Alkenyl nitrile compound and preparation method thereof

Abstract

According to the alkenyl nitrile compound and the preparation method thereof, the structural formula of the alkenyl nitrile compound is # imgabs0, in the formula, R1 is a group containing carboxylic acid, an ester group and phosphine, or an electron-withdrawing substituent, phenyl, naphthyl, an aromatic substituent containing electron donating, an aromatic substituent containing an electron-withdrawing group, and heteroaryl; r2 is a cyano group, an aryl group or a heteroaryl group; and R3 is aryl or alkyl. According to the preparation method of the alkenyl nitrile compound, provided by the invention, under simple and mild conditions, the alkenyl nitrile reaction which is difficult to realize by a traditional method is realized in one step by utilizing a photocatalytic multi-component reaction, and the prepared alkenyl nitrile compound is high in additional value, diversified in form and rich in substituent group variety, and has an important application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical chemistry, and particularly to an alkenyl nitrile compound and a preparation method thereof. Background Art

[0002] Alkenyl nitrile compounds have good biological activities and are widely used in the production and preparation of drugs, agrochemicals, etc. In the medical field, they can be used as drugs for treating Parkinson's disease, anti-cancer, anti-fungal, etc. In the field of pesticides, due to their advantages such as high activity, high selectivity and low toxicity, they are widely used in the manufacture of herbicides and fungicides. In addition, the cyano group can also be used as a useful synthetic precursor for further conversion into desired functional groups, such as amines, carbonyls, amides and carboxylic acids.

[0003] Alkenyl nitrile compounds are very important pharmaceutical intermediates and organic synthesis intermediates. It is not difficult to see from the literature that although many methods for synthesizing alkenyl nitriles have been developed at present, the references are such as Chem.Commun.2003,2438–2439; J.Am.Chem.Soc.2017,139,1710-11713; Angew.Chem.2009,121,4598–4601; Org.Lett.2010,12,1052-1055; Org.Biomol.Chem.2015,13,5918–5923; Adv.Synth.Catal.2017,359,1339–1350; Org.Biomol.Chem.,2023,21,2894–2898; ACS.Catal.2018,8,2473-247, etc. The methods provided in these literatures have promoted the related research of alkenyl nitriles to a certain extent, but most of the reactions also have some deficiencies. For example, the substrate applicability is not high, the functional group tolerance is poor, the reaction conditions are harsh (such as high-temperature heating is required, with high safety risks), and the raw material synthesis is difficult (such as expensive noble metal catalysts are used in the reaction), etc. Summary of the Invention

[0004] Based on this, it is necessary to provide an alkenyl nitrile compound and a preparation method thereof for at least one of the above-mentioned problems.

[0005] In the first aspect, the present application provides an alkenyl nitrile compound, and the structural formula of the alkenyl nitrile compound is:

[0006]

[0007] Wherein, R 1is a group containing a carboxylic acid, an ester group, and a phosphine, or an electron-withdrawing substituent, a phenyl group, a naphthyl group, an aromatic substituent containing an electron-donating group, an aromatic substituent containing an electron-withdrawing group, a heteroaryl group; R 2 is a cyano group, an aryl group, or a heteroaryl group; R 3 is an aryl group or an alkyl group.

[0008] In certain embodiments of the first aspect, the group containing a carboxylic acid, an ester group, and a phosphine is a phosphonate, and the electron-withdrawing substituent is CO2H, CO2R 4 , PO(OR 5 )2, PO(R 6 )2, NO2, CONHPG, CONR 7 R 8 , SO2R 9 , SOR 10 , SR 11 or at least one of them, where R 4-11 is selected from one of methyl, ethyl, propyl, aryl, or heterocycle, PG is a protecting agent Ts, Ns, Boc, Ms, or Ac, or methyl, ethyl, propyl, aryl, heterocycle.

