A method for synthesizing allylic tertiary amines

Abstract

The application provides a method for synthesizing allyl tertiary amine, which can selectively synthesize allyl tertiary amine from alkyl secondary amine through allyl amination with high efficiency. The application uses metal-phosphine complex as a homogeneous catalyst, and simultaneously adds a cocatalyst ketoxime to selectively catalyze the cleavage of the primary allyl C-H bond of olefin to synthesize allyl amine. The method can be extended to a wide range of olefins, has atom economy, makes the synthesis of allyl tertiary amine compounds simpler and more efficient, the catalyst can be recycled, and excellent chemical region selectivity and functional group tolerance are exhibited.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a method for synthesizing allyl tertiary amine from olefin and alkyl secondary amine. BACKGROUND

[0002] Amine compounds (including primary amine, secondary amine, tertiary amine and quaternary ammonium salt) are widely used, and can be used for biological enzyme ligand, promotion of catalytic activity and selectivity of enzyme, and also can be used as extractant, wherein tertiary amine and quaternary ammonium salt are more used, and the tertiary amine and the like medium-strength basic extractant has the advantages of good selectivity, good radiation migration point and the like, and the tertiary amine can also be applied to refining and processing of nuclear fuel such as uranium and plutonium, separation of rare earth elements and non-ferrous metals, and the aliphatic tertiary amine is also an important intermediate in the surfactant industry.

[0003] Allyl-substituted tertiary amine compounds are a kind of very important organic synthesis intermediates, and play an important role in natural product synthesis and organic drug synthesis. When the compounds are traditionally synthesized, pre-functionalized substrates need to be used. For example, the most commonly used synthesis method of tertiary amine compounds is to realize the coupling reaction of allyl bromide and secondary amine compounds by using NaH, butyllithium or noble metal catalysis, which needs to discharge halide harmful to the environment, and the method is cumbersome and has poor atom economy; in addition, a series of tertiary amine compounds are synthesized by using Michael addition product of acrylonitrile and secondary amine and halogenated hydrocarbon to occur quaternary ammonium, and Hoffmann elimination reaction of quaternary ammonium salt.

[0004] It is of great application value to develop a more environmentally friendly and more efficient synthesis method. In recent years, the construction of carbon-nitrogen bond through direct amination of carbon-hydrogen bond has become a new method for synthesizing amine compounds, which avoids the use of halogenated hydrocarbon, has better atom economy and environmental friendliness, and the existing methods have certain limitations, mainly that the substrate application range is narrow, and the method cannot be applied to alkyl amine, aromatic amine and certain heterocyclic secondary amine compounds at the same time. Direct cross-coupling of C-N bond from inert C-H bond is an ideal method for synthesizing saturated nitrogen heterocyclic compounds. Therefore, it is in line with the development requirements of green chemistry to develop a high-efficiency recyclable metal-based catalyst to construct allyl tertiary amine compounds through oxidative coupling reaction of alkyl secondary amine and olefin compounds, and it is of great application value. SUMMARY

[0005] The present application aims to provide a method for preparing allyl tertiary amine compounds, which is a site-selective amination of olefins and secondary alkyl amines under the catalysis of metal-phosphine complexes and the assistance of ketoxime to construct carbon-nitrogen bonds to obtain allyl tertiary amine compounds. The present application proposes a more economical and efficient method for producing allyl tertiary amine compounds, which does not use dangerous butyl lithium, NaH, etc., and does not generate pollutants. In order to achieve the above-mentioned purpose, the technical solution adopted by the present application specifically includes the following contents:

[0006] A method for synthesizing allyl tertiary amine compounds is carried out according to the following steps:

[0007] The method uses olefins and secondary alkyl amines as raw materials, and under the action of a metal-phosphine complex catalyst, an oxidant and an oxime catalyst, it catalyzes the selective amination to obtain allyl tertiary amine compounds.

[0008] In a specific embodiment, the reaction step includes: laying a certain amount of solvent at the bottom of a high-pressure autoclave reactor, adding catalysts, oxidants and catalysts, placing the reaction system in a nitrogen atmosphere, continuously adding the reaction raw materials, and carrying out a one-step amination reaction under certain conditions to obtain allyl tertiary amine compounds.

[0009] The olefins are one or more of C4-C10 straight-chain or branched-chain terminal olefins or terpenes;

[0010] The secondary alkyl amine includes one or more of C3-C8 straight-chain / cyclic alkyl secondary amines.

[0011] The molar ratio of the amination reaction raw materials, olefins and secondary alkyl amines, is 0.5-3, preferably 0.7-1.

