Method for producing cyanide compounds

Abstract

This invention provides a method for efficiently producing cyanide compounds without using cyanogen chloride as a cyanating agent. [Solution] A method for producing a cyanide compound, comprising carrying out a reaction between a reaction substrate and at least one cyanating agent selected from the group consisting of trialkylsilyl cyanides and hydrogen cyanide, in the presence of at least one oxidizing agent selected from the group consisting of alkali metal hypochlorite and alkali metal hypochlorite hydrate, and alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrate, and an organic solvent, wherein the oxidizing agent is solid when added.

Description

[Technical Field]

[0001] This invention relates to a method for producing cyanide compounds. [Background technology]

[0002] Cyanide compounds are compounds that contain a cyano group (-C≡N) in their molecule and are widely used, for example, in pharmaceuticals, pesticides, polymer materials, and as raw materials for these. Synthetic reactions to obtain cyanide compounds include nucleophilic cyanation and electrophilic cyanation. Of these, the stable chemical species is the cyanide ion ( - Nucleophilic cyanation reactions using C≡N) or its salts as cyanating agents have been the primary method used, and the number of cyanating agents that can be used in electrophilic cyanation reactions has been limited.

[0003] In response to the above problem, Non-Patent Document 1 successfully obtained S-cyanated tosyl cyanide derivatives by an electrophilic cyanation reaction using sodium p-toluenesulfinate and its derivatives as starting materials and cyanogen chloride as the cyanating agent. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Cox, JM; Ghosh, R. Tetrahedron Lett. 1969, 10, 3351-3352. [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] However, cyanogen chloride is a gas at room temperature and an unstable compound, making it difficult to handle and sometimes difficult to obtain.

[0006] Therefore, an object of the present invention is to provide a means capable of efficiently producing a cyanide compound without using cyanogen chloride as a cyanating agent.

Means for Solving the Problems

[0007] The inventors of the present invention conducted intensive studies to solve the above problems. As a result, they found that a cyanide compound can be produced by using trimethylsilyl cyanide or hydrogen cyanide as a cyanating agent and allowing an oxidizing agent to coexist therewith, and thus completed the present invention.

[0008] That is, one embodiment of the present invention relates to a method for producing a cyanide compound, which includes carrying out a reaction between a reaction substrate and at least one cyanating agent selected from the group consisting of trialkylsilyl cyanide and hydrogen cyanide in the presence of at least one oxidizing agent selected from the group consisting of alkali metal hypochlorite and its hydrate, and alkaline earth metal hypochlorite and its hydrate, and an organic solvent. In this production method, it is characterized in that the oxidizing agent is solid when added.

Effects of the Invention

[0009] According to the present invention, a cyanide compound can be efficiently produced without using cyanogen chloride as a cyanating agent.

Modes for Carrying Out the Invention

[0010] The embodiments for carrying out the present invention will be described in detail below. The embodiments shown herein are illustrative examples to embody the technical idea of ​​the present invention and do not limit the present invention. Therefore, all other implementable forms, methods of use, and operating techniques that can be conceived by those skilled in the art without departing from the spirit of the present invention are included in the scope and spirit of the present invention, as well as in the claims and their equivalents. The embodiments described herein can be combined in any way to form other embodiments. In this specification, "X~Y" indicating a range means "X or more and Y or less". Unless otherwise specified, operations and measurements of physical properties, etc., are performed under conditions of room temperature (20~25°C) / relative humidity 40~60%.

[0011] One embodiment of the present invention is a method for producing a cyanide compound, comprising carrying out a reaction between a reaction substrate and at least one cyanating agent selected from the group consisting of trialkylsilyl cyanides and hydrogen cyanide, in the presence of an oxidizing agent selected from the group consisting of alkali metal hypochlorite and alkali metal hypochlorite hydrates, and alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrates, and an organic solvent, wherein the oxidizing agent is solid when added.