[0009] Combining the first aspect and the above embodiments, in certain embodiments of the first aspect, the aromatic substituent containing an electron-donating group is at least one of p-methylphenyl, p-methoxyphenyl, m-trifluoromethoxyphenyl, p-phenoxyphenyl, p-benzyloxyphenyl, o-methylphenyl, o-methoxyphenyl, m-ethylphenyl, m-methoxyphenyl, p-hydroxymethylphenyl, or p-alkenylphenyl.

[0010] Combining the first aspect and the above embodiments, in certain embodiments of the first aspect, the aromatic substituent containing an electron-withdrawing group is at least one of p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-boronatephenyl, p-esterphenyl, p-acetylphenyl, p-cyanophenyl, m-cyanophenyl, p-amidephenyl, m-sulfonylphenyl, p-aldehyde phenyl, 3,5-difluorophenyl, 2,5-dichlorophenyl, 3-methyl-4-fluorophenyl, p-alkynylphenyl, p-phosphonatephenyl, m-bromophenyl, m-iodophenyl, m-fluorophenyl, o-trifluoromethylphenyl, o-difluoromethylphenyl, or p-trifluoromethylphenyl.

[0011] Combining the first aspect and the above embodiments, in certain embodiments of the first aspect, the heteroaryl group is at least one of indolyl, benzofuranyl, pyridyl, pyrimidinyl, thienyl, benzothienyl, quinolinyl, isoquinolinyl, pyrrolyl, or piperidinyl.

[0012] In a second aspect, the present invention provides a method for preparing an alkenyl nitrile compound for preparing the alkenyl nitrile compound as described in any one of the first aspects of the present invention, and the reaction formula is:

[0013]

[0014] Wherein PC is a photocatalyst, solvent is a solvent, blue LED lamp is a blue-light-emitting LED light source, S1 is a first substrate, S2 is a second substrate, and S3 is a third substrate;

[0015] It includes the following steps:

[0016] After mixing the first substrate, the second substrate, the third substrate, the photocatalyst and the first organic solvent evenly, stir and react at room temperature under the irradiation of a blue light source for 48 hours until the reaction is complete by TLC detection to obtain a post-reaction mixed solution; the first substrate is an olefin derivative, the second substrate is an arylsulfinate sodium, such as sodium benzenesulfinate, sodium p-toluenesulfinate, sodium p-chlorosulfinate, sodium m-bromobenzenesulfinate, etc.; the third substrate is an alcohol compound, such as methanol, ethanol, etc.; the photocatalyst is selected from one of carbazole-based photocatalysts, benzophenone-based photocatalysts, thioxanthone-based photocatalysts, Ir and Ru metal-based photocatalysts.

[0017] Dilute the post-reaction mixed solution with ethyl acetate, extract with water and saturated brine respectively, combine the organic phases, dry and concentrate, and then perform column chromatography treatment to obtain the alkenyl nitrile compound.

[0018] In certain implementations of the second aspect, the first organic solvent is one of dimethyl sulfoxide, dioxane, ethyl acetate, acetonitrile, propionitrile, dichloromethane, dichloroethane, tetrahydrofuran, ethanol, N,N-dimethylformamide, chloroform or ether.

[0019] Combining the second aspect and the above implementations, in certain implementations of the second aspect, the photocatalyst is selected from one of carbazole-based photocatalysts, benzophenone-based photocatalysts, thioxanthone-based photocatalysts, Ir and Ru metal-based photocatalysts.

[0020] Combining the second aspect and the above implementations, under optimized conditions, based on 1.0 equivalent of the olefin derivative, the second substrate is 2.0 equivalents, the third substrate is 5.0 equivalents, and the dosage of the photocatalyst is 2% of the olefin derivative; based on the olefin derivative, the first organic solvent is dichloroethane, the reaction temperature of the system is room temperature, and the reaction time is 48 hours.

