A method for electrocatalytic synthesis of 1-iodine acetylenic compounds

Abstract

The present invention discloses a method for the electrocatalytic synthesis of 1-iodinated acetylenic compounds. In an air atmosphere, an alkyne substrate is used in a mixed solvent system of acetonitrile and water with sodium iodide as an electrolyte to successfully prepare a series of 1-iodinated acetylenic compounds. Compared with existing methods, the technical advantages of the present invention are that no protective atmosphere is required, which reduces process costs, equipment requirements, and operational difficulty, reduces the amount of organic solvent used, improves atom economy, does not use metal catalysts, bases, oxidants, and / or other reaction aids, and the reaction conditions are mild, simple, and easy to operate.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for electrocatalytically synthesizing 1-iodine acetylene compounds. Background Art

[0002] 1-Iodoalkynes are important intermediates in organic synthesis and are widely used as precursors for various higher-order structures, such as conjugated diynes, enynes, substituted alkenes, heterocycles, and functional polymers. Due to their unique structure, which allows for controlled electrophilicity and nucleophilicity, they are also considered difunctionalized molecules. Prior art reports describe the preparation of 1-iodoalkynes using terminal alkynes as starting materials using a variety of metal catalysts, hypervalent iodine salts, ionic liquids, bases, phase transfer catalysts, ultrasonication, iodine oxides, Grignard reagents, and / or n-butyllithium methods.

[0003] Organic electrosynthesis is an efficient and mild synthetic tool that can achieve redox reactions in the absence of exogenous oxidants and reductants through anodic oxidation and cathodic reduction. Environmental protection is one of the advantages of electrochemical synthesis. Traditional methods are usually carried out at high temperatures or high pressures, while electrochemical reactions are usually carried out under milder conditions. Traditional reactions usually require quenching, while electrochemical reactions can be stopped at any time by turning off the power switch. Due to the high reaction efficiency of electrochemical reactions, the reaction time is usually short, which is easy to scale up and has great potential in industrial applications. Electrocatalytic technology has broad advantages and multiple uses, and can be regulated by catalysts, electrolytes, interfaces, potentials, etc.

[0004] Through extensive literature research, only one document in the prior art disclosed a method for electrocatalytic synthesis of 1-iodine (Synlett 2000, No. 1, 89–91). This method uses methanol as solvent and sodium iodide as electrolyte at 7.5 mA / cm 2 A series of 1-iodine alkynes were prepared under a nitrogen atmosphere at 25°C and a current density of 1.0. However, this method requires strict inert atmosphere protection, significantly reducing the yield of the target product or even preventing it from proceeding in air. Furthermore, the solvent system, methanol, is an organic solvent, and atom economy still needs to be improved. Summary of the Invention

[0005] The present invention aims to overcome the shortcomings of the prior art by providing a method for the electrocatalytic synthesis of 1-iodine acetylenes. Under an air atmosphere, an alkyne substrate is reacted with sodium iodide as an electrolyte in a mixed solvent system of acetonitrile and water to successfully prepare a series of 1-iodine acetylenes. Compared to prior art methods, the present invention offers the advantages of eliminating the need for a protective atmosphere, reducing process costs, equipment requirements, and operational difficulty, reducing the amount of organic solvent used, and improving atom economy. It also eliminates the use of metal catalysts, bases, oxidants, and / or other reaction aids, resulting in mild reaction conditions and ease of operation.

[0006] According to the present invention, a method for electrocatalytic synthesis of 1-iodine acetylenic compounds comprises the following steps:

[0007] The alkyne compound represented by formula I, iodine salt, acetonitrile and water are sequentially added to the reactor, and the reaction is carried out under air atmosphere and room temperature with a controlled current of 6-12 mA. After the reaction is complete, the 1-iodine alkyne compound represented by formula II is obtained by post-treatment.

