A method for synthesizing N-NO compounds

Abstract

The present invention discloses a method for synthesizing N-NO compounds. This method uses readily available organic amines as starting materials. In the presence of a nitrating agent, the N-NO compounds are reacted in an organic solvent under stirring at 25-100°C to obtain the N-NO compounds. This method has the advantages of readily available and inexpensive raw materials, mild reaction conditions, a simple preparation process, good chemical selectivity, a wide range of substrate applicability, and ease of scale-up. It has great application potential and lays a good foundation for industrial production.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and specifically relates to a synthesis N -NO compounds. Background Art

[0002] Nitrosation is the process of introducing nitroso (-NO) into organic compound molecules. N -NO compounds are present in various foods, cosmetics and natural products ([1] N-Nitroso Compounds : Occurrence and Biological Effects, IARC Scientific Publishers, Lyon, 1982). Due to its unique carcinogenic and mutagenic properties, it has also attracted increasing attention ([2] Chem. Rev., 2002, 102 , 1091-1134). There are many N -NO compounds are used in various treatments, including cancer, cardiovascular disease, central nervous system diseases, and diseases related to immune and physiological disorders. In addition to their important biological significance, N -NO compounds are also valuable intermediates in organic synthesis ([3] Org.Prep.Proced.Int., 1987, 19 , 85-159), for example, the preparation of α-disubstituted hydrazines ([4] J. Am. Chem. Soc., 1951 , 73, 4996–4996; [5] J. Org. Chem, 1958, 23 , 529–531) and meso-ionic-heterocyclic compounds ([6] Tetrahedron, 2010 , 66, 553–568;[7] Chem. Rev., 1964 , 64, 129–147). Recently, it was reported N -NO acts as a traceless directing group in combination with transition metals to activate the inert CH bonds in the aromatic ring. ([8] J. Am. Chem. Soc., 2013, 135 ,468–473;[9] J. Am. Chem. Soc., 2013, 135 ,16625–16631;

[10] Org. Lett., 2013, 15 , 5294–5297;

[11] J. Org. Chem., 2015, 80 , 12588–12593). These C-H activation reactions provide a fruitful approach for constructing a variety of biologically important heterocyclic compounds.

[0003] The traditional method for synthesizing this type of compound is mainly to use sodium nitrite and concentrated inorganic acid (such as HCl, H2SO4) to generate nitrous acid in situ (

[12] Chem. Ber., 1964, 97 , 2713–2714;

[13] Synth.Commun., 2010, 40 , 654–660). Currently, it is also produced in laboratories and factories N -NO compounds. In addition to this traditional reagent, nitrosyl chloride (

[14] J. Chem. Res., Synop., 2000, 420–422 ), nitroso tetrafluoroborate (

[15] Chem. Ber., 1956, 89 , 2374–2377), nitroso crown ether adducts (

[16] J. Org. Chem., 2001, 66 ,3619–3620), Fremy's salt (

[17] J. Chem. Soc., Chem. Commun., 1983, 301–302) and nitrogen oxides (

[18] J. Am. Chem. Soc., 1955, 77 , 6008–6010) (N2O3, N2O4, etc.) are also used to synthesize various N -NO compounds. In the past decade, the use of sodium nitrite with solid acid (

[19] Tetrahedron Lett., 2003, 44 , 3345–3349;

[20] Synlett, 2002, 1621–162418;

[21] J. Appl. Polym. Sci., 2009, 114 , 2134–2138) or nitrogen oxides with different solid supports (

[22] Tetrahedron Lett., 2010, 51 , 2277–2280;

[23] Synth. Commun., 2005, 35 , 1517–1526;

[24] Synthesis, 2003, 1591–1597) and developed various heterogeneous systems. However, most of these methods use strongly acidic conditions, which limits their application in complex syntheses. Recently, the synthesis of nitromethane (CH3NO2) under oxidative conditions (such as IBX or KI / TBHP or [Cu] / O2) has been reported (

[25] Chem. Commun., 2015, 51 , 11638–11641;

[26] J. Org. Chem., 2013, 78 , 11366–11372;

[27] J. Org. Chem., 2012, 77 , 626–631) can be used as an example of an alternative source for the generation of nitroso (NO). This strategy has some inherent problems, such as poor functional group tolerance and low yields, due to the exogenous oxidant and harsh reaction conditions. Due to the limitations of current reagents, commercially available tert-butyl nitrite (TBN) (

[28] Green Chem., 2016, 18 , 2323–2330) has attracted the interest of chemists as a nitration reagent. Unlike inorganic nitrites, TBN does not require strong acid conditions, making the reaction relatively simple. However, TBN is susceptible to light decomposition and air-mediated oxidation at room temperature, requiring low-temperature storage under an inert atmosphere.

[0004] Although the nitrosation strategy has made significant progress, there is still much room for improvement in terms of reaction efficiency, substrate universality and product diversity. Therefore, it is necessary to develop efficient and concise new synthetic methods using simple and readily available raw materials. N -NO compounds remain a hot topic and a difficult issue in the field of nitrosation reactions. Summary of the Invention

[0005] In order to solve the deficiencies in the prior art, the present invention provides a synthetic N The method uses cheap and readily available raw materials, mild reaction conditions, a simple preparation process, good chemical selectivity, a wide range of substrate applicability, and can be scaled up.

[0006] The technical solutions provided by the present invention are as follows:

[0007] A synthetic N A method for producing a NO compound comprising the steps of:

[0008] Under a protective gas atmosphere, organic amine A is used as the starting material, a nitrating agent B is added, and the mixture is stirred in an organic solvent C until the reaction is complete. After the reaction is completed, the reactants are separated to obtain the compound shown in Formula I. N -NO compounds;

[0009] The reaction equation is as follows:

[0010]

[0011] R 1 、R 2 are independent groups or the two form a cyclic group; if R 1 、R 2 are all independent groups, and are selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl and substituted aryl; if R 1 、R 2To form a cyclic group, the cyclic group is selected from cycloalkyl, substituted cycloalkyl, heterocycloalkyl and substituted heterocycloalkyl;

[0012] R 3 is hydrogen, alkyl;

[0013] R 4 is one or more of alkyl, hydroxyl, mercapto, silyl, amino, cyano, nitro, halogen, -COR; wherein R is an alkyl;

[0014] x represents R 4 The number of groups is 0≤x≤3; when x≥2, the two groups may be the same or different.