[0012] [Reaction substrate] The reaction substrate used in the production method according to the present invention is a chemical species that undergoes electrophilic attack in the cyanation reaction. Examples of reaction substrates include aromatic compounds. Among these, chemical species in which a heteroatom is bonded to an aromatic ring are preferred, chemical species in which a nitrogen atom or sulfur atom is bonded to an aromatic ring are more preferred, chemical species in which a sulfur atom is bonded to an aromatic ring are even more preferred, and compounds represented by the following chemical formula 1 are particularly preferred:

[0013] [ka]

[0014] In the above chemical formula 1, R 1 ~R5 is, independently of one another, a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group, an alkoxyalkyl group, an alkoxyalkyloxy group, an alkyloxycarbonyloxy group, a nitro group, or an aryl group, M is an alkali metal.

[0015] In the above Chemical Formula 1, R 1 ~R 5 is preferably at least one selected from the group consisting of a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group, an alkoxyalkyl group, an alkoxyalkyloxy group, and an aryl group, more preferably at least one of a hydrogen atom, an alkyl group, and an alkoxy group, and even more preferably a hydrogen atom or an alkyl group. The alkyl group is, for example, a linear or branched alkyl group having 1 to 20 carbon atoms, preferably a linear or branched alkyl group having 1 to 10 carbon atoms, more preferably a linear or branched alkyl group having 1 to 6 carbon atoms, and even more preferably a linear or branched alkyl group having 1 to 4 carbon atoms. Examples of the linear or branched alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group, with a methyl group being preferred.

[0016] In the above Chemical Formula 1, it is preferable that at least 3 of R 1 ~R 5 are hydrogen atoms, more preferably at least 4 of R 1 ~R 5 are hydrogen atoms, particularly preferably R 1 , R 2 , R 4 , and R 5 are hydrogen atoms, and most preferably R 1 , R 2 , R 4 , and R 5 are hydrogen atoms and R 3 is an alkyl group.

[0017] In the above chemical formula 1, M is preferably a sodium cation or a potassium cation, and a sodium cation is particularly preferred.

[0018] In one embodiment, the reaction substrate is preferably at least one of sodium benzenesulfinate and sodium p-toluenesulfinate, and more preferably sodium p-toluenesulfinate.

[0019] [Cyanogenic agent] In the production method according to the present invention, the cyanating agent is at least one selected from the group consisting of trialkylsilyl cyanides and hydrogen cyanide (HCN). When the above cyanating agent is used, the electrophilic cyanation reaction can proceed efficiently. In one embodiment, the trialkylsilyl cyanide is preferably trimethylsilyl cyanide (TMSCN). In this specification, the cyanating agent refers to a compound having a cyanogen source that is added to the reaction system. That is, it does not refer to reaction intermediates or reactive species that are generated as a cyanogen source during the reaction.

[0020] [Oxidizing agent] In the manufacturing method according to the present invention, the oxidizing agent is at least one selected from the group consisting of alkali metal hypochlorite and alkali metal hypochlorite hydrates, and alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrates. Furthermore, the oxidizing agent used is a compound that is solid at room temperature (25°C) and atmospheric pressure (1 atm). When the above oxidizing agent is used, the electrophilic cyanation reaction proceeds smoothly. In one embodiment, the oxidizing agent is preferably at least one selected from the group consisting of alkali metal hypochlorite hydrates and alkaline earth metal hypochlorite hydrates, and is particularly preferably alkali metal hypochlorite hydrate.

[0021] Examples of alkali metal ions in alkali metal hypochlorite and alkali metal hypochlorite hydrates include lithium, sodium, potassium, rubidium, and cesium. Among these, at least one selected from the group consisting of lithium, sodium, and potassium is preferred as the alkali metal ion, with sodium being particularly preferred. Furthermore, sodium hypochlorite pentahydrate is preferred as the alkali metal hypochlorite hydrate.

[0022] Examples of alkaline earth metal ions in alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrates include beryllium, magnesium, calcium, scandium, barium, and radium. Among these, at least one selected from the group consisting of magnesium and calcium is preferred as the metallic species of the alkaline earth metal ion.

