PROCESS FOR PREPARING ISOCYANATE COMPOUND

Abstract

A process for preparing an isocyanate compound is provided. The process includes a step of reacting an amine compound A having at least one primary amino group with CO.sub.2 and an organotin compound S having at least one radical OR.sup.3 attached to the tin atom of the organotin compound to convert at least one of the primary amino groups in the amine compound A into a carbamate group to obtain a carbamate compound C; a step of cleaving the carbamate groups in the obtained carbamate compound C to form the isocyanate compound and an alcohol R.sup.3OH, without separation of the tin compounds; and a step of obtaining the isocyanate compound. The radical R.sup.3 is a C-bound organic radical of 1-30 carbon atoms with 1, 2, or 3 carbon atoms optionally replaced by oxygen or nitrogen.

Claims

1. A process for preparing an isocyanate compound, the process comprising: a) reacting an amine compound A comprising at least one primary amino group with CO.sub.2 and an organotin compound S comprising at least one radical OR.sup.3 attached to the tin atom of the organotin compound, wherein R.sup.3 is a C-bound organic radical comprising from 1 to 30 carbon atoms, wherein 1, 2 or 3 carbon atoms are optionally replaced by oxygen or nitrogen, to convert at least one of the primary amino groups in the amine compound A into a carbamate group, thereby obtaining a carbamate compound C; b) cleaving the carbamate groups group in the carbamate compound C obtained in a) to form the isocyanate compound and an alcohol R.sup.3OH, without separation of the tin compounds formed in a); and c) obtaining the isocyanate compound from the reaction mixture of b).

2. The process of claim 1, wherein the organotin compound S is employed in an amount of from 0.9 to 10 mol per mol of primary amino groups in the amine compound A.

3. The process of claim 1, wherein a) is carried out in bulk or in an aprotic organic solvent.

4. The process of claim 1, wherein a) is carried out by introducing CO.sub.2 in a reaction mixture containing the amine compound A and the organotin compound S.

5. The process of claim 1, wherein b) is carried out as a distillation of the reaction mixture obtained in a) to obtain the isocyanate compound.

6. The process of claim 1, wherein unreacted starting material of a) is removed before b) is carried out.

7. The process of claim 1, further: adding an alcohol R.sup.3OH to the reaction mixture of b) after having obtained the isocyanate compound from the reaction mixture of b) in order to regenerate the organotin compound from the organotin compounds formed in a) or b).

8. The process of claim 7, wherein at least a part of the alcohol R.sup.3OH used to regenerate the organotin compound from the organotin compounds formed in a) or b) is the alcohol formed in b).

9. The process of claim 1, wherein the isocyanate compound has a lower vapor pressure than the organotin compounds.

10. The process of claim 1, wherein the organotin compound S is represented by formula (I)
R.sup.1R.sup.2Sn(OR.sup.3).sub.2 (I) wherein R.sup.1 and R.sup.2 are independently a C-bound organic radicals radical having from 1 to 30 carbon atoms, and R.sup.3 is as defined in claim 1.

11. The process of claim 10, wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of C.sub.1-C.sub.18-alkyl, C.sub.1-C.sub.8-alkoxy-C.sub.1-C.sub.8-alkyl, C.sub.3-C.sub.16-cycloalkyl, C.sub.3-C.sub.16-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy.

12. The process of claim 1, wherein R.sup.3 is selected from the group consisting of C.sub.1-C.sub.18-alkyl, C.sub.3-C.sub.16-cycloalkyl, C.sub.3-C.sub.16-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy.

13. The process of claim 1, wherein the amine compound A comprises 1 or 2 primary NH.sub.2 groups.

14. The process of claim 13, wherein the amine compound A is a compound of formula (II) or a compound of formula (III):
H.sub.2NR.sub.4 (II)
H.sub.2NXN H.sub.2 (III), wherein R.sup.4 is an organic radical comprising from 1 to 30 carbon atoms, wherein 1, 2 or 3 carbon atoms are optionally replaced by oxygen or nitrogen; and X is a bivalent organic radical comprising from 2 to 30 carbon atoms, wherein 1, 2 or 3 carbon atoms are optionally replaced by oxygen or nitrogen.

