A method for electrochemically synthesizing aryl nitrile using aryl dialkyl phosphate

Abstract

The present invention relates to a method for electrochemically synthesizing aryl nitrile by utilizing aryl dialkyl phosphate. The method comprises the following steps: a carbon rod anode and a carbon rod cathode are loaded into a reaction bottle and connected to a DC voltage-regulated power supply; a compound 1, aryl dialkyl phosphate, a compound 2, tert-butyl isocyanide, an organic solvent, an electrolyte, and a base are then added to the reaction bottle; the reaction solution is electrolyzed at a temperature of 10-70°C using a DC constant voltage for 12-20 hours; after the reaction is completed, ethyl acetate is added, the reaction solution is washed with water, the organic phase is dried, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target compound 3, aryl nitrile; the synthesis route is as follows: #imgabs0# The method utilizes inexpensive phenol-derived aryl dialkyl phosphate and tert-butyl isocyanide as substrates, has the advantages of simple operation, mild conditions, low cost, high yield, and environmental friendliness, thus broadening existing synthesis technology.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing aromatic nitriles by an electrochemical method using phenol-derived dialkyl aryl phosphate and tert-butyl isocyanide as substrates. Background Art

[0002] Aryl nitriles are an important class of organic compounds, not only widely present in many drug molecules, dyes, insecticides, pesticides and electronic materials, but also because nitriles can be converted into other functional groups (such as amines, amides, aldehydes, ketones, carboxylic acids, and heterocycles), they are a very important class of organic synthons. The industrial production of aryl nitriles mainly relies on the following three types of reactions:

[0003] (1) Sandmeyer reaction: Generally, under strongly acidic conditions (hydrochloric acid and sulfuric acid), an aromatic primary amine reacts with sodium nitrite to form a diazonium salt. The diazonium salt then reacts with an aqueous solution of potassium cyanide in cuprous cyanide at 60-70°C to form an aromatic nitrile. The reaction uses the highly toxic cuprous cyanide reagent, and the diazonium salt is highly reactive and easily explosive, making the actual operation quite dangerous. [T. Sandmeyer, Ueber die Ersetzung der Amid-gruppe durch Chlor, Brom und Cyanin den aromatictischen Substanzen, Ber. Dtsch. Chem. Ges., 1884, 17, 2650.].

[0004] (2) Rosenmund-von Braun reaction: Aryl halides and excess cuprous cyanide are refluxed in a high-boiling-point polar solvent (such as DMF) to produce aromatic nitriles. This reaction not only uses excessive amounts of highly toxic cuprous cyanide and high temperatures, but also requires high-boiling-point solvents for post-processing and purification. [K. W. Rosenmund and E. Struck, Das am Ringkohlenstoff gebundene Halogen undsein Ersatz durch andere Substituenten. I. Mitteilung: Ersatz des Halogens durch die Carboxylgruppe, Ber. Dtsch. Chem. Ges. B, 1919, 52, 1749.].

[0005] (3) Transition metal-catalyzed coupling reactions: (quasi) halogenated hydrocarbons and cyano equivalents undergo coupling reactions catalyzed by transition metals such as palladium to produce aryl nitriles. This type of reaction requires the use of transition metals as catalysts and generally requires high temperatures. [G. Yan, Y. Zhang, J. Wang, Recent Advances in the Synthesis of Aryl Nitrile Compounds, Adv. Synth. Catal., 2017, 359, 4068.].

[0006] Therefore, it is urgent to research and develop a new synthesis method of aromatic nitriles with simple operation, mild conditions and environmental friendliness. Summary of the Invention

[0007] The present invention aims to overcome the shortcomings of the prior art by providing a method for the facile electrochemical synthesis of aryl nitriles using dialkyl aryl phosphates and tert-butyl isocyanide. This method, which uses inexpensive phenol-derived dialkyl aryl phosphates and tert-butyl isocyanide as substrates, boasts simple operation, mild conditions, low cost, high yield, and environmental friendliness, broadening existing synthesis techniques.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0009] A method for electrochemically synthesizing aryl nitrile using aryl dialkyl phosphate, comprising: placing a carbon rod anode and a carbon rod cathode into a reaction flask and connecting the flask to a DC regulated power supply; then adding compound 1, aryl dialkyl phosphate (1.0 mmol), compound 2, tert-butyl isocyanide (X eq), an organic solvent, an electrolyte (Y eq), and a base (Z eq) into the reaction flask; electrolyzing the reaction solution at a temperature of 10-70°C using a DC constant voltage for 12-20 hours; after completion of the reaction, adding ethyl acetate, washing with water, and drying and concentrating the organic phase under reduced pressure, followed by separation and purification by column chromatography to obtain the target compound 3, aryl nitrile;