[0008] The reaction formula is as follows:

[0009]

[0010] Wherein, m represents an integer of 1, 2, 3, 4, or 5;

[0011] Each R substituent is the same or different and is independently selected from hydrogen, halogen, -CN, -NO2, -OH, -SH, C 1-10 Alkyl, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Halogenated alkyl, C 6-20 Aryl, C 1-10 Alkylcarbonyl, C 1-10 Alkoxycarbonyl;

[0012] and / or halogen, -CN, -NO2, -OH, -SH, C 1-10 Alkyl, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Halogenated alkyl, C 6-20 Aryl, C 1-10 Alkylcarbonyl, C 1-10 Alkoxycarbonyl substituted C 6-20 aryl;

[0013] And / or two adjacent R substituents are connected to each other, and together with the aromatic ring carbon atoms connecting the two R substituents, form a five- to seven-membered cyclic structural unit containing or not containing heteroatoms.

[0014] Preferably, m represents an integer of 1, 2, 3, 4, or 5;

[0015] Each R substituent is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, -CN, -NO2, -OH, -SH, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkyl, C 6-12 Aryl, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl;

[0016] and / or halogen, -CN, -NO2, C 1-3 Alkyl, C 1-3 Alkoxy, substituted C 6-20 aryl;

[0017] And / or two adjacent R substituents are connected to each other, and together with the aromatic ring carbon atoms connecting the two R substituents, form a five- to seven-membered cyclic structural unit without heteroatoms.

[0018] Further preferably, m represents an integer of 1, 2, 3, 4, or 5;

[0019] Each R substituent is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, -CN, -NO2, methoxy, ethoxy, propoxy, methyl, ethyl, propyl, phenyl, acetyl, tert-butoxycarbonyl; and / or two R substituents are connected to each other and together with the aromatic ring carbon atoms connecting the two R substituents constitute a benzene ring structural unit.

[0020] According to the aforementioned method of the present invention, the iodine salt is sodium iodide or potassium iodide, preferably sodium iodide.

[0021] According to the aforementioned method of the present invention, the volume ratio of acetonitrile to water is (2.5~8):1, preferably 5:1.

[0022] According to the aforementioned method of the present invention, the current is preferably 8 mA, and the time required for the complete reaction is 2 to 5 hours, preferably 3 to 4 hours.

[0023] According to the aforementioned method of the present invention, the molar ratio of the alkyne compound represented by Formula I to the iodine salt is 1:(2-4), preferably 1:3.

[0024] According to the aforementioned method of the present invention, the post-processing operation is as follows:

[0025] The reaction solution was transferred to a separatory funnel, and ethyl acetate and saturated sodium thiosulfate solution were added. The separated liquid was washed and extracted. The organic phase was dried, filtered, and concentrated to obtain a crude product. The crude product was separated by column chromatography to obtain the 1-iodoacetylene compound shown in Formula II.

[0026] Compared with the prior art, the method for electrocatalytic synthesis of 1-iodine alkyne of the present invention has the following significant advantages:

[0027] 1) The electrocatalytic synthesis of 1-iodine alkyne according to the present invention uses only sodium iodide as the electrolyte, without the use of metal catalysts, bases, oxidants, and / or other reaction aids. The reaction conditions are mild, simple, and easy to operate, and the yield of the target product is as high as over 88%.

[0028] 2) Compared with the electrocatalytic synthesis method of the prior art (Synlett 2000, No. 1, 89–91), the electrocatalytic synthesis method of 1-iodine no longer requires strict inert atmosphere protection, significantly reduces the requirements for reaction equipment, process costs and operations, reduces the amount of organic solvent used, and improves the atom economy of the process. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The product prepared in Example 8 1 H NMR spectrum.

[0030] Figure 2 The product prepared in Example 8 13 C NMR spectrum.

[0031] Figure 3 The product prepared in Example 22 1 H NMR spectrum.

[0032] Figure 4 The product prepared in Example 22 13 C NMR spectrum.

[0033] Figure 5 The product prepared in Example 23 1 H NMR spectrum.

[0034] Figure 6 The product prepared in Example 23 13 C NMR spectrum.

[0035] Figure 7 The product prepared in Example 24 1 H NMR spectrum.

[0036] Figure 8 The product prepared in Example 24 13 C NMR spectrum.

