Phosgenation sources

Trichloromethyl-chloroformate has been proposed as a relatively safe phosgene source for small-scale diisocyanate and polyurethane production units. Phosgene is produced upon fragmentation of this compound on a hot iron contact. 

Diphosgene was employed as a phosgene source for the preparation of diisopropyl and di-n-propyl carbamoyl chloride 188 [118]. 

Carbamates are generally prepared from isocyanates or chloroformates (see Scheme 4.2). Since isocyanates and chloroformates are usually prepared with phosgene, the corresponding synthetic routes are subject to the relevant safety considerations regarding the phosgene source (for a safe phosgene source, see Chapter 7). Moreover, the handling of several lower alkyl isocyanates is associated with a similar hazard level (toxicity), and therefore the search for a less hazardous procedure has been intense. 

Typical procedures. AOC- and MPC-amino acids. Method A [379] Amyl chloro-formate Dried phosgene (105 g, 1.06 mol) (for a phosgene source, see Chapter 7) was introduced into a solution of t-amyl alcohol (46 g, 0.52 mol) in dry diethyl ether (500 mL), and then the mixture was cooled to 60 °C in an acetone/dry-ice bath. A solution of pyridine (41 g, 0.52 mol) in dry diethyl ether (500 mL) was added dropwise to the cooled mixture with vigorous stirring. Then the reaction mixture was stored overnight in a deep freezer at —20 °C. The formed pyridine hydrochloride was removed by filtration, and the mother liquor was concentrated to a small volume (about 120 mL) in an ice/water bath under reduced pressure. The product thus obtained was used without further purification in the following reactions. Its purity was determined by acylating a known amount of phenylalanine methyl ester as described below it was found that about 4 mL of the product corresponded to 0.01 mol. The yield was about 60%. 

D,L-Trifluoroalanine N-carboxy anhydride (d,l-TFANCA) 1217, a reactive intermediate for the synthesis of low surface energy polypeptides, has been synthesized by phosgenation of 3,3,3-D,L-trifluoroalanine in THE [896]. Solid triphosgene was used as the phosgene source and the procedure of Daly and Poche [893] for natural... 

Scheme 7.1. Safety Phosgenation equipment with an external phosgene source.

Not used in the treatment of phosgene Source Adapted from U.S. Army, 1999a. 

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