[0015] Further, R 1 、R 2 are all independent groups, the alkyl group is a C1-C4 alkyl group; the substituent of the substituted alkyl group is , R5, R6 are independently selected from hydrogen, C1-C4 alkyl, R7 is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, furyl, pyridyl, C1-C4 alkenyl, C1-C4 alkylamine, C6-C12 aryl, 、 、 , -COOMe; cycloalkyl is C6-C12 cycloalkyl; aryl is C6-C12 aryl; substituted aryl is -Ar-R8, R8 is selected from halogen and cyano.

[0016] Furthermore, R 1 、R 2 It is a C1-C4 alkyl group, specifically a methyl group, an ethyl group, an isopropyl group or a butyl group.

[0017] Further, R 1 、R 2 Forming a cyclic group, the cycloalkyl group is a C6-C12 cycloalkyl group; the substituted cycloalkyl group is -C-R9 (structural formula), wherein the cycloalkyl group is a C5-C12 cycloalkyl group, and R9 is a cyclohexyl group, a phenyl group, 、-COOMe、 、 ; Heterocycloalkyl is a C5-C7 cycloalkyl containing N, S or O; substituted heterocycloalkyl is -N-R10 (structural formula), wherein heterocycloalkyl is a C5-C7 cycloalkyl, and R10 is methylsulfonyl, benzoyl or phenyl.

[0018] Furthermore, the R 3 In the example, the alkyl group is a C1-C6 alkyl group.

[0019] Furthermore, the R 4 In -COR, the alkyl group is a C1-C6 alkyl group; in -COR, R is a C1-C6 alkyl group.

[0020] Furthermore, the nitrating agent B is 1,4-dinitropyrazole, N -nitropyrazole, 5-methyl-1,3-dinitropyrazole, 4-cyano-1-nitropyrazole, 4-iodo-1-nitropyrazole, 4-methyl-1-nitropyrazole, 1,3-dinitropyrazole.

[0021] Furthermore, the solvent C is methanol, ethanol, isopropanol, tert-butanol, hexafluoroisopropanol, tetrahydrofuran, 2-methyltetrahydrofuran, ether, dimethyl ethyl diether, methyl tert-butyl ether, 1,4-dioxane, 1,3-dioxane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, C 4-12 Saturated alkanes, C 3-12 Fluorinated or chlorinated alkanes, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N , N -dimethylformamide, N , N -Dimethylacetamide, acetone, N -Methylpyrrolidone, acetonitrile, C 3-12 Preferably, solvent D is hexafluoroisopropanol.

[0022] Furthermore, the protective gas is argon or nitrogen.

[0023] Furthermore, the reaction temperature is 25-100°C. Preferably, the reaction temperature is 80 o C.

[0024] Furthermore, the reaction time is 1-72 hours, preferably 16 hours.

[0025] Furthermore, the method for separating the reactants is to concentrate the reaction mixture and purify it by column chromatography. The concentration process can be carried out by methods such as vacuum distillation, for example, by using a rotary evaporator to concentrate under reduced pressure. The purification method can be carried out by column chromatography separation and purification.

[0026] The method of the present invention can efficiently prepare N -NO compound, compared with the prior art, the present invention has the following beneficial effects:

[0027] i) The main raw materials and solvents involved in the present invention are commercial reagents, low-cost, and available in a wide variety. The nitrating reagent is easy to prepare and can be obtained in just one step.

[0028] ii) The reaction conditions of the present invention are simple and do not require acid or additional oxidant;

[0029] iii) The method of the present invention has a wide range of substrate applicability and functional group compatibility;

[0030] iv) The method of the present invention can be prepared in large quantities (gram level) N -NO compounds have great application potential and have laid a good foundation for industrial production. DETAILED DESCRIPTION

[0031] The present invention is further described below by way of examples. It should be noted that the present invention is not limited to the following embodiments.

[0032] Example 1: Preparation of Compound I-1

[0033]

[0034] Under argon atmosphere, add N -Methyl-phenylethylamine (27.0 mg, 0.2 mmol), 1,4-dinitropyrazole (31.6 mg, 0.2 mmol) and hexafluoroisopropanol (1.0 mL) were added and the resulting mixture was stirred at 80 o C for 16 hours. After the reaction, the mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 66% yield). 1 H NMR (400 MHz, CDCl3): δ 7.35 – 7.28 (m, 2.67H), 7.28 – 7.22 (m, 1.38H), 7.23 – 7.14 (m, 2.7H), 4.46 – 4.29 (t, J = 7.4Hz, 2H), 3.83 – 3.77 (t, J = 7.4 Hz, 0.64H), 3.57 (s, 1H), 3.06 (t, J = 7.4 Hz,2H), 3.00 (s, 3H), 2.81 (t, J = 7.4 Hz, 0.65H); 13 C NMR (100 MHz, CDCl3): δ 138.1,137.4, 129.0, 128.9, 128.8, 128.8, 127.1, 127.0, 55.2, 47.3, 39.9, 35.3,32.2, 32.0;HRMS(ESI-TOF):calc'd for C9H 12 N2NaO + [M+Na + ] 187.0842, found187.0847.

[0035] Preparation of compound I-1 under other nitrating reagent conditions

[0036] Under argon atmosphere, add N -Methyl-phenylethylamine (27.0 mg, 0.2 mmol), 4-cyano-1-nitropyrazole (27.6 mg, 0.2 mmol) and hexafluoroisopropanol (1.0 mL) were added and the resulting mixture was heated at 80 o C for 16 hours. After the reaction, the mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 47% yield).

[0037] Under argon atmosphere, add N -Methyl-phenylethylamine (27.0 mg, 0.2 mmol), 4-methyl-1-nitropyrazole (34.2 mg, 0.2 mmol) and hexafluoroisopropanol (1.0 mL) were added and the resulting mixture was stirred at 80 o C for 16 hours. After the reaction, the mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 37% yield).

[0038] Under argon atmosphere, add N -Methyl-phenylethylamine (27.0 mg, 0.2 mmol), 1,3-dinitropyrazole (31.6 mg, 0.2 mmol) and hexafluoroisopropanol (1.0 mL) were added and the resulting mixture was stirred at 80 o C for 16 hours. After the reaction was completed, the mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 20% yield).

[0039] Under argon atmosphere, add N -Methyl-phenylethylamine (27.0 mg, 0.2 mmol), 5-methyl-1,3-dinitropyrazole (34.4 mg, 0.2 mmol) and hexafluoroisopropanol (1.0 mL) were added and the resulting mixture was stirred at 80 o C for 16 hours. After the reaction, the mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 64% yield).

