A method for synthesizing N,N-diaryl-O-allylhydroxylamine compounds from nitroaromatic hydrocarbons

Abstract

The invention discloses a method for synthesizing N, N-diaryl-O-allyl hydroxylamine compounds from nitroaromatics, and its general structural formula is: The synthesis method comprises the following steps: (1) using cheap and readily available nitroaromatics as starting materials, preparing N-aryl hydroxylamines under the action of a loaded metal catalyst; (2) N-aryl hydroxylamines react with allyl methyl carbonate and the like in the presence of a palladium catalyst to prepare N-aryl-N-allyl hydroxylamines; (3) N-aryl-N-allyl hydroxylamines react with aromatic acetylene precursors under the action of an initiator fluoride, and N, N-diaryl-O-allyl hydroxylamine compounds are prepared by room temperature reaction. The invention has the advantages that the use of toxic and harmful, explosive strong oxidants can be effectively avoided, and the problems of limited or expensive raw material sources, harsh reaction conditions, and low reaction selectivity in existing synthesis methods are solved at the same time, and new ideas are provided for the development of N, N-diaryl-O-allyl hydroxylamine compounds.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for synthesizing N,N-diaryl-O-allylhydroxylamine compounds from nitroaromatic hydrocarbons. Background Art

[0002] N,N-disubstituted-O-allylhydroxylamine compounds are an important class of chemical products. Due to their excellent antioxidant activity, they are usually used as antioxidant stabilizers for organic polymer materials (such as polyolefins, polyesters, polyurethanes, and elastomeric polymers).

[0003] At present, there are two main methods for the synthesis of this type of compound: (1) The first method is to use an allyl halide to undergo a nucleophilic substitution reaction with a secondary amine to prepare a trisubstituted allylamine compound, and then prepare an N-allyl tertiary amine nitrogen oxide in the presence of a strong oxidant, which undergoes a rearrangement reaction under high temperature conditions to prepare an N,N-disubstituted-O-allylhydroxylamine compound; (2) The second method is to start with the corresponding hydroxylamine, usually N,N-disubstituted hydroxylamine, and undergo a nucleophilic substitution reaction with an allyl halide in the presence of a strong base to prepare an N,N-disubstituted-O-allylhydroxylamine compound.

[0004] The above two methods have obvious disadvantages: (1) The strong oxidants used in the first method include highly toxic compounds such as SeO2, which limits the scope of application of this method, and the higher reaction temperature causes more side reactions; (2) The number of commercially available N,N-disubstituted hydroxylamines in the second method is small, and the raw materials are relatively expensive. The strongly alkaline reaction system limits the compatibility of functional groups, and synthetic chemists rarely choose this method when synthesizing such compounds.

[0005] In recent years, studies have shown that N,N-diaryl-O-allylhydroxylamine compounds have better antioxidant properties and are also used in antibacterial and anti-inflammatory preparations. However, there are currently no reports on the synthesis of such compounds, especially N,N-asymmetric diaryl-O-allylhydroxylamine compounds.

[0006] In view of the defects of the above two commonly used synthesis methods, it is of great practical value to develop a new synthesis method that is efficient, convenient and low-cost. Summary of the invention

[0007] The object of the present invention is to provide a method for synthesizing N,N-diaryl-O-allylhydroxylamine compounds from nitroaromatic hydrocarbons, which can effectively avoid the use of toxic, harmful and explosive strong oxidants, and solve the problems of limited or expensive raw material sources, harsh reaction conditions and low reaction selectivity in existing synthesis methods.

[0008] In order to achieve the purpose, the present invention adopts the following technical scheme:

[0009] The N,N-diaryl-O-allylhydroxylamine compound of the present invention has the following general structural formula:

[0010]

[0011] In the formula, R1 and R2 are each independently selected from hydrogen, fluorine, methyl, methoxy or acetyl.

