A method for the dehalogenative reduction of electron-rich aryl halides

Abstract

The application discloses a method for dehalogenation reduction of electron-rich aryl halide. The aryl halide is used as raw material, and is heated to react in the presence of phosphorous acid, iodine and a solvent, so that the corresponding aromatic hydrocarbon compound is prepared. The method directly avoids the defects of the current mainstream method, i.e. the need of using expensive transition metal catalyst and equivalent metal reagent. The electron-rich aryl halide is reduced to the corresponding aromatic hydrocarbon by one step through using the cheap, low-toxic and stable phosphorous acid as a reducing agent and iodine as a catalyst. The method has the advantages of no need of metal participation, simple operation, low cost, green environmental protection and the like, avoids the use of metal reagent and the limitation of special equipment which is not easy to be enlarged for production. After the reaction of the phosphorous acid is completed, the by-product is generally phosphoric acid and the corresponding phosphorus salt, which can be quickly removed through water washing, and the post-treatment is simple, so that the industrialized production is facilitated.

Description

Technical Field

[0001] This invention relates to a method for the dehalogenation reduction of electron-rich aryl halides to the corresponding aromatic hydrocarbons, belonging to the field of fine chemical synthesis technology. Background Technology

[0002] The dehalogenation reduction of aryl halides is a fundamental and irreplaceable functional group transformation reaction in organic synthesis, industrial production, environmental remediation, and pharmaceutical materials. According to relevant literature, the main methods for the dehalogenation reduction of aryl halides to the corresponding aromatic hydrocarbons are as follows:

[0003] The first method, currently the most common reduction method, starts with aryl halides and reduces them to the corresponding aryl groups in the presence of an stoichiometric reducing agent and a transition metal catalyst. However, this reduction process mostly requires hydrogen, which is not very safe, and it also requires expensive transition metals, making it uneconomical. Furthermore, there is a risk of metal residue in the target product.

[0004] .

[0005] The second method involves reducing aryl halides to the corresponding aromatic hydrocarbons in the presence of an equimolar metal reducing agent. This requires a highly reactive metal reducing agent, is more complex to operate, less economical, and generates metal waste, making it environmentally unfriendly and less practical.

[0006] .

[0007] The third method involves reducing aryl halides to the corresponding aromatic hydrocarbons using specialized equipment, such as microwave reactors or photochemical reactors. However, this method requires specialized equipment and expensive photocatalytic reagents, and is not easily scaled up for production, resulting in poor feasibility and practicality.

[0008] . Summary of the Invention

[0009] To address the problems existing in the reduction of aromatic halides to their corresponding aromatic hydrocarbons, the present invention aims to provide a method that uses inexpensive, readily available, low-toxicity, and safe phosphorous acid as a reducing agent to replace traditional metal reducing agents and hydrogen, and uses a catalytic amount of iodine instead of transition metal catalysis to dehalogenate electron-rich aryl halides to their corresponding aromatic hydrocarbons. This method avoids the use of expensive metal catalysts and equivalent metal reducing agents, and has the advantages of low production cost, inexpensive and readily available raw materials, simple reaction conditions, green and environmentally friendly production, and is conducive to industrial production.

[0010] To achieve the above objectives, the present invention adopts the following technical solution:

[0011] A method for the dehalogenation reduction of electron-rich aryl halides involves using aryl halides as raw materials and reacting them under heating conditions in the presence of phosphorous acid, elemental iodine, and a solvent to obtain the corresponding aromatic compounds. The reaction equation is shown in Formula I.

[0012] Formula I;

[0013] In the aryl halide, the aromatic ring is an aromatic ring containing an electron-rich substituent, which is one or more of the following: hydrocarbon group, methoxy group, amino group, imino group, and subamino group. The position and number of substituents are not limited and can be the same or different. The aromatic ring is a benzene ring or a naphthalene ring or a benzene ring or a naphthalene ring containing an alkyl substituent, such as methyl, ethyl, isopropyl, tert-butyl, etc. X is Cl, Br, or I.

[0014] Preferably, the aryl halide is selected from one of the following structural formulas:

[0015] , , , , , , , , , , , , .

[0016] Preferably, the molar ratio of the aryl halide to phosphorous acid is 1:1 to 8, more preferably 1:2 to 5; the molar ratio of the aryl halide to elemental iodine is 1:0.01 to 1, more preferably 1:0.05 to 0.5; and the concentration of the aryl halide in the solvent is 0.2 to 1.0 mol / L.

[0017] Preferably, the solvent is 1,2-dichloroethane, chlorobenzene, chloroform, dichloromethane, benzene, or toluene.