[0010] The synthetic route is as follows:

[0011]

[0012] Ar is an aromatic group, or may have an electron-donating group (such as an alkyl, alkoxy, or amino group) in the ortho, meta, or para position, or may contain an electron-withdrawing group (such as a halogen, cyano, keto, ester, or trifluoromethyl aromatic group); R is a methyl, ethyl, or isopropyl group. The value of X in the present invention may range from 3 to 5; the value of Y may range from 1 to 3; and the value of Z may range from 2 to 4.

[0013] Specifically, the molar ratio of dialkyl aryl phosphate to tert-butyl isocyanide may be 1:3-5.

[0014] Specifically, the molar ratio of the dialkyl aryl phosphate to the electrolyte may be 1:1-3.

[0015] Specifically, the molar ratio of the dialkyl aryl phosphate to the base may be 1:2-4.

[0016] Furthermore, the organic solvent of the present invention can be one of acetonitrile (MeCN), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), etc. The amount of the organic solvent used in the present invention is: 4 mL to 8 mL of organic solvent per mmol of dialkyl aryl phosphate.

[0017] Furthermore, the electrolyte used in the present invention is mainly: n Bu4NPF6, LiBF4, LiPF6, Et4NOTs, LiClO4 or n Bu4NClO4, etc.

[0018] Furthermore, the base used in the present invention can be LiOAc, NaOAc or KOAc.

[0019] The DC voltage used in the electrochemical synthesis of aryl nitrile using aryl dialkyl phosphate is -4.0 V to -6.0 V. The eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate, preferably in a volume ratio of 5-25:1.

[0020] The reaction mechanism of the present invention is as follows: aryl dialkyl phosphate ester 1 is reduced to aryl radical 1 at the cathode. I adds to tert-butyl isonitrile 2 and undergoes anodic oxidation and deisobutylene to obtain aryl nitrile. The reaction mechanism diagram is shown in FIG. Figure 1 .

[0021] The dialkyl aryl phosphates containing different substituents required by the present invention can be conveniently prepared by referring to the literature method [DR Edwards, CT Liu, GE Garrett, AA Neverov, RS Brown, Leaving Group Assistance in the La 3+ -Catalyzed Cleavage of Dimethyl(o-Methoxycarbonyl)arylPhosphate Triesters in Methanol, J. Am. Chem. Soc. 2009, 131, 13738.].

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1) The raw materials used in the method of the present invention, such as dialkyl aryl phosphate and tert-butyl isocyanide, are cheap and readily available, and can be easily industrialized.

[0024] 2) The method of the present invention adopts an electrochemical method with mild reaction conditions, does not generate excess metal waste, has no complicated intermediate links, is simple and safe to operate, and conforms to the concept of green chemistry.

[0025] 3) The method of the present invention has a wide range of substrates and broadens the synthesis methods of aromatic nitrile compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the reaction mechanism of the method of the present invention. DETAILED DESCRIPTION

[0027] The technical solutions and effects of the present invention are further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

[0028] In the following examples, the raw materials used are all commercially available products that can be directly purchased, or can be prepared by conventional methods in the art. For example, the dialkyl aryl phosphates containing different substituents used in the following examples can be referred to the literature [DR Edwards, CT Liu, GE Garrett, AA Neverov, RS Brown, Leaving Group Assistance in the La 3+ It was prepared by the method of [Catalyzed Cleavage of Dimethyl(o-Methoxycarbonyl)arylPhosphate Triesters in Methanol, J.Am.Chem.Soc.2009,131,13738.].

[0029] Room temperature refers to 25±5°C.

[0030] Example 1 Synthesis of benzonitrile:

[0031]

[0032] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply. Aryl dimethyl phosphate 1a (1.0 mmol), tert-butyl isocyanide (3 eq), DMF (4 mL), nBu4NPF6 (2 eq) and LiOAc (2 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -5.0 V) for 18 hours. After TLC indicated complete reaction of starting material 1a, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 20:1 volume ratio of petroleum ether / ethyl acetate as the eluent to obtain 89.7 mg of the desired product, benzonitrile 3a, as a colorless oil in an 87% yield. The chromatographic data are as follows:

[0033] 1 H NMR (500MHz, CDCl3) δ7.68–7.64(m,2H),7.64–7.59(m,1H),7.48(t,J=7.9Hz,2H); 13 C NMR (126MHz, CDCl3) δ132.8,132.1,129.2,118.9,112.4.

