Method for Producing Cyclic Guanidine Derivatives

Abstract

The present invention relates to a compound of formula I The present invention relates to a method for preparing a cyclic guanidine derivative of TIFF2022553692000013.tif36148 or a mixture thereof (Formula I) by reacting a triamine in the presence of a C1 source and a solid material in the gas or liquid phase under an inert atmosphere.

Description

[Technical field]

[0001] The present invention relates to a compound of formula I

[0002] [ka] or a mixture thereof by reacting a triamine in the presence of a C1 source and a solid material in the gas or liquid phase under an inert atmosphere. [Background technology]

[0003] R 1 From R 13 Cyclic guanidine derivatives of formula I, where is independently selected from the group of H and C1 to C4-alkyl groups, are useful and active chemical products. They are used as catalysts for a variety of different chemical reactions. As described in US-A1 2009 / 0281314, published methods for synthesizing bicyclic guanidines are often complex, often involve the use of multi-step synthetic methods, and / or require the use of very expensive starting materials that can be harmful in various ways.

[0004] Furthermore, cyclic guanidine derivatives, such as 7-methyl-1,5,7-triazabicyclo[5.5.0]dec-5-ene (Me-TBD), can be used as ionic liquids when treated with organic acids to give cationic 1,5,7-triazabicyclo[4.4.0]dec-5-enium moieties and anions. These ionic liquids can be used as solvents in the methods for making cellulose fibers or films described in WO 2018 / 138416. They show good hydrothermal stability and are capable of dissolving wood pulp. The resulting solutions are used for spinning textile fibers.

[0005] WO 2019 / 030197 describes a method for producing cyclic urea units by reacting triamines with CO. The use of triamines with CO in the gas or liquid phase in the presence of solid materials or strong organic bases to produce cyclic guanidine derivatives is not disclosed.

[0006] US-A1 2009 / 0281314 describes a method for preparing bicyclic guanidines by heating a reaction mixture containing urea and a dehydrating agent, such as hexamethyldisilazane (HMDS), tetraethoxysilane (TEOS), disilazane, an alkoxy-substituted silane, or a combination thereof, to a temperature of ≧90° C. US-A1 2009 / 0281314 does not disclose a method for preparing bicyclic guanidines in the gas or liquid phase in the presence of a solid material. A method for preparing cyclic guanidine derivatives in only one process step is also not disclosed in US-A1 2009 / 0281314. Summary of the Invention [Problem to be solved by the invention]

[0007] It is therefore an object of the present invention to provide a process for the preparation of cyclic guanidine derivatives of formula I which is environmentally friendly, produces less waste than the processes described above and has a maximum of three process steps, preferably in one process step. [Means for solving the problem]

[0008] Surprisingly, this corresponds to formula I

[0009] [ka] (In the formula, R 1 From R 13 are independently selected from the group of H and C1 to C4 alkyl, and n and m are natural numbers independently selected from the group of 0 and 1. or mixtures thereof, by reacting a triamine in the presence of a C1 source and a solid material in the gas or liquid phase under an inert atmosphere at a temperature of at least 90° C. and a pressure of 1 to 320 bar. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The process of the present invention is advantageous when the solid material is selected from the group of inert materials and solid acid catalysts.

[0011] The process of the invention is advantageous when the solid material is a solid acid catalyst selected from the group of aluminium silicates, aluminium oxides and zeolites.

[0012] The process of the invention is advantageous when the triamine and the C1 source are dissolved in a solvent selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

[0013] The process of the invention is advantageous when the solvent is methanol, diethylene glycol or butyl diglycol.

[0014] The process of the invention is advantageous when the triamine is selected from the group N-(3-aminopropyl)propane-1,3-diamine (DPTA), N-(2-aminoethyl)ethane-1,2-diamine (DETA) and N-(2-aminoethyl)-1,3-propanediamine.

[0015] The process of the invention is advantageous when the C1 source is selected from the group of dimethyl carbonate, urea, dimethylformamide dimethyl acetal, carbon dioxide, ethylene carbonate, propylene carbonate, phosgene and cyanamide.