[0021] Combined with the second aspect and the above implementation manners, in some implementation manners of the second aspect, the solvent used in the process of column chromatography treatment is a mixed solvent of a second organic solvent and a third organic solvent, the second organic solvent is petroleum ether or an alkane solvent, and the third organic solvent is ethyl acetate, ether or methanol; the volume ratio of the second organic solvent to the third organic solvent is 20:1 to 1:20.

[0022] The technical solutions provided in the embodiments of the present invention bring the following beneficial technical effects:

[0023] The preparation method of the alkenyl nitrile compound provided by the present invention realizes the alkenyl nitrilation reaction that is difficult to synthesize by traditional methods in one step by using a photocatalytic multi-component reaction under simple and mild conditions. The prepared alkenyl nitrile compounds have high added value, various forms, rich substituent types, and have important application prospects. Moreover, the synthesis method has a simple process, cheap and easily available raw materials and auxiliary materials, strong functional group compatibility, a wide substrate range, simple and easy-to-operate reaction conditions, can be synthesized in large quantities, and the product purification is convenient.

[0024] The additional aspects and advantages of the present application will be given in the subsequent parts and will be understood in detail from the subsequent description, or will be understood through the specific implementation of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a schematic flow chart of the preparation method of the alkenyl nitrile compound in an embodiment of the present invention;

[0026] Figure 2 It is for the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P1 synthesized in Example 1 of the present invention;

[0027] Figure 3 It is for the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P2 synthesized in Example 2 of the present invention;

[0028] Figure 4 It is for the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P3 synthesized in Example 3 of the present invention;

[0029] Figure 5 It is for the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P4 synthesized in Example 4 of the present invention;

[0030] Figure 6 It is for the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P5 synthesized in Example 5 of the present invention;

[0031] Figure 7For the synthesis of the alkenyl nitrile compound P6 in Example 6 of the present invention 1 1H NMR characterization spectrum diagram. Detailed implementation mode

[0032] For ease of understanding the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. The possible embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments already described herein through the drawings. The embodiments described by referring to the drawings are exemplary and are used to make the understanding of the disclosure of the present invention more thorough and comprehensive, and should not be construed as a limitation of the present invention. In addition, if the detailed description of the known technology is not necessary for the features of the present invention shown, these technical details may be omitted.

[0033] Those skilled in the relevant art can understand that unless otherwise defined, all terms (including technical terms and scientific terms) used herein have the same meaning as the general understanding of those of ordinary skill in the field to which the present invention belongs. It should also be understood that terms such as those defined in a general dictionary should be understood to have a meaning consistent with the meaning in the prior art and will not be interpreted with an idealized or overly formal meaning unless specifically defined as here.

[0034] Those skilled in the art of the present technology can understand that unless specifically stated, the singular forms "a", "an", "the" and "said" used herein may also include the plural forms. It should be further understood that the term "comprising" used in the specification of the present application means the presence of the stated features, integers, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or their groups. It should be understood that the phrase "and / or" used herein includes all or any unit and all combinations of one or more related listed items.

[0035] The technical solution of the present invention and how this technical solution solves the above technical problems will be described in detail below with specific embodiments.

[0036] An embodiment of the first aspect of the present application provides an alkenyl nitrile compound, and the structural formula of the alkenyl nitrile compound is:

[0037]

[0038] Wherein, R 1 is a group containing a carboxylic acid, an ester group and a phosphine, or an electron-withdrawing substituent, a phenyl group, a naphthyl group, an aromatic substituent containing an electron-donating group, an aromatic substituent containing an electron-withdrawing group, a heteroaryl group; R 2 is a cyano group, an aryl group or a heteroaryl group; R 3is an aryl or an alkyl group.

[0039] The alkenyl nitrile compounds provided by the present invention have high added value, various forms, rich substituent types, important application prospects, and the synthesis method has simple process, cheap and easily available raw materials and auxiliary materials, strong functional group compatibility, and wide substrate range.

