A catalyst and a method for catalytic oxidative coupling of organic primary amines to synthesize imines

Abstract

The present application discloses a catalyst and a method for catalytic oxidative coupling of organic primary amines to synthesize imines, belonging to the technical field of organic synthesis. The catalyst comprises an organic nitrile compound and an organic phosphide; the molar ratio of the organic nitrile compound to the organic phosphide is 0.001-10:0.01-10. In an oxidative environment, a material containing an organic primary amine is contacted with the catalyst and reacted to obtain an imine. This method has low cost, no metal pollution, high yield, uses oxygen as an oxygen source for oxidative coupling to generate imines, has a high conversion rate of organic primary amines and a high selectivity for imines, and has broad application prospects.

Description

Technical Field

[0001] The present application relates to a catalyst and a method for catalytic oxidative coupling of organic primary amines to synthesize imines, belonging to the technical field of organic synthesis. Background Art

[0002] Imines are an important class of organic synthesis intermediates and have been widely concerned in the fields of medicine and biology. In recent years, the reported methods for synthesizing imines include hydrogenation coupling of nitro compounds, oxidative dehydrogenation of secondary amines, oxidative condensation of amines and alcohols, oxidative coupling of organic primary amines, etc. Among them, the oxidative coupling of organic primary amines is one of the atom - economic routes for preparing imines.

[0003] Currently, the catalytic systems for the oxidative coupling of organic primary amines to synthesize imines include metal systems and non - metal systems. Metal catalytic systems are limited in the application of imines in the field of drug synthesis because metal ions will remain in the reaction system. The non - metal system does not leave metal ions in the reaction system. Therefore, the non - metal system has obvious advantages in the process of preparing imines by oxidative coupling of organic primary amines. However, the reported non - metal systems, such as mesoporous carbon (ACS Catal. 2015, 5, 2788 - 2794), graphite oxide (Green Chem. 2012, 14, 930 - 934), carbon nanotubes and nitrogen - boron - doped graphene (Chem. Commun. 2014, 50, 7517 - 7520), covalent triazine framework materials (ChemistrySelect 2019, 4, 5073 - 5080), etc., have problems such as large dosage and low efficiency, which limit their further application. Summary of the Invention

[0004] The present application provides a method for catalytic oxidative coupling of organic primary amines to synthesize imines by using an organic nitrile compound and an organic phosphide in cooperation. Using the organic primary amine as a substrate, a catalytic system composed of the organic nitrile compound and the organic phosphide is dispersed in the organic primary amine, and oxygen is introduced, then the imine can be obtained by reaction. This method uses oxygen or air as the oxygen source, and has the characteristics of high efficiency, low cost, and small pollution, and has broad application prospects.

[0005] According to one aspect of the present application, a catalyst is provided, the catalyst comprising an organic nitrile compound and an organic phosphide; the molar ratio of the organic nitrile compound to the organic phosphide is 0.001 - 10:0.01 - 10.

[0006] Optionally, the organic nitrile compound is selected from at least one of arene substituted by cyano or alkene substituted by cyano.

[0007] Optionally, the cyano-substituted aromatic hydrocarbon is selected from at least one of pyromellitic tetracarbonitrile, phthalonitrile, isophthalonitrile, terephthalonitrile, 4-nitro-phthalonitrile, 4,5-difluoro-phthalonitrile, 4,5-dimethyl-phthalonitrile, 2,6-pyridinedicarbonitrile, trimellitic tricarbonitrile, and tetracyanoquinodimethane; the cyano-substituted olefin is selected from tetracyanoethylene.

[0008] Optionally, the organic phosphide is selected from organic phosphides having at least one phenyl substitution.

[0009] Optionally, the organic phosphide is selected from at least one of triphenylphosphine, phenylbis(2,4,6-trimethylbenzoyl)phosphine, diphenyl ethoxyphosphine, phenyldiethoxyphosphine, and (3-chlorobenzyl)diethylphosphine.

[0010] The catalyst described in the present application can be used for the oxidative coupling of organic primary amines to synthesize imines.

[0011] According to one aspect of the present application, a method for preparing the above catalyst is provided, in which the organic nitrile compound and the organic phosphide are mixed in a molar ratio.

[0012] According to one aspect of the present application, a method for catalytically oxidatively coupling organic primary amines to synthesize imines is provided. In an oxidative atmosphere, a material containing an organic primary amine is contacted with a catalyst and reacted to obtain an imine;

[0013] The catalyst is selected from one of the above catalysts.

