Synthesis of Isocyanates

Isocyanates (RNCO) are industrially relevant compounds which find application in several fields [9, 106]. Many isocyanates serve as the starting materials for the manufacture of plant protection agents, pesticides, dyes, resins and plastics, textile waterproofing agents, detergents, bleaches, and adhesives. They are also widely used in surface coatings such as paints, sealants and finishes, and in the manufacture of rubbery plastics such as those used to coat wires. Traditionally, diisocyanates are the primary feedstock for the production of polyurethanes. The global market for diisocyanates in the year 2000 was 4.4 million tonnes, of which 61.3% was methylene diphenyl diisocyanate (MDI), 34.1% was toluene diisocyanate 

Isocyanates may be prepared via a number of routes, including the thermal cracking of urethanes or silylurethanes [107], or the reaction of N-alkylcarbamate esters with boron trichloride [108] or chloroboranes [109] or chorosilanes [110] in the presence of bases (NEt3). To date, however, only amine phosgenation is practiced on a significant industrial scale [10, 106], 

The direct synthesis of isocyanates from C02 is a challenging task, as the building up of the isocyanate group from C02 requires deoxygenation of the heterocu-mulene. A number of metal systems are capable of promoting such a transformation in their coordination sphere. 

In 1976, Saegusa reported the copper(I) t-butoxide-promoted deoxygenation of C02 by t-butyl isocyanide to produce t-butyl isocyanate and CO (Equation 6.13) [111a]. 

This reaction can take place in mesitylene or tetralin at high temperature (373-423 K). Under the correct conditions (t-BuOCu/t-BuCN = l 5mol/mol C02/Cu = ca. 82 mol/mol tetralin as solvent 393 K, 3 h), the reaction produced up to 119% CO (based on copper) and an equivalent amount of isocyanate which, upon the addition of n-butyl alcohol, was converted in situ into (t-Bu)NHC02Bu carbamate. An interesting question pertaining to the mechanism of Equation 6.13 is whether the CO carbon atom derives from C02 or from t-BuNC. Unfortunately, the study did not provide any information on the mechanistic details of the process. 

The interaction of carbon monoxide with organic nitro compounds is a thermodynamically highly favourable process. For reaction (1)  

The catalytic reduction of organic nitro compounds by carbon monoxide can take place without the incorporation of CO into the products (see Chapters 4 and 5), or with the addition of a CO molecule to the intermediates of the reductive carbonylation process (to afford e.g. isocyanates, carbamates, or ureas, see also Chapter 3). 

By varying the nature of the catalyst, the reaction medium and the reaction conditions, it is possible to modify both the reaction pathway and the yields of the products. A very important role is also played in many cases by the nature of the cocatalyst and ligands. An important point, difficult to clarify in many cases, is related to the nature of the catalytic system, that is which is the real catalytically active species and, moreover, in which cases we can clearly distinguish between homogeneous and heterogeneous catalysis. This unsatisfactory situation is primarily due to the fact that, with few exceptions, the catalytic carbonylation reactions of nitro compounds proceed at high pressures and temperatures and these reaction conditions interfere with studies of the mechanism of these 

From a practical point of view, isocyanates, together with carbamates and ureas (Chapter 3), are the most important organic products discussed in this book. Their synthesis from nitroarenes has indeed been the subject of many patents. There are also limited examples of aliphatic isocyanates obtained by this route. Organic mono- and diisocyanates may be prepared in a continues liquid phase method by treating the appropriate amine with phosgene. However, the reaction is rather complex [6] and, besides the use of the dangerous phosgene, the formation of the corrosive hydrochloric acid creates several problems. Aliphatic isocyanates can also be obtained from olefins with isocyanate ion in the presence of a salt of a coordination compound of palladium or platinum [7], from olefins with isocyanic acid in the vapour phase over Pt/ALOs [8], and from formamides, by oxidation over a silver catalyst [9]. Apparently only the last reaction seems to have some potential practical applications [10]. 

Nevertheless, this does not seem to be a useful route from an industrial point of view. Similarly, the use of solid triphosgene, CO(OCCb)2, in place of phosgene in the reaction with amines [12], although useful as far as transport and storage are concerned, does not appear to be a significant solution to the industrial problems. Note that triphosgene is prepared by reaction of chlorine with dimethyl carbonate. 