[0040] Specifically, in some implementation manners of the embodiments of the first aspect, the group containing carboxylic acid, ester group and phosphine is phosphonate, and the electron-withdrawing substituent is specifically CO2H, CO2R 4 , PO(OR 5 )2, PO(R 6 )2, NO2, CONHPG, CONR 7 R 8 , SO2R 9 , SOR 10 , SR 11 ), where R 4-11 is selected from one of methyl, ethyl, propyl, aryl or heterocycle, PG is a protecting agent Ts, Ns, Boc, Ms or Ac, or methyl, ethyl, propyl, aryl, heterocycle.

[0041] Specifically, combining the embodiments of the first aspect and the above implementation manners, in some other implementation manners, the electron-donating aryl substituent is at least one of p-methylphenyl, p-methoxyphenyl, m-trifluoromethoxyphenyl, p-phenoxyphenyl, p-benzyloxyphenyl, o-methylphenyl, o-methoxyphenyl, m-ethylphenyl, m-methoxyphenyl, p-hydroxymethylphenyl or p-alkenylphenyl.

[0042] Specifically, in some other implementation manners of the embodiments of the first aspect, the aromatic substituent containing an electron-withdrawing group is at least one of p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-borate phenyl, p-ester phenyl, p-acetylphenyl, p-cyanophenyl, m-cyanophenyl, p-amide phenyl, m-sulfonylphenyl, p-aldehyde phenyl, 3,5-difluorophenyl, 2,5-dichlorophenyl, 3-methyl-4-fluorophenyl, p-alkyne phenyl, p-phosphonate phenyl, m-bromophenyl, m-iodophenyl, m-fluorophenyl, o-trifluoromethylphenyl, o-difluoromethylphenyl or p-trifluoromethylphenyl.

[0043] Optionally, the heteroaryl is at least one of indolyl, benzofuranyl, pyridyl, pyrimidinyl, thienyl, benzothienyl, quinolinyl, isoquinolinyl, pyrrolyl or piperidinyl.

[0044] The embodiments of the second aspect of the present invention provide a preparation method of an alkenyl nitrile compound for preparing the alkenyl nitrile compound according to any one of the first aspect of the present invention, and the reaction formula is:

[0045]

[0046] Wherein, PC is a photocatalyst, solvent is a solvent, blue LED lamp is a blue-light-emitting LED light source, S1 is the first substrate, S2 is the second substrate, and S3 is the third substrate;

[0047] As Figure 1 shown, it includes the following steps:

[0048] S100: After uniformly mixing the first substrate, the second substrate, the third substrate, the photocatalyst and the first organic solvent, stir and react under blue light irradiation at room temperature for 48 hours until the reaction is complete by TLC (thin-layer chromatography) detection to obtain a post-reaction mixed solution. The first substrate is an olefin derivative, the second substrate is an arylsulfinate sodium, such as sodium benzenesulfinate, sodium p-toluenesulfinate, sodium p-chlorosulfinate, sodium m-bromobenzenesulfinate, etc.; the third substrate is an alcohol compound, such as methanol, ethanol, etc.

[0049] S200: Dilute the post-reaction mixed solution with ethyl acetate, extract with water and saturated brine respectively, combine the organic phases, dry and concentrate, and then perform column chromatography treatment to obtain alkenyl nitrile compounds.

[0050] The preparation method of alkenyl nitrile compounds provided by the present invention realizes the alkenyl cyanation reaction that is difficult to achieve by traditional methods in one step by using photocatalytic multicomponent reaction under simple and mild conditions. The prepared alkenyl nitrile compounds have high added value, various forms, rich substituent types, and have important application prospects. Moreover, the synthesis method has a simple process, cheap and easily available raw materials and auxiliaries, strong functional group compatibility, a wide substrate range, simple and easy-to-operate reaction conditions, can be synthesized in large quantities, and the product purification is convenient.

[0051] Specifically, in some implementation manners of the second aspect embodiment, the first organic solvent is one of dimethyl sulfoxide, dioxane, ethyl acetate, acetonitrile, propionitrile, dichloromethane, dichloroethane, tetrahydrofuran, ethanol, N,N-dimethylformamide, chloroform or ether.