[0014] Optionally, the organic primary amine includes aliphatic primary amines and aromatic primary amines.

[0015] Optionally, the dosage of the organic nitrile compound is 0.001 mol% to 10 mol% of the molar amount of the organic primary amine.

[0016] Optionally, the dosage of the organic nitrile compound is independently selected from any value of 0.001 mol%, 0.005 mol%, 0.01 mol%, 0.05 mol%, 0.1 mol%, 0.5 mol%, 1.0 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 6 mol%, 8 mol%, 10 mol% or a range value between any two of them of the molar amount of the organic primary amine.

[0017] Optionally, the dosage of the organic phosphide is 0.01 mol% to 10 mol% of the molar amount of the organic primary amine.

[0018] Optionally, the dosage of the organic phosphide is independently selected from any value of 0.01 mol%, 0.05 mol%, 0.1 mol%, 0.5 mol%, 1.0 mol%, 1.5 mol%, 2 mol%, 3.0 mol%, 4 mol%, 5 mol%, 6 mol%, 8 mol%, 10 mol% of the molar amount of the primary organic amine or the range value between any two of them.

[0019] Optionally, the oxidation atmosphere contains oxygen, and the oxygen accounts for 2.5% - 100% of the oxidation atmosphere.

[0020] Optionally, in the oxidation atmosphere, the oxygen partial pressure is 0.1 - 4.0 MPa.

[0021] When the oxygen accounts for 100% of the oxidation atmosphere, the oxygen pressure is 4.0 MPa.

[0022] Optionally, the oxygen partial pressure is 0.1 - 2.0 MPa.

[0023] Optionally, the upper limit of the oxygen partial pressure is independently selected from 0.2 MPa, 0.5 MPa, 0.6 MPa, 0.8 MPa, 1.0 MPa, 1.2 MPa, 1.5 MPa, 1.6 MPa, 1.8 MPa, 2.0 MPa, 2.2 MPa, 2.4 MPa, 2.8 MPa, 3.0 MPa, 3.5 MPa, 3.8 MPa, 4.0 MPa; the lower limit of the oxygen partial pressure is independently selected from 0.1 MPa, 0.5 MPa, 0.6 MPa, 0.8 MPa, 1.0 MPa, 1.2 MPa, 1.5 MPa, 1.6 MPa, 1.8 MPa, 2.0 MPa, 2.2 MPa, 2.4 MPa, 2.8 MPa, 3.0 MPa, 3.5 MPa.

[0024] Optionally, the temperature of the reaction is 30 - 150 °C; the time of the reaction is 0.5 - 48 h.

[0025] Optionally, the temperature of the reaction is 50 - 120 °C; the time of the reaction is 2 - 36 h.

[0026] Optionally, the upper limit of the reaction temperature is independently selected from 50 °C, 70 °C, 80 °C, 90 °C, 100 °C, 110 °C, 120 °C, 130 °C, 140 °C, 150 °C; the lower limit of the reaction temperature is independently selected from 30 °C, 50 °C, 70 °C, 80 °C, 90 °C, 100 °C, 110 °C, 120 °C, 130 °C.

[0027] Optionally, the upper limit of the reaction time is independently selected from 1 h, 2 h, 4 h, 5 h, 6 h, 8 h, 9 h, 10 h, 12 h, 13 h, 15 h, 17 h, 18 h, 20 h, 24 h, 26 h, 32 h, 36 h, 45 h, 48 h; the lower limit of the reaction time is independently selected from 0.5 h, 1 h, 2 h, 4 h, 5 h, 6 h, 8 h, 9 h, 10 h, 12 h, 13 h, 15 h, 17 h, 18 h, 20 h, 24 h, 26 h, 32 h, 36 h, 45 h.

[0028] Optionally, the reaction is carried out under solvent-free conditions.

[0029] The present application provides a method for the synthesis of imines by the oxidative coupling of organic primary amines using an organic nitrile compound and an organic phosphide in a synergistic manner. In this method, oxygen or air is used as the oxygen source, and an organic nitrile compound and an organic phosphide are used as catalysts to catalyze the oxidative coupling of organic primary amines to synthesize imines under solvent-free conditions.