[0016] The method of the present invention comprises the following three steps: I) reacting a triamine in the presence of a C1 source at a temperature of at least 90° C. to form a compound of formula II

[0017] [ka] (In the formula, R 1 From R 13 and n and m have the same meanings as in formula I. a step of obtaining a urea compound of the formula: II) dissolving the crude urea compound of formula II of step I) in a solvent; and III) cyclization of the crude urea compound of formula II from step II) in the gas or liquid phase under an inert atmosphere in the presence of a solid material at a temperature of at least 120° C. and a pressure in the range of 1 to 320 bar. This is advantageous when providing

[0018] The process of the invention is advantageous if the process is carried out in the gas phase at a temperature of at least 150° C. and a pressure of from 1 to 35 bar.

[0019] The process of the invention is advantageous when, in step I of the process of the invention, a catalytic amount of an organic base or acid is present.

[0020] The process according to the invention is advantageous when the solvent of step II) of the process according to the invention is selected from the group of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyldiglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

[0021] The process according to the invention is advantageous when, in step I of the process according to the invention, a solvent is used which is selected from the group: methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

[0022] The process according to the invention is advantageous when step II) of the process according to the invention is included in step I), if the solvents for step II) and step I) are the same.

[0023] The process of the invention is advantageous when the cyclic guanidine derivative of formula I is a mixture of 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene.

[0024] The process of the invention is advantageous when the cyclic guanidine derivative of formula I is 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.

[0025] The process of the invention is advantageous when the cyclic guanidine derivative of formula I is a mixture of 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole.

[0026] Using the method of the present invention, a compound of formula I

[0027] [ka] In formula I, n and m are natural numbers independently selected from the group consisting of 0 and 1, and it is preferred that m and n are the same natural number, and it is particularly preferred that m and n are 1.

[0028] R in Formula I 1 From R 13 is independently selected from the group of H and C1 to C4 alkyl groups. C1 to C4 alkyl groups mean methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl and tert-butyl. R 1 From R 13 is preferably independently selected from the group H and methyl; R 2 From R 13 is H and R 1 It is particularly preferred that is selected from the group of H and methyl.

[0029] Preferred cyclic guanidine derivatives of formula I obtainable by the process of the invention are selected from the group of 1,5,7-triazabicyclo[4.4.0]dec-5-ene, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine, 8-methyl-1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine, 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole.

[0030] Preferred mixtures of cyclic guanidine derivatives of formula I are those comprising 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine and 8-methyl-1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine or 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole.

[0031] In the process of the invention, a triamine is reacted with the C1 source. The triamine used in the process of the invention 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. The use of N-(3-aminopropyl)propane-1,3-diamine (DPTA) is preferred.

[0032] The C1 source used in the process of the present invention is selected from the group of dimethyl carbonate, urea, dimethylformamide dimethyl acetal, carbon dioxide, ethylene carbonate, propylene carbonate, phosgene and cyanamide. The use of dimethyl carbonate, urea, carbon dioxide, ethylene carbonate or propylene carbonate is preferred. The use of dimethyl carbonate, urea or carbon dioxide is more preferred.

[0033] During the process of the present invention, the C1 source is always used in excess, which means that the C1 source is used in an amount of 1.01 to 1.50 molar equivalents, preferably 1.01 to 1.20 molar equivalents, compared to the triamine used. When carbon dioxide is used as the C1 source, a large excess of carbon dioxide in the range of 10 to 500 molar equivalents compared to the triamine used is used.

[0034] In the process of the present invention, the starting triamine and C1 source can be dissolved in a solvent or can be reacted without a solvent. The reaction of the triamine and C1 source without a solvent is preferred. If a solvent is used, the solvent is a protic solvent selected from the group of methanol, ethanol, isopropanol, butanol, diethylene glycol and butyl diglycol or an aprotic solvent selected from the group of tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone. Solvents selected from the group of methanol, butyl diglycol and tetrahydrofuran are preferred. Solvents such as methanol, diethylene glycol and butyl diglycol are particularly preferred.

[0035] The process of the present invention can be carried out with the solid material in the gas phase or in the liquid phase, preferably with the solid material in the gas phase.

[0036] The solid material is placed in the reactor. The process of the invention is in principle suitable for pressure-resistant reactors customarily used for reactions on heterogeneous catalysts with feeding of one gaseous reactant and, if applicable, one or more liquid reactants to the reactor. These include generally customary reactors for gas-phase and liquid-phase reactions, such as tubular reactors, shell-and-tube reactors and gas circulation reactors. A specific embodiment of a tubular reactor is that of a shaft reactor. Reactors of this type are in principle known to those skilled in the art. More particularly, cylindrical reactors with a vertical longitudinal axis are used, which have an injection device or several injection devices at the bottom or top of the reactor for feeding a reaction mixture comprising at least one gaseous component and, if applicable, at least one liquid component. If desired, a substream of gaseous and / or liquid reactants can further be fed to the reactor by at least one further feeding device.

