Method for synthesizing aryl nitrile under catalysis of cobalt by taking terephthalonitrile as cyaniding reagent

Abstract

According to the method, industrial chemicals which are low in cost, easy to obtain, stable, safe and easy to operate are developed to serve as the cyaniding reagent, and common cyaniding reagents such as highly toxic metal cyanide, complex organic nitrile molecules and extremely unstable hydrogen cyanide are replaced. The cyanidation reaction of various substituted aromatic hydrocarbons is realized under conventional thermal reaction conditions. The method is simple in system, mild in condition and easy to operate, does not need to use high-toxicity metal cyanide or complex organic nitrile as a cyaniding reagent, does not need to add an additional activating reagent, does not need to use special production equipment, is relatively high in reaction economic benefit, is harmless to the environment, is simple in post-treatment, not only solves the problem of safe and efficient production of aryl nitrile, but also has a good application prospect. Meanwhile, a novel cyaniding reagent is developed to be used for synthesizing aryl nitrile, is in accordance with the current chemical concept of pursuing safety, environmental protection, economy and green, and has good practicability and industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of aromatic nitrile, and particularly relates to a method for synthesizing aromatic nitrile by using terephthalonitrile as a cyaniding reagent and cobalt as a catalyst. Background Art

[0002] Aryl nitriles are one of the most important structural units in organic chemistry and are widely found in dyes, electronic materials, drugs and bioactive molecules. Therefore, the development of new green, economical and efficient methods for the synthesis of aryl nitriles has always been a key research topic in the field of organic synthetic chemistry.

[0003] To date, the synthesis methods of aromatic nitriles mainly include the following three categories: (1) Using metal cyanides such as sodium cyanide, potassium cyanide, zinc cyanide, etc. as nucleophilic cyanide sources, transition metals catalyze the synthesis of aromatic nitriles from halogenated aromatic hydrocarbons (or their analogs) (Chem. Soc. Rev., 2011, 40, 5049-5067; Tetrahedron Lett., 2014, 55, 1271-1280; J. Organomet. Chem., 2020, 920, 121377). This type of cyaniding reagent has been widely used in industrial production for nearly a hundred years due to its mild reaction conditions, simple catalytic system, and wide range of substrate applications. However, these reagents are generally highly toxic compounds, a large amount of metal waste will be generated during the reaction, and the toxic effect of cyanide anions on transition metal catalysts is inevitable. (2) Organic small molecules containing cyano groups are used as cyanation reagents to synthesize aromatic nitriles under different catalytic systems (Angew. Chem. Int. Ed., 2012, 51, 11948-11959; Org. Biomol. Chem., 2019, 17, 11-23). ​​This type of reagent is mainly composed of carbon, nitrogen, oxygen, and sulfur-based nitrile compounds, which participate in the reaction as electrophilic cyanation reagents. Some compounds such as acetone cyanohydrin also participate in the reaction as nucleophilic cyanation reagents. This method provides a new low-toxic, mild, and green synthesis route for aromatic nitriles, but it also has limitations such as difficulty in activating cyanation reagents and complex catalytic systems. (3) Synthesis of aromatic nitriles by transformation of different types of functional groups (Angew. Chem. Int. Ed., 2004, 43, 5375-5377; J. Org. Chem., 2015, 80, 11624-11628; Nat. Commun., 2017, 8, 15240; Chem, 2018, 4, 2883-2893; Nat. Commun., 2020, 11, 4096.). For example, aromatic nitriles are synthesized by ammoxidation reaction using aromatic aldehydes, ketones, carboxylic acids and other compounds as raw materials; aromatic nitriles are synthesized by using formamide or a combination of carbon dioxide and ammonia as a cyanide source. This type of method provides an alternative route for the synthesis of aromatic nitriles from different types of substrates, but most of the transformation steps are complicated and the reaction conditions are harsh.

[0004] Therefore, developing more economical, friendly and safe cyanidation reagents and developing simple and efficient new cyanidation reaction methods remain one of the important goals of current cyanidation reaction research. Summary of the invention

[0005] The purpose of the present invention is to provide a method for synthesizing aromatic nitrile with terephthalonitrile as a cyaniding agent, which has mild conditions, simple operation and economical and effective process. The method does not need to use highly toxic metal cyanide or complex organic nitrile as a cyaniding agent, does not need to add additional activation reagents, and does not need to use special production equipment.

