A novel process for the synthesis of cyanoacrylates

Abstract

The application discloses a new method for synthesizing cyanoacrylate, which comprises the following steps: S1, adding p-methylene quinone, cyanoacetate, elemental sulfur, an organic solvent and an alkali into a reaction container and stirring at high temperature; and S2, after the reaction is completed, diluting the mixture by adding saturated sodium bicarbonate and ethyl acetate, stirring, extracting, separating and purifying to obtain cyanoacrylate compounds; the application adopts an efficient and metal-catalyst-free route, the synthetic route design is novel, the operation method is simple, and the reaction can directly obtain the product under mild conditions.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of compound synthesis, and particularly relates to a new method for synthesizing cyanoacrylate. BACKGROUND

[0002] Cyanoacrylate has wide biological activity and is usually used in the fields of herbicides, insecticides, fungicides and the like, and its herbicidal activity is one of the hotspots in the field of herbicide research at present. In addition, cyanoacrylate is often used as a monomer to synthesize polymers and is widely used as an adhesive and a support material in material science. In addition to these wide applications, cyanoacrylate is also used for the synthesis of these cyano equivalents such as primary amines, tetrazoles, aldehydes / ketones, acrylic acid derivatives and related functional groups. The 2006 Master's Thesis of Guizhou University, entitled 'Synthesis and Biological Activity Research of Chiral Derivatives of Cyanoacrylate', introduces the action of a plurality of cyanoacrylate derivatives in detail.

[0003] The classical synthetic routes of cyanoacrylate derivatives include two methods, that is, by using cyanoacetate, carbon disulfide, a nucleophilic reagent and a methylation agent as substrates under alkaline conditions, or by using aldehyde / ketone and cyanoacetate as raw materials under acidic conditions (for example, TiCl4). Although these methods are still widely used in the field of synthesizing cyanoacrylate derivatives, however, these methods have been plagued by the limitations of the application range, stability, toxicity, serious environmental pollution problems, laborious post-experimental treatment and single molecular structure of the product of the substrates. Therefore, it is necessary and suitable for the needs of social development to continuously develop new strategies to improve the previous methods for synthesizing cyanoacrylate derivatives. SUMMARY

[0004] In view of the above problems, the present application provides a new method for synthesizing cyanoacrylate, which is simple in operation, mild in reaction conditions and non-toxic.

[0005] To achieve the above purpose, the present application provides the following technical solutions:

[0006] The present application provides a new method for synthesizing cyanoacrylate, which comprises the following steps:

[0007] S1, adding p-methylenedioxybenzene, cyanoacetate, elemental sulfur (S8), an organic solvent and a base into a reaction container and stirring at high temperature;

[0008] S2, after the reaction is completed, diluting the mixture with saturated sodium bicarbonate and ethyl acetate, stirring, extracting, separating and purifying to obtain a cyanoacrylate compound.

[0009] Preferably, in step S1, the preparation method of the p-quinone methide compound comprises: reacting 2,6-di-tert-butylphenol / 2,6-diisopropylphenol, different substituent benzaldehyde, toluene, piperidine, acetic anhydride in a reflux system.

[0010] Preferably, the chemical formula of the p-quinone methide compound is:

[0011]

[0012] wherein R 1 including tert-butyl, isopropyl; R 2 including methyl, methoxy, isopropyl, N,N-dimethyl, nitro, cyano, fluorine, bromine, and di-substituted (chlorine) and tri-substituted (methoxy) electron-withdrawing and electron-donating groups, and heterocyclic rings of pyridine, thiophene, naphthalene;

[0013] and the chemical reaction formula of step S1 is:

[0014]

[0015] wherein R 1 including tert-butyl, isopropyl; R 2 including methyl, methoxy, isopropyl, N,N-dimethyl, nitro, cyano, fluorine, bromine, and di-substituted (chlorine) and tri-substituted (methoxy) electron-withdrawing and electron-donating groups, and heterocyclic rings of pyridine, thiophene, naphthalene; R 3 including methyl, ethyl, tert-butyl.

[0016] Preferably, in step S1, the organic solvent includes N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, 1,4-dioxane.

[0017] Preferably, in step S1, the base includes potassium carbonate, triethylamine, potassium hydroxide, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicycloundec-7-ene (DBU), sodium bicarbonate, potassium acetate.

[0018] Preferably, in step S1, the molar ratio of the p-quinone methide compound, cyanoacetate, elemental sulfur (S8), base is (1-2):(1-2):(0.25-0.5):(1-2); further preferably, the molar ratio of the p-quinone methide (p-QMs), cyanoacetate, elemental sulfur, base is 1:1:4:1.

[0019] Preferably, in step S1, the stirring condition is 90-120℃ for 6-10 hours; further preferably, the temperature is 100℃ and the time is 8h.