[0023] In the manufacturing method according to the present invention, the oxidizing agent added to the reaction system (reaction vessel) is a solid. That is, it does not include a form in which the oxidizing agent is dissolved in water or an organic solvent beforehand and added to the reaction system in a solution (for example, an aqueous solution).

[0024] [organic solvent] In the manufacturing method according to the present invention, an organic solvent is used. Examples of organic solvents include methanol, ethanol, acetonitrile, ethyl acetate, butyl acetate, diethyl ether, t-butyl methyl ether (MTBE), tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), benzene, toluene, dichloromethane, 1,2-dichloroethane, and chloroform. In particular, the organic solvent is preferably at least one selected from the group consisting of ethyl acetate, butyl acetate, diethyl ether, t-butyl methyl ether (MTBE), tetrahydrofuran (THF), dichloromethane, 1,2-dichloroethane, and chloroform, more preferably at least one selected from the group consisting of ethyl acetate, butyl acetate, and dichloromethane, and dichloromethane is particularly preferred. The organic solvent may be used alone or as a mixture of two or more.

[0025] Furthermore, the water content in the organic solvent is, for example, 0% by mass or more and 5% by mass or less, preferably 0% by mass or more and 1% by mass or less, more preferably 0% by mass or more and 0.1% by mass or less, and even more preferably 0% by mass or more and 0.01% by mass or less.

[0026] [Phase transfer catalyst] In the manufacturing method according to the present invention, a phase transfer catalyst may be further added. Adding a phase transfer catalyst can further improve the reaction. Examples of phase transfer catalysts include crown ethers, quaternary ammonium salts, and phosphonium salts. Among these, it is preferable that the phase transfer catalyst be at least one selected from the group consisting of crown ethers and ammonium salts. Only one phase transfer catalyst may be used, or two or more may be used in combination.

[0027] Examples of ring-constituting atom numbers for crown ethers include 12, 15, 18, 21, and 24. In the production method according to the present invention, when the raw material to be added contains a sodium salt, the ring-constituting atom number of the crown ether is preferably at least one of 12, 15, and 18, and particularly preferably 15. Examples of crown ethers that can be used include 12-crown-4, 15-crown-5, 18-crown-6, benzo-12-crown-4, benzo-15-crown-5, dibenzo-18-crown-6, dicyclohexyl-18-crown, dibenzo-24-crown-8, and dicyclohexyl-24-crown-8. In particular, when the added raw materials contain sodium salts, the crown ether is preferably at least one selected from the group consisting of 15-crown-5, 18-crown-6, benzo-12-crown-4, benzo-15-crown-5, dibenzo-18-crown-6, and dicyclohexyl-18-crown, and more preferably at least one of 15-crown-5 and benzo-15-crown-5.

[0028] Examples of quaternary ammonium salts include, but are not limited to, tetramethylammonium salt, tetraethylammonium salt, tetrabutylammonium salt, benzyltrimethylammonium salt, benzyltriethylammonium salt, benzyltributylammonium salt, decyltrimethylammonium salt, hexadecyltrimethylammonium salt, methyltrioctylammonium salt, benzyldimethyltetradecylammonium salt, and ethylhexadecyldimethylammonium salt. In one embodiment, tetrabutylammonium salt is preferred as the quaternary ammonium salt. Examples of counterions for the quaternary ammonium cation include chloride ions, bromide ions, iodide ions, cyanide ions, and bisulfate ions. Among these, at least one of chloride ions and bisulfate ions is preferred. Examples of quaternary ammonium salts that can be used include tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium cyanide, and tetrabutylammonium bisulfate. Among these, at least one of tetrabutylammonium chloride and tetrabutylammonium bisulfate is preferred.

[0029] Examples of phosphonium salts include tetrabutylphosphonium bromide, tetraethylphosphonium hexafluorophosphate, tributyldodecylphosphonium bromide, tributylhexadecylphosphonium bromide, tetraethylphosphonium bromide, hexadecyltributylphosphonium bromide, and benzyltriphenylphosphonium chloride.