[0034] Example 2 Synthesis of 4-methoxybenzonitrile:

[0035]

[0036] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply. Aryl dimethyl phosphate 1b (1.0 mmol), tert-butyl isocyanide (3 eq), DMF (4 mL), n Bu4NPF6 (2 eq) and LiOAc (2 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -5.0 V) for 18 hours. After TLC indicated complete reaction of starting material 1b, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 20:1 volume ratio of petroleum ether / ethyl acetate as the eluent to obtain 113.2 mg of the target product, 4-methoxybenzonitrile 3b, as a colorless oil in an 85% yield. The chromatographic data are as follows:

[0037] 1 H NMR (500MHz, CDCl3) δ7.57 (dd, J=8.8, 1.6Hz, 2H), 6.95 (dd, J=8.8, 1.6Hz, 2H), 3.85 (s, 3H); 13 C NMR (126MHz, CDCl3) δ162.9,134.0,119.2,114.8,103.9,55.6.

[0038] Example 3 Synthesis of 4-methylbenzonitrile:

[0039]

[0040] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diethyl arylphosphate 1c (1.0 mmol), tert-butyl isocyanide (3 eq), DMF (4 mL), LiBF4 (2 eq), and LiOAc (2 eq) were then added. The reaction solution was electrolyzed at 50°C with a DC constant potential (V = -5.0 V) for 18 hours. After TLC indicated complete reaction of the starting material 1c, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 20:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 105.4 mg of the target product, 4-methylbenzonitrile 3c, as a colorless oil in a 90% yield. The chromatographic data are as follows:

[0041] 1 H NMR (400MHz, CDCl3) δ7.48 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H); 13 C-NMR (100MHz, CDCl3) δ143.30,131.50,129.44,118.65,108.79,21.29.

[0042] Example 4 Synthesis of 4-(benzyloxy)benzonitrile:

[0043]

[0044] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diethyl arylphosphate 1d (1.0 mmol), tert-butyl isocyanide (3 eq), MeCN (5 mL), LiBF4 (1 eq), and NaOAc (3 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -5.0 V) for 18 hours. After TLC indicated complete reaction of the starting material 1d, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 20:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 167.4 mg of the target product, 4-(benzyloxy)benzonitrile 3d, as a colorless oil in an 80% yield. The chromatographic data are as follows:

[0045] 1H NMR (500MHz, CDCl3) δ7.63–7.59(m,2H),7.47–7.33(m,4H),7.42–7.36(m,1H),7.06–7.03(m,2H),5.14(s,2H); 13 C NMR (126MHz, CDCl3) δ162.0,135.7,134.0,128.8,128.5,127.5,119.2,115.6,104.3,70.3.

[0046] Example 5 Synthesis of 4-(2-carbonyl-1-pyrrolyl)benzonitrile:

[0047]

[0048] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diethyl arylphosphate 1e (1.0 mmol), tert-butyl isocyanide (3 eq), MeCN (5 mL), LiPF6 (1 eq), and NaOAc (3 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -6.0 V) for 18 hours. After TLC indicated complete reaction of the starting material 1e, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 5:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 135.9 mg of the target product, 4-(2-carbonyl-1-pyrrolyl)benzonitrile 3e, as a colorless oil in a 73% yield. The chromatographic data are as follows:

[0049] 1 H NMR (400MHz, CDCl3) δ7.78(d,J=9.2Hz,2H),7.63(d,J=9.0Hz,2H),3.87(t,J=7.0Hz,2H),2.64(t,J=8.1Hz,2H),2.26–2.14(m,2H); 13 C NMR (101MHz, CDCl3) δ174.9,143.3,133.1,119.3,119.0,107.2,48.4,32.9,17.9.

[0050] Example 6 Synthesis of 4-bromobenzonitrile:

[0051]

[0052] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Aryl phosphate diethyl ester 1f (1.0 mmol), tert-butyl isocyanide (4 eq), MeCN (5 mL), LiPF6 (1 eq), and NaOAc (3 eq) were then added. The reaction solution was electrolyzed at 60°C with a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1f, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 20:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 132.9 mg of the target product, 4-bromobenzonitrile 3f, as a colorless oil in a 73% yield. The chromatographic data are as follows:

[0053] 1 H NMR (500MHz, CDCl3) δ7.68–7.62(m,2H),7.60–7.51(m,2H); 13 C NMR (126MHz, CDCl3) δ133.4,132.7,128.0,118.1,111.3.