[0052] Combining the second aspect and the above implementation manners, specifically, in some other implementation manners of the second aspect embodiment, the photocatalyst is selected from one of carbazole-based photocatalysts, benzophenone-based photocatalysts, thioxanthone-based photocatalysts, Ir and Ru metal-based photocatalysts.

[0053] Specifically, under optimized conditions, based on 1.0 equivalent of the olefin derivative, the second substrate is 2.0 equivalents, the third substrate is 5.0 equivalents, and the dosage of the photocatalyst is 2% of the olefin; based on the olefin derivative, the first organic solvent is dichloroethane, the reaction temperature of the system is room temperature, and the reaction time is 48 hours.

[0054] Specifically, the solvent used in the column chromatography process is a mixed solvent of a second organic solvent and a third organic solvent. The second organic solvent is petroleum ether or an alkane solvent, and the third organic solvent is ethyl acetate, diethyl ether, or methanol; the volume ratio of the second organic solvent to the third organic solvent is 20:1 to 1:20.

[0055] The following are specific examples:

[0056] The products of each example are:

[0057] Example 1: Synthesis of alkenyl nitrile compound P1

[0058]

[0059] In a nitrogen atmosphere, olefin S1 (40 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. The blue 30W LED light was turned on, and the distance between the bulb and the reaction flask was 5 - 10 cm. The mixture was stirred at room temperature for 48 hours, and the reaction was monitored by TLC (thin - layer chromatography). After the reaction was completed, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, the organic phase was concentrated, and the crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 38 mg (colorless liquid) of product compound P1, with a yield of 95% and a purity of ≥95%. Figure 2 It is the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P1 synthesized in Example 1 of the present invention application.

[0060] The 1H NMR data of P1 are as follows:

[0061] 1 1H NMR (400 MHz, CDCl3) δ H 7.40 (d, J = 7.2 Hz, 2H), 7.38–7.31 (m, 3H), 5.95 (s, 1H), 5.83 (s, 1H), 3.84 (t, J = 7.5 Hz, 1H), 2.47 (t, J = 7.7 Hz, 2H), 2.17 (q, J = 7.6 Hz, 2H) ppm.

[0062] HRMS (ESI + ) calcd. for C 13 H 13 N2 [M + H]+ 197.1079, found 197.1078.

[0063] Example 2: Synthesis of alkenyl nitrile compound P2

[0064]

[0065] Under a nitrogen atmosphere, alkene S1 (45 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. The blue 30 W LED light was turned on, and the distance between the bulb and the reaction flask was 5 - 10 cm. The mixture was stirred at room temperature for 48 h, and the reaction was monitored by TLC (thin - layer chromatography). After completion of the reaction, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, and the organic phase was concentrated. The crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 44 mg (colorless liquid) of product compound P2, with a yield of 98% and a purity of ≥95%. Figure 3 is the alkenyl nitrile compound P2 synthesized in Example 2 of this invention application 1 1H NMR characterization spectrum.

[0066] The 1H NMR data of P2 are as follows:

[0067] 1 1H NMR (400 MHz, CDCl3) δ H 7.43–7.38 (m, 1H), 7.36–7.30 (m, 1H), 7.03–6.97 (m, 1H), 6.91 (d, J = 8.2 Hz, 1H), 5.93 (s, 1H), 5.83 (d, J = 1.4 Hz, 1H), 4.25–4.17 (m, 1H), 3.87 (s, 3H), 2.53–2.42 (m, 2H), 2.22–2.02 (m, 2H) ppm.

[0068] HRMS (ESI + ) calcd. for C 14 H 15 N2O [M + H] + 227.1184, found 227.1185.