[0020] Preferably, in step S2, the organic phase obtained by extraction and separation is washed with saturated sodium bicarbonate, and the aqueous phase is washed with ethyl acetate.

[0021] Preferably, in step S2, the organic phase obtained by extraction and separation is dried with anhydrous sodium sulfate and then concentrated and purified by separation.

[0022] Preferably, the extraction method comprises:

[0023] R1, extraction with low-concentration ethyl acetate,

[0024] R2, extraction with high-concentration ethyl acetate;

[0025] R3, the organic phase obtained by extraction and separation is washed with saturated sodium bicarbonate, and the aqueous phase is washed with ethyl acetate;

[0026] R4, the organic phase is dried with anhydrous sodium sulfate and then concentrated.

[0027] Preferably, the concentration of high-concentration ethyl acetate is 3 times that of low-concentration ethyl acetate.

[0028] Preferably, in step S2, the separation and purification is column chromatography separation and purification, and the eluent used is a mixture of petroleum ether and ethyl acetate; further preferably, the volume ratio of petroleum ether to ethyl acetate is 30:1.

[0029] Preferably, a new method for synthesizing cyanoacrylate is provided, and the chemical reaction formula is:

[0030]

[0031] In a dry 25ml flask, p-QMs, cyanoacetate, elemental sulfur (S8), DMSO and DBU are sequentially added, the mixture is stirred at 100℃ until the reaction is complete, ethyl acetate (EtOAc) and saturated sodium bicarbonate are added for dilution, stirring, separation into two layers, extraction with EtOAc, and the crude product is separated by column chromatography to obtain the corresponding cyanoacrylate.

[0032] Compared with the prior art, the beneficial effects and significant progress of the technical solution of the present application are:

[0033] 1. The new method for synthesizing cyanoacrylate provided by the present application has wide applicability, and compared with the previous method, the method of the present application adopts a high-efficiency and metal-catalyst-free route, and the synthetic route is novel, the operation method is simple, and the product can be directly obtained under mild reaction conditions.

[0034] 2. The method of the present application expands the synthetic route of cyanoacrylate, obtains more structurally rich compounds, and has important significance for the synthetic route of cyanoacrylate. BRIEF DESCRIPTION OF DRAWINGS

[0035] Fig. 1 a single crystal spectrum of the product of Example 1, tert-butyl 2-cyano-3-(3,5-di-tert- butyl-4-hydroxyphenyl)-3-phenylacrylate;

[0036] Fig. 2 a nuclear magnetic resonance hydrogen spectrum of the product of Example 1, ethyl 2-cyano-3- (3,5-di-tert-butyl-4-hydroxyphenyl)-3-phenylacrylate;

[0037] Fig. 3 a nuclear magnetic resonance carbon spectrum of the product of Example 1, ethyl 2-cyano-3- (3,5-di-tert-butyl-4-hydroxyphenyl)-3-phenylacrylate. DETAILED DESCRIPTION

[0038] The present application is further illustrated by the following specific examples. The examples are intended to be illustrative only and are not intended to limit the scope of the present application. Furthermore, it is to be understood that various modifications and changes can be devised by those skilled in the art who are familiar with the disclosure herein, and that the scope of the present application is to be limited only by the appended claims.

[0039] Example 1

[0040] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added in sequence, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain ethyl 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-phenylacrylate with a yield of 90%. The single crystal spectrum, nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum of ethyl 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-phenylacrylate are shown in Figs. 1-3

[0041] 1 H NMR (400 MHz, CDC13) δ 7.49 - 7.33 (m, 4H), 7.27 (d, J = 13.6 Hz, 2H), 7.18 (d, J = 6.9 Hz, 1H), 5.71 (s, 1H), 4.16 - 4.07 (m, 2H), 1.38 (d, J = 5.6 Hz, 18H), 1.16 - 1.07 (m, 3H). 13 ​CNMR (101 MHz, CDC13) δ 170.42, 163.54, 157.51, 135.70, 130.08, 129.51, 129.12, 128.77, 128.32, 127.98, 127.79, 118.13, 100.68, 61.80, 34.32, 29.93, 13.79. HRMS: calcd. for C 27 H 33 NO3[M+Na]+428.2196; found 428.2195.

[0042] Example 2

[0043] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(p-tolyl)acrylic acid ethyl ester with a yield of 80%.