[0054] Example 7 Synthesis of 4-chlorobenzonitrile:

[0055]

[0056] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. 1 g (1.0 mmol) of diethyl arylphosphate, 4 eq of tert-butyl isocyanide, 6 mL of DMF, 3 eq of LiPF6, and 3 eq of KOAc were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of 1 g of the starting material, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 20:1 (volume ratio) of petroleum ether / ethyl acetate as the eluent. The target product, 4-chlorobenzonitrile, was obtained as a colorless oil (110.0 mg), yielding 3 g (80%). The chromatographic data are as follows:

[0057] 1 H NMR (400MHz, CDCl3) δ7.61 (d, J = 8.4Hz, 2H), 7.47 (d, J = 8.4Hz, 2H); 13 C NMR (100MHz, CDCl3): δ139.6,133.4,129.7,117.9,110.8.

[0058] Example 8 Synthesis of 4-(trifluoromethyl)benzonitrile:

[0059]

[0060] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diisopropyl arylphosphate 1h (1.0 mmol), tert-butyl isocyanide (4 eq), DMF (6 mL), Et4NOTs (3 eq), and KOAc (3 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1h, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 20:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 133.5 mg of the target product, 4-(trifluoromethyl)benzonitrile 3h, as a colorless oil in a 78% yield. The chromatographic data are as follows:

[0061] 1 H NMR (500MHz, CDCl3) δ7.83 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H); 13 C NMR (101MHz, CDCl3) δ134.5 (q, J = 26.9Hz), 132.7, 126.2 (q, J = 9.1Hz), 123.1 (q, J = 219.0Hz), 117.4, 116.1; 19 F NMR (471 MHz, CDCl3) δ-63.6.

[0062] Example 9 Synthesis of methyl 4-cyanobenzoate:

[0063]

[0064] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diisopropyl arylphosphate 1i (1.0 mmol), tert-butyl isocyanide (4 eq), NMP (6 mL), Et4NOTs (3 eq), and KOAc (4 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1i, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 10:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 112.2 mg of the target product, methyl 4-cyanobenzoate 3i, as a colorless oil in a 69% yield. The chromatographic data are as follows:

[0065] 1 H NMR (500MHz, CDCl3) δ8.18–8.11(m,2H),7.83–7.70(m,2H),3.96(s,3H); 13 CNMR (126MHz, CDCl3) δ165.4,133.9,132.2,130.1,118.0,116.4,52.7.

[0066] Example 10 Synthesis of 4-acetylbenzonitrile:

[0067]

[0068] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Diisopropyl arylphosphate 1j (1.0 mmol), tert-butyl isocyanide (4 eq), NMP (6 mL), Et4NOTs (1 eq), and LiOAc (4 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1j, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 5:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 94.4 mg of the target product, 4-acetylbenzonitrile 3j, as a colorless oil in a 65% yield. The chromatographic data are as follows:

[0069] 1 H NMR (500MHz, CDCl3) δ8.13–8.02(m,2H),7.87–7.72(m,2H),2.67(s,3H); 13CNMR (126MHz, CDCl3) δ196.5,139.9,132.5,128.7,117.9,116.4,26.8.

[0070] Example 11 Synthesis of terephthalonitrile:

[0071]

[0072] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Aryl dimethyl phosphate 1k (1.0 mmol), tert-butyl isocyanide (4 eq), NMP (6 mL), LiClO₄ (1 eq), and LiOAc (2 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1k, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography using a 15:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 97.4 mg of the target product, terephthalonitrile 3k, as a colorless oil in a 76% yield. The chromatographic data are as follows:

[0073] 1 H NMR (500MHz, CDCl3) δ7.82 (d, J = 1.2Hz, 4H); 13 C NMR (126MHz, CDCl3) δ132.8,117.0,116.7.

