Process for the catalytic hydrogenation of thiourea compounds, ruthenium-based polydentate ligand compounds and use thereof

Abstract

The application provides a catalytic hydrogenation method of a thiourea compound, a ruthenium-based multidentate ligand compound and application thereof. The method comprises contacting the thiourea compound with hydrogen in the presence of a catalyst and a solvent; the structural general formula of the thiourea compound is shown in the description; the catalyst is obtained from a composition comprising a ruthenium-based compound and a ligand; the structural general formula of the ligand is shown in the description; and the method has the advantages of high selectivity, mild reaction condition, good atom economy, environmental friendliness and the like.

Description

Technical Field

[0001] This invention relates to the field of fine chemical technology, specifically to a catalytic hydrogenation method for thiourea compounds, ruthenium-based polydentate ligand compounds, and their uses. Background Technology

[0002] Methanethiol, as a key organic synthesis intermediate, has wide and important applications in numerous industries, including pesticides, pharmaceuticals, food, feed additives, and synthetic materials. Particularly in the pharmaceutical and feed sectors, methanethiol is primarily used to synthesize methionine. Methionine is one of the nine essential amino acids, widely used not only as an animal feed additive but also possessing significant nutritional value for humans. In recent years, with the rapid development of the methionine synthesis industry, methanethiol, as the source of the sulfur atom and methyl group that constitute the characteristic functional group (methylthio group) of the methionine molecule, has become an indispensable basic raw material in this synthesis process.

[0003] Currently, various industrial processes for producing methanethiol have been developed, including the methanol-hydrogen sulfide method, the methanol-carbon disulfide method, the high-sulfur syngas method, the chloromethane-alkali sulfide method, and the thiourea-dimethyl sulfate method. However, these traditional methods generally suffer from byproduct generation, resulting in unsatisfactory atom economy. Therefore, optimizing processes to reduce waste generation at the source and developing green and atom-economical methanethiol synthesis methods has become an important direction for development in this field.

[0004] Compared with existing methods, the direct hydrogenation of thiourea to prepare methanethiol shows significant research potential in both concept and application. Thiourea can be conveniently synthesized from carbon disulfide (CS2) or carbonyl sulfide (COS) with amine compounds, and its catalytic hydrogenation is equivalent to an indirect and highly selective conversion of CS2 or COS, which can directionally generate methanethiol and recyclable amines. The amines generated in this process can be completely recovered for the resynthesis of thiourea, thus forming a closed-loop process, greatly improving material utilization, achieving almost zero waste emissions, and highly conforming to the principles of green chemistry.

[0005] While the direct hydrogenation of CS2 or COS to produce methanethiol is attractive, existing catalytic processes typically require high temperatures (250–400 °C), and reaction selectivity is difficult to control. Common side reactions include further hydrogenation of methanethiol to methane and the condensation of two molecules of methanethiol to dimethyl sulfide, which reduce the practicality and economics of this route. In contrast, the technology for efficiently converting CS2 or COS to thiourea is relatively mature and well-studied. Therefore, achieving the catalytic hydrogenation of thiourea to methanethiol under mild conditions would provide a promising alternative route for the indirect acquisition of methanethiol from CS2 or COS.

[0006] In recent years, significant progress has been made in the research on the conversion of carboxylic acids, esters, amides, and even carbonates, carbamates, and ureas into corresponding alcohols and amines with the participation of hydrogen. Thioureas are compounds with structures similar to ureas; however, in stark contrast, the catalytic hydrogenation of structurally similar thioureas, whether via heterogeneous or homogeneous systems, has rarely been reported in existing technologies. This may be because sulfur-containing molecules have strong coordination abilities, readily occupying the active sites of metal catalysts, leading to catalyst deactivation and thus inhibiting the normal operation of traditional metal-catalyzed hydrogenation systems.

[0007] Against this backdrop, developing a method for the efficient and selective catalytic hydrogenation of thiourea compounds under mild conditions is not only of significant scientific importance, but also provides a new technological approach for achieving an atom-economical, green, and sustainable methanethiol synthesis process. Summary of the Invention

[0008] The purpose of this invention is to provide a catalytic hydrogenation method for thiourea compounds, a ruthenium-based polydentate ligand compound, and its uses.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] One aspect of this invention is to provide a catalytic hydrogenation method for thiourea compounds, comprising contacting the thiourea compound with hydrogen gas in the presence of a catalyst and a solvent. The thiourea compound has the structure shown in general formula (1).