[0030] The beneficial effects that can be produced by the present application include:

[0031] The method for the synthesis of imines by the oxidative coupling of organic primary amines provided by the present application uses an organic nitrile compound and an organic phosphide to synergistically catalyze the oxidative coupling of organic primary amines to synthesize imines for the first time. This catalyst system has high activity, low dosage, is cheap and easily available, is solvent-free, has good product selectivity, is environmentally friendly and economical. The reaction conditions are mild, the catalytic system used is simple, the conversion rate of organic primary amines is high, the selectivity of imines is high, using oxygen as the oxygen source, it has low cost, low pollution, high yield, is environmentally friendly, and has broad application prospects. Detailed Embodiments

[0032] The present application will be described in detail below with reference to the embodiments, but the present application is not limited to these embodiments.

[0033] Unless otherwise specified, the raw materials and catalysts in the embodiments of the present application are purchased through commercial channels. Unless otherwise specified, the testing methods are all conventional methods, and the instrument settings are all the settings recommended by the manufacturers.

[0034] The analysis methods in the embodiments of the present application are as follows:

[0035] The conversion rate of organic primary amines and the selectivity of imines are both calculated based on the carbon molar number:

[0036]

[0037]

[0038] Example 1

[0039] 4 mmol of benzylamine, 1.0 mol% of pyromellitonitrile and 2.0 mol% of triphenylphosphine were added to a 15 mL reactor. The reactor was closed, filled with 0.5 MPa of oxygen, heated to 80 °C, and reacted at this temperature for 30 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and subjected to gas chromatography analysis, and the conversion rate of the organic primary amine and the selectivity of the imine were calculated respectively. The conversion rate of benzylamine was 99%, and the selectivity of the imine was 97%.

[0040] In this example, "1.0 mol% of pyromellitonitrile" means that the molar amount of pyromellitonitrile is 1.0 mol% of benzylamine, and "2.0 mol% of triphenylphosphine" means that the molar content of triphenylphosphine is 2.0 mol% of benzylamine. In the catalyst, similar representations in other examples are similar to this explanation.

[0041] Example 2

[0042] 4 mmol of o-methylbenzylamine, 0.5 mol% of phthalonitrile and 1.5 mol% of phenylbis(2,4,6-trimethylbenzoyl)phosphine were added to a 15 mL reactor. The reactor was closed, filled with 1.0 MPa of oxygen, heated to 100 °C, and reacted at this temperature for 16 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and subjected to gas chromatography analysis, and the conversion rate of the organic primary amine and the selectivity of the imine were calculated respectively. The conversion rate of the organic primary amine was 99%, and the selectivity of the imine was 89%.

[0043] Example 3

[0044] 4 mmol of m-methylbenzylamine, 8 mol% of isophthalonitrile and 5 mol% of phenylbis(2,4,6-trimethylbenzoyl)phosphine were added to a 15 mL reactor. The reactor was closed, filled with 2.0 MPa of oxygen, heated to 100 °C, and reacted at this temperature for 5 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and subjected to gas chromatography analysis, and the conversion rate of m-methylbenzylamine and the selectivity of the imine were calculated respectively. The conversion rate of m-methylbenzylamine was 99%, and the selectivity of the imine was 98%.

[0045] Example 4

[0046] 4 mmol of p-methylbenzylamine, 0.001 mol% of pyromellitonitrile and 1.0 mol% of diphenylethoxyphosphine were added to a 15 mL reactor. The reactor was closed, filled with 1.5 MPa of oxygen, heated to 70 °C, and reacted at this temperature for 40 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and subjected to gas chromatography analysis, and the conversion rate of p-methylbenzylamine and the selectivity of the imine were calculated respectively. The conversion rate of p-methylbenzylamine was 99%, and the selectivity of the imine was 99%.

[0047] Example 5

[0048] 4 mmol of p-methoxybenzylamine, 6.0 mol% of 4-nitro-phthalonitrile and 6.0 mol% of phenyldiethoxyphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 0.1 MPa of oxygen, heated to 120 °C, and reacted at this temperature for 3 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and analyzed by gas chromatography. The conversion rate of p-methoxybenzylamine and the selectivity of imine were calculated respectively. The conversion rate of p-methoxybenzylamine was 97%, and the selectivity of imine was 98%.

[0049] Example 6

[0050] 4 mmol of p-fluorobenzylamine, 1.2 mol% of 2,6-pyridinedicarbonitrile and 2.5 mol% of (3-chlorobenzyl)diethylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 2.5 MPa of oxygen, heated to 150 °C, and reacted at this temperature for 8 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and analyzed by gas chromatography. The conversion rate of p-fluorobenzylamine and the selectivity of imine were calculated respectively. The conversion rate of p-fluorobenzylamine was 99%, and the selectivity of imine was 98%.