[0012] The present invention also provides a method for synthesizing the N,N-diaryl-O-allylhydroxylamine compounds, and the reaction formula thereof is shown below:

[0013]

[0014] The specific steps of the synthesis method are:

[0015] Step 1, dissolving nitroaromatic hydrocarbon in a first organic solvent and placing the mixture in a high-pressure reactor, introducing H2 in the presence of a supported metal catalyst, and heating the mixture under stirring to react; after the reaction is completed, cooling the mixture to room temperature, filtering, concentrating under reduced pressure, and separating the mixture through silica gel column chromatography to obtain N-arylhydroxylamine I;

[0016] Step 2, dissolving N-arylhydroxylamine I, allyl methyl carbonate and palladium catalyst in a second organic solvent, reacting under nitrogen protection, and tracking the reaction progress by TLC spot plate; after the reaction is completed, concentrating under reduced pressure, and separating by silica gel column chromatography to obtain N-aryl-N-allylhydroxylamine II;

[0017] Step 3, under nitrogen protection, using N-aryl-N-allylhydroxylamine II and arylacene precursor as raw materials, fluoride as initiator, dissolved in a third organic solvent and reacted at room temperature, and [2,3]-σ rearrangement occurred through the allylic amine oxygen zwitterion intermediate. After the reaction, separation was performed by silica gel column chromatography to obtain N,N-diaryl-O-allylhydroxylamine compound III.

[0018] Furthermore, the supported metal catalyst in step 1 is one of Ru-WOx / HZSM-5 and Ru-WOx / HAP, preferably Ru-WOx / HAP.

[0019] Further, in step 1: H2 is introduced to a pressure of 0.4-1.2MPa, preferably 0.8MPa; the first organic solvent is tetrahydrofuran or acetone, preferably tetrahydrofuran; the heating reaction temperature is 40-80°C, the reaction time is 4-8h, preferably 60°C for 5 hours; the ratio of nitroaromatic hydrocarbon to supported metal catalyst is 1mol:5-15mg, preferably 1mol:10mg; the eluent V used for silica gel column chromatography separation 石油醚 :V 乙酸乙酯 It is 1 to 10:1, preferably 5:1.

[0020] Further, in step 2: the palladium catalyst is Pd(PPh3)4, PdCl2 or Pd(CH3COO)2, preferably Pd(PPh3)4; the second organic solvent is tetrahydrofuran, acetone or acetonitrile, preferably tetrahydrofuran; the reaction temperature is 20-40°C, the reaction time is 1-3h, preferably 25°C for 2 hours; the eluent V used for silica gel column chromatography separation is 石油醚 :V 乙酸乙酯 It is 5 to 20:1, preferably 10:1.

[0021] Furthermore, in step 2, the molar ratio of the N-arylhydroxylamine I: allyl methyl carbonate: palladium catalyst is 1:1-2:0.01-0.05, preferably 1:1.2:0.01.

[0022] Further, in step 3: the initiator is one of sodium fluoride, potassium fluoride, cesium fluoride and tetrabutylammonium fluoride, preferably cesium fluoride; the aromatic acetylene precursor is 2-(trimethylsilyl)phenyl trifluoromethanesulfonate or R2-substituted 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; the third organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane and N,N-dimethylformamide, preferably acetonitrile; the reaction time at room temperature is 4-12 hours, preferably 6 hours at 40°C; the eluent V used for silica gel column chromatography separation is 石油醚 :V 乙酸乙酯 It is 10 to 100:1, preferably 80:1.

[0023] Furthermore, in step 3, the molar ratio of N-aryl-N-allylhydroxylamine II: aromatic acetylene precursor: initiator is 1:1-2:1-3, preferably 1:1.2:2.4.

[0024] Further, the reaction mechanism of step 3 is as follows:

[0025]

[0026] The aryl yne precursor A generates the aryl yne in situ under the initiation of fluoride (such as CsF), and then the more nucleophilic nitrogen in N-aryl-N-allylhydroxylamine II attacks the aryl yne to obtain the aryl anion B. The generated aryl anion extracts the active hydrogen on the ortho-oxygen to generate a similar allylic amine oxygen zwitterion intermediate C. Finally, a [2,3]-σ rearrangement reaction occurs at room temperature to obtain the expected product N,N-diaryl-O-allylhydroxylamine III.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0028] 1. Starting from cheap and readily available nitroaromatics, N-arylhydroxylamines are prepared by hydrogenation reduction using a supported solid metal catalyst. This method has high yield and simple post-treatment, is applicable to substrates substituted with various functional groups, and the supported metal catalyst can be recycled many times, which greatly improves the practicality of this method.