[0011] , (1)

[0013] In the general formula (1), R 1 R 2 R 3 and R 4 Each is an independent monovalent organic group, or any two or more of them are connected to each other to form a ring structure;

[0014] The catalyst is obtained from a composition comprising a ruthenium-based compound and a ligand;

[0015] The structure of the ligand is shown in general formula (2).

[0016] , (2)

[0018] In the general formula (2), Q is a single bond, or an organic group containing one or more of carbon, nitrogen, and phosphorus atoms; the two Ls are each independently a divalent linker or a single bond; the two Ys are each independently a phosphorus atom or a nitrogen atom, and each Y is connected to two Rs. 5Each is an independent monovalent organic group, and the R groups attached to different Y groups are... 5 They are the same or different from each other.

[0019] The inventors unexpectedly discovered that using a ruthenium-based compound with a polydentate ligand as a catalyst exhibits excellent catalytic selectivity when catalyzing thiourea compounds of the general formula (1), without generating additional byproducts. This catalyst can directionally generate methanethiol and recyclable amine compounds. Furthermore, the amine compounds can be completely recovered for the synthesis of thiourea, resulting in a very high material utilization rate and almost zero waste discharge throughout the process, conforming to the principles of green chemistry.

[0020] In this invention, the monovalent organic group is not particularly limited in principle and can be selected from the types of compounds already available in the art. In some specific embodiments, the monovalent organic group can be selected from hydrogen atoms, straight-chain or branched or cyclic hydrocarbon groups, hydrocarbon groups with unsaturated structures (or aromatic structures), and these hydrocarbon groups can optionally have substituents. Preferably, these substituents can be halogens or halogen-containing groups; or, the carbon atom in the above-mentioned hydrocarbon group can be replaced by other N, O, or S atoms.

[0021] In some preferred embodiments, the monovalent organic group may be selected from hydrogen atoms, straight-chain, branched, cyclic saturated or unsaturated hydrocarbon groups of C1 to C25 (preferably C1 to C15), and these groups may optionally have halogenated substituents or may optionally have carbon aromatic or heteroaromatic structures.

[0022] In some more preferred embodiments, the monovalent organic group may be selected from one or more of hydrogen atoms, C1-C10 alkyl groups (methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, etc.), cycloalkyl (4-6 membered ring), phenyl, pyridyl, and imidazolyl, and these groups optionally have alkyl groups or halogen-containing substituents, such as one or more chlorine atoms, fluorine atoms, bromine atoms, trifluoromethyl, methyl, ethyl, isopropyl, tert-butyl, etc.

[0023] In this invention, the cyclic structure formed by two or more groups is not particularly limited in principle and can be selected according to the types of compounds already available in the art. In some specific embodiments, it is a cyclic hydrocarbon group (cycloalkanes, phenyl or other unsaturated cyclic hydrocarbon groups) or a heteroaryl group, and these groups optionally have alkyl, halogen-containing substituents, such as one or more chlorine atoms, fluorine atoms, bromine atoms, trifluoromethyl, methyl, ethyl, isopropyl, tert-butyl, etc.

[0024] In some preferred embodiments, R in the general formula (1) 1 R 2One and only one of them is hydrogen, and the other is the C1-C10 alkyl group, the cycloalkane, or the phenyl group, or is combined with the R group. 3 R 4 One of them forms the aforementioned ring structure; the R 3 R 4 There is one and only one hydrogen.

[0025] In some preferred embodiments, when R in the general formula (1) 1 R 2 R 3 and R 4 When any two or more elements are interconnected to form a ring structure, the ring structure is an optionally substituted aromatic ring. The substituents used for substitution are as described above and will not be repeated here.

[0026] Furthermore, as preferred reaction substrates of the present invention, compounds with the following structures can be listed:

[0027] , , , , , , , , , , , .

[0028] In this invention, the ruthenium-based compound is a ruthenium(II) complex and / or a ruthenium(III) complex.

[0029] In some preferred embodiments, the ligands in the ruthenium(II) complex and / or ruthenium(III) complex comprise one or more of organophosphorus ligands (e.g., triphenylphosphine), halogen ligands, carbonyl ligands, hydrogen ligands, olefin ligands, and acetylacetone ligands.

[0030] Furthermore, as preferred ruthenium-based compounds of the present invention, they include one or more of tris(triphenylphosphine)dichloride ruthenium(II), dichlorotetra(triphenylphosphine)ruthenium(II), triphenylphosphine carbonyl ruthenium(II), dichlorotetra(triphenylphosphine)ruthenium(II), dihydrotetra(triphenylphosphine)ruthenium(II), carbonyl dihydrotris(triphenylphosphine)ruthenium(II), carbonyl chloride hydrogen tris(triphenylphosphine)ruthenium(II), bis(2-methylallyl)(1,5-cyclooctadiene)ruthenium(II), and acetylacetone ruthenium(III).