15. The process of claim 14, wherein the amine compound A is a compound of the formula (II), where R.sup.4 is selected from C.sub.1-C.sub.12-alkyl, C.sub.3-C.sub.12-cycloalkyl, C.sub.3-C.sub.12-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.14-aryl and C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl, which are unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, or the amine compound A is a compound of formula (III), where X is C.sub.2-C.sub.12-alkanediyl, C.sub.3-C.sub.12-cycloalkanediyl, C.sub.6-C.sub.14-arylene, L-R.sup.x, or R.sup.x-L-R.sup.x, wherein C.sub.3-C.sub.12-cycloalkanediyl and C.sub.6-C.sub.14-arylene are unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, L is C.sub.1-C.sub.12-alkanediyl, C.sub.3-C.sub.12-cycloalkanediyl or C.sub.6-C.sub.14-arylene, L is O, S, SO.sub.2, C.sub.1-C.sub.12-alkanediyl, C.sub.3-C.sub.12-cycloalkanediyl or C.sub.6-C.sub.14-arylene, R.sup.x, R.sup.x independently of each other are selected from C.sub.3-C.sub.12-cycloalkandiyl or C.sub.6-C.sub.14-arylene, both of which are unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy.

16. The process of claim 14, wherein the amine compound A is 1,6-diaminohexane, a diaminotoluene, or a mixture of isomers thereof.

Description

[0154] The invention is illustrated in detail by the examples below.

[0155] Analytic:

[0156] Gas chromatograph (GC): Agilent Technologies 6890N Network GC System HPLC: HPLC Chiralpka IB using a mixture of hexane/isopropanol, wherein the ratio of hexane and isopropanol is:

[0157] from 0 to 5 min: 5% isopropanol, 95% hexane,

[0158] from 5 to10 min: 15% isopropanol, 85% hexane

[0159] from 1 to 25 min: 25% isopropanol, 75% hexane

[0160] from 25 min: 50% isopropanol, 50% hexane.

[0161] .sup.1H-NMR spectrometer:

[0162] IR spectrometer:

[0163] Commercial carbamate, Methyl N-phenylcarbamate (>98.0%): TCI

[0164] Dimethyltin(IV) dichloride (96%): Sigma Aldrich

[0165] 2,4-diaminotoluene (>98%): TCI

[0166] Dimethyltin(IV) oxide (96%): Sigma Aldrich

[0167] 4,4-methylenedianliline:

[0168] 1. Preparation of the Tin Compounds

EXAMPLE 1-1

Synthesis of Dimethyltin(IV)Dimethoxide

[0169] In a glovebox a Schlenk tube was charged with sodium methoxide (1.79 g; 33.15 mmol). Dry methanol (100 mL) was added and the obtained solution was cooled to 40 C. (dry-ice bath). To this mixture, dimethyltin(IV) dichloride (3.64 g; 16.57 mmol) was added in portions within 20 minutes. The reaction mixture was allowed to warm up to room temperature within 5 hours. After this, sodium chloride was removed by filtration of the crude mixture through a Celite path. Methanol was then distillated off under 1 atm. The desired compound was eventually recrystallized in pentane at 40 C. to give a crystalline colorless solid (1.19 g; 29%).

EXAMPLE 1-2

Synthesis of Dimethyltin(IV)Dimethoxide

[0170] In a glovebox a 200 mL Schlenk flask was charged with sodium methoxide (1.79 g; 33.15 mmol). Under an atmosphere of argon dry methanol (70 mL) was added to the flask and the obtained solution was cooled to 0 C. (water-ice bath). To this mixture, dimethyltin(IV) dichloride (3.64 g; 16.57 mmol) was added in portions within 20 minutes. The reaction mixture was allowed to warm up to room temperature within 13 hours. The resulting mixture was transferred into a round-bottom flask (250 mL) surmounted by a distillation apparatus. Methanol was distilled off (95% of the overall volume). The resulting colorless oil was transferred into the glovebox and 100 mL dry pentane was added. Insoluble material was filtered off over cellite. The desired compound (colorless crystals; 72%; 2.53 g) was obtained by crystallization from the pentane solution by storing it for 24 h at 40 C.

[0171] The synthesis of dimethyltin(IV) bis(2,2,2-trifluoroethanol) and dibutyltin(IV) bis(2,2,2-trifluoroethanol) have been prepared similarly to the example 1-1 or 1-2 mentioned above.

