Process for the preparation of trisubstituted ureas by reductive carbonylation

Abstract: Preparing a trisubstituted urea by reacting a nitroarene with carbon monoxide and a secondary amine in the presence of a Group VIII transition metal catalyst and optionally one or more promoters selected from primary amines, halide ion-containing compounds, chelating phosphorus and nitrogen compounds, water, hydrogen, compounds containing at least one active hydrogen atom and redox metals.

Description: The invention relates to the field of urea synthesis. More specifically, a process is disclosed for preparing trisubstituted ureas by reductive carbonylation of a nitroarene in the presence of a secondary amine and a Group VIII transition metal catalyst. The ureas are useful precursors to aromatic isocyanates. BACKGROUND OF THE INVENTION : Reductive carbonylation of nitroarenes and/or arylamines in the presence of various catalysts is an effective strategy for preparing N,N′-diarylureas. For example, Heck et al. ( J. Org. Chem. 40 (1975) 2819) describe the synthesis of various symmetric diarylureas from the reaction of nitroarenes, aromatic amines, and carbon monoxide in the presence of a oalladium catalyst. The authors also note, however, that complicated mixtures of ureas result when aromatic amines and nitroarenes containing different substituents react in this process. For example, the reaction of aniline with p-chloronitrobenzene gives N,N′-diphenylurea and N,N′-bis(p-chlorophenyl)urea in addition to the expected N-phenyl-N′-(p-chlorophenyl)urea. Similarly, Watanabe et al. ( J. Organometal. Chem. 290 (1985) 249) reported that n-butylamine reacts with nitrobenzene and carbon monoxide in the presence of a platinum compound to give a mixture of N,N′-dibutylurea (46%), N-butyl-N′-phenylurea (46%), and N,N′-diphenylurea (6%). UK Patent Application GB 2 233 973A teaches a process in which a primary aliphatic amine reacts with a nitroarene and carbon monoxide in the presence of a rhodium catalyst to give only the symmetric N,N′-dialkylurea and a primary aromatic amine. No unsymmetric urea is produced. When a secondary aliphatic amine is used in place of the primary aliphatic amine, only traces of urea products are detected. East German Patent No. 227,700 ( Chem. Abstracts 104 224726v) teaches to prepare N,N-dimethyl-N′-phenylurea from nitrobenzene, CO, and dimethylamine in the presence of a sulfur/vanadium pentoxide catalyst system. The reference teaches the criticality of the vanadium pentoxide, and does not suggest using a Group VIII metal catalyst for the process. The references discussed in the preceding paragraphs make it clear that a synthesis of an unsymmetric urea from a nitroarene and a secondary amine using a Group VIII transition metal catalyst is likely to give, if anything, a complicated mixture of urea products. On the other hand, a selective process for producing trisubstituted ureas, especially N′-aryl-N,N-dialkylureas, is desirable because these ureas are easily cracked in the presence of various promoters to give aryl isocyanates. The present invention is a process for preparing a trisubstituted urea. EP-A-0250037 and EP-A-0319111 each describe the reaction of a nitroarene with carbon monoxide and a secondary amine in the presence of a Group VIII metal catalyst to form a trisubstituted urea. EP-A-0250037 requires the additional presence of a bidentate ligand and a strong acid or transition metal salt of the acid as promoters; EP-A-0319111 recommends the presence of a bidentate ligand and a derivative of a strong acid. According to the present invention there is provided a process for making a trisubstituted urea, said process comprising: reacting a nitroarene with carbon monoxide and a secondary amine in the presence of a Group VIII transition metal catalyst and, as promoters, a primary amine and a halide ion-containing compound. High yields of trisubstituted ureas are obtained under optimum conditions. In the process of the invention, a nitroarene is reacted with carbon monoxide and a