[0030] When dichloromethane is used as the organic solvent, the phase transfer catalyst is preferably a crown ether and an ammonium salt, and more preferably a crown ether. Furthermore, when ethyl acetate and / or butyl acetate is used as the organic solvent, the phase transfer catalyst is preferably a crown ether and an ammonium salt, and more preferably an ammonium salt.

[0031] [Reaction conditions] In the manufacturing method according to the present invention, reaction conditions can be appropriately selected by referring to conventionally known techniques. For example, predetermined amounts of the reaction substrate, cyanating agent, oxidizing agent, organic solvent, and optionally added components are weighed or measured, and added sequentially or simultaneously in any order to a reaction vessel set to a predetermined temperature and pressure, and then mixed for a predetermined time using appropriate mixing means. It is preferable that the reaction substrate be added last. In one embodiment, the manufacturing method according to the present invention includes adding a reaction substrate, cyanating agent, oxidizing agent, organic solvent, and phase transfer catalyst. In this embodiment, the amount of water added relative to the total mass of the reaction substrate, cyanating agent, oxidizing agent, organic solvent, and phase transfer catalyst is, for example, 0% by mass or more than 0% by mass and 5% by mass or less, preferably 0% by mass or more and 1% by mass or less, and more preferably 0% by mass or more and 0.1% by mass or less. The above water includes the water contained in the raw materials, and the amount of water added refers to the amount including the amount of water contained in the raw materials to be added.

[0032] The reaction temperature is, for example, 0°C to 100°C, preferably 0°C to 25°C, and more preferably above 0°C and below 15°C. Means for controlling the reaction temperature to a value within the above range include performing heat exchange using a heat exchanger such as a jacket or tubing, or thoroughly stirring the reaction solution.

[0033] The pressure and atmosphere within the reaction system are not particularly limited. The pressure can be normal (atmospheric), reduced pressure, or pressurized. However, from the viewpoint of increasing the reaction rate, it is preferable to carry out the reaction process under normal (atmospheric) pressure. The atmosphere within the reaction system can be air, but it is preferable to have an inert atmosphere. For example, it is preferable to replace the system with an inert gas such as nitrogen before starting the reaction.

[0034] There are no particular restrictions on the reaction time, but the time allowed for the reaction to proceed after adding all the raw materials (maturation time) is preferably 10 minutes to 3 hours, more preferably 10 minutes to 1 hour, and even more preferably 10 minutes to 30 minutes. If the maturation time is 3 hours or less, it is possible to suppress the consumption of the product by unwanted side reactions after the desired product has been obtained.

[0035] [Cyanide compounds] In the production method according to the present invention, a cyanide compound is produced by the electrophilic cyanation reaction of the above-mentioned reaction substrate. For example, if the reaction substrate is a chemical species in which a sulfur atom is bonded to an aromatic ring, the resulting cyanide compound is an S-cyanide. Furthermore, if the reaction substrate is a compound represented by the above chemical formula 1, the resulting cyanide compound is a compound represented by the following chemical formula 2:

[0036] [ka]

[0037] R in the above chemical formula 2 1 ~R 5 And M are the same as those described in Chemical Formula 1 in the [Reaction Substrate] section above. The compound represented by Chemical Formula 2 above can be used as a cyanating agent in electrophilic cyanation reactions. Since the compound represented by Chemical Formula 2 has low toxicity and a boiling point above room temperature, when the reaction substrate is the compound represented by Chemical Formula 1, an easy-to-handle cyanating agent can be obtained. When the reaction substrate is p-toluenesulfinate, the cyanide compound is tosylcyanide. Since tosylcyanide has low toxicity and is a solid at room temperature (25°C), when the reaction substrate is p-toluenesulfinate, a low-toxicity, easy-to-handle cyanating agent can be obtained.