[0074] Example 12 Synthesis of isophthalonitrile:

[0075]

[0076] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Aryl dimethyl phosphate 1L (1.0 mmol), tert-butyl isocyanide (3 eq), DMSO (7 mL), LiClO₄ (2 eq), and LiOAc (2 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -4.0 V) for 16 hours. After TLC indicated complete reaction of the starting material 1L, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography using a 15:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 97.5 mg of the target product, isophthalonitrile 3L, as a colorless oil in a 76% yield. The chromatographic data are as follows:

[0077] 1 H NMR (500MHz, CDCl3) δ7.98 (s, 1H), 7.93 (d, J = 7.9Hz, 2H), 7.68 (t, J = 7.9Hz, 1H); 13 C NMR (126MHz, CDCl3) δ136.0,135.4,130.4,116.6,114.2.

[0078] Example 13 Synthesis of 3-methoxybenzonitrile:

[0079]

[0080] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply; aryl phosphate diethyl ester 1 m (1.0 mmol), tert-butyl isocyanide (3 eq), DMSO (7 mL), n Bu4NClO4 (2 eq) and NaOAc (3 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -6.0 V) for 16 hours. After TLC indicated complete reaction of the starting material 1m, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 15:1 volume ratio of petroleum ether / ethyl acetate as the eluent. The target product, 3-methoxybenzonitrile 3m, was obtained as a colorless oil (106.5 mg) in an 80% yield. The chromatographic data are as follows:

[0081] 1 H NMR (500MHz, CDCl3) δ7.56 (ddd, J=9.7, 5.7, 2.7Hz, 2H), 7.11–6.94 (m, 2H), 3.94 (s, 3H). 13 C NMR (126MHz, CDCl3) δ161.3,134.4,133.8,120.8,116.5,111.3,101.8,56.0.

[0082] Example 14 Synthesis of 3,4-dimethylbenzonitrile:

[0083]

[0084] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply; aryl phosphate diethyl ester 1n (1.0 mmol), tert-butyl isocyanide (5 eq), DMSO (7 mL), nBu4NClO4 (2 eq) and NaOAc (3 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -6.0 V) for 16 hours. After TLC indicated complete reaction of the starting material 1n, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 20:1 volume ratio of petroleum ether / ethyl acetate as the eluent. The target product, 3,4-dimethylbenzonitrile 3n, was obtained as a colorless oil (106.3 mg) in an 81% yield. The chromatographic data are as follows:

[0085] 1 H NMR (500MHz, CDCl3) δ7.45–7.36 (m, 2H), 7.23 (d, J = 7.7Hz, 1H), 2.34 (s, 3H), 2.30 (s, 3H). 13 C NMR (126MHz, CDCl3) δ142.5,137.9,132.8,130.3,129.6,119.3,109.5,20.1,19.6.

[0086] Example 15 Synthesis of Benzo[d][1,3]dioxin-5-Carbonitrile

[0087]

[0088] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply. Aryl phosphate diethyl ester 1o (1.0 mmol), tert-butyl isocyanide (5 eq), DMF (8 mL), n Bu4NPF6 (1 eq) and KOAc (4 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -6.0 V) for 16 hours. After TLC indicated complete reaction of the starting material 1o, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 10:1 volume ratio of petroleum ether / ethyl acetate as the eluent. The target product, benzo[d][1,3]dioxin-5-carbonitrile 3o, was obtained as a colorless oil (122.1 mg) in an 83% yield. The chromatographic data are as follows:

[0089] 1 H NMR (500MHz, CDCl3) δ7.22 (dd, J = 8.1, 1.7Hz, 1H), 7.04 (d, J = 1.7Hz, 1H), 6.87 (d, J = 8.0Hz, 1H), 6.08 (s, 2H); 13C NMR (126MHz, CDCl3) δ151.6,148.1,128.2,118.9,111.4,109.1,104.9,102.3.

[0090] Example 16 Synthesis of 2-(trifluoromethyl)benzonitrile

[0091]

[0092] A three-necked flask was loaded with a carbon rod anode and cathode (both 1 cm × 0.5 cm in size) and connected to a DC power supply. Aryl phosphate diethyl ester 1p (1.0 mmol), tert-butyl isocyanide (5 eq), DMF (8 mL), LiBF4 (1 eq), and KOAc (4 eq) were then added. The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -6.0 V) for 12 hours. After TLC indicated complete reaction of the starting material 1p, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL × 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography using a 15:1 (volume ratio) petroleum ether / ethyl acetate solution yielded 140.3 mg of the target product, 2-(trifluoromethyl)benzonitrile 3p, as a colorless oil in an 82% yield. The chromatographic data are as follows:

[0093] 1 H NMR (500MHz, CDCl3) δ7.63 (dd, J=7.7, 1.5Hz, 1H), 7.60–7.55 (m, 1H), 7.53 (s, 1H), 7.49 (d, J=8.4Hz, 1H); 13 C NMR (126MHz, CDCl3) δ149.2 (q, J = 1.3Hz), 131.0, 130.6, 125.6, 124.4, 120.2 (q, J = 259.6Hz), 117.2, 114.1. 19 F NMR (471 MHz, CDCl3) δ-58.2.