[0012] In the metal-phosphine complex used in the amination reaction, the metal precursor is one or more of cobalt, iridium, rhodium, platinum, copper and nickel precursors, preferably one or more of iridium, cobalt and copper precursors, such as CuCl2, Cu(NO3)2, (OAc)2Co, CoCl2, IrCl3, IrBr, etc.; the phosphine ligand is selected from one or more of triphenylphosphine, Ph-Phos, CyJohn-Phos, Dave-Phos, BINAP, Bisbi and Dppx;

[0013] The preparation method of the metal-phosphine complex catalyst is: the metal precursor and the phosphine ligand are fed into a hydrothermal reactor at a ratio of 1:1.5, stirred at 20-50°C for 10-30 min, and the metal-phosphine complex catalyst is prepared. The amount of the catalyst is 0.2-5wt% of the total reaction raw materials (the total mass of olefins and secondary alkyl amines), preferably 0.2-2wt%.

[0014] The oxidizing agent is a silver salt or oxygen, wherein the silver salt is selected from one or more of silver benzoate, silver oxide, silver nitrate, silver acetate;

[0015] The silver salt is used in an amount of 0.5-5 wt% of the total reaction raw materials, preferably 0.5-2 wt%.

[0016] The oxime cocatalyst is selected from one or more of acetophenone oxime, benzophenone oxime, cyclohexanone oxime, 1-indanone oxime, bis(2-pyridyl) ketone oxime, phenyl-2-pyridyl ketone oxime;

[0017] The cocatalyst is used in an amount of 0.1-2 wt% of the total reaction raw materials, preferably 0.2-1 wt%.

[0018] The combination of the metal-phosphine complex catalyst and the oxime can enable site-selective amination of the olefin with the secondary alkyl amine to obtain an allylic tertiary amine. The steric hindrance of the phosphine ligand can be adjusted in a wide range, and the electronic properties of the ligand and the spatial properties are coordinated, which comprehensively affects each step of the catalytic reaction, and plays a key role in efficiently catalyzing the transition metal reaction.

[0019] The solvent is selected from at least one of toluene, diphenyl, p-xylene, ethyl acetate, hexafluoroisopropyl alcohol, preferably toluene and hexafluoroisopropyl alcohol.

[0020] Preferably, the mass ratio of the allylic amination total reaction raw materials to the solvent is 1:0.5-3.

[0021] The allylic amination reaction temperature is 10-80°C, preferably 20-60°C; the raw material feeding mode is continuous feeding, and the feeding speed is 0.2-2 g / min; the reaction time is 4-24 h, preferably 4-8 h.

[0022] The initial pressure of the allylic amination reaction is 1-10 bar, preferably 1-4 bar.

[0023] The reaction liquid obtained by the allylic amination reaction is subjected to distillation to remove the catalyst and the cocatalyst to obtain an allylic tertiary amine crude product, and then subjected to rectification purification to obtain an allylic tertiary amine with a purity of 98%, or even more than 99.0%.

[0024] The present application is exemplified by the following reaction equation:

[0025]

[0026] The positive effects of the present application are:

[0027] (1) The scheme of the present application can use a wide range of olefins as raw materials to perform one-step amination with secondary alkyl amines to prepare branched or heterocyclic tertiary amine compounds containing allylic amines, and the reaction steps are simple and the yield is high.

[0028] (2) The present application provides a homogeneous catalytic system scheme, which uses a combination of metal-phosphine complex catalyst and oxime to catalyze amination, improves the reaction selectivity, has high catalytic activity, can be recycled, and has good substrate tolerance and functional group tolerance. DETAILED DESCRIPTION

[0029] The present application will be further described below through specific examples, but the present application is not limited to the following examples. The medicines used are as follows:

[0030] Olefins / alkyl secondary amine: Aldrin;

[0031] Metal precursor: Sigma;

[0032] Oxime co-catalyst: Haikun Chemical;

[0033] Solvent: Aldrin;

[0034] The gas chromatography test conditions of the present application are as follows:

[0035] Instrument model: Agilent 7890B

[0036] Chromatographic column: DB-5 (30 m x 0.25 mm x 0.25 μm)

[0037] Column temperature: initial temperature 30℃, temperature rising to 120℃ at 10℃ / min, holding for 5 min, then temperature rising to 240℃ at 10℃ / min, holding for 10 min

[0038] Injection port temperature: 250℃

[0039] FID detector temperature: 240℃

[0040] Split injection, split ratio 30:1

[0041] Injection amount: 2.0 μm

[0042] N2flow rate: 40 ml / min

[0043] H2flow rate: 400 ml / min.