[0029] 2. The aryl acetylene precursor is in situ generated by an initiator (such as CsF). Due to the high reactivity of aryl acetylene, it can react with N-aryl-N-allylhydroxylamine at room temperature, and undergo [2,3]-σ rearrangement through the allylic amine oxygen zwitterion intermediate to synthesize the target compound. This step reacts at room temperature, has good reaction selectivity, few side reactions, high reaction yield and wide applicability of reaction substrates.

[0030] 3. The present invention synthesizes N,N-asymmetric diaryl-O-allylhydroxylamine compounds for the first time by selecting nitroaromatic hydrocarbons and arylacene precursors containing different substituents, thereby expanding the substrate range of N,N-disubstituted-O-allylhydroxylamine compounds and providing a wider source of materials for the application research of such compounds.

[0031] 4. The synthesis method of the present invention can effectively avoid the use of toxic, harmful and explosive strong oxidants, and at the same time solve the problems of limited or expensive raw material sources, harsh reaction conditions and low reaction selectivity in existing synthesis methods, providing a new idea for the development of N,N-diaryl-O-allylhydroxylamine compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The N,N-diphenyl-O-allylhydroxylamine prepared in Example 1 1 HNMR spectrum.

[0033] Figure 2 The N,N-diphenyl-O-allylhydroxylamine prepared in Example 1 13 CNMR spectrum.

[0034] Figure 3 The N-(4-methoxyphenyl)-N-phenyl-O-allylhydroxylamine prepared in Example 2 1 HNMR spectrum.

[0035] Figure 4 The N-(4-methoxyphenyl)-N-phenyl-O-allylhydroxylamine prepared in Example 2 13 CNMR spectrum. DETAILED DESCRIPTION

[0036] The following contents are merely examples and explanations of the concept of the present invention. The technical personnel in this technical field may make various modifications or additions to the specific implementation cases described or replace them with similar methods. As long as they do not deviate from the concept of the invention or exceed the scope defined by the claims, they should all fall within the protection scope of the present invention.

[0037] Example 1

[0038] A method for synthesizing N,N-diphenyl-O-allylhydroxylamine:

[0039]

[0040] Step 1: Take nitrobenzene (1.23 g, 10 mmol), 100 mg Ru-WOx / HAP catalyst and 20 mL tetrahydrofuran and add them to a high pressure reactor, fill with hydrogen to 0.8 MPa, and stir at 60°C for 5 hours. After the reaction is completed, cool to room temperature, pour saturated brine into the reaction solution, extract with ether, combine the organic phases, dry with anhydrous sodium sulfate, spin dry and separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 The product N-phenylhydroxylamine (yellow solid, 0.92 g, yield 84%) was obtained.

[0041] Step 2: Take N-phenylhydroxylamine (0.55 g, 5 mmol), allyl methyl carbonate (0.70 g, 6 mmol), and tetrakis(triphenylphosphine)palladium (57.8 mg, 0.05 mmol), dissolve in tetrahydrofuran, replace nitrogen three times, stir at room temperature for 2 hours, and stop the reaction. After the reaction is completed, separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 10:1) to give N-phenyl-N-allylhydroxylamine (colorless oil, 0.65 g, yield is 87%).

[0042] Step 3: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to the reaction bottle equipped with a magnet, followed by N-phenyl-N-allylhydroxylamine (0.60 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne precursor (i.e., 2-(trimethylsilyl)phenyl trifluoromethanesulfonate) (1.43 g, 4.8 mmol), respectively. The mixture was reacted at room temperature for 6 hours, cooled to room temperature, and separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 80:1) to give N,N-diphenyl-O-allylhydroxylamine (light yellow oil, 0.80 g, yield 89%).

[0043] The product was characterized by NMR spectrum, and the data are as follows:

[0044] 1 HNMR(400MHz, CDCl3)δ7.31(t,J=7.5Hz,4H),7.20–7.05(m,6H),6.04(dq,J=11.4, 6.0Hz,1H),5.34(d,J=17.2Hz,1H),5.24(d,J=10.4Hz,1H),4.44(d,J=5.9Hz,2H); 13 CNMR (100MHz, CDCl3) δ148.65,133.39,128.88,124.32,120.94,118.80,74.63.

