KR101897899B1 - Heterogeneous copper-catalyzed aerobic oxidative conversion of alcohols to corresponding nitriles - Google Patents

Abstract

TECHNICAL FIELD The present invention relates to a method for aerobic oxidative conversion of an alcohol to nitrile, and more particularly, to a method for aerobic oxidative conversion of an alcohol to nitrile, and more particularly, to a process for producing a heterogeneous copper catalyst (Cu @ C) pyrolyzed HKUST- (For example, benzene alcohol) is converted into an aromatic aldehyde (for example, benzaldehyde) and then an ammonia source (for example, ammonia water) is added in a one-pot manner to obtain an aromatic aldehyde Nitriles can be obtained in high yields for various substrates by oxidizing them to nitriles (e.g., benzonitrile), and the heterogeneous copper catalyst maintains its structure even in the presence of an ammonia source, Oxidative conversion of alcohol to nitrile using a heterogeneous copper catalyst, which can be reused at least three times, And optimization of the reaction conditions applied thereto.

Description

TECHNICAL FIELD [0001] The present invention relates to a method for converting an alcohol into nitrile using an inhomogeneous copper catalyst, and more particularly, to a method for converting an alcohol into nitrile by an aerobic oxidative conversion of alcohol to a nitrous oxide catalyst.

TECHNICAL FIELD The present invention relates to a method for aerobic oxidative conversion of an alcohol to nitrile, and more particularly, to a method for aerobic oxidative conversion of an alcohol to nitrile, and more particularly, to a process for producing a heterogeneous copper catalyst (Cu @ C) pyrolyzed HKUST- (For example, benzene alcohol) is converted into an aromatic aldehyde (for example, benzaldehyde) and then an ammonia source (for example, ammonia water) is added in a one-pot manner to obtain an aromatic aldehyde Nitriles can be obtained in high yields for various substrates by oxidizing them to nitriles (e.g., benzonitrile), and the heterogeneous copper catalyst maintains its structure even in the presence of an ammonia source, Oxidative conversion of alcohol to nitrile using a heterogeneous copper catalyst, which can be reused at least three times, And optimization of the reaction conditions applied thereto.

Synthesis of benzonitrile is very useful in the field of organic chemistry because nitrile groups are used as multipurpose intermediates for synthesizing various functional groups and hetero rings. The nitrile group itself is also a key moiety for medicinal and pesticide compounds.

In general, the synthesis of benzonitrile relies on the cross-coupling of Ar-X (X = Cl, Br, I or N ₂ ) and toxic metal cyanide using a transition metal as a catalyst. Recently, protocols have been developed that use less toxic cyanide and non-metal cyanide sources such as K ₃ [Fe (CN) ₆ ] to avoid the use of such toxic metal cyanide.

However, these protocols have the disadvantage of not producing large amounts of halide byproducts or inorganic / organic wastes and thus not meeting green chemistry.

From the point of view of green chemistry, aerobic oxidative conversion of benzaldehyde using ammonia sources is considered to be an eco-friendly approach for the synthesis of benzonitrile, which can utilize inexpensive ammonia Only water is produced as a by-product.

However, to date, examples of aerobic oxidation of aldehydes or alcohols to nitrile using ammonia sources have remained only in some cases. On the other hand, anaerobic methods using stoichiometric oxidants such as (Bu ₄ N) ₂ S ₂ O ₈ , I ₂ , tert-butyl hydroperoxide (TBHP) and hypervalent iodine have been reported State.

In 2009, Mizuno and colleagues found that when using ammonia solutions dissolved in THF, alumina-supported heterogeneous ruthenium catalysts act as effective catalysts for the aerobic oxidation of aldehydes or alcohols to nitriles. After this Mizuno study, MnO ₂ Other types of heterogeneous catalyst systems have also been established.

In the case of homogeneous catalysts, the Cu / TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) system is one of the most efficient catalysts for the oxidation of aerobic alcohol, Oxidative conversion can be successfully promoted. In 2013, Tao, Huang, Muldoon and Stahl each have found that Cu / TEMPO systems can catalyze the synthesis of aerobic oxidizing nitriles under relatively mild conditions as ammonia water is used.

However, there is no example in which a heterogeneous Cu catalyst is applied in this conversion, and in particular, a nitrile is synthesized from a starting material alcohol using a heterogeneous Cu catalyst by a continuous process in a single reaction vessel.