[0031] In this invention, the ligand of the general formula (2) is a bidentate or higher ligand, preferably a tridentate or tetradentate ligand. There are no particular restrictions on the divalent linking group that can be used for L in the general formula (2), and commonly used linking groups in the art can be used. In some preferred embodiments, the divalent group can be a C1-C10 (preferably C1-C6) hydrocarbon group. Y in the general formula (2) is preferably a phosphorus atom. R in the general formula (2) 5 Preferably, it is a straight-chain, branched, or aromatic hydrocarbon group of C1 to C20 (preferably C2 to C15, more preferably C3 to C10).

[0032] In some preferred embodiments, the ligand of general formula (2) includes one or more of the structures shown in general formulas (2-1), (2-2), (2-3), (2-4), and (2-5).

[0033] 4-n (R 6 -)C(-LY(R 5 )2) n ,

[0034] (2-1)

[0035] (R 5 )2Y—L—L—Y(R 5 )2,

[0036] (2-2)

[0037] 3-m (R 6 -)N(-LY(R 5 )2) m ,

[0038] (2-3)

[0039] 3-m (R 6 -)P(-LY(R 5 )2) m ,

[0040] (2-4)

[0041] ,

[0042] (2-5)

[0043] Where n is 2, 3, or 4; m is 2 or 3; R 6 It is a monovalent organic group;

[0044] In general formula (2-1), C represents a carbon atom;

[0045] In general formula (2-3), N is a nitrogen atom;

[0046] In general formula (2-4), P represents a phosphorus atom;

[0047] In general formula (2-5), cyclic structure A represents a ring with an aromatic structure, N represents a nitrogen atom, and all three covalent bonds of the nitrogen atom are attached to the cyclic structure A.

[0048] Furthermore, in general formulas (2-1), (2-3), and (2-4), R 6 The monovalent organic group is preferably a hydrogen atom or a straight-chain, branched, or aromatic hydrocarbon group of C1-C20 (preferably C2-C15, more preferably C3-C10). In the general formulas (2-5), the ring (the smallest unit ring) to which the nitrogen atom is attached is preferably an aromatic nitrogen heterocycle. In some other specific embodiments, the cyclic structure A is a cyclic structure containing 4 to 20 carbon atoms in its cyclic skeleton, preferably containing 6 to 18 carbon atoms. Such a cyclic structure can be composed of one or more rings that can be linked by single bonds or share at least one carbon atom, for example, by forming the cyclic structure A in a fused manner. In a further preferred embodiment, the cyclic structure A can be a structure derived from pyridine, pyrrole, (poly)benzopyridine, or (poly)benzopyrrole, and these structures may optionally have substituents such as alkyl groups.

[0049] Furthermore, as preferred ligands of the present invention, they include one or more of 1,1,1-tris(diphenylphosphinemethyl)ethane, 1,2-bis(diphenylphosphine)ethane, 2,6-bis[(diphenylphosphineyl)methyl]pyridine, 2,6-bis((di-tert-butylphosphineyl)methyl)pyridine, bis(2-(di-tert-butylphosphineyl)ethyl)amine hydrochloride, ((phenylphosphinediyl)bis(ethane-2,1-diyl))bis(diphenylphosphine), and tris(2-(diphenylphosphineyl)ethyl)phosphine.

[0050] In this invention, the catalyst can be obtained by reacting a composition containing the ruthenium-based compound and a ligand having the structure of the general formula (2). In some specific embodiments, the ruthenium-based compound is reacted with a ligand having the structure of the general formula (2) under alkaline conditions to obtain the catalyst. There are no particular limitations on the base that can be used, and it can generally be an organic base and / or an inorganic base. In some preferred embodiments, the organic base includes potassium tert-butoxide (KO42-K2O4). tBu), sodium triethylborohydride (NaHBEt3); inorganic bases include potassium hydroxide (KOH), sodium hydroxide (NaOH), cesium carbonate (Cs2CO3), sodium carbonate (Na2CO3), and sodium bicarbonate (NaHCO3). It should be noted that the catalyst can be added to the subsequent hydrogenation reaction system after the complete catalyst is formed, or the ruthenium-based compound, the ligand having the structure of the general formula (2), and the base can be directly added to the reaction vessel, and then the hydrogenation reaction reactants can be added in situ in the vessel after the catalyst is formed. In addition, if desired, the formation of the catalyst can be carried out in the presence of a solvent. The solvent can be the same as or different from the solvent used in the catalytic hydrogenation reaction described below, preferably the same.

