抱水クロラール 化学特性,用途語,生産方法
外観
無色澄明の液体
性質
2,2,2-trichloro-1,1-ethanediol．C2H3Cl3O2(165.41)．Cl3CCH(OH)2．抱水クロラールは，トリクロロアセトアルデヒドに必要量の水を加えると得られる．白色の結晶．刺激臭，苦味がある．融点57 ℃，沸点98 ℃．沸点でクロラールと水に分解する．水に易溶，エタノール，エーテル，クロロホルムに可溶．トリクロロアセトアルデヒド (クロラール) の水和物であり，加熱すると 96℃でクロラールと水に分解する。不安定なクロラールの保存形態として利用される。アルカリを作用させるとクロロホルムを生成し，アンモニア性硝酸銀を還元する．LD50 1100 mg/kg(マウス，経口)．
溶解性
水に易溶, エタノール, エーテルに可溶。水に極めて溶けやすく、エタノール及びアセトンに溶けやすい。
用途
睡眠?抗痙攣剤(有機化合物辞典(1985))GLUE PEPTIZING AGENT; MEDICINE (SEDATIVE), MANUFACTURE OF DDT, LINAMENTS. ; MANUFACTURE OF DICHLOROACETIC ACID IN THE LABORATORY.(HSDB(2010))
医薬用
抱水クロラールは，睡眠・抗けいれん剤。古くから合成されており、日本薬局方には第一版より収載されている。バルビツール酸系睡眠剤が開発される以前には繁用されたが、現在ではまれにしか用いられない。小児のけいれん抑止、催眠・鎮静を目的とし、直腸から注入する。内服では胃粘膜を刺激するので、大量の水とともに服用する。劇薬。極量は1回2グラム、1日5グラム。［幸保文治］
効能
抗不安薬, 催眠鎮静薬
商品名
エスクレ (久光製薬); エスクレ (久光製薬)
使用上の注意
強い吸湿性があり、強酸化剤と激しく反応する。
説明
Chloral hydrate is one of the oldest sedatives used for dental sedation. It was first synthesized in 1832 by Justus von Liebig and was the first synthetic central nervous system (CNS) depressant. It was used to treat delirium tremens, insomnia, and anxiety, although it is considered an unapproved drug by the US Food and Drug Administration. Initially considered to be a safer alternative to opium, it was noted to produce rapid unconsciousness when combined with ethanol. Physical dependence can occur with chronic use.
Chloral hydrate is classified as a sedative-hypnotic and is known to induce sleep in children. It has been very popular in pediatric dentistry since the mid-1950s. Chloral hydrate is rapidly absorbed following oral administration and is converted through its first pass in the liver to trichloroethanol，its active form. Trichloroethanol is conjugated in the liver and excreted in the urine. Like other agents that are metabolized in the liver, chloral hydrate may interact with other drugs, herbs, or foods resulting in clinically significant alterations of the agents (e.g.,warfarin).
使用
Trichloroacetaldehyde Hydrate is a useful chemical reagent used as a sedative/hypnotic agent for the short-term treatment of insomnia. First developed in 1832, chloral hydrate is the oldest sleep medication still in use today. This medication is also used to calm you just before surgery or other procedures. It works by affecting certain parts of the brain to cause calmness.
Studies have shown that when used in pediatric sedation side effects such as hallucination, excessive sleep and seizures were observed. Drowsiness and trouble waking up in the morning, nausea, vomiting, stomach pain, diarrhea, and headache may occur. Stomach problems can be reduced by taking chloral hydrate with a full glass of water. It is sometimes administered to patients being treated with cyclophosphamide and it is known to inhibit some aldehyde dehydrogenases.
Besides, Chloral hydrate is a starting point for the synthesis of other organic compounds. It is the starting material for the production of chloral, which is produced by the distillation of a mixture of chloral hydrate and sulfuric acid, which serves as the desiccant.
定義
ChEBI: Chloral hydrate is an organochlorine compound that is the hydrate of trichloroacetaldehyde. It has a role as a sedative, a general anaesthetic, a mouse metabolite and a xenobiotic. It is an organochlorine compound, an aldehyde hydrate and an ethanediol.
生物学の機能
Chloral hydrate (Noctec, Somnos) was developed in
the late 1800s and is still used as a sedative–hypnotic
agent. It is a hydrated aldehyde with a disagreeable
smell and taste that is rapidly reduced in vivo to
trichloroethanol, which is considered to be the active
metabolite. It produces a high incidence of gastric irritation
and allergic responses, occasionally causes cardiac
arrhythmias, and is unreliable in patients with liver
damage.
一般的な説明
Chloral hydrate, trichloroacetaldehydemonohydrate, CCl
3CH(OH)
2 (Noctec), is analdehyde hydrate stable enough to be isolated. The relativestability of this gem-diol is largely a result of an unfavorabledipole–dipole repulsion between the trichloromethyl carbonand the carbonyl carbon present in the parent carbonylcompound.