At least 90 % of the worldwide production of isocyanates is accounted for by two aromatic isocyanates, toluene diisocyanate (TDI), a distilled compound, and polymethylene polyphenylene polyisocyanate (PMDI), an undistilled isocyanate mixture with a low vapor pressure (Structures 1-3). Together these two products cur- 

Numerous patents [3, 11-13] and other publications [3, 14-16] describe the direct carbonylation of nitroaromatic compounds to isocyanates or alternatively a modified carbonylation to urethanes in the presence of alcohol, followed by a thermal transformation to isocyanates [4, 17-19] (eq. (2)). 

In the first reported direct A -carbonylation of nitroaromatics to isocyanates, simple Pd- or Rh-based systems were used to catalyze the reaction of aromatic mononitro compounds with carbon monoxide [11, 12]. Later, it became possible to work without the drastic reaction conditions that had been required initially, by using Lewis acid co-catalysts [13], Various catalysts and catalyst mixtures, normally based on Ru, Rh, or Pd complexes with co-catalysts, were described in numerous patents and publications [1, 3, 14—16], The careful choice of the composition of the triad consisting of metal salt, co-catalysts and ligand (preferably aromatic amines) led to efficient catalyst systems [14a-e] for the direct reductive carbonylation process. A quite active Pd-phenanthroline-H system with noncoordinating carboxylic acids such as 2,4,6-trimethlybenzoic acid as proton source is worth mentioning [14 d]. 

However, although promising results have been achieved with mononitro compounds, dinitro compounds can be converted only with low selectivities and using high catalyst concentrations. Furthermore, in spite of extensive investigations of the reaction mechanism (see Section 3.3.5.3.1), questions that still remain unanswered are, whether the active catalytic species is a heterogeneous one or a soluble species generated in situ, and what the function of the cocatalyst is. 

Summarizing, from the investigations in this field it can be concluded that from an industrial viewpoint the direct carbonylation of nitroaromatics to isocyanates represents no economically feasible alternative, for the conventional phosgenation process, for the following reasons  

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More convenient is the use of aryl a2ides which are readily converted into isocyanates upon heating in nonreactive solvents via the loss of nitrogen. The latter method is useful for the synthesis of isocyanates with additional substituents which could not be prepared with phosgene (20). 

Synthesis of Isocyanates, Isothiocyanates, Aminoisocyanates, Aminoisothiocyanates, and A-Sulfinylamines... 

Analogous to the synthesis of isocyanates, isothiocyanates are obtained in good yield by reacting AyV -thiocarbonyldiimidazole (ImCSIm) with primary aliphatic or aromatic amines in equimolar amount. In chloroform at room temperature the dissociation equilibrium of imidazole-A-thiocarboxamides is shifted completely to isocyanates. 

If A/ V -carbonyldi-1,2,4-triazole or A/ V -carbonyldibenzimidazole is used for the synthesis of isocyanates instead of CDI, the yields are lower.[1],[3] For the synthesis of isocyanates and isothiocyanates according to this method see also references [8] and [9]. 

Reductive carbonylation of nitro compounds (in particular aromatic dinitro compounds) is an important target in industry for making diisocyanates, one of the starting materials for polycarbamates. At present diisocyanates are made from diamines and phosgene. Direct synthesis of isocyanates from nitro compounds would avoid the reduction of nitro compounds to anilines, the... 

C., Castillon Miranda, S., Salagre Carnero, P. and Aghmiz, A. (2008) One-pot catalytic process for the synthesis of isocyanates, European Patent EP1870398. 

The reversed reaction, i.e. attack of CO on the corresponding transition metal azido complex, sometimes also provides an attractive route for the synthesis of isocyanate complexes, e.g. the reaction of CO with, for example, Co(N3)(DH)2(PPh3),344 Rh(f/5-C5Me5)(N3)4276 or Rh(N3)(cod).344... 

Calderazzo has reported the synthesis of isocyanates from metal N-alkyl carbamates and acyl or aroyl chlorides (Scheme 6.27), used in this context as oxygen... 

Scheme 6.27 Metal-assisted synthesis of isocyanates from C02, amines, and an acylating agent.

Scheme 6.28 Synthesis of isocyanates from primary amines and C02, using Mitsunobu chemistry...

Fig. 6. 33. Carbonic acid derivatives and their interconversions (plus cross-reference to a chlorine-free option for the synthesis of isocyanates).