[0172] .sup.1H NMR (400 MHz, [D.sub.8]Toluene): =3.35 (s, 6H; MeO), 0.30 ppm (t, .sup.3J(HH)=3.6 Hz, 6H; CH.sub.3);

[0173] .sup.13C NMR (100 MHz, [D.sub.8]Toluene): =50.9, 1.7 ppm

[0174] .sup.119Sn NMR (298 K; 111.82 MHz; [D.sub.8]Toluene): =133.1 ppm

[0175] 2. Preparation of the Carbamate Compounds:

EXAMPLE 2-1

Synthesis of 2,4-toluene Dimethylcarbamate

[0176] In a glovebox, a stainless 60 mL steel Premex autoclave was charged with dibutyltin(IV) dimethoxide (1.68 g; 6 mmol), 2,4-diaminotoluene (0.122 g.; 1 mmol) and pentane (10 mL). The autoclave was sealed and, outside the glovebox, pressurized with 50 bar of carbon dioxide. The mixture was stirred and after 10 minutes an equilibrium of the CO.sub.2 uptake was achieved. Then the mixture was heated to 135 C. After 3 hours, the autoclave was cooled by a water ice-bath. After 30 minutes, the pressure was released. The autoclave was then unsealed. The crude mixture was filtered and the yellow solid was washed with cold pentane (three times). Analytically pure 2,4-toluene dimethylcarbamate was obtained (77% ,185 mg). The tin species remains in the organic solvent and can be regenerated from this phase and reused in carbamation reaction.

[0177] .sup.1H NMR (200 MHz, [D.sub.2]Dichloromethane): =7.78 (s, 1H; H.sub.ar), 7.16-7.03 (m, 2H; H.sub.ar), 6.79 (bs, 1H; NH), 6.48 (bs, 1H; NH), 3.73 (s, 3H; NHCO.sub.2CH.sub.3), 3.71 (s, NHCO.sub.2CH.sub.3, 3H), 2.16 ppm (s, 3H; ArCH.sub.3);

[0178] .sup.13C NMR (100 MHz, [D.sub.2]Dichloromethane): =154.5, 154.3, 137.2, 136.8, 131.0 (3C), 52.7, 52.5, 17.1 ppm;

[0179] Elementar Analysis: calcd (%) for C.sub.11H.sub.14N.sub.2O.sub.4 (238.1): C 55.46, H 5.92, N 11.76; found:

[0180] C 54.66, H 6.64, N 11.19.

[0181] MS (El): m/z(%): 256.43 [M+H.sub.2O])

[0182] The cleavage of 2,4-toluene dimethylcarbamate to 2,4-toluene diisocyanate can be carried out in analogy to the example 3-1 to 3-3 mentioned below.

EXAMPLE 2-2

Synthesis of Methylene diphenyl-4,4-dimethylcarbamate

[0183] In a glovebox, a stainless 60 mL steel Premex autoclave was charged with dibutyltin(IV) dimethoxide (1.68 g; 6 mmol), 4,4-methylenedianliline (0.204 g; 1 mmol) and pentane (10 mL). The autoclave was sealed and, outside the glovebox, pressurized with 50 bar of carbon dioxide. The mixture was stirred and after 10 minutes an equilibrium of the CO.sub.2 uptake was achieved. Then the mixture was heated to 135 C. After 3 hours, the autoclave was cooled by a water ice-bath. After 30 minutes, the pressure was released. The autoclave was then unsealed. The crude mixture was filtered and the yellow solid was washed with cold pentane (three times). Analytically pure methylene diphenyl-4,4-dimethylcarbamate was obtained (42% ,185 mg). The tin species remains in the organic solvent and can be regenerated from this phase and reused in the subsequent carbamation reaction.

[0184] .sup.1H NMR (400 MHz, [D.sub.6]dimethylsulfoxide): =9.52 (bs, 2H; NH), 7.35 (d, .sup.3J(HH)=8.4 Hz, 4H; H.sub.ar), 7.11 (d, .sup.3J(HH)=8.4 Hz, 4H; H.sub.ar), 3.79 (s, 2H; CH.sub.2), 3.64 ppm (s, 6H; NHCO.sub.2CH.sub.3);

[0185] .sup.13C NMR (100 MHz, [D.sub.6]dimethylsulfoxide): =154.0, 137.0, 135.5, 128.8, 118.4, 114.0, 51.5 ppm

[0186] Elementar Analysis: calcd (%) for C.sub.17H.sub.18N.sub.2O.sub.4 (314.1): C 64.96, H 5.77, N 8.91; found C 65.5, H 5.8, N 9.1.

