A cobalt-catalyzed method for synthesizing alkyne

Abstract

The application discloses a method for synthesizing alkynes by using cobalt as a catalyst, and belongs to the technical field of chemical medicine synthesis. The synthesis method comprises the following steps: mixing an alkyne chloride derivative, a boronic acid derivative, a cobalt salt, a ligand, a base and a solvent, and heating the mixture to obtain the product under an inert gas atmosphere. The method has the following beneficial effects: the application proposes a new reaction for synthesizing alkynes from alkyne halides and boronic acid derivatives, uses a cobalt-based catalyst, and uses a boronic acid derivative as a coupling reagent. The cobalt has low cost and high reactivity, the boronic acid derivative is simple to prepare, easy to operate, safe, has good functional group compatibility, and generates no large amount of waste after reaction, thus meeting the requirements of green development.

Description

Technical Field

[0001] This invention relates to the field of chemical drug synthesis technology, and more specifically to a method for synthesizing alkynes using cobalt catalysis. Background Technology

[0002] In recent decades, transition metal-catalyzed carbon-carbon cross-coupling reactions have been among the most efficient reactions in organic chemistry, widely used in pharmaceuticals, agriculture, and the synthesis of fine compounds. This synthetic strategy of transition metal-catalyzed carbon-carbon bond construction has attracted increasing research and attention. Traditionally, palladium-catalyzed coupling reactions are the most widely used transition metal catalysts, such as Suzuki coupling, Negishi coupling, and Stille coupling. Although palladium-catalyzed cross-coupling reactions are widely applied, palladium is too expensive and has high biotoxicity. However, first transition metals (iron, cobalt, nickel, and copper) are inexpensive, and using first transition metals instead of palladium as catalysts greatly reduces reaction costs. In particular, cobalt-catalyzed carbon-carbon cross-coupling has been extensively studied.

[0003] Common cobalt-catalyzed reactions require the use of stoichiometric organometallic reagents and alkynyl halides. However, organometallic reagents, such as Grignard reagents or organozinc reagents, pose risks during transportation and storage, and exhibit poor functional group compatibility. This method discovers a way to synthesize alkynes using cobalt-based catalysts from alkynyl halides and boric acid derivatives. This method, due to its economy, low toxicity, and unique reaction mode, can shorten the synthetic route and offers better functional group compatibility.

[0004] Traditionally, this reaction most commonly uses palladium catalysts, which are expensive and highly biotoxic, severely limiting their application in pharmaceutical and industrial synthesis. Research has shown that cobalt catalysts offer milder reaction conditions, higher chemoselectivity, and lower cost, making them a viable alternative to expensive and toxic palladium catalysts. Common cobalt catalysts require the use of equivalent organometallic reagents, which are hazardous during transportation and storage, making industrial scale-up difficult. Most of these reactions are incompatible with relevant functional groups (such as hydroxyl, amine, and carboxylic acids), requiring additional reaction steps for protection and deprotection. Furthermore, the reaction requires the disposal of large amounts of residual metals or metal halides, hindering green development.

[0005] Japanese patent application JP2011247033A discloses a method for synthesizing acetylenyl benzophenone compounds and their derivatives. The reaction uses 4-bromobenzophenone and phenylacetylene as starting materials, and prepares the acetylenyl benzophenone compound in the presence of an organic base using bis(triphenylphosphine)palladium chloride as a catalyst. This method has a broad substrate scope, is simple, and is easy to operate. However, the catalyst is expensive, and the target product yield is relatively low. Summary of the Invention

[0006] The technical problem to be solved by this invention is how to solve the problems of complex preparation steps, low yield and high cost of existing alkyne compounds.

[0007] The present invention solves the above-mentioned technical problems through the following technical means:

[0008] A cobalt-catalyzed method for synthesizing alkynes includes the following steps: mixing an alkyne chloride derivative, a boric acid derivative, a cobalt salt, a ligand, a basic substance, and a reaction solvent, and heating the mixture under an inert gas atmosphere to obtain the desired alkyne.

[0009] Beneficial effects: This invention proposes a novel reaction for synthesizing alkynes from alkynyl halides and boric acid derivatives, using a cobalt catalyst and a boric acid derivative as a coupling agent. Cobalt is low in cost and highly reactive; the boric acid derivative is simple to prepare, easy to operate, safe, has good functional group compatibility, and does not generate large amounts of waste after the reaction, thus conforming to green development principles.

[0010] Preferably, the cobalt salt includes, but is not limited to, one or more of cobalt chloride, cobalt bromide, cobalt trifluoromethanesulfonate, and cobalt chloride hexahydrate.

[0011] Preferably, the molar ratio of the acetylacetic chloride derivative, boric acid derivative, cobalt salt, ligand and alkaline substance is 1:(2-4):(0.01-0.2):(0.01-0.2):(0.5-2).