[0037] Figure 9 The product prepared in Example 25 1 H NMR spectrum.

[0038] Figure 10 The product prepared in Example 25 13 C NMR spectrum. DETAILED DESCRIPTION

[0039] The present invention will be further described below with reference to specific examples. In the following, unless otherwise specified, the methods used are all conventional methods in the art, and the raw materials and reagents used are all purchased through conventional commercial channels and / or prepared based on classical methods in the field of organic synthesis.

[0040] Example 1-17 Reaction Condition Optimization Test

[0041] Using phenylacetylene and sodium iodide as template substrates, the effects of different electrocatalytic synthesis conditions on yield were explored. The reaction formula is as follows:

[0042] .

[0043] Table 1:

[0044]

[0045] Basic reaction conditions: phenylacetylene 0.2 mmol, room temperature, air.

[0046] Taking Example 8 as an example, the typical test operation is as follows:

[0047] Sodium iodide (0.6 mmol), phenylacetylene (0.2 mmol), 2.5 mL of acetonitrile, and 0.5 mL of water were added to a 10 mL three-necked flask. The mixture was incubated at room temperature, in air, and at a current of 8 mA. The reaction was complete after 3 hours. The mixture was transferred to a separatory funnel, and 20 mL of ethyl acetate was added. The mixture was washed with a saturated sodium thiosulfate solution (10 mL x 2). The ethyl acetate organic phase was dried over anhydrous MgSO4, filtered, and the solvent was evaporated under reduced pressure to obtain a crude product. The target product, 1-iodo-2-phenylacetylene, was obtained by column chromatography (eluted with petroleum ether) in an 88% yield. 1 H NMR (400 MHz, CDCl3) δ 7.45 – 7.43 (m, 2H), 7.33 – 7.31 (m, 3H); 13 C NMR (100 MHz, CDCl3) δ 132.31, 128.79, 128.23, 123.36, 94.12, 6.10.

[0048] Table 1 shows that the solvent is a major factor affecting the electrocatalytic synthesis of 1-iodine in the present invention. When the solvent is an acetone / water mixture, the reaction fails. However, when the solvent is replaced with methanol / water, a 47% yield of the target product is achieved. Interestingly, when methanol is used exclusively as the solvent, the reaction under air only yields a 38% yield of the target product, demonstrating that the prior art method (Synlett 2000, No. 1, 89–91) requires strict inert atmosphere for successful implementation. After optimizing various process conditions, including solvent system, current level, reaction time, and electrolyte dosage, the optimal reaction conditions for the present invention are: acetonitrile:water volume ratio = 5:1, room temperature, air atmosphere, current of 8 mA, and 3 molar equivalents of sodium iodide.

[0049] Examples 18-21 Iodized Salt Substrate Extension Test

[0050] On the basis of obtaining the optimal reaction conditions, the effects of different iodized salts on the reaction were further explored. That is, only the type of iodized salt was changed and the reaction was carried out under the operating conditions of Example 8. The reaction formula is as follows:

[0051] .

[0052] Table 2:

[0053] iodized salt Yield 18 Ammonium iodide 0% 19 Potassium iodide 85% 20 Zinc iodide <10% 21 Tetrabutylammonium iodide 30%

[0054] As can be seen from Table 2, the reaction cannot proceed when ammonium iodide is used as the electrolyte, potassium iodide is basically equivalent to sodium iodide as the electrolyte, and the yield is significantly reduced when other iodine metal salts such as zinc iodide and quaternary ammonium salts such as tetrabutylammonium iodide are used as electrolytes.

[0055] Example 22-25 Alkyne Substrate Extension Test

[0056] Only the alkyne-based reaction substrate was replaced, and the reaction was carried out under the operating conditions of Example 8. The reaction formula is as follows:

[0057] .