[0094] Example 17 Synthesis of 2-methylbenzonitrile:

[0095]

[0096] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply; 1 q (1.0 mmol) of aryl dimethyl phosphate, 5 eq of tert-butyl isocyanide, 5 mL of MeCN, nBu4NClO4 (3 eq) and KOAc (4 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -5.0 V) for 14 hours. After TLC indicated complete reaction of the starting material 1q, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 20:1 volume ratio of petroleum ether / ethyl acetate as the eluent to obtain 104.3 mg of the target product, 2-methylbenzonitrile 3q, as a colorless oil in an 89% yield. The chromatographic data are as follows:

[0097] 1 H NMR (500MHz, CDCl3) δ7.51 (dd, J=7.6, 1.2Hz, 1H), 7.40 (td, J=7.6, 1.4Hz, 1H), 7.27-7.13 (m, 2H), 2.47 (s, 3H); 13 C NMR (75MHz, CDCl3): δ141.9,132.7,132.5,130.2,126.2,118.2,112.7,20.5.

[0098] Example 18 Synthesis of 2-methoxybenzonitrile:

[0099]

[0100] A carbon rod anode and cathode (both 1 cm × 0.5 cm in size) were placed in a three-necked flask and connected to a DC power supply. Aryl dimethyl phosphate 1r (1.0 mmol), tert-butyl isocyanide (5 eq), MeCN (5 mL), n Bu4NClO4 (3 eq) and KOAc (4 eq). The reaction solution was electrolyzed at room temperature using a DC constant potential (V = -5.0 V) for 14 hours. After TLC indicated complete reaction of the starting material 1r, the mixture was poured into ethyl acetate (20 mL) and washed three times with water (5 mL x 3). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Purification was then performed by column chromatography using a 15:1 volume ratio of petroleum ether / ethyl acetate as the eluent to obtain 106.5 mg of the target product, 2-methoxybenzonitrile 3r, as a colorless oil in an 80% yield. The chromatographic data are as follows:

[0101] 1 H NMR(400MHz, CDCl3)δ3.03(3H,s),6.97-7.57(4H,m); 13 C NMR (100MHz, CDCl3) δ55.9,101.7,111.2,116.5,120.7,133.7,134.3,161.2.

[0102] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate, characterized in that: A carbon rod anode and a carbon rod cathode are placed in a reaction flask and connected to a DC regulated power supply. Compound 1, dialkyl aryl phosphate, compound 2, tert-butyl isocyanide, an organic solvent, an electrolyte, and a base are then added to the reaction flask. The reaction solution is electrolyzed at a temperature of 10-70°C using a DC constant voltage for 12-20 hours. After the reaction is completed, ethyl acetate is added, the mixture is washed with water, and the organic phase is dried, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the target compound 3, aryl nitrile. The synthetic route is as follows: ； Ar is an aryl group, or an aryl group having an alkyl group, an alkoxy group, an amino group, a halogen group, a cyano group, a keto group, an ester group or a trifluoromethyl group at the ortho, meta or para position; R is a methyl group, an ethyl group or an isopropyl group.

2. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The molar ratio of the dialkyl aryl phosphate to the tert-butyl isocyanide is 1:3-5.

3. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The molar ratio of the dialkyl aryl phosphate to the electrolyte is 1:1-3.

4. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The molar ratio of the dialkyl aryl phosphate to the base is 1:2-4.

5. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The organic solvent is one of acetonitrile, dimethyl sulfoxide, N-methylpyrrolidone and N,N-dimethylformamide.

6. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate as claimed in claim 3, characterized in that: The electrolytes used are mainly: n Bu4NPF6, LiBF4, LiPF6, Et4NOTs, LiClO4 or n Bu4NClO4.

7. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 4, wherein: The base used was LiOAc, NaOAc or KOAc.

8. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The DC voltage used is -4.0 V to -6.0 V.

9. The method for electrochemically synthesizing aryl nitrile using dialkyl aryl phosphate according to claim 1, wherein: The eluent selected for the column chromatography is a mixture of petroleum ether and ethyl acetate.

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