[0012] Preferably, the molar ratio of the acetylacetic chloride derivative, boric acid derivative, cobalt salt, ligand and alkaline substance is 1:3:0.1:0.1:1.

[0013] Preferably, the boric acid derivative includes arylboronic acid, alkenylboronic acid, and heterocyclic boric acid derivatives. More preferably, the boric acid derivative includes, but is not limited to, one of the following structural formulas:

[0014]

[0015] Preferably, the acetylenic chloride derivative includes arylacenic chloride, alkylacetylenic chloride, alkenylacetylenic chloride, and silylacetylenic chloride. More preferably, the acetylenic chloride derivative is not limited to one of the following structural formulas:

[0016]

[0017] Preferably, the alkaline substance includes, but is not limited to, one or more of potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide.

[0018] Preferably, the ligand includes, but is not limited to, one or more of 2,3-bis(diphenylphosphine)butane, 1,2-bis(diphenylphosphine)benzene, 1,2-bis(diphenylphosphine)ethane, and cis-1,2-bis(diphenylphosphine)ethylene.

[0019] Preferably, the reaction solvent includes, but is not limited to, acetonitrile, isobutyronitrile, and mixed solvents containing nitrile solvents.

[0020] Preferably, the heating reaction temperature is 60-100℃ and the reaction time is 6-10h.

[0021] Preferably, the heating reaction temperature is 80°C and the reaction time is 8 hours.

[0022] The advantages of this invention are:

[0023] 1. This invention proposes a novel reaction for synthesizing alkynes from alkynyl halides and boric acid derivatives. A cobalt catalyst with high catalytic activity is obtained by complexation with a cobalt salt and ligands, and a boric acid derivative is used as a coupling agent. Cobalt is low in cost and has high reactivity; the boric acid derivative is simple to prepare, easy to operate, safe, has good functional group compatibility, and does not generate large amounts of waste after the reaction, thus conforming to green development principles.

[0024] 2. This invention can reduce reaction costs, as the price of cobalt is much lower than that of palladium, its biotoxicity is also lower than that of palladium catalysts, and the reaction is excellent.

[0025] 3. Compared with other cobalt-catalyzed reactions, the raw material used in this invention is a boric acid derivative, which does not require the use of equivalent organometallic reagents. The raw material preparation is easy, the reaction conditions are milder, and the compatibility with functional groups is better. Attached Figure Description

[0026] Figure 1 The 1H NMR spectrum of diphenylacetylene obtained in Example 1 of this invention;

[0027] Figure 2 The 1H NMR spectrum of 1-methyl-4-(phenylethynyl)benzene obtained in Example 2 of this invention;

[0028] Figure 3 The 1H NMR spectrum of 1-isopropyl-4-(phenylethynyl)benzene obtained in Example 3 of this invention;

[0029] Figure 4The 1H NMR spectrum of 1-chloro-4-(phenylethynyl)benzene obtained in Example 4 of this invention;

[0030] Figure 5 The 1H NMR spectrum of 1-iodo-4-(phenylethynyl)benzene obtained in Example 5 of this invention;

[0031] Figure 6 The 1H NMR spectrum of 4-(phenylethynyl)phenol prepared in Example 6 of this invention;

[0032] Figure 7 The 1H NMR spectrum of 1-(4-(phenylethynyl)phenyl)ethane-1-one obtained in Example 7 of this invention;

[0033] Figure 8 The 1H NMR spectrum of (cyclohex-1-en-1-ylethynyl)benzene obtained in Example 8 of this invention;

[0034] Figure 9 The 1H NMR spectrum of 2-(phenylethynyl)furan obtained in Example 9 of this invention;

[0035] Figure 10 The 1H NMR spectrum of 1-methyl-4-(oct-1-yn-1-yl)benzene prepared in Example 10 of this invention;

[0036] Figure 11 The 1H NMR spectrum of 1-(cyclopent-1-en-1-ethynyl)cyclohex-1-ene obtained in Example 11 of this invention;

[0037] Figure 12 The 1H NMR spectrum of ((3-bromo-5-chlorophenyl)ethynyl)(tert-butyl)dimethylsilane prepared in Example 12 of this invention. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0039] The technical solution of the present invention will be described in more detail below with reference to embodiments:

[0040] Example 1: Preparation of diphenylacetylene

[0041]

[0042] Weigh out 68 mg of acetylene chloride derivative. 1 eq (0.5 mmol), 195 mg phenylboronic acid (3.2 eq, 1.6 mmol), 69 mg potassium carbonate (1 eq, 0.5 mmol), 6.5 mg cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product A was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0043] The target product was a white solid. The yield of diphenylacetylene was calculated to be 99% based on the yield calculation of the acetylene chloride derivative. The relevant characterization data are as follows: 1H NMR (600MHz, CDCl3) δ 7.60-7.54 (m, 4H), 7.41-7.32 (m, 6H).