[0040] Example 2: Preparation of Compound I-2

[0041]

[0042] The operation steps are the same as those in Example 1, except that the organic amine used is N -methylbenzylamine (24.2 mg) to give compound I-2 (yellow oily liquid, 64% yield). 1 H NMR (400 MHz, CDCl3): δ 7.57-7.04 (m, 5H), 5.30 (s, 1.35H), 4.80 (s, 0.37H), 3.69 (s, 0.57H), 2.94 (s, 2.58H); 13 C NMR(100 MHz, CDCl3): δ 134.6, 133.9, 129.2, 129.1, 128.7, 128.5, 128.2, 128.1, 57.8, 47.9,38.6, 31.1;HRMS(ESI-TOF):calc'd for C8H 10 N2NaO + [M+Na + ] 173.0685, found173.0690.

[0043] Example 3: Preparation of Compound I-3

[0044]

[0045] The operation steps are the same as those in Example 1, except that the organic amine used is N -benzylisopropylamine (29.8 mg) to give compound I-3 (yellow oily liquid, 95% yield). 1 H NMR (400 MHz, CDCl3): δ 7.34 – 7.22 (m, 3.88H), 7.13 – 7.04 (m, 2.17H), 5.25 (s, 0.33H), 4.94 (p, J = 6.8 Hz, 0.21H), 4.77 (s, 2H), 4.58 (p, J = 6.8 Hz, 1H), 1.42 (d, J = 6.8 Hz, 6H), 1.00 (d, J = 6.7Hz, 1.13H); 13C NMR (100 MHz, CDCl3): δ 136.7, 135.2, 128.9, 128.8, 128.3, 128.0,127.8, 127.7, 55.1, 53.0, 45.7, 45.5, 21.9, 19.3;HRMS(ESI-TOF):calc'd forC 10 H 14 N2NaO + [M+Na + ] 201.0998, found 201.0998.

[0046] Example 4: Preparation of Compound I-4

[0047]

[0048] The operation steps are the same as those in Example 1, except that the organic amine used is N -methyl-2-naphthylmethylamine (34.2 mg) to give compound I-4 (yellow oily liquid, 81% yield). 1 H NMR (400 MHz, CDCl3): 8.13 – 8.08 (m, 0.96H), 7.93 – 7.83 (m, 2.88H), 7.70 – 7.64 (m, 0.44H), 7.57 – 7.49 (m, 3H), 7.49 – 7.46 (m, 0.92H), 7.45 – 7.41 (m, 1.24H), 7.35 – 7.29 (m, 0.43H), 5.78(s, 2H), 5.25 (s, 0.88H), 3.54 (s, 1.32H), 2.93 (s, 3H);

[0049] 13 C NMR (100 MHz, CDCl3): δ134.2, 133.9, 131.8, 131.3, 129.9, 129.8,129.4, 129.1, 129.0, 128.2, 128.0, 127.2, 127.2, 126.5,126.5, 125.4,125.4,123.2,123.1, 55.9, 45.9, 38.2, 30.8;HRMS(ESI-TOF):calc'd for C 12 H 12 N2NaO + [M+Na + ] 223.0842, found 223.0842.

[0050] Example 5: Preparation of Compound I-5

[0051]

[0052] The operation steps were the same as those in Example 1, except that the organic amine used was 1,2,3,4-tetrahydroisoquinoline (26.6 mg), to obtain compound I-5 (yellow oily liquid, 66% yield). 1 H NMR (400 MHz, CDCl3): δ 7.37 – 7.07 (m, 4H), 5.40 (s, 0.55H), 4.84 (s, 1.3H), 4.55 (t, J = 5.9 Hz, 1.3H), 3.89 (t, J = 6.5 Hz, 0.55H), 3.11 (t, J = 5.9 Hz, 1.3H), 2.97 (t, J = 6.5 Hz, 0.55H); 13 C NMR (100 MHz, CDCl3): δ 135.1, 134.0, 132.5, 130.1, 128.8, 128.2, 128.1, 127.4 (d, J = 3.3 Hz), 127.3, 126.3, 51.4, 47.9, 44.6, 40.9, 29.9, 27.5;HRMS(ESI-TOF):calc'd for C9H 10 N2NaO + [M+Na + ] 185.0685, found 185.0684.

[0053] Example 6: Preparation of Compound I-6

[0054]

[0055] The operation steps were the same as those in Example 1, except that the organic amine used was decahydroquinoline (27.8 mg), to obtain compound I-6 (yellow oily liquid, 91% yield). 1 H NMR (400 MHz, CDCl3): δ 5.26 (ddt, J = 13.4, 4.2,2.0 Hz, 1H), 3.33 (td, J = 10.7, 3.4 Hz, 1H), 2.47 (dd, J= 13.4, 3.0 Hz, 1H),2.34 (td, J = 13.0, 3.4 Hz, 1H), 2.05 – 1.84 (m, 2H), 1.76 (tdd, J = 11.2, 5.4,2.7 Hz, 4H), 1.46 – 1.25 (m, 5H), 1.26 – 1.10 (m, 1H); 13 C NMR (100 MHz, CDCl3): δ 67.3, 44.0, 40.8, 32.7, 32.1, 29.0, 25.6, 25.5, 25.0; HRMS (ESI-TOF): calc'dfor C9H 16 N2NaO + [M+Na + ] 191.1155, found 191.1149.

[0056] Example 7: Preparation of Compound I-7

[0057]

[0058] The operation steps were the same as those in Example 1, except that the organic amine used was cycloheximide (19.8 mg), to obtain compound I-7 (yellow oily liquid, 64% yield). 1 H NMR (400 MHz, CDCl3): δ 4.34 – 4.28 (m, 2H), 3.67 – 3.60 (m, 2H), 1.90 – 1.84 (m, 2H), 1.77 (ddt, J = 10.9, 7.8, 4.4 Hz, 2H),1.59 (td, J = 7.8, 7.1, 3.6 Hz, 4H);

[0059] 13 C NMR (100 MHz, CDCl3): δ 52.2, 46.4, 29.5, 28.8, 28.2, 24.7; HRMS (ESI-TOF): calc'd for C6H 12 N2NaO + [M+Na + ] 151.0842, found 151.0840.

[0060] Example 8: Preparation of Compound I-8

[0061]

[0062] The operation steps were the same as those in Example 1, except that the organic amine used was morpholine (17.4 mg), to obtain compound I-8 (yellow oily liquid, 61% yield). 1 H NMR (400 MHz, CDCl3): δ 4.29 (t, J = 5.0 Hz, 2H), 3.87(dt, J = 12.0, 5.1 Hz, 4H), 3.65 (t, J = 5.2 Hz, 2H); 13 C NMR(100 MHz, CDCl3): δ67.4, 66.0, 50.1, 40.5;HRMS(ESI-TOF): calc'd for C4H8N2NaO2 + [M+Na + ] 139.0478,found 139.0474.

[0063] Example 9: Preparation of Compound I-9

[0064]

[0065] The operation steps were the same as those in Example 1, except that the organic compound used was thiomorpholine (20.6 mg), to obtain compound I-9 (yellow oily liquid, 57% yield). 1 H NMR (400 MHz, CDCl3): δ 4.50 (t, J = 5.4 Hz, 2H),4.06 (t, J = 5.4 Hz, 2H), 2.85 (t, J = 5.4 Hz, 2H), 2.58 (t, J = 5.4 Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ 52.6, 41.4, 29.1, 27.4; HRMS (ESI-TOF): calc'd for C4H8N2SNaO + [M+Na + ] 291.0105, found 291.0109.

[0066] Example 10: Preparation of Compound I-10

[0067]

[0068] The operation steps were the same as those in Example 1, except that the organic amine used was 1-(methylsulfonyl)piperazine (32.8 mg), to obtain compound I-10 (yellow solid, 41% yield). 1 H NMR (400 MHz, CDCl3): δ 4.45 – 4.34 (m, 2H), 4.00 – 3.89 (m, 2H), 3.56 – 3.42 (m, 2H), 3.23 (t, J = 5.4 Hz, 2H), 2.83 (s,3H); 13 C NMR (100 MHz, CDCl3): δ 49.4, 46.5, 45.0, 39.1, 36.0; HRMS (ESI-TOF): calc'd for C5H 11 N2SNaO3 + [M+Na + ] 216.0413, found 216.0412.

[0069] Example 11: Preparation of Compound I-11

[0070]

[0071] The operation steps were the same as those in Example 1, except that the organic amine used was bis(2-methoxyethyl)amine (26.6 mg), to obtain compound I-11 (yellow oily liquid, 87% yield). 1 H NMR (400 MHz, CDCl3): δ 4.36 (t, J =5.3 Hz, 2H), 3.85 (t, J = 5.4 Hz, 2H), 3.72 (t, J = 5.3 Hz, 2H), 3.45 (t, J = 5.4Hz, 2H), 3.36 (s, 3H), 3.29 (s, 3H);

[0072] 13 C NMR (100 MHz, CDCl3): δ 71.0, 69.0, 59.0, 58.9, 53.1, 44.8; HRMS (ESI-TOF): calc'd for C6H 14 N2NaO3 + [M+Na + ] 185.0897, found 185.0897.

[0073] Example 12: Preparation of Compound I-12

[0074]

[0075] The operation steps were the same as those in Example 1, except that the organic amine used was dibutylamine (25.8 mg), to obtain compound I-12 (yellow oily liquid, 90% yield). 1 H NMR (400 MHz, CDCl3): δ 4.07 (t, J = 7.3 Hz, 2H),3.58-3.45 (m, 2H), 1.82-1.66 (m, 2H), 1.46 (tdd, J = 7.7, 6.4, 3.5 Hz, 1H),1.38 (q, J = 7.5 Hz, 2H), 1.30 (dt, J = 15.0, 7.5 Hz, 2H), 0.97 (t, J = 7.4 Hz,3H), 0.91 (t, J = 7.3 Hz, 3H); 13 C NMR(100 MHz, CDCl3): δ 52.2, 43.6, 30.5, 28.3,20.6, 19.9, 13.8, 13.8;HRMS(ESI-TOF): calc'd for C8H 18 N2HO + [M+H + ] 159.1492,found 159.1490.

[0076] Example 13: Preparation of Compound I-13

[0077]

[0078] The operation steps were the same as those in Example 1, except that the organic amine used was dibenzylamine (39.5 mg), to obtain compound I-13 (yellow oily liquid, 79% yield). 1 H NMR (400 MHz, CDCl3): δ 7.40 – 7.36 (m, 3H), 7.32 –7.28 (m, 3H), 7.25 (dt, J = 7.0, 1.9 Hz, 2H), 7.07 – 7.03 (m, 2H), 5.21 (s, 2H), 4.67 (s, 2H); 13C NMR(100 MHz, CDCl3): δ 134.6, 134.0, 129.2, 129.0, 128.7,128.6, 128.5, 128.0, 55.1, 45.0;HRMS(ESI-TOF): calc'd for C 14 H 14 N2NaO + [M+Na + ]249.0988, found 249.1000.

[0079] Example 14: Preparation of Compound I-14

[0080]

[0081] The operation steps were the same as those in Example 1, except that the organic amine used was dicyclohexylamine (36.3 mg), to obtain compound I-14 (yellow solid, 83% yield). 1 H NMR (400 MHz, CDCl3): δ 4.86 (tt, J = 11.8, 3.8 Hz,1H), 3.70 (tt, J = 9.8, 4.6 Hz, 1H), 1.97 – 1.83 (m, 6H), 1.78 (dt, J = 13.1, 3.1Hz, 2H), 1.69 (td, J = 13.6, 5.7 Hz, 2H), 1.62 – 1.54 (m, 2H), 1.49 – 1.29 (m,6H), 1.24 (dt, J = 12.7, 3.1 Hz, 1H), 1.20 – 1.11 (m, 1H);

[0082] 13 C NMR(100 MHz, CDCl3): δ 58.7, 52.4, 34.5, 29.5, 26.2, 25.6, 25.5,25.4; HRMS(ESI-TOF): calc'd for C 12 H 22 N2NaO + [M+Na + ] 233.1624, found 233.1625.