[0051] Example 7

[0052] 4 mmol of p-chlorobenzylamine, 3.2 mol% of benzene-1,3,5-tricarbonitrile and 0.05 mol% of (3-chlorobenzyl)diethylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 1.8 MPa of oxygen, heated to 30 °C, and reacted at this temperature for 45 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and analyzed by gas chromatography. The conversion rate of p-chlorobenzylamine and the selectivity of imine were calculated respectively. The conversion rate of p-chlorobenzylamine was 94%, and the selectivity of imine was 99%.

[0053] Example 8

[0054] 4 mmol of p-bromobenzylamine, 0.1 mol% of benzene-1,2,4,5-tetracarbonitrile and 0.7 mol% of triphenylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 3.8 MPa of oxygen, heated to 90 °C, and reacted at this temperature for 18 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and analyzed by gas chromatography. The conversion rate of p-bromobenzylamine and the selectivity of imine were calculated respectively. The conversion rate of p-bromobenzylamine was 99%, and the selectivity of imine was 98%.

[0055] Example 9

[0056] 4 mmol of 2-thiophene methylamine, 0.05 mol% of 4,5-difluoro-phthalonitrile and 1.0 mol% of triphenylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 0.8 MPa of oxygen, heated to 120 °C, and reacted at this temperature for 9 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and subjected to gas chromatography analysis, and the conversion rate of 2-thiophene methylamine and the selectivity of imine were calculated respectively. The conversion rate of 2-thiophene methylamine was 97%, and the selectivity of imine was 98%.

[0057] Example 10

[0058] 4 mmol of 3-pyridine methylamine, 1.6 mol% of tetracyanoethylene and 2.2 mol% of triphenylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 1.2 MPa of oxygen, heated to 100 °C, and reacted at this temperature for 1.3 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and subjected to gas chromatography analysis, and the conversion rate of 3-pyridine methylamine and the selectivity of imine were calculated respectively. The conversion rate of 3-pyridine methylamine was 99%, and the selectivity of imine was 88%.

[0059] Example 11

[0060] 4 mmol of 2-furan methylamine, 1.4 mol% of tetracyanoquinodimethane and 2.0 mol% of phenyldiethoxyphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 1.6 MPa of oxygen, heated to 110 °C, and reacted at this temperature for 7 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and subjected to gas chromatography analysis, and the conversion rate of 2-furan methylamine and the selectivity of imine were calculated respectively. The conversion rate of 2-furan methylamine was 99%, and the selectivity of imine was 95%.

[0061] Example 12

[0062] 4 mmol of n-hexylamine, 8 mol% of pyromellitic tetranitrile and 8 mol% of triphenylphosphine were added to a 15 mL reaction kettle. The kettle was closed, filled with 1.4 MPa of oxygen, heated to 120 °C, and reacted at this temperature for 29 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, sampled and subjected to gas chromatography analysis, and the conversion rate of n-hexylamine and the selectivity of imine were calculated respectively. The conversion rate of n-hexylamine was 95%, and the selectivity of imine was 93%.

[0063] Example 13

[0064] 4 mmol of cyclohexylamine, 0.4 mol% of 2,6-pyridinedicarbonitrile and 1.2 mol% of triphenylphosphine were added to a 15 mL reactor. The reactor was closed, filled with 0.6 MPa of oxygen, heated to 90 °C, and reacted at this temperature for 25 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and analyzed by gas chromatography, and the conversion rate of cyclohexylamine and the selectivity of imine were calculated respectively. The conversion rate of cyclohexylamine was 98%, and the selectivity of imine was 97%.

[0065] Example 14

[0066] 4 mmol of n-butylamine, 3.5 mol% of isophthalonitrile and 0.02 mol% of triphenylphosphine were added to a 15 mL reactor. The reactor was closed, filled with 0.8 MPa of oxygen, heated to 100 °C, and reacted at this temperature for 12 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and analyzed by gas chromatography, and the conversion rate of n-butylamine and the selectivity of imine were calculated respectively. The conversion rate of n-butylamine was 95%, and the selectivity of imine was 92%.