[0044] Example 2: Preparation of 1-methyl-4-(phenylethynyl)benzene

[0045]

[0046] Weigh out 68 mg of acetylene chloride derivative. 218 mg of 4-tolylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product B was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0047] The target product was a white solid, with a yield of 99% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.57-7.53 (m, 2H), 7.48-7.44 (m, 2H), 7.39-7.31 (m, 3H), 7.20-7.16 (m, 2H), 2.39 (s, 3H).

[0048] Example 3: Preparation of 1-isopropyl-4-(phenylethynyl)benzene

[0049]

[0050] Weigh out 68 mg of acetylene chloride derivative. 262 mg of 4-isopropylphenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product C was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0051] The target product is a pale yellow liquid, with a yield of 97% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.56–7.51 (m, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.38–7.30 (m, 3H), 7.22 (d, J = 8.1 Hz, 2H), 2.92 (m, 1H), 1.27 (d, J = 6.9 Hz, 6H).

[0052] Example 4: 1-Chloro-4-(Phenylacetyl)benzene

[0053]

[0054] Weigh out 68 mg of acetylene chloride derivative. 250 mg of 4-chlorophenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product D was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0055] The target product was a white solid, with a yield of 99% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.54–7.51 (m, 2H), 7.47–7.44 (m, 2H), 7.37–7.34 (m, 3H), 7.34–7.31 (m, 2H).

[0056] Example 5: 1-Iodo-4-(phenylethynyl)benzene

[0057]

[0058] Weigh out 68 mg of acetylene chloride derivative. 396 mg of 4-iodophenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product E was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0059] The target product was a white solid, with a yield of 83% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.69 (d, J = 8.3 Hz, 2H), 7.56–7.50 (m, 2H), 7.38–7.33 (m, 3H), 7.26 (d, J = 8.4 Hz, 2H).

[0060] Example 6: 4-(Phenylacetyl)phenol

[0061]

[0062] Weigh out 68 mg of acetylene chloride derivative. 221 mg of 4-hydroxyphenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 8:1 as the eluent). After the reaction was completed, the target product F was obtained by silica gel column chromatography (petroleum ether:ethyl acetate = 80:1 as the eluent).

[0063] The target product was a white solid, with a yield of 91% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.55–7.48 (m, 2H), 7.46–7.40 (m, 2H), 7.38–7.29 (m, 3H), 6.86–6.77 (m, 2H), 5.38 (s, 1H).

[0064] Example 7: 1-(4-(phenylethynyl)phenyl)ethane-1-one

[0065]

[0066] Weigh out 68 mg of acetylene chloride derivative. 262 mg of 4-acetylphenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 6:1 as the eluent). After the reaction was completed, the target product G was obtained by silica gel column chromatography (petroleum ether:ethyl acetate = 60:1 as the eluent).

[0067] The target product was a white solid, with a yield of 75% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.94 (d, J = 8.1 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 7.57–7.52 (m, 2H), 7.40–7.34 (m, 3H), 2.62 (s, 3H).

[0068] Example 8: (cyclohexyl-1-en-1-ylethynyl)benzene

[0069]

[0070] Weigh out 68 mg of acetylene chloride derivative. 202 mg of 1-cyclohexene-1-ylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product H was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0071] The target product is a yellow gel, with a yield of 98% calculated based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.44–7.41 (m, 2H), 7.32–7.26 (m, 3H), 6.21 (tt, J = 4.1, 1.9 Hz, 1H), 2.26–2.21 (m, 2H), 2.17–2.12 (m, 2H), 1.71–1.65 (m, 2H), 1.65–1.59 (m, 2H).

[0072] Example 9: 2-(Phenylacetyl)furan

[0073]

[0074] Weigh out 68 mg of acetylene chloride derivative. 179 mg of 2-furanboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product I was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0075] The target product was a colorless liquid, with a calculated yield of 55% based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.55–7.51 (m, 2H), 7.43 (dd, J = 1.9, 0.8 Hz, 1H), 7.37–7.33 (m, 3H), 6.66 (dd, J = 3.4, 0.9 Hz, 1H), 6.43 (dd, J = 3.4, 1.9 Hz, 1H).

[0076] Example 10: 1-Methyl-4-(oct-1-yn-1-yl)benzene

[0077]

[0078] Weigh out 72 mg of acetylene chloride derivative. 218 mg of 4-tolylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product J was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0079] The target product was a colorless liquid, with a calculated yield of 90% based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.29 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 2.40 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 1.63–1.56 (m, 2H), 1.49–1.42 (m, 2H), 1.37–1.28 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H).

