KR20190102853A - Process for preparing dicyanonorbornane compound - Google Patents

Abstract

The present invention relates to a method for manufacturing a dicyano norbornane isomer compound by hydro-cyanolating a carbon-carbon double bond of 5-norbornenecarbonitrile with a metal cyan compound. According to the present invention, a dicyano norbornane compound can be efficiently manufactured by using a divalent nickel catalyst in an aqueous solution.

Description

Process for preparing dicyanonorbornane compound

The present invention relates to a process for the preparation of dicyanonobonan compounds. More specifically, the present invention relates to a method for producing a dicyanobornane isomeric compound by hydro-cyanolating a carbon-carbon double bond of 5-norbornenecarbonitrile using a metal cyan compound.

The present invention is in accordance with the results of research conducted by the Ministry of Trade, Industry and Energy and the Korea Institute of Industrial Technology Promotion (R & D, A018200288).

Novonandinitrile compounds are compounds useful for preparing pharmaceuticals, pesticides, functional pigment materials, functional polymers, and the like as intermediate materials for synthesizing carboxylic acid, ester, amine and amide raw materials and intermediate compounds. As a conventional method for producing a dicyano nobonane compound, there is a method using a nickel catalyst (see Patent Documents 1 and 2). The method using the poisonous hydrogen cyanide in the prior patents 1 and 2 separately separates the divalent nickel compound from zinc or metals such as cadmium, iron, cobalt, beryllium, aluminum and divalent zinc compounds, The process of synthesis using organophosphorus ligands such as phosphine or phosphite is configured separately. Then, hydrogen cyanide is slowly injected to obtain dicyanobonoranane.

This preparation method requires the use of hydrogen cyanide or the like as the nitrile source. Hydrogen cyanide is extremely explosive and highly toxic. Therefore, the problem of restricting the distribution of hydrogen cyanide or the leakage of the gas or the reaction liquid has a high adverse effect on human life and the environment, so the cost of constructing or maintaining safety facilities is higher than the cost of manufacturing them. In addition, there is a disadvantage of using a nonionic zero-valent nickel complex catalyst, which is difficult to store in the air, it is necessary to thoroughly manage the moisture and oxygen during storage or reaction of the catalyst for reproducible production.

Since the prior art uses hydrogen cyanide, it is necessary to take measures to prevent leakage, to prevent corrosion of the reactor, and to prevent leakage of the reaction solution. There has also been a demand for a production method capable of producing desired dicyano nobonane compounds under stabilized conditions without the use of zero-valent nickel metal complexes that are difficult to store and handle in the air.

Patent Document 1: EP 0438638 Patent document 2: WO2008 / 001490

The object of the present invention is to provide a divalent nickel salt compound that can be handled under reaction conditions in an aqueous solution, using a stable metal cyanide compound, without using hydrogen cyanide as a dicyano bonanic source in view of the problems of the prior art. An object is to produce an efficient dicyanonobonan compound.

As an aspect for achieving the object of the present application, the present application is a catalyst combination containing a 5-norbornene carbon-2-nitrile and a metal cyan compound, a metal powder, a divalent nickel compound, an organophosphorus compound in an aqueous solvent solution and Together under an acid compound to provide a process for producing dicyanobornane.

The present application can use divalent nickel compounds, which are much cheaper and easier to handle than the nonionic nickel complex catalysts used in the existing methods, and can also use mixed solvent aqueous solutions that can reduce the risk of fire. Therefore, the present application can propose a method for producing dicyano bonanone safely and easily.

As a result of a careful study on the manufacturing method of the dicyano bonan compound which has the above characteristics, this invention was made based on the discovery which can obtain a dicyano bonan compound without using hydrogen cyanide. In particular, in the present invention, 5-norbornene carbo- under catalytic conditions consisting of a divalent nickel compound, a phosphorus ligand to coordinate with nickel, and a metal powder to act as a reducing agent in a ketone solvent mixed with an aqueous solution and an alcohol-based mixed solvent. The present invention was completed by reacting a 2-nitrile compound with a metal cyan compound to add a nitrile group. Representing the present invention in one specific reaction scheme is as follows:

According to one embodiment of the present application, the metal cyanide compound may be at least one selected from the group consisting of sodium cyanide, potassium cyanide, silver cyanide, copper cyanide, mercury cyanide, cobalt cyanide, and potassium ferricyanide. In the present application, the metal cyanide compound will serve as a nitrile source and can be in either anhydride or hydrate form.