[0067] Comparative Example 1

[0068] 4 mmol of benzylamine and 1.0 mol% of pyromellitonitrile were added to a 15 mL reactor. The reactor was closed, filled with 0.5 MPa of oxygen, heated to 80 °C, and reacted at this temperature for 30 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and analyzed by gas chromatography, and the conversion rate of benzylamine and the selectivity of imine were calculated respectively. The conversion rate of benzylamine was 69%, and the selectivity of imine was 60%.

[0069] Comparative Example 2

[0070] 4 mmol of benzylamine and 2.0 mol% of triphenylphosphine were added to a 15 mL reactor. The reactor was closed, filled with 0.5 MPa of oxygen, heated to 80 °C, and reacted at this temperature for 30 h. After the reaction was completed, the reaction mixture was naturally cooled to room temperature. An internal standard was added, samples were taken and analyzed by gas chromatography, and the conversion rate of benzylamine and the selectivity of imine were calculated respectively. The conversion rate of benzylamine was 4%, and the selectivity of imine was 54%.

[0071] It can be seen from Comparative Example 1 that when using an organic nitrile compound alone, the substrate conversion rate is not high and the selectivity of the target product imine is low; it can be seen from the comparison with Comparative Example 2 that when using an organic phosphine compound alone, the substrate is basically not converted; compared with the previous examples, when using an organic nitrile compound and an organic phosphide in combination, a higher conversion rate of primary organic amine and selectivity of the target product imine can be obtained.

[0072] The above are only several embodiments of the present application, and do not impose any form of limitation on the present application. Although the present application is disclosed above with preferred embodiments, it is not intended to limit the present application. Any person skilled in the art, without departing from the scope of the technical solution of the present application, making some changes or modifications using the technical content disclosed above is equivalent to equivalent embodiments and all fall within the scope of the technical solution.

Claims

1. A catalyst, characterized in that, The catalyst is an organic nitrile compound and an organic phosphide; the molar ratio of the organic nitrile compound to the organic phosphide is 0.001-10:0.01-10; The organic nitrile compound is selected from at least one of a cyano-substituted aromatic hydrocarbon or a cyano-substituted olefin; The cyano-substituted aromatic hydrocarbon is selected from at least one of pyromellitic tetracarbonitrile, phthalonitrile, isophthalonitrile, terephthalonitrile, 4-nitro-phthalonitrile, 4,5-difluoro-phthalonitrile, 4,5-dimethyl-phthalonitrile, trimellitic tricarbonitrile, tetracyanoquinodimethane; the cyano-substituted olefin is selected from tetracyanoethylene; The organic phosphide is selected from at least one of triphenylphosphine, phenylbis(2,4,6-trimethylbenzoyl)phosphine, diphenylethoxyphosphine, phenyldiethoxyphosphine, (3-chlorobenzyl)diethylphosphine.

2. The preparation method of the catalyst according to claim 1, characterized in that, The organic nitrile compound and the organic phosphide are mixed according to the molar ratio.

3. A method for catalytic oxidative coupling of primary organic amines to synthesize imines, characterized in that, In an oxidative atmosphere, a material containing an organic primary amine is contacted with the catalyst and reacted to obtain an imine; The catalyst is selected from the catalyst described in claim 1; The organic primary amine is benzylamine, o-methylbenzylamine, m-methylbenzylamine, p-methylbenzylamine, p-methoxybenzylamine, p-fluorobenzylamine, p-chlorobenzylamine, p-bromobenzylamine, 2-thiophene methylamine, 3-pyridine methylamine, 2-furan methylamine, n-hexylamine, cyclohexylamine or n-butylamine.

4. The method according to claim 3, wherein The dosage of the organic nitrile compound is 0.001 mol% - 10 mol% of the molar amount of the organic primary amine; the dosage of the organic phosphide is 0.01 mol% - 10 mol% of the molar amount of the organic primary amine.

5. The method according to claim 3, characterized in that, In the oxidative atmosphere, the oxygen pressure is 0.1 - 4.0 MPa.

6. The method according to claim 5, characterized in that The oxygen pressure is 0.1 - 2.0 MPa.

7. The method according to claim 3, characterized in that, The temperature of the reaction is 30~150 o °C; the time of the reaction is 0.5~48h.

8. The method according to claim 3, wherein The temperature of the reaction is 50~120 o °C; the time of the reaction is 2~36 h.

9. The method according to claim 3, wherein The reaction is carried out under solvent-free conditions.

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