[0058] Table 3:

[0059] Alkynes Reaction time temperature Yield 22 #timg# 3 hours Room temperature 91% 23 #timg# 3 hours Room temperature 90% 24 #timg# 3 hours Room temperature 94% 25 #timg# 4 hours Room temperature 88%

[0060] As can be seen from Table 3, the electrocatalytic synthesis of 1-iodine alkyne of the present invention has good functional group universality and is suitable for preparing various types of 1-iodine alkyne compounds.

[0061] The above embodiments are only preferred embodiments of the present invention and are not exhaustive of the feasible implementations of the present invention. For those skilled in the art, any obvious modifications made thereto without departing from the principles and spirit of the present invention should be considered to be included in the scope of protection of the claims of the present invention.

Claims

1. A method for electrocatalytic synthesis of 1-iodine acetylenic compounds, characterized in that: The steps include: The alkyne compound represented by formula I, iodine salt, acetonitrile and water are sequentially added to a reactor, and the reaction is carried out under air atmosphere and room temperature with a controlled current of 6-12 mA. After the reaction is complete, the 1-iodine alkyne compound represented by formula II is obtained by post-treatment; The reaction formula is as follows: Wherein, m represents an integer of 1, 2, 3, 4, or 5; Each R substituent is the same or different and is independently selected from hydrogen, halogen, -CN, -NO2, -OH, -SH, C 1-10 Alkyl, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Halogenated alkyl, C 6-20 Aryl, C 1-10 Alkylcarbonyl, C 1-10 Alkoxycarbonyl; and / or halogen, -CN, -NO2, -OH, -SH, C 1-10 Alkyl, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Halogenated alkyl, C 6-20 Aryl, C 1-10 Alkylcarbonyl, C 1-10 Alkoxycarbonyl substituted C 6-20 aryl; and / or two adjacent R substituents are connected to each other and, together with the aromatic ring carbon atoms connecting the two R substituents, form a five- to seven-membered cyclic structural unit containing or not containing heteroatoms; The iodine salt is sodium iodide or potassium iodide; the volume ratio of acetonitrile to water is (2.5-8):

1.

2. The method according to claim 1, characterized in that m represents an integer of 1, 2, 3, 4, or 5; Each R substituent is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, -CN, -NO2, -OH, -SH, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkyl, C 6-12 Aryl, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl; and / or halogen, -CN, -NO2, C 1-3 Alkyl, C 1-3 Alkoxy-substituted C 6-20 aryl; And / or two adjacent R substituents are connected to each other, and together with the aromatic ring carbon atoms connecting the two R substituents, form a five- to seven-membered cyclic structural unit without heteroatoms.

3. The method according to claim 2, characterized in that m represents an integer of 1, 2, 3, 4, or 5; Each R substituent is the same or different and is independently selected from hydrogen, fluorine, chlorine, bromine, -CN, -NO2, methoxy, ethoxy, propoxy, methyl, ethyl, propyl, phenyl, acetyl, tert-butoxycarbonyl; and / or two R substituents are connected to each other and together with the aromatic ring carbon atoms connecting the two R substituents constitute a benzene ring structural unit.

4. The method according to any one of claims 1 to 3, characterized in that The iodized salt is sodium iodide.

5. The method according to any one of claims 1 to 3, characterized in that The volume ratio of acetonitrile and water was 5:

1.

6. The method according to any one of claims 1 to 3, characterized in that The current is 8 mA and the time required for the reaction to be complete is 2 to 5 hours.

7. The method according to claim 6, characterized in that The time required for the reaction to be complete is 3 to 4 hours.

8. The method according to any one of claims 1 to 3, characterized in that The molar ratio of the alkyne compound represented by formula I to the iodine salt is 1:(2-4).

9. The method according to claim 8, characterized in that The molar ratio of the alkyne compound represented by formula I to the iodine salt is 1:

3.

10. The method according to any one of claims 1 to 3, characterized in that: The post-processing operation is as follows: The reaction solution was transferred to a separatory funnel, and ethyl acetate and saturated sodium thiosulfate solution were added. The separated liquid was washed and extracted. The organic phase was dried, filtered, and concentrated to obtain a crude product. The crude product was separated by column chromatography to obtain the 1-iodoacetylene compound shown in Formula II.

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