[0069] Example 3: Synthesis of alkenyl nitrile compound P3

[0070]

[0071] In a nitrogen atmosphere, olefin S1 (45 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. A 30 W blue LED light was turned on, and the distance between the bulb and the reaction flask was 5 - 10 cm. The mixture was stirred at room temperature for 48 h, and the reaction was monitored by TLC (thin - layer chromatography). After the reaction was completed, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, the organic phase was concentrated, and the crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 36 mg (colorless liquid) of product compound P3, with a yield of 81% and a purity of ≥95%. Figure 4 It is the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P3 synthesized in Example 3 of this invention application.

[0072] The 1H NMR data of P3 are as follows:

[0073] 1 1H NMR (400 MHz, CDCl3) δ H 7.36–7.29 (m, 2H), 7.25–7.17 (m, 3H), 5.91 (s, 1H), 5.81 (d, J = 1.5 Hz, 1H), 2.98–2.85 (m, 1H), 2.81–2.70 (m, 1H), 2.60–2.48 (m, 2H), 2.45–2.33 (m, 1H), 2.04–1.95 (m, 1H), 1.94–1.82 (m, 3H) ppm.

[0074] HRMS (ESI + ) calcd. for C 15 H 17 N2 [M + H] + 225.1392, found 225.1393.

[0075] Example 4: Synthesis of alkenyl nitrile compound P4

[0076]

[0077] In a nitrogen atmosphere, alkene S1 (43 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. The blue 30W LED light was turned on, and the distance between the bulb and the reaction flask was 5 - 10 cm. The mixture was stirred at room temperature for 48 hours, and the reaction was monitored by TLC (thin - layer chromatography). After the reaction was completed, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, and the organic phase was concentrated. The crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 22 mg (colorless liquid) of product compound P4, with a yield of 50% and a purity of ≥95%. Figure 5 is the 1 1H NMR characterization spectrum of the alkenyl nitrile compound P4 synthesized in Example 4 of this invention application.

[0078] The 1H NMR data of P4 are as follows:

[0079] 1 1H NMR (400 MHz, CDCl3) δ H 7.24–7.19 (m, 1H), 7.01–6.94 (m, 2H), 5.94 (s, 1H), 5.84 (d, J = 1.4 Hz, 1H), 3.25–3.10 (m, 2H), 2.89–2.79 (m, 1H), 2.63–2.51 (m, 1H), 2.50–2.40 (m, 1H), 1.98–1.79 (m, 2H) ppm.

[0080] HRMS (ESI + ) calcd. for C 12 H 13 N2S [M + H] + 217.0799, found 217.0798.

[0081] Example 5: Synthesis of alkenyl nitrile compound P5

[0082]

[0083] In a nitrogen atmosphere, olefin S1 (84 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. A 30 W blue LED light was turned on, and the bulb was 5 - 10 cm away from the reaction flask. The mixture was stirred at room temperature for 48 h, and the reaction was monitored by TLC (thin - layer chromatography). After the reaction was completed, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, and the organic phase was concentrated. The crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 26 mg (colorless liquid) of product compound P5, with a yield of 51% and a purity of ≥95%. Figure 6 1H NMR characterization spectrum of the alkenyl nitrile compound P5 synthesized in Example 5 of this invention application 1 1H NMR characterization spectrum

[0084] The 1H NMR data of P5 are as follows:

[0085] 1 1H NMR (400 MHz, CDCl3) δ H 7.56–7.50 (m, 2H), 7.49–7.42 (m, 3H), 7.36–7.30 (m, 2H), 7.30–7.25 (m, 1H), 7.12–7.08 (m, 2H), 6.83 (d, J = 11.5 Hz, 1H), 5.79–5.69 (m, 1H), 3.25–3.20 (m, 2H) ppm.

[0086] HRMS (ESI + ) calcd. for C 18 H 15 N2 [M + H] + 259.1253, found 259.1255.