[0044] Example 1

[0045] In a 1000 mL autoclave, 100 g of toluene was added to the bottom of the reactor as a solvent, and 100 g of piperidine, 0.75 g of cobalt-Ph-Phos catalyst (0.5 wt% of the total reaction raw materials), 0.75 g of silver oxide, and 0.75 g of bis(2-pyridyl) ketoxime (0.5 wt% of the total reaction raw materials) were mixed uniformly, and the air in the reaction system was replaced with nitrogen. Then, 600 rpm stirring and temperature control were started, the initial nitrogen pressure in the system was 2 bar, and the reaction temperature was 40°C. 50 g of isobutene was pumped into the reaction system at a rate of 0.5 g / min, and the pumping was completed in about 1.67 h. The reaction was continued for 4 h. After the reaction was completed, the conversion of the raw material isobutene was calculated to be 97.1%, and the product selectivity was 98.5%. The obtained reaction liquid was distilled to remove the catalyst and the auxiliary agent to obtain 1-(2-methylallyl)piperidine crude product, and then purified by a rectification column to obtain 1-(2-methylallyl)piperidine product with a purity of 99.2%.

[0046] The obtained product was analyzed by 1 H NMR (CDCI3) confirmed that δ 5.23 ppm (singlet, 1H), δ 5.11 ppm (singlet, 1H), δ 3.03 ppm (singlet, 2H), δ 2.44-2.45 ppm (triplet, 3H), δ 1.82 ppm (singlet, 3H), δ 1.52-1.60 ppm (multiplet, 6H) were consistent with the structure of 1-(2-methylallyl)piperidine.

[0047] Example 2

[0048] In a 1000 mL autoclave, 100 g of toluene was added to the bottom of the reactor as a solvent, and 80 g of diethylamine, 0.65 g of iridium-Dave-Phos catalyst (0.5 wt% of the total reaction raw materials), 1 g of silver oxide, and 0.65 g of cyclohexanone oxime (0.5 wt% of the total reaction raw materials) were mixed uniformly, and the air in the reaction system was replaced with nitrogen. Then, 600 rpm stirring and temperature control were started, the initial nitrogen pressure in the system was 2 bar, and the reaction temperature was 40°C. 50 g of isobutene was pumped into the reaction system at a rate of 0.25 g / min, and the pumping was completed in about 3.3 h. The reaction was continued for 4 h. After the reaction was completed, the conversion of the raw material isobutene was calculated to be 98.4%, and the product selectivity was 98.7%. The obtained reaction liquid was distilled to remove the catalyst and the auxiliary agent to obtain N,N-diethyl-2-methylallyl-1-amine crude product, and then purified by a rectification column to obtain N,N-diethyl-2-methylallyl-1-amine product with a purity of 98.7%.

[0049] Example 3

[0050] In a 1000 mL high-pressure reactor, 150 g of hexafluoroisopropanol was added to form a solvent bed, and 60 g of N-methylethylamine, 0.55 g (0.5 wt% of the total reaction raw materials) of cobalt-triphenylphosphine catalyst, 0.75 g of silver benzoate, and 0.55 g of bis(2-pyridine) ketoxime (0.5 wt% of the total reaction raw materials) were mixed uniformly, and the reaction system was replaced with nitrogen. Then, 600 rpm stirring and temperature control were started, the initial nitrogen pressure in the system was 2 bar, and the reaction temperature was 40°C. 50 g of isobutene was pumped into the reaction system at a rate of 0.5 g / min, and the pumping was completed in about 1.67 h. The reaction was continued for 4 h. After the reaction was completed, the conversion rate of the raw material isobutene was calculated to be 97.7%, and the product selectivity was 99.1%. The obtained reaction liquid was distilled to remove the catalyst and adjuvant to obtain N-ethyl-N,2-dimethylallyl-1-amine crude product, which was then purified by a rectifying column to obtain N-ethyl-N,2-dimethylallyl-1-amine product with a purity of 98.9%.

[0051] Example 4

[0052] In a 1000 mL high-pressure reactor, 100 g of p-xylene was added to form a solvent bed, and 80 g of piperidine, 0.65 g (0.5 wt% of the total reaction raw materials) of copper-BINAP catalyst, 0.75 g of silver oxide, and 1.3 g of phenylethanone oxime (1 wt% of the total reaction raw materials) were mixed uniformly, and the reaction system was replaced with nitrogen. Then, 600 rpm stirring and temperature control were started, the initial nitrogen pressure in the system was 1 bar, and the reaction temperature was 60°C. 50 g of methyl isopropenyl ether was pumped into the reaction system at a rate of 0.25 g / min, and the pumping was completed in about 3.3 h. The reaction was continued for 5 h. After the reaction was completed, the conversion rate of the raw material methyl isopropenyl ether was calculated to be 98.6%, and the product selectivity was 96.9%. The obtained reaction liquid was distilled to remove the catalyst and adjuvant to obtain 1-(2-methoxyallyl)piperidine crude product, which was then purified by a rectifying column to obtain 1-(2-methoxyallyl)piperidine product with a purity of 98.4%.

