Phosgene-free isocyanates

Syntheses of N-arylurethanes and N,N -diarylureas for an approach to phosgene-free isocyanates could be accomplished by ruthenium complex-catalyzed dehydro-genative reactions of N-arylformamides, which are prepared by the carbonylation of aminoarenes (see Eq. 11.8), with alcohols [106] and aminoarenes [107], respectively. 

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... 

Reductive carbonylation of nitro compounds is catalyzed by various Pd catalysts. Phenyl isocyanate (93) is produced by the PdCl2-catalyzed reductive carbonylation (deoxygenation) of nitrobenzene with CO, probably via nitrene formation. Extensive studies have been carried out to develop the phosgene-free commercial process for phenyl isocyanate production from nitroben-zene[76]. Effects of various additives such as phenanthroline have been stu-died[77-79]. The co-catalysts of montmorillonite-bipyridylpalladium acetate and Ru3(CO) 2 are used for the reductive carbonylation oLnitroarenes[80,81]. Extensive studies on the reaction in alcohol to form the A -phenylurethane 94 have also been carried out[82-87]. Reaction of nitrobenzene with CO in the presence of aniline affords diphenylurea (95)[88]. 

The oxidative carbonylation of amines to give ureas is at present one of the most attractive ways for synthesizing this very important class of carbonyl compounds via a phosgene-free approach. Ureas find extensive application as agrochemicals, dyes, antioxidants, resin precursors, synthetic intermediates (also for the production of carbamates and isocyanates), and HIV-inhibitors. Many transition metals (incuding Au [244], Co [248,253-255], Cu [242], Mn [249,256-258], Ni [259], Rh [246,247,260-262], Ru [224,260,263] and especially Pd [219,225,226,264-276], and, more recently, W [277-283]) as well as main-group elements (such as sulfur [284-286] and selenium [287— 292]) have been reported to promote the oxidative carbonylation of amines, usually under catalytic conditions. In some cases, carbamates and/or oxamides are formed as byproducts, thus lowering the selectivity of the process. 

A phosgene-free route to aromatic isocyanates, such as M DI and TDI, was reported by Fernandez et al. [42] (Scheme 5.7) According to the patent, the one-pot synthesis involves the use of an immobilized Schiff base type of ligand catalyst that facilitates the oxidative carbonylation of aromatic amines to the corresponding isocyanates. However, 2,2,2-trifluoroethanol (TFE), 1,2-dichlorobenzene, and carbon monoxide were used in this process, so this would not be a totally environmentally friendly process even if these reagents could be recycled and reused. 

The most common industrial syntheses of carbamate esters are based on either the alcoholysis of phosgene, followed by aminolysis of the intermediate chlorofor-mate, or the reaction of an alcohol with an isocyanate, usually prepared from COCl2 [6, 7]. The development of phosgene-free routes to carbamates represents an important synthetic challenge, and several synthetic strategies are currently under investigation in this area. 

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]. 

Another interesting bromide ion-catalyzed reaction is the anodic oxidation (undivided cell) of secondary formamides in methanol leading to urethanes [232]. This reaction proceeds via the intermediate A-bromo amide, which under elimination of HBr forms the isocyanate, which is attacked by methanol. Thus, a phosgene-free technical synthesis of urethanes is made possible. Urethanes can be used as stable isocyanate equivalents [Eq. (42)]. 

In another example, surprisingly, we found that the phosgenation of a substituted isoxazolamine hydrochloride doesn t afford the expected free isocyanate but a peculiar dimer according to the mechanism depicted on scheme 126 (Ref. 179). 

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 ... 

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. 

Phosgene-free synthesis of isocyanates directly from carboxylic acids and diphenylphos-phonic azide (PhO)2P(0)N3 in combination with proton sponge 1 followed by Curtius rearrangement has been also described222. 

Specifications for the analysis of phosgene will depend upon the end-use application, but a typical analysis of the liquid commercial product may be as given in Table 4.4 [ICI69,ICI78]. Military specifications for use in munitions (COClj, >98% free Cl, <1% acid (HCl), <0.5% residue, <0.5%) also exist [1394a], and the analysis of phosgene for isocyanate manufacture (for polyurethane production) has been described in detail [4S8a]. 

An enormous e-f-fort has been made on -finding new, phosgene—free routes to isocyanates. Phosgene, produced by reaction o-f carbon monoxide with chlorine, is an energy-intensive material, very poisonous and corrosive since it is a hydrolyzable chlorine derivative. One such process involves reductive carbonyl at i on o-f the nitro compounds by reaction with carbon monoxide 2,3,53 ... 

H. Blattmann, M. Fleischer, M. Bahr, R. Mulhaupt, Isocyanate- and phosgene-free routes to polyfunctional cyclic carbonates and green polyurethanes by fixation of carbon dioxide, Macromol. Rapid Commun. 35 (July 2014) 1238-1254. 

Alternative Phosgene-Free Process to Methyl Isocyanate... 

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. 

Monsanto s Phosgene-Free, Co-Based Process for Urethanes, Isocyanates, Ureas... 

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... 

The second major area in which publications have appeared is that of new routes to isocyanate products. A phosgene-free route is clearly desirable, and one such has been developed by Atlantic Richfield to the stage of building a full-scale plant. Their route (Scheme 1) has been the subject of considerable patent activity by a number... 

Many examples of phosgene-free processes, mainly concerning the carbonylation of aryl nitro derivatives, have been claimed. Some of the most representative, cited in part in the Kirk-Othmer Encyclopedia of Chemical Technology (4th ed., vol. 19), are illustrated belotv. 2,4-Dinitrotoluene undergoes reductive carbonylation with CO to form 2,4-toluene diisocyanate (TDI) in the presence of palladium catalysts [209-213]. A variation on this process involves capturing the isocyanate formed with methanol, followed by thermolysis of the bis(carbamate) 326 [212]. 

Aliphatic isocyanates are produced by either phosgene-based processed or phosgene-free processes (note that the molecule named phosgene contains... 

While the use of phosgene allows direct conversion of the alkylamine into the isocyanate, the phosgene-free route requires for the same transformation three sequential reaction steps. First, the alkylamine is reacted with urea. The resulting urea derivative is then reacted with an alcohol to give the corresponding urethane. The urethane can then be cleaved in a third step to the desired isocyanate while liberating the applied alcohol again. 

The high toxicity of phosgene has resulted in intensive work on the development of phosgene-free processes for diisocyanate manufacture. The development has been successful for only a few aliphatic diisocyanates, but ca. 95 % of all isocyanates produced in an industrial scale are aromatic. 

Dry CO2 passed at 20-50° into trimethylsilylmethylamine until no further weight increase is observed trimethylsilyl methylcarbamate (Y 90%) heated with phenyltridilorosilane at 105-110° methyl isocyanate (Y 82%). - This is a phosgene-free prepn. of isocyanates. F. e., also with isolation of intermediate silyl N-silylcarbamates, s. V. F. Mironov, V. P. Kozyukov, and V. P. Bulatov, 3C. 43, 2089 (1973) C. A. 80, 37216. 

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. 

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