[0037] In the preferred gas phase reaction, the starting compounds, e.g. triamine, C1 source, inert gas and optionally solvent, are evaporated in an evaporator before reaching the solid material in the reactor. The evaporator may be an evaporator bed inside the reactor, made of an inert material selected from the group of Raschig rings, glass spheres, steel wire mesh or wire gauze rings, heated by the heating of the reactor, or it may be an additional oil or steam heated evaporator device located outside the reactor before the top of the reactor. The evaporation temperature is in the range of 80 to 280°C, preferably in the range of 120 to 250°C. During the evaporation, the pressure is in the range of 1 to 35, preferably 1 to 25 bar.

[0038] In the case of gas phase reaction, the starting compound is contacted with the solid material after evaporation. In the case of liquid phase reaction, the starting compound, e.g. triamine, C1 source, inert gas and optionally solvent, is directly contacted with the solid material. When the compound of formula II is dissolved in a solvent in step II of the method of the present invention, this is done inside or outside the reactor before reaching the solid material. The flow direction of the gas or liquid phase through the reactor is vertical. The flow direction can be from the top to the bottom of the reactor or vice versa. A flow direction from the top to the bottom of the reactor is preferred.

[0039] The solid materials used in the gas or liquid phase are selected from the group of inert materials, solid acid catalysts or mixtures or layers of inert materials and solid acid catalysts. The inert materials are selected from the group of Raschig rings, glass spheres, steel wire mesh, wire gauze rings and ceramic materials. The solid acid catalysts are selected from the group of aluminum silicates, aluminum oxides, zeolites or mixtures of these solid acids. The solid materials can have different shapes and sizes. All shapes and sizes of solid materials known to those skilled in the art are possible, provided they allow a constant flow rate through the reactor. These shaped bodies are selected from the group of tablets, extrudates, splits, spherical materials. Regardless of the type and shape of the material, the diameter of these shaped bodies is in the range of 1 mm to 20 mm.

[0040] The solid material is fixed inside the reactor and is a reactor bed. The reactor bed can contain only inert material or inert material and one or more solid acid catalysts. A preferred reactor bed contains inert material and one or more solid acid catalysts. As part of the reactor bed, inert material is at the beginning and end of the reactor bed to fix the position of the bed inside the reactor. When a solid acid catalyst is used, the solid acid catalyst is located between the inert material at the beginning and end of the reactor bed. The solid acid catalyst may be a single solid acid catalyst or may be two or more different solid acid catalysts mixed or arranged in layers, with an inert material located between each layer. A preferred reactor bed contains inert material at the beginning and end of the reactor bed and a solid acid catalyst selected from the group of aluminum silicate, aluminum oxide, and mixtures thereof.

[0041] During the gas and / or liquid phase reaction, an inert gas selected from the group of N2 and argon is used. The inert gas can be used to control the space velocity of the reaction. Usually, the space velocity is in the range of 50 to 10000 l / h.

[0042] The temperature of the reaction is at least 90° C., preferably between 150° C. and 350° C., more preferably in the range of 220° C. and 300° C. The pressure during the process of the invention is in the range between 1 and 100 bar. During the gas phase reaction of the process of the invention, the pressure is preferably in the range of 1 to 35 bar. During the liquid phase reaction of the process of the invention, the preferred pressure is below 100 bar.

[0043] The process of the present invention can be a single-step, two-step or three-step process. In the single-step process, the triamine, the C1 source, the inert gas and optionally the solvent react directly in the gas phase or liquid phase to form one compound of formula I or a mixture of compounds of formula I. In the two-step process, the solvent in step I is the same as that in step II. In this case, step II is included in step I, and the urea compound of formula II can be directly introduced in step III of the cyclization. If no solvent is used in step I or if a different solvent is used in step II than in step I, the process of the present invention is carried out in three steps. The single-step and three-step processes of the process of the present invention are preferred. The single-step process is particularly preferred.