Chloral hydrate is unstable in alkaline solutions, undergoingthe last step of the haloform reaction to yield chloroformand formate ion. In hydroalcoholic solutions, it formsthe hemiacetal with ethanol. Whether or not this compoundis the basis for the notorious and potentially lethal effect of the combination of ethanol and chloral hydrate (the “MickeyFinn”) is controversial. Synergism between two differentCNS depressants also could be involved. Additionally,ethanol, by increasing the concentration of nicotinamideadenine dinucleotide (NADH), enhances the reduction ofchloral to the more active metabolite trichloroethanol, andchloral can inhibit the metabolism of alcohol because it inhibitsalcohol dehydrogenase. Chloral hydrate is a weak acidbecause its CCl
3 group is very strong electron withdrawing.A 10% aqueous solution of chloral hydrate has pH 3.5 to4.4, which makes it irritating to mucous membranes in thestomach. As a result, GI upset commonly occurs for thedrug if undiluted or taken on an empty stomach. Chloral hydrateas a capsule, syrup, or suppository is currently available.
空気と水の反応
Water soluble.
反応プロフィール
Chloral hydrate is incompatible with alkalis, alkaline earth metals, alkali carbonates and soluble barbiturates. Chloral hydrate is decomposed by sodium hydroxide. Chloral hydrate reduces ammoniacal silver nitrate. Chloral hydrate liquefies when triturated with an equal quantity of menthol, camphor or thymol. . Reaction of Chloral hydrate with hydroxylamine produces toxic hydrogen cyanide gas, Org. Synth., 1941, Vol. 1, 377.
危険性
Overdose toxic, hypnotic drug, dangerous
to eyes. Probable carcinogen.
火災危険
Flash point data for Chloral hydrate are not available; however, Chloral hydrate is probably combustible.
臨床応用
Although it is suggested that chloral hydrate per semay act as a hypnotic,chloral hydrate is very quickly convertedto trichloroethanol, which is generally assumed toaccount for almost all of the hypnotic effect. Thetrichloroethanol is metabolized by oxidation to chloral andthen to the inactive metabolite, trichloracetic acid, which is also extensively metabolized to acylglucuronidesvia conjugation with glucuronic acid. It appears tohave potent barbiturate-like binding to GABA
Areceptors.Although an old drug, it still finds use as a sedative in nonoperatingroom procedures for the pediatric patient.
安全性プロファイル
A human poison by
ingestion and possibly other routes. Poison
experimentally by ingestion, intravenous,
and rectal routes. Moderately toxic by
subcutaneous, parenteral, and intraperitoneal
routes, Experimental reproductive effects.
Human systemic effects by ingestion:
general anesthetic, cardiac arrhythmias,
blood pressure depression, eye effects,
coma, pulse rate increase, arrhythmias.
Human mutation data reported.
Questionable carcinogen with experimental
carcinogenic and tumorigenic data by skin
contact. A sedative, anesthetic, and narcotic.
Combustible when exposed to heat or
flame. When heated to decomposition it
emits toxic fumes of Cl-.
職業ばく露
Chloral is used as an intermediate
in the manufacture of such pesticides as DDT, methoxychlor, DDVP, naled, trichlorfon, and TCA. Chloral is
also used in the production of chloral hydrate; used as
a therapeutic agent with hypnotic, sedative, and narcotic
effects; used in a time prior to the introduction of
barbiturates
発がん性
Chloral hydrate has not been adequately tested for teratogenicity,
reproductive effects, or chronic toxicity. Similarly, no
histological evaluations have been conducted.
環境運命予測
Chloral hydrate is a CNS depressant, but its mechanism of
action is not well known. Coingestion with ethanol produces
enhanced effects by several mechanisms. First, ethanol
competes for alcohol and aldehyde dehydrogenase, which then
prolongs the half-life of ethanol. The metabolism of ethanol
generates the reduced form of NADH, which is a cofactor for
the metabolism of chloral hydrate to its active metabolite
trichloroethanol. Finally, ethanol inhibits the conjugation of
trichloroethanol to its inactive form urochloralic acid. This
results in enhanced CNS depression.
輸送方法
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
不和合性
Chloral hydrate reacts with strong bases
forming chloroform. Contact with acids, or exposure to
light may cause polymerization. Reacts with water, forming
chloral hydrate. Reacts with oxidizers, with a risk of fire or
explosions.
廃棄物の処理
Incineration after mixing with
another combustible fuel; care must be taken to assure complete combustion to prevent phosgene formation; an acid
scrubber is necessary to remove the halo acids produced.
抱水クロラール 上流と下流の製品情報
原材料
準備製品
クロラール
5-メトキシ-1H-インダゾール-3-カルボン酸
テニダプ
エトドラク
6-ブロモイサチン
タクリン
5-メトキシイサチン
2-アミノ-5,6-ジクロロ安息香酸
トリクロロ酢酸
クロフェノタン
2-Oxiranecarboxylicacid, 3-(trichloromethyl)-, ethyl ester
5-クロロ-1H-インドール-2,3-ジオン
ジクロラール尿素
1H,1H,9H-ヘキサデカフルオロ-1-ノナノール
4,7-ジフルオロインドリン-2,3-ジオン
5,6-ジフルオロインドリン-2,3-ジオン
2,2,3,3,4,4,4-ヘプタフルオロ-1-ブタノール