[0044] 1 H NMR (400 MHz, CDC13) δ 7.35 - 7.25 (m, 2H), 7.20 (dd, J = 16.9, 7.9 Hz, 2H), 7.09 - 6.94 (m, 2H), 5.69 (s, 1H), 4.14 (p, J = 7.0 Hz, 2H), 2.41 (d, J = 2.2 Hz, 3H), 1.38 (d, J = 6.2 Hz, 18H), 1.15 (dt, J = 14.5, 7.1 Hz, 3H). 13 CNMR (101 MHz, CDC13) δ 171.04, 163.77, 157.48, 136.31, 135.57, 130.95, 129.86, 129.34, 128.90, 128.72, 118.41, 99.97, 61.79, 34.32, 30.14, 21.58, 13.88. HRMS: calcd. for C 27 H 33 NO3[M+Na]+442.2352; found 442.2351.

[0045] Example 3

[0046] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(m-tolyl)acrylic acid ethyl ester in a yield of 74%.

[0047] 1 H NMR (400 MHz, CDC13) δ 7.31 - 7.17 (m, 4H), 7.01 - 6.94 (m, 2H), 5.70 (s, 1H), 4.13 (p, J = 7.1 Hz, 2H), 2.36 (d, J = 11.7 Hz, 3H), 1.38 (d, J = 6.2 Hz, 18H), 1.13 (td, J = 7.1, 4.5 Hz, 3H).13C NMR (101 MHz, CDC13) δ 170.66, 163.68, 157.47, 139.27, 137.63, 135.59, 130.93, 130.04, 128.78, 127.88, 126.76, 118.23, 100.50, 61.79, 34.51, 30.19, 21.33. HRMS: calcd. for C 27 H 33 NO3[M+Na]+442.2352; found 442.2351.

[0048] Example 4

[0049] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(m-tolyl)acrylic acid ethyl ester in a yield of 74%.

[0050] 1H NMR (400 MHz, CDC13) δ 7.34 (dd, J = 22.0, 8.0 Hz, 1H), 7.28 - 7.07 (m, 4H), 6.95 (s, 1H), 5.68 (s, 1H), 4.12 (qd, J = 7.1, 3.7 Hz, 2H), 2.96 (p, J = 6.9 Hz, 1H), 1.38 (d, J = 4.5 Hz, 18H), 1.31 - 1.24 (m, 6H), 1.10 (dt, J = 12.6, 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 170.68, 163.91, 157.43, 151.49, 136.72, 135.55, 129.97, 128.89, 127.80, 126.01, 118.39, 100.03, 61.72, 34.49, 34.32, 30.12, 23.84, 13.75. HRMS: calcd. for C 29 H 37 NO3[M+Na]+470.2665; found 470.2667.

[0051] Example 5

[0052] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(4-methoxyphenyl) acrylate with a yield of 73%.

[0053] 1 H NMR (400 MHz, CDC13) δ 7.34 (dd, J = 22.0, 8.0 Hz, 1H), 7.28 - 7.07 (m, 4H), 6.95 (s, 1H), 5.68 (s, 1H), 4.12 (qd, J = 7.1, 3.7 Hz, 2H), 2.96 (p, J = 6.9 Hz, 1H), 1.38 (d, J = 4.5 Hz, 18H), 1.31 - 1.24 (m, 6H), 1.10 (dt, J = 12.6, 7.1 Hz, 3H). 13C NMR (101 MHz, CDC13) δ 170.79, 164.01, 161.67, 157.51, 135.57, 133.09, 132.10, 129.06, 127.93, 118.65, 113.37, 99.07, 61.74, 55.37, 34.48, 30.16, 13.99. HRMS: calcd. for C 27 H 33 NO4[M+Na]+458.2301; found 458.2299.

[0054] Example 6

[0055] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-methoxyphenyl) acrylate in a yield of 68%.

[0056] 1 H NMR (400 MHz, CDC13) δ 7.38 (ddd, J = 8.5, 6.9, 2.5 Hz, 1H), 7.29 (d, J = 22.9 Hz, 2H), 7.01 - 6.90 (m, 3H), 5.63 (s, 1H), 4.14 (dq, J = 14.3, 7.1 Hz, 2H), 3.75 (d, J = 26.1 Hz, 3H), 1.37 (d, J = 9.5 Hz, 18H), 1.16 (dt, J = 12.8, 7.2 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 170.79, 164.01, 161.67, 157.51, 135.57, 133.09, 132.10, 129.06, 127.93, 118.65, 113.37, 99.07, 61.74, 55.37, 34.48, 30.16, 13.99. HRMS: calcd. for C 27 H 33 NO4[M+Na]+458.2301;

[0057] found 458.2299.

[0058] Example 7

[0059] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(4-hydroxyphenyl)acrylic acid ethyl ester with a yield of 82%.