[0038] Although the detailed mechanism by which cyanide compounds are obtained by the method described above is not clear, the following mechanism is hypothesized. When trimethylsilyl cyanide (TMSCN) is used as the cyanating agent, the reaction shown in chemical equation 1 below proceeds, generating hydrogen cyanide.

[0039] [ka]

[0040] The hydrogen cyanide generated in the above chemical reaction equation 1, or the hydrogen cyanide added as a cyanating agent, reacts with the oxidizing agent to produce cyanogen chloride (chemical reaction equation 2). Chemical reaction equation 2 shows the case when sodium hypochlorite is used as the oxidizing agent.

[0041] [ka]

[0042] As described above, the cyanogen chloride produced has positively charged carbon atoms. Therefore, it performs electrophilic attacks on electron-rich chemical species.

[0043] If the reaction substrate is sodium p-toluenesulfinate, the reaction shown in chemical equation 3 will proceed further.

[0044] [ka]

[0045] As a result, tosyl cyanide (p-toluenesulfonic acid cyanide) can be obtained in which the sulfur atom of sodium p-toluenesulfinate is cyanated.

[0046] If the above chemical reaction equation 3 does not proceed rapidly, hypochlorite or hypochlorous acid generated from hypochlorite may undergo electrophilic attack on sodium p-toluenesulfinate. In this case, tosyl chloride (p-toluenesulfonic acid chloride) is produced, which is a chlorinated form of sodium p-toluenesulfinate.

[0047] Non-Patent Document 1 is thought to describe a reaction similar to that described in Chemical Equation 3 above. In Non-Patent Document 1, water is used as the reaction solvent for the above reaction. However, according to the inventors' studies, when trimethylsilyl cyanide or hydrogen cyanide is used as the cyanating agent, the electrophilic cyanation reaction proceeds smoothly and the desired cyanide compound is obtained when the starting materials do not contain a large amount of water. It should be noted that the above mechanism is based on speculation, and its accuracy does not affect the technical scope of the present invention.

[0048] The following embodiments are also included within the scope of the present invention: Item 1: A method for producing a cyanide compound, comprising carrying out a reaction between a reaction substrate and at least one cyanating agent selected from the group consisting of trialkylsilyl cyanides and hydrogen cyanide, in the presence of at least one oxidizing agent selected from the group consisting of alkali metal hypochlorite and alkali metal hypochlorite hydrates, and alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrates, and an organic solvent, wherein the oxidizing agent is solid when added; Item 2: A method for producing the cyanide compound according to Item 1, wherein the reaction is an electrophilic cyanation reaction; Item 3: A method for producing the cyanide compound according to item 1 or 2, wherein the cyanide compound is an S-cyanide; Item 4 The reaction substrate is a compound represented by the following chemical formula 1, A method for producing a cyanide compound according to any one of items 1 to 3, wherein the cyanide compound is a compound represented by the following chemical formula 2:

[0049] [ka]

[0050] In the aforementioned chemical formulas 1 and 2, R 1 ~R 5 These are, independently, a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group, an alkoxyalkyl group, an alkoxyalkyloxy group, an alkyloxycarbonyloxy group, a nitro group, and an aryl group. M is an alkali metal; Item 5: In the above chemical formulas 1 and 2, R 1 , R 2 , R 4 , and R 5 The method for producing the cyanide compound described in item 4 is a hydrogen atom; Item 6: A method for producing a cyanide compound according to any one of items 1 to 5, wherein the reaction substrate is p-toluenesulfinate. Item 7: A method for producing a cyanide compound according to any one of items 1 to 6, further comprising the coexistence of a phase transfer catalyst in the system of the reaction; Item 8: A method for producing a cyanide compound according to any one of items 1 to 7, wherein the water content in the organic solvent is 0% by mass or more and 0.1% by mass or less; Item 9: A method for producing a cyanide compound according to any one of items 1 to 8, wherein the reaction temperature is greater than 0°C and 15°C or less; Item 10: The method for producing a cyanide compound according to Item 7, wherein the phase transfer catalyst is at least one selected from the group consisting of crown ethers and quaternary ammonium salts. [Examples]

[0051] The present invention will be described in more detail below with reference to examples. However, the technical scope of the present invention is not limited to the following examples. Unless otherwise specified, raw materials were purchased from reagent manufacturers and used without purification. TMSCN was manufactured by Nippo Chemical Co., Ltd. Dichloromethane (CH2Cl2) was distilled from CaH2 and dried in MS4A. The equivalent amounts of each raw material are based on the amount of p-toluenesulfinate sodium added.