[0051] In some preferred embodiments, the molar ratio of the base to the ruthenium compound is (0~4):1, more preferably (2~3).

[0052] In some preferred embodiments, the molar ratio of ruthenium-based compound to ligand in the composition used to prepare the catalyst is 1:(0.01~10), more preferably 1:(1~3), for example 1:1, 1:1.5, 1:2, 1:2.5, 1:3.

[0053] In this invention, catalytic hydrogenation is achieved by contacting a thiourea compound with hydrogen gas, and under the action of a catalyst, catalytic hydrogenation occurs to obtain the desired product. Depending on the degree of hydrogenation, it can be carried out in the following manner:

[0054]

[0055] For method (a), thioformamide compounds and amine compounds can be obtained. Furthermore, due to the presence of symmetrical and asymmetrical structures in the reaction substrate, one or two different thioformamide compounds can be obtained. For method (b), in addition to amine compounds, methanethiols can also be obtained.

[0056] The reaction can be carried out under high pressure. In some specific embodiments, the reaction pressure is below 100 bar, preferably 5-90 bar, more preferably 10-80 bar, and most preferably 20-50 bar. Therefore, the hydrogenation reaction can be carried out in a high-pressure reactor. Furthermore, there is no particular limitation on the reaction temperature in the hydrogenation reaction step; this may depend on the type of reactants. It is typically below 160°C, preferably 80-160°C, and more preferably 100-140°C. The reaction time is not particularly limited in this invention, and those skilled in the art can adjust it according to actual conditions. Generally, under lower reaction temperatures and / or lower reaction pressures, the reaction time can be appropriately extended to ensure the reaction proceeds fully; correspondingly, under higher reaction temperatures and / or higher reaction pressures, the reaction time can be appropriately shortened to avoid unnecessary energy consumption or side reactions. As an example, the reaction time can be 1 h to 60 h, preferably 6 h to 50 h, more preferably 10 h to 36 h, such as 10 h, 12 h, 18 h, 24 h, 30 h, or 36 h.

[0057] In this invention, the amount of catalyst used, based on the molar amount of ruthenium therein, is 30% or less of the molar amount of the thiourea compound, preferably 0.1 to 25%, more preferably 0.5 to 15%, and even more preferably 1 to 5%.

[0058] In this invention, the solvent is not particularly limited, as long as it is sufficient to dissolve the catalyst. In some specific embodiments, the solvent may include one or more of nitrogen heterocyclic solvents, oxygen heterocyclic solvents, benzene solvents, alcohol solvents, or sulfone solvents. More specifically, the solvent may be one or more of 1,4-dioxane, toluene, tetrahydrofuran, isopropanol, and dimethyl sulfoxide, with tetrahydrofuran being particularly preferred.

[0059] In this invention, the source of the thiourea compounds is not particularly limited. As an example, the thiourea compounds can be synthesized using carbon disulfide or carbonyl sulfide as the sulfur source. Further, they can be obtained by reacting carbon disulfide or carbonyl sulfide with amine compounds.

[0060] A second aspect of the present invention is to provide a method for preparing methanethiol, comprising reacting a thiourea compound with hydrogen in the presence of a catalyst and a solvent to generate methanethiol. The thiourea compound, catalyst, and solvent are as described above.

[0061] A third aspect of the present invention is to provide a method for preparing thioformamide compounds and amine compounds, comprising reacting a thiourea compound with hydrogen in the presence of a catalyst and a solvent. The general structural formulas of the thioformamide compounds and amine compounds are referenced to the reaction products of the above-described reaction equation (a).

[0062] A fourth aspect of the present invention is to provide a ruthenium-based polydentate ligand compound obtained from a composition comprising a ruthenium-based compound and a ligand, wherein the ruthenium-based compound and the ligand are respectively the ruthenium-based compound and the ligand as described above.

[0063] A fifth aspect of the present invention is to provide the use of the ruthenium-based polydentate ligand compound as described above in the catalytic hydrogenation reaction of thiourea compounds.