[0060] 1 H NMR (400 MHz, CDC13) δ 7.34 - 7.24 (m, 2H), 7.07 - 7.03 (m, 1H), 6.96 (s, 1H), 6.83 - 6.72 (m, 2H), 4.17 (dq, J = 35.5, 7.1 Hz, 2H), 1.38 (d, J = 7.5 Hz, 18H), 1.18 (dt, J = 50.8, 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 172.20, 164.81, 159.00, 157.80, 135.66, 133.39, 132.44, 129.26, 128.20, 115.22, 98.00, 62.14, 34.48, 30.13, 13.96. HRMS: calcd. for C 26 H 31 NO4[M+Na]+444.2145; found 444.2137.

[0061] Example 8

[0062] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(4-(dimethylamino)phenyl)acrylic acid ethyl ester with a yield of 81%.

[0063] 1H NMR (400 MHz, CDC13) δ 7.41 - 7.25 (m, 2H), 7.09 - 6.96 (m, 2H), 6.68 - 6.57 (m, 2H), 5.53 (s, 1H), 4.22 - 4.02 (m, 2H), 3.05 (d, J = 4.7 Hz, 6H), 1.40 (d, J = 7.2 Hz, 18H), 1.25 (t, J = 7.1 Hz, 1H), 1.06 (t, J = 7.1 Hz, 2H). 13 C NMR (101 MHz, CDC13) δ 171.07, 165.05, 156.42, 152.81, 135.31, 133.63, 130.57, 128.08, 124.94, 119.79, 110.75, 95.58, 61.29, 40.04, 34.31, 30.29, 13.91. HRMS: calcd. for C 28 H 36 N2O3[M+Na]+ 471.2618; found 471.2625.

[0064] Example 9

[0065] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(4-fluorophenyl) acrylate with a yield of 77%.

[0066] 1 H NMR (400 MHz, CDC13) δ 7.41 - 7.25 (m, 2H), 7.09 - 6.96 (m, 2H), 6.68 - 6.57 (m, 2H), 5.53 (s, 1H), 4.22 - 4.02 (m, 2H), 3.05 (d, J = 4.7 Hz, 6H), 1.40 (d, J = 7.2 Hz, 18H), 1.25 (t, J = 7.1 Hz, 1H), 1.06 (t, J = 7.1 Hz, 2H). 13C NMR (101 MHz, CDC13) δ 169.52, 165.15, 163.40, 162.65, 157.70, 135.80, 133.06, 131.75, 129.03, 128.80, 118.07, 115.34, 115.12, 100.63, 61.94, 34.51, 30.21, 13.89. HRMS: calcd. for C 26 H 30 FNO3[M+Na]+446.2101; found 446.2100.

[0067] Example 10

[0068] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-fluorophenyl) acrylate with a yield of 79%.

[0069] 1 H NMR (400 MHz, CDC13) δ 7.43 (tdd, J = 7.2, 5.2, 1.8 Hz, 1H), 7.34 - 7.24 (m, 2H), 7.19 - 6.99 (m, 3H), 5.71 (d, J = 1.4 Hz, 1H), 4.18 (q, J = 7.3 Hz, 2H), 1.39 (s, 18H), 1.20 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 163.53, 162.60, 160.54, 157.55, 135.81, 131.04, 128.17, 123.85, 117.72, 115.50, 102.83, 61.97, 34.53, 30.08, 13.91. HRMS: calcd. for C 26 H 30 FNO3

[0070] [M+Na]+446.2101; found 446.2100.

[0071] Example 11

[0072] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(4-bromophenyl)acrylate in a yield of 77%.

[0073] 1 H NMR (400 MHz, CDC13) δ 7.59 - 7.48 (m, 2H), 7.29 (d, J = 25.9 Hz, 2H), 7.08 - 6.90 (m, 2H), 5.73 (s, 1H), 4.15 (q, J = 7.1 Hz, 2H), 1.38 (d, J = 6.8 Hz, 18H), 1.16 (dt, J = 14.6, 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 169.38, 163.21, 157.74, 138.13, 135.85, 131.70, 131.28, 128.73, 127.79, 124.73, 117.95, 100.91, 62.03, 34.53, 30.16, 13.88. HRMS: calcd. for C 26 H 30 BrNO3[M+Na]+508.1282; found 508.1287.

[0074] Example 12

[0075] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(2-bromophenyl)acrylate in a yield of 58%.

[0076] 1H NMR (400 MHz, CDC13) δ 7.65 - 7.56 (m, 1H), 7.41 - 7.19 (m, 4H), 7.11 - 7.06 (m, 1H), 5.70 (s, 1H), 4.16 - 4.04 (m, 2H), 1.42 (s, 3H), 1.39 (s, 15H), 1.19 - 1.02 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 168.14, 162.14, 157.48, 140.38, 135.87, 132.66, 129.97, 129.27, 128.00, 127.06, 125.12, 121.67, 117.55, 102.84, 61.93, 34.56, 30.07, 13.85. HRMS: calcd. for C 26 H 30 BrNO3[M+Na]+508.1282; found 508.1287.

