An N-aryl-N-alkyl-O-allyl hydroxylamine compound and its synthesis method

Abstract

The present invention discloses an N-aryl-N-alkyl-O-allylhydroxylamine compound and its synthesis method. The general structural formula is as follows: The synthesis method includes the following steps: Using cheap and easily available aldehydes or ketones as starting materials, reacting with hydroxylamine hydrochloride to form oximes, and then preparing N-alkylhydroxylamines under the action of a supported metal catalyst; N-alkylhydroxylamines react with (R4-substituted) allyl bromide, etc. in the presence of a weak base to prepare N-alkyl-N-allylhydroxylamines; N-alkyl-N-allylhydroxylamines react with aryl alkyne precursors under the action of an initiator fluoride at room temperature to prepare N-aryl-N-alkyl-O-allylhydroxylamine compounds. The 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 raw material sources, high prices, harsh reaction conditions, and low reaction selectivity in the existing synthesis methods.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing N-aryl-N-alkyl-O-allylhydroxylamine compounds from aldehydes and ketones. Background Art

[0002] N,N-disubstituted-O-allylhydroxylamine compounds are important chemical products and are usually used as antioxidant stabilizers for organic polymer materials (such as polyolefins, polyesters, polyurethanes, and elastomeric polymers) due to their good antioxidant activity. In recent years, studies have shown that N-aryl-N-alkyl-O-allylhydroxylamine compounds are also used in antibacterial and anti-inflammatory preparations in addition to having better antioxidant properties.

[0003] Currently, there are mainly two methods for synthesizing such compounds: (1) The first method is to use allyl halides to undergo nucleophilic substitution reactions with secondary amines to prepare trisubstituted allylamine compounds, and then prepare N-allyl tertiary amine oxides under strong oxidants, and undergo rearrangement reactions under high-temperature conditions to prepare N,N-disubstituted-O-allylhydroxylamine compounds; (2) The second method starts from the corresponding hydroxylamine, usually N,N-disubstituted hydroxylamine, and undergoes nucleophilic substitution reactions with allyl halides under strong bases to prepare N,N-disubstituted-O-allylhydroxylamine compounds.

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

[0005] In view of the defects of the above two synthesis methods, it has high practical value to develop a new synthesis method that is efficient, convenient, has a mild reaction system, and is low in cost. Summary of the Invention

[0006] The purpose of the present invention is to provide a class of N-aryl-N-alkyl-O-allylhydroxylamine compounds and their synthesis methods, which can effectively avoid the use of toxic, harmful, and explosive strong oxidants, and at the same time solve the problems of limited raw material sources, high prices, harsh reaction conditions, and low reaction selectivity in existing synthesis methods.

[0007] To achieve the purpose, the present invention adopts the following technical solutions:

[0008] An N-aryl-N-alkyl-O-allylhydroxylamine compound, the general structural formula thereof is as follows:

[0009]

[0010] In the formula: R 1 is furfurylidene, thiophenemethylene, phenyl, benzyl, naphthyl, etc.; R 2 is hydrogen or methyl; R 3 is hydrogen, fluorine, methyl, methoxy or acetyl; R 4 is hydrogen, methyl, n-pentyl or phenyl.

[0011] The present invention also provides a method for synthesizing the N-aryl-N-alkyl-O-allylhydroxylamine compounds, and the reaction formula is as follows:

[0012]

[0013] The specific steps of the synthesis method are as follows:

[0014] Step 1, add aldehyde or ketone, hydroxylamine hydrochloride, base and a first organic solvent into a round-bottom flask, heat under reflux, track the reaction process by TLC plate, stop the reaction after all the raw materials disappear, cool to room temperature, wash the reaction solution with water twice, combine the aqueous phases and extract with tetrahydrofuran, dry the organic phase over anhydrous sodium sulfate, and concentrate under reduced pressure to remove the solvent to obtain the crude product oxime;

[0015] Step 2, dissolve the crude product oxime obtained in Step 1 in a second organic solvent and place it in a high-pressure reaction kettle. In the presence of a supported metal catalyst, introduce H 2 , heat and react with stirring; after the reaction is completed, cool to room temperature, filter and concentrate under reduced pressure, and separate by silica gel column chromatography to obtain N-alkylhydroxylamine I. The supported metal catalyst can be reused after being washed with water;

[0016] Step 3, dissolve N-alkylhydroxylamine I, base, (R 4 -substituted) allyl bromide in a third organic solvent, react at room temperature, concentrate under reduced pressure after the reaction is completed, and separate by silica gel column chromatography to obtain N-alkyl-N-allylhydroxylamine II;

[0017] Step 4, under nitrogen protection, use N-alkyl-N-allylhydroxylamine II and aryl alkyne precursor as raw materials, fluoride as an initiator, dissolve in a fourth organic solvent and react at room temperature. Through the allyl-type amine-oxide zwitterionic intermediate, [2,3]-σ rearrangement occurs. After the reaction is completed, separate by silica gel column chromatography to obtain N-aryl-N-alkyl-O-allylhydroxylamine compounds III.