[0052] Furthermore, the yields of tosylcyanide (TsCN, δ7.96 ppm) and tosylloride (TsCl, δ7.93 ppm) in Examples 2-23 and Comparative Examples 1-3 below were obtained using 1,1,2,2-tetrachloroethane (δ5.98 ppm) as an internal standard. 1 The determination was made by 1H-NMR spectroscopy. 1 The conditions for 1H NMR measurement are as follows:

[0053] < 1 H NMR measurement conditions> Measuring device: Varian 400-MR or JEOL ECS-400 Frequency: 400MHz Measurement solvent: CDCl3 Reference substance: CHCl3 (δ7.26ppm).

[0054] Examples of cyanide compound production. [Example 1] In a dried and argon-purged 20 mL two-necked flask, 15-Crown-5 (9.4 mg, 0.043 mmol) was dissolved in CH2Cl2 (1 mL) as an organic solvent cooled to 10°C. Trimethylsilyl cyanide (TMSCN; 36.6 mg, 0.37 mmol), NaOCl·5H2O (81.3 mg, 0.49 mmol), and sodium p-toluenesulfinate (36.3 mg, 0.20 mmol) were sequentially added to the solution. After stirring at 10°C for 30 minutes, the mixture was filtered, and the filtrate was concentrated under vacuum to obtain a crude mixture. The crude mixture was purified by silica gel column chromatography eluting with hexane:ethyl acetate (10:1) to obtain tosyl cyanide as a colorless solid (24.9 mg, 0.14 mmol, 67%).

[0055] [Investigation of oxidizing agents and cyanating agents] [Example 2] In a dry, argon-purged 20 mL two-necked flask, 15-Crown-5 (8.8 mg, 0.040 mmol, 20 mol%) was dissolved in 1 mL of CH2Cl2 cooled to 10°C. TMSCN (39.7 mg, 0.40 mmol, 2.0 equivalents), NaOCl·5H2O (98.7 mg, 0.60 mmol, 3.0 equivalents), and sodium p-toluenesulfinate (36.3 mg, 0.20 mmol, 1 equivalent) were added sequentially. After stirring at 10°C for 60 minutes, the mixture was filtered, sampled from the filtrate, and vacuum-dried. The residue was then analyzed. 1 1H NMR measurements were performed.

[0056] [Comparative Example 1] The reaction was carried out in the same manner as in Example 2, except that an aqueous NaOCl solution (effective chlorine concentration 5%, 848 mg, 0.60 mmol) was used as the oxidizing agent. 1 1H NMR measurements were performed.

[0057] [Comparative Example 2] The reaction was carried out in the same manner as in Example 2, except that tBuOCl was used as the oxidizing agent. 1 1H NMR measurements were performed.

[0058] [Comparative Example 3] The reaction was carried out in the same manner as in Example 2, except that sodium cyanide (NaCN) was used as the cyanating agent. 1 1H NMR measurements were performed.

[0059] The results for Example 2 and Comparative Examples 1-3 are shown in Table 1. In the table below, "ND" indicates that the compound was not detected.

[0060] [Table 1]

[0061] As shown in Table 1, in Example 2, where solid sodium hypochlorite pentahydrate was used as the oxidizing agent and trimethylsilyl cyanide (TMSCN) was used as the cyanating agent, the target product, tosyl cyanide, was obtained. On the other hand, in Comparative Example 1, where the oxidizing agent was a solution of sodium hypochlorite aqueous solution instead of a solid, and in Comparative Example 2, where tert-butyl hypochlorite was used, tosyl cyanide was not obtained. Furthermore, in Comparative Example 3, where sodium cyanide was used as the cyanating agent, tosyl cyanide was also not obtained.