[0077] Example 13

[0078] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(4-nitrophenyl) acrylate with a yield of 79%.

[0079] 1 H NMR (400 MHz, CDC13) δ 8.31 - 8.23 (m, 2H), 7.39 - 7.23 (m, 4H), 5.78 (s, 1H), 4.15 (q, J = 7.0 Hz, 2H), 1.37 (d, J = 5.3 Hz, 18H), 1.20 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 168.00, 162.46, 158.04, 148.29, 145.89, 136.19, 129.98, 128.44, 127.92, 123.26, 117.34, 102.09, 62.32, 34.58, 30.02, 13.91. HRMS: calcd. for C 26 H 30N2O5[M+Na]+ 473.2046; found 473.2042.

[0080] Example 14

[0081] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-nitrophenyl) acrylate in a yield of 76%.

[0082] 1 H NMR (400 MHz, CDC13) δ 7.43 (tdd, J = 7.9, 5.5, 1.5 Hz, 1H), 7.33 (d, J = 1.2 Hz, 2H), 7.19 - 7.01 (m, 3H), 5.71 (d, J = 1.4 Hz, 1H), 4.18 (q, J = 7.2 Hz, 2H), 1.40 - 1.38 (m, 18H), 1.20 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 186.43, 163.46, 159.86, 156.27, 151.68, 148.87, 148.36, 135.45, 133.15, 131.88, 131.72, 131.04, 130.97, 130.89, 129.83, 128.98, 128.83, 128.68, 123.86, 123.83, 115.95, 115.73, 35.26, 33.76, 30.78, 29.78, 28.05. HRMS: calcd. for C 26 H 30 N2O5[M+Na]+ 473.2046; found 473.2042.

[0083] Example 15

[0084] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(2,6-dichlorophenyl)acrylate with a yield of 78%.

[0085] 1 H NMR (400 MHz, CDC13) δ 7.72 - 7.67 (m, 2H), 7.31 (s, 1H), 7.24 (s, 2H), 5.78 (s, 1H), 4.14 (q, J = 7.1 Hz, 2H), 1.38 (s, 18H), 1.18 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 168.31, 162.56, 157.97, 144.03, 136.12, 131.76, 129.77, 128.51, 128.04, 118.34, 113.33, 101.86, 62.25, 34.57, 30.03, 13.88. HRMS: calcd. for C 26 H 29 Cl2NO3[M+Na]+496.1416; found 496.1418.

[0086] Example 16

[0087] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)acrylate with a yield of 87%.

[0088] 1H NMR (400 MHz, CDC13) δ 7.33 - 6.96 (m, 2H), 6.60 (d, J = 31.4 Hz, 1H), 6.39 (s, 1H), 5.72 (s, 1H), 4.12 (p, J = 7.4 Hz, 2H), 3.94 - 3.72 (m, 9H), 1.38 (d, J = 7.1 Hz, 18H), 1.17 - 1.04 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 169.59, 163.95, 157.70, 152.75, 139.90, 135.66, 134.49, 129.00, 128.13, 118.22, 107.53, 100.08, 61.87, 61.09, 56.32, 34.53, 30.15, 13.94. HRMS: calcd. for C 29 H 37 NO6[M+Na]+518.2513; found 518.2507.

[0089] Example 17

[0090] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(naphthalen-2-yl)acrylic acid ethyl ester with a yield of 89%.

[0091] 1 H NMR (400 MHz, CDC13) δ 7.33 - 6.96 (m, 2H), 6.60 (d, J = 31.4 Hz, 1H), 6.39 (s, 1H), 5.72 (s, 1H), 4.12 (p, J = 7.4 Hz, 2H), 3.94 - 3.72 (m, 9H), 1.38 (d, J = 7.1 Hz, 18H), 1.17 - 1.04 (m, 3H). 13C NMR (101 MHz, CDC13) δ 170.48, 163.67, 157.59, 136.68, 135.75, 133.97, 132.59, 129.64, 129.17, 128.89, 128.64, 127.87, 127.60, 126.96, 126.68, 126.13, 118.26, 100.98, 61.87, 34.52, 30.14, 13.80. HRMS: calcd. for C 30 H 33 NO3[M+Na]+478.2352; found 478.2345.

[0092] Example 18

[0093] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(thiophen-2-yl)acrylic acid ethyl ester in 81% yield.

