちに麻痺(まひ)させる。その作用はシアン化物と同じくらい速く、成人の経口致死量は0.06グラムで、これは1本の葉巻タバコに含まれる量にほぼ相当するが、喫煙による摂取量ははるかに少ない。喫煙の習慣はほとんど精神的な欲求によるもので嗜癖(しへき)はみられない。ただし慢性中毒になると、咽頭(いんとう)や喉頭(こうとう)などのカタルをはじめ、心臓障害、視力減弱、めまい、動脈硬化などの症状がみられる。一方ニコチンは、ビタミンB1の合成原料として使われるほか、その硫酸塩は農業用殺虫剤として温室をいぶして駆虫するのに用いられる。
効能
禁煙補助薬
農薬用途
殺虫剤
商品名
ニコチネル (グラクソ・スミスクライン・コンシューマー・ヘルスケア・ジャパン)
説明
Nicotine is an alkaloid obtained from the dried leaves
of Nicotiana tabacum and Nicotiana rustica. Nicotine
stimulates acetylcholine receptors of the postsynaptic
membrane at nerve synapses resulting in depolarization
of the membrane. Toxic doses cause stimulation that is
rapidly followed by blockade of nerve transmission.
化学的特性
Nicotine is a pale yellow to dark brown, oily
liquid. Slight, fishy or pyridine-like odor when warm. It is
also available as a powder.
使用
(S)-(-)-Nicotine is a prototype nicotinic acetylcholine receptor agonist. (S)-(-)-Nicotine is the naturally occurring isomer. Nicotine can be absorbed through the alimentary canal, respiratory tract and intact skin. Nicotine is used in the treatment of smoking withdrawal syndrome. Nicotine has been used as an anthelmintic.
定義
ChEBI: An optically active form of nicotine having S-configuration.
調製方法
The nicotine molecule consists of a pyrrolidine ring attached to a pyridine ring by a bondbetween carbon atoms in the two-ring systems. Nicotine was isolated in impure form fromtobacco in 1809 by Louis Nicholas-Vauquelin (1763–1829). Vauquelin called the substancenicotianine. In 1826, Wilhelm Posselt (1806–1877) and Karl Ludwig Reimann (1804–1872),medical students at Heidelberg University, isolated pure nicotine and published dissertationson its pharmacology in 1828. Louis Henri Melsens (1814–1886) determined nicotine’sempirical formula. Amé Pictet (1857–1937) and P. Crépieux reported the synthesis of nicotine in 1903.
一般的な説明
Liquids. Toxic by inhalation, ingestion, and skin absorption. More dense than water. Flash points usually below 140°F. Contact may irritate skin, eyes, and mucous membranes. If available, obtain the technical name of the material from the shipping papers and contact CHEMTREC, (800-424-9300) for specific response information.
空気と水の反応
Flammable. Slightly soluble in water.
反応プロフィール
An alkaloid produced from tobacco. Colorless, oily liquid, combustible, highly toxic. When heated to decomposition L-Nicotine emits very toxic fumes of carbon monoxide and oxides of nitrogen [Lewis, 3rd ed., 1993, p. 919].
危険性
Toxic by ingestion, inhalation, and skin
absorption. Gastrointestinal damage, central nervous system impairment, and cardiac impairment
健康ハザード
L-Nicotine is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg or a taste (less than 7 drops) for a 70 kg (150 lbs.) person. It may be assumed that ingestion of 40-60 mg of nicotine is lethal to humans. There is fundamental difference between acute toxicity from use of nicotine as insecticide or from ingestion, and chronic toxicity that may be caused by prolonged exposure to small doses as occurs in smoking. Maternal smoking during pregnancy is associated with increased risk of spontaneous abortion, low birth weight and still-birth. Nicotine was found as a co-carcinogen in animals.
火災危険
There is a moderate explosion hazard when exposed to heat or flame. When heated to decomposition, L-Nicotine emits nitrogen oxides, carbon monoxide and other highly toxic fumes. Avoid oxidizing materials. Stable under normal conditions. Avoid heat or flames.
农业用途
Insecticide: Nicotine is used in some drugs and insecticides.
Classified for restricted use as an insecticide, limited to use
by or under the direct supervision of a certified applicator.
Not listed for use in EU countries. Registered for use in
the U.S. and Canada. A U.S. EPA restricted Use Pesticide
(RUP).
製品名
BLACK LEAF®; CAMPBELL'S NICOSOAP
®; DESTRUXOL ORCHARD SPRAY®; EMONIB
®; FLUX MAAG®; FUMETO-TENDUST®; BAC®;
MACH-NIC®; NIAGARA P. A. DUST®; NICODUST®;
NICOFUME®; NICOCIDE®; ORTHO N-4 DUST®; XL
ALL INSECTICIDE®
職業ばく露
An alkaloid produced from tobacco.
Nicotine is used in some drugs; and in tanning. At one
time, nicotine was used in the United States as an insecticide
and fumigant; however, it is no longer produced or
used in the United States for this purpose.
発がん性
Nicotine has low carcinogenic
potential. One study found that diets containing
60 ppm nicotine and administered to rats for 300 days
reduced the growth rate. The authors concluded that reduced
body weight gains were only partially attributable to reduced
food intake. No pathology on the rats and no evidence of
carcinogenicity were reported. Rats were injected subcutaneously
(5 days/week) for 26 weeks followed by an approximate
2-month observation period. Similarly, dogs were
injected subcutaneously (5 days/week) for the same period.
