Phosgene-free methods

The reductive carbonylation of nitroarenes with transition metal catalysts is a very important process in industry, as the development of a phosgene-free method for preparing isocyanate is required. Ruthenium, rhodium, and palladium complex catalysts have all been well studied, and ruthenium catalysts have been shown to be both highly active and attractive. The reduction of nitroarene with CO in the presence of alcohol and amine gives urethanes and ureas [95], respectively, both of which can be easily converted into isocyanates [3,96]. 

Very recently, phosgene-free methods for producing organic isocyanates have been developed. One method involves reductive carbonylation of a nitro compound in the presence of a monoalcohol to produce a urethane compound, followed by thermal dissociation of the resulting urethane compound, as shown below ... 

Another phosgene-free method was developed by Akzo Co. to product p-phenylene diisocyanate (32). 

Reductive carbonylation of nitro compounds, especially nitroaromatic compounds according to eq. (1), has been the subject of thorough industrial research starting in 1962 and continuing until the beginning of the 1990s due to the demand for a new, phosgene-free method for the production of isocyanates [1] and the discussions on the chlorine cycle in industry. 

The foregoing examples of phosgene-free methods for synthesis of carbamates, isocyanates, ureas, polycarbonates, dyes, polymers, and other pharmaceutical or agrochemical intermediates and products all illustrate ways that green chemistry reduces the environmental impact... 

Peng, W. Zhao, N. Xiao, F. Wei, W Surr, Y. Recent Progress in Phosgene-free Methods for Synthesis of Dimethyl Carbonate. Pure Appl. Chem.2012,84,603-620. 

A variation of this method involves the conversion of the amine into the amine hydrochloride prior to treatment with phosgene. This method has the advantage of producing generally cleaner products by retarding the secondary reaction of the free amine with carbamoyl chloride. 

This method of transesterification is of high technical interest. Particularly the reaction of bisphenol A with diphenyl carbonate is a preferred phosgene-free process because biphenyl carbonate can be obtained directly from phenol and dimethyl carbonate.The latter is an industrial product made from CO and methanol. 

The DuPont process not only eliminates the use of phosgene as a starting material, but also avoids the production of large amounts of hydrochloric acid as an unwanted by-product. In this method, methyl-amine reacts with carbon monoxide to yield the corresponding aldehyde, which is then catalytically converted to isocyanate. This phosgene-free replacement synthesis also supports the trend in the chemical process industry to seek to reduce inventories on plant sites of hazardous synthetic reagents. Methyl isocyanate produced from this process is converted in situ to an agrochemical product. 

Di-tert-butyl dicarbonate, B0C2O Unfortunately, most of the known methods for transforming amines into isocyanates are not mild enough and furnish undefined products as a result of uncontrolled side reactions. However, 4-dimethylaminopyr-idine (DMAP)-catalyzed reaction with activated carbonates as Ci building blocks constitutes a convenient laboratory method for the phosgene-free isocyanation of amines. A procedure has been described whereby alkyl- and arylamines are converted into isocyanates in high yields by reaction with activated carbonates (for... 

The following section illustrates the use of phosgene equivalents for the synthesis of ureas, with particular emphasis on the advantages of completely phosgene-free synthetic methods based on the use of alkyl carbonates, CO, CO2, and other miscellaneous carbonylating reagents. 

Synthesis and Polymerization of Leuchs Anhydrides. The N-carboxy-a-amino acid anhydrides, referred to as Leuchs anhydrides or as NCAs, are synthesized either from N-alkoxycarbonyl derivatives of a-amino acids or from free amino acids. Cyclization of the amino acid derivative by SOCl2 or similar reagents was described first by Leuchs in 1906, but direct synthesis involves treating the a-amino acid or its hydrochloride with phosgene as shown in Figure 4. This method, commonly termed the Fuchs-Farthing method, is the one that is used most frequently since the N-carboxyanhydride may be freed easily from the carbamyl chloride, isocyanate derivative, and hydrogen chloride by crystallization. 

A carboxyl group can be introduced in almost any compound by various methods. In cases where a free thiol is present, the carboxyl group can be introduced easily by reaction with bromo- or iodoacetic acid. This reaction is very mild and is usually performed at pH around 8-9. When the hapten contains a hydroxyl group, carboxylic acid may be introduced by one of the following methods (a) carboxymethylation of the hydroxyl group with bromo- or iodoacetic acid (b) esterification with dicarboxylic acid anhydrides, such as succinic anhydride, to yield hemi-succinates, which are unstable above pH 9 (c) reaction with phosgene, which results in the formation of chlorocarbonates. ... 

The Sodium Iodide Method. The determination of phosgene by this method, due to the Chemisch-Technischen Reichsanstalt, is carried out by titrating the iodine liberated when a gas mixture containing phosgene but free from acid gases, reacts with a solution of sodium iodide in acetone. The reaction is as follows ... 

The resuiting chloride is determined by titration with standardized siiver nitrate soiution, according to established methods (c/. Sections 3.2.1.1 and 3.2.4), to provide the total phosgene composition. In most cases, this method is sufficiently accurate, because free dichlorine and hydrogen chloride, which would interfere with the test are present in only low concentration. If, however, free dichlorine or HCl are present (see below), the dichlorine equivalent is deducted from the total chlorine and the difference calculated to the percentage value of phosgene. 

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