[0064] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0065] The catalytic hydrogenation method for thiourea compounds of the present invention has advantages such as high selectivity, mild reaction conditions, good atom economy, and environmental friendliness. Attached Figure Description

[0066] Figure 1 The MS-ESI spectrum of the catalytically active component detected in the reaction solution of Example 1 is shown. The detection conditions were: positive ion mode, full scan (retention time: 0.133 min), fragmentation voltage = 50.0 V, and the spectrum was processed by background noise subtraction.

[0067] Figure 2 The chemical structural formula of the catalytically active component in the reaction solution of Example 1 is shown. Detailed Implementation

[0068] The present invention will be further described below with reference to embodiments. However, the present invention is not limited to the following embodiments. The implementation conditions used in the embodiments can be further adjusted according to different requirements of specific use, and the implementation conditions not specified are conventional conditions in the industry. The technical features involved in the various embodiments of the present invention can be combined with each other as long as they do not conflict with each other. Unless otherwise specified, all raw materials used in the following embodiments and comparative examples are commercially available or prepared by conventional methods in the art.

[0069] In this invention, unless the context explicitly requires otherwise, the numerical range referred to as "numerical value A to numerical value B" refers to the range including the endpoints A and B. The numerical range referred to as "above" or "below" refers to the numerical range including the stated number. "Optional" or "optional" indicates that certain substances, components, execution steps, application conditions, etc., may or may not be used, and there is no limitation on the manner of use.

[0070] In this invention, unless the context explicitly requires otherwise, all numerical parameters modified by terms such as "left and right" (including but not limited to time, temperature, pressure, concentration, weight percentage, pH value, and size) should be understood to cover a reasonable range centered on the stated value, based on the fluctuation range of conventional experimental or production equipment. Specifically, this range typically includes ±10% of the stated value, and may be extended to ±20% of the stated value in certain embodiments or where conventional precision in the art allows. Such deviations should be understood as inherent fluctuations caused by differences in measuring instruments, operating methods, environmental conditions, or material batches, and the technical solutions within this range of fluctuations can achieve the core objectives and beneficial effects of this invention.

[0071] In this invention, unless otherwise specified, the qualitative and quantitative methods of the products are based on gas chromatography-programmed temperature detection (Chem. Eur. J. 2023, e202300106), and the instrument used is GC-2010 (Shimadzu, Japan) with an HP-1 column.

[0072] Example 1:

[0073] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine) ruthenium(II) chloride and 0.05 mmol of potassium tert-butoxide (KO) were added. t Bu) and 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand were added to a high-pressure reactor containing 4 mL of tetrahydrofuran solvent and stirred for about 5 min. Then, 2 mmol of 1,3-diphenylthiourea was added.

[0074] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (charge the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeating this cycle 4-6 times). Finally, pressurize it to 50 bar with hydrogen and heat it at 140°C with stirring to carry out the hydrogenation reaction. After the reaction is complete, cool it in an ice bath for about 30 minutes, then slowly release the gas to atmospheric pressure. Add the internal standard biphenyl and take a sample for GC analysis. The conversion rate of 1,3-diphenylthiourea and the yield of methanethiol are shown in Table 1.

[0075] Examples 2 to 7:

[0076] These examples illustrate the effect of different ligands of the present invention on catalytic performance. The operational procedures are basically the same as in Example 1, except that different ligands are used. The conversion rates of 1,3-diphenylthiourea and the yields of methanethiol when using different ligands of the present invention are shown in Table 1 below.

[0077] Table 1

[0078]

[0079] As shown in Table 1, the catalyst systems formed by different ligands and tris(triphenylphosphine)ruthenium dichloride used in this invention all exhibit good catalytic effects on the substrate 1,3-diphenylthiourea, with conversion rates all greater than 99% and methanethiol yields reaching 81% or higher. Among them, the ligand with the best effect is 1,1,1-tris(diphenylphosphinemethyl)ethane, followed by 1,2-bis(diphenylphosphine)ethane and tris(2-(diphenylphosphineyl)ethyl)phosphine.

[0080] Examples 8 to 14:

[0081] These examples illustrate the effect of different ruthenium-based compounds on catalytic performance. The operational procedures are essentially the same as in Example 1, except that different ruthenium-based compounds are used. The conversion rates of 1,3-diphenylthiourea and the yields of methanethiol when different ruthenium-based compounds are selected are shown in Table 2 below.