[0083] Example 15: Preparation of Compound I-15

[0084]

[0085] The operation steps are the same as those in Example 1, except that the organic amine used is N -methyl- N -furylamine (22.2 mg) to give compound I-15 (yellow oily liquid, 53% yield). 1 H NMR (400 MHz, CDCl3): δ 7.42 (t, J = 1.4Hz, 1H), 7.35 (dd, J = 1.9, 0.9 Hz, 0.43H), 6.38 (d, J = 1.4 Hz, 2H), 6.33 (dd, J =3.3, 1.9 Hz, 0.43H), 6.30 – 6.27 (m, 0.43H), 5.30 (s, 2H), 4.75 (s, 0.86H), 3.73 (s, 1.3H), 3.00 (s, 3H); 13 C NMR(100 MHz, CDCl3): δ 148.2, 147.3, 143.6,142.9, 110.9, 110.8, 110.1, 109.9, 50.4, 40.8, 38.6, 31.0; HRMS(ESI-TOF):calc'd for C6H8N2SHO + [M+H + ] 157.0430, found 157.0426.

[0086] Example 16: Preparation of Compound I-16

[0087]

[0088] The operation steps are the same as those in Example 1, except that the organic amine used is N- methyl- N -(3-methylpyridinyl)amine (24.3 mg) to give compound I-16 (yellow oily liquid, 43% yield). 1 H NMR (400 MHz, CDCl3): δ 8.63 (d, J = 4.9 Hz, 1H), 8.59 (d, J = 2.2 Hz, 1H), 8.55 (d, J = 4.9 Hz, 0.45H), 8.46(s, 0.45H), 7.60 (dd, J= 7.6, 2.1 Hz, 1H), 7.46 (dd, J = 7.7, 2.0 Hz, 0.45H),7.34 (dd, J = 7.9, 4.8 Hz, 1H), 7.26 (q, J = 5.1 Hz, 0.45H), 5.34 (s, 2H), 4.80 (s, 0.9H), 3.75 (s, 1.35H), 2.95 (s, 3H); 13 C NMR(100 MHz, CDCl3): δ 150.4,149.7, 149.6, 149.6, 136.3, 135.9, 130.4, 124.2, 124.0, 55.1, 45.6, 38.7,31.1;HRMS(ESI-TOF): calc'd for C7H9N3NaO + [M+Na + ] 174.0638, found 174.0639.

[0089] Example 17: Preparation of Compound I-17

[0090]

[0091] The operation steps are the same as those in Example 1, except that the organic amine used is N -allylbenzylamine (29.4 mg) to give compound I-17 (yellow oily liquid, 66% yield). 1 H NMR (400 MHz, CDCl3): δ 7.36 – 7.32 (m, 2H), 7.29 – 7.23 (m, 2H), 7.09 – 7.06 (m, 1H), 5.86 (ddt, J = 16.6, 10.2, 6.3 Hz,0.51H), 5.52 (ddt, J = 16.5, 10.2, 6.1 Hz, 0.61H), 5.33 – 5.27 (m, 0.81H), 5.24(s, 1.51H), 5.13 (dd, J = 10.3, 1.3 Hz, 0.63H), 5.00 (dd, J = 17.1, 1.4 Hz,0.61H), 4.75 (s, 1.03H), 4.63 (dt, J= 6.2, 1.4 Hz, 1.07H), 4.04 (dt, J = 6.1,1.5 Hz, 1.22H); 13 C NMR(100 MHz, CDCl3): δ 134.8, 134.2, 131.9, 129.3, 129.2,129.0, 128.7, 128.5 (d, J = 7.0 Hz), 128.0, 120.6, 119.5, 55.4, 54.1, 45.4,45.0;HRMS(ESI-TOF): calc'd for C 10 H 12 N2NaO + [M+Na + ] 199.0842, found 199.0839.

[0092] Example 18: Preparation of Compound I-18

[0093]

[0094] The operation steps are the same as in Example 1, except that 1 H NMR (400 MHz, CDCl3): δ 7.58 – 7.52 (m,2H), 7.48 (dd, J = 8.9, 7.0 Hz, 2H), 7.40 – 7.31 (m, 2H), 3.46 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ 142.5, 129.6, 127.5, 119.4, 31.7; HRMS (ESI-TOF): calc'd forC7H8N2HO + [M+H + ] 137.0709, found 137.0708.

[0095] Example 19: Preparation of Compound I-19

[0096]

[0097] The operation steps are the same as those in Example 1, except that the organic amine used is 4-bromo- N , N -dimethylaniline (40.0 mg) to give compound I-19 (yellow solid, 80% yield). 1 H NMR (400 MHz, CDCl3): δ 7.59 (d,J = 8.8Hz, 2H), 7.43 (d, J = 8.9 Hz, 2H), 3.42 (s, 3H); 13 C NMR(100 MHz, CDCl3): δ 141.5,132.7, 120.8, 120.5, 31.3;HRMS(ESI-TOF): calc'd for C7H7N2BrHO + [M+H + ] 214.9815,found 214.9814.

[0098] Example 20: Preparation of Compound I-20

[0099]

[0100] The operation steps were the same as those in Example 1, except that the organic amine used was 4-dimethylaminobenzonitrile (29.2 mg), to obtain compound I-20 (yellow oily liquid, 75% yield). 1 H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 8.9Hz, 2H), 7.71 (d, J = 8.9 Hz, 2H), 3.44 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ 145.7,133.8, 118.4 (d, J = 5.1 Hz), 110.5, 30.3;HRMS(ESI-TOF): calc'd for C8H7N3HO + [M+H + ] 162.0662, found 162.0659.

[0101] Example 21: Preparation of Compound I-21

[0102]

[0103] The operation steps are the same as those in Example 1, except that the organic amine used is 4-bromo -N- Ethyl -N- Methylaniline (42.8 mg) was added to give compound I-21 (yellow oily liquid, 63% yield). 1 H NMR (400 MHz, CDCl3): δ 7.60 (d, J =8.9 Hz, 1H), 7.43 (d,J = 8.9 Hz, 1H), 4.05 (q, J = 7.1 Hz, 2H), 1.16 (t, J = 7.2Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ 140.6, 132.8, 127.7, 120.9, 39.1, 11.9.

[0104] Example 22: Preparation of Compound I-22

[0105]

[0106] The operation steps were the same as those in Example 1, except that the organic amine used was indoline (23.8 mg), to obtain compound I-22 (yellow oily liquid, 59% yield). 1 H NMR (400 MHz, CDCl3): δ 7.90 – 7.80 (m, 1H), 7.36 –7.31 (m, 2H), 7.25 – 7.21 (m, 1H), 4.19 – 4.12 (m, 2H), 3.25 – 3.18 (m, 2H); 13 C NMR(100 MHz, CDCl3): δ 141.0, 132.2, 128.5, 127.2, 126.3, 112.3, 46.3,26.2; HRMS(ESI-TOF): calc'd for C8H8N2HO + [M+H + ] 149.0704, found 149.0704.