According to another embodiment of the present application, at least one acid compound selected from the group consisting of acetic acid, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, methane sulfonic acid, and paratoluenesulfonic acid potassium ferricyanide will be used. Such acid compounds may be used as they are supplied from the manufacturer, but are preferably diluted with water or a solvent.

According to another embodiment of the present application, the divalent nickel compound is selected from nickel halogen salts, or nickel carboxylate compounds. Specific nickel compounds include nickel fluoride, nickel chloride, nickel bromide, nickel iodide, nickel hydroxide, nickel sulfate, nickel nitrate, nickel phosphate, nickel perchlorate, nickel sulfonate, nickel formate, nickel acetate, nickel trifluoroacetic acid, nickel succinate, Nickel Oxalate, Nickel Lactate, Nickel Tartrate, Nickel Citrate, Nickel Benzoate, Nickel Octane, Nickel Oleate, Nickel Stearate, Nickel Bis (2,4-pentanedionate), Bis (1,1,1,5,5,5,5 -Hexafluoro-2,4-pentanedionate) nickel and bis (2,2,6,6-tetramethyl-3,5-heptanedionato). Such a nickel compound may be an anhydride or a hydrate. Such nickel compound is preferably dissolved in an aqueous solution mixed solvent. Among these nickel compounds, nickel acetate is preferred.

According to another embodiment of the present application, the organophosphorus compound functions as a ligand of nickel. The organophosphorus compound may be alkylphosphine or arylphosphine represented by the following formula (1):

(R1, R2, R3 each represent an alkyl or aryl group having 1 to 10 carbon atoms)

In addition, the organophosphorus compound may be a bidentate alkyl or aryl phosphine represented by the following formula (2):

(R1, R2, R3, and R4 each represent an alkyl or aryl group having 6 carbon atoms, and n is 1-6.)

In addition, the organophosphorus compound may be alkyl phosphite or aryl phosphite represented by the following formula (3):

(R1, R2, R3 are each an alkyl or aryl group having 1-7 carbon atoms).

According to another embodiment of the present application, the metal powder may be at least one selected from the group consisting of zinc, magnesium, and aluminum. The metal powder acts as a reducing agent. As the metal powder, a powder metal having an average particle diameter of 1 μm to 200 μm, which is an arithmetic mean of the particle diameters, may be used. The average particle diameter of the metal powder is particularly preferably 6 µm to 10 µm.

According to another embodiment of the present application, the aqueous solution mixed solvent is a mixture of a ketone-based solvent and an alcohol-based solvent, and the solvent is a group consisting of a ketone-based compound of acetone, methyl ethyl ketone, cyclohexanone, and benzophenone At least one selected from will be used. In addition, the mixed solution of the aqueous solution when reacting with an organic compound having a carbon-carbon double bond and a metal cyan compound can be selected as a solvent of a ketone compound alcohol compound, an amide compound and an ether compound series. As a ketone compound, acetone, methyl ethyl ketone, cyclohexanone, benzophenone, etc. may be used as a reaction solvent. Examples of the alcohol compound include methanol, ethanol, 1-propanol, 2-propanol, and the like. Examples of the amide compound include N-methylpyrrolidinone, dimethylformamide, dimethylacetamide, and the like. Tetrahydrofuran etc. are mentioned as an ether compound. Moreover, nitrile solvents, such as acetonitrile, or aromatic solvents, such as toluene and xylene, etc. are mentioned.

According to another embodiment of the present application, the amount of the metal cyanide compound used is preferably 0.8 to 1.5 equivalents, more preferably 0.9 to 1.2 equivalents, and more preferably 1.0 equivalent to 5-norbornenecarbonitrile. . The acid compound is preferably 0.9 equivalent to 1.5 equivalents, more preferably 0.95 equivalent to 1.1 equivalents, and most preferably 1.0 equivalent to the amount of the metal cyanide compound used.

As the amount of the catalyst used, the amount of the nickel compound is preferably 3 mol% to 20 mol%, more preferably 4 mol% to 10 mol%, and more preferably 5 mol% with respect to 5-norbornene carbononitrile. The amount of the organophosphorus compound used is preferably 1 to 4 equivalents, more preferably 1.5 equivalents and 2.5 equivalents, and more preferably 2 equivalents to the nickel compound. The amount of the metal powder used is preferably 2 equivalents to 20 equivalents, more preferably 5 equivalents to 15 equivalents, and even more preferably 10 equivalents to the nickel compound.

In the reaction of 5-norbornene carbon-2-nitrile and metal cyanide, the temperature at which the acidic compound is added is preferably 0 ° C to 20 ° C, more preferably 5 ° C to 10 ° C. 50 degreeC-100 degreeC is preferable and, as for the reaction temperature after adding an acid, 55 degreeC-70 degreeC is more preferable. In some cases, where the reaction temperature is lower than 50 ° C., the yield of the dicyano bonanone compound may decrease. In addition, when the reaction temperature is higher than 100 ℃, the reaction proceeds excessively in some cases, the raw material may decompose or side reactions such as polymerization reaction may proceed.

Until now, as a method for producing a dicyano nobonane compound, a 5-norbornene carbon-2-nitrile compound and a metal cyan compound were added to a catalyst system including a nickel compound, an organophosphorus compound, and a metal powder, and then, mainly based on an acid treatment step. Explained. However, the present production method may be composed of (1) the step of adding the acid compound, followed by the step of (2) heating the intermediate product obtained in the step of adding the acid compound. Will not be.

The contents not described herein may be sufficiently recognized and inferred by those skilled in the art or similar fields of the present application, and thus descriptions of the remaining parts will be omitted.

According to the present invention, dicyano bonanone compounds are obtained as metal cyanide compounds without using hydrogen cyanide and organic cyanide compounds as the nitrile source. Moreover, according to this invention, a dicyano no bonan compound can be manufactured efficiently by using a bivalent nickel catalyst in aqueous solution.

In addition, there would be no need to use poisonous hydrogen cyanide or organic compounds such as acetonecyanhydrin, trimethylsilylcyanine as the nitrile source under anhydride conditions.

Although the present application will be described in detail with reference to the following Synthesis Examples and Examples, the following Synthesis Examples and Examples are provided by way of example, the present application is not limited thereto.

(Preparation of dicyano bonan compound using various nickel compounds)

Synthesis Example 1. Synthesis of 5-norbornenecarboni-2-nitrile

Liquid paraffin oil (four in 1 L reactor with mechanical stirrer, thermometer, column with structured packing (ID 5 cm, length 25 cm) and electric metering pump (ProMinent, gamma / L) 300 ml of E-IL ESOL industrial Co., Ltd, ESOL-P27) was added and the reaction internal temperature was heated to 200-240 ° C. using a mantle. At this time, dicyclopentadiene (DCPD) prepared in the metering pump was introduced at a rate of about 3 ml / min. Cyclopentadiene (CPD), discharged at about 40-42 ° C. through the column top, was collected via a cooling column. In this experiment, the CPD generated through the decomposition reaction was collected without distillation for 6 hours without distillation, and then, through a Teflon hose, 682 g (12.86 mol, 1 equivalent) of acrylonitrile, which was previously adjusted to 25 ° C., was added thereto. Immediately added to the reaction proceeded. CPD collected for about 6 hours was the amount of distilled through independent experiments, 850g yield was 85%, purity was 99%. After the completion of the CPD dosing reaction was terminated by an additional 2 hours.

Gas chromatographic analysis showed that 1,517 g of 5-norbornenecarbono-2-nitrile having an isomer (endo / exo) ratio of 1.27 was obtained at a theoretical yield of 100% with a purity of 99%.

In order to compare the deactivation of the catalyst of the nickel catalyst when the acid compound was added, the acid treatment at low temperature and the acid treatment at high temperature were carried out separately into Synthesis Example 2 and Synthesis Example 3. In particular, the high activity of the catalyst was expected to decrease the activity of the catalyst, but the activity of the catalyst was maintained.

Synthesis Example 2 Synthesis of Dicyano nobonane

72 g (0.604 mol, 1 equivalent) of 5-norbornenecarbononitrile, 39.4 g (0.604 mol, 1 equivalent) of potassium cyanide, nickel chloride (II) 6 in a 1 L reactor equipped with a mechanical stirrer, thermometer and dropping funnel 7.2 g (0.03 mol, 0.05 equivalent) of hydrate, 15.84 g (0.06 mol, 0.1 equivalent) of triphenylphosphine, 20.66 g (0.3 mol, 0.5 equivalent) of zinc powder were added, and acetone (100 ml), methanol (200 ml) and distilled water were added. (100 ml) was added. 36.3 g (0.604 mol, 1 equivalent) of acetic acid was added over 2 hours while maintaining the reaction internal temperature at 5 to 10 ° C.

After the addition, the reaction internal temperature was raised to 70 ° C. and stirred for 2 hours. Gas chromatography analysis confirmed that the reaction was completed, and the reaction internal temperature was cooled to 25 ℃. 300 ml of toluene was added to the reaction mixture to extract the dicyanobornane produced. The organic layer was washed three times with 300 ml of 2N hydrochloric acid, and the organic layer was passed through a silica pad and concentrated to obtain 77 g of dicyanobornane having a purity of 99%. Yield was 98%.

Synthesis Example 3 Synthesis of Dicyano nobonane

72 g (0.604 mol, 1 equivalent) of 5-norbornenecarbononitrile, 39.4 g (0.604 mol, 1 equivalent) of potassium cyanide, nickel chloride (II) in a 1 L reactor equipped with a mechanical stirrer, thermometer and dropping funnel. 7.2 g (0.03 mol, 0.05 equivalent) of hydrate, 15.84 g (0.06 mol, 0.1 equivalent) of triphenylphosphine, 20.66 g (0.3 mol, 0.5 equivalent) of zinc powder were added, and acetone (100 ml), methanol (200 ml) and distilled water were added. (100 ml) was added. 36.3 g (0.604 mol, 1 equivalent) of acetic acid was added over 2 hours while maintaining the reaction internal temperature at 70 ° C.

After the addition, it was confirmed that the reaction was completed through gas chromatography analysis, and the reaction internal temperature was cooled to 25 ° C. After distilling 300 ml of toluene into the reaction mixture, the resulting dicyano bonan was extracted, and the organic layer was washed three times with 300 ml of a 2N hydrochloric acid aqueous solution. The organic layer was passed through a silica pad and concentrated to obtain 74 g of dicyano bonan having a purity of 99%. Yield 94%.

According to Synthesis Examples 2 and 3, the yield obtained according to each example by varying the content and temperature of the reactants is shown in Table 1 below.

Example NBCN NiCl2 6H2O Zn PPh3 KCN Temperature Acetic acid Synthesis Example yield 1-1 One 0.01 0.05 0.01 One 70 One 2 35 1-2 0.01 0.5 0.02 2 70 One 2 63 1-3 0.05 0.05 0.1 One 70 One 2 57 1-4 0.05 0.5 0.05 One 70 One 2 68 1-5 0.05 0.5 0.1 One 60 One 2 95 1-6 0.05 0.1 0.1 One 70 One 2 72 1-7 0.05 0.5 0.1 One 70 One 2 98 1-8 0.05 0.5 0.1 One 70 One 3 94

As can be seen from the yield value of Table 1, the synthesis result of the dicyano nobonane nickel chloride 0.05 equivalents, metal zinc powder 0.5 equivalents, triphenylphosphine 0.1 equivalents, potassium chloride 1 equivalent of the reaction result at 70 ℃ 1-7 and 1-8 were the best. In Synthesis Example 2, 1 equivalent of acetic acid was added at 5 to 10 ° C., and then the temperature was increased to 70 ° C., or 1 equivalent of acetic acid was added at reaction temperature of 70 ° C. to obtain a high yield of dicyanobornane without deactivation of the catalyst. there was.

Instead of the solvents used in Synthesis Examples 2 and 3, a dicyano bonan compound was prepared by reaction with a combination of a solvent in a ketone series, water, alcohol series, and amide series solvent, and the results are shown in Table 2 below. It was.

Example Acetone Cyclohexane water Methanol ethanol DMF yield 2-1 O X O O X X 98 2-2 X O O O X X 82 2-3 O X O X O X 93 2-4 O X O X X O 88 2-5 O X O X X X 85 Comparative Example 2-1 O X X X X X 0 Comparative Example 2-2 X X O O X O 0 Comparative Example 2-3 X X O X X X 0 Comparative Example 2-4 X X X O X X 0 Comparative Example 2-5 X X X X O X 0 Comparative Example 2-6 X X X X X O 0

In Table 2, it was found that only one solvent could not be used to obtain a dicyano nobonane compound. In particular, the dicyano bonan compound could not be obtained without the ketone solvent, and the dicyano bonan compound could be obtained by the combination of the ketone solvent and water, but the alcohol or the amide solvent may increase the yield. Could.