[0082] Table 2

[0083]

[0084] As shown in Table 2, the catalytic systems formed by different ruthenium compounds and the ligand 1,1,1-tris(diphenylphosphinemethyl)ethane used in this invention all exhibit good catalytic effects on the substrate 1,3-diphenylthiourea, with conversion rates all greater than 99% and methanethiol yields of 90% or higher. Among them, the ruthenium compounds with the best effects are tris(triphenylphosphine)dichloride ruthenium(II), carbonyl dihydrotris(triphenylphosphine)ruthenium(II), and dihydrotetrahydrotriphenylphosphine(II), followed by dichlorotetra(triphenylphosphine)ruthenium(II) and carbonyl chloride hydrogen tris(triphenylphosphine)ruthenium(II).

[0085] Examples 15 to 18:

[0086] These examples illustrate the effect of different solvents on the catalytic performance of the reaction system of the present invention. The operating procedure is basically the same as in Example 1, except that the solvent used in the reaction system is different. The conversion rate of 1,3-diphenylthiourea and the yield of methanethiol when different solvents are used are shown in Table 3 below.

[0087] Table 3

[0088]

[0089] As shown in Table 3, under the conditions of this invention, different solvents can be used for the hydrogenation reaction of 1,3-diphenylthiourea. Different solvents have a certain influence on the yield of methanethiol, but the overall performance is good. Among them, the yield of methanethiol is the highest when tetrahydrofuran is used as a solvent, followed by 1,4-dioxane.

[0090] Examples 19 to 22:

[0091] These examples illustrate the effect of reaction temperature. The operational procedures are essentially the same as in Example 1, except that the reaction temperature used in the reaction system is different, and the H2 pressure of the reaction system is 30 bar in all cases. The conversion rates of 1,3-diphenylthiourea and the yields of thioformamide and methanethiol at different reaction temperatures are shown in Table 4 below.

[0092] Table 4

[0093]

[0094] Table 4 shows that the yield of methanethiol first increases and then decreases with decreasing reaction temperature, indicating that under the same H2 pressure and reaction time, the reaction temperature affects the product yield. When the temperature drops to 100℃ or lower, the yield of methanethiol decreases sharply. This may be because the reaction rate decreases with decreasing reaction temperature, thus hindering the hydrogenation of the intermediate thioformamide to methanethiol, resulting in the accumulation of thioformamide. With prolonged reaction time, the accumulated thioformamide can continue to be hydrogenated to methanethiol.

[0095] Examples 23 to 24:

[0096] These examples illustrate the effect of H2 pressure in the reaction system. The operational procedures are basically the same as in Example 1, except that the H2 pressure used in the reaction system is different, and the reaction temperature is 100°C and the reaction time is 12 h. The conversion rate of 1,3-diphenylthiourea and the yields of thioformamide and methanethiol under different H2 pressures are shown in Table 5 below.

[0097] Table 5

[0098]

[0099] Table 5 shows that reducing H2 pressure leads to a decrease in the conversion rate of 1,3-diphenylthiourea and the yield of methanethiol, while simultaneously increasing the yield of thioformamide. This is likely because the reduced H2 pressure decreases the reaction rate, thus hindering the hydrogenation of the intermediate thioformamide to methanethiol, resulting in the accumulation of thioformamide. With prolonged reaction time, the accumulated thioformamide can continue to be hydrogenated to methanethiol.

[0100] Examples 26 to 30:

[0101] These examples illustrate the effect of base in the reaction system. The operational procedures are basically the same as in Example 1, except that the base used in the reaction system is different, and the reaction temperature is 100°C and the reaction time is 36 h. The conversion rate of 1,3-diphenylthiourea and the yield of methanethiol when using different bases are shown in Table 6 below.

[0102] Table 6

[0103]

[0104] As shown in Table 6, under the conditions of this invention, different bases can promote the reaction of ruthenium compounds with ligands to form a catalyst system, which can then be used for the hydrogenation reaction of 1,3-diphenylthiourea.

[0105] Example 31:

[0106] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-bis(4-chlorophenyl)thiourea was added.

[0107] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 100°C for 24 hours.

[0108] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yield of methanethiol is shown in Table 7.

[0109] Example 32:

[0110] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-bis[3,5-bis(trifluoromethyl)phenyl]thiourea was added.

[0111] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (charge the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeating this cycle 4-6 times). Finally, pressurize it with hydrogen to 30 bar and stir and heat it at 100°C for 24 h. After the reaction is complete, cool it in an ice bath for about 30 minutes, then slowly release the gas to atmospheric pressure. Add the internal standard biphenyl and take a sample for GC analysis. The yield is shown in Table 7.

[0112] Example 33:

[0113] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-bis(4-methylphenyl)thiourea was added.

[0114] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 100 °C for 36 h.

[0115] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0116] Example 34:

[0117] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-bis(2-methylphenyl)thiourea was added.