[0107] Example 23: Preparation of Compound I-23

[0108]

[0109] The operation steps were the same as those in Example 1, except that the organic amine used was 1,2,3,4-tetrahydroquinoline (26.6 mg), to obtain compound I-23 (yellow solid, 40% yield). 1 H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.1 Hz,1H), 7.33 – 7.26 (m, 2H), 7.22 (d, J = 4.1 Hz, 1H), 3.90 (t, J= 6.4 Hz, 2H),2.88 – 2.73 (m, 2H), 2.01 (p, J = 6.3 Hz, 2H); 13 C NMR(100 MHz, CDCl3): δ 137.7,129.3, 127.8, 127.0, 126.4, 116.5, 42.6, 27.3, 21.0;HRMS(ESI-TOF): calc'd forC9H0N2HO + [M+H + ] 163.0866, found 163.0866.

[0110] Example 24: Preparation of Compound I-24

[0111]

[0112] The operation steps are the same as those in Example 1, except that the organic amine used is N,N- Dimethylethylenediamine (17.6 mg) and the nitrating agent B were increased to 2.0 equivalents, and the reaction was carried out at 25°C for 16 h to obtain compound I-24 (yellow oily liquid, 62% yield). 1 HNMR (400 MHz, CDCl3): δ 4.54 (s, 6H), 4.28 (t, J = 6.2 Hz, 2.4H), 3.96 (t, J = 6.2Hz, 2.4H), 3.79 (s, 3H), 3.75 (s, 1.3H), 3.70 (s, 1H), 3.07 (s, 6H), 3.04 (s,3H); 13 C NMR(100 MHz, CDCl3): δ 51.3, 49.4, 42.9, 41.5, 40.1, 39.6, 32.4, 31.9; HRMS(ESI-TOF): calc'd for C4H 10 N4NaO2 + [M+Na + ] 169.0696, found 169.0693.

[0113] Example 25: Preparation of Compound I-25

[0114]

[0115] The operation steps were the same as those in Example 1, except that carvedilol (81.3 mg) was used as the organic amine to obtain compound I-25 (yellow oily liquid, 65% yield). 1 H NMR (400 MHz, CDCl3): δ 8.33 (d, J = 7.8 Hz, 0.7H),8.29 (d, J = 7.8 Hz, 1H), 8.15 (d, J = 6.0 Hz, 1.4H), 7.37 (ddd, J = 8.3, 3.9, 1.5Hz, 3H), 7.34 – 7.29 (m, 2H), 7.17 (dddd, J = 9.0, 8.0, 6.5, 1.6 Hz, 2H), 7.06(dd, J = 8.1, 5.4 Hz, 2H), 6.99 – 6.91 (m, 2H), 6.89 (dd, J = 4.7, 2.7 Hz, 2H),6.83 (dt, J = 7.8, 2.1 Hz, 2H), 6.69 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 8.0 Hz,0.7H), 4.77 (ddd, J = 14.8, 10.7, 4.4 Hz, 3H), 4.67 (ddd, J = 14.6, 6.3, 3.7 Hz,1H), 4.55 (dd, J = 14.6, 9.0 Hz, 1H), 4.50 – 4.38 (m, 4H), 4.37 – 4.30 (m, 2H), 4.28 – 4.17 (m, 5H), 4.11 (ddd, J = 12.7, 5.9, 2.9 Hz, 1H), 4.00 (dd, J = 13.7,7.8 Hz, 0.7H), 3.77 (s, 3H), 3.72 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ 155.0, 155.0, 149.6, 148.9, 147.5, 147.4, 141.1, 138.9 (d, J= 2.8 Hz), 126.8, 125.3,125.3, 123.2, 123.1, 122.6, 122.4, 122.1, 121.2, 121.1, 112.0, 114.0, 113.1,112.9, 112.8, 111.9, 111.6, 110.2, 110.2, 104.3, 104.3, 101.4,70.3, 70.1,69.1, 68.8, 68.4, 65.4, 58.3, 55.8, 55.7, 53.5, 49.7, 46.6;

[0116] HRMS(ESI-TOF): calc'd for C 24 H 25 N3HO5 + [M+H + ] 436.1867, found 436.1865.

[0117] Example 26: Preparation of Compound I-26

[0118]

[0119] The operation steps were the same as those in Example 1, except that the organic amine used was troxipicide (58.9 mg), to obtain compound I-26 (white solid, 54% yield). 1 H NMR (400 MHz, CDCl3): δ 6.96 (s, 1H), 6.92 (s, 1H), 6.47 (d, J = 7.5 Hz, 0.5H), 6.34 (d, J = 7.2 Hz, 0.5H), 4.55 (dd, J = 13.1, 4.0 Hz,0.5H), 4.44 – 4.23 (m, 1H), 4.13 (ddd, J = 20.7, 13.0, 5.3 Hz, 2H), 3.85 (d, J =3.9 Hz, 9H), 3.76 – 3.61 (m, 1H), 2.15 – 2.02 (m, 1H), 2.00 – 1.90 (m, 0.5H), 1.89 – 1.67 (m, 1.5H), 1.58 (ddd, J = 9.8, 7.0, 3.8 Hz, 0.5H); 13C NMR (100 MHz, CDCl3): δ 167.2, 167.0, 153.3 (d, J = 2.1 Hz), 141.2 (d, J = 9.2 Hz), 129.6,129.5, 104.7, 104.6, 61.0, 56.5 (d, J = 3.6 Hz), 54.3, 50.3, 46. 7, 46.4, 43.8,39.4, 29.7, 29.6, 23.4, 21.6;HRMS(ESI-TOF): calc'd for C 15 H 21 N3HO5 + [M+H + ]324.1554, found 324.1559.

[0120] Example 27: Preparation of Compound I-27

[0121]

[0122] The operation steps were the same as those in Example 1, except that the organic amine used was vortioxetine (59.7 mg), to obtain compound I-27 (white solid, 57% yield). 1 H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.8 Hz, 1H), 7.17(d, J = 2.0 Hz, 1H), 7.12 – 7.02 (m, 2H), 7.00 (dd, J = 7.9, 1.5 Hz, 1H), 6.92(td, J = 7.6, 1.4 Hz, 1H), 6.56 (dd, J = 7.9, 1.5 Hz, 1H), 4.58 – 4.35 (m, 2H), 4.15 – 3.90 (m, 2H), 3.28 (t, J = 5.1 Hz, 2H), 3.04 (t, J = 5.3 Hz, 2H), 2.37 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0, 142.4 139.7, 136.2, 134.9,132.0, 128.1, 127.5, 126.7, 125.9, 125.5, 120.3, 52.3, 50.8, 50.5, 40.3,21.4, 20.8;HRMS(ESI-TOF): calc'd for C 18 H 21 N3SHO + [M+H + ] 328.1478, found328.1478.