[0094] 1 H NMR (400 MHz, CDC13) δ 7.81 (dd, J = 3.9, 1.2 Hz, 1H), 7.64 (ddd, J = 17.9, 5.1, 1.2 Hz, 1H), 7.22 - 7.14 (m, 1H), 7.06 (s, 2H), 5.57 (s, 1H), 4.13 (dq, J = 76.5, 7.1 Hz, 2H), 1.41 (d, J = 3.2 Hz, 18H), 1.27 - 1.22 (m, 1H), 1.03 (t, J = 7.1 Hz, 2H). 13 C NMR (101 MHz, CDC13) δ 163.83, 160.49, 156.42, 141.42, 135.48, 134.43, 133.70, 129.86, 128.24, 127.20, 118.30, 98.04, 61.80, 34.36, 30.24, 13.77. HRMS: calcd. for C 24 H 29 NO3S[M+Na]+434.1760; found 434.1759.

[0095] Example 19

[0096] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain tert-butyl 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-phenylacrylate in 79% yield.

[0097] 1 H NMR (400 MHz, CDC13) δ 7.48 - 7.41 (m, 1H), 7.41 - 7.34 (m, 2H), 7.25 (d, J = 5.0 Hz, 2H), 7.20 - 6.91 (m, 2H), 5.65 (s, 1H), 1.38 (s, 20H), 1.30 (s, 7H). 13 C NMR (101 MHz, CDC13) δ 168.60, 162.70, 157.19, 139.68, 135.54, 130.63, 129.60, 128.60, 127.96, 127.42, 118.31, 102.84, 82.86, 34.49, 30.11, 27.56. HRMS: calcd. for C 28 H 25 NO3[M+Na]+ 456.2509; found 456.2512.

[0098] Example 20

[0099] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain tert-butyl 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(m-tolyl)acrylate in 75% yield.

[0100] 1H NMR (400 MHz, CDC13) δ 7.25 (d, J = 5.3 Hz, 4H), 7.02 - 6.92 (m, 2H), 5.65 (s, 1H), 2.36 (d, J = 7.3 Hz, 3H), 1.39 (d, J = 2.2 Hz, 20H), 1.31 (s, 7H). 13 C NMR (101 MHz, CDC13) δ 168.72, 162.88, 157.16, 139.56, 137.52, 135.50, 130.66, 130.19, 128.60, 127.90, 127.41, 126.84, 118.36, 102.70, 82.75, 34.50, 30.15, 27.55, 21.30. HRMS: calcd. for C 29 H 37 NO3[M+Na]+

[0101] 470.2665; found 470.2668.

[0102] Example 21

[0103] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain tert-butyl 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-bromophenyl) acrylate with a yield of 77%.

[0104] 1 H NMR (400 MHz, CDC13) δ 7.69 - 7.56 (m, 1H), 7.39 - 7.22 (m, 4H), 7.15 - 7.08 (m, 1H), 5.47 (d, J = 144.9 Hz, 1H), 1.44 - 1.33 (m, 18H), 1.29 - 1.20 (m, 9H). 13 C NMR (101 MHz, CDC13) δ 165.92, 161.49, 157.13, 140.73, 135.76, 132.70, 129.59, 127.76, 125.32, 117.68, 105.25, 84.02, 82.95, 49.68, 44.02, 34.54, 30.09, 27.55. HRMS: calcd. for C 28H 34 BrNO3[M+Na]+

[0105] 536.1594; found 536.1598.

[0106] Example 22

[0107] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(naphthalen-2-yl)acrylic acid tert-butyl ester in 73% yield.

[0108] 1 H NMR (400 MHz, CDC13) δ 7.93 - 7.75 (m, 3H), 7.47 (td, J = 17.5, 8.5 Hz, 2H), 7.21 (dd, J = 38.0, 2.2 Hz, 2H), 5.19 (d, J = 2.0 Hz, 1H), 4.75 (ddd, J = 12.2, 8.9, 2.1 Hz, 1H), 4.22 (dt, J = 9.1, 2.9 Hz, 1H), 1.43 (dd, J = 7.6, 2.0 Hz, 18H), 1.23 (dd, J = 6.4, 1.8 Hz, 9H). 13 CNMR (101 MHz, CDC13) δ 164.18, 153.22, 137.19, 136.12, 133.38, 132.70, 129.80, 129.04, 128.64, 128.05, 127.65, 126.79, 126.32, 126.10, 124.77, 116.57, 83.90, 51.47, 45.01, 34.42, 30.24, 27.47. HRMS: calcd. for C 32 H 37 NO3[M+Na]+ 506.2665; found 506.2663.

[0109] Example 23

[0110] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain tert-butyl 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)acrylate in 76% yield.