HKUST-1 (Cu ₃ (BTC) ₂ , BTC = 1,3,5-benzenetricarboxylate) is a commercially available MOF and is used as a heterogeneous Cu catalyst in various organic chemical transformations.

The present inventors have investigated the catalytic activity of HKUST-1 in relation to the aerobic oxidative conversion of benzaldehyde to benzonitrile using ammonia. As a result of the preliminary test, it was confirmed that HKUST-1 can catalyze the synthesis of benzonitrile.

However, in this case, the MOF structure of HKUST-1 disappeared and could no longer exist as a heterogeneous catalyst after the reaction, which is believed to be due to the strong interaction between copper and ammonia disrupting the MOF structure of HKUST-1.

a) M. Sundermeier, A. Zapf, S. Mutyala, W. Baumann, J. Sans, S. Weiss, M. Beller, Chem. Eur. J. 2003, 9, 1828-1836; b) P. Anbarasan, T. Schareina, M. Beller, Chem. Soc. Rev. 2011, 40, 5049-5067.

As a result of intensive studies, the inventors of the present invention have found that a heterogeneous catalyst (Cu @ C) in which copper is supported on a carbon support can maintain its structural stability even in the presence of ammonia, and is also capable of oxidative conversion of aldehyde to nitrile , And can be a highly efficient heterogeneous catalyst for the aerobic oxidative conversion of alcohol to nitrile, leading to the present invention.

Accordingly, a technical object of the present invention is to provide a novel method for one-pot synthesis of nitrile through aerobic oxidation conversion of alcohols and aldehydes using a heterogeneous copper catalyst, and to provide optimal reaction conditions necessary for the one-pot synthesis .

In order to achieve the above object,

A method for producing nitrile using an aromatic primary alcohol as a starting material,

A first step of converting an aromatic primary alcohol into an aromatic aldehyde by aerobic oxidation; And

And a second step of converting an aromatic aldehyde to a nitrile by adding an ammonia source as a reactant to the same reaction vessel in which an aromatic aldehyde is formed,

The first and second steps are performed in a solvent under the condition of supplying oxygen (O ₂ ) by using heterogeneous copper catalyst and TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) And,

The heterogeneous copper catalyst is a pyrolysis of HKUST-1 (copper benzene-1,3,5-tricarboxylate; Cu ₃ (BTC) ₂ ) ) ≪ / RTI >

Wherein the first step and the second step are performed by a one-pot sequential reaction method.

An aerobic oxidative conversion of an aromatic primary alcohol to a nitrile using a heterogeneous copper catalyst is provided (see FIG. 1).

That is, the present invention relates to a process for converting an aromatic primary alcohol into an aldehyde by aerobic oxidation using a Cu @ C / TEMPO catalyst system, adding an ammonia source to the one-pot, Lt; / RTI > The one-pot synthesis method according to the present invention is a two-step oxidation reaction involving "aromatic primary alcohol → aldehyde" and "imine generated from aldehyde → nitrite" The nitrile can be obtained in high yield.

The first step is a step of converting an aromatic primary alcohol into a corresponding aromatic aldehyde by applying a Cu @ C / TEMPO catalyst system, an oxygen condition, and a reaction solvent to an aromatic primary alcohol as a starting material (substrate). The method according to the present invention is performed by a one-pot sequential reaction method, and the Cu @ C / TEMPO catalyst system, the oxygen supply condition, and the reaction solvent applied in the first step are applied as they are in the second step do.

In the second step, an ammonia source is added as a one-pot to the aromatic aldehyde produced through the first step, and the reaction and oxidative conversion are performed to finally obtain nitrile as a target material.

In the present invention, the nitrile is obtained by aerobic oxidation of an imine compound formed by condensation of the aromatic aldehyde produced in the first stage and the ammonia source added in the second stage.

That is, the present invention is directed to oxidative conversion of alcohol to nitrile using a heterogeneous copper catalyst system under aerobic conditions, wherein various aromatic primary alcohols (such as benzyl alcohol) are converted to aromatic aldehydes (such as benzaldehyde) The aromatic aldehyde is condensed with an ammonia source (for example, ammonia water), and each nitrile (for example, benzonitrile) as a target material can be selectively synthesized through subsequent aerobic oxidation.

