A method for synthesizing a 3-selenocyanato spiro[4.5]trienone derivative

Abstract

This invention discloses a method for synthesizing 3-selenocyanospiro[4.5]trienone derivatives, belonging to the field of organic synthesis. Using readily available N-arylpropynamide compounds as substrates, elemental selenium and trimethylcyanosilane as selenocyaniding reagents, and dimethyl sulfoxide as solvent and oxidant, this invention efficiently prepares 3-selenocyanospiro[4.5]trienone derivatives. The synthesis method of this invention is green, environmentally friendly, and efficient, with good functional group compatibility, a wide range of applicable substrates, inexpensive and readily available raw materials, mild reaction conditions, and simple operation, showing good application potential in industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing a 3-selenocyanospiro[4.5]trienone derivative. Background Technology

[0002] Spiro[4.5]trienones are an important structural unit in medicinal chemistry and are widely found in a variety of natural products. Spiro[4.5]trienone derivatives have a wide range of biological activities, such as antihypertensive, antiviral, antioxidant, antitumor and antibacterial properties. Meanwhile, organoselenium compounds have outstanding importance in almost every aspect of chemistry, and these compounds have wide applications in organic transformation and materials science (Chem. Rev. 2001, 101, 2125; Chem. Rev. 2004,104, 6255; Org. Chem. Front. 2019, 6, 2999; Catal. Sci. Technol. 2019, 9,1073-1091). Existing methods for synthesizing 3-selenocyanospiro[4.5]trienone derivatives mostly use N-(p-methoxyaryl)propynamide and selenocyanate as substrates, which are synthesized via dearomatization reactions. However, this reaction has drawbacks such as pollution from transition metal catalysts or strong oxidants, the need to use pre-synthesized selenocyano precursor compounds, the need for complex steps to synthesize reaction raw materials, and narrow substrate applicability (J. Org. Chem. 2020, 85, 15521–15531; J. Org. Chem. 2022, 87,13089;). Therefore, developing efficient and green methods for preparing 3-selenocyanospiro[4.5]trienone derivatives has important scientific research significance and industrial application value.

[0003] Summary of the Invention

[0004] To address the above problems, this invention provides a method for synthesizing 3-selenocyanospiro[4.5]trienone derivatives. Compared with traditional synthesis methods, this method has mild reaction conditions, requiring only heating; the reaction method is highly efficient and green, avoiding pollution from transition metals and strong oxidants; the operation is simple, all operations can be carried out under air conditions, and it is not sensitive to water and oxygen; the raw materials are readily available, the functional groups are compatible, and the substrates have a wide range of applications.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A method for preparing a 3-selenocyanospiro[4.5]trienone derivative includes the following steps:

[0007] A. Compound 1, elemental selenium 2, cyaniding reagent 3 and solvent are added sequentially to the reaction tube;

[0008] B. The above compounds are stirred and reacted under certain temperature conditions;

[0009] C. After the reaction was completed, the 3-selenocyanospiro[4.5]trienone derivative 4 was obtained by column chromatography purification.

[0010] The reaction equation is as follows:

[0011]

[0012] Among them, R 1 Independently selected from hydrogen atom, phenyl, phenoxy, substituted phenyl, naphthyl, thiophene, halogen, C1-C6 alkyl, C1-C6 alkoxy, with no limitation on the number and position of substituents; X is selected from any one of hydrogen, C1-C6 alkoxy, halogen, and nitro; R 2 Independently selected from any one of C1-C6 alkyl, phenyl, and substituted phenyl groups; R 3 It is independently selected from any one of phenyl, substituted phenyl, naphthyl, and thiophene.

[0013] Among them, R 4 Compound 3 is trimethylsilyl, which acts as a cyaniding agent, providing a cyano group.

[0014] Preferably, X is selected from any one of hydrogen, methoxy, F, and nitro; R 1 Selected from hydrogen, methoxy, F; R 2 Selected from methyl, benzyl, n-propyl, propenyl, n-butyl; R 3 Selected from phenyl, substituted phenyl, naphthyl, and thiophene.

[0015] Preferably, the solvent in step (A) is dimethyl sulfoxide. In some embodiments of the present invention, dimethyl sulfoxide can be used as both a solvent and an oxidizing agent.

[0016] Preferably, in step (A), the molar ratio of compound 1, elemental selenium 2 and compound 3 is 1:(1-10):(1-10); the ratio of compound 1 to solvent is 1 mmol:(6-15) mL.

[0017] Preferably, the reaction temperature in step (B) is 60-140 °C and the reaction time is 12-24 hours.

