Benzylic chloroformates

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

Chloroformates are shipped in nonretumable 208-L (55-gal) polyethylene dmms with carbon steel overpacks or high density polyethylene dmms. Eor bulk shipments, insulated stainless-steel tank containers and tmcks provide secure protection. Tank tmck and rail car quantities are shipped using equipment dedicated for these types of products. Materials such as isopropyl chloroformate, benzyl chloroformate, and j -butyl chloroformate that require refrigeration are precooled when shipped in bulk containers. Bulk shipments that are precooled must proceed to the destination without layover. Dmm shipments of IPCE, BCE, and SBCE must be shipped in refrigerated containers. Many of the chloroformates are only shipped in tmck load shipments. The U.S. Department of Transportation (DOT) Hazardous Materials Regulations control the shipments of chloroformates, as described in Table 3. 

Nearly all of the benzyl chloride [100-44-7], henzal chloride [98-87-3], and hen zotrichl oride /P< -(97-i manufactured is converted to other chemical intermediates or products by reactions involving the chlorine substituents of the side chain. Each of the compounds has a single primary use that consumes a large portion of the compound produced. Benzyl chloride is utilized in the manufacture of benzyl butyl phthalate, a vinyl resin plasticizer benzal chloride is hydrolyzed to benzaldehyde hen zotrichl oride is converted to benzoyl chloride. Benzyl chloride is also hydrolyzed to benzyl alcohol, which is used in the photographic industry, in perfumes (as esters), and in peptide synthesis by conversion to benzyl chloroformate [501-53-1] (see Benzyl ALCOHOL AND p-PHENETHYL ALCOHOL CARBONIC AND CARBONOCm ORIDIC ESTERS). 

A benzyl carbonate was prepared in 83% yield from the sodium alkoxide of glycerol and benzyl chloroformate (20°, 24 h). It is cleaved by hydrogenolysis (H2/ Pd-C, EtOH, 20°, 2 h, 2 atm, 76% yield) and electrolytic reduction (-2.7 V, R4N X, DMF, 70% yield). A benzyl carbonate was used to protect the hy-droxyl group in lactic acid during a peptide synthesis. 

Benzoyl chloride Benzyl bromide Benzyl chloride Benzyl chloroformate... 

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Ammonium thiocyanate Anisoyl chloride Benzhydry bromide (diphenyl methyl bromide) Benzoyl chloride Benzyl bromide Benzyl chloride Benzyl chloroformate (benzyl chlorocarbonate) Butyl acid phosphate Chloracetyl chloride... 

Benzyl alcohol, 23, 14 Benzylamini, a-METHYL-, 23, 68 Benzyl carbamate, 23,14 Benzyl chloride, 21, 99 Benzyl chloroformate, 23,13 Benzyl cyanide, 23, 71... 

B) Benzyl Carbamate.—A measured aliquot (suitably 10 cc.) of the solution of benzyl chloroformate, prepared as described above, is added slowly and with vigorous stirring to five volumes of cold concentrated ammonium hydroxide (sp. gr. 0.90), and the reaction mixture is allowed to stand at room temperature for thirty minutes. The precipitate is filtered with suction, washed with cold water, and dried in a vacuum desiccator. The yield of practically pure benzyl carbamate, melting at 85-86°, is 7.0-7.2 g. (91-94 per cent of the theoretical amount based on the benzyl alcohol used in. 4). Pure benzyl carbamate melting at 87° is obtained by recrystallizing the slightly impure material from two volumes of toluene. 

C) Carbobenzoxyglycine.—A solution of 7.5 g. (0.1 mole) of glycine in 50 cc. of 2 N sodium hydroxide is placed in a 200-cc. three-necked flask fitted with a mechanical stirrer and two dropping funnels. The flask is cooled in an ice bath, and 17 g. (0.1 mole) of benzyl chloroformate (21-24 g. of the solution obtained in A) and 25 cc. of 4 iV sodium hydroxide are added simultaneously to the vigorously stirred solution over a period of twenty to twenty-five minutes. The mixture is stirred for an additional ten minutes. The toluene layer is separated, and the aqueous... 

Carbobenzoxyalanine (m.p. 114-115°) is obtained in 80-90 per cent yield from alanine and benzyl chloroformate by the same procedure. 

Benzyl chloroformate has been prepared by action of phosgene on benzyl alcohol.1 2 The methods described here for the preparation of benzyl chloroformate and the carbobenzoxy deriva-... 

After being stirred for 5 hours at room temperature, the mixture was made basic with sodium hydroxide (2.4 g). The organic solvents were removed under reduced pressure using a rotary evaporator. The aqueous residue was washed with diethyl ether (2 x 10 mL) and then benzyl chloroformate (3.41 g) was added. The mixture was stirred for 20 hours at room temperature. 

Dibenzyl peroxydicarbonate, (QHsCFMDCOj) (1). The reagent is obtained by reaction of benzyl chloroformate with H202 in a basic medium. It is stable to water and is not readily detonated. 

Acetyl bromide, 0728 f Acetyl chloride, 0735 f Aciyloyl chloride, 1093 Azidocarbonyl fluoride, 0339 Benzenesulfinyl chloride, 2234 Benzenesulfonyl chloride, 2235 Benzoyl chloride, 2675 Benzyl chloroformate, 2931... 

During the preparation of aryl chloroformates, it is essential to keep the reaction mixture really cold during water washing to prevent vigorous decomposition. Phenyl and naphthyl chloroformates may be distilled, but benzyl chloroformate is too thermally unstable. 

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