In the present invention, the nitrile, which is the target substance, is determined according to the aromatic primary alcohol used as the starting material (substrate) in the first step and may be selected from the group of compounds represented by the following structural formulas, It is not.

The ammonia source is an additional reactant added as a one-pot for the second-step reaction. The ammonia source is an NH ₄ X -type ammonium compound capable of forming an imine compound by condensation with the aromatic aldehyde produced through the first step Compound, and preferably ammonia water (Aqueous ammonia) is used. The ammonia source (for example, ammonia water) is suitably used at about 1.2 to 4.8 eq.

In the first step of the present invention, unlike the second step, an ammonia source (for example, ammonia water) is not added.

The present inventors investigated the yield of aromatic primary alcohol → aldehyde according to the presence or absence of addition of an ammonia source (for example, ammonia water) under predetermined optimized conditions. As a result, the yield was lower when ammonia source was added. These results indicate that the ammonia source required for the nitrile synthesis in the second step is rather an obstacle to the aerobic alcohol oxidation in the first step.

The heterogeneous copper catalyst is a metal-organic framework (MOF) in which copper is supported on a carbon support (Cu @ C) and copper (Cu) is bonded to it. HKUST-1 (Copper Benzene- 3,5-carboxylate; Cu ₃ (BTC) ₂₎ was prepared, and the HKUST-1 the thermal cracking (pyrolysis for 6 to 10 hours of high-temperature 800 ~ 1000 ℃) the carbon (C) copper on a support (Cu) -supported mesoporous structure.

The MOF-based organic reaction catalyst can be produced through the pyrolysis during or after the reaction without straying the structure. Specifically, it is possible to produce CuO (≠ CuO) in HKUST-1 C remains. The pyrolysis product is present in a form that copper (C) is supported on the carbon (C) support, so that the divalent Cu acts as a catalyst in the nitrile synthesis reaction. The surface area of MOF decreases after pyrolysis, and the pore structure changes from microporous to mesoporous.

The pyrolysis can be carried out at a temperature of 800 DEG C for 6 hours. Specifically, the pyrolysis is carried out by moving an alumina boat containing HKUST-1 into a tube furnace, making the inside of the tube furnace into a vacuum state, injecting argon (Ar) gas into the tube furnace, min to a temperature of 800 ° C, followed by maintaining the temperature at 800 ° C for 6 hours, followed by natural cooling to room temperature.

The heterogeneous copper catalyst may be used in a catalytic amount suitable for the reaction, for example, in an amount of 2.5 to 5 mol% based on the aromatic primary alcohol.

In addition, the heterogeneous copper catalyst has excellent catalytic activity and structural stability, and is excellent in reproducibility so that the catalyst once used can be washed and reused at least three times.

The catalyst system of the present invention uses TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) together with a heterogeneous copper catalyst as an auxiliary agent.

The TEMPO is preferably used in an amount of 5 to 10 mol% based on the aromatic primary alcohol in view of maximizing the yield.

In addition, when 1-methylimidazole (NMI) is added as an organic base together with the heterogeneous copper catalyst and TEMPO, the reactivity associated with the conversion of an aromatic primary alcohol to an aldehyde can be improved.

The first step and the second step reaction according to the present invention can proceed at atmospheric conditions as long as oxygen is supplied. However, it is more preferable to perform the reaction under the condition that only oxygen is supplied, in terms of increasing the yield of nitrile .

In one embodiment, the oxygen (O ₂ ) atmosphere of the present invention may be formed using an O ₂ balloon.

As the reaction solvent in the present invention, it is preferable to use a polar solvent such as DMF (N, N-dimethylformamide) and DMSO (dimethylsulfoxide).

Specifically, the present inventors have confirmed through experimentation that DMF or DMSO is used as a reaction solvent under the same conditions as in the case of using CH ₃ CN.

In the present invention, the reaction temperature and time in the first step and the second step may be appropriately controlled depending on the type of substrate (or intermediate product) and the like. However, if the reaction is carried out at too high a temperature, the aldehyde may be directly oxidized in the second step, and a large amount of by-products such as benzoic acid may be produced.

In one embodiment, the reaction of the present invention may be carried out at a temperature condition of 50 to 70 DEG C (e.g., 70 DEG C), for the first stage for 6 hours, and for the second stage for 12 hours.