[0118] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 100 °C for 36 h.

[0119] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0120] Example 35:

[0121] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. tBu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-dicyclohexylthiourea was added.

[0122] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 120 °C for 16 h.

[0123] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0124] Example 36:

[0125] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-di-tert-butylthiourea was added.

[0126] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 120 °C for 24 h.

[0127] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0128] Example 37:

[0129] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-diisopropylthiourea was added.

[0130] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 120 °C for 24 h.

[0131] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0132] Example 38:

[0133] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 1,3-diethylthiourea was added.

[0134] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 120 °C for 24 h.

[0135] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0136] Example 39:

[0137] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of tetramethylthiourea was added.

[0138] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 140 °C for 24 h.

[0139] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0140] Example 40:

[0141] In a glove box under N2 atmosphere, 0.02 mmol of tris(triphenylphosphine)ruthenium(II) dichloride, 0.03 mmol of 1,1,1-tris(diphenylphosphinemethyl)ethane ligand, and 0.05 mmol of KO were added. t Bu and 4 mL of tetrahydrofuran solvent were added to a high-pressure reactor and stirred for about 5 min. Then, 2 mmol of 5-bromo-1,3-dihydro-2H-benzimidazole-2-thione was added.

[0142] Remove the sealed high-pressure reactor from the glove box and flush it with hydrogen 4-6 times (fill the reactor with hydrogen until the pressure reaches 50 bar, then release it to about 2 bar, repeat this cycle 4-6 times), finally pressurize it with hydrogen to 30 bar and stir and heat it at 140 °C for 24 h.

[0143] After the reaction was complete, the mixture was cooled in an ice bath for about 30 minutes, and then slowly vented to atmospheric pressure. Internal standard biphenyl was added, and samples were taken for GC analysis. The yields are shown in Table 7.

[0144] Table 7

[0145]

[0146] As shown in Table 7, the catalyst system of the present invention exhibits a wide range of applicability to the hydrogenation reactions of various thiourea derivatives.

[0147] Comparative Examples 1 to 5:

[0148] These comparative examples examined the effects of different metal precursors. The operating procedures were basically the same as in Example 1, except that equimolar amounts of other metal precursors were used to replace tris(triphenylphosphine) ruthenium(II) dichloride in the reaction system. The conversion rates of 1,3-diphenylthiourea and the yields of thioformamide and methanethiol when using different metal precursors are shown in Table 8 below.

[0149] Table 8

[0150]

[0151] As shown in Table 8, when metal precursors such as cobalt-based, copper-based, nickel-based, or manganese-based compounds are used, the catalyst system composed of them and the ligands of the present invention cannot effectively catalyze the hydrogenation reaction of thiourea derivatives to generate methanethiol.

[0152] Comparative Examples 6 to 9:

[0153] These comparative examples examined the effects of different ligands. The operational procedures were basically the same as in Example 1, except that 1,1,1-tris(diphenylphosphinemethyl)ethane was replaced with an equimolar amount of other ligands in the reaction system. The conversion rates of 1,3-diphenylthiourea and the yields of thioformamide and methanethiol when using different ligands are shown in Table 9 below.

[0154] Table 9

[0155]

[0156] As shown in Table 9, when other ligands different from those in this invention are used, the catalyst systems composed of them and ruthenium-based compounds cannot effectively catalyze the hydrogenation reaction of thiourea derivatives to generate methanethiol.

[0157] The present invention has been described in detail above, with the aim of enabling those skilled in the art to understand and implement the invention. However, this description should not be construed as limiting the scope of protection of the invention. All equivalent changes or modifications made in accordance with the spirit and essence of the invention should be included within the scope of protection of the invention.