[0062] [Equivalent analysis of TMSCN] [Example 3] The reaction was carried out in the same manner as in Example 2, except that the amount of TMSCN was set to 1.5 equivalents. 1 1H NMR measurements were performed.

[0063] [Example 4] The reaction was carried out in the same manner as in Example 2, except that the amount of TMSCN was set to 1.8 equivalents. 1 1H NMR measurements were performed.

[0064] [Example 5] The reaction was carried out in the same manner as in Example 2, except that the amount of TMSCN was set to 2.5 equivalents. 1 1H NMR measurements were performed.

[0065] The results for Examples 2-5 are shown in Table 2.

[0066] [Table 2]

[0067] [Equivalent amount study of NaOCl·5H2O] [Example 6] The reaction was carried out in the same manner as in Example 4, except that the equivalent amount of NaOCl·5H2O was set to 2.0 equivalents. 1 1H NMR measurements were performed.

[0068] [Example 7] The reaction was carried out in the same manner as in Example 4, except that the equivalent amount of NaOCl·5H2O was set to 2.5 equivalents. 1 1H NMR measurements were performed.

[0069] [Example 8] The reaction was carried out in the same manner as in Example 4, except that the equivalent amount of NaOCl·5H2O was set to 4.0 equivalents. 1 1H NMR measurements were performed.

[0070] The results for Examples 4 and 6-8 are shown in Table 3.

[0071] [Table 3]

[0072] [Consideration of reaction temperature] [Example 9] The reaction was carried out in the same manner as in Example 7, except that the reaction temperature after adding sodium p-toluenesulfinate was set to 30°C. 1 1H NMR measurements were performed.

[0073] [Example 10] The reaction was carried out in the same manner as in Example 7, except that the reaction temperature after adding sodium p-toluenesulfinate was set to 0°C. 1 1H NMR measurements were performed.

[0074] The results for Examples 7 and 9-10 are shown in Table 4.

[0075] [Table 4]

[0076] [Investigation of phase-transfer catalysts] [Example 11] The reaction was carried out in the same manner as in Example 7, except that the equivalent amount of 15-Crown-5 was set to 10 mol%. 1 1H NMR measurements were performed.

[0077] [Example 12] The reaction was carried out in the same manner as in Example 7, except that the equivalent amount of 15-Crown-5 was set to 5 mol%. 1 1H NMR measurements were performed.

[0078] [Example 13] The reaction was carried out in the same manner as in Example 7, except that the phase transfer catalyst was tetrabutylammonium cyanide (Bu4NCN). 1 1H NMR measurements were performed.

[0079] [Example 14] The reaction was carried out in the same manner as in Example 7, except that tetrabutylammonium chloride (Bu4NCl) was used as the phase transfer catalyst. 1 1H NMR measurements were performed.

[0080] [Example 15] The reaction was carried out in the same manner as in Example 7, except that the phase transfer catalyst was tetrabutylammonium bromide (Bu4NBr). 1 1H NMR measurements were performed.

[0081] [Example 16] The reaction was carried out in the same manner as in Example 7, except that the phase transfer catalyst was tetrabutylammonium hydrogen sulfate (Bu4NHSO4). 1 1H NMR measurements were performed.

[0082] The results for Example 7 and Examples 11-16 are shown in Table 5.

[0083] [Table 5]

[0084] [Investigation of reaction time] [Example 17] The reaction was carried out in the same manner as in Example 7, except that the reaction time after adding sodium p-toluenesulfinate was set to 30 minutes. 1 1H NMR measurements were performed.

[0085] [Example 18] The reaction was carried out in the same manner as in Example 7, except that the reaction time after adding sodium p-toluenesulfinate was set to 10 minutes. 1 1H NMR measurements were performed.

[0086] The results of Example 7 and Examples 17-18 are shown in Table 6.