[0018] Preferably, the atmosphere for the heating reaction is an air atmosphere or a protective atmosphere, more preferably a protective atmosphere, such as nitrogen or argon.

[0019] Preferably, the heating reaction temperature is 60~100℃, and the heating reaction time is not less than 18 h.

[0020] Preferably, after the heating reaction is completed, the reaction solution is extracted, dried and filtered, rotary evaporated, and then purified by column chromatography.

[0021] The beneficial effects of this invention are:

[0022] This invention provides a cheap, readily available, low-toxicity, and safe method for the dehalogenation reduction of electron-rich aryl halides, directly avoiding the shortcomings of current mainstream methods that require expensive transition metal catalysts and equivalent metal reagents. This method uses inexpensive, low-toxicity, and relatively stable phosphorous acid as a reducing agent and elemental iodine as a catalyst to dehalogenate electron-rich aryl halides into the corresponding aromatic hydrocarbons in one step. It has advantages such as no metal involvement, simple operation, low cost, and environmental friendliness. It avoids the limitations of using metal reagents and the difficulty of scaling up production with specialized equipment. After the phosphorous acid reaction, the byproducts are generally phosphoric acid and its corresponding phosphate salts, which can be quickly removed by washing with water. The post-treatment is simple and conducive to industrial production. Attached Figure Description

[0023] Figure 1 The image shows the 1H NMR spectrum of the sample prepared in Example 1.

[0024] Figure 2 The image shows the carbon NMR spectrum of the sample prepared in Example 1.

[0025] Figure 3 The image shows the 1H NMR spectrum of the sample obtained in Example 2.

[0026] Figure 4 The image shows the carbon NMR spectrum of the sample obtained in Example 2.

[0027] Figure 5 The image shows the 1H NMR spectrum of the sample prepared in Example 3.

[0028] Figure 6 The image shows the carbon NMR spectrum of the sample obtained in Example 3.

[0029] Figure 7 The image shows the 1H NMR spectrum of the sample obtained in Example 4.

[0030] Figure 8 The image shows the carbon NMR spectrum of the sample obtained in Example 4.

[0031] Figure 9 The image shows the 1H NMR spectrum of the sample obtained in Example 5.

[0032] Figure 10 The image shows the carbon NMR spectrum of the sample obtained in Example 5.

[0033] Figure 11 The image shows the 1H NMR spectrum of the sample prepared in Example 6.

[0034] Figure 12 The image shows the carbon NMR spectrum of the sample obtained in Example 6.

[0035] Figure 13 The image shows the 1H NMR spectrum of the sample obtained in Example 7.

[0036] Figure 14 The image shows the carbon NMR spectrum of the sample obtained in Example 7.

[0037] Figure 15 The image shows the 1H NMR spectrum of the sample obtained in Example 8.

[0038] Figure 16 The image shows the carbon NMR spectrum of the sample obtained in Example 8.

[0039] Figure 17 The image shows the 1H NMR spectrum of the sample obtained in Example 9.

[0040] Figure 18 The image shows the carbon NMR spectrum of the sample obtained in Example 9.

[0041] Figure 19 The image shows the 1H NMR spectrum of the sample prepared in Example 10.

[0042] Figure 20 The image shows the carbon NMR spectrum of the sample obtained in Example 10. Detailed Implementation

[0043] The following examples are intended to further illustrate the present invention, but do not limit the scope of protection of the claims of the present invention.

[0044] Example 1

[0045] Under a nitrogen atmosphere, 4-bromophenol (0.3 mmol), phosphorous acid (0.75 mmol), elemental iodine (0.06 mmol), and 1,2-dichloroethane (0.6 mL) were added to a reaction flask. The mixture was stirred under closed contact at 80 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography as a white solid. The yield was 66%.

[0046] (2) Same as (1), except that the amount of phosphorous acid used is 1.5 mmol and the yield is 30%.

[0047] (3) Same as (1), except that the amount of iodine used is 0.015 mmol and the yield is 62%.

[0048] (4) Same as (1), except that the amount of iodine used is 0.21 mmol and the yield is 41%.

[0049] (5) Same as (1), except that the solvent is toluene and the yield is 37%.

[0050] (6) Same as (1), except that the solvent is chloroform and the yield is 58%.

[0051] (7) Same as (1), except that the solvent is dichloromethane and the yield is 56%.

[0052] (8) Same as (1), except that the solvent is chlorobenzene and the yield is 48%.

[0053] (9) Same as (1), except that the solvent is benzene and the yield is 41%.

[0054] (10) Same as (1), except that the reaction atmosphere is air and the yield is 46%.