[0087] Example 6: Synthesis of alkenyl nitrile compound P6

[0088]

[0089] In a nitrogen atmosphere, olefin S1 (67 mg, 0.200 mmol, 1.00 equiv), second substrate S2 PhSO2Na (66 mg, 0.400 mmol, 2.0 equiv), third substrate S3 EtOH (46 mg, 1.0 mmol, 5.0 equiv), photocatalyst 4CzIPN (2 mol%), and organic solvent DCE were added to a reaction flask. The blue 30 W LED light was turned on, and the bulb was 5 - 10 cm away from the reaction flask. The mixture was stirred at room temperature for 48 h, and the reaction was monitored by TLC (thin - layer chromatography). After the reaction was completed, it was diluted with ethyl acetate and then extracted with water and saturated brine respectively. The organic layer was dried, and the organic phase was concentrated. The crude product was directly obtained by column chromatography with V petroleum ether / V ethyl acetate = 10:1 to give 59 mg (yellow solid) of product compound P6, with a yield of 88% and a purity of ≥95%. Figure 7 1H NMR characterization spectrum of the alkenyl nitrile compound P6 synthesized in Example 6 of this invention application 1

[0090] The 1H NMR data of P6 are as follows:

[0091] 1 1H NMR (400 MHz, CDCl3) δ H 7.27 (s, 4H), 5.98 (s, 1H), 5.87 (d, J = 1.3 Hz, 1H), 3.83 (t, J = 7.4 Hz, 1H), 2.56–2.47 (m, 3H), 2.19 (q, J = 7.6 Hz, 2H), 1.91 (d, J = 11.6 Hz, 4H), 1.51–1.43 (m, 2H), 1.35–1.32 (m, 4H), 1.27 (s, 2H), 1.10 (t, J = 12.0 Hz, 2H), 0.94 (q, J = 5.0, 3.5 Hz, 3H), 0.86 (d, J = 11.3 Hz, 1H) ppm.

[0092] HRMS (ESI + ) calcd. for C 23 H 31 N2 [M + H] + 335.2487, found 335.2488.

[0093] ​Those skilled in the art can understand that the various operations, methods, steps, measures, and solutions in the processes discussed in this application can be alternated, changed, combined, or deleted. Further, other steps, measures, and solutions in the various operations, methods, and processes discussed in this application can also be alternated, changed, rearranged, decomposed, combined, or deleted. Further, the steps, measures, and solutions in the prior art that are the same as those disclosed in the various operations, methods, and processes in this application can also be alternated, changed, rearranged, decomposed, combined, or deleted.

[0094] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of this application, unless otherwise specified, the meaning of "a plurality" is two or more.

[0095] In the description of this specification, specific features, structures, materials, or characteristics may be combined in a suitable manner in any one or more embodiments or examples.

[0096] The above are only some embodiments of this application. It should be noted that for those of ordinary skill in the art, without departing from the principle of this application, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of this application.

Claims

1. An alkenyl nitrile compound, characterized in that The structural formula of the alkenyl nitrile compound is: Among them, R 1 is a group containing carboxylic acid, ester group and phosphine, or an electron-withdrawing substituent, phenyl, naphthyl, an aromatic substituent containing an electron-donating group, an aromatic substituent containing an electron-withdrawing group, or a heteroaryl group; R 2 is cyano, aryl or heteroaryl; R 3 is an aryl group or an alkyl group.

2. The alkenyl nitrile compound according to claim 1, characterized in that The group containing carboxylic acid, ester group and phosphine is a phosphonate, and the electron-withdrawing substituent is CO2H, CO2R 4 ,PO(OR 5 2. PO(R 6 )2, NO2, CONHPG, CONR 7 R 8 、SO2R 9 、SOR 10 , SR 11 At least one of the following, where R 4-11 is selected from one of methyl, ethyl, propyl, aryl or heterocyclic ring, and PG is a protecting agent Ts, Ns, Boc, Ms or Ac, or methyl, ethyl, propyl, aryl or heterocyclic ring.