[0087] [Table 6]

[0088] [Investigation of solvent and phase transfer catalyst combinations] [Example 19] The reaction was carried out in the same manner as in Example 17, except that the phase transfer catalyst was tetrabutylammonium hydrogen sulfate (Bu4NHSO4). 1 1H NMR measurements were performed.

[0089] [Example 20] The reaction was carried out in the same manner as in Example 17, except that ethyl acetate was used as the organic solvent. 1 1H NMR measurements were performed.

[0090] [Example 21] The reaction was carried out in the same manner as in Example 20, except that the phase transfer catalyst was tetrabutylammonium hydrogen sulfate (Bu4NHSO4). 1 1H NMR measurements were performed.

[0091] [Example 22] The reaction was carried out in the same manner as in Example 21, except that the organic solvent was isopropyl acetate. 1 1H NMR measurements were performed.

[0092] The results of Example 17 and Examples 19-22 are shown in Table 7.

[0093] [Table 7]

[0094] Furthermore, hydrogen cyanide (HCN) was used as the cyanating agent to produce cyanide compounds via electrophilic cyanation reactions.

[0095] [Example 23] In a dried and argon-purged 100 mL four-necked flask, 15-Crown-5 (351 mg, 1.59 mmol) was dissolved in CH2Cl2 (40 mL) cooled to 10°C, and HCN (387 mg, 14.3 mmol), NaOCl·5H2O (3.27 g, 19.9 mmol), and sodium p-toluenesulfinate (1.42 g, 7.97 mmol) were added sequentially. After stirring at 10°C for 60 minutes, the mixture was filtered, sampled from the filtrate, and vacuum-dried. The residue was then analyzed. 1 ¹H NMR measurements were performed to calculate the yield of tosyl cyanide, which was found to be 87%.

[0096] The results from Example 23 showed that tosyl cyanide, the target product, can also be obtained when hydrogen cyanide is used as the cyanating agent. Therefore, it was found that cyanide compounds can be obtained by electrophilic cyanation reaction using the method for producing cyanide compounds of the present invention, even without adding chloride cyanide.

Claims

1. At least one oxidizing agent selected from the group consisting of alkali metal hypochlorite and alkali metal hypochlorite hydrates, and alkaline earth metal hypochlorite and alkaline earth metal hypochlorite hydrates, Organic solvents, In the presence of, Reaction substrate and, The process involves carrying out a reaction with at least one cyanating agent selected from the group consisting of trialkylsilyl cyanides and hydrogen cyanide. A method for producing a cyanide compound, wherein the oxidizing agent is solid when added.

2. The method for producing a cyanide compound according to claim 1, wherein the cyanide compound is an S-cyanide.

3. The reaction substrate is a compound represented by the following chemical formula 1, A method for producing a cyanide compound according to claim 1, wherein the cyanide compound is a compound represented by the following chemical formula 2: 【Chemistry 1】 In the aforementioned chemical formulas 1 and 2, R １ ~R ５ Each of these is independently a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a haloalkyl group, an alkoxyalkyl group, an alkoxyalkyloxy group, an alkyloxycarbonyloxy group, a nitro group, or an aryl group. M is an alkali metal.

4. In the above chemical formulas 1 and 2, R １ , R ２ , R ４ , and R ５ The method for producing the cyanide compound according to claim 3, wherein is a hydrogen atom.

5. The method for producing a cyanide compound according to claim 4, wherein the reaction substrate is p-toluenesulfinate.

6. A method for producing a cyanide compound according to claim 1, further comprising coexisting a phase transfer catalyst in the reaction system.

7. The method for producing a cyanide compound according to claim 1, wherein the water content in the organic solvent is 0% by mass or more and 0.1% by mass or less.

8. A method for producing a cyanide compound according to claim 1, wherein the reaction temperature is greater than 0°C and less than or equal to 15°C.

9. The method for producing a cyanide compound according to claim 6, wherein the phase transfer catalyst is at least one selected from the group consisting of crown ethers and quaternary ammonium salts.

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