[0055] (11) Same as (1), except that the reaction temperature is 60℃ and the yield is 50%.

[0056] (12) Same as (1), except that the reaction temperature is 100℃ and the yield is 46%.

[0057] (13) Same as (1), the only difference is that the raw material is The yield was 72%.

[0058] 1 H NMR (400 MHz CDCl3): δ 7.23–7.196 (m, 2H), 6.94–6.90 (m, 1H), 6.83(d, J = 8.0 Hz (2H), 5.94 (s, 1H).

[0059] 13 C (NMR (100 MHz CDCl3): δ 155.2, 129.8, 120.8, 115.4.

[0060] Example 2

[0061] Under a nitrogen atmosphere, 0.3 mmol of 4-bromo-2-methylphenol, 0.75 mmol of phosphorous acid, 0.06 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 80 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a colorless liquid. The yield was 56%.

[0062] 1 H NMR (400 MHz CDCl3): δ7.14–7.07 (m, 2H), 6.87-6.83 (m, 1H), 7.78 (d, J=8Hz, 1H), 4.72 (s, 1H), 2.26 (s, 3H).

[0063] 13 C NMR (100 MHz CDCl3): δ 154.1, 131.3, 127.4, 124.1, 121.1, 115.1, 16.0.

[0064] Example 3

[0065] Under a nitrogen atmosphere, 0.3 mmol of 4-bromonaphthol, 0.75 mmol of phosphorous acid, 0.06 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 80 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a yellow solid. The yield was 51%.

[0066] 1 H NMR (400 MHz CDCl3): δ 8.22 (d, J=4Hz, 1H), 7.85(d, J=4Hz, 1H), 7.53–7.47 (m, 3H), 7.35–7.30 (m, 1H), 6.82 (d, J=8Hz 1H), 5.52(s, 1H).

[0067] 13 C NMR (100 MHz CDCl3): δ 150.7, 134.1, 126.9, 125.7, 125.1, 124.5, 123.6, 120.9, 119.9, 107.9.

[0068] Example 4

[0069] Under a nitrogen atmosphere, 0.3 mmol of 1-bromo-4-methoxybenzene, 0.75 mmol of phosphorous acid, 0.12 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 60 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a colorless liquid. The yield was 54%.

[0070] 1 H NMR (400 MHz CDCl3): δ 7.35–7.31 (m, 2H), 7.00–6.94 (m, 3H), 3.84 (s, 3H).

[0071] 13 C NMR (100 MHz CDCl3): δ 159.7, 129.4, 120.6, 113.5, 55.2.

[0072] Example 5

[0073] (1) Under air atmosphere, 1-bromo-2,6-dimethoxybenzene (0.3 mmol), phosphorous acid (0.75 mmol), elemental iodine (0.06 mmol), and 1,2-dichloroethane (0.6 mL) were added to a reaction flask. The mixture was stirred under closed conditions at 80°C for 36 hours. After the reaction was completed, a saturated saline solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a colorless and transparent liquid. The yield was 87%.

[0074] (2) Same as (1), the only difference is that the raw material is The yield was 75%.

[0075] 1 H NMR (400 MHz CDCl3): δ 7.22–7.18 (m, 1H), 6.53 (d, J = 3.6 Hz, 1H), 6.51 (d, J = 2.4Hz, 1H), 6.488–6.476 (m, 1H), 3.81 (s, 6H).

[0076] 13 C NMR (100 MHz CDCl3): δ 160.7, 129.9, 106.2, 100.5, 55.2.

[0077] Example 6

[0078] (1) Under a nitrogen atmosphere, 4-bromoaniline (0.3 mmol), phosphorous acid (0.75 mmol), elemental iodine (0.06 mmol), and 1,2-dichloroethane (0.6 mL) were added to a reaction flask. The mixture was stirred under closed contact at 100 °C for 60 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a yellow-brown liquid. The yield was 91%.

[0079] (2) Same as (1), except that the amount of phosphorous acid used is 1.5 mmol and the amount of iodine used is 0.06 mmol. The temperature is 100 ℃, the reaction time is 36 h, and the yield is 67%.

[0080] 1 H NMR (400 MHz CDCl3): δ 7.25–7.22 (m, 2H), 6.86– 6.83(m, 1H), 6.73(d, J = 8.4 Hz, 2H), 3.66 (s, 2H).

[0081] 13 C NMR (100 MHz CDCl3): δ 145.9, 129.1, 117.9, 114.7.