This time, by changing the nickel compound and ligand used in Synthesis Examples 2 and 3 and proceeding the same synthesis process is shown in Table 3 below.

Example Ni compound Ligand metal Synthesis Example Reaction 3-1 Nickel Chloride Heptahydrate PPh3 zinc 3 O 3-2 Nickel Acetate Tetrahydrate PPh3 zinc 3 O 3-3 Nickel Chloride Heptahydrate P (OPh) 3 zinc 3 0 3-4 Nickel Acetate Tetrahydrate P (OPh) 3 zinc 3 0 Comparative Example 3-1 Nickel Acetate Tetrahydrate PPh3 - 3 X Comparative Example 3-2 Nickel Acetate Tetrahydrate - - 3 X Comparative Example 3-3 Tetrakis (triphenylphosphite) nickel - - 2 X Comparative Example 3-4 Tetrakis (triphenylphosphite) nickel - - 3 X

Nickel compounds used nickel chloride hexahydrate and nickel acetate tetrahydrate, and ligands were all reacted in a catalyst combination using triphenylphosphine and triphenylphosphite, but in Comparative Examples 3-1 to 3-2, The reaction does not proceed even without any of the metals.

Comparative Examples 3-3 to 3-4 are both in Synthesis Examples 2 and 3 when the catalyst was applied to the tetrakis (triphenylphosphite) nickel complex used in the method for preparing the dicyano bonan compound in the prior patents 1 and 2 Since the reaction did not proceed, it was confirmed that the present invention is different from the prior art.

Claims (10)

A method for producing dicyanobornane by reacting a 5-norbornenecarbonitrile and a metal cyanide compound with a catalyst combination containing a metal powder, a divalent nickel compound and an organophosphorus compound in a solvent aqueous solution, under an acid compound. . The method of claim 1, wherein the metal cyanide compound is at least one selected from the group consisting of sodium cyanide, potassium cyanide, silver cyanide, copper cyanide, mercury cyanide, cobalt cyanide, and potassium ferricyanide. The method according to claim 1 or 2, wherein the acid compound is at least one selected from the group consisting of acetic acid, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, methane sulfonic acid, and paratoluenesulfonic acid potassium ferricyanide. The said organophosphorus compound is an alkyl or aryl phosphine represented by following formula (1), the bidentate alkyl or aryl phosphine represented by following formula (2), or a following formula (3) Wherein the alkyl phosphite or aryl phosphite is represented by:

(R1, R2, R3 each represent an alkyl or aryl group having 1 to 10 carbon atoms);

(R1, R2, R3, R4 each represent an alkyl or aryl group having 6 carbon atoms, n is 1-6.); And

(R1, R2, R3 are each an alkyl or aryl group having 1-7 carbon atoms). The method according to claim 1 or 2, wherein the divalent nickel compound is selected from nickel halogen salts or nickel carboxylate compounds. The method according to claim 1 or 2, wherein the metal powder is at least one selected from the group consisting of zinc, magnesium, and aluminum. The method of claim 1, wherein the aqueous solvent is a mixture of a ketone-based solvent and an alcohol-based solvent, wherein the solvent is at least selected from the group consisting of ketone-based compounds of acetone, methyl ethyl ketone, cyclohexanone, and benzophenone. One kind, method. The method according to claim 7, wherein the reaction temperature is 55 ~ 70 ℃ in the aqueous solution in which the ketone solvent and the alcohol solvent is mixed. The method according to claim 1 or 2, wherein the amount of the metal cyanide compound is 1.0 equivalent or more based on 5-norbornene carbonitrile and the acid compound is 0.9 equivalent to 1.5 equivalents based on the amount of the metal cyanide compound. The method of claim 9, wherein the amount of the nickel compound is 3 mol% to 20 mol% with respect to 5-norbornenecarbonitrile, the amount of the organophosphorus compound is 2 equivalents or more with respect to the nickel compound, The usage-amount is 5 equivalent or more with respect to the said nickel compound.