According to the one-pot method of the present invention, it is possible to obtain the target nitrile with high yield according to the substrate and reaction conditions.

이 90% 이상에 이르는 매우 높은 총 수율(Yield)로 얻어졌다.In one embodiment, 2.4 equivalents (eq) of ammonia water is used as the ammonia source, the heterogeneous copper catalyst is used in an amount of 2.5 mol% relative to the aromatic primary alcohol, and TEMPO is used in an amount of 5 mol% relative to the aromatic primary alcohol Methylimidazole (NMI) was used in an amount of 2.5 mol% based on the aromatic primary alcohol, oxygen (O ₂ ) supply conditions were formed using an O ₂ balloon, and DMF When the first step reaction was conducted at 70 캜 for 6 hours and the second step reaction was conducted at 70 캜 for 12 hours,

Was obtained with a very high total yield (Yield) of over 90%.

According to the present invention, a nitrile compound having high utilization in the field of organic synthesis from alcohols as a starting material can be obtained through a one-pot process using a heterogeneous copper catalyst (Cu @ C) and TEMPO at a high yield . ≪ / RTI >

In addition, the nitrile selectively corresponding to various alcohol substrates can be obtained, and a universal high yield can be realized, so that the application range is wide.

In addition, the uneven copper catalyst (Cu @ C) of the present invention can maintain the MOF structure even in the presence of an ammonia source and is excellent in stability and excellent in reproducibility so that it can be washed and reused at least three times after the reaction.

In addition, the present invention can maximize yield and maximize reaction efficiency by establishing optimal reaction conditions associated with the aerobic oxidative conversion of aromatic primary alcohol to nitrile.

Further, since nitrile can be synthesized in a one-pot manner without isolating or purifying an intermediate product or the like, the process efficiency and economical efficiency are excellent.

In addition, since toxic metal cyanide is not used and by-products such as halide are not produced, it can effectively respond to the green chemistry policy.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view showing an example of a reaction process related to the oxidation of alcohol to nitrile using an irregular copper catalyst according to the present invention. FIG.
2 is a view showing a result of a recycling test of a heterogeneous copper catalyst used in the present invention. (* Reaction conditions: 1h (5.0 mmol), aqueous NH 3 (2.4 equiv), Cu @ C (2.5 mol%), TEMPO (5 mol%), DMF (5 mL))

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. It should be understood, however, that these examples are for illustrative purposes only and are not intended to limit the scope of the invention in any way.

Example

(1) Experimental conditions

All compounds and solvents were used as received commercially unless otherwise noted.

Analytical thin layer chromatography (TLC) was performed on precoated silica gel 60 F254 plates.

TLC visualization was performed using UV light (254 nm) and heating after phosphomolybdic acid stain treatment.

Flash chromatography was performed using silica gel 60 (Merck, particle size 40-63 um, 230-400 mesh).

^{The 1} H and ¹³ C NMR spectra were recorded on an Agilent 400 MHz NMR (Agilent Technologies, 400 MHz for ¹ H, 101 MHz for ¹³ C) spectrometer.

Chemical shift values were obtained in ppm for internal TMS (0.00 ppm for ¹ H) or CDCl ₃ (77.06 ppm for ¹³ C).

The following abbreviations are appropriately used to describe the peak splitting pattern: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet, dd = of doublet, dt = double of triplet, td = triple of doublet.

The coupling constant ( J ) was recorded in hertz units (Hz).

High resolution mass spectra were obtained from Korea Basic Science Research Institute (Daegu) by EI method.

Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) was commissioned by Korea Basic Science Research Institute (Seoul).

(2) Production of heterogeneous copper catalyst (Cu @ C)

0.9314 g of Cu (NO ₃ ) ₂ .3H ₂ O was dissolved in distilled water and 0.4402 g of trimesic acid was completely dissolved in ethanol.

Then, each solution was put in a Teflon reactor, sealed, and reacted in an oven at 140 ° C for 24 hours to synthesize MOF (HKUST-1).

About 500 mg of the synthesized HKUST-1 was put into an alumina boat, and the alumina boat containing the sample was transferred to the inside of the tube furnace, and the inside of the tube furnace was evacuated.

