501-53-1 Usage
Description
Benzyl chloroformate, also known as benzyl chlorocarbonate or Z-chloride, is the benzyl ester of chloroformic acid. It can be 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. Benzyl chloroformate was first prepared by Leonidas Zervas in the early 1930s and is often used for amine group protection.
Uses
Used in Plastic Industry:
Benzyl chloroformate is used as a reactive chemical intermediate for the introduction of carboxybenzyl (Cbz) protecting group for amines such as aniline in organic synthesis, which is essential in the production of certain plastics.
Used in Pharmaceutical Industry:
Benzyl chloroformate is used as a reagent in peptide synthesis to protect the amine functionality as the benzyloxycarbonyl (Cbz or Z) derivative. This protection is crucial for the controlled synthesis of peptides and pharmaceutical compounds.
Used in Agricultural Industry:
Benzyl chloroformate is utilized as a chemical intermediate in the synthesis of various agricultural chemicals, contributing to the development of new and improved products for the industry.
Used in Organic Chemicals:
Benzyl chloroformate is involved in the synthesis of 1,2,4-oxadiazoles, which are important organic compounds with various applications in different fields.
Used in Peptide Synthesis:
Benzyl chloroformate is used as a protecting reagent in peptide synthesis, where it helps protect amino groups during the synthesis process, ensuring the successful formation of the desired peptide.
Preparation
Benzyl chloroformate is prepared in the lab by treating benzyl alcohol with phosgene:PhCH2OH + COCl2→ PhCH2OC(O)Cl + HClPhosgene 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.
Air & Water Reactions
Decomposes in moist air. Decomposes slowly in water to give corrosive hydrochloric acid and organic acids.
Reactivity Profile
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].
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.
Check Digit Verification of cas no
The CAS Registry Mumber 501-53-1 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,0 and 1 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 501-53:
(5*5)+(4*0)+(3*1)+(2*5)+(1*3)=41
41 % 10 = 1
So 501-53-1 is a valid CAS Registry Number.
InChI:InChI=1/C8H7ClO2/c9-8(10)11-6-7-4-2-1-3-5-7/h1-5H,6H2
501-53-1Relevant articles and documents
COMPOUNDS AND USES THEREOF
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Page/Page column 157; 158, (2021/08/06)
The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
supporting information, p. 12324 - 12332 (2020/08/06)
Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.