[0006] In view of the above purpose, the technical scheme adopted by the present invention is: adding an aromatic compound represented by formula I, terephthalonitrile, cobalt (II), a nitrogen ligand, a reducing agent and a base to a solvent, stirring and reacting in a range of room temperature to 100° C. under argon conditions, separating and purifying after the reaction to obtain an aromatic nitrile represented by formula II;

[0007]

[0008] In the formula, Ar represents an aryl group or a substituted aryl group, and the substituent in the substituted aryl group is selected from any one of hydrogen, halogen, phenyl, triphenylmethyl, C1-C8 alkyl, hydroxyl, C1-C6 alkoxy, phenoxy, amide, vinyl, and benzyl; X represents any one of trifluoromethylsulfonate, 4-methylbenzenesulfonate, methylsulfonate, chlorine, bromine, and iodine.

[0009] The cobalt (II) is any one of cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetate, cobalt carbonate and cobalt acetylacetonate. Preferably, the amount of cobalt (II) is 2% to 20% of the molar amount of the aromatic compound.

[0010] The nitrogen ligand is any one of 2,2-bipyridine, 4,4-dimethyl-2,2-bipyridine and 4,4-tert-butyl-2,2-bipyridine. The amount of the nitrogen ligand is preferably 2% to 20% of the molar amount of the aromatic compound.

[0011] The reducing agent is zinc powder, and the amount of the reducing agent used is 0.1 to 2.0 times the molar amount of the aromatic compound.

[0012] The base is any one of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine. Preferably, the amount of the base used is 0.2 to 3.0 times the molar amount of the aromatic compound.

[0013] Furthermore, it is preferred that the amount of the terephthalonitrile used is 1.0 to 3.0 times the molar amount of the aromatic compound.

[0014] Furthermore, it is preferred that the solvent is any one of acetonitrile, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and N-methylpyrrolidone.

[0015] Furthermore, the above method is preferably carried out under argon conditions with stirring at 50-80°C.

[0016] Furthermore, the preferred reaction time of the above method is 6 to 24 hours.

[0017] The beneficial effects of the present invention are as follows:

[0018] The invention uses terephthalonitrile as a cyaniding agent, does not need to use highly toxic metal cyanide, does not need to use complex reaction conditions when using complex organic nitrile as a cyaniding agent, has a simple system, mild conditions, and is easy to operate. The reaction has high economic benefits, is harmless to the environment, and has simple post-processing. It not only solves the problem of safe and efficient production of aromatic nitrile, but also develops a new cyaniding agent for the synthesis of aromatic nitrile, which is consistent with the current pursuit of safe, environmentally friendly, economical, and green chemical concepts, and has very important application prospects. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0020] Example 1

[0021] Terephthalonitrile (0.8mmol, 102.5mg), cobalt iodide (0.04mmol, 12.5mg), 4,4-dimethyl-2,2-bipyridine (0.04mmol, 7.4mg), and zinc powder (0.24mmol, 15.7mg) were added in sequence to a 10mL reaction tube (with a branch tube) equipped with a magnetic stirrer, the lid was tightened, and the argon gas was replaced three times using a double-row tube; (4-tert-butyl)phenyl trifluoromethanesulfonate (0.4mmol, 112.8mg), 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine (0.6mmol, 67.3mg) and 1.0mL N,N-dimethylacetamide were added to the reaction tube in sequence using a syringe in the argon flow, the reaction tube was sealed, and then placed in a metal bath at 50°C and stirred for 24 hours. After the reaction was completed and the temperature was cooled to room temperature, the reaction solution was extracted with ethyl acetate and water, the organic phase was dried over anhydrous sodium sulfate and concentrated, and the eluent was petroleum ether and ethyl acetate in a volume ratio of 150:1. The mixture was separated by column chromatography to obtain 4-tert-butylbenzonitrile as a colorless oil with the following structural formula, and the yield was 86%.

[0022]

[0023] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.58 (d, J = 8.4Hz, 2H), 7.47 (d, J = 8.4Hz, 2H), 1.33 (s, 9H). 13 C NMR(100MHz, CDCl3)δ156.7,132.0,126.2,119.2,109.3,35.3,31.0.HRMS(ESI-TOF)m / z C 11 H 13 NNa[M+Na] + : Theoretical value 182.0940, measured value 182.0939.