[0044] In another embodiment of the invention, the reaction can be separated into more than one step. Three steps are preferred. In the first step, a triamine is reacted with a C1 source to give a compound of formula II

[0045] [ka] (In the formula, R 1 ~R 13 , m and n have the same meanings as in formula I. and the corresponding urea compound of the formula: ##STR00013## In the reaction of the triamine and the C1 source in step I of the process of the present invention, a catalytic amount of an organic base or an organic acid can be used. The catalytic amount is an amount in the range of 0.01 to 10 mol %, preferably 0.1 to 5 mol %, of the triamine used. In step I of the process of the present invention, either an organic base or an organic acid can be used. The organic base has a pk a The organic acid is selected from the group of strong organic bases having a value of 0.1 to 0.5. The organic acid is selected from the group of sulfonic acids or carboxylic acids. Nitrogen-containing organic bases, such as guanidine, are particularly preferred.

[0046] The reaction of the triamine and the C1 source can be carried out in the presence of a solvent or without a solvent. A solvent-free reaction is preferred. If a solvent is used, it is a protic or aprotic solvent. The protic solvent of step I is selected from the group of methanol, ethanol, isopropanol, butanol, diethylene glycol and butyl diglycol. The aprotic solvent of step I is selected from the group of tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone. The solvent is preferably selected from the group of methanol, diethylene glycol, butyl diglycol and tetrahydrofuran. Methanol or butyl diglycol is particularly preferred as the solvent.

[0047] The reaction temperature of the reaction in step I is at least 90° C. If the C1 source is not gaseous, the pressure in step I is atmospheric pressure. If the C1 source is CO2 in step I of the process of the present invention, the pressure is in the range of 20 to 100 bar.

[0048] After step I of the process of the present invention, a crude urea compound of formula II is available. By "crude" it is meant that the mixture contains small amounts of by-products. These by-products are the starting products, e.g., triamines, C1 sources, alkylated cyclic urea derivatives and smaller amounts of R 1 is H. The lesser amount is selected from the group of compounds of formula I, wherein R 1is H.

[0049] The amount of minor by-products is in the range of 0.01 to 10 wt % depending on the urea compound of formula II. The obtained crude urea compound of formula II is dissolved in a solvent. The solvent can be a protic or aprotic solvent. It is selected from the group of methanol, ethanol, isopropanol, butanol, diethylene glycol and butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone. The solvent is preferably selected from the group of methanol, diethylene glycol and butyl diglycol and tetrahydrofuran. Particularly preferred solvents are methanol, diethylene glycol and butyl diglycol. When a solvent is used in step I, the preferred solvent in step II is the same as that in step I.

[0050] Afterwards, the crude urea compound of formula II is fed together with an inert gas and a solvent into the liquid or gas phase of a reactor filled with solid material for cyclization. When cyclization is carried out in the gas phase, an evaporator is located before the reactor bed. This can be done at the top of the reactor or inside the reactor before the reactor bed. In the evaporator, the crude urea and the solvent are evaporated together before this combined gas is fed together with an inert gas into the reactor bed containing solid material. When cyclization is carried out in the liquid phase, the crude urea compound of formula II is first dissolved in a solvent and then fed together with an inert gas into the top or bottom of the reactor.

[0051] The temperature of the cyclization in step III of the process of the present invention is at least 120° C., preferably at least 150° C., more preferably in the range of from 150 to 300° C. The pressure during step III is in the range of from 1 to 320 bar, preferably in the range of from 1 to 200 bar.

[0052] Preferably step III is carried out in the gas phase at a temperature of at least 150° C. and a pressure of from 1 to 35 bar.

[0053] In many cases, the method of the invention provides a mixture of cyclic guanidine derivatives of formula I. Preferred mixtures include 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine and 8-methyl-1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine or 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole. A particularly preferred mixture is a mixture of 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene.

[0054] [Example] For further examples, the following abbreviations have the following meanings: DPTA: Dipropylenetriamine (3,3'-diaminodipropylamine) DPTU: 1-(3-aminopropyl)tetrahydropyrimidin-2(1H)-one TBD: 1,5,7-triazabicyclo[4.4.0]dec-5-ene Me-TBD: 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene

[0055] Reaction of DPTA with CO2:

[0056] [Example 1] 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 increased again to 5 bar and the stirrer was started. Within 20 minutes, carbon dioxide was injected in small portions to establish a pressure of 8 to 10 bar. The autoclave was then heated to 180° C. Once 180° C. was reached, the pressure was increased to 61 bar by injecting more carbon dioxide. Once 61 bar was reached, the reaction mixture was stirred for 16 hours. The reaction mixture was then 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 solvent) was given in area percent as follows: 11% DPTU 6% TBD 20% 1-Methyltetrahydropyrimidin-2(1H)-one 27% 1-Ethyltetrahydropyrimidin-2(1H)-one