Then, Ar gas was injected at a rate of 1 NL / min and flowed. Then, the temperature was raised at a rate of 5 캜 / min to reach a target temperature (800 캜), and then maintained at that temperature for 6 hours. The temperature was again lowered to room temperature through cooling. (* Weight after pyrolysis = about 187 mg)

(3) aromatic primary alcohol Nightly  Cu @ C-catalytic aerobic Oxidative  Optimization process for conversions

First, an optimization procedure for the Cu @ C-catalytic aerobic oxidation conversion of aldehydes to nitriles corresponding to the second step was performed (Table 1).

A 15 mm flame-dried test tube equipped with a magnetic stir bar was filled with Cu @ C (40 wt% Cu), TEMPO and NH ₄ X (2.4 equiv, 2.4 mmol) And then refilled with oxygen.

After 0.5 mL of the solvent was added, 4-methylbenzaldehyde (1 mmol) and a solvent (0.5 mL) were added in this order.

The resulting reaction mixture was stirred at a temperature of 70 캜 for 12 hours under an oxygen balloon (O ₂ balloon), and then cooled to room temperature.

The resultant was diluted by adding EtOAc and water, filtered through a silica plug, and the silica was washed several times with EtOAc.

The resulting solution was diluted with EtOAc and water.

The two layers were separated and the aqueous layer was extracted with EtOAc.

The combined organic layer was concentrated to dryness, and vacuum filtered over MgSO _4.

The ¹ H NMR yield of the target substance was determined through integration using an internal standard (1,1,2,2-tetrachloroethane).

Next, the optimization conditions obtained above are combined with the Cu @ C-catalytic aerobic oxidation conversion of the aromatic primary alcohol corresponding to the first step to the aldehyde, thereby deriving the optimum conditions for the first and second steps (Figure 1).

(4) An aromatic primary alcohol using Cu @ C as a catalyst Nightly  One-pot aerobic Oxidative  transform

Cu (2.5 mol%, 0.025 mmol), TEMPO (5 mol%, 0.05 mmol) and alcohol (1 mmol; solid in a 15 mm flame-dried test tube equipped with a magnetic stir bar ), Exhausted (introduced), and then filled again with oxygen.

After adding 0.5 mL of DMF, NMI (5 mol%, 0.05 mmol), alcohol (1 mmol; in the case of liquid) and DMF (0.5 mL) were added in this order.

The resulting solution was stirred at 70 째 C for 6 hours under an oxygen balloon (O ₂ balloon) and NH ₃ (aq) (2.4 equiv, 2.4 mmol) was added.

The reaction mixture was then stirred for 12 hours and then allowed to cool to room temperature.

The resultant was diluted with EtOAc, filtered through a silica plug, and the silica plug was washed several times with EtOAc.

The resulting solution was diluted with EtOAc and water.

The two layers were separated and the aqueous layer was extracted with EtOAc.

Drying and filtration the combined organic layers over MgSO _4, and concentrated in vacuo.

The ¹ H NMR yield of the target substance was determined through integration using an internal standard (1,1,2,2-tetrachloroethane).

(5) Various Nightly  NMR data for the product

Experimental Example

(1) Investigation of catalyst activity and search for optimum conditions

First, with respect to the optimum conditions of the second step, the catalytic activity of the heterogeneous catalyst Cu @ C on the aerobic oxidative conversion of 4-methylbenzaldehyde (1a) to 4-methylbenzonitrile (2a) was investigated in the presence of TEMPO (Table 1).

As expected, the Cu @ C / TEMPO system was able to catalyze the aerobic oxidative conversion of 1a and ammonia in a CH ₃ CN solvent at 70 ° C oxygen atmosphere to produce 2a, and NH ₃ (aq) Proved (Entries 1-4).

In addition, reactions in polar solvents such as DMF and DMSO showed higher yields than in CH ₃ CN (Entries 4-6).

On the other hand, attempts were made to reduce the reaction temperature, but the yield decreased as the reaction temperature decreased (Entries 6-8).

In addition, when 2.4 equivalents of NH ₃ (aq) was used, the yield was fairly high even though 2.5 mol% Cu @ C and 5 mol% TEMPO were used (Entries 9-10).

Control experiments have shown that Cu @ C and TEMPO are essential for the transformation of the present invention (Entries 11-12), and aerobic oxidative conversion is relatively poor under atmospheric conditions (Entry 13).

[Table 1] Optimization of aerobic oxidative synthesis conditions of aldehyde to nitrile using Cu @ C catalyst

Next, the Cu @ C-catalyzed aerobic oxidative conversion of aromatic primary alcohol to nitrile was tested by applying the optimization conditions established above.

Methylbenzenal alcohol (3a) was oxidatively oxidized with 4-methylbenzonitrile (2a) using the Cu @ C / TEMPO catalyst system under the above-obtained optimum conditions. As a result, 4-methylbenzaldehyde (1a) And 4-methylbenzonitrile (2a) were produced in yields of 68% and 14%, respectively.

On the other hand, when the same reaction was carried out using NMI as an organic base, the yield of 4-methylbenzonitrile (2a) was increased to 16%, which was confirmed by the conversion of aromatic primary alcohol to aldehyde And the reactivity associated with the < RTI ID = 0.0 >

Figure 1: Aerobic oxidative conversion of alcohol to nitrile using Cu @ C / TEMPO catalyst system (preliminary test)

However, even when NMI was added, a considerable amount of unreacted alcohol was still recovered.

These results indicate that the conversion of aromatic primary alcohol to aldehyde is limited by the presence of ammonia water.

One-pot sequential reaction method was tried to prevent the generation of aldehyde by the presence of ammonia water.

In the presence of Cu @ C, TEMPO and NMI in DMF, the reaction was carried out under oxygen conditions for 6 hours to oxidize 3a once, then add ammonia water and stir for 12 hours.

This one-pot sequential reaction method was successful, and the yield of 2a was as high as 99%.

In short, in the present invention, the optimum conditions for the first step and the second step,

Reaction Scheme: One-pot sequential reaction

Ammonia source: Ammonia water (added only in the second stage) (e.g. 2.4 equivalents)

Cu @ C: 2.5 mol%

TEMPO: 5 mol%

NMI: 2.5 mol%

Oxygen (O ₂ ) Feeding conditions: for example, using an O ₂ balloon

Solvent: DMF

Reaction temperature and time in the first step: 70 ° C, 6 hours

Reaction temperature and time in the second step: 70 ° C, 12 hours

(Fig. 1).

(2) Various aromatic primary alcohols using Cu @ C as a catalyst Nightly  One-pot Oxidative Oxidation Conversion Experiment

At the derived optimized conditions, various aromatic primary alcohols could be converted to nitriles and the results are shown in Table 2 below.

As shown in the following Table 2, the one-pot oxygen-oxidative conversion method of the present invention successfully oxidizes each step to produce a corresponding nitrite with a high overall yield for various substrates .

Specifically, various benzyl alcohols such as 4-methyl or 4-methoxybenzyl alcohol can be oxidatively converted to give the corresponding nitrile in high yield (2a, 2d). The corresponding nitrile was obtained in very high yield (2 g) even with a possible halide substituent for the coupling reaction. The multi-ring substrate was also highly efficiently converted to the corresponding nitrile (2k, 2n).

[Table 2] Yield yield of nitrile by substrate under optimized conditions

(3) Reusability test of catalyst

To test the reusability of Cu @ C, the reaction was carried out on 4-chlorobenzyl alcohol in the presence of 20 mg of Cu @ C on a 5 mmol scale.

After each run, the catalyst separated by centrifugation was washed with ethyl acetate and dried.

The collected catalyst was then used without calcination.

Approximately 83% of the catalysts were recovered in each experiment and could be reused at least three times without significant loss of activity (FIG. 2).

In the fourth experiment, the yield of the product was slightly reduced, which is considered to be due to the partial disappearance of Cu @ C in the separation process.

Analysis of ICP-AES showed that 35.4 ppm copper was present in the filtrate, indicating that only 3.3% of the total Cu content (wt.) Of the Cu @ C catalyst was leached into the reaction mixture .

(4) Possibility of application to the synthesis of biologically active compounds

The heterogeneous copper catalyst of the present invention was applied to the synthesis of biologically active compounds (Figure 2).

For the synthesis of 5- (1- (3-Fluorophenyl) -1H-pyrazol-4-yl) -2H-tetrazole (LQFM 021) known to be used as a PDE- 1H-pyrazole-4-carbonitrile) (2t) is required as a core intermediate.

The reported 2t synthesis method relies on dehydration of 1t of aldehyde using NH ₂ OH and NaI.

"DR Martins, F. Pazini, V. de Medeiros Alves, S. Santana de Moura, LM Liao, MT Quezado de Magalhaes, MC Valadares, CH Andrade, R. Menegatti, ML Rocha, Chem. Pharm. Bull. 2013, 61 , 524-531. "As a result of applying the protocol according to the present invention to 1 t, the oxidation-to-oxygen conversion was smoothly carried out, and the yield of 2t reached 99%.

[Figure 2] Application of Cu @ C / TEMPO system for the synthesis of biologically active compounds

Review results

The present invention can smoothly perform aerobic oxidation conversion of benzyl alcohol to benzonitrile through a one-pot method using a heterogeneous copper catalyst (Cu @ C) produced by pyrolysis of HKUST-1.

By the Cu @ C / TEMPO system, the benzaldehyde formed from various benzyl alcohols was condensed with the ammonia source and then converted to the corresponding benzonitrile via subsequent aerobic oxidation.

In addition, the heterogeneous catalyst according to the present invention can be reused at least three times.

Claims (16)

A method for producing nitrile using an aromatic primary alcohol as a starting material,
A first step of converting an aromatic primary alcohol into an aromatic aldehyde by aerobic oxidation; And
And a second step of converting an aromatic aldehyde to a nitrile by adding an ammonia source as a reactant to the same reaction vessel in which an aromatic aldehyde is formed,
The first and second steps are performed using a heterogeneous copper catalyst, TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) and 1-methylimidazole (NMI) as an organic base, Is performed in a solvent under the condition that oxygen (O ₂ ) is supplied,
The heterogeneous copper catalyst is a pyrolysis of HKUST-1 (copper benzene-1,3,5-tricarboxylate; Cu ₃ (BTC) ₂ ) ) ≪ / RTI >
The catalyst is collected by centrifugation after the reaction and can be reused without calcination. The catalyst is characterized in that the yield of the product is the same even if it is reused up to three times,
Wherein the first step and the second step are performed by a one-pot sequential reaction method.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Characterized in that the aromatic primary alcohol is benzyl alcohol.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Wherein the aromatic primary alcohol is selected from the group of compounds represented by the following structural formulas:
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalyst:

.
The method according to claim 1,
Characterized in that the ammonia source is aqueous ammonia.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
5. The method of claim 4,
Characterized in that the ammonia water is used in an amount of 1.2 to 4.8 eq.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
The heterogeneous copper catalyst may be,
HKUST-1 (copper-benzene-1,3,5-tricarboxylate; Cu ₃ (BTC) ₂ ) was prepared as a metal-organic framework (MOF)
The HKUST-1 is pyrolyzed at a high temperature of 800 to 1000 ° C. for 6 to 10 hours,
Characterized in that it is produced by forming a mesoporous structure in the form of supporting copper (Cu) on a carbon (C) support.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Wherein the heterogeneous copper catalyst is used in an amount of 2.5 to 5 mol% based on the aromatic primary alcohol.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
delete The method according to claim 1,
Wherein the TEMPO is used in an amount of 5 to 10 mol% based on the aromatic primary alcohol.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Characterized in that the condition under which the oxygen (O ₂ ) is supplied is formed by using an oxygen balloon (O ₂ balloon)
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Wherein the solvent is DMF (N, N-dimethylformamide) or DMSO (dimethylsulfoxide).
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
The method according to claim 1,
Wherein the reaction is carried out at 50 to 70 占 폚.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
delete 14. The method of claim 13,
The ammonia source is used in an amount of 2.4 eq as ammonia water,
The heterogeneous copper catalyst is used in an amount of 2.5 mol% based on the aromatic primary alcohol,
The TEMPO is used in an amount of 5 mol% based on the aromatic primary alcohol,
The 1-methylimidazole (NMI) is used in an amount of 2.5 mol% based on the aromatic primary alcohol,
The conditions under which the oxygen (O ₂ ) is supplied are formed using an O ₂ balloon,
The solvent is DMF,
Wherein the reaction is carried out at 70 DEG C for 6 hours and at 70 DEG C for 12 hours.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalysts.
15. The method of claim 14,
The nitrile is selected from the group of compounds represented by the following structural formulas,
Wherein the reaction yield is 90% or more.
Oxidative Oxidation of Aromatic Primary Alcohols to Nitrile Using Uniform Copper Catalyst:

.
delete

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