[0024] In this example, 4,4-dimethyl-2,2-bipyridine was replaced with an equal mole of 2,2-bipyridine, and the yield of the obtained product was 75%.

[0025] In this example, 4,4-dimethyl-2,2-bipyridine was replaced with an equal mole of 4,4-tert-butyl-2,2-bipyridine, and the yield of the obtained product was 80%.

[0026] Example 2

[0027] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-n-octyl)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 72%.

[0028]

[0029] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.55(d,J=8.2Hz,2H),7.27(d,J=8.2Hz,2H),2.67-2.62(m,2H),1.66-1.56(m,2H),1.37-1.19(m,10H),0.88(q,J=6.8Hz,3H). 13 C NMR(100MHz, CDCl3)δ148.7,132.2,129.3,119.3,109.6,36.2,31.9,31.1,29.5,29.3,22.7,14.2.HRMS(ESI-TOF)m / z C 17 H 19 NNa[M+Na] + : Measured value 260.1410, theoretical value 260.1411.

[0030] Example 3

[0031] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-triphenylmethyl)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 72%.

[0032]

[0033] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.53 (d, J = 8.5Hz, 2H), 7.36 (d, J = 8.5Hz, 2H), 7.28-7.15 (m, 15H).13 C NMR(100MHz, CDCl3)δ152.5,145.8,131.9,131.5,131.1,128.0,126.5,119.0,110.0,65.4.HRMS(ESI-TOF)m / zC 26 H 19 NNa[M+Na] + : Theoretical value 368.1410, measured value 368.1411.

[0034] Example 4

[0035] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-phenyl)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 84%.

[0036]

[0037] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.74-7.66(m,4H),7.62-7.55(m,2H),7.53-7.41(m,3H). 13 C NMR(100MHz, CDCl3)δ145.7,139.2,132.7,129.2,128.8,127.8,127.3,119.0,111.0.HRMS(ESI-TOF)m / z C 13 H9NNa[M+Na] + : Theoretical value 202.0627, measured value 202.0623.

[0038] Example 5

[0039] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-methoxy)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 79%.

[0040]

[0041] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.56 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H). 13C NMR(100MHz, CDCl3)δ162.9,134.0,119.3,114.8,104.0,55.6.HRMS(ESI-TOF)m / z C8H7NONa[M+Na] + : Theoretical value 156.0420, measured value 156.0421.

[0042] Example 6

[0043] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with (4-phenoxy)phenyl trifluoromethanesulfonate in equal moles, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 82%.

[0044]

[0045] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.59 (d, J = 8.8Hz, 2H), 7.41 (t, J = 7.9Hz, 2H), 7.26-7.20 (m, 1H), 7.06 (d, J = 7.8Hz, 2H), 7.0 (d, J = 8.8Hz, 2H). 13 C NMR(100MHz, CDCl3)δ161.8,154.9,134.2,130.3,125.2,120.5,118.9,118.0,105.9.HRMS(ESI-TOF)m / z[M+Na] + : Theoretical value 218.0576, measured value 218.0578.

[0046] Example 7

[0047] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-acetamido)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 84%.

[0048]

[0049] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, DMSO-d6) δ10.37(s,1H),7.80-7.69(m,4H),2.09(s,3H). 13C NMR(100MHz,DMSO-d6)δ169.2,143.5,133.3,119.1,119.0,104.8,24.2.HRMS(ESI-TOF)m / z C9H8N2ONa[M+Na] + : Theoretical value 183.0529, measured value 183.0527.

[0050] Example 8

[0051] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (4-vinyl)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 78%.

[0052]

[0053] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.61(d,J=8.3Hz,2H),7.48(d,J=8.3Hz,2H),6.72(d,J=17.6,10.9Hz,1H),5.87(d,J=17.6Hz,1H),5.44(d,J=10.9Hz,1H). 13 C NMR (100 MHz, CDCl3) δ 142.0, 135.5, 132.5, 126.9, 119.0, 117.9, 111.2. GCMS m / z C9H7N: theoretical value 129, found value 129.

[0054] Example 9

[0055] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced with an equal mole of (2-benzyl)phenyl trifluoromethanesulfonate, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 59%.