secondary amine in the presence of a Group VIII transition metal compound as catalyst and a primary amine and a halide ion-containing compound as promoters. The nitroarene may be aromatic compound having one or more nitro substituents. The aromatic ring or rings may be substituted with one or more additional substituents selected from the group consisting of amino, halogen, alkoxy, and C₁-C₁₀ alkyl. Examples of suitable nitroarenes include, but are not limited to, nitrobenzene, nitrotoluenes, nitronaphthalenes, dinitrobenzenes, dinitrotoluenes, nitrochlorobenzenes, nitroanisoles, nitrotoluidines, bis(nitrophenyl) ethers, bis(nitrophenyl)-alkylenes, nitro-substituted biphenyls, alkylated nitroarenes and the like, and mixtures thereof. Specific examples are 2,4-dinitrotoluene, 2,6-dinitrotoluene, 4,4'-bis(nitrophenyl)-methylene, 4,4'-bis(nitrophenyl)-ether, 2,2-bis(4-nitrophenyl)-propane, 1,1-bis(4-nitrophenyl)-1-phenylethane, nitrosubstituted ethylbenzenes and 4,4'-dinitrobiphenyl; particularly one or more dinitrotoluene isomers. Secondary amines useful in the process of the invention have the general formula HNRR′, in which R and R′, which may be the same or different, are aryl, aralkyl, or alkyl groups having from 1 to 30 carbons. For example, R and R′, which may each be an alkyl or cycloalkyl group, as in dimethylamine, diethylamine, di-n-butylamine, methyl-n-butylamine, ethylcyclohexylamine, N,N-dicyclohexylamine, and the like. Alternativley, R and R′ may both be aryl groups, as in diphenylamine. Mixed aryl-alkyl amines, such as N-methylaniline, N-cyclohexylaniline, and N-cyclohexylbenzylamine, and the like, are suitable. R and R′ may also form a ring. Cyclic secondary amines such as piperidine, pyrrolidine, and the like, and cyclic secondary amines that contain heteroatoms, such as morpholine and substituted morpholines, are suitable. Mixtures of secondary amines may be used. Preferred secondary amines, for reasons of availability and effectiveness, are aliphatic amines such as dimethylamine, diethylamine, diisopropylamine and the like. Any amount of secondary amine may be employed. For economic reasons, it is preferred to use an amount less than about 5 equivalents of secondary amine per nitro group equivalent. More preferably, an amount of secondary amine within the range of about 0.5 to 2.0 equivalents per nitro group equivalent is used. The Group VIII transition metal catalysts of the invention are transition metal compounds containing iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium, or platinum. The metal may be present in supported or unsupported elemental form, or in the form of a salt or other transition metal complex containing the metal. Carbonyls, halides, oxides, sulfates, nitrates, acetates, and other transition metal salts may be used provided that at least one Group VIII metal is present. Mixtures of various Group VIII metal compounds may be used. Bimetallic and poly-metallic compounds may also be used provided that at least one Group VIII transition metal compound is present. Examples of suitable Group VIII transition metal compounds include, but are not limited to, triruthenium dodecacarbonyl, ruthenium trichloride, ruthenium oxide, triosmium dodecacarbonyl, platinum(II) chloride, platinum(IV) chloride, platinum black, platinum on alumina, platinum(IV) oxide, palladium, palladium(II) acetate, palladium(II) nitrate hydrate, bis(triphenylphosphine)palladium(II) chloride, cobalt(II) chloride hexahydrate, cobalt oxide, cobalt(II) sulfate hydrate, iron pentacarbonyl, iron(II) sulfate heptahydrate, and the like, and mixtures thereof. The process of the invention is performed in the presence, as promotors, of a primary amine and a halide ion-containing compound. Optionally, chelating phosphorus and nitrogen compounds may also be used as promoters. Examples of suitable primary amines include methylamine, ethylamine, aniline, ethylene diamine, n-butylamine, isopropylamine, and mixtures thereof. Suitable halide ion-containing compounds include any source of fluoride, chloride, bromide, or iodide. Examples of suitable halide ion-containing compounds include tetraalkylammonium halides, alkali metal halide salts, alkaline earth metal halide salts, iminium halide salts and mixtures thereof; e.g. bis(triphenylphosphine)iminium chloride and tetraalkylammonium chloride compounds. Examples of suitable chelating N and P compounds include, but are not limited to bis(diphenylphosphino)methane, bis(diphenylphosphino)propane, 2,2'-bipyridine, 1,10-phenanthroline, 2,9-dimethylphenanthroline, 4,7-diphenylphenanthroline, 3,4,7,7-tetramethylphenanthroline and mixtures thereof. Compounds having the general formula R₂X - (CH₂) n -- XR₂ in which R is an alkyl or aryl group, X is phosphorus or nitrogen, and n is an integer from 1 to 10 are generally suitable. Any desired amount of primary amine, halide ion containing compound, and optional phosphorus/nitrogen chelating compound may be used in the process of the invention. Generally, it is preferred to use the halide ion-containing compound in an amount within the range of 0.1 to 10 equivalents, and more preferably in an amount within the range of 0.5 to 5 equivalents, per equivalent of transition metal compound employed. The primary amine is preferably used in an amount of up to 1 equivalent per equivalent of nitroarene. One preferred embodiment employs aniline as the primary amine, triruthenium dodecacarbonyl and at least one mole of halide ion-containing compound per mole of the dodecacarbonyl The process of the invention may be performed at any desired temperature. Preferably, the process is performed at a temperature within the range of 40°C to 250°C. More preferred is the range from 90°C to 200°C. Trisubstituted ureas that are substantially free of by-products can be prepared at temperatures within the range of 90°C to 200°C. A particularly preferred temperature range is from 100°C to 170°C. At temperatures below 40°C, the reaction is ordinarily too slow to be useful. At temperatures greater than 250°C, yields of the desired trisubstituted ureas are diminished at the expense of various side products. Interestingly, N,N-dialkyl-N',N'-dialkylureas (bis(dialkylureas)) are absent from the product mixture when a dialkyl amine is reacted with a nitroarene according to the process of this invention. This result is surprising in view of the observation by Watanabe ( J. Organometal. Chem. 290 (1985) 252) that N,N'-dibutylurea is a major product in the reaction of nitrobenzene with n-butylamine. The process of the invention may be performed under an atmosphere of carbon monoxide as pressures within the range of 0.01 to 5 MPa (1 atmosphere to 500 atmospheres) Preferably, the process is performed at pressures within the range of 0.1 to 1.7 MPa (10 atm. to 170 atm). The reactor atmosphere optionally may include a percentage of inert gas, such as nitrogen, helium, argon, carbon dioxide, or the like. The process of the invention is optionally performed in the presence of an inert organic solvent. Suitable solvents include, but are not limited to: aromatic hydrocarbons; alkyl-substituted aromatic hydrocarbons; linear, branched, and cyclic alkanes, e.g having up to 20 carbons; halogenated and nitrated aromatic and aliphatic hydrocarbons; and aromatic and aliphatic ethers, tertiary amines, sulfones, sulfoxides, nitriles, esters, and ketones. Specific examples of such solvents include benzene, toluene, xylenes, mesitylene, tetrahydronaphthalene, n-hexane, n-heptane, octane, nonane, cyclohexane, dodecane, octadecane, 2-methylhexane, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, diphenyl ether, tetrahydrofuran, dibutyl ether, triethylamine, pyridine, dimethyl sulfoxide, sulfolane, methyl sulfone, propylene glycol dimethyl ether, ethyl acetate, methyl benzoate, acetone, acetophenone, acetonitrile, benzonitrile and mixtures thereof. The process of the invention may be performed in any suitable reactor. Preferably, the reactor is equipped with a means for controlling temperature and an agitating means. Heating and cooling means may be applied