[0123] Example 28: Preparation of Compound I-28

[0124]

[0125] The operation steps were the same as those in Example 1, except that the organic amine used was fluoxetine (61.9 mg), to obtain compound I-28 (colorless oily liquid, 57% yield). 1 H NMR (400 MHz, CDCl3): δ 7.44 (dd, J = 9.0, 3.0 Hz,2.66H), 7.39 – 7.27 (m, 4.06H), 6.88 (dd, J = 9.1, 2.9 Hz, 2.94H), 5.22 (dd, J =8.4, 4.2 Hz, 2.56H), 5.12 (dd, J = 8.5, 4.4 Hz, 1H), 4.41 (dt, J = 14.3, 7.3 Hz,0.33H), 4.30 (ddd, J = 13.8, 7.7, 5.8 Hz, 1H), 3.84 – 3.76 (m, 0.66H), 3.75 (s,1H), 3.07 (s, 3H), 2.45 (dtd, J = 14.0, 8.0, 5.8 Hz, 1H), 2.30 (dtd, J = 14.5,7.4, 4.2 Hz, 1H), 2.19 – 2.04 (m, 0.66H); 13C NMR (150 MHz, CDCl3): δ 160.2,160.1, 140.0, 139.0, 129.2, 129.1, 128.5, 128.4, 127.02 (q, J = 3.7 Hz), 125.9,125.9, 124.4 (d, J = 269.7 Hz), 123.4 (q, J = 32.7 Hz), 78.1, 77.6, 50.6, 42.6,39.7, 37.2, 34.7, 32.0; 19 F NMR (376 MHz, CDCl3): δ -61.64 (d, J = 5.7 Hz);HRMS(ESI-TOF): calc'd for C 17 H 17 N2F3HO2 + [M+H + ] 339.1315, found 339.1314.

[0126] Example 29: Preparation of Compound I-29

[0127]

[0128] The operation steps are the same as those in Example 1, except that the organic amine used is L- Proline methyl ester (25.8 mg) was added to give compound I-29 (yellow oily liquid, 75% yield). 1 H NMR (400 MHz, CDCl3): δ 5.28 (dd, J = 8.2, 3.4Hz, 0.55H), 4.56-4.48 (m,1H), 4.45 (q, J = 6.3, 5.8 Hz, 1H), 4.42-4.32 (m, 1H), 3.79 (s, 1.76H), 3.71 (s, 3H), 3.69-3.58 (m, 1H), 2.33 (tdd, J = 13.1, 7.3, 3.6Hz, 2H), 2.21 (t, J = 6.3 Hz, 1H), 2.14 -1.99 (m, 3H);

[0129] 13C NMR(100 MHz, CDCl3): δ 171.1, 169.3, 62.1, 58.1, 53.1, 52.7, 50.1,45.8, 29.1, 28.0, 23.4, 21.3;HRMS(ESI-TOF): calc'd for C6H 10 N2HO3 + [M+H + ]181.0584, found 181.0580.

[0130] Example 30: Preparation of Compound I-30

[0131]

[0132] The operation steps are the same as those in Example 1, except that the organic amine used is N -Methylalanine methyl ester hydrochloride (38.1 mg), bromide is 2-bromo-3-methyl- N -(2-tert-butyl-4-phenylphenyl)benzamide (30.7 mg) to give compound I-30 (yellow oily liquid, 59% yield). 1 H NMR(400 MHz, CDCl3):5.50 (q, J = 7.4 Hz, 1H), 5.22(q, J = 7.4 Hz, 0.33H), 3.80 (s, 1H), 3.78 (s, 3H), 3.70 (s, 1H), 3.02 (s,3H), 1.68 (d, J = 7.4 Hz, 3H), 1.43 (d, J = 7.4 Hz, 1H); 13 C NMR(150 MHz, CDCl3): δ169.9, 168.6, 59.7, 52.0, 51.8, 49.9, 35.3, 28.6, 14.8, 12.3; HRMS(ESI-TOF):calc'd for C5H 10 N2HO3 + [M+H + ] 147.0764, found 147.0760.

[0133] Example 31: Preparation of Compound I-31

[0134]

[0135] The operation steps are the same as those in Example 1, except that the iodide used isL- Prolyl -L- Phenylephrine -L- Methyl valerate (71.5 mg) was added to give compound I-31 (yellow oily liquid, 40% yield). 1 H NMR (400 MHz, CDCl3): δ 7.32– 7.20 (m, 3H), 7.22 – 7.12 (m, 2H), 6.63 (dd, J = 16.0, 7.8 Hz, 1H), 6.34 (t, J = 9.3 Hz, 1H), 5.14 (dd, J = 8.3, 2.8 Hz, 0.36H), 4.77 – 4.63 (m, 1H), 4.60 (q, J = 7.4 Hz, 0.72H), 4.44 (ddd, J = 8.2, 5.0, 2.5 Hz, 1H), 4.39 (td, J = 6.6, 6.0,2.0 Hz, 0.38H), 4.20 – 4.08 (m, 0.75H), 3.71 (d, J = 2.8 Hz, 3H), 3.57 (dt, J =14.3, 8.5 Hz, 0.46H), 3.45 (ddd, J = 14.1, 7.1, 2.8 Hz, 0.42H), 3.19 – 3.07 (m,1H), 3.09 – 2.95 (m, 1H), 2.35 (dd, J = 6.7, 3.2 Hz, 0.4H), 2.26 (dt, J = 9.6,4.9 Hz, 0.73H), 2.19 – 1.93 (m, 4H), 1.93 – 1.84 (m, 1H), 1.82 – 1.53 (m,2H), 0.88 (dd, J = 6.9, 2.5 Hz, 3.52H), 0.84 (dd, J = 6.9, 3.7 Hz, 4H);

[0136] 13 C NMR (100 MHz, CDCl3): δ 170.9, 169.4 (d, J= 4.8 Hz), 168.6, 166.9,135.5, 135.3, 128.5, 128.5, 127.9, 127.8, 126.3, 126.2, 62.4, 58.7, 56.6,53.9 (d, J = 2.2 Hz), 51.3 (d, J = 5.0 Hz), 49.6, 45.3, 45.0, 36.9 (d, J = 6.0 Hz),30.3 (d, J = 4.9 Hz), 27.5, 26.0, 22.2, 18.0, 16.9 (d, J = 5.0 Hz);HRMS(ESI-TOF):calc'd for C 20 H 28 N4HO5 + [M+H + ] 405.2132, found 405.2128.