[0187] MS (EI): mlz(%): 314.53 [M+H.sub.2O])

[0188] The cleavage of methylene diphenyl-4,4-dimethylcarbamate to diphenylmethane-4,4-diisocyanat can be carried out in analogy to the example 3-1 to 3-3 mentioned below.

[0189] 3. Preparation of the Isocyanate Compound

EXAMPLE 3-1

Synthesis of Ethyl N-phenylcarbamate and Phenyl Isocyanate

[0190] In a glovebox, a stainless steel Premex autoclave was charged with dibutyltin(IV) dimethoxide (3 equiv.; 930 mg; 3 mmol), aniline (1 equiv.; 93.1 mg; 1 mmol) and 1,2,4-trichlorobenzene (10 mL). The autoclave was sealed and, outside the glovebox, pressurized with 50 bar of carbon dioxide. The mixture was stirred and after 10 minutes an equilibrium of the CO.sub.2 uptake was achived (41 bar). Heating to the desired temperature was eventually started (pressure of 69 bar at 135 C.). After 3 hours of reaction, the autoclave was cooled down to room temperature. The pressure was released and the autoclave was unsealed and opened up in the glovebox. The crude mixture was transferred into a round-bottom flask (25 mL). Outside the glovebox, methyl N-phenyl methyl carbamate and 1,2,4-trichlorobenzene were distillated off at 60 C. (oil bath temperature) under 1.10.sup.3 mbar leaving bis(dimethylmethoxytin(IV)) oxide which was converted to dimethyltin(IV) dimethoxide. The flask containing the solution of methyl N-phenylcarbamate (MPC) in 1,2,4-trichlorobenzene was surmounted by a condenser and the solution was heated to 230 C. for 5 hours. The solution was then cooled down to room temperature and absolute ethanol (5 mL) was added. The resulting mixture was heated again to 100 C. for 3 hours. The crude mixture was coiled down to room temperature. An aliquot was taken for HPLC analysis. After this, absolute ethanol (5 mL) was added. The resulting mixture was heated again to 100 C. for 3 hours. After cooling down the crude to room temperature, a sample was taken for HPLC analysis.

[0191] Before the addition of ethanol, phenyl isocyanate was identified.

[0192] Similar results were obtained when decalin was used as a solvent instead.

[0193] HPLC data were collected from HPLC Chiralpka IB using a mixture of hexane/isopropanol, wherein the ration of hexane and isopropanol is as defined above. Commercial phenyl isocyanate (with the UV fingerprint) were used as referenced for HPLC analysis: t=12.90; area [%]=100.

[0194] The H PLC-spectra for an aliquot of the crude mixture after 1 hour shows the following peaks:

[0195] aniline (identified by UV fingerprint): t=11.779, area [%]=2.295,

[0196] phenyl isocyanate: t=12.902, area [%]=25.173,

[0197] diphenylurea (identified by UV fingerprint and HPLC-MS):t=13.251, area [%]=1,705,

[0198] methyl N-phenylcarbamate: t=24.653, area [%]=70.827.

[0199] The H PLC-spectra for an aliquot of the crude mixture after 2 hour shows the following peaks:

[0200] phenyl isocyanate: t=13.014, area [%]=55.869,

[0201] methyl N-phenylcarbamate: t=25.101, area [%]=44.131.

[0202] The IR-spectra of the crude mixture after 2 hour (see FIG. 1) shows a signal at 2261 cm.sup.1, which can be assigned to characteristic signal of the phenylisocyanat (in accordance with the IR spectra of commercial phenylisocyanate as well as the values given in literature).

[0203] After quenching the isocyanate with absolute ethanol and reaction under the conditions described above (5 hours of thermolysis), the HPLC-spectra shows the following peaks:

[0204] methyl Aphenylcarbamate: t=24.918, area [%]=37.882,

[0205] ethyl N-phenylcarbamate: t=26.099, area [%]=62.118.