[0058] [Example 2] 40 mL of 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 increased again to 5 bar and the stirrer was started. Within 20 minutes, carbon dioxide was injected in small portions to establish a pressure of 20 bar. The autoclave was then heated to 180° C. Once 180° C. was reached, the pressure was increased to 61 bar by injecting more carbon dioxide. Once 62 bar was reached, the reaction mixture was stirred for 16 hours. Afterwards, the reaction mixture was cooled to room temperature and the autoclave was depressurized to ambient pressure. The reaction mixture was analyzed by gas chromatography.

[0059] The composition of the reaction mixture (without solvent) was given in area percent as follows: 31% DPTU 6% TBD 16% 1-Methyltetrahydropyrimidin-2(1H)-one 22% 1-Ethyltetrahydropyrimidin-2(1H)-one

[0060] [Example 3] 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 increased again to 5 bar and the stirrer was started. Within 20 minutes, carbon dioxide was injected in small portions to establish a pressure of 15 bar. The autoclave was then heated to 180° C. Once 180° C. was reached, the pressure was increased to 61 bar by injecting more carbon dioxide. Once 64 bar was reached, the reaction mixture was stirred for 16 hours. The reaction mixture was then cooled to room temperature and the autoclave was depressurized to ambient pressure. The reaction mixture was analyzed by gas chromatography.

[0061] The composition of the reaction mixture (without solvent) was given in area percent as follows: 31% DPTU 5% TBD 13% 1-Methyltetrahydropyrimidin-2(1H)-one 20% 1-Ethyltetrahydropyrimidin-2(1H)-one

[0062] Reaction of DPTA with dimethyl carbonate

[0063] [Example 4] A 1000 mL three-neck flask equipped with a reflux condenser was charged with 100 g (0.76 mol) of DPTA and 6.9 g (0.05 mol) of TBD. The mixture was cooled to 8° C. by using an ice bath. 75 g (0.83 mol, 1.09 eq.) of dimethyl carbonate was added dropwise after 2 h. The reaction mixture was then warmed to 20° C. After reaching 20° C., the mixture was heated to 90° C. in an oil bath and held at this temperature for 6 h. The reflux condenser was then replaced with a distillation bridge and the resulting methanol was distilled off using an oil bath temperature of up to 130° C. at atmospheric pressure. After distillation, the solution was cooled to 20° C. and used as received in the next step(s) without further purification.

[0064] Exemplary product mixture compositions: The composition of the reaction mixture (without solvent) was given in area percent as follows: 78% DPTU 11% DPTA 6% TBD

[0065] Steps II and III:

[0066] [Example 5] Gas-phase cyclization of 1-(3-aminopropyl)tetrahydropyrimidin-2(1H)-one (DPTU) to 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)

[0067] [ka]

[0068] An oil-heated double-walled glass reactor 1000 mm long and 40 mm in diameter was installed vertically with a quartz frit at the bottom, inlets for liquid and gas feeds at the top connected to a pump, the gas feed (N2) was measured by a rotameter, and the outlet (bottom) was connected to a collecting flask. The off-gas was connected to the exhaust of a laboratory hood. In the center of the reactor, a glass tube was placed from top to bottom and a flexible thermocouple was introduced in this tube. The reactor was filled in three layers. First, 200 mL of Raschig rings made of steel mesh (5 mm diameter) were loaded on the quartz frit. Then the catalyst (100 mL, 3 mm splits / extrudates) was introduced. The height of the catalyst bed was about 80 mm. On top of the catalyst bed, 700 mL of Raschig rings were loaded, which served as an evaporator and heating zone for the liquid and gas feeds.

[0069] The tubular reactor was heated to the reaction temperature (253° C.).

[0070] DPTU was used as a crude solution from the reaction of dimethyl carbonate with DPTA using a catalytic amount of TBD as disclosed in Example 4 (85 area % DPTU, 10 area % DPTA, 2 area % TBD).

[0071] The crude DPTU obtained as described in Example 4 was dissolved in a solvent (10-25 wt% crude DPTU) and the resulting solution was fed directly into the reactor on top of the evaporator bed. Nitrogen was fed into the reactor from the top of the evaporator bed downwards through the reactor at 1 bar. The DPTU solution was evaporated by the combined action of heating and constant entrainment with nitrogen, and the evaporator bed acted as a heater for the DPTU / nitrogen stream.

[0072] The combined gas stream of DPTU, solvent and nitrogen was passed over the catalyst bed and condensed in a collection flask, and liquid samples were periodically withdrawn from the flask.

[0073] The composition of the liquid samples was determined by gas chromatography to obtain the area percentages of the major components TBD and Me-TBD.

[0074] [Table 1]

[0075] [Example 6] An electrically heated steel reactor was used with a length of 770 mm, a wall thickness of 3 mm and an internal diameter of 12 mm. The reactor was filled in three layers. First, the reactor was filled with 3-5 gauze rings (3 mm) and 5 mL of glass spheres, then with catalyst A of Example 5 (90 mL, 3 mm split) or steatite rings (70 mL, 4 x 3.5 x 2 mm), then again with 5 mL of glass spheres and 3-5 gauze rings (3 mm). A solution of starting materials containing crude DPTU and solvent was added by pump and evaporated using an oil heated evaporator at 255 °C. Nitrogen gas was introduced into the plant in front of the evaporator. The reactor outlet was heated to 70-100 °C and connected to a collection vessel. Another feed (typically a solvent) can also be added after the reactor outlet to dilute the product feed.

[0076] The reactor was heated to the reaction temperature (up to 350° C.).

[0077] Crude DPTU obtained as described in Example 4 was dissolved in solvent (20-25 wt%) and fed directly into the evaporator of the plant. The combined gas stream of DPTU, solvent and nitrogen was passed over the catalyst bed, additional solvent was added after the reactor and the product mixture was condensed in a collection flask. Liquid samples were periodically withdrawn from the flask.

[0078] The composition of the liquid samples was determined by gas chromatography to obtain the area percentages of the major components.

[0079] [Table 2]

[0080] The results in Table 2 compared to Table 1 show that the formation of compounds of formula I can be controlled by the pressure of the reaction, with higher pressures resulting in the formation of alkylated guanidines.

[0081] [Table 3] This specification includes the following: [1] Formula I [ka] (In the formula, R 1 From R 13 H and C 1 From C 4 alkyl, and n and m are natural numbers independently selected from the group consisting of 0 and 1. A method for producing a cyclic guanidine derivative of formula C or a mixture thereof, comprising reacting a triamine with 1 2. A process for the preparation of a tertiary amine comprising reacting a tertiary amine compound with a tertiary amine in the presence of a source of tertiary amine in a reactor packed with a solid material selected from the group of inert materials, aluminum silicate, aluminum oxide, zeolite or mixtures or layers thereof in the gas or liquid phase under an inert atmosphere at a temperature of at least 90° C. and a pressure of 1 to 320 bar. [2] Triamine and C 1 The method according to [1], wherein the source is dissolved in a solvent selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone. [3] The method according to [1] or [2], wherein the solvent is methanol, diethylene glycol or butyl diglycol. [4] The method according to any one of [1] to [3], wherein the triamine is selected from the group consisting of N-(3-aminopropyl)propane-1,3-diamine (DPTA), N-(2-aminoethyl)ethane-1,2-diamine (DETA) and N-(2-aminoethyl)-1,3-propanediamine. [5]C 1 The method according to any of [1] to [4], wherein the source is selected from the group consisting of dimethyl carbonate, urea, dimethylformamide dimethyl acetal, carbon dioxide, ethylene carbonate, propylene carbonate, phosgene and cyanamide. [6] The following three steps: I) Triamine to C 1 at a temperature of at least 90° C. in the presence of a source of formula II [ka] (In the formula, R 1 From R 13 and n and m have the same meanings as in formula I. a step of obtaining a urea compound of the formula: II) dissolving the crude urea compound of formula II of step I) in a solvent; III) cyclization of the crude dissolved urea compound of formula II from step II) in the gas or liquid phase under an inert atmosphere in the presence of a solid material at a temperature of at least 120° C. and a pressure in the range of 1 to 320 bar. The method according to any one of [1] to [6], further comprising: [7] The method according to any of [1] to [6], wherein the method is carried out in the gas phase at a temperature of at least 150° C. and a pressure of 1 to 35 bar. [8] The method according to [6] or [7], wherein in step I) of the method, a catalytic amount of an organic base or acid is present. [9] The method according to any of [6] to [8], wherein the solvent in step II) of the method is selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

[10] The method according to any of [6] to [9], wherein in step I) of the method, a solvent is used selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

[11] The method according to any one of [6] to

[10] , wherein when the solvents used in step II) and step I) are the same, step II) is included in step I).

[12] The method according to any one of [1] to

[11] , wherein the cyclic guanidine derivative of formula I is a mixture of 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene.

[13] The method according to any one of [1] to

[11] , wherein the cyclic guanidine derivative of formula I is a mixture of 1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine and 8-methyl-1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine.

[14] The method according to any one of [1] to

[11] , wherein the cyclic guanidine derivative of formula I is a mixture of 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole.

Claims

1. Formula I 【Chemistry 1】 (In the formula, R 1 From R 13 H and C 1 From C 4 alkyl, and n and m are natural numbers independently selected from the group consisting of 0 and 1. A method for producing a cyclic guanidine derivative of formula C or a mixture thereof, comprising reacting a triamine with 1 1. A process for the preparation of a process for the preparation of a tertiary amine comprising reacting a tertiary amine compound with a tertiary amine in the presence of a source of tertiary amine in a reactor packed with a solid material selected from the group of inert materials, aluminum silicate, aluminum oxide, zeolites or mixtures or layers thereof in the gas or liquid phase under an inert atmosphere at a temperature of at least 90° C. and a pressure of 1 to 320 bar, wherein the inert material is selected from the group of Raschig rings, glass spheres, steel wire mesh, gauze rings and ceramic materials.

2. Triamine and C 1 2. The method of claim 1, wherein the source is dissolved in a solvent selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide, and N-methylpyrrolidone.

3. 3. The method of claim 2, wherein the solvent is methanol, diethylene glycol or butyl diglycol.

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

5. C 1 5. The method according to any one of claims 1 to 4, wherein the source is selected from the group of dimethyl carbonate, urea, dimethylformamide dimethyl acetal, carbon dioxide, ethylene carbonate, propylene carbonate, phosgene and cyanamide.

6. The three steps are: I) Triamine to C 1 at a temperature of at least 90° C. in the presence of a source of formula II 【Chemistry 2】 (In the formula, R 1 From R 13 and n and m have the same meanings as in formula I. a step of obtaining a urea compound of the formula: II) dissolving the crude urea compound of formula II of step I) in a solvent; III) cyclization of the crude dissolved urea compound of formula II from step II) in the gas or liquid phase under an inert atmosphere in the presence of a solid material at a temperature of at least 120° C. and a pressure in the range of 1 to 320 bar. The method according to any one of claims 1 to 6, further comprising providing

7. 7. The process according to any one of claims 1 to 6, wherein the process is carried out in the gas phase at a temperature of at least 150°C and a pressure of 1 to 35 bar.

8. 8. The process according to claim 6 or 7, wherein in process step I) a catalytic amount of an organic base or acid is present.

9. 9. The process according to any one of claims 6 to 8, wherein the solvent of process step II) is selected from the group of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

10. 10. The process according to any one of claims 6 to 9, wherein in process step I) a solvent is used which is selected from the group consisting of methanol, ethanol, isopropanol, butanol, diethylene glycol, butyl diglycol, tetrahydrofuran, diglyme, proglyme, triglyme, tetraglyme, toluene, dichlorobenzene, N,N-dimethylformamide and N-methylpyrrolidone.

11. 11. The method according to any one of claims 6 to 10, wherein step II) is included in step I), if the solvents of step II) and step I) are the same.

12. 12. The method according to any one of claims 1 to 11, wherein the cyclic guanidine derivative of formula I is a mixture of 1,5,7-triazabicyclo[4.4.0]dec-5-ene and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene.

13. 12. The method according to any one of claims 1 to 11, wherein the cyclic guanidine derivative of formula I is a mixture of 1,2,3,5,6,7-hexyhydroimidazole[1,2-a]pyrimidine and 8-methyl-1,2,3,5,6,7-hexahydroimidazole[1,2-a]pyrimidine.

14. 12. The method according to any one of claims 1 to 11, wherein the cyclic guanidine derivative of formula I is a mixture of 2,3,5,6-tetrahydro-1H-imidazole[1,2-a]imidazole and 1-methyl-2,3,5,6-tetrahydroimidazole[1,2-a]imidazole.

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