[0053] Example 5

[0054] 150g of toluene was added to a 1000mL high-pressure reactor as a solvent base, followed by 120g of N-methylcyclohexylamine, 0.85g (0.5wt%) of iridium-BINAP catalyst, 1.0g of silver acetate, and 0.85g of phenyl-2-pyridyl ketoxime (0.5wt%). The mixture was thoroughly mixed, and the air in the reaction system was completely purged with nitrogen. The system was then stirred at 600rpm with temperature control. The initial nitrogen pressure was 2 bar, and the reaction temperature was 50℃. 50g of isobutylene was pumped into the reaction system at a feed rate of 0.25g / min, completed in approximately 3.3 hours. The reaction was then maintained at this temperature for another 6 hours. After the reaction, the isobutylene conversion was calculated to be 98.9%, and the product selectivity was 98.3%. The resulting reaction solution was distilled to remove the catalyst and auxiliaries to obtain crude N-methyl-N-(2-methylallyl)cyclohexylamine, which was then purified by a distillation column to obtain N-methyl-N-(2-methylallyl)cyclohexylamine product with a purity of 99.0%.

[0055] Comparative Example 1

[0056] 100g of toluene was added to a 1000mL high-pressure reactor as a solvent base, followed by 100g of piperidine, 0.75g (0.5wt%) of cobalt catalyst, 0.75g of silver oxide, and 0.75g of di(2-pyridinone)oxime (0.5wt%). The mixture was thoroughly mixed, and the air in the reaction system was completely purged with nitrogen. The system was then stirred at 600rpm with temperature control. The initial nitrogen pressure was 2 bar, and the reaction temperature was 40℃. 50g of isobutylene was pumped into the reaction system at a feed rate of 0.5g / min, completing the pumping in approximately 1.67h. The reaction was then maintained at this temperature for another 4h. The conversion rate of the isobutylene was calculated after the reaction was completed.

[0057] The yield was 84.4%, and the product selectivity was 80.7%. The resulting reaction solution was filtered and distilled to remove the catalyst and auxiliaries, yielding crude 1-(2-methylallyl)piperidine. This crude product was then purified by a distillation column to obtain the 1-(2-methylallyl)piperidine product with a purity of 96.4%.

Claims

1. A process for the synthesis of allylic tertiary amines, characterized in that, The allyl tertiary amine compound is obtained by reacting an olefin and an alkyl secondary amine as raw materials under the action of a metal-phosphine complex catalyst, an oxidant and a ketoxime cocatalyst; The olefin is one or more of C4-C10 straight-chain or branched-chain terminal olefin or terpene, and the alkyl secondary amine is one or more of C3-C8 straight-chain / cyclic alkyl secondary amine; The metal precursor in the metal-phosphine complex is selected from one or more of cobalt, iridium, rhodium, platinum, copper and nickel precursor, and the phosphine ligand is selected from one or more of triphenylphosphine, Ph-Phos, CyJohn-Phos, Dave-Phos, BINAP, Bisbi and Dppx; The oxidant is silver salt or oxygen, wherein the silver salt is selected from one or more of silver benzoate, silver oxide, silver nitrate and silver acetate; The cocatalyst is selected from one or more of acetophenone oxime, benzophenone oxime, cyclohexanone oxime, 1-indanone oxime, bis(2-pyridyl) ketone oxime and phenyl-2-pyridyl ketone oxime.

2. The method of claim 1, wherein, The molar ratio of the olefin to the alkyl secondary amine is 0.5-3.

3. The method of claim 1, wherein, The amount of the catalyst is 0.2-5wt% of the total reaction raw materials.

4. The method of claim 1, wherein, The amount of the catalyst is 0.2-2wt% of the total reaction raw materials.

5. The method of claim 1, wherein, The amount of the silver salt is 0.5-5wt% of the total reaction raw materials.

6. The method of claim 1, wherein, The amount of the cocatalyst is 0.1-2wt% of the total reaction raw materials.

7. The method of claim 1, wherein, The amount of the cocatalyst is 0.2-1wt% of the total reaction raw materials.

8. The method according to any one of claims 1 to 7, characterized in that, The reaction temperature is 10-80℃, and the reaction time is 4-24h.

9. The method according to any one of claims 1 to 7, characterized in that, The reaction is carried out in a nitrogen atmosphere, and the initial reaction pressure is 1-10bar.

10. The method according to any one of claims 1 to 7, characterized in that, The reaction is carried out in a nitrogen atmosphere, and the initial reaction pressure is 1-4bar.

11. The method according to any one of claims 1 to 7, characterized in that, The obtained reaction liquid is subjected to catalyst and cocatalyst removal to obtain an allyl tertiary amine crude product, and then the allyl tertiary amine compound is obtained by purification.

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