[0018] Furthermore, in Step 1: the base is one of potassium hydroxide, sodium hydroxide, potassium carbonate, DBU and triethylamine; the first organic solvent is one of tetrahydrofuran, acetone and acetonitrile; the molar ratio of aldehyde or ketone: hydroxylamine hydrochloride: base is 1: 1-2: 1-3.

[0019] Further, in step 2: the supported metal catalyst is one of Ru-WOx / HZSM-5 and Ru-WOx / HAP; H is introduced 2 to a pressure of 0.4 - 1.2 MPa; the second organic solvent is one of tetrahydrofuran and acetone; the temperature for the heating reaction is 40 - 80 °C and the reaction time is 4 - 8 h; the ratio of oxime to supported metal catalyst is 1 mol: 5 - 15 mg; the eluent V used for silica gel column chromatography separation 石油醚 : V 乙酸乙酯 is 1:1 - 5.

[0020] Further, in step 3: the base is one of potassium hydroxide, sodium hydroxide, potassium carbonate, DBU, and triethylamine; the third organic solvent is one of tetrahydrofuran, acetone, and acetonitrile; the reaction time at room temperature is 4 - 10 h; the molar ratio of N-alkylhydroxylamine I: (R 4 substituted) allyl bromide: base is 1:1 - 2:1 - 3; the eluent V used for silica gel column chromatography separation 石油醚 : V 乙酸乙酯 is 1 - 10:1.

[0021] Further, in step 4: the initiator is one of sodium fluoride, potassium fluoride, cesium fluoride, and tetrabutylammonium fluoride; the arynes precursor is 2-(trimethylsilyl)phenyl trifluoromethanesulfonate or R 2 substituted 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; the fourth organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane, and N,N-dimethylformamide; the reaction time at room temperature is 8 - 14 h; the eluent V used for silica gel column chromatography separation 石油醚 : V 乙酸乙酯 is 10 - 100:1.

[0022] Further, in step 4, the molar ratio of N-alkyl-N-allylhydroxylamine II: arynes precursor: initiator is 1:1 - 2:1 - 3.

[0023] The reaction mechanism of step 4 is as follows:

[0024]

[0025] The arynes precursor A in situ generates arynes under the initiation of fluoride (such as CsF). Then, the nitrogen with stronger nucleophilicity in N-alkyl-N-allylhydroxylamine II attacks the arynes to obtain the aryl anion B. The generated aryl anion extracts the active hydrogen on the adjacent oxygen to generate a similar allyl-type amine-oxygen zwitterionic intermediate C. Finally, a [2,3]-σ rearrangement reaction occurs at room temperature to obtain the desired product N-aryl-N-alkyl-O-allylhydroxylamine III.

[0026] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0027] 1. Starting from cheap and easily available aldehydes or ketones, oximes are prepared with hydroxylamine hydrochloride, and N-alkylhydroxylamines are prepared by hydrogenation reduction using a supported metal catalyst. This method has a high yield, simple post-treatment, is applicable to substrates substituted with various functional groups, and the supported metal catalyst can be recycled multiple times, greatly enhancing the practicality of this method.

[0028] 2. Arynes are in-situ generated from aryne precursors under the action of an initiator fluoride (such as CsF). Due to the high reactivity of aryne, it can react with N-alkyl-N-allylhydroxylamine at room temperature, and undergo a [2,3]-σ rearrangement through an allylic amine-oxide zwitterionic intermediate to synthesize the target compound. This step reacts at room temperature, has good reaction selectivity, few side reactions, a relatively high reaction yield, and a wide range of applicable reaction substrates.

[0029] 3. 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 raw material sources, high prices, harsh reaction conditions, and low reaction selectivity in existing synthesis methods. Description of the Drawings

[0030] Figure 1 HNMR spectrum of N-phenyl-N-benzyl-O-allylhydroxylamine prepared in Example 1 1 HNMR spectrum.

[0031] Figure 2 CNMR spectrum of N-phenyl-N-benzyl-O-allylhydroxylamine prepared in Example 1 13 CNMR spectrum.

