Benzyl chloroformate

Structural formula
General
Surname	Benzyl chloroformate
other names	Benzyl chlorocarbonate; Benzyl chloroformate; Benzyloxycarbonyl chloride; Z-chloride; CAB;
Molecular formula	C 8 H 7 ClO 2
Brief description	colorless, pungent smelling liquid
External identifiers / databases
EC number	207-925-0
ECHA InfoCard	100.007.205
PubChem	10387
ChemSpider	9958
Wikidata	Q419534
properties
Molar mass	170.60 g mol −1
Physical state	liquid
density	1.22 g cm −3
Melting point	−18 ° C
boiling point	178-180 ° C
Vapor pressure	9.3 h Pa (85-87 ° C)
solubility	violent decomposition with water
Refractive index	1.5190 (20 ° C)
safety instructions
H and P phrases	H: 330-314-335-350-410
	P: 201-273-280-301 + 330 + 331-305 + 351 + 338-308 + 310
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Benzyl chloroformate , also known as benzyl chloroformate , correctly referred to as benzyl chlorocarbonate , is an organic chemical substance. As a monoester of carbonic acid, it also belongs to the group of carboxylic acid chlorides . In the synthesis of peptides , benzyl chloroformate is used as a reagent to introduce the benzyloxycarbonyl group , which is mostly used as a protective group for amino groups .

properties

Benzyl chloroformate is a pungent and suffocating smelling liquid that irritates tears. It is soluble in most organic solvents , but is decomposed solvolytically by protic solvents such as water or alcohols . Carbonic acid esters are formed with alcohols . Benzyl chloroformate reacts with amines to form urethanes .

Manufacturing

In the laboratory by adding benzyl alcohol dropwise to liquid phosgene at around -20 ° C, with a deficit of benzyl alcohol being added in order to minimize the formation of the diester. Alternatively, the phosgene can also be dissolved in toluene or DMF , and these solvents can interfere with subsequent reactions .

use

In synthetic organic chemistry, and especially in peptide synthesis, the benzyloxycarbonyl group is introduced with benzyl chloroformate in the presence of a weak base . The Cbz group can be easily introduced into a molecule to protect an amino group by reacting the amine (e.g. amino acid 2 ) with benzyloxycarbonyl chloride 1 in the presence of a weak base. This creates a Cbz -protected amino acid 3 :

The protected amine (e.g. in 3 ) can be deprotected again by catalytic hydrogenation with hydrogenolytic cleavage of the benzyl heteroatom bond with subsequent decarboxylation of the unstable carbamic acid thus formed or treatment with acids.

nomenclature

The common name "benzyl chloroformate" is incorrect because it is a derivative of carbonic acid , not a derivative of formic acid . Strictly speaking, it is a monochloride and at the same time the monobenzyl ester of carbonic acid.

Hazard warnings

Since benzyl chloroformate decomposes hydrolytically through humidity and on the skin with the formation of hydrochloric acid, it has a very caustic effect on contact. Inhaled it can lead to pulmonary edema .

Contains commercially available benzyl production reasons the classified as a carcinogen benzyl chloride as an impurity. Some manufacturers, for example Merck KGaA , therefore also describe the benzyl chloroformate as carcinogenic and also give the GHS pictogram 08 (hazardous to health) next to the H statements314-335-350-410 and the P-sentences 201-273-280-301 + 330 + 331-305 + 351 + 338-308 + 310 on.

literature

J. Clayden, N. Greeves, S. Warren, P. Wothers: Organic Chemistry . Oxford University Press, 2001

Individual evidence

↑ ^a ^b ^c Data sheet for benzyl chloroformate (stabilized) for synthesis (PDF) from Merck , accessed on February 1, 2018.
↑ ^a ^b ^c ^d ^e ^f Entry on benzyl chloroformate in the GESTIS substance database of the IFA , accessed on January 8, 2018(JavaScript required) .
↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-42.
↑ Entry on Benzyl chloroformate in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
↑ L. Hough, JE Priddle: 621. Carbonate derivatives of methyl α- D -mannopyranoside and of D -mannose . In: Journal of the Chemical Society . 1961, p. 3178-3181 , doi : 10.1039 / JR9610003178 .
^ Siegfried Hauptmann : Organic Chemistry , 2nd revised edition, VEB Deutscher Verlag für Grundstoffindustrie, Leipzig, 1985, p. 661, ISBN 3-342-00280-8 .

[merck-1] Data sheet for benzyl chloroformate (stabilized) for synthesis (PDF) from Merck , accessed on February 1, 2018.

[GESTIS-2] ↑ ^a ^b ^c ^d ^e ^f Entry on benzyl chloroformate in the GESTIS substance database of the IFA , accessed on January 8, 2018(JavaScript required) .

[CRC90_3_42-3] David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-42.

[CLP_100.007.205-4] Entry on Benzyl chloroformate in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .

[5] L. Hough, JE Priddle: 621. Carbonate derivatives of methyl α- D -mannopyranoside and of D -mannose . In: Journal of the Chemical Society . 1961, p. 3178-3181 , doi : 10.1039 / JR9610003178 .

[Hauptmann-6] Siegfried Hauptmann : Organic Chemistry , 2nd revised edition, VEB Deutscher Verlag für Grundstoffindustrie, Leipzig, 1985, p. 661, ISBN 3-342-00280-8 .