Claims

1. A method for the catalytic hydrogenation of thiourea compounds, characterized in that: The method involves contacting a thiourea compound with hydrogen in the presence of a catalyst and a solvent; The structure of the thiourea compounds is shown in general formula (1). ， （1） In the general formula (1), R 1 R 2 R 3 and R 4 Each is independently a monovalent organic group, or any two or more of them are interconnected to form a cyclic structure, wherein the monovalent organic group is hydrogen, or optionally substituted straight-chain, branched, or cyclic hydrocarbon groups, when R 1 R 2 R 3 and R 4 When any two or more of the elements are interconnected to form a ring structure, the ring structure is an optionally substituted aromatic ring; The catalyst is obtained from a composition comprising a ruthenium-based compound and a ligand; The ruthenium compound is a ruthenium(II) complex and / or a ruthenium(III) complex, wherein the ligands in the ruthenium(II) complex and / or the ruthenium(III) complex include one or more of organophosphorus ligands, halogen ligands, carbonyl ligands, hydrogen ligands, olefin ligands, and acetylacetone ligands; The ligands in the composition have one or more structures as shown in general formulas (2-1), (2-2), (2-3), (2-4), and (2-5). 4-n (R 6 -)C(-L-Y(R 5 )2) n , （2-1） (R 5 )2Y—L—L—Y(R 5 )2, （2-2） 3-m (R 6 -)N(-L-Y(R 5 )2) m , （2-3） 3-m (R 6 -)P(-L-Y(R 5 )2) m , （2-4） ， （2-5） Where n is 2, 3, or 4; m is 2 or 3; R 5 It is a straight-chain, branched, or aromatic hydrocarbon group of C3-C10; R 6 L is a hydrogen atom or a straight-chain, branched, or aromatic hydrocarbon group of C3-C10; Y is a C1-C6 hydrocarbon group; and Y is a phosphorus atom. In general formula (2-1), C represents a carbon atom; In general formula (2-3), N is a nitrogen atom; In general formula (2-4), P represents a phosphorus atom; In general formula (2-5), the cyclic structure A is selected from pyridine, pyrrole, benzopyridine or benzopyrrole.

2. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The ruthenium-based compounds include one or more of the following: tris(triphenylphosphine)dichloride ruthenium(II), dichlorotetra(triphenylphosphine)ruthenium(II), dihydrotetra(triphenylphosphine)ruthenium(II), triphenylphosphine carbonyl ruthenium(II), dichlorotetra(triphenylphosphine)ruthenium(II), carbonyl dihydrotris(triphenylphosphine)ruthenium(II), carbonyl chloride hydrogen tris(triphenylphosphine)ruthenium(II), bis(2-methylallyl)(1,5-cyclooctadiene)ruthenium(II), and acetylacetone ruthenium(III).

3. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The R 1 R 2 One and only one of them is hydrogen, and the other is an optionally substituted C1-C10 alkyl, 4-6 membered cycloalkyl or phenyl, or is related to the R. 3 R 4 One of them forms the aromatic ring; the R 3 R 4 There is one and only one hydrogen.

4. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The ligands include one or more of 1,1,1-tris(diphenylphosphinemethyl)ethane, 1,2-bis(diphenylphosphine)ethane, 2,6-bis[(diphenylphosphineyl)methyl]pyridine, 2,6-bis((di-tert-butylphosphineyl)methyl)pyridine, bis(2-(di-tert-butylphosphineyl)ethyl)amine hydrochloride, ((phenylphosphinediyl)bis(ethane-2,1-diyl))bis(diphenylphosphine), and tris(2-(diphenylphosphineyl)ethyl)phosphine.

5. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The thiourea compound reacts with the hydrogen gas at a temperature of 80°C to 160°C and at a pressure of 100 bar or less.

6. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: In the composition, the molar ratio of ruthenium-based compound to ligand is 1:(0.01~10); and / or, The composition further includes a base, which is selected from one or more organic bases and inorganic bases, and the molar ratio of the base to the ruthenium-based compound is (0~4):

1.

7. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The amount of catalyst used, based on the molar number of ruthenium, is 30% or less of the molar number of the thiourea compound.

8. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The solvent is an organic solvent capable of dissolving the catalyst.

9. The catalytic hydrogenation method for thiourea compounds according to claim 1, characterized in that: The thiourea compounds are synthesized using carbon disulfide or carbonyl sulfide as the sulfur source.

10. A method for preparing methanethiol, characterized in that: The thiourea compound is reacted with hydrogen in the presence of a catalyst and a solvent to obtain the methanethiol; wherein the thiourea compound, the catalyst, and the solvent are the thiourea compound, the catalyst, and the solvent as described in any one of claims 1 to 9.

11. A ruthenium-based polydentate ligand compound, characterized in that: Obtained from a composition comprising a ruthenium-based compound and a ligand, wherein the ruthenium-based compound is any one of claims 1 to 9, and the ligand in the composition is a ligand represented by general formula (2-1), general formula (2-2), general formula (2-3), general formula (2-4), or general formula (2-5) as described in any one of claims 1 to 9.

12. The use of the ruthenium-based polydentate ligand compound as described in claim 11 in the catalytic hydrogenation reaction of thiourea compounds, characterized in that: The thiourea compound is any one of the thiourea compounds according to claims 1 to 9.

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