[0018] Preferably, in step (C), the eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is (20~5):1.

[0019] Beneficial effects of this invention:

[0020] (1) This method uses readily available acetylacetamide and selenium powder as raw materials. Acetylene amide can be prepared from the corresponding aniline by conventional methods in the field, and selenium powder can be purchased directly.

[0021] (2) This method is a universal method and is applicable to a variety of substituted N-arylpropynamide substrates.

[0022] (3) This method can be operated under air conditions, is not sensitive to water and oxygen, has relatively mild reaction conditions, and is simple to operate.

[0023] (4) This method is highly efficient and green, avoiding pollution from transition metal catalysts and strong oxidants.

[0024] (5) This method only requires one pot to prepare 3-selenocyanospiro[4.5]trienone derivatives. It has good functional group compatibility and simple post-processing. It provides a simple synthetic method for the preparation of such key intermediates and has good application potential in scientific research and industrial production. Detailed Implementation

[0025] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0026] Example 1

[0027]

[0028] Compound 1 (0.5 mmol, 117.5 mg), elemental selenium (Se, 1–4 eq., TMSCN, 3–6 eq.), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, volume ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4. The yields under each experimental condition are shown in Table 1.

[0029] Table 1. Yields under different equivalents of elemental selenium powder and TMSCN.

[0030] serial number Se (eq.) TMSCN (eq.) Yield (%) 1 2 4 49 2 4 4 48 3 1 4 39 4 2 3 41 5 2 6 47

[0031] Using compound 1, elemental selenium, and the cyaniding reagent TMSCN as substrates, the equivalence of the reactants was screened. The results showed that when the equivalence ratio of compound 1: elemental selenium: TMSCN was 1:2:4, the yield of product 4 was 49% (No. 1); when the equivalence ratio changed to 1:4:4, the yield of product 4 was 48%, showing no significant increase (No. 2); when the equivalence ratio was 1:1:4, the yield of product 4 decreased to 39% (No. 3); when the equivalence ratio was 1:2:3, the yield of product 4 decreased to 41% (No. 4); and when the equivalence ratio was 1:1:6, the yield of product 4 was 47%, showing no significant increase (No. 5).

[0032] That is, compound 1 (0.5 mmol, 117.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL). The reaction was stirred at 80 °C for 12 hours. After separation and purification, 3-selenocyanospiro[4.5]trienone derivative 4 was obtained as a yellow solid with a yield of 49%. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.41–7.31 (m, 3H), 7.17–7.15 (m, 2H), 6.52–6.46 (m, 2H), 6.45–6.40 (m, 2H), 2.88 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.3,166.0, 157.7, 143.2, 133.7, 130.8, 129.5, 128.9, 127.6, 122.1, 97.0, 69.6,26.6. HRMS (ESI) m / z: Calcd for C 17 H 13 N₂O₂Se (M + H) + 357.0137; Found 357.0137.

[0033] Example 2

[0034]

[0035] Compound 1 (0.5 mmol, 155.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a white solid, in 75% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.36–7.26 (m, 3H), 7.21–7.14 (m, 5H), 7.09–7.04 (m, 2H), 6.29 (d, J = 10.1 Hz,2H), 6.19 (d, J = 10.1 Hz, 2H), 4.51 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ183.5, 166.2, 158.0, 143.3, 136.5, 132.8, 130.7, 129.3, 128.8, 128.7, 128.5,128.0, 127.6, 122.1, 97.0, 70.0, 45.3. HRMS (ESI) m / z: Calcd for C 23 H 17 N₂O₂Se(M + H) + 433.0450; Found 433.0452.

[0036] Example 3

[0037]

[0038] Compound 1 (0.5 mmol, 131.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow oily liquid, in 48% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ7.52–7.37 (m, 3H), 7.24–7.15 (m, 2H), 6.59 (d, J = 10.1 Hz, 2H), 6.46 (d, J =10.0 Hz, 2H), 3.34–3.22 (m, 2H), 1.72–1.58 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.5, 166.2, 157.3, 157.3, 143.6, 133.1, 130.7,129.5, 128.8, 127.7, 122.5, 96.9, 70.0, 43.6, 22.8, 11.3. HRMS (ESI) m / z:Calcd for C 19 H 17 N₂O₂Se (M + H) + 385.0450; Found 385.0457.

