| Identification | More | [Name]
Benzyl chloroformate | [CAS]
501-53-1 | [Synonyms]
BCF
BENZYLOXYCARBONYL CHLORIDE
CARBOBENZOXY CHLORIDE
CARBONOCHLORIDE ACID BENZYL ESTER
CARBONOCHLORIDIC ACID, PHENYLMETHYL ESTER
CBZ
CBZ CHLORIDE
CBZ-CL
CHLOROCARBONYL ACID BENZYL ESTER
CHLOROFORMIC ACID BENZYL ESTER
Z-CHLORIDE
Z-CL
Benzyl carbonochloridate
Benzyl chloridocarbonate
Benzyl chlorocarbonate
benzylcarbonochloridate
Benzylcarbonyl chloride
benzylcarbonylchloride
benzylchlorocarbonate
Bzcf | [EINECS(EC#)]
207-925-0 | [Molecular Formula]
C8H7ClO2 | [MDL Number]
MFCD00000640 | [Molecular Weight]
170.59 | [MOL File]
501-53-1.mol |
| Chemical Properties | Back Directory | [Appearance]
light yellow liquid | [Melting point ]
-20 °C
| [Boiling point ]
103 °C20 mm Hg(lit.)
| [density ]
1.212 g/mL at 20 °C
| [vapor density ]
1 (vs air)
| [vapor pressure ]
1.39 psi ( 20 °C)
| [refractive index ]
n20/D 1.519(lit.)
| [Fp ]
197 °F
| [storage temp. ]
2-8°C
| [solubility ]
Miscible with ether, acetone and benzene. | [form ]
Solution | [color ]
slightly yellow to slightly pink | [Odor]
Irritating; sharp, penetrating. | [Stability:]
Stable. Incompatible with water, oxidizing agents. Combustible. | [Water Solubility ]
decomposes | [Sensitive ]
Moisture Sensitive | [Detection Methods]
T | [Merck ]
14,1801 | [CAS DataBase Reference]
501-53-1(CAS DataBase Reference) | [NIST Chemistry Reference]
Benzyl chloroformate(501-53-1) | [Storage Precautions]
Moisture sensitive | [EPA Substance Registry System]
501-53-1(EPA Substance) |
| Safety Data | Back Directory | [Hazard Codes ]
T,C,N,F | [Risk Statements ]
R45:May cause cancer.
R20:Harmful by inhalation.
R34:Causes burns.
R48/22:Harmful: danger of serious damage to health by prolonged exposure if swallowed .
R50/53:Very Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment .
R67:Vapors may cause drowsiness and dizziness.
R65:Harmful: May cause lung damage if swallowed.
R63:Possible risk of harm to the unborn child.
R48/20:Harmful: danger of serious damage to health by prolonged exposure through inhalation .
R11:Highly Flammable. | [Safety Statements ]
S53:Avoid exposure-obtain special instruction before use .
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S60:This material and/or its container must be disposed of as hazardous waste .
S61:Avoid release to the environment. Refer to special instructions safety data sheet .
S62:If swallowed, do not induce vomiting: seek medical advice immediately and show this container or label .
S46:If swallowed, seek medical advice immediately and show this container or label .
S36/37:Wear suitable protective clothing and gloves . | [RIDADR ]
UN 2924 3/PG 2
| [WGK Germany ]
3
| [RTECS ]
LQ5860000
| [F ]
19 | [Autoignition Temperature]
590 °C | [TSCA ]
Yes | [HazardClass ]
8 | [PackingGroup ]
I | [HS Code ]
29159000 | [Hazardous Substances Data]
501-53-1(Hazardous Substances Data) | [Toxicity]
LD50 orally in Rabbit: 3000 mg/kg |
| Hazard Information | Back Directory | [Description]
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. | [Chemical Properties]
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. | [Uses]
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. | [Application]
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. | [Preparation]
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. | [General Description]
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. | [Air & Water Reactions]
Decomposes in moist air. Decomposes slowly in water to give corrosive hydrochloric acid and organic acids. | [Reactivity Profile]
Benzyl chloroformate(501-53-1) 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]. | [Hazard]
Highly toxic, emits very toxic phosgene fumes at 100C. Irritant to eyes. | [Health Hazard]
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. | [Safety Profile]
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. | [Synthesis]
Benzyl chloroformate (CbzCl) was synthesized by combining the carbonylation of benzyl alcohol with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of DBU, with the chlorination using sulfuryl chloride.
https://doi.org/10.1016/S0040-4039(02)01834-8 | [storage]
Store at temperature at or below –15°C (5°F) in a dry, well‐ventilated location. All equipment and storage vessels must be constructed of Teflon or glass‐lined steel. Keep container tightly closed. Protect from sunlight and avoid any contact with iron.Product is stable when stored properly at recommended storage temperature. Storage in recommended temperatures and conditions will ensure product quality for minimum 12 months before retesting may be needed to determine assay. Storage in conditions between –15°C (5°F) and –5°C (23°F) may require retesting after 6 months to determine assay. Storage above 0°C (32°F) not recommended. | [Purification Methods]
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. |
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