クロロぎ酸ベンジル 化学特性,用途語,生産方法
外観
無色～うすい黄色透明液体
外観
無色～ほとんど無色透明液体
溶解性
エーテル, ベンゼン, クロロホルムに可溶。アセトンに極めて溶けやすく、水及び熱エタノールによって分解する。
用途
有機過酸化物(重合触媒)?樹脂改質剤?医薬?農薬原料 、ペプチド合成時のアミノ基ブロック剤
用途
ペプチド合成用
使用上の注意
本品は、保存中に徐々に分解して、塩化ベンジル、二酸化炭素及び塩化水素を生じる。不活性ガス封入
説明
Benzyl chloroformate, also known as benzyl chlorocarbonate or Z-chloride, is the benzyl ester of chloroformic acid. It can be also described as the chloride of the benzyloxycarbonyl (Cbz or Z) group. In its pure form it is a water-sensitive oily colorless liquid, although impure samples usually appear yellow. It possesses a characteristic pungent odor and degrades in contact with water.
The compound was first prepared by Leonidas Zervas in the early 1930s who used it for the introduction of the benzyloxycarbonyl protecting group, which became the basis of the Bergmann-Zervas carboxybenzyl method of peptide synthesis he developed with Max Bergmann. This was the first successful method of controlled peptide chemical synthesis and for twenty years it was the dominant procedure used worldwide until the 1950s. To this day, benzyl chloroformate is often used for amine group protection.
化学的特性
colorless or light yellow oily liquid with rancid odor. soluble in ether, acetone, benzene and other organic solvents. It is used to protect amino groups in peptide synthesis.
使用
Benzyl chloroformate is widely used as a reactive chemical intermediate in plastic, pharmaceutical, agricultural and organic chemicals. It is useful for the introduction of carboxybenzyl (cbz) protecting group for amines such as aniline in organic synthesis. It is also involved in the synthesis of 1,2,4-oxadiazoles.
製造方法
Benzyl chloroformate is prepared in the lab by treating benzyl alcohol with phosgene:
PhCH2OH + COCl2→ PhCH2OC(O)Cl + HCl
Phosgene is used in excess to minimise the production of the carbonate (PhCH2O)2C=O.
The use of phosgene gas in the lab preparation carries a very large health hazard, and has been implicated in the chronic pulmonary disease of pioneers in the usage of the compound such as Zervas.
主な応用
Benzyl chloroformate is used as a reagent in peptide synthesis to protect the amine functionality as the benzyloxycarbonyl (Cbz or Z) derivative.
Cbz-protected anilines were prepared directly from aromatic carboxylic acids, sodium azide and Cbz-Cl.
Protecting reagent in peptide synthesis.
一般的な説明
Benzyl chloroformate appears as a colorless liquid with an acrid odor. Vapors irritate eyes and mucous membranes. Corrosive to metals and tissue. Long-term inhalation of low concentrations or short-term inhalation of high concentrations can result in adverse health effects.
空気と水の反応
Decomposes in moist air. Decomposes slowly in water to give corrosive hydrochloric acid and organic acids.
反応プロフィール
Benzyl chloroformate decomposes slowly in water forming benzyl alcohol, HCl, and CO2. Gives off HCl fumes in moist air. Reacts with bases, both organic and inorganic. Attacks many metals especially in humid atmosphere [Handling Chemicals Safely 1980. p. 476]. Catalytic impurity incidents involving the iron catalyzed decomposition of benzoyl chloroformate have caused several explosions. The iron presumably comes from corrosion of steel storage tanks [Loss Prev. Bull., 1975, (003), 2]. May react vigorously or explosively if mixed with diisopropyl ether or other ethers in the presence of trace amounts of metal salts [J. Haz. Mat., 1981, 4, 291].
危険性
Highly toxic, emits very toxic phosgene fumes at 100C. Irritant to eyes.
健康ハザード
Inhalation causes mucous membrane irritation. Eyes are irritated by excessive exposure to vapor. Liquid causes severe irritation of eyes and irritates skin. Ingestion causes irritation of mouth and stomach.
安全性プロファイル
Poison by ingestion andinhalation routes. A powerful corrosive irritant. Thermallyunstable. Will react with water or steam to produce toxic and corrosive fumes and heat. Iron salts catalyze theexplosive decomposition of the ester. When heated todecomp.
純化方法
The commercial material is usually better than 95% pure and may contain some toluene, benzyl alcohol, benzyl chloride and HCl. After long storage (e.g. two years at 4o, Greenstein and Winitz [The Chemistry of the Amino Acids Vol 2 p. 890, J Wiley and Sons NY, 1961] recommended that the liquid should be flushed with a stream of dry air, filtered and stored over sodium sulfate to remove CO2 and HCl which are formed by decomposition. It may further be distilled from an oil bath at a temperature below 85o because Thiel and Dent [Annalen 301 257 1898] stated that benzyloxycarbonyl chloride decarboxylates to benzyl chloride slowly at 100o and vigorously at 155o. Redistillation at higher vacuum below 85o yields material which shows no other peaks than those of benzyloxycarbonyl chloride by NMR spectroscopy. [Beilstein 6 IV 2278.] LACHRYMATORY and TOXIC.
クロロぎ酸ベンジル 上流と下流の製品情報
原材料
準備製品