[0137] Example 32: Preparation of Compound I-32

[0138]

[0139] The operation steps are the same as those in Example 1, except that the organic amine used is L- Prolyl -L- Phenylalanylglycine methyl ester (38.1 mg), bromide as 2-bromo-3-methyl- N -(2-tert-butyl-4-phenylvinylphenyl)benzamide (66.7 mg) to give compound I-32 (yellow oily liquid, 37% yield). 1 H NMR (400 MHz, CDCl3): δ 7.35 – 7.21 (m, 3.6H), 7.20 – 7.09 (m, 2H), 6.70 (dd, J = 43.8, 8.0 Hz, 1H), 6.51 (dt, J = 35.1,5.4 Hz, 1H), 5.14 (dd, J = 8.3, 2.8 Hz, 0.35H), 4.76 (td, J = 8.2, 6.5 Hz,0.35H), 4.65 (ddd, J= 8.0, 5.1, 2.9 Hz, 1H), 4.46 – 4.30 (m, 0.67H), 4.20 –4.08 (m, 0.67H), 4.07 – 3.98 (m, 1H), 3.98 – 3.89 (m, 1H), 3.73 (s, 3H), 3.55(dt, J = 10.3, 7.0 Hz, 0.34H), 3.42 (ddd, J = 14.4, 8.6, 3.4 Hz, 0.34H), 3.18(ddd, J = 14.1, 6.5, 2.8 Hz, 1H), 3.09 (q, J = 7.3 Hz, 0.64H), 3.00 (ddd, J = 14.0,8.0, 3.4 Hz, 1H), 2.33 (ddd, J = 13.1, 6.7, 3.3 Hz, 0.41H), 2.26 – 2.09 (m,1H), 2.10 – 1.93 (m, 2H), 1.87 (ddq, J = 13.1, 7.4, 3.6 Hz, 0.42H), 1.64 (dddd, J = 15.1, 8.9, 7.5, 4.4 Hz, 0.34H); 13 C NMR(100 MHz, CDCl3):δ 170.8 (d, J = 5.0Hz), 170.1 (d, J = 4.3 Hz), 169.7, 168.0, 136.6, 136.5, 129.5, 129.3, 128.9,128.8, 127.3, 127.2, 63.6, 59.8, 54.7 (d, J = 2.8 Hz), 52.6 (d, J = 4.1 Hz),50.6, 46.3, 46.0, 41.4, 37.9, 37.8, 28.4, 27.0, 23.1, 21.2;HRMS(ESI-TOF):calc’d for C 17 H 22 N4HO5 + [M+H + ] 363.1663, found 363.1656。

[0140] Example 33: Gram-scale preparation of compound I-28

[0141]

[0142] Under argon atmosphere, carvedilol (2.03 g, 5.0 mmol), 1,4-dinitropyrazole (790.0 mg, 5 mmol) and hexafluoroisopropanol (10.0 mL) were added to a dry 50 mL reaction tube equipped with a magnetic stirrer. The resulting mixture was stirred at 80 o C for 16 hours. After the reaction, the mixture was cooled to room temperature, and the solvent was removed by distillation under reduced pressure. The mixture was separated and purified by column chromatography to obtain compound I-1 (yellow oily liquid, 1.48 g, 68% yield).

[0143] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent replacements and improvements made by any technician familiar with this technical field within the technical scope disclosed by the present invention should be included in the scope of protection of the invention.

Claims

1. A synthesis N -NO compound method, characterized in that, The following steps are involved: Under a protective gas atmosphere, organic amine A is used as the starting material, a nitrating agent B is added, and the mixture is stirred in an organic solvent C until the reaction is complete. After the reaction is completed, the reactants are separated to obtain the compound shown in Formula I. N -NO compounds; The reaction equation is as follows: R 1 、R 2 are independent groups or the two groups form a cyclic group; If R 1 、R 2 are all independent groups, and are selected from alkyl, substituted alkyl, cycloalkyl, aryl and substituted aryl; alkyl is C1-C4 alkyl; substituted alkyl is , R5, R6 are independently selected from hydrogen, C1-C4 alkyl, R7 is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, furyl, pyridyl, C1-C4 alkenyl, C6-C12 aryl, 、 、 , -COOMe; cycloalkyl is a C6-C12 cycloalkyl; aryl is a C6-C12 aryl; substituted aryl is -Ar-R8, R8 is selected from halogen, cyano, Ar is a C6-C12 aryl; If R 1 、R 2 To form a cyclic group, the cyclic group is selected from cycloalkyl, substituted cycloalkyl, heterocycloalkyl and substituted heterocycloalkyl; the cycloalkyl is a C6-C12 cycloalkyl; the substituted cycloalkyl structure is -C-R9, wherein C is a C5-C12 cycloalkyl, R9 is a cyclohexyl, phenyl, 、-COOMe、 、 ; Heterocycloalkyl is a C5-C7 heterocycloalkyl containing N, S or O; the structural formula of substituted heterocycloalkyl is -heterocycloalkyl-R10, wherein heterocycloalkyl is a C5-C7 heterocycloalkyl, and R10 is methylsulfonyl, benzoyl or phenyl; R 3 is hydrogen, C1-C6 alkyl; R 4 is one or more of C1-C6 alkyl, nitro, and -COR; wherein R is C1-C6 alkyl; x represents R 4 The number of groups is 0≤x≤3; when x≥2, the two groups can be the same or different; The organic solvent C is hexafluoroisopropanol.

2. The method according to claim 1, wherein: The protective gas is argon or nitrogen.

3. The method according to claim 1, wherein: The reaction temperature is 25-100°C.

4. The method according to claim 1, wherein: The reaction time is 1-72h.

5. The method according to claim 1, wherein: The method for separating the reactants is to concentrate the reaction mixture and purify it by column chromatography.

Images