The diimide (37) reacts with CO to yield an isocyanate complex (38) (86), having a characteristic infrared absorption at 1280 cm-1 (88). This remarkable reaction suggests several catalytic schemes which might be useful for the synthesis of organic compounds containing the —N—C(O)— unit. This latter complex (38) could be viewed as the key intermediate in any catalytic cycle for the synthesis of isocyanates or urea from CO and NH3 (or N2 and H2).2 However, in our work we could not... 

The alkyl-, alky laryl- and diarylcarbodiimides are the diimides derived from carbon dioxide, however, no direct formation of carbodiimides from amines and carbon dioxide is known. Interestingly, carbodiimides can be obtained from amines and carbon dioxide via a switteri-onic titanium complex (see Section 2.2.8). The major starting materials for the synthesis of carbodiimides are isocyanates, 1,3-disubstituted ureas or 1,3-disubstituted thioureas. The synthesis of isocyanates requires the use of the toxic carbonyl chloride or its oligomers. A book on the synthesis and reactions of isocyanates appeared in 1996. ... 

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. 

Synthesis of Isocyanates. In a typical procedure a mixture of lauroyl chloride and acetone is added from a dropping funnel with cooling and stirring to a solution of sodium azide in water at a rate such as to maintain a temperature of 10-15°. After the reaction Is complete (cu. 1 hr.), the lower aqueous layer is removed carefully by suction through a glass capillary lube. The upper layer of crude acyl azide is... 

Synthesis of isocyanates,12 Thermal cleavage of urethanes gives low yields of isocyanates because of the high temperatures necessary (200-300°). However, if the urethane is N-silylated, cleavage occurs at much lower temperatures. Thus the urethane (1) is treated with trimethylchlorosilane and triethylamine in refluxing... 

From the hydrolysis of a polyether-based PU a diamine (or a polyamine) such as toluene diamine or diphenylmethane diamine, a polyol and carbon dioxide are formed. The resulting diamines are the precursors used for the synthesis of isocyanates [11,12,16,18]. The resulting polyol is the polyether polyol used for the initial synthesis of PU. Carbon dioxide results from the decomposition of the very unstable carbamic acid formed by the hydrolysis (20.2) ... 

The phosgene toxicity, separation of hydrochloric acid from excess phosgene, and the use of chlorinated solvents as a reaction medium are the major drawbacks of this reaction process. Extensive studies have suggested that carbamate and dicarbamate can serve as environmentally benign precursors for the synthesis of isocyanate and diisocyanate (1-5). Figure 1 illustrates nonphosgene routes for the synthesis of two important diisocyanates [i.e., 4,4 -diphenylmethane diisocyanate (MDI) and toluene diisocyanate(TDI)] via carbonate and carbamate. 

Recent work has considerably extended the synthesis of isocyanates from ureas, making isocyanates available that cannot be obtained by direct reaction of phosgene and amines.633... 

Carbonyl azides are usually obtained from the hydrazides, although in principle they can also be prepared directly from the carbonyl chlorides and sodium azide. They are frequently used as intermediates for synthesis of isocyanates, urethanes, ureas, amines, etc., and are often used in such work without isolation. 

A general scheme for synthesis of isocyanate and isothiocyanate derivatives is the reaction with amines (equation 39). This yields derivatives of urea or thiourea, however, the methods should be developed in accordance with the intended application as an analytical tool. 

Sigurdsson et al. developed the synthesis of isocyanates from aliphatic amines [21]. Thus, the reaction of an aliphatic amine with trichloromethyl chloroformate (diphosgene) in the presence of Proton Sponge (1) (2 equiv.) at 0°C gave isocyanate in 81% yield. Azide isocyanate was synthesized from azide amine by means of a similar procedure by Keyes et al. [22] (Scheme 8.8). 

Ureas and Carbonates. Reagent (1) may be used as a direct replacement for the highly toxic Phosgene in reactions with alcohols and amines. Reaction of (1) with two equivalents of a primary aliphatic or aromatic amine at room temperature rapidly yields a symmetrical urea (eq 9). If only one equivalent of a primary amine is added to (1), then the imidazole-Al-carboxamide (4) is formed (eq 10). These compounds can dissociate into isocyanates and imidazole, even at room temperature, and distillation from the reaction mixture provides a useful synthesis of isocyanates (eq 10).7 Secondary amines react only at one side of (1) at room temperature, again giving the imidazole-Al-carboxamide of type... 

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