[0045] Example 2

[0046] A method for synthesizing N-(4-methoxyphenyl)-N-phenyl-O-allylhydroxylamine

[0047]

[0048] Step 1: p-Methoxynitrobenzene (1.53 g, 10 mmol), 100 mg Ru-WOx / HAP catalyst and 20 mL tetrahydrofuran were added to a high pressure reactor, hydrogen was introduced to 0.8 MPa, and the mixture was stirred at 60°C for 5 hours. After the reaction was completed, the mixture was cooled to room temperature, saturated brine was poured into the reaction solution, and then extracted with ether. The organic phases were combined and dried over anhydrous sodium sulfate, and separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 5:1), and the product N-methoxyphenylhydroxylamine (yellow solid, 1.10 g, yield 79%) was obtained.

[0049] Step 2: Take N-p-methoxyphenylhydroxylamine (0.70 g, 5 mmol), allyl methyl carbonate (0.70 g, 6 mmol), and tetrakis(triphenylphosphine)palladium (57.8 mg, 0.05 mmol), dissolve in tetrahydrofuran, replace nitrogen three times, stir at room temperature for 2 hours, and stop the reaction. After the reaction is completed, separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 The ratio of the reaction mixture to the reaction mixture was 10:1) to give N-(4-methoxyphenyl)-N-allylhydroxylamine (yellow oil, 0.82 g, yield 92%) with a yield of 92%.

[0050] Step 3: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to the reaction bottle equipped with a magnet, followed by N-methoxyphenyl-N-allylhydroxylamine (0.72 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne precursor (i.e., 2-(trimethylsilyl)phenyl trifluoromethanesulfonate) (1.43 g, 4.8 mmol), respectively. The mixture was reacted at room temperature for 6 hours, cooled to room temperature, and separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 80:1) to give N-(4-methoxyphenyl)-N-phenyl-O-allylhydroxylamine (colorless oil, 1.01 g, yield 99%).

[0051] The product was characterized by NMR spectrum, and the data are as follows:

[0052] 1 HNMR (400MHz, CDCl3) δ7.18–7.09(m,4H),6.87(dd,J=7.2,5.0Hz,2H),6.75(t,J=8.4Hz,3H),5.93(ddt,J=15.4,10. 0,4.9Hz,1H),5.25(dd,J=17.2,1.6Hz,1H),5.15(dd,J=10.3,1.5Hz,1H),4.28(dd,J=3.3,1.6Hz,2H),3.80(s,3H); 13 CNMR (100MHz, CDCl3) δ151.76,137.50,133.46,129.30,128.88,128.20,127.37,122.54,118.14,117.12,74.74,63.75.

[0053] Example 3

[0054] Take 1g of antioxidant and 1kg of polypropylene powder and premix them in a plastic bag, then use a high-speed mixer to fully mix them. The mixture is represented by different numbers according to the different antioxidants added. Then, extrusion granulation is carried out on a single-screw extruder, the main screw speed is 60r / min, and the temperatures of each zone of the extruder are 180℃, 210℃, 220℃ and 180℃ respectively. After granulation, dry at 80℃ for 4h, and perform injection molding. The injection molding temperature is 220℃, the injection molding time is 18s, the holding pressure is 30MPa, and the cooling time is 13s.

[0055] Among them, 0# is a sample without adding antioxidant, 1# is a sample with adding commercially available antioxidant 1010, 2# is a sample with adding N,N-diphenyl-O-allylhydroxylamine prepared in Example 1, and 3# is a sample with adding N-(4-methoxyphenyl)-N-phenyl-O-allylhydroxylamine prepared in Example 2.

[0056] Melt flow rate test: The melt flow rate is tested according to GB / T3682.1-2018. Nitrogen is passed before the test, the temperature is raised to 230℃ and kept constant for 0.5h, a 2.16kg weight is set, and a sample of about 4g is taken for testing. The sample is cut once every 5 seconds, and a total of 5 cuts are weighed and calculated, and the average value is taken, and the cycle is repeated 5 times. The test results are shown in Table 1.