[0032] Figure 3 HNMR spectrum of N-phenyl-N-furfurylidene-O-allylhydroxylamine prepared in Example 2 1 HNMR spectrum.

[0033] Figure 4 CNMR spectrum of N-phenyl-N-furfurylidene-O-allylhydroxylamine prepared in Example 2 13 CNMR spectrum.

[0034] Figure 5 HNMR spectrum of N-phenyl-N-thiophenemethylene-O-allylhydroxylamine prepared in Example 3 1 HNMR spectrum.

[0035] Figure 6 CNMR spectrum of N-phenyl-N-thiophenemethylene-O-allylhydroxylamine prepared in Example 3 13 CNMR spectrum.

[0036] Figure 71H NMR spectrum of N-phenyl-N-(2,3-dihydro-1H-indenyl)-O-allylhydroxylamine prepared in Example 4 1 HNMR spectrum

[0037] Figure 8 1H NMR spectrum of N-phenyl-N-(2,3-dihydro-1H-indenyl)-O-allylhydroxylamine prepared in Example 4 13 CNMR spectrum

[0038] Figure 9 1H NMR spectrum of N-phenyl-N-phenethyl-O-(3-buten-2-yl)hydroxylamine prepared in Example 5 1 HNMR spectrum

[0039] Figure 10 1H NMR spectrum of N-phenyl-N-phenethyl-O-(3-buten-2-yl)hydroxylamine prepared in Example 5 13 CNMR spectrum

[0040] Figure 11 1H NMR spectrum of N-(m-tolyl)-N-phenethyl-O-allylhydroxylamine prepared in Example 6 1 HNMR spectrum

[0041] Figure 12 1H NMR spectrum of N-(m-tolyl)-N-phenethyl-O-allylhydroxylamine prepared in Example 6 13 CNMR spectrum Detailed implementation mode

[0042] The following content is only an example and illustration of the concept of the present invention. Those skilled in the art of the present technology can make various modifications or supplements to the described specific implementation cases or use similar methods to replace them. As long as they do not deviate from the concept of the invention or exceed the scope defined by this claim book, they should all fall within the protection scope of the present invention.

[0043] Example 1

[0044] A synthesis method of N-phenyl-N-benzyl-O-allylhydroxylamine:

[0045]

[0046] Step 1: Add benzaldehyde (1.23 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol) and 20 mL of tetrahydrofuran to a 100 mL round-bottom flask, heat under reflux for 3 hours, stop the reaction and cool to room temperature, wash the reaction solution twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain the crude product benzaldehyde oxime.

[0047] Step 2: Coarsely produced benzaldoxime (1.53 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran were added to a high-pressure reactor. Hydrogen was charged to 0.8 MPa, and the mixture was stirred at 60 °C for 5 hours. After the reaction was completed, it was cooled to room temperature. Saturated brine was poured into the reaction solution, and then extracted with ether. The combined organic phases were dried over anhydrous sodium sulfate, and after evaporation, it was separated by silica gel column chromatography (eluent V 石油醚 : V 乙酸乙酯 was 5:1), to obtain N-benzylhydroxylamine I (white solid, 0.95 g, yield 77%).

[0048] Step 3: N-benzylhydroxylamine I (0.62 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol), and allyl bromide (0.73 g, 6 mmol) were dissolved in 20 mL of tetrahydrofuran, and the reaction was carried out at room temperature for 8 hours. After the reaction was completed, it was concentrated under reduced pressure and separated by silica gel column chromatography (eluent V 石油醚 : V 乙酸乙酯 was 1:1), to obtain N-benzyl-N-allylhydroxylamine II (colorless oil, 0.66 g, yield 81%).

[0049] Step 4: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to a reaction flask equipped with a magnetic stirrer. Then, N-benzyl-N-allylhydroxylamine (0.72 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne (1.43 g, 4.8 mmol) were added respectively. The reaction was carried out at room temperature for 12 hours. After cooling to room temperature, it was separated by silica gel column chromatography (eluent V 石油醚 : V 乙酸乙酯 was 40:1) to obtain the target product N-phenyl-N-benzyl-O-allylhydroxylamine III (colorless oil, 0.95 g, yield 99%).

[0050] The product was characterized by nuclear magnetic resonance spectroscopy, and the data are as follows:

[0051] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.41 (d, J = 7.4 Hz, 2H), 7.31 (dt, J = 14.1, 7.2 Hz, 5H), 7.13 (d, J = 8.1 Hz, 2H), 7.00 (t, J = 7.3 Hz, 1H), 5.79 (dq, J = 11.5, 6.1 Hz, 1H), 5.17 (d, J = 17.3 Hz, 1H), 5.10 (d, J = 10.4 Hz, 1H), 4.40 (s, 2H), 4.09 (d, J = 6.0 Hz, 2H); 13 13C NMR (101 MHz, CDCl 3)δ151.76,137.50,133.46,129.30,128.88,128.20,127.37,122.54,118.14,117.12,74.74,63.75.

[0052] Example 2

[0053] A synthetic method of N-phenyl-N-furfurylidene-O-allylhydroxylamine:

[0054]

[0055] Step 1: Add furfural (0.96 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol) and 20 mL of tetrahydrofuran into a 100 mL round-bottom flask, heat under reflux for 3 hours, stop the reaction and cool to room temperature. Wash the reaction solution twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain the crude product furfural oxime.

[0056] Step 2: Take the crude product furfural oxime (1.11 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran and add them into a high-pressure reactor. Charge 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, then extract with ether. Combine the organic phases, dry over anhydrous sodium sulfate, and spin-dry. Then, perform silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 5:1) to obtain N-furfurylidenehydroxylamine I (white solid, 0.95 g, yield 84%).

[0057] Step 3: Dissolve N-furfurylidenehydroxylamine I (0.57 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol), allyl bromide (0.73 g, 6 mmol) in 20 mL of tetrahydrofuran and react at room temperature for 5 hours. After the reaction is completed, concentrate under reduced pressure and separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 1:1) to obtain N-furfurylidene-N-allylhydroxylamine II (colorless oil, 0.67 g, yield 88%).

[0058] Step 4: Under nitrogen protection, add cesium fluoride (1.46 g, 9.6 mmol) to a reaction flask equipped with a magnetic stirrer. Then, add N-furfurylidene-N-allylhydroxylamine II (0.61 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne (1.43 g, 4.8 mmol) respectively and react at room temperature for 12 hours. After cooling to room temperature, perform silica gel column chromatography (eluent V石油醚 : V 乙酸乙酯 (40:1) to obtain the target compound N-phenyl-N-(furan-2-ylmethylene)-O-allylhydroxylamine III (colorless oil, 0.84 g, yield 91%).

[0059] The product was characterized by NMR spectroscopy, and the data are as follows:

[0060] 1 HNMR (400 MHz, CDCl 3 ) δ 7.40 (d, J = 13.5 Hz, 1H), 7.29 (q, J = 7.7 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.05–6.94 (m, 1H), 6.29 (dd, J = 38.9, 9.2 Hz, 2H), 6.00–5.78 (m, 1H), 5.28–5.08 (m, 2H), 4.74 (s, 1H), 4.38 (s, 1H), 4.14 (d, J = 6.0 Hz, 1H), 3.89 (d, J = 6.1 Hz, 1H); 13 CNMR (101 MHz, CDCl 3 ) δ 151.21, 151.01, 150.90, 142.93, 142.01, 133.55, 133.52, 128.86, 122.85, 122.34, 118.30, 118.22, 117.30, 116.82, 110.39, 109.16, 74.75, 67.33, 61.49, 55.88.

[0061] Example 3

[0062] A method for synthesizing N-phenyl-N-(thiophen-2-ylmethylene)-O-allylhydroxylamine:

[0063]

[0064] Step 1: Add 2-thiophenecarboxaldehyde (1.12 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol) and 20 mL of tetrahydrofuran to a 100 mL round-bottom flask, heat under reflux for 3 hours, stop the reaction and cool to room temperature. Wash the reaction mixture twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain the crude product thiophene-2-carboxaldoxime.

[0065] Step 2: The crude product thiophene-2-carboxaldoxime (1.27 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran were added to a high-pressure reactor, and hydrogen was charged to 0.8 MPa, and the reaction was stirred at 60 °C for 5 hours. After the reaction was completed, it was cooled to room temperature, saturated brine was poured into the reaction solution, and then extracted with ether. The combined organic phases were dried over anhydrous sodium sulfate, and after evaporation, it was separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 was), to obtain N-thiophenemethylene hydroxylamine I (white solid, 1.18 g, yield 91%).

[0066] Step 3: N-thiophenemethylene hydroxylamine I (0.65 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol), allyl bromide (0.73 g, 6 mmol) were dissolved in 20 mL of tetrahydrofuran, and the reaction was carried out at room temperature for 7 hours. After the reaction was completed, it was concentrated under reduced pressure and separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 was 5:1), to obtain N-thiophenemethylene-N-allyl hydroxylamine II (colorless oil, 0.73 g, yield 86%).

[0067] Step 4: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to a reaction flask equipped with a magnetic stirrer, and then N-thiophenemethylene-N-allyl hydroxylamine II (0.68 g, 4 mmol), anhydrous acetonitrile (20 mL), benzyne (1.43 g, 4.8 mmol) were added successively, and the reaction was carried out at room temperature for 12 hours. After cooling to room temperature, it was separated by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 was 80:1) to obtain the target product N-phenyl-N-thiophenemethylene-O-allyl hydroxylamine III (colorless oil, 0.87 g, yield 89%).

[0068] The product was characterized by NMR spectroscopy, and the data are as follows:

[0069] 1 HNMR(400MHz,CDCl 3 )δ7.40(d,J=13.5Hz,1H),7.29(q,J=7.7Hz,2H),7.14(d,J=8.0Hz,1H),7.08(d,J=8.0Hz,1H),7.05–6.94(m,1H),6.29(dd,J=38.9,9.2Hz,2H),6.00–5.78(m,1H),5.28–5.08(m,2H),4.74(s,1H),4.38(s,1H),4.14(d,J=6.0Hz,1H),3.89(d,J=6.1Hz,1H); 13CNMR(101MHz,CDCl 3 )δ150.93,139.35,133.49,128.90,127.05,126.40,125.41,122.92,118.26,117.53,74.64,57.80.

[0070] Example 4

[0071] A method for synthesizing N-phenyl-N-(2,3-dihydro-1H-indene)-O-allylhydroxylamine:

[0072]

[0073] Step 1: Add 2-indanone (1.32 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol) and 20 mL of tetrahydrofuran into a 100 mL round-bottom flask, heat under reflux for 3 hours, stop the reaction and cool to room temperature. Wash the reaction solution twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent, obtaining the crude product 2-indanone oxime.

[0074] Step 2: Take the crude product 2-indanone oxime (1.47 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran and add them into a high-pressure reactor. Charge hydrogen to 0.8 MPa and stir the reaction at 60 °C for 5 hours. After the reaction is completed, cool to room temperature, pour saturated brine into the reaction solution, and then extract with ether. Combine the organic phases and dry over anhydrous sodium sulfate. After rotary evaporation, separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 2:1), obtaining N-(2,3-dihydro-1H-indene)hydroxylamine I (gray solid, 1.09 g, yield 73%).

[0075] Step 3: Dissolve N-(2,3-dihydro-1H-indene)hydroxylamine I (0.75 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol) and allyl bromide (0.73 g, 6 mmol) in 20 mL of tetrahydrofuran, and react at room temperature for 5 hours. After the reaction is completed, concentrate under reduced pressure and separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 3:1), obtaining N-(2,3-dihydro-1H-indene)-N-allylhydroxylamine II (gray solid, 0.83 g, yield 88%).

[0076] Step 4: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to a reaction flask equipped with a magnetic stirrer. Then, N-thiophenemethylene-N-allylhydroxylamine II (0.61 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne (1.43 g, 4.8 mmol) were added successively. The reaction was carried out at room temperature for 12 hours. After cooling to room temperature, the product was separated by silica gel column chromatography (eluent V 石油醚 : V 乙酸乙酯 was 80:1) to obtain the target product N-phenyl-N-(2,3-dihydro-1H-indene)-O-allylhydroxylamine III (colorless oil, 1.03 g, yield 97%).

[0077] 1 HNMR (400 MHz, CDCl 3 ) δ 7.32 (t, J = 7.9 Hz, 2H), 7.23–7.19 (m, 2H), 7.18–7.09 (m, 4H), 7.06 (t, J = 7.3 Hz, 1H), 5.90 (ddt, J = 16.5, 10.5, 6.0 Hz, 1H), 5.22 (dd, J = 17.3, 1.5 Hz, 1H), 5.14 (d, J = 10.4 Hz, 1H), 4.37 (p, J = 8.0 Hz, 1H), 4.25 (d, J = 5.9 Hz, 2H), 3.22 (dd, J = 15.6, 8.2 Hz, 2H), 2.94 (dd, J = 15.6, 7.8 Hz, 2H); 13 CNMR (100 MHz, CDCl 3 ) δ 151.56, 142.18, 133.97, 129.45, 126.86, 124.96, 124.13, 119.92, 118.48, 75.00, 69.37, 35.53.

[0078] Example 5

[0079] A method for synthesizing N-phenyl-N-phenethyl-O-(3-buten-2-yl)hydroxylamine:

[0080]

[0081] Step 1: Benzaldehyde (1.20 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol), and 20 mL of tetrahydrofuran were added to a 100 mL round-bottom flask. The mixture was heated under reflux for 3 hours. The reaction was stopped and cooled to room temperature. The reaction solution was washed with water twice, and the combined aqueous phase was extracted with tetrahydrofuran. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent, obtaining the crude product benzaldehyde oxime.

[0082] Step 2: Take crude product phenylacetaldoxime (1.35 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran and add them to a high-pressure reactor. Fill the reactor with hydrogen to 0.8 MPa and stir the reaction at 60 °C for 5 hours. After the reaction is completed, cool it to room temperature, pour saturated brine into the reaction solution, extract it with ether, combine the organic phases, dry them with anhydrous sodium sulfate, and concentrate by rotary evaporation. Then, separate it by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 5:1) to obtain N-phenethylhydroxylamine I (white solid, 1.17 g, yield 85%).

[0083] Step 3: Dissolve N-phenethylhydroxylamine I (0.69 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol), and crotyl bromide (0.81 g, 6 mmol) in 20 mL of tetrahydrofuran and react at room temperature for 8 hours. After the reaction is completed, concentrate under reduced pressure and separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 1:1) to obtain N-phenethyl-N-(2-butenyl)hydroxylamine II (colorless oil, 0.75 g, yield 78%).

[0084] Step 4: Under nitrogen protection, add cesium fluoride (1.46 g, 9.6 mmol) to a reaction flask equipped with a magnetic stirrer. Then, add N-phenethyl-N-(2-butenyl)hydroxylamine II (0.61 g, 4 mmol), anhydrous acetonitrile (20 mL), and benzyne (1.43 g, 4.8 mmol) successively and react at 25 °C for 12 hours. After cooling to room temperature, separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 80:1) to obtain the target product N-phenyl-N-phenethyl-O-(3-buten-2-yl)hydroxylamine III (colorless oil, 0.92 g, yield 86%).

[0085] The product was characterized by NMR spectra, and the data are as follows:

[0086] 1 HNMR(400MHz,CDCl 3 )δ7.28(dd,J=9.4,6.4Hz,4H),7.21–7.16(m,3H),7.10(d,J=7.7Hz,2H),6.96(t,J=7.2Hz,1H),6.00–5.86(m,1H),4.33–4.20(m,1H),3.58–3.45(m,2H),2.93–2.81(m,2H),1.33(d,J=6.3Hz,3H); 13 CNMR(101MHz,CDCl 3)δ151.80,140.06,139.55,128.83,128.77,128.45,126.05,121.96,117.06,116.16,79.26,60.56,32.01,19.47.

[0087] Example 6

[0088] A synthetic method of N-(m-tolyl)-N-phenethyl-O-allylhydroxylamine:

[0089]

[0090] Step 1: Add phenylacetaldehyde (1.20 g, 10 mmol), hydroxylamine hydrochloride (1.04 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol) and 20 mL of tetrahydrofuran into a 100 mL round-bottom flask, heat under reflux for 3 hours, stop the reaction and cool to room temperature. Wash the reaction solution twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent, obtaining the crude product phenylacetaldoxime.

[0091] Step 2: Take the crude product phenylacetaldoxime (1.35 g, 10 mmol), Ru-WOx / HAP catalyst (100 mg) and 20 mL of tetrahydrofuran and add them into a high-pressure reactor. Charge hydrogen to 0.8 MPa and stir and react at 60 °C for 5 hours. After the reaction is completed, cool to room temperature, pour saturated brine into the reaction solution, and then extract with ether. Combine the organic phases and dry over anhydrous sodium sulfate. After rotary evaporation, separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 5:1), obtaining N-phenethylhydroxylamine I (white solid, 1.17 g, yield 85%).

[0092] Step 3: Dissolve N-phenethylhydroxylamine I (0.69 g, 5 mmol), potassium carbonate (1.38 g, 10 mmol), allyl bromide (0.73 g, 6 mmol) in 20 mL of tetrahydrofuran and react at room temperature for 8 hours. After the reaction is completed, concentrate under reduced pressure and separate by silica gel column chromatography (eluent V 石油醚 :V 乙酸乙酯 is 1:1), obtaining N-phenethyl-N-allylhydroxylamine II (colorless oil, 0.74 g, yield 83%).

[0093] Step 4: Under nitrogen protection, cesium fluoride (1.46 g, 9.6 mmol) was added to a reaction flask equipped with a magnetic stir bar. Subsequently, N-phenethyl-N-allylhydroxylamine II (0.61 g, 4 mmol), anhydrous acetonitrile (20 mL), and 3-methylphenyne (1.43 g, 4.8 mmol) were added respectively. The reaction was carried out at 25 °C for 12 hours. After cooling to room temperature, silica gel column chromatography (eluent V 石油醚 : V 乙酸乙酯 was 80:1) was used to separate the target product N-(m-tolyl)-N-phenethyl-O-allylhydroxylamine III (colorless oil, 0.94 g, yield 88%).

[0094] The product was characterized by NMR spectroscopy, and the data are as follows:

[0095] 1 HNMR (400 MHz, CDCl 3 ) δ 7.29 (t, J = 7.4 Hz, 2H), 7.21 (dd, J = 16.1, 7.8 Hz, 4H), 6.89 (d, J = 7.1 Hz, 2H), 6.81 (d, J = 7.4 Hz, 1H), 6.10–5.94 (m, 1H), 5.34 (dd, J = 17.3, 1.1 Hz, 1H), 5.23 (d, J = 10.4 Hz, 1H), 4.30 (d, J = 6.0 Hz, 2H), 3.52 (dd, J = 9.1, 6.5 Hz, 2H), 2.96 (dd, J = 9.1, 6.6 Hz, 2H), 2.33 (s, 3H); 13 CNMR (101 MHz, CDCl 3 ) δ 151.28, 140.01, 138.75, 133.64, 128.80, 128.46, 126.10, 123.20, 118.27, 117.60, 114.04, 74.45, 60.39, 32.60, 21.73.

[0096] Example 7

[0097] 1 g of antioxidant was premixed with 1 kg of polypropylene powder in a plastic bag, and then thoroughly mixed using a high-speed mixer. The mixed materials were represented by different numbers according to the different antioxidants added. Then, extrusion granulation was carried out on a single-screw extruder. The main screw speed was 60 r / min, and the temperatures of each zone of the extruder were 180 °C, 210 °C, 220 °C, and 180 °C respectively. After granulation, it was dried at 80 °C for 4 h, and then injection molding was carried out to prepare samples. The injection molding temperature was 220 °C, the injection molding time was 18 s, the holding pressure was 30 MPa, and the cooling time was 13 s.

[0098] Among them, 0# is the sample without antioxidant, 1# is the sample with commercially available antioxidant 1010, 2# is the sample with N-phenyl-N-benzyl-O-allyl hydroxylamine prepared in Example 1, 3# is the sample with N-phenyl-N-furfurylidene-O-allyl hydroxylamine prepared in Example 2, 4# is the sample with N-phenyl-N-thiophenemethylene-O-allyl hydroxylamine prepared in Example 3, 5# is the sample with N-phenyl-N-(2,3-dihydro-1H-indene)-O-allyl hydroxylamine prepared in Example 4, 6# is the sample with N-phenyl-N-phenethyl-O-(3-buten-2-yl) hydroxylamine prepared in Example 5, and 7# is the sample with N-(m-tolyl)-N-phenethyl-O-allyl hydroxylamine.

[0099] Melt flow rate test: The melt flow rate was tested according to GB / T3682.1-2018. Before the test, nitrogen was passed through, and after heating to 230 °C, it was kept constant for 0.5 h. A 2.16 kg weight was set, and about 4 g of the sample was taken for testing. The sample was cut every 5 seconds, cut 5 times in total, weighed and calculated, and the average value was taken, and the cycle was repeated 5 times. The test results are shown in Table 1.

[0100] Table 1

[0101]

[0102] The relative change in the melt flow rate of polypropylene between the first and fifth extrusions indicates that after adding allyl hydroxylamine antioxidants, the melt flow rate of the test samples is lower than that of the blank sample, indicating that allyl hydroxylamine antioxidants can protect polypropylene from oxidative degradation during high-temperature processing, and the antioxidant effects of the 6 kinds of allyl hydroxylamine are equivalent to those of the commonly used polypropylene antioxidant 1010 in the current market.

[0103] Mechanical property test: The tensile properties of the material were tested according to GB / T1040-1992. The tensile strength and elongation at break of polypropylene were tested using an electronic universal testing machine, and the tensile rate was 50 mm / min. The test results are shown in Table 2.

[0104] Table 2

[0105]

[0106]

[0107] As can be seen from the above table, the tensile strength and elongation at break of pure polypropylene are both small, while the mechanical properties of polypropylene have been improved to varying degrees after adding allyl hydroxylamine antioxidants, and the antioxidant effects are equivalent to those of the commonly used antioxidant 1010.

[0108] The above are only exemplary embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A N -aryl- N -alkyl- O -allylhydroxylamine compound synthesis method, It is characterized in that The reaction formula is as follows: ； In the reaction formula, R 1 is furfurylidene, thiophenemethylene, phenyl, benzyl or naphthyl; R 2 is hydrogen or methyl; R 3 is hydrogen, fluorine, methyl, methoxy or acetyl; R 4 is hydrogen, methyl, n-pentyl or phenyl; The specific steps of the synthesis method are as follows: Step 1: Add aldehyde or ketone, hydroxylamine hydrochloride, base and the first organic solvent into a round-bottom flask, heat under reflux, track the reaction progress by TLC plate monitoring. Stop the reaction after all the raw materials disappear. After cooling to room temperature, wash the reaction solution twice with water, combine the aqueous phases and extract with tetrahydrofuran. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain the crude product oxime; Step 2: Dissolve the crude product oxime obtained in Step 1 in a second organic solvent and place it in a high-pressure reactor. In the presence of a supported metal catalyst, introduce H 2 , and heat the reaction with stirring; after the reaction is completed, cool to room temperature, filter, and then concentrate under reduced pressure. Separate by silica gel column chromatography to obtain N -alkylhydroxylamine I. The supported metal catalyst can be reused after being washed with water; Step 3, dissolve N -alkylhydroxylamine I, a base, and R 4 -substituted allyl bromide in a third organic solvent, react at room temperature, and after the reaction is completed, concentrate under reduced pressure and separate by silica gel column chromatography to obtain N -alkyl- N -allylhydroxylamine II; Step 4, under nitrogen protection, using N -alkyl- N -allylhydroxylamine II and arynes precursor as raw materials, fluoride as initiator, dissolved in the fourth organic solvent and reacted at room temperature, underwent [2,3]-σ rearrangement through an allylic amino-oxy zwitterionic intermediate. After the reaction was completed, it was separated by silica gel column chromatography to obtain N -aryl- N -alkyl- O -allylhydroxylamine compounds III.

2. The synthesis method according to claim 1, It is characterized in that In Step 1: The base is one of potassium hydroxide, sodium hydroxide, potassium carbonate, DBU and triethylamine; the first organic solvent is one of tetrahydrofuran and acetonitrile; the molar ratio of aldehyde or ketone: hydroxylamine hydrochloride: base is 1: 1-2: 1-3.

3. The synthesis method according to claim 1, It is characterized in that In Step 2: the supported metal catalyst is one of Ru-WOx / HZSM-5 and Ru-WOx / HAP; H 2 is introduced until the pressure reaches 0.4 - 1.2 MPa; the second organic solvent is one of tetrahydrofuran and acetone; the temperature for the heating reaction is 40 - 80 °C and the reaction time is 4 - 8 h; Oxime: The ratio of the supported metal catalyst is 1 mol: 5 - 15 mg; the eluent used for silica gel column chromatography V 石油醚 : V 乙酸乙酯 is 1: 1 - 5.

4. The synthesis method according to claim 1, It is characterized in that In Step 3: the base is one of potassium hydroxide, sodium hydroxide, potassium carbonate, DBU and triethylamine; the third organic solvent is one of tetrahydrofuran, acetone and acetonitrile; the reaction time at room temperature is 4 - 10 h; N - Alkylhydroxylamine I: R 4 Substituted allyl bromide: the molar ratio of the base is 1: 1 - 2: 1 - 3; the eluent used for silica gel column chromatography V 石油醚 : V 乙酸乙酯 is 1 - 10:

1.

5. The synthesis method according to claim 1, It is characterized in that In Step 4: the initiator is one of sodium fluoride, potassium fluoride, cesium fluoride, and tetrabutylammonium fluoride; the aryl alkyne precursor is 2-(trimethylsilyl)phenyl trifluoromethanesulfonate or R 3 substituted 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; the fourth organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane, N,N N,N-dimethylformamide; the reaction time at room temperature is 8 - 14 hours; the eluent used for silica gel column chromatography V 石油醚 : V 乙酸乙酯 is 10 - 100:

1.

6. The synthesis method according to claim 1, It is characterized in that: In Step 4, N -alkyl- N -allylhydroxylamine II: aryne precursor: initiator molar ratio is 1:1 - 2:1 - 3.

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