No tumors were observed in the test animals, although
hyaline thickening and fibrosis of the vasculature of the
kidney, lung, brain, and heart were evident.
代謝経路
Nicotine has been used as an insecticide for at least 200 years but this
naturally occurring compound lacks persistence and can be hazardous in
use (Corbett et al., 1984). It has been replaced with more effective synthetic
insecticides such as those in the neonicotinoid class. Most of the mformation
on metabolism derives from research into the fate of nicotine after
tobacco smoking as well as from the use of nicotine in agriculture and
horticulture or through the biosynthesis of the alkaloid by plants and
vegetables used as normal foodstuffs. Up to eight metabolites have been
isolated and identified in man with six primary pathways. The main
pathway is N-carbon oxidation of the pyrrolidine ring to form cotinine,
others being N-oxidation of the pyrrolidine ring to form nicotine N-oxide,
N-methylation of the pyridine ring to form an N-methylnicotinium ion
and N-demethylation of the pyrrolidine ring to form nornicotine. Two
other pathways are formation of a nicotine enamhe and of a nicotine
glucuronide (Gabrielsson and Gumbleton, 1993). There is little information
on the fate of nicotine in soil.
代謝
Nicotine is well absorbed from the mucous membranes
in the oral cavity, gastrointestinal tract, and respiratory
system. If tobacco smoke is held in the mouth for 2 seconds,
66 to 77% of the nicotine in the smoke will be absorbed
across the oral mucosa. If tobacco smoke is inhaled,
approximately 90 to 98% of the nicotine will be
absorbed. Nicotine is distributed throughout the body,
readily crossing the blood-brain and placental barriers.
The liver, kidney, and lung metabolize approximately 80
to 90% of the alkaloid. The kidney rapidly eliminates
nicotine and its metabolites.
輸送方法
UN1654 Nicotine, Hazard Class: 6.1; Labels:
6.1-Poisonous materials.
純化方法
(-)-Nicotine is a very pale yellow hygroscopic oil with a characteristic odour (tobacco extract) which turns brown in air on exposure to light. It is purifed by fractional distillation under reduced pressure in an inert atmosphere. A freshly distilled sample should be stored in dark sealed containers under N2. It is a strong base; a 0.05 M aqueous solution has a pH of 10.2. It is very soluble in organic solvents. It is soluble in H2O and readily forms salts. [UV: Parvis J Chem Soc 97 1035 1910, Dobbie & Fox J Chem Soc 103 1194 1913.] The hydrochlorides (mono-and di-) form deliquescent crystals soluble in H2O and EtOH but insoluble in Et2O. It has also been purified via the ZnCl2 double salt. [Ratz Monatsh Chem 26 1241 1905, Biosynthesis: Nakan & Hitchinson J Org Chem 43 3922 1978.] The picrate has m 218o (from EtOH). [Beilstein 23/6 V 64.] POISONOUS.
不和合性
Incompatible with strong 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. Incompatible with
strong acids. Attacks some forms of plastics, rubber, and
coatings.
廃棄物の処理
Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator
equipped with an afterburner and scrubber. All federal,
state, and local environmental regulations must be
observed. In accordance with 40CFR165, follow
recommendations for the disposal of pesticides and pesticide
containers. Must be disposed properly by following
package label directions or by contacting your local or
federal environmental control agency, or by contacting
your regional EPA office. Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contaminant
(≥100 kg/mo) must conform with EPA regulations
governing storage, transportation, treatment, and waste
disposal.
参考文献
Pictet, Rotschy., Ber., 33, 2533 (1900)
Tschitschibabin, Buchholz.,J. Russ. Phys. Chern. Soc., 50, 548 (1920)
Spath, Biniecki., Ber., 72, 1809 (1939)
Shmuk, Borozdina., CampI. rend. Acad. Sci., USSR, 12,1582 (1939)
Shmuk, Borozdina., J. Appl. Chern. Russ., 14,864 (1941)
Smith, Smith., J. Agric. Res., 65, 347 (1942)
Pal, Narasinham.,!. Ind. Chern. Soc., 20, 181 (1943)
Marion., Can. J. Res., 23B, 165 (1945)
Bottomley, Nottle, White., Austral. J. Sci., 8, 18 (1945)
Biosynthesis:
Leete.,!. Amer. Chern. Soc., 89,7081 (1967)
14C-NMR spectrum:
Ganz, Kelsey, Geiling., Bot. Gaz., 113, 195 (1951)
13C-NMR spectrum:
Crain, Wilderman, Roberts., J. Amer. Chern. Soc., 93,990 (1971)
Pharmacology :
Rolleston., Lancet., 210,961 (1926)
Laessing., Med. Welt., 12, 1485 (1938)
Coon, Rothman., Proc. Soc. Exp. Bioi. Med., 42, 231 (1939)
Straub, Amann., Klin. Woch., 19,169 (1940)
Coon, Rothman., J. Pharm. Exp. Ther. Froc., 72, 9 (1941)
Perlman, Dannesborg, Sokoloff., J. Amer. Med. Assoc., 120, 1003 (1942)
Roth, McDonald, Sheard., ibid, 125,761 (1944)
Burn, Truelove, Burn., Brit. Med. J., i, 403 (1945)
ニコチン 上流と下流の製品情報
原材料
準備製品