[0082] Example 7

[0083] Under a nitrogen atmosphere, 0.3 mmol of 4-bromo-2,6-dimethylaniline, 0.75 mmol of phosphorous acid, 0.06 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 100 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a pale yellow liquid. The yield was 92%.

[0084] 1 H NMR (400 MHz CDCl3): δ 7.05 (d, J=5.2Hz, 2H), 6.78–6.74 (m, 1H), 3.61 (s, 2H), 2.30 (s, 6H).

[0085] 13 C NMR (100 MHz CDCl3): δ 142.5, 127.6, 120.9, 117.2, 17.1.

[0086] Example 8

[0087] Under a nitrogen atmosphere, 0.3 mmol of 4-bromo-1-naphthylamine, 0.75 mmol of phosphorous acid, 0.06 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 80 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a light purple solid. The yield was 51%.

[0088] 1 H NMR (400 MHz CDCl3): δ 7.85 (s, 2H), 7.50–7.49 (m, 2H), 7.39-7.31 (m, 2H), 6.81 (d, J = 8.0 Hz, 1H), 4.1 (s, 2H).

[0089] 13 C NMR (100 MHz CDCl3): δ 142.3, 134.7, 128.8, 126.6, 126.1, 125.1, 123.9, 121.1.

[0090] Example 9

[0091] Under a nitrogen atmosphere, 0.3 mmol of 4-bromo-N-methylaniline, 0.75 mmol of phosphorous acid, 0.06 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 100 °C for 36 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a brown liquid. The yield was 90%.

[0092] 1 H NMR (400 MHz CDCl3): δ 7.2–7.16 (m, 2H), 6.72–6.69 (m, 1H), 6.60(d, J= 8.0 Hz, 2H), 3.56 (s, 1H), 2.81 (s, 3H).

[0093] 13 C NMR (100 MHz CDCl3): δ 149.3, 129.4, 117.2, 112.2, 31.1.

[0094] Example 10

[0095] Under a nitrogen atmosphere, 0.3 mmol of 4-bromo-N,N-dimethylaniline, 7.5 mmol of phosphorous acid, 0.03 mmol of elemental iodine, and 0.6 mL of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred under closed contact at 100 °C for 60 hours. After the reaction was complete, a saturated saline solution was added to the reaction mixture, and the solution was extracted with dichloromethane. The organic phase was dried, filtered, and the solvent was evaporated. Finally, the product was obtained by column chromatography. The obtained product was a yellow liquid. The yield was 92%.

[0096] 1 H NMR (400 MHz CDCl3): δ 7.26–7.22 (m, 2H), 6.76-6.70 (m, 3H), 2.94 (s, 6H).

[0097] 13 C NMR (100 MHz CDCl3): δ 151.2, 129.6, 117.1, 112.9, 40.7.

Claims

1. A method for dehalogenation and reduction of electron-rich aryl halides, characterized in that, Using aryl halides as raw materials, the corresponding aromatic compounds are prepared by heating in the presence of phosphorous acid, elemental iodine, and solvent. The reaction equation is shown in Formula I. Equation I; In the aryl halide, the aromatic ring is an aromatic ring containing an electron-rich substituent, which is one or more of the following: hydrocarbon group, methoxy group, amino group, imino group, and subamino group; the aromatic ring is a benzene ring or a naphthalene ring; and X is Cl, Br, or I.

2. The method according to claim 1, characterized in that, The aryl halide is selected from one of the following structural formulas: 、 、 、 、 、 、 、 。 3. The method according to claim 1 or 2, characterized in that, The molar ratio of the aryl halide to phosphorous acid is 1:1~8; the molar ratio of the aryl halide to elemental iodine is 1:0.01~1; and the concentration of the aryl halide in the solvent is 0.2~1.0 mol / L.

4. The method according to claim 3, characterized in that, The molar ratio of the aryl halide to phosphorous acid is 1:2~5; the molar ratio of the aryl halide to elemental iodine is 1:0.05~0.

5.

5. The method according to claim 1 or 2, characterized in that, The solvent is 1,2-dichloroethane, chlorobenzene, chloroform, dichloromethane, benzene, or toluene.

6. The method according to claim 1 or 2, characterized in that, The heating reaction takes place in an air atmosphere or a protective atmosphere.

7. The method according to claim 6, characterized in that, The atmosphere for the heating reaction is a protective atmosphere.

8. The method according to claim 1 or 2, characterized in that, The heating reaction temperature is 60~100℃, and the heating reaction time is not less than 18 h.

9. The method according to claim 1 or 2, characterized in that, After the heating reaction is completed, the reaction solution is extracted, dried and filtered, rotary evaporated, and then purified by column chromatography.

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