[0111] 1 H NMR (400 MHz, CDC13) δ 7.25 (s, 1H), 7.13 (s, 1H), 6.67 (s, 1H), 6.58 (s, 1H), 5.19 (d, J = 5.1 Hz, 1H), 4.45 (dd, J = 14.0, 8.5 Hz, 1H), 4.05 - 3.96 (m, 1H), 3.85 (d, J = 7.6 Hz, 6H), 3.81 (d, J = 3.7 Hz, 3H), 1.42 (d, J = 5.6 Hz, 18H), 1.23 (d, J = 4.9 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 164.06, 153.21, 137.31, 136.07, 135.52, 128.76, 124.63, 116.59, 105.34, 83.85, 60.88, 56.10, 53.47, 52.07, 45.97, 34.43, 30.23, 27.43. HRMS: calcd. for C 31 H 41 NO6 [M+Na]+ 546.2826; found 546.2827.

[0112] Example 24

[0113] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain tert-butyl 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)acrylate in 76% yield.

[0114] 1 H NMR (400 MHz, CDC13) δ 7.52 - 7.25 (m, 5H), 7.22 - 6.93 (m, 2H), 5.67 (d, J = 38.6 Hz, 1H), 3.72 (d, J = 22.2 Hz, 3H), 1.38 (d, J = 6.3 Hz, 18H). 13 C NMR (101 MHz, CDC13) δ 171.39, 163.83, 157.65, 139.15, 135.68, 130.78, 129.54, 128.88, 128.33, 128.01, 118.26, 99.86, 52.66, 34.51, 30.10. HRMS: calcd. for C 25 H 29 NO3[M+Na]+414.2039; found 414.2039.

[0115] Example 25

[0116] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(p-tolyl) acrylic acid methyl ester with a yield of 79%.

[0117] 1 H NMR (400 MHz, CDC13) δ 7.52 - 7.25 (m, 5H), 7.22 - 6.93 (m, 2H), 5.67 (d, J = 38.6 Hz, 1H), 3.72 (d, J = 22.2 Hz, 3H), 1.38 (d, J = 6.3 Hz, 18H). 13 C NMR (101 MHz, CDC13) δ

[0118] 168.67, 162.64, 153.47, 139.49, 133.63, 131.18, 130.28, 129.71, 127.98, 127.08, 118.22, 103.04, 82.97, 27.57, 27.15, 22.53. HRMS: calcd. for C 26 H 31NO3[M + Na]+ 464.2196; found 464.2197.

[0119] Example 26

[0120] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(naphthalen-2-yl)acrylic acid methyl ester in 76% yield.

[0121] 1 H NMR (400 MHz, CDC13) δ 7.91 - 7.79 (m, 3H), 7.69 - 7.47 (m, 3H), 7.34 - 7.00 (m, 3H), 5.72 (s, 1H), 3.72 (d, J = 41.2 Hz, 3H), 1.37 (d, J = 3.5 Hz, 18H). 13 C NMR (101 MHz, CDC13) δ 171.34, 163.95, 157.71, 136.51, 135.77, 134.02, 132.59, 131.52, 129.75, 128.97, 128.72, 128.26, 127.89, 127.60, 126.94, 126.65, 118.33, 100.19, 52.71, 34.52, 30.12. HRMS: calcd. for C 29 H 31 NO3[M + Na]+ 464.2196; found 464.2197.

[0122] Example 27

[0123] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(4-bromophenyl) acrylate with a yield of 81%.

[0124] 1 H NMR (400 MHz, CDC13) δ 7.60 - 7.50 (m, 2H), 7.33 - 7.21 (m, 2H), 7.10 - 6.91 (m, 2H), 5.74 (s, 1H), 3.74 (d, J = 8.3 Hz, 3H), 1.38 (d, J = 7.2 Hz, 18H). 13 C NMR (101 MHz, CDC13) δ 170.09, 163.53, 157.84, 137.93, 135.90, 131.70, 131.31, 128.78, 128.09, 124.87, 117.98, 100.22, 52.77, 34.53, 30.09. HRMS: calcd. for C 25 H 28 BrNO3[M+Na]+494.1125; found 494.1117.

[0125] Example 28

[0126] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, followed by EtOAc (3 x 15 ml), the crude product was isolated by column chromatography to obtain 2-cyano-3-(3,5-di-tert-butyl-4- hydroxyphenyl)-3-(4-bromophenyl) acrylate with a yield of 81%.

[0127] 1H NMR (400 MHz, CDC13) δ 7.51 - 7.34 (m, 3H), 7.22 - 7.09 (m, 3H), 5.60 - 5.47 (m, 1H), 4.15 (dq, J = 17.9, 7.1 Hz, 2H), 3.12 (hept, J = 6.8 Hz, 2H), 1.18 (t, J = 6.8 Hz, 12H), 1.12 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 170.61, 163.57, 153.85, 139.19, 133.77, 130.31, 129.67, 127.99, 127.28, 118.08, 100.79, 61.91, 27.13, 22.55, 13.80. HRMS: calcd. for C 24 H 27 NO3[M+Na]+400.1883; found 400.1886.