either internally or externally as desired to maintain the reactor temperature within the desired range. The process of the invention may be performed batchwise or continuously, as desired. In a typical batch process, for example, the nitroarene, solvent, secondary amine, transition metal catalyst, and promoters are charged to the reactor and heated to the desired reaction temperature under an atmosphere of carbon monoxide, and optionally an inert gas. If desired, a solution containing the catalyst can be introduced following combination and heating of the other reactants. Alternatively, any of the substrates can be added to a mixture that contains the catalyst. The trisubstituted urea product may be recovered from the reaction mixture by any suitable method, including, for example, filtration, distillation or extraction. In a preferred embodiment of the invention, the unsymmetric urea product is heated in the vapor phase or while dissolved or slurried in an inert organic solvent, optionally in the presence of one or more reaction promoters, to produce an aryl isocyanate. Such a process, which is known in the art as cracking, is described in U.S. Patent Nos. 4,871,871, 4,873,364, and 4,883,908. The teachings of these patents are incorporated herein by reference. Any of the promoters known in the art may be used. Preferred promoters include, but are not limited to, mineral acids, amine halide salts, sulfonic acids, and the like. The following examples merely illustrate the invention. Examples 1-18 Preparation of N′-Phenyl-N,N-diethylurea General Procedure A 300-mL autoclave reactor was charged with nitrobenzene (8.1 g), diethylamine (1-5 equivalents), aniline (0-1 equivalents), solvent (90 mL), triruthenium dodecacarbonyl (0.39 g), and chloride ion-containing promoter (1-5 equivalents based on the amount of Ru catalyst). Carbon monoxide (60 atm) was added, and the contents were heated to the desired reaction temperature with stirring. Carbon monoxide was periodically added to replenish any that was consumed in the reaction. After the desired reaction time, the reaction products were analyzed by gas chromatography and high-performance liquid chromatography to determine the percent conversion of nitrobenzene and the selectivity to various reaction products. The desired product was the unsymmetric urea, N′-phenyl-N,N-diethylurea (DEPU). Other products observed were N,N′-diphenylurea (DPU), N-ethylaniline (EA), and N-ethylformanilide (EF). The halide ion-containing compound used as a reaction promoter was bis(triphenylphosphine)iminium chloride (PPNCl) in all cases except for Example 4, in which tetraethylammonium chloride (TEAC) was used. The effect of using various reaction promoters is illustrated in Table 1; Examples 1 to 3 are comparative Examples: Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Promoters Ex Temp (°C) Time (h) Aniline (eq) Cl-cpd (eq) Conv. (%) Selectivity (%) Net % aniline DEPU DPU 1 140 2.0 0 0 30 10 - 63 2 140 1.0 0 5.0 41 40 4.5 34 3 140 1.0 1.0 0 43 22 2.2 17 4 140 0.5 1.0 5.0 98 62 13 -6.2 5 140 0.5 1.0 5.0 99 73 22 -4.2 6 140 1.0 1.0 1.0 79 59 7 6.1 As shown in Table 1, the desired unsymmetric urea DEPU can be prepared without adding either a primary amine or a halide-containing promoter (Comparative Example 1); most of the charged nitrobenzene was reduced to aniline. When both aniline and a chloride ion source (TEAC) were used, conversion was 98%, and selectivity to DEPU was 62%. With only a chloride source (Comparative Example 2), conversion after 1 hour was 41% and selectivity to DEPU was 40%. When only aniline was used as a promoter (Comparative Example 3), conversion was 43% and selectivity to DPU was 22%. With aniline present and bis(triphenylphosphine)iminium chloride (PPNCl) as the halide source, 99% conversion and 73% selectivity to DEPU were achieved. (Example 5). Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Temperature Ex Temp (°C) Time (h) Conv. (%) Selectivity (%) Net % Aniline DEPU DPU EA EF 5 140 0.5 99 73 22 -- -- -4.2 7 110 1.0 40 49 2.2 -- -- 10 8 170 0.5 99 30 -- 40 40 -- The effect of reaction temperature is illustrated in Table 2. At 140°C (Example 5), conversion was nearly quantitative within 30 minutes, and selectivity to DEPU was high (73%). Decreasing the temperature to 110°C (Example 7) resulted in incomplete conversion (40%) of the nitrobenzene after one hour. At 170°C, conversion was complete within 30 minutes, but selectivity to DEPU decreased; two new products, N-ethylaniline and N-ethylcarbanilide, were formed. Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Solvent Ex Temp (°C) Time (h) Solvent Conv. (%) Selectivity (%) Net % Aniline DEPU DPU 5 140 0.5 p-xylene 99 73 22 -4.2 9 140 0.5 tetrahydrofuran 99 83 9.4 2.8 10 140 0.5 1,4-dioxane 85 65 4.1 17 11 140 0.5 acetonitrile 81 77 3.8 13 12 140 0.5 o-dichlorobenzene 99 63 13 6.5 The process of the invention may be performed in a wide range of solvents. As shown in Table 3, aromatic hydrocarbons, ethers, nitriles, and halogenated aromatic hydrocarbons are all suitable. Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Amount of Aniline Charged Ex Temp (°C) Time (h) Aniline charged (eq/eq NO₂) Conv (%) Selectivity (%) Net % Aniline DEPU DPU 13 140 0.5 0 82 47 3.6 9.1 14 140 0.5 0.5 91 77 10 8.8 5 140 0.5 1.0 99 73 22 -4.2 Table 4 illustrates the effect of changing the amount of aniline used. Incomplete conversion was observed when aniline was omitted (Comparative Example 13). With one equivalent of aniline (Example 5), conversion was complete within 30 minutes, and selectivity to DEPU was 73%. With 0.5 equivalents of aniline (Example 14), conversion after 30 minutes was 91%, and selectivity was 77%. Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Amount of Diethylamine Ex Temp (°C) Time (h) DEA (eq) Solvent Conv. (%) Selectivity (%) Net % Aniline DEPU DPU 15 140 0.25 1.0 THF 92 91 5.7 -1.2 9 140 0.50 2.0 THF 99 83 9.4 2.8 16 140 2.0 5.0 p-xylene 84 49 7.8 19 As shown in Table 5, the proportion of diethylamine used also impacts the selectivity to DEPU. With 5 equivalents of DEA (Example 16), 49% selectivity to DEPU was observed, and there was a large increase in the amount of aniline produced. With 1-2 equivalents of DEA (Examples 9, 15), good conversions (92-99%) and high selectivities to DEPU (83-91%) were achieved. Synthesis of N'-Phenyl-N,N-diethylurea by Carbonylation Effect of Group VIII Metal Ex Catalyst Time (h) Conv. (%) Selectivity (%) Net % Aniline DEPU DPU 15 Ru₃(CO)₁₂ 0.25 92 91 5.7 -1.2 17 PdCl₂(PPh₃)₂ 1.0 18 65 7.8 11.1 18 RhCl(PPh₃)₃ 1.0 1.5 90 8.0 0.5 ¹Products: DEPU = N,N-diethyl-N'-phenylurea; DPU = N,N'-diphenylurea ²All reactions were performed in THF at 140°C and 60 atm. CO with 0.5 eq. aniline/eq. nitrobenzene. Substrate/catalyst =100. TPPCl (5 eq./eq. catalyst) was used in Example 15 only. Table 6 shows how other Group VIII metals can be used as catalysts for the process of the invention. Table 7 illustrates the carbonylation reaction for various nitroarenes. Nitroarene Carbonylation Ex Substrate Time (h) Conv. (%) Products (%) 15 Nitrobenzene 0.25 92 DEPU (91 %), DPU (5.7%) 19 4,4'-dinitrodiphenylmethane 0.50 83 MBPDEU (21%) 20 4,4'-dinitrobiphenyl 1.0 40 BPDEU (60%) ¹Products: DEPU = N,N-diethyl-N'-phenylurea; DPU = N,N'-diphenylurea MBPDEU =4,4'-methylene-bis-(N'-phenyl-N,N-diethylurea) BPDEU=4,4'-bis-(N'-phenyl-N,N-diethylurea) ²All reactions were performed in THF at 140°C and 60 atm. CO with 0.5 eq. aniline/eq. substrate using triruthenium dodecacarbonyl as the catalyst. Substrate/catalyst/TPPCl=100/5/1. One eq. of diethylamine/eq. substrate was used. Example 21 Preparation of N'-Phenyl-N,N-pyrrolidinylurea The procedure of Examples 1-18 was generally followed with nitrobenzene (8.1 g), pyrrolidine (1 eq.), triruthenium dodecacarbonyl (0.39 g), aniline (1 eq.), bis(triphenylphosphine) iminium chloride (5 eq based on catalyst), and tetrahydrofuran (90 mL). After 30 minutes at 140°C, conversion of nitrobenzene was 97%. The products obtained were N'-phenyl-N,N-pyrrolidinylurea (49%), N,N'-diphenylurea (9%), and aniline (about 40%).