EXAMPLE 3-2

Synthesis of Methyl N-phenylcarbamate and Phenylisocyanate

[0206] In a glovebox, a 60 mL stainless-steel Premex autoclave was charged with dimethyltin(IV)dimethoxide (211 mg; 1 mmol) and aniline (93 mg, 1 mmol). The solvent according to table 1 below was added and the autoclave was sealed. The autoclave was pressurized with carbon dioxide (50 bar) at room temperature and the mixture stirred for ten minutes. The pressure dropped to 30 bar. Afterwards, the autoclave was heated to 150 C., whereby the pressure increased to the pressure given below in table 1. After the reaction, the conversion and yield of carbamate/isocyanate was measured directly from the crude reaction mixture by gas chromatography. The gas chromatogram showed that isocyanate is formed directly out of the crude reaction mixture, obtaining the tin residue, by cleaving the carbamate under the conditions of the evaporation in the GC-oven (250 C., ambient pressure). The carbamate was cleaved into phenyl isocyanate and aniline. It was observed that the ratio of the phenyl isocyanate to aniline varied as a function of the injection temperature. The reaction can be carried in toluene, 1,2,4-trichlorobenzene, acetonitrile, dichloromethane or pentane. It was also observed that an increase of tin alkoxides equivalents improved the conversion.

[0207] A mixture of commercial carbamate (methyl N-phenylcarbamate) and dimethyltin(IV) oxide in dichloromethane was also analyzed by GC. Depending of the injection temperature, different ratios of aniline, isocyanate and carbamate were detected, whereas a single peak was observed after injection of a solution of carbamate in dichloromethane. This supports that dimethyltin(IV) oxide also forms during the reaction between aniline, carbon dioxide and diemthyltin(IV)dimethoxide and that the dimethyltin(IV) oxide is responsible for carbamate cleavage during the GC injection.

[0208] Reaction of dimethyltin(IV) bis(2,2,2-trifluoroethanol) or dibutyltin(IV) bis(2,2,2-trifluoroethanol) with aniline and carbon dioxide under the same conditions resulted in the formation of phenyl isocyanate after GC injection.

TABLE-US-00001 TABLE 1 Conversion Ratio Pressure at Aniline [%]; PhNCO:PhNHCOOMe; Solvent Reaction time 150 C. determined by determined by Entry [mL] [h] [bar] GC-Area % GC-Area % 1 Toluene (10) 16 71 48 17:31 2 Toluene (10) 27 71 54 16:38 3 Toluene (20) 16 71 28 9:19 4 CH.sub.2Cl.sub.2 (10) 16 71 71 26:37 5 Pentane (10) 27 16 67 23:44

EXAMPLE 3-3

Cracking of the Crude Mixture Containing Methyl N-phenylcarbamate, Dimethyltin(IV)oxide and the Solvent:

[0209] In a glovebox, a 25 mL round-bottom flask was charged with methyl N-phenyl carbamate (1.65 g, 10 mmol) and dimethyltin(IV) oxide (1.52 g, 10 mmol). 1,2,4-trichlorobenzene (25 mL) was added and the flask was connected to a head-column. The mixture was heated at 180 C. under vacuum (5.10.sup.2 bar) for 16 hours. Isocyanate was detected in GC.

EXAMPLE 3-4

Synthesis of Methyl N-[3-(methoxycarbonylamino)-4-methyl-phenyl]-carbamate and 2,4-diisocyanato-1-methyl-benzene

[0210] In a glovebox, a 60 mL stainless-steel Premex autoclave was charged with dimethyltin(IV)dimethoxide (422 mg; 2 mmol) and 2,4-diaminotoluene (122 mg, 1 mmol). Dry dichloromethane (10 mL) was added. The autoclave was pressurized with carbon dioxide (50 bar) at room temperature and the mixture stirred for ten minutes. The pressure dropped to 30 bar. Afterwards, the autoclave was heated to 150 C., whereby the pressure increased to 70 bar. .sup.1H-NMR-spectrum of the crude mixture evidenced the formation of the desired compound, the dicarbamate methyl N-[3-(methoxycarbonylamino)-4-methyl-phenyl]carbamate.

[0211] The crude mixture containing methyl N-[3-(methoxycarbonylamino)-4-methyl-phenyl]-carbamate was placed in a sublimation apparatus (cold finger filled with dry-ice/acetone) and heated under vacuum to 200 C. The 2,4-diisocyanato-1-methyl-benzene was collected and observed by .sup.1H-N MR-spectrum.