[0057] Table 1

[0058]

[0059] The relative change in the melt flow rate of polypropylene between the first and fifth extrusions shows that after the addition of allylhydroxylamine antioxidants, the melt flow rates of the 2# and 3# test samples are lower than those of the blank samples, indicating that allylhydroxylamine antioxidants can protect polypropylene from oxidative degradation during high-temperature processing, and the antioxidant effects of the two allylhydroxylamines are comparable to the commonly used polypropylene antioxidant 1010 on the market.

[0060] Mechanical properties test: According to GB / T1040-1992, the tensile properties of the material were tested. The tensile strength and elongation at break of polypropylene were tested using an electronic universal testing machine at a tensile rate of 50 mm / min. The test results are shown in Table 2.

[0061] Table 2

[0062]

[0063] As can be seen from the above table, the tensile strength and elongation at break of pure polypropylene are relatively small, while the mechanical properties of polypropylene are improved to varying degrees after adding allylhydroxylamine antioxidant, and the antioxidant effect is comparable to that of the commonly used antioxidant 1010.

[0064] The above are merely exemplary embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing N,N-diaryl-O-allylhydroxylamine compounds, characterized in that: The reaction formula is as follows: In the reaction formula, R1 and R2 are independently selected from hydrogen, fluorine, methyl, methoxy or acetyl; The specific steps of the synthesis method are: Step 1, dissolving nitroaromatic hydrocarbon in a first organic solvent and placing the mixture in a high-pressure reactor, introducing H2 in the presence of a supported metal catalyst Ru-WOx / HAP, and heating the mixture under stirring for reaction; after the reaction is completed, cooling the mixture to room temperature, filtering, concentrating under reduced pressure, and separating the mixture through silica gel column chromatography to obtain N-arylhydroxylamine I; Step 2, dissolving N-arylhydroxylamine I, allyl methyl carbonate and palladium catalyst in a second organic solvent, reacting under nitrogen protection, and tracking the reaction progress by TLC spot plate; after the reaction is completed, concentrating under reduced pressure, and separating by silica gel column chromatography to obtain N-aryl-N-allylhydroxylamine II; Step 3, under nitrogen protection, using N-aryl-N-allylhydroxylamine II and arylacene precursor as raw materials, cesium fluoride as initiator, dissolved in a third organic solvent and reacted at room temperature, and [2,3]-σ rearrangement occurred through the allylic amine oxygen zwitterion intermediate. After the reaction, separation was performed by silica gel column chromatography to obtain N,N-diaryl-O-allylhydroxylamine compound III.

2. The synthesis method according to claim 1, characterized in that In step 1, H2 is introduced to a pressure of 0.4-1.2 MPa; the first organic solvent is tetrahydrofuran or acetone; the heating reaction temperature is 40-80°C and the reaction time is 4-8 hours; the ratio of nitroaromatic hydrocarbon to supported metal catalyst is 1 mol: 5-15 mg; the eluent used for silica gel column chromatography separation is V 石油醚 :V 乙酸乙酯 It is 1 to 10:

1.

3. The synthesis method according to claim 1, characterized in that In step 2: the palladium catalyst is Pd(PPh3)4, PdCl2 or Pd(CH3COO)2; the second organic solvent is tetrahydrofuran, acetone or acetonitrile; the reaction temperature is 20-40°C and the reaction time is 1-3h; the eluent used for silica gel column chromatography is V 石油醚 :V 乙酸乙酯 It is 5 to 20:

1.

4. The synthesis method according to claim 1, characterized in that: In step 2, the molar ratio of the N-arylhydroxylamine I: allyl methyl carbonate: palladium catalyst is 1:1-2:0.01-0.

05.

5. The synthesis method according to claim 1, characterized in that In step 3: the aromatic alkyne precursor is 2-(trimethylsilyl)phenyl trifluoromethanesulfonate or R2-substituted 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; the third organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane and N,N-dimethylformamide; the reaction time at room temperature is 4-12 hours; the eluent used for silica gel column chromatography separation is V 石油醚 :V 乙酸乙酯 It is 10 to 100:

1.

6. The synthesis method according to claim 1, characterized in that: In step 3, the molar ratio of N-aryl-N-allylhydroxylamine II: aromatic acetylene precursor: initiator is 1:1-2:1-3.

Images