[0039] Example 4

[0040]

[0041] Compound 1 (0.5 mmol, 138.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow oily liquid, in 56% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.42–7.31 (m, 3H), 7.15–7.09 (m, 2H), 6.51 (d, J = 10.1 Hz, 2H), 6.39 (d, J =10.1 Hz, 2H), 3.25 (t, J = 7.4 Hz, 2H), 1.58–1.47 (m, 2H), 1.30–1.20 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ HRMS (ESI) m / z: calcd for C 20 H 19 N₂O₂Se (M + H) + 399.0606, found 399.0606.

[0042] Example 5

[0043]

[0044] Compound 1 (0.5 mmol, 110.0 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow oily liquid, in 50% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ7.49–7.38 (m, 3H), 7.24–7.16 (m, 2H), 6.55 (d, J =10.1 Hz, 2H), 6.45 (d, J =10.1 Hz, 2H), 5.86–5.76 (m, 1H), 5.20–5.10 (m, 2H), 4.00 (d, J = 10.1 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 183.6, 166.0, 157.9, 143.4, 133.27, 132.3,130.9, 129.4, 128.9, 127.7, 122.3, 119.5, 96.8, 70.0, 44.2. HRMS (ESI) m / z:calcd for C 19 H 15 N₂O₂Se (M + H) + 383.0293, found 383.0295.

[0045] Example 6

[0046]

[0047] Compound 1 (0.5 mmol, 132.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 74% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.17(d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.46 (s, 4H), 3.75 (s, 3H), 2.86 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.5, 166.3, 161.5, 157.7, 143.7,133.6, 129.3, 121.8, 120.4, 114.4, 97.4, 69.3, 55.3, 26.4. HRMS (ESI) m / z:calcd for C 18 H 15 N₂O₃Se (M + H) + 387.0242, found 387.0243.

[0048] Example 7

[0049]

[0050] Compound 1 (0.5 mmol, 142.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 73% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.93(dd, J = 7.8, 2.4 Hz, 2H), 7.60–7.52 (m, 3H), 7.45 (dd, J = 8.3, 7.2 Hz, 1H), 7.26 (dd, J = 7.2, 1.1 Hz, 1H), 3.04 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.1, 166.0, 155.3, 142.7,142.7, 134.4, 133.4, 133.3, 131.0, 130.0, 129.5, 127.7, 126.8, 126.6, 125.7,125.5, 124.5, 123.4, 96.3, 71.1, 27.0. HRMS (ESI) m / z: calcd for C 21 H 15 N₂O₂Se(M + H) + 407.0293, found 407.0297.

[0051] Example 8

[0052]

[0053] Compound 1 (0.5 mmol, 120.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 43% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.65–7.61 (m, 1H), 7.41 (ddd, J = 3.9, 2.9, 1.4 Hz, 1H), 7.31 (d, J = 5.1 Hz, 1H), 6.58 – 6.51 (m, 4H), 2.90 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ13C NMR (101 MHz, CDCl3) δ 183.5, 166.3, 152.6, 144.0, 133.5, 129.9, 128.2, 127.4, 126.3,119.4, 97.4, 68.6, 26.3. HRMS (ESI) m / z: calcd for C 15 H 11 N2O2SSe (M + H) + 362.9701, found 362.9701.

[0054] Example 9

[0055]

[0056] Compound 1 (0.5 mmol, 162.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 91% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.41–7.30 (m, 3H), 7.16–7.09 (m, 2H), 5.35 (s, 2H), 3.63 (s, 6H), 2.86 (s, 3H). 13 CNMR (100 MHz, CDCl3) δ 174.9, 165.5, 160.7, 153.6, 130.7, 129.8, 128.9,127.5, 120.6, 110.0, 97.4, 69.9, 56.0, 26.1. HRMS (ESI) m / z: calcd forC 19 H 17 N₂O₄Se (M + H) + 417.0348, found 417.0346.

[0057] Example 10

[0058]

[0059] Compound 1 (0.5 mmol, 141.5 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 45% yield. The NMR and high-resolution data of the target product 4 are as follows:1 H NMR (400 MHz, CDCl3) δ 7.38(ddd, J = 14.4, 8.0, 6.2 Hz, 3H), 7.14 (dd, J = 8.0, 1.6 Hz, 2H), 6.54 (dd, J= 9.9, 2.7 Hz, 1H), 6.46 (dd, J = 9.9, 6.6 Hz, 1H), 6.10 (dd, J = 11.0, 2.7Hz, 1H), 2.90 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 176.5 (d, J = 22 Hz), 165.6,157.1, 155.8 (d, J = 269 Hz),, 144.5 (d, J = 2 Hz), 132.7 (d, J = 4 Hz), 131.0, 129.2, 129.1, 127.6, 122.5, 119.4 (d, J = 15 Hz), 96.8, 71.0 (d, J = 8Hz), 26.6. 19 F NMR (376 MHz, CDCl3) δ -120.12. HRMS (ESI) m / z: calcd forC 17 H 12 FN2O2Se (M + H) + 375.0043, found 375.0043.