[0056]

[0057] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.49 (d, J = 7.6Hz, 1H), 7.37-7.32 (m, 1H), 7.21-7.04 (m, 7H), 4.06 (s, 2H). 13C NMR (100MHz, CDCl3) δ145.1,138.9,133.1,133.0,130.2,129.1,128.8,126.9,126.8,118.3,112.7,40.3.HRMS (ESI-TOF) m / zC 14 H 11 NNa[M+Na] + : Theoretical value 216.0784, measured value 216.0784.

[0058] In this example, 1,8-diazabicyclo[5.4.0]undec-7-ene was replaced by an equal mole of 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine, and the yield of the product was 56%.

[0059] Example 10

[0060] In this example, (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 was replaced by an equal mole of (2-phenyl)phenyl trifluoromethanesulfonate, the metal bath temperature was changed from 50° C. to 80° C., and the other steps were the same as in Example 1 to obtain a product with the following structural formula, and the yield was 70%.

[0061]

[0062] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.77 (d, J = 7.7Hz, 1H), 7.67-7.62 (m, 1H), 7.60-7.55 (m, 2H), 7.54-7.42 (m, 5H). 13 C NMR(100MHz, CDCl3)δ145.6,138.3,133.9,132.9,130.2,128.9,128.8,127.7,118.8,111.4.HRMS(ESI-TOF)m / zC 13 H9NNa[M+Na] + : Theoretical value 202.0627, measured value 202.0625.

[0063] Embodiment 11

[0064] In this example, (3,5-dimethoxy)phenyl trifluoromethanesulfonate was used to replace (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 in equal moles, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 71%.

[0065]

[0066] The NMR spectrum data of the obtained product are: 1H NMR (400MHz, CDCl3) δ6.76 (d, J = 2.2Hz, 2H), 6.65 (t, J = 2.2Hz, 1H), 3.80 (s, 6H). 13 C NMR(100MHz, CDCl3)δ161.0,118.7,113.4,109.9,105.7,55.7.HRMS(ESI-TOF)m / z C9H9NO2Na[M+Na] + : Theoretical value 186.0525, measured value 186.0525.

[0067] Example 12

[0068] In this example, (3,4-methylenedioxy)phenyl trifluoromethanesulfonate was used to replace (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 in equal moles, and the other steps were the same as in Example 1 to obtain a product with the following structural formula, with a yield of 68%.

[0069]

[0070] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.21 (dd, J = 8.1, 1.4Hz, 1H), 7.03 (d, J = 1.3Hz, 1H), 6.86 (d, J = 8.1Hz, 1H), 6.07 (s, 2H). 13 C NMR(100MHz, CDCl3)δ151.7,148.2,128.4,119.0,111.5,109.3,105.1,102.4.HRMS(ESI-TOF)m / z C8H5NO2Na[M+Na] + : Theoretical value 170.0212, measured value 170.0215.

[0071] Example 13

[0072] In this example, 2-dibenzofuran trifluoromethanesulfonate was used in place of (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 in equal moles, the metal bath temperature was changed from 50° C. to 80° C., and the other steps were the same as in Example 1 to obtain a product having the following structural formula with a yield of 52%.

[0073]

[0074] The NMR spectrum data of the obtained product are: 1H NMR (400MHz, CDCl3) δ8.24(d,J=1.5Hz,1H),7.96(d,J=7.7Hz,1H),7.73(dd, J=8.5,1.6Hz,1H),7.67-7.59(m,2H),7.58-7.49(m,1H),7.47-7.36(m,1H). 13 C NMR (100MHz, CDCl3) δ158.1,156.9,131.0,128.9,125.5,125.3,123.9,122.7,121.2,119.3,112.9,112.2,106.7.HRMS(ESI-TOF)m / zC 13 H7NONa[M+Na] + : Theoretical value 216.0420, measured value 216.0425.

[0075] Embodiment 14

[0076] In this example, 4-chlorophenyl trifluoromethanesulfonate was used in place of (4-tert-butyl)phenyl trifluoromethanesulfonate in Example 1 in equal moles, the metal bath temperature was changed from 50° C. to 80° C., and the other steps were the same as in Example 1 to obtain a product having the following structural formula with a yield of 44%.

[0077]

[0078] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.60 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 139.7, 133.5, 129.8, 118.1, 110.9. GCMS m / z C7H4ClN: theoretical value 137, found value 137.

Claