A method for preparing hydroxylamine compounds from nitrones without metal catalysts

Abstract

This invention discloses a method for preparing hydroxylamine compounds by reducing nitroketone compounds without a metal catalyst. This method uses benzylsilane as a hydrogen source and toluene as a solvent, requiring no additional metal catalyst. The reduction product is obtained by stirring the reaction at 70–80°C under inert gas protection and a closed system. This invention employs a metal catalyst-free system for the reduction of nitroketone compounds, offering advantages such as low cost, mild reaction conditions, and high selectivity. It avoids the use of special equipment such as hydrogen and autoclaves, as well as excessive sodium borohydride reducing agents.

Description

Technical Field

[0001] This invention belongs to the field of hydrogenation technology of nitrones, specifically relating to a method for the highly selective preparation of hydroxylamine compounds from nitrone compounds without a metal catalyst. Background Technology

[0002] Hydroxylamine and its derivatives play important roles in biological and physiological activities, and are also important structural units of drugs and bioactive compounds. The NO unit contained in the hydroxylamine molecule endows it with unique chemical properties and can serve as an attractive metal binding site in organisms. Therefore, the synthesis of hydroxylamine compounds has attracted widespread attention from chemists. Currently, reports on the synthesis of hydroxylamine compounds mainly focus on the catalytic asymmetric hydrogenation of oxime compounds, the oxidative kinetic resolution of racemic amines, and the asymmetric hydroaminooxylation of conjugated dienes.

[0003] In 1994, Tatsuki Shiota's group first reported the asymmetric synthesis of N,N-disubstituted hydroxylamines via the hydrosilylation reaction of nitrones, using Ru as a catalyst and Ph₂SiH₂ as a hydrogen source, achieving the hydrogenation of nitrones under mild conditions (J. Chem. Soc., Chem. Commun., 1994, 725-726). The catalytic oxidation of secondary amines and the asymmetric hydrosilylation reaction of nitrones obtained through this system opened up a general and efficient strategy for the synthesis of optically active N-hydroxylamines from secondary amines.

[0004] In 2000, Murahashi's group reported a system using Ir as a catalyst and hydrogen as a hydrogen source to achieve the asymmetric hydrogenation of nitrones to obtain optically active N-hydroxylamines (Chem. Commun., 2000, 409-410). This method has low catalyst loading, short reaction time, and mild conditions. Furthermore, this catalytic system yields corresponding N-hydroxylamine compounds, which are important bioactive compounds and amine precursors, exhibiting high enantioselectivity.

[0005] In 2017, Zhang Xingxian's research group reported a magnesium(II) ether-catalyzed Strecker addition reaction of aldehydes and imines with TMSCN, achieving highly chemoselective reduction of nitrone substrates under mild conditions (Synthetic Communications., 2017, 47, 1765–1770). This magnesium-catalyzed Strecker addition reaction is rapid, mild, environmentally friendly, and simple to operate. It also demonstrated that the iodide counterion, the weakly coordinated peripheral ether ligand Mg(II), and the non-coordinated reaction medium are key factors contributing to the unique reactivity of this catalytic system, indicating high application potential.

[0006] In 2022, Zhang's research group developed a method for synthesizing a series of chiral hydroxylamine compounds in the presence of Lewis and Brnsted acids using chiral Ir / Zhaophos complexes as catalysts, achieving yields of up to 95% and enantiomeric efficiency (ee) of up to 96% (Am. Chem. Soc., 2022, 144, 39, 17763-17768). This system also exhibits good substrate extensibility, being compatible with most functional groups, and demonstrates high efficiency and good selectivity. Furthermore, gram-scale experiments retaining yield and enantiomeric selectivity confirmed the synthetic potential of this reaction.

[0007] In 2024, Chen Genqiang's team used TsDPEN-derived cyclopentadienylrhodium(III) as a catalyst, hydrogen as the hydrogen source, and toluene as the solvent to achieve asymmetric hydrogenation and transfer hydrogenation reactions of nitrones under mild conditions, synthesizing a series of chiral hydroxylamine compounds (Angew. Chem. Int. Ed., 2024, e202319662). This system exhibits excellent substrate applicability, is compatible with most functional groups, and consistently achieves excellent yields and high ee values. Furthermore, gram-scale catalytic reactions and subsequent transformations demonstrate the practical value of this method.

[0008] The methods described above have drawbacks, including the need for stoichiometric amounts of catalysts and precious metals, excessively long reaction times, stringent conditions, and complex operations. These drawbacks lead to environmental pollution and economic costs, particularly severe in large-scale industrial production. Therefore, developing a mild and efficient strategy for preparing hydroxylamine compounds is of significant scientific research importance. Summary of the Invention

[0009] The purpose of this invention is to provide a metal-free catalyst system for the highly selective reduction of nitroketone compounds to prepare hydroxylamine compounds in a non-hydrogen atmosphere using benzylsilane as a hydrogen source.

[0010] To achieve the above objectives, the technical solution adopted by the present invention is as follows: adding the nitrone compound of formula I, II, or III and the benzylsilane to toluene, stirring and reacting at 70-80°C under inert gas protection and closed conditions, and separating and purifying the product after the reaction to obtain the hydroxylamine compound of formula I′, II′, or III′.

[0011]

[0012] In formulas I and I′, R1 represents any one of phenyl, halophenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, trifluoromethyl-substituted phenyl, biphenyl, thienyl, naphthyl, and benzofuranyl, and R2 represents any one of hydrogen, methyl, ethyl, and cyclopropyl.

[0013]

[0014] In formulas II and II′, R3 represents any one of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy, and Ar represents any one of phenyl, halophenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, methylthio-substituted phenyl, naphthyl, furanyl, benzofuranyl, styrylyl, and benzodioxane.

[0015]

[0016] In equations III and III′, n represents an integer from 1 to 3.

[0017] In the above preparation method, preferably, the amount of benzylsilane added is 2 to 4 times the molar amount of the nitrone compound.

[0018] In the above preparation method, the stirring reaction time is preferably 20 to 30 hours.

[0019] In the above preparation method, the inert gas is nitrogen.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] This invention reports for the first time a metal-free catalyst system for the reduction of nitrone compounds, expanding the research scope of metal-free catalytic systems. The method uses benzylsilane instead of hydrogen as the hydrogen source, avoiding the need for specialized equipment such as autoclaves, thus improving reaction safety. Furthermore, the post-processing eliminates the need for acid-base hydrolysis, reducing waste generation and lowering costs. The reaction conditions are mild (70–80°C), the operation is simple, and the target product has high selectivity. It also exhibits good compatibility with various functional groups, including halogen, methylthio, methoxy, trifluoromethyl, furanyl, thiophene, naphthyl, and benzofuranyl, making it suitable for a wide range of substrates. In addition, since no metal catalyst is required, there are no metal residues in the product, eliminating the need for additional metal removal steps. The resulting hydroxylamine compounds have high purity, making it particularly suitable for the synthesis of pharmaceutical intermediates with strict requirements on metal residues. Moreover, the reaction system is simple, easily scaled up to gram scale, and has promising prospects for industrial application. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited to these embodiments.

[0023] Example 1

[0024] Synthesize N-methyl-N-1-phenylethylhydroxylamine with the following structural formula.

[0025]

[0026] 49 μL (0.4 mmol) of benzylsilane and 0.0298 g (0.2 mmol) of (E)-N-methyl-1-phenylethyl-1-imine oxide were added to a 25 mL high-pressure reaction tube. The tube was filled and purged three times using a double-row tube. 2.5 mL of toluene was added under a nitrogen stream. After sealing the tube, the reaction was stirred at 70 °C for 24 hours. The reaction was quenched by adding 10 mL of saturated sodium carbonate aqueous solution. The tube was extracted with ethyl acetate (10 mL each time, 3 times). The extracts were combined and dried with anhydrous sodium sulfate. The product was separated by column chromatography using a 2:1 volume ratio of petroleum ether to ethyl acetate as the developing solvent to obtain a white solid N-methyl-N-1-phenylethylhydroxylamine with a yield of 95%.

[0027] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.35-7.19 (m, 5H),3.63 (d, J = 7.3 Hz, 1H), 2.49 (s, 3H), 1.48 (d, J = 6.8 Hz, 3H); 13 C NMR (100MHz, CDCl3): δ = 142.4, 128.4, 127.8, 127.4, 69.3, 45.9, 19.9.

[0028] Example 2

[0029] Synthesize N-methyl-N-(1-(naphthyl-1-yl)ethyl)hydroxylamine with the following structural formula.

[0030]

[0031] In this embodiment, (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with equimolar (Z)-N-methyl-1-(naphth-1-yl)ethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-methyl-N-(1-(naphth-1-yl)ethyl)hydroxylamine with a yield of 93%.

[0032] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 8.28 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.61 (s, 1H), 7.51(dd, J= 18.3, 8.2 Hz, 3H), 4.55 (d, J = 7.0 Hz, 1H), 2.61 (s, 3H), 1.62 (d, J = 5.8 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 139.0, 133.9, 131.2, 128.9, 127.7, 126.0, 125.6, 125.5, 124.7, 123.3, 64.6, 46.1, 19.7.

[0033] Example 3

[0034] Synthesize N-methyl-N-(1-(thiophen-2-yl)ethyl)hydroxylamine with the following structural formula.

[0035]

[0036] In this embodiment, (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with equimolar (E)-N-methyl-1-(thiophen-2-yl)ethyl-1-imine oxide. The reaction was stirred at 80°C for 24 hours, and the other steps were the same as in Example 1, to obtain N-methyl-N-(1-(thiophen-2-yl)ethyl)hydroxylamine with a yield of 60%.

[0037] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.27-7.23 (m, 1H), 7.00-6.91 (m, 2H), 4.13-4.01 (m, 1H), 2.54 (d, J = 9.9 Hz, 3H), 1.55 (dd, J =10.0, 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 144.0, 126.2, 125.4, 124.9, 63.5, 44.8, 19.9.

[0038] Example 4

[0039] Synthesize N-methyl-N-(1-(p-tolyl)ethyl)hydroxylamine with the following structural formula.

[0040]

[0041] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-1-(p-tolyl)ethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-methyl-N-(1-(p-tolyl)ethyl)hydroxylamine with a yield of 63%.

[0042] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.24-7.17 (m, 2H),7.14 (d, J = 7.8 Hz, 2H), 3.63 (s, 1H), 2.50 (s, 3H), 2.35 (d, J = 7.6 Hz, 3H), 1.49 (d, J = 6.9 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 139.5, 137.1, 129.1, 127.7, 69.3, 45.9, 21.1, 20.0.

[0043] Example 5

[0044] Synthesize N-(1-(2-fluorophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0045]

[0046] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(2-fluorophenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(2-fluorophenyl)ethyl)-N-methylhydroxylamine with a yield of 62%.

[0047] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.42 (s, 1H), 7.27-7.20 (m, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.03 (t, J = 8.6 Hz, 1H), 4.10 (s,1H), 2.52 (s, 3H), 1.49 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ =160.5 (d,J = 244.6 Hz), 129.18, 128.8 (d, J = 8.4 Hz), 124.2 (d, J = 2.0Hz), 115.4 (d, J = 22.7 Hz), 60.6, 45.8, 18.5; 19 F NMR (376 MHz, CDCl3) δ = -117.89.

[0048] Example 6

[0049] Synthesize N-(1-(2-chlorophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0050]

[0051] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(2-chlorophenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(2-chlorophenyl)ethyl)-N-methylhydroxylamine with a yield of 80%.

[0052] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.49 (s, 1H), 7.36(dd, J = 7.5, 3.7 Hz, 1H), 7.26 (s, 1H), 7.21-7.14 (m, 1H), 4.31 (s, 1H), 2.55 (s, 3H), 1.43 (dd, J = 6.7, 3.5 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ =139.8, 133.6, 129.5, 128.7, 128.3, 127.0, 63.8, 45.8, 18.7.

[0053] Example 7

[0054] Synthesize N-(1-(4-fluorophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0055]

[0056] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(4-fluorophenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(4-fluorophenyl)ethyl)-N-methylhydroxylamine with a yield of 79%.

[0057] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.27 (q, J = 5.1,3.7 Hz, 2H), 7.05-6.96 (m, 2H), 3.63 (q, J = 6.2 Hz, 1H), 2.49 (s, 3H), 1.44(d, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 162.1 (d, J = 244.3 Hz),137.93, 129.36, 115.2 (d, J =20.6 Hz), 68.34, 45.67, 19.78; 19 F NMR (376 MHz, CDCl3) δ = -114.99.

[0058] Example 8

[0059] Synthesize N-(cyclopropyl(phenyl)methyl)-N-methylhydroxylamine with the following structural formula.

[0060]

[0061] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-cyclopropyl-N-methyl-1-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(cyclopropyl(phenyl)methyl)-N-methylhydroxylamine with a yield of 93%.

[0062] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.32 (d, J= 4.5Hz, 5H), 2.78-2.53 (m, 4H), 1.30-1.16 (m, 1H), 0.76-0.67 (m, 1H), 0.55-0.45(m, 1H), 0.44-0.34 (m, 1H), 0.12-0.01 (m, 1H); 13 C NMR (100 MHz, CDCl3): δ =141.3, 128.3, 128.2, 127.3, 79.2, 45.8, 14.7, 7.6.

[0063] Example 9

[0064] Synthesize N-methyl-N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)hydroxylamine with the following structural formula.

[0065]

[0066] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-imine oxide, and the other steps were the same as in Example 1, to obtain N-methyl-N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)hydroxylamine with a yield of 88%.

[0067] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.18-7.06 (m, 4H),5.17 (s, 1H), 3.59 (d, J = 6.3 Hz, 1H), 3.28 (t, J = 12.6 Hz, 1H), 2.68-2.47(m, 4H), 2.21 (s, 1H), 2.02 (d, J = 11.2 Hz, 1H), 1.88 (s, 1H), 1.70 (t, J =13.2 Hz, 2H), 1.43 (q, J = 11.6 Hz, 1H); 13 C NMR (100 MHz, CDCl3): δ = 142.8, 141.1, 130.2, 130.0, 127.3, 125.7, 75.7, 46.1, 35.4, 30.6, 28.1, 25.7.

[0068] Example 10

[0069] Synthesize N-methyl-N-(1-(4-(trifluoromethyl)phenyl)ethyl)hydroxylamine with the following structural formula.

[0070]

[0071] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-1-(4-trifluoromethylphenyl)ethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-methyl-N-(1-(4-(trifluoromethyl)phenyl)ethyl)hydroxylamine with a yield of 78%.

[0072] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 3.65 (t, J = 1.3 Hz, 3H), 2.43 (t, J = 1.3 Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ = 146.2, 139.6, 131.2 (q, J = 32.8 Hz), 128.1, 126.0 (q, J = 3.6 Hz), 49.05, 20.18; 19 F NMR (376 MHz, CDCl3) δ = -62.85.

[0073] Example 11

[0074] Synthesize N-(1-(4-bromophenyl)propyl)-N-methylhydroxylamine with the following structural formula.

[0075]

[0076] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(4-bromophenyl)-N-methylpropyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(4-bromophenyl)propyl)-N-methylhydroxylamine with a yield of 87%.

[0077] The spectral data of the obtained product are as follows: 1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 3.32 (dd, J = 10.3, 4.2 Hz, 1H), 2.47 (s, 3H), 2.15 (s, 1H), 1.72 (dd, J = 16.7, 8.9 Hz, 1H), 0.70 (t, J = 7.5 Hz, 3H); 13 CNMR (100 MHz, CDCl3): δ = 139.0, 131.4, 130.4, 121.3, 75.5, 46.1, 26.1, 10.6.

[0078] Example 12

[0079] Synthesize N-(1-(3-chlorophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0080]

[0081] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(3-chlorophenyl)-N-methylethyl-1-imine oxide, the reaction temperature was increased to 80°C, and the other steps were the same as in Example 1, to obtain N-(1-(3-chlorophenyl)ethyl)-N-methylhydroxylamine with a yield of 78%.

[0082] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.32 (s, 1H), 7.25(dd, J = 4.8, 1.9 Hz, 2H), 7.19 (d, J = 4.2 Hz, 1H), 3.62 (q, J = 6.6 Hz,1H), 2.52 (s, 3H), 1.44 (d, J = 6.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ =144.5, 134.2, 129.7, 128.0, 127.6, 126.0, 68.7, 45.8, 19.7.

[0083] Example 13

[0084] Synthesize N-(1-(4-methoxyphenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0085]

[0086] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(4-methoxyphenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(4-methoxyphenyl)ethyl)-N-methylhydroxylamine with a yield of 81%.

[0087] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.25-7.19 (m, 2H),6.86 (dd, J = 8.4, 5.9 Hz, 2H), 3.79 (d, J = 5.7 Hz, 3H), 3.64 (s, 1H), 2.48(s, 3H), 1.47 (d, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 158.9, 134.0,128.9, 113.8, 68.5, 55.2, 45.5, 19.9

[0088] Example 14

[0089] Synthesize N-(1-(4-bromophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0090]

[0091] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(4-bromophenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(4-bromophenyl)ethyl)-N-methylhydroxylamine with a yield of 88%.

[0092] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.45 (dd, J = 8.4, 4.8 Hz, 2H), 7.18 (d, J= 7.7 Hz, 2H), 3.60 (q, J = 6.3 Hz, 1H), 2.48 (s,3H), 1.43 (d, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 141.3, 131.5, 129.6, 121.2, 68.5, 45.8, 19.7.

[0093] Example 15

[0094] Synthesize N-(1-([1,1'-biphenyl]-4-yl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0095]

[0096] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-([1,1'-biphenyl]-4-yl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-([1,1'-biphenyl]-4-yl)ethyl)-N-methylhydroxylamine in a yield of 83%.

[0097] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.64-7.56 (m, 4H),7.50-7.34 (m, 5H), 3.76 (d, J = 13.1 Hz, 1H), 2.58 (s, 3H), 1.57 (q, J = 7.5, 6.8 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 141.0, 140.7, 140.5, 128.8, 128.3, 127.2, 127.0, 127.0, 68.7, 45.7, 18.1.

[0098] Example 16

[0099] Synthesize N-(1-(benzofuran-2-yl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0100]

[0101] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(benzofuran-2-yl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(benzofuran-2-yl)ethyl)-N-methylhydroxylamine with a yield of 76%.

[0102] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 5.8 Hz, 1H), 7.48 (d, J = 9.1 Hz, 1H), 7.29-7.19 (m, 2H), 6.64 (s, 1H), 4.03 (q, J =6.8 Hz, 1H), 2.62 (s, 3H), 1.57 (d, J = 6.9 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 157.2, 154.6, 128.1, 124.0, 122.7, 120.8, 111.2, 104.6, 61.7, 44.8, 15.8.

[0103] Example 17

[0104] Synthesize N-(2,3-dihydro-1H-inden-1-yl)-N-methylhydroxylamine with the following structural formula.

[0105]

[0106] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-2,3-dihydro-1H-indene-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(2,3-dihydro-1H-indene-1-yl)-N-methylhydroxylamine with a yield of 76%.

[0107] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.86 (s, 1H), 7.51-7.38 (m, 1H), 7.21 (d, J = 24.6 Hz, 2H), 4.31 (s, 1H), 3.05 (s, 1H), 2.85 (s,1H), 2.56 (d, J= 12.8 Hz, 3H), 2.32 (s, 1H), 2.21-2.05 (m, 1H); 13 C NMR (100MHz, CDCl3): δ = 145.1, 140.8, 128.2, 126.3, 126.1, 124.7, 73.0, 43.7, 30.9, 26.9.

[0108] Example 18

[0109] Synthesize N-methyl-N-(1-(m-tolyl)ethyl)hydroxylamine with the following structural formula.

[0110]

[0111] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-1-(m-tolyl)ethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-methyl-N-(1-(m-tolyl)ethyl)hydroxylamine with a yield of 69%.

[0112] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.22 (t, J = 7.5Hz, 1H), 7.15-7.06 (m, 3H), 3.63 (q, J = 6.8, 5.9 Hz, 1H), 2.52 (s, 3H), 2.35(s, 3H), 1.48 (d, J = 6.5 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 142.2, 138.1, 128.4, 128.3, 124.8, 69.4, 48.0, 21.4, 20.0.

[0113] Example 19

[0114] Synthesize N-(1-(4-chlorophenyl)ethyl)-N-methylhydroxylamine with the following structural formula.

[0115]

[0116] In this embodiment, the (E)-N-methyl-1-phenyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-1-(4-chlorophenyl)-N-methylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-(1-(4-chlorophenyl)ethyl)-N-methylhydroxylamine with a yield of 78%.

[0117] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.28 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 3.61 (q, J = 6.6 Hz, 1H), 2.48 (s, 3H), 1.42(d, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ = 140.8, 133.1, 129.2, 128.6, 68.4, 45.8, 19.7.

[0118] Example 20

[0119] Synthesize N-benzyl-N-phenylhydroxylamine with the following structural formula

[0120]

[0121] In this embodiment, (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with equimolar (Z)-N,1-diphenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-benzyl-N-phenylhydroxylamine with a yield of 87%.

[0122] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.44-7.29 (m, 7H),7.21 (d, J = 8.0 Hz, 2H), 7.04 (q, J = 6.8 Hz, 1H), 5.57 (s, 1H), 4.39 (d, J = 7.6 Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.6, 137.2, 129.1, 128.8, 128.4, 127.6, 122.6, 116.9, 64.3.

[0123] Example 21

[0124] Synthesize N-(4-chlorobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0125]

[0126] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(4-chlorophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(4-chlorobenzyl)-N-phenylhydroxylamine with a yield of 80%.

[0127] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.30 (d, J = 8.0 Hz, 6H), 7.17 (d, J = 8.0 Hz, 2H), 7.04 (t, J = 7.4 Hz, 1H), 5.74 (s, 1H), 4.31(s, 2H); 13 C NMR (100MHz, CDCl3): δ = 152.3, 135.5, 133.4, 130.6, 128.8, 128.5, 122.9, 117.1, 63.8.

[0128] Example 22

[0129] Synthesize N-(4-chlorobenzyl)-N-(4-chlorophenyl)hydroxylamine with the following structural formula.

[0130]

[0131] In this embodiment, (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with equimolar (Z)-N,1-di(4-chlorophenyl)methylimine oxide, and the other steps were the same as in Example 1, to obtain N-(4-chlorobenzyl)-N-(4-chlorophenyl)hydroxylamine with a yield of 69%.

[0132] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.33-7.24 (m, 6H),7.09 (t, J = 7.4 Hz, 2H), 5.62 (s, 1H), 4.29 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 150.9, 135.0, 133.6, 130.5, 128.8, 128.6, 118.4, 114.0, 63.7.

[0133] Example 23

[0134] Synthesize N-(4-bromobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0135]

[0136] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(4-bromophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(4-bromobenzyl)-N-phenylhydroxylamine with a yield of 70%.

[0137] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.43 (d, J = 7.9 Hz, 2H), 7.31 (t, J = 7.7 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.05 (t, J = 7.4 Hz, 1H), 5.89 (s, 1H), 4.28 (s, 2H); 13 C NMR (100MHz, CDCl3): δ = 152.3, 135.9, 131.4, 130.9, 128.8, 123.0, 121.5, 117.2, 63.8.

[0138] Example 24

[0139] Synthesize N-(4-iodobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0140]

[0141] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(4-iodophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(4-iodobenzyl)-N-phenylhydroxylamine with a yield of 69%.

[0142] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 6.0 Hz, 2H), 7.31 (t, J = 7.9 Hz, 2H), 7.14 (dd, J = 19.3, 8.1 Hz, 4H), 7.08-7.00 (m,1H), 5.81 (s, 1H), 4.29 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.3, 137.4, 131.2, 128.8, 122.9, 117.1, 117.0, 93.1, 63.9.

[0143] Example 25

[0144] Synthesize N-(naphthyl-2-ylmethyl)-N-phenylhydroxylamine with the following structural formula.

[0145]

[0146] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(naphthyl-2-yl)-N-phenylmethyleneamine oxide, and the other steps were the same as in Example 1, to obtain N-(naphthyl-2-ylmethyl)-N-phenylhydroxylamine with a yield of 79%.

[0147] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 7.4 Hz, 4H), 7.52 (d, J = 10.8 Hz, 3H), 7.31 (t, J = 7.8 Hz, 2H), 7.23 (d, J = 7.9Hz, 2H), 7.04 (t, J = 6.7 Hz, 1H), 5.87 (s, 1H), 4.52 (s, 2H); 13 C NMR (100MHz, CDCl3): δ = 152.6, 134.6, 133.3, 132.8, 128.8, 128.1, 127.8, 127.6,127.0, 126.1, 125.8, 122.6, 121.7, 117.0, 64.5.

[0148] Example 26

[0149] Synthesize N-benzyl-N-(4-iodophenyl)hydroxylamine with the following structural formula.

[0150]

[0151] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-N-(4-iodophenyl)-1-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-benzyl-N-(4-iodophenyl)hydroxylamine with a yield of 60%.

[0152] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.3Hz, 2H), 7.41-7.29 (m, 5H), 6.95 (d, J = 8.4 Hz, 2H), 5.52 (s, 1H), 4.36 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.3, 137.5, 136.6, 129.1, 128.5, 127.7,118.9, 85.2, 63.9.

[0153] Example 27

[0154] Synthesize N-benzyl-N-(4-bromophenyl)hydroxylamine with the following structural formula.

[0155]

[0156] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-N-(4-bromophenyl)-1-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-benzyl-N-(4-bromophenyl)hydroxylamine with a yield of 80%.

[0157] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.43-7.31 (m, 7H),7.07 (d, J = 8.3 Hz, 2H), 5.47 (s, 1H), 4.36 (s, 2H); 13C NMR (100MHz, CDCl3): δ = 151.6, 136.6, 131.6, 129.1, 128.5, 127.7, 118.6, 115.0, 64.1.

[0158] Example 28

[0159] Synthesize N-cinnamyl-N-phenylhydroxylamine with the following structural formula.

[0160]

[0161] In this embodiment, (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with equimolar (1Z,2E)-N,3-diphenylprop-2-ene-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-cinnamyl-N-phenylhydroxylamine with a yield of 90%.

[0162] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.31 (q, J = 7.1,6.5 Hz, 6H), 7.25-7.21 (m, 2H), 7.04 (t, J = 6.8 Hz, 1H), 6.62 (d, J = 16.0Hz, 1H), 6.49 (s, 1H), 6.50-6.32 (m, 1H), 4.08 (t, J = 5.9 Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.2, 136.6, 134.2, 128.8, 128.5, 127.6, 126.4, 124.4,122.7, 117.1, 62.3.

[0163] Example 29

[0164] Synthesize N-(2-chlorobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0165]

[0166] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(2-chlorophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(2-chlorobenzyl)-N-phenylhydroxylamine with a yield of 84%.

[0167] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.49-7.16 (m, 8H),7.05 (s, 1H), 6.10 (s, 1H), 4.42 (d, J = 14.0 Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.6, 134.5, 131.8, 129.5, 129.0, 128.9, 128.7, 126.6, 122.9, 117.0, 62.5.

[0168] Example 30

[0169] Synthesize N-(3-chlorobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0170]

[0171] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(3-chlorophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(3-chlorobenzyl)-N-phenylhydroxylamine with a yield of 77%.

[0172] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.41 (s, 1H), 7.35-7.28 (m, 2H), 7.25 (s, 3H), 7.18 (d, J = 7.7 Hz, 2H), 7.04 (t, J = 7.4 Hz,1H), 5.78 (s, 1H), 4.31 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ = 152.3, 139.2, 134.2, 129.6, 129.2, 128.8, 127.7, 127.2, 123.0, 117.1, 63.9.

[0173] Example 31

[0174] Synthesize N-(4-methylbenzyl)-N-phenylhydroxylamine with the following structural formula.

[0175]

[0176] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-N-phenyl-1-(p-tolyl)methyleneamine oxide, and the other steps were the same as in Example 1, to obtain N-(4-methylbenzyl)-N-phenylhydroxylamine with a yield of 80%.

[0177] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.29 (dd, J = 20.8, 7.9 Hz, 4H), 7.17 (dd, J = 16.9, 7.6 Hz, 4H), 7.07-6.99 (m, 1H), 5.84 (s,1H), 4.32 (s, 2H), 2.36 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ = 152.5, 137.2, 133.9, 129.2, 129.0, 128.7, 122.6, 117.1, 64.1, 21.1.

[0178] Example 32

[0179] Synthesize N-(benzofuran-2-ylmethyl)-N-phenylhydroxylamine with the following structural formula.

[0180]

[0181] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(benzofuran-2-yl)-N-phenylmethylimine oxide. The reaction was stirred at 80°C for 24 hours, and the other steps were the same as in Example 1, to obtain N-(benzofuran-2-ylmethyl)-N-phenylhydroxylamine with a yield of 88%.

[0182] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.36-7.27 (m, 3H), 7.26-7.19 (m, 3H), 7.04 (t, J = 7.2 Hz, 1H), 6.67 (s, 1H), 5.63 (s, 1H), 4.57 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 153.9, 153.5, 152.0, 128.9, 128.2, 124.2, 122.9, 122.8, 120.9, 116.9, 111.2, 106.0, 57.4.

[0183] Example 33

[0184] Synthesize N-[4-(methylthio)benzyl]-N-phenylhydroxylamine with the following structural formula.

[0185]

[0186] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(4-methylthiophenyl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-[4-(methylthiophenyl)benzyl]-N-phenylhydroxylamine with a yield of 93%.

[0187] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.29 (q, J = 7.8Hz, 4H), 7.22-7.12 (m, 4H), 7.06-6.98 (m, 1H), 5.93 (s, 1H), 4.29 (s, 2H), 2.47 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ = 152.4, 137.6, 133.7, 129.8, 128.7, 126.4, 122.7, 117.1, 63.9, 15.8.

[0188] Example 34

[0189] Synthesize N-[(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)methyl]-N-phenylhydroxylamine with the following structural formula.

[0190]

[0191] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-[(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)methyl]-N-phenylhydroxylamine in a yield of 85%.

[0192] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.33-7.25 (m, 2H),7.21-7.15 (m, 2H), 7.00 (t, J = 6.7 Hz, 1H), 6.91 (d, J = 2.0 Hz, 1H), 6.87-6.76 (m, 2H), 6.02 (s, 1H), 4.24 (s, 2H), 4.21 (d, J = 3.8 Hz, 4H); 13 C NMR (100 MHz, CDCl3): δ = 152.5, 143.2, 142.9, 130.3, 128.7, 122.4, 122.2, 118.0,117.0, 117.0, 64.2, 64.2, 63.6.

[0193] Example 35

[0194] Synthesize N-benzyl-N-(4-methoxyphenyl)hydroxylamine with the following structural formula.

[0195]

[0196] In this embodiment, (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with equimolar (Z)-N-(4-methoxyphenyl)-1-phenylmethylimine oxide, and the amount of phenylsilane was increased to 98 μL (0.8 mmol). The reaction was stirred at 80 °C for 24 hours, and the other steps were the same as in Example 1, to obtain N-benzyl-N-(4-methoxyphenyl)hydroxylamine with a yield of 62%.

[0197] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.40-7.30 (m, 4H),7.29-7.25 (m, 1H), 6.78 (dd, J = 8.9, 2.4 Hz, 2H), 6.64-6.57 (m, 2H), 4.28(s, 2H), 3.73 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ = 152.3, 142.6, 139.8, 128.7, 127.7, 127.3, 115.0, 114.2, 55.9, 49.3.

[0198] Example 36

[0199] Synthesize N-(furan-2-ylmethyl)-N-phenylhydroxylamine with the following structural formula.

[0200]

[0201] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (Z)-1-(furan-2-yl)-N-phenylmethylimine oxide, and the other steps were the same as in Example 1, to obtain N-(furan-2-ylmethyl)-N-phenylhydroxylamine with a yield of 60%.

[0202] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.37 (s, 1H), 7.35-7.25 (m, 2H), 7.22-7.15 (m, 2H), 7.03 (t, J = 7.3 Hz, 1H), 6.32 (dd, J = 3.3, 1.9 Hz, 1H), 6.26 (d, J = 3.2 Hz, 1H), 6.11 (s, 1H), 4.39 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ = 151.9, 150.6, 142.3, 128.7, 123.0, 117.2, 110.3, 109.3, 56.8.

[0203] Example 37

[0204] Synthesize N-(4-fluorobenzyl)-N-phenylhydroxylamine with the following structural formula.

[0205]

[0206] In this embodiment, (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with equimolar (Z)-1-(4-fluorophenyl)-N-phenylmethylimine oxide. The reaction was stirred at 80°C for 24 hours, and the other steps were the same as in Example 1, to obtain N-(4-fluorobenzyl)-N-phenylhydroxylamine with a yield of 60%.

[0207] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.36-7.30 (m, 4H),7.17 (d, J= 8.2 Hz, 2H), 7.01 (q, J = 9.0 Hz, 3H), 5.47 (d, J = 33.1 Hz, 1H), 4.32 (s, 2H); 13 C NMR (101 MHz, CDCl3): δ = 162.3 (d, J = 244.4 Hz), 152.4, 130.9 (d, J = 7.9 Hz), 128.8, 122.8, 117.1, 115.2 (d, J = 21.2 Hz), 63.7, 29.7; 19 F NMR (376 MHz, CDCl3) δ = -114.87.

[0208] Example 38

[0209] Synthesize N-benzyl-N-methylhydroxylamine with the following structural formula.

[0210]

[0211] In this embodiment, the (E)-N-methyl-1-phenylmethylimine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-1-phenylethyl-1-imine oxide, and the other steps were the same as in Example 1, to obtain N-benzyl-N-methylhydroxylamine with a yield of 85%.

[0212] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.31 (s, 5H), 3.72 (s, 2H), 2.56 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ = 137.0, 129.8, 128.3, 127.5, 66.5, 47.6.

[0213] Example 39

[0214] Synthesize N-(4-bromobenzyl)-N-methylhydroxylamine with the following structural formula.

[0215]

[0216] In this embodiment, the (E)-N-methyl-1-phenylethyl-1-imine oxide in Example 1 was replaced with an equimolar (E)-N-methyl-1-(4-bromophenyl)methylimine oxide, and the other steps were the same as in Example 1, to obtain N-(4-bromobenzyl)-N-methylhydroxylamine with a yield of 77%.

[0217] The spectral data of the obtained product are as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.29 (d, J = 8.6 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 3.69 (d, J = 8.7 Hz, 2H), 2.57 (d, J = 8.9 Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ = 135.5, 133.4, 131.0, 128.4, 65.6, 47.8.

Claims

1. A method for preparing hydroxylamine compounds by reducing nitroketone compounds without a metal catalyst, characterized in that: Nitroketone compounds and benzylsilanes of Formula I, II, or III are added to toluene and reacted under inert gas protection and closed conditions at 70–80 °C with stirring. After the reaction is completed, the products are separated and purified to obtain hydroxylamine compounds of Formula I′, II′, or III′. In formulas I and I′, R1 represents any one of phenyl, halophenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, trifluoromethyl-substituted phenyl, biphenyl, thienyl, naphthyl, and benzofuranyl, and R2 represents any one of hydrogen, methyl, ethyl, and cyclopropyl. In formulas II and II′, R3 represents any one of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy, and Ar represents any one of phenyl, halophenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, methylthio-substituted phenyl, naphthyl, furanyl, benzofuranyl, styryl, and benzodioxane. In equations III and III′, n represents an integer from 1 to 3.

2. The method for preparing hydroxylamine compounds by reducing nitroketone compounds without a metal catalyst according to claim 1, characterized in that: The amount of benzylsilane added is 2 to 4 times the molar amount of the nitrone compound.

3. The method for preparing hydroxylamine compounds by reducing nitroketone compounds without a metal catalyst according to claim 1, characterized in that: The stirring reaction takes 20 to 30 hours.

4. The method for preparing hydroxylamine compounds by reducing nitroketone compounds without a metal catalyst according to claim 1, characterized in that: The inert gas is nitrogen.

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