[0060] Example 11

[0061]

[0062] Compound 1 (0.5 mmol, 126.7 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 42% yield. The NMR and high-resolution data of the target product 4 are as follows: 1H NMR (400 MHz, CDCl3) δ 7.41–7.31 (m, 3H), 7.17–7.15 (m, 2H), 6.52–6.46 (m, 2H), 6.45–6.40 (m, 2H), 2.88 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.3, 166.0, 157.7, 143.2, 133.7, 130.8,129.5, 128.9, 127.6, 122.1, 97.0, 69.6, 26.6. HRMS (ESI) m / z: Calcd forC 17 H 13 N₂O₂Se (M + H) + 357.0137; Found 357.0137.

[0063] Example 12

[0064]

[0065] Compound 1 (0.5 mmol, 140.2 mg), elemental selenium 2 (Se, 1 mmol, 79 mg), compound 3 (TMSCN, 2 mmol, 198 mg), and dimethyl sulfoxide (3 mL) were added to a 25 mL reaction tube. The reaction mixture was stirred at 120 °C for 12 h. The reaction mixture was then poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with 15 mL of brine and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the residue was purified by rapid chromatography [silica gel, petroleum ether: ethyl acetate, v / v ratio 10:1] to give 3-selenocyanospiro[4.5]trienone derivative 4, a yellow solid, in 54% yield. The NMR and high-resolution data of the target product 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ7.41–7.31 (m, 3H), 7.17–7.15 (m, 2H), 6.52–6.46 (m, 2H), 6.45–6.40 (m, 2H), 2.88 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 183.3, 166.0, 157.7, 143.2, 133.7,130.8, 129.5, 128.9, 127.6, 122.1, 97.0, 69.6, 26.6. HRMS (ESI) m / z: Calcdfor C17 H 13 N₂O₂Se (M + H) + 357.0137; Found 357.0137.

[0066] In summary, this invention uses acetylacetamide compounds, elemental selenium, and trimethylcyanosilane as raw materials to prepare 3-selenocyanospiro[4.5]trienone derivatives in a one-pot process under solvent addition and heating conditions. Compared with traditional methods, this method avoids contamination from transition metals and strong oxidants. It also features mild reaction conditions, convenient operation, and high reaction efficiency.

[0067] It should be noted that all parts not described in detail in this invention are well-known techniques to those skilled in the art. The above embodiments are only used to further illustrate a method for preparing a 3-selenocyanospiro[4.5]trienone derivative of this invention, but this invention is not limited to the embodiments. All equivalent changes and modifications made to the above embodiments based on the technical essence of this invention are included within the protection scope of the technical solution of this invention.

Claims

1. A method for synthesizing a 3-selenocyanospiro[4.5]trienone derivative, characterized in that, The reaction includes the following steps: adding compound 1, elemental selenium, trimethylcyanosilane, and dimethyl sulfoxide to a reactor and stirring the mixture at 60-140°C to obtain 3-selenocyanospiro[4.5]trienone derivative 4; the reaction equation is as follows: ， Among them, R 1 One or more substituents on the benzene ring are independently selected from hydrogen, phenyl, phenoxy, substituted phenyl, naphthyl, thiophene, halogen, C1-C6 alkyl, and C1-C6 alkoxy; X is selected from any one of hydrogen, C1-C6 alkoxy, halogen, and nitro; R 2 Selected from any one of C1-C6 alkyl, phenyl, and substituted phenyl groups; R 3 It is selected from any one of phenyl, substituted phenyl, naphthyl, and thiophene.

2. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 1, characterized in that, The molar ratio of compound 1, elemental selenium, and trimethylcyanosilane is 1:(1-10):(1-10).

3. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 1, characterized in that, The ratio of compound 1 to dimethyl sulfoxide was 1 mmol:(6-15) mL.

4. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 1, characterized in that, The reaction time is 12-24 hours.

5. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 1, characterized in that, It also includes separation and purification steps after the reaction is completed.

6. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 5, characterized in that, The separation and purification includes column chromatography purification.

7. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 6, characterized in that, The eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate.

8. The method for synthesizing the 3-selenocyanospiro[4.5]trienone derivative according to claim 7, characterized in that, The volume ratio of petroleum ether to ethyl acetate is (20~5):1.

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