[0080] Example 11: 1-(cyclopent-1-en-1-ethynyl)cyclohexyl-1-ene

[0081]

[0082] Weigh out 70 mg of acetylene chloride derivative. 179 mg of cyclopenten-1-ylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product K was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0083] The target product was a brown gel, with a calculated yield of 82% based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 6.11–6.07 (m, ¹H), 6.00–5.97 (m, ¹H), 2.47–2.39 (m, 4H), 2.16–2.12 (m, 2H), 2.12–2.07 (m, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.66–1.60 (m, 2H), 1.60–1.56 (m, 2H).

[0084] Example 12: ((3-bromo-5-chlorophenyl)ethynyl)(tert-butyl)dimethylsilane

[0085]

[0086] Weigh out 87 mg of acetylene chloride derivative. 376 mg of 3-bromo-5-chlorophenylboronic acid (3.2 eq, 1.6 mmol), 69 mg of potassium carbonate (1 eq, 0.5 mmol), 6.5 mg of cobalt chloride (0.1 eq, 0.05 mmol), and 22 mg of 2,3-bis(diphenylphosphine)butane (0.1 eq, 0.05 mmol) were added to a reaction tube. Then, 2 mL of acetonitrile was added to the reaction tube, and the air was replaced with argon using a double-row tube. The reaction was carried out at 80 °C for 8 h. The reaction was monitored by TLC (petroleum ether as the eluent). After the reaction was completed, the target product L was obtained by silica gel column chromatography (petroleum ether as the eluent).

[0087] The target product was a colorless liquid, with a calculated yield of 77% based on the acetylacetonate chlorine derivative. The relevant characterization data are as follows: ¹H NMR (600 MHz, CDCl₃) δ 7.49–7.48 (m, ¹H), 7.45 (t, J = 1.8 Hz, ¹H), 7.37 (dd, J = 2.0, 1.4 Hz, ¹H), 0.98 (s, 9H), 0.18 (s, 6H).

[0088] Example 13:

[0089] The difference between this embodiment and Example 1 is that: phenylboronic acid (2 eq, 1.0 mmol), cobalt chloride (0.01 eq, 0.005 mmol), 2,3-bis(diphenylphosphine)butane (0.01 eq, 0.005 mmol), and potassium carbonate (0.5 eq, 0.25 mmol) are used, while the other steps are the same as in Example 1.

[0090] Example 14:

[0091] The difference between this embodiment and Example 1 is that: phenylboronic acid (4 eq, 2.0 mmol), cobalt chloride (0.2 eq, 0.1 mmol), 2,3-bis(diphenylphosphine)butane (0.2 eq, 0.1 mmol), and potassium carbonate (2 eq, 1.0 mmol) are used, while the other steps are the same as in Example 1.

[0092] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing alkynes using cobalt catalysis, characterized in that, Includes the following steps: The acetylene chloride derivative, boric acid derivative, cobalt salt, ligand, basic substance, and reaction solvent are mixed and reacted under an inert gas atmosphere by heating. The cobalt salt is one or more of cobalt chloride, cobalt bromide, cobalt trifluoromethanesulfonate, and cobalt chloride hexahydrate. The ligand is one or more of 2,3-bis(diphenylphosphine)butane, 1,2-bis(diphenylphosphine)benzene, 1,2-bis(diphenylphosphine)ethane, and cis-1,2-bis(diphenylphosphine)ethylene. The heating temperature is 60-100℃, and the reaction time is 6-10 h. The acetylene chloride derivative has one of the following structural formulas: , , , The boric acid derivative is one of the following structural formulas: 、 、 、 、 、 、 、 、 、 。 2. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The cobalt salt is cobalt chloride.

3. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The molar ratio of the acetylacetic chloride derivative, boric acid derivative, cobalt salt, ligand and alkaline substance is 1:(2-4):(0.01-0.2):(0.01-0.2):(0.5-2).

4. The method for synthesizing alkynes by cobalt catalysis according to claim 3, characterized in that, The molar ratio of the acetylacetic chlorine derivative, boric acid derivative, cobalt salt, ligand and alkaline substance is 1:3:0.1:0.1:

1.

5. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The boric acid derivative is: .

6. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The acetylacetic chloride derivative is .

7. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The alkaline substance is one or more of potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide.

8. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The ligand is 2,3-bis(diphenylphosphine)butane.

9. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The heating reaction was carried out at a temperature of 60°C for 10 hours.

10. The method for synthesizing alkynes by cobalt catalysis according to claim 1, characterized in that, The heating reaction was carried out at a temperature of 80°C for 8 hours.

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