[0128] Example 29

[0129] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added sequentially, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain tert-butyl 2-cyano-3-(4-hydroxy-3,5-diisopropylphenyl)-3- phenylacrylate in a yield of 69%.

[0130] 1 H NMR (400 MHz, CDC13) δ 7.28 - 7.16 (m, 4H), 7.07 (t, J = 6.8 Hz, 2H), 5.69 (s, 1H), 2.41 (s, 3H), 1.40 (d, J = 4.9 Hz, 21H). 13 C NMR (101 MHz, CDC13) δ 171.80, 164.07, 157.59, 140.86, 135.59, 129.90, 129.37, 128.75, 127.63, 124.44, 118.49, 99.25, 52.63, 34.49, 30.13, 21.61. HRMS: calcd. for C 26 H 31 NO3[M+Na]+428.2196; found 428.2188.

[0131] Example 30

[0132] In a dry 25 ml flask, p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml) were added in sequence, the mixture was stirred at 100 °C until the reaction was complete, diluted with EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirred, separated into two layers, extracted with EtOAc, then extracted with EtOAc (3 x 15 ml), the crude product was separated by column chromatography to obtain 2-cyano-3-(4-hydroxy-3,5-diisopropylphenyl)-3-phenylacrylate methyl ester with a yield of 72%.

[0133] 1 H NMR (400 MHz, CDC13) δ 7.52 - 7.33 (m, 3H), 7.20 - 7.12 (m, 3H), 7.03 - 6.82 (m, 1H), 5.39 (s, 1H), 3.77 - 3.64 (m, 3H), 3.11 (hept, J = 6.8 Hz, 2H), 1.19 (t, J = 7.0 Hz, 12H). 13 C NMR (101 MHz, CDC13) δ 171.22, 163.80, 153.82, 138.98, 133.68, 130.41, 129.67, 128.01, 127.35, 118.13, 100.20, 52.69, 27.17, 22.53. HRMS: calcd. for C 23 H 25 NO3[M+Na]+386.1726; found 386.1725.

[0134] Applicant(s) states that, during the course of the description above:

[0135] The terms "the present embodiment", "the present embodiment of the invention", "as shown", "further", "further improved technical solutions" and the like mean that the specific features, structures, materials or characteristics described in the embodiment or example are contained in at least one embodiment or example of the present invention; in the present specification, the illustrative description of the above terms is not necessarily directed to the same embodiment or example, and the specific features, structures, materials or characteristics described can be combined or combined in any one or more embodiments or examples in a suitable manner; in addition, the person of ordinary skill in the art can combine or combine the different embodiments or examples described in the present specification and the features of the different embodiments or examples without contradiction.

[0136] Finally, it should be noted that:

[0137] The above embodiments are only used to illustrate the technical solutions of the present application, and are not intended to limit the present application;

[0138] Although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those skilled in the art that the technical solutions recorded in the foregoing embodiments can be modified, or some or all of the technical features can be replaced by equivalents, and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application. Non-essential improvements, adjustments or replacements made by those skilled in the art based on the content of the present application are within the scope of the present application.

Claims

1. A method of synthesizing a cyanoacrylate, characterized by, The method comprises the following steps: S1, adding p-methane-quinone compound, cyanoacetate, elemental sulfur S8, organic solvent, base into a reaction container, and stirring at high temperature; S2, after the reaction is completed, adding saturated sodium bicarbonate and ethyl acetate into the mixture, stirring, extracting, separating and purifying to obtain cyanoacrylate; wherein, the chemical formula of the p-methane-quinone compound is: and the chemical reaction formula of step S1 is: Among them, R 1 Selected from tert-butyl and isopropyl; R 2 Selected from methyl, methoxy, isopropyl, N,N-dimethylamino, nitro, cyano, fluorine, bromine; R 3 Selected from methyl, ethyl, and tert-butyl; in step S1, the organic solvent is dimethyl sulfoxide; in step S1, the base is 1,8-diazabicycloundec-7-ene; in step S1, the molar ratio of the p-methane-quinone compound, cyanoacetate, elemental sulfur S8 and base is (1-2) : (1-2)：(0.25-0.5)：(1-2)； in step S1, the stirring condition is 90-120℃ for 6-10 hours.

2. A method of synthesizing a cyanoacrylate according to claim 1, wherein, in step S1, the preparation method of the p-methane-quinone compound comprises: mixing 2,6-di-tert-butyl phenol / 2,6-di-isopropyl phenol, benzaldehyde with different substituents, toluene, piperidine and acetic anhydride in a reflux system and reacting.

3. A method of synthesizing a cyanoacrylate according to claim 1, wherein, in step S2, the separation and purification is column chromatography separation and purification, and the eluent used is a mixture of petroleum ether and ethyl acetate.

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