Claims: A process for making a trisubstituted urea, said process comprising: reacting a nitroarene with carbon monoxide and a secondary amine in the presence of a Group VIII transition metal catalyst and, as promoters, a primary amine and a halide ion-containing compound. A process as claimed in claim 1 characterised in that the nitroarene is selected from nitrobenzene, nitrotoluenes, nitronaphthalenes nitrotoluidines, dinitrobenzenes, dinitrotoluenes, nitrochlorobenzenes, nitroanisoles alkylated nitroarenes, bis(nitrophenyl) ethers, nitro-substituted biphenyls, and bis(nitrophenyl) alkylenes. A process as claimed in claim 1 characterised in that the nitroarene is selected from 2,4-dinitrotoluene, 2,6-dinitrotoluene, 4,4'-bis(nitrophenyl)-methylene, 4,4'-bis(nitrophenyl)-ether, 2,2-bis(4-nitrophenyl)-propane, 1,1-bis(4-nitrophenyl)-1-phenylethane, nitro-substituted ethylbenzenes, and 4,4'-dinitrobiphenyl. A process as claimed in any one of claims 1 to 3 characterised in that the process is performed at a temperature within the range of 40°C to 250°C. A process as claimed in claim 4 characterised in that the process is performed at a temperature within the range of 90°C to 200°C. A process as claimed in any one of claims 1 to 5 characterised in that the process is performed in the presence of one or more organic solvents selected from aromatic hydrocarbons, alkyl-substituted aromatic hydrocarbons, alkanes, cycloalkanes, halogenated aliphatic and aromatic hydrocarbons, nitro compounds, tertiary amines, sulfones, sulfoxides, and aromatic and aliphatic ethers, ketones, esters, and nitriles. A process as claimed in any one of claims 1 to 6 characterised in that the process is performed at a pressure within the range of 0.01 to 5 MPa (1 to 500 atmospheres). A process as claimed in claim 7 characterised in that the process is performed at a pressure within the range of 0.1 to 1.7 MPa (10 to about 170 atmospheres). A process as claimed in any one of claims 1 to 8 characterised in that the Group VIII transition metal catalyst is a ruthenium compound. A process as claimed in claim 9 characterised in that the ruthenium compound is selected from triruthenium dodecacarbonyl, ruthenium trichloride, and ruthenium oxide. A process as claimed in claim 10 characterised in that the process is performed in the presence of aniline and at least one mole of halide ion-containing compound per mole of triruthenium dodecacarbonyl. A process as claimed in any one of claims 1 to 11 characterised in that the secondary amine is selected from dimethylamine, diethylamine, and diisopropylamine. A process as claimed in claim 12 characterised in that the nitroarene is one or more dinitrotoluene isomers. A process as claimed in any one of claims 1 to 13 characterised in that the chloride ion-containing compound is selected from bis(triphenylphosphine)iminium chloride and tetralkylammonium chloride compounds. A process as claimed in any one of claims 1 to 14 characterised in that the trisubstituted urea is thermally converted to an aryl isocyanate by heating in the vapor phase or in an organic solvent, optionally in the presence of a promoter.

Inventors: KESLING HAVEN S JR, SAXTON ROBERT J, SHAWL EDWARD T, SHUM WILFRED PO-SUM, ZAJACEK JOHN G, KESLING, HAVEN S., JR., SAXTON, ROBERT J., SHAWL, EDWARD T., SHUM, WILFRED PO-SUM, ZAJACEK, JOHN G.
Applicants: ARCO CHEM TECH, ARCO CHEMICAL TECHNOLOGY, L.P.
Application year: 1992
Main classification: C07C273
IPC codes: B01J23, B01J27, C07C261, C07D295, C07C275, C07C273, C07B61