Isocyanate dehydrating agents

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

Monsanto has disclosed the use of carbon dioxide—amine complexes which are dehydrated, at low temperatures, with phosphoryl chloride [10025-87-3] or thionyl chloride [7719-09-7] as a viable route to a variety of aUphatic isocyanates. The process rehes on the facile formation of the intermediate salt (30).REPLACEVariations of this process, in which phosgene is used as a dehydrating agent, have been reported earlier (84). Table 2 Hsts commercially available aUphatic isocyanates. 

Carbodiimide functionality can be produced by reacting isocyanates at elevated temperature with proper catalysis (Scheme 4.15). Although carbodiimides undergo a variety of reactions,23 most commonly as dehydrating agents, in the presence of excess isocyanate they will form uretone imines. This not only increases the average functionality of the isocyanate product but also lowers its freezing point. For example, a liquefied (or modified) version of 4,4,-MDI can... 

Dehydration of primary nitroalkanes with phenyl isocyanate or acetic anhydride in the presence of catalytic triethylamine affords nitrile oxides, which may be trapped as their 1,3-dipolar cycloadducts or allowed to dimerize to the corresponding furoxans. Other dehydrating agents that have been used include diketene, sulfuric acid and, when the a-methylene group is activated by electron-withdrawing groups, boron trifluoride in acetic anhydride, trifluoroacetic anhydride with triethylamine, and nitric acid in acetic acid. 

It is well known that oxalyl chloride reacts with non-substituted amides to afford acyl isocyanates in high yields (Ref. 214). In contrast, phosgene acts as a dehydrating agent to give nitriles as shown in scheme 160. This interesting reaction, its mechanism and applications will be discussed in volume 2. 

Phenyl isocyanate reacts with ammonia to form phenylurea (1) and with aniline to give diphenylurea (2). When used as a dehydrating agent it apparently adds water... 

Isothiocyanates. Both a-chloro aldoximes and nitroalkanes give isothiocyanates on reaction with thiourea. The former needs a base (e.g., E N) to generate nitrile oxides in situ, and the latter requires both a base and a dehydrating agent, such as 4-chlorophenyl isocyanate. 

Generation of Organic Isocyanates from Amines, Carbon Dioxide, and Electrophilic Dehydrating Agents... 

In previous accounts the use of electrophilic dehydrating agents in the direct generation of isocyanates from amines and carbon dioxide has been discussed, equations 1-2 (1-3). 

Conversion of Linear Anhydride to o-Sulfobenzoic Add Anhydride Critical to the successful use of o-sulfobenzoic acid anhydride as a dehydrating agent for the production of isocyanates is the ability to recycle the anhydride. Since direct conversion from the isolated by-product appears to be unlikely, another pathway must be demonstrated. A reasonable route is shown below in Scheme m, and progress in each of the steps shown has been made. 

Subsequently, the Monsanto researchers developed a variation of this activated carbon dioxide chemistry process whereby activated carbamate anions derived from primary amines could be reacted rapidly with electrophilic dehydrating agents, such as acid halides, to produce the corresponding isocyanates in excellent yields, according to the following reaction ... 

This has proven to be a very versatile reaction, which can start with a variety of electrophilic dehydrating agents and organic bases. Furthermore, the mild reaction conditions allow for the use of amine precursors, which can possess a number of different functional groups. Thus the Monsanto activated carbon dioxide process not only eliminates the use of phosgene as a starting material, but also provides additional benefits, including milder reaction conditions, urethane and isocyanate products in quantitative yields, reductions in problem impurities and by-products, and broader possibilities in choice of amine feedstock. 

Chlorosulfonyl isocyanate, Cl-S02-N=00, is an effective dehydrating agent for the preparation of various aryl- and alkyl-nitriles from the corresponding amides and aldoximes in yields of 74-87% and 75-86%, respectively [1128],... 

It has been recently reported that carbamate anions, obtained by reaction of primary amines, carbon dioxide, and an added base e.g. NEts), undergo rapid reaction with electrophilic dehydrating agents e.g. POCI3, P4O10) to afford the corresponding isocyanates in excellent yields (Scheme 1) [11]. 

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