PROCESS FOR THE PRODUCTION OF CYCLIC GUANIDINE DERIVATES

Abstract

The present invention relates to a process for the production of cyclic guanidine derivates of formula I or mixtures of them (formula I) by reacting a triamine in the present of a C.sub.1-source and a solid material in the gas or liquid phase under inert atmosphere.

##STR00001##

Claims

1-14. (canceled)

15. A Process for the production of cyclic guanidine derivates of formula I or mixtures of them ##STR00008## wherein R.sup.1 to R.sup.—are independently selected from the group of H and C.sub.1- to C.sub.4 alkyl and n and m are a natural number independently selected from the group of 0 and 1 by reacting a triamine in the present of a C.sub.1-source in a reactor filled with a solid material selected from the group of inert material, aluminium silicates, aluminium oxide, zeolites or mixtures or layers of these in the gas or liquid phase under inert atmosphere at a temperature of at least 90° C. and a pressure of 1 to 320 bar.

16. The process according to claim 15, wherein the triamine and C.sub.1-source are solved in a solvent selected from the group of methanol, ethanol, iso-propanol, butanol, diethyleneglycol, butyldiglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

17. The process according claim 15, wherein the solvent is methanol, diethyleneglycol or butyldiglycol.

18. The process according to claim 15, wherein the triamine is selected from the group of N-(3-aminopropyl)propane-1,3-diamine (DPTA), N-(2-aminoethyl)ethane-1,2-diamine (DETA) and N-(2-aminoethyl)-1,3-propanediamine.

19. The process according to claim 15, wherein the C.sub.1-source is selected from the group of dimethyl carbonate, urea, dimethylformamide dimethyl acetal, carbon dioxide, ethylene carbonate, propylene carbonate, phosgene and cyanamide.

20. The process according to claim 15 wherein the process provides the following three steps: I) reaction of the triamine in the present of the C.sub.1-source at a temperature of at least 90° C. to an urea compound of formula II ##STR00009## wherein R.sup.1 to R.sup.13 and n and m have the same meaning as in formula I II) dissolving the crude urea compound of formula II of step I) in a solvent III) cyclisation of the crude and solved urea compound of formula II from step II) in the gas or liquid phase under inert atmosphere in the present of the solid material at a temperature of at least 120° C. and a pressure in the range of 1 to 320 bar.

21. The process according to claim 15, wherein the process is made in the gas phase at a temperature of at least 150° C. and a pressure of 1 to 35 bar.

22. The process according to claim 20, wherein in step I) of the process catalytical amounts of an organic base or acid are present.

23. The process according to claim 20, wherein the solvent of step II) of the process is selected from the group of methanol, ethanol, iso-propanol, butanol, diethyleneglycol, butyldiglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

24. The process according to claim 20, wherein in step I) of the process a solvent selected from the group of methanol, ethanol, iso-propanol, butanol, diethyleneglycol, butyldiglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone is used.

25. The process according to claim 20, wherein step II) is included in step I) when the solvents of step II) and step I) are the same.

26. The process according to claim 15, wherein cyclic guanidine derivates of formula I are a mixture of 1,5,7-triazabicyclo[4.4.0]dec-5-en and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-en.

27. The process according to claim 15, wherein cyclic guanidine derivates of formula I are a mixture of 1,2,3,5,6,7-hexyhydroimidazol[1,2-a]pyrimidine and 8-methyl-1,2,3,5,6,7-hexahydroimidazol[1,2-a]pyrimidine.

28. The process according to claim 15, wherein cyclic guanidine derivates of formula I are a mixture of 2,3,5,6-tetrahydro-1H-imidazol[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazol[1,2-a]imidazole.

Description

EXAMPLES

[0051] For the further examples the following abbreviation will have the following meaning: [0052] DPTA: dipropylenetriamine (3,3′-diaminodipropylamine) [0053] DPTU: 1-(3-aminopropyl)tetrahydropyrimidin-2(1H)-one [0054] TBD: 1,5,7-triazabicyclo[4.4.0]dec-5-en [0055] Me-TBD: 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-en
Reaction of DPTA with CO.sub.2:

Example 1

[0056] 40 mL of a 50 wt % solution of DPTA in methanol was transferred to a 0.3 L high-pressure laboratory autoclave equipped with an overhead stirrer and a gas inlet. At room temperature, the autoclave was purged three times with carbon dioxide (5 bar). The pressure was then again increased to 5 bar and the stirrer was started. Within 20 min, carbon dioxide was injected in portions to establish a pressure of 8 to 10 bar. Then, the autoclave was heated to 180° C. Upon reaching 180° C., the pressure was increased to 61 bar by injecting further carbon dioxide. Upon reaching 61 bar, the reaction mixture was stirred for 16 hours. Thereafter, the reaction mixture was cooled to room temperature and the autoclave was depressurized to ambient pressure. The reaction mixture was analyzed by gas chromatography.

[0057] The composition of the reaction mixture (without solvents) is given in area percent and was as follows: [0058] 11% DPTU [0059] 6% TBD [0060] 20% 1-methyltetrahydropyrimidin-2(1H)-one [0061] 27% 1-ethyltetrahydropyrimidin-2(1H)-one

Example 2

[0062] 40 mL DPTA was transferred to a 0.3 L high-pressure laboratory autoclave equipped with an overhead stirrer and a gas inlet. At room temperature, the autoclave was purged three times with carbon dioxide (3 bar). The pressure was then again increased to 5 bar and the stirrer was started. Within 20 min, carbon dioxide was injected in portions to establish a pressure of 20 bar. Then, the autoclave was heated to 180° C. Upon reaching 180° C., the pressure was increased to 61 bar by injecting further carbon dioxide. Upon reaching 62 bar, the reaction mixture was stirred for 16 hours. Thereafter, the reaction mixture was cooled to room temperature and the autoclave was depressurized to ambient pressure. The reaction mixture was analyzed by gas chromatography.

[0063] The composition of the reaction mixture (without solvents) is given in area percent and was as follows: [0064] 31% DPTU [0065] 6% TBD [0066] 16% 1-methyltetrahydropyrimidin-2(1H)-one [0067] 22% 1-ethyltetrahydropyrimidin-2(1H)-one

Example 3

[0068] 40 mL of a 50 wt % solution of DPTA in N-methylpyrrolidone was transferred to a 0.3 L high-pressure laboratory autoclave equipped with an overhead stirrer and a gas inlet. At room temperature, the autoclave was purged three times with carbon dioxide (3 bar). The pressure was then again increased to 5 bar and the stirrer was started. Within 20 min, carbon dioxide was injected in portions to establish a pressure of 15 bar. Then, the autoclave was heated to 180° C. Upon reaching 180° C., the pressure was increased to 61 bar by injecting further carbon dioxide. Upon reaching 64 bar, the reaction mixture was stirred for 16 hours. Thereafter, the reaction mixture was cooled to room temperature and the autoclave was depressurized to ambient pressure. The reaction mixture was analyzed by gas chromatography.

[0069] The composition of the reaction mixture (without solvents) is given in area percent and was as follows: [0070] 31% DPTU [0071] 5% TBD [0072] 13% 1-methyltetrahydropyrimidin-2(1H)-one [0073] 20% 1-ethyltetrahydropyrimidin-2(1H)-one
Reaction of DPTA with dimethyl carbonate

Example 4

[0074] A 1000 mL three-necked flask equipped with a reflux condenser was charged with 100 g (0.76 mol) DPTA and 6.9 g (0.05 mol) TBD. The mixture was cooled to 8 ° C. by using an ice bath. 75 g (0.83 mol, 1.09 equiv) Dimethyl carbonate were added dropwise after 2 h. The reaction mixture was then allowed to warm to 20° C. After reaching 20° C., the mixture was heated to 90° C. with an oil bath and was kept at this temperature for 6 h. The reflux condenser was then substituted by a distillation bridge and the generated methanol was distilled off under atmospheric pressure with an oil bath temperature of up to 130° C. After distillation, the solution was cooled to 20° C. and was used for the next step(s) as received and without further purification.

Exemplary product mixture composition:

[0075] The composition of the reaction mixture (without solvents) is given in area percent and was as follows [0076] 78% DPTU [0077] 11% DPTA [0078] 6% TBD

Step II and III:

Example 5

[0079] Gas phase cyclization of 1-(3-aminopropyl)tetrahydropyrimidin-2(1H)-one (DPTU) to 1,5,7-triazabicyclo[4.4.0]dec-5-en (TBD)

##STR00007##

[0080] A double-walled glass reactor of 1000 mm length, diameter 40 mm with oil heating, a quartz frit at the bottom, an inlet for liquid and gaseous feeds at the top connected to a pump and gaseous feeds (N.sub.2) measured via rotameters, was set up vertically and the outlet (bottom) was connected to a collecting flask. The off-gas was connected to a laboratory hood vent. Into the center of the reactor, a glass tube was put from the top down and a flexible thermocouple was introduced into this tube. The reactor was filled in three layers. First, 200 mL of Raschig rings composed of steel wire mesh (diameter 5 mm) were loaded onto the quartz frit. Then a catalyst (100 mL, 3 mm split/excrudates) was introduced. The height of the catalyst bed was about 80 mm. Above the catalyst bed, 700 mL of Raschig rings were loaded that served as an evaporator and heating zone for the liquid feed and the gas feed.