3. The alkenyl nitrile compound according to claim 1, characterized in that The electron-donating aryl substituent is at least one of p-methylphenyl, p-methoxyphenyl, m-trifluoromethoxyphenyl, p-phenoxyphenyl, p-benoxyphenyl, o-methylphenyl, o-methoxyphenyl, m-ethylphenyl, m-methoxyphenyl, p-hydroxymethylphenyl or p-olefinphenyl.

4. The alkenyl nitrile compound according to claim 1, characterized in that The aromatic substituent containing an electron-withdrawing group is at least one of p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-boronate phenyl, p-ester phenyl, p-acetyl phenyl, p-cyanophenyl, m-cyanophenyl, p-amide phenyl, m-sulfonyl phenyl, p-aldehyde phenyl, 3,5-difluorophenyl, 2,5-dichlorophenyl, 3-methyl-4-fluorophenyl, p-alkyne phenyl, p-phosphonate phenyl, m-bromophenyl, m-iodophenyl, m-fluorophenyl, o-trifluoromethylphenyl, o-difluoromethylphenyl or p-trifluoromethylphenyl.

5. The alkenyl nitrile compound according to claim 1, characterized in that The heteroaryl group is at least one of an indolyl group, a benzofuranyl group, a pyridyl group, a pyrimidyl group, a thienyl group, a benzothienyl group, a quinolyl group, an isoquinolyl group, a pyrrolyl group or a piperidinyl group.

6. A method for preparing an alkenyl nitrile compound, characterized in that: For preparing the alkenyl nitrile compound according to any one of claims 1 to 5, the reaction formula is: Wherein PC is a photocatalyst, solvent is a solvent, blue LED is a blue light emitting LED light source, S1 is the first substrate, S2 is the second substrate, and S3 is the third substrate; The following steps are involved: After uniformly mixing a first substrate, a second substrate, a third substrate, a photocatalyst and a first organic solvent, stirring and reacting at room temperature for 48 hours under irradiation with a blue light source until the reaction is complete as detected by TLC, to obtain a mixed solution after reaction; the first substrate is an olefin derivative; the second substrate is sodium arylsulfinate, and the third substrate is an alcohol compound; The mixed solution after the reaction is diluted with ethyl acetate, and then extracted with water and saturated brine respectively. The organic phases are combined, dried and concentrated, and then treated by column chromatography to obtain the alkenyl nitrile compound.

7. The method for preparing alkenyl nitrile compounds according to claim 6, characterized in that: The first organic solvent is one of dimethyl sulfoxide, dioxane, ethyl acetate, acetonitrile, propionitrile, dichloromethane, dichloroethane, tetrahydrofuran, ethanol, dimethylformamide, chloroform or diethyl ether.

8. The method for preparing alkenyl nitrile compounds according to claim 6, characterized in that: The second substrate is sodium arylsulfinate, such as sodium phenylsulfinate, sodium p-methylphenylsulfinate, sodium p-chlorosulfinate, sodium m-bromophenylsulfinate, etc.; the third substrate is an alcohol compound, such as methanol, ethanol, etc.; the photocatalyst is selected from one of carbazole photocatalysts, benzophenone photocatalysts, thioxanthone photocatalysts, Ir and Ru metal photocatalysts.

9. The method for preparing alkenyl nitrile compounds according to claim 6, characterized in that: Under the optimized conditions, the olefin derivative is 1.0 equivalent, the second substrate is 2.0 equivalent, the third substrate is 5.0 equivalent, and the amount of the photocatalyst is 2% of the olefin derivative; based on the olefin derivative, the first organic solvent is dichloroethane, the reaction temperature of the system is room temperature, and the reaction time is 48 hours.

10. The method for preparing alkenyl nitrile compounds according to claim 6, characterized in that: The solvent used in the column chromatography process is a mixed solvent of a second organic solvent and a third organic solvent, the second organic solvent is petroleum ether or an alkane solvent, and the third organic solvent is ethyl acetate, diethyl ether or methanol; the volume ratio of the second organic solvent to the third organic solvent is 20:1 to 1:20.

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