[0081] The tubular reactor was heated up to the reaction temperature (253° C.).

[0082] DPTU was used as a crude solution (85 area % DPTU, 10 area % DPTA, 2 area % TBD) from the reaction of dimethyl carbonate with DPTA with catalytic amounts of TBD as disclosed in example 4.

[0083] The crude DPTU, which was obtained as described in example 4, was dissolved in a solvent (10-25 wt.-% crude DPTU) and the resulting solution was directly fed on top of the evaporator bed in the reactor. Nitrogen was fed into the reactor from the top of the evaporator bed downwards through the reactor at 1 bar. The DPTU solution evaporated through the combined action of the heating and constant entrainment by nitrogen and the evaporator bed served as a heater for the DPTU/nitrogen stream.

[0084] The combined gas stream of DPTU, solvent and nitrogen passed over the catalyst bed and was condensed in the collecting flask. Liquid samples were withdrawn regularly from the flask. The composition of the liquid sample was determined by gas chromatography yielding the area percentage of the major components TBD and Me-TBD.

TABLE-US-00001 TABLE 1 DPTU in feed (%), Molar Catalyst Me- Run Feed solvent Temperature ratio Load TBD TBD DPTU No (wt.-%) excluded Catalyst (° C.) solvent N.sub.2/DPTU (kg/L/h) (%) (%) (%) 1 25 85 A 253 MeOH 60 0.05 60 8 8 2 25 85 A 253 MeOH 92 0.03 63 10 5 3 50 85 A 253 MeOH 46 0.06 63 4 13 4 25 85 A 253 THF 55 0.05 69 7 2 5 25 85 B 253 MeOH 59 0.03 60 10 5 6 25 85 B 253 MeOH 92 0.05 63 10 3 Catalyst A is a silica-doped aluminum oxide, 3 mm split Catalyst B an amorph aluminum oxide, 3 mm extrudates

Example 6

[0085] A steel reactor of 770 mm length, wall thickness 3 mm and inner diameter 12 mm with electric heating was used. The reactor was filled in three layers. First, the reactor was filled with 3-5 wire gauze rings (3 mm) and 5 mL glass spheres, then with the catalyst A of example 5 (90 mL, 3 mm split) or steatite rings (70 mL, 4×3.5×2 mm) and then again with 5 mL glass spheres and 3-5 wire gauze rings (3 mm). The solution of the starting material comprising crude DPTU and the solvent was added via pump and was evaporated using an oil heated evaporator at 255° C. Nitrogen gas was introduced into the plant in front of the evaporator. The outlet tubing of the reactor was heated to 70 to 100° C. and was connected to a collecting container. Another feed (typically solvent) could be added after the outlet of the reactor to dilute the product feed. The reactor was heated to reaction temperature (up to 350° C.).

[0086] The crude DPTU, which was obtained as described in example 4, was dissolved in a solvent (20-25 wt.-%) and directly fed into the evaporator of the plant. The combined gas stream of DPTU, solvent and nitrogen passed over the catalyst bed, additional solvent was added after the reactor and the product mixture was condensed in the collecting flask. Liquid samples were withdrawn regularly from the flask.

[0087] The composition of the liquid sample was determined by gas chromatography yielding the area percentage of the major components.

TABLE-US-00002 TABLE 2 Results with catalyst A. DPTU in feed (%), Temperature Molar Catalyst Me- Run Feed solvent Pressure reactor ratio Load TBD TBD DPTU No (wt.-%) excluded (bar) solvent (° C.) N.sub.2/DPTU (kg/L/h) (%) (%) (%) 1 25 72 20 MeOH 260 50 0.05 0 21 6 2 25 76 10 MeOH 280 50 0.05 4 37 3 3 20 72 1 Butyl- 270 50 0.05 33 0 34 diglycol 4 20 72 1 Butyl- 275 50 0.03 41 0 19 diglycol

[0088] The results of table 2 as compared to table 1 show that the formation of compounds of formula I can be controlled by the pressure of the reaction. A higher pressure results in the formation of alkylated guanidines.

TABLE-US-00003 TABLE 3 Results with steatite rings (4 × 3.5 × 2 mm) DPTU in feed Inert (%), Temperature Molar Material Me- Run Feed solvent Pressure reactor ratio Load TBD TBD DPTU No (wt.-%) excluded (bar) solvent (° C.) N.sub.2/DPTU (kg/L/h) (%) (%) (%) 1 25 76 10 MeOH 280 50 0.05 29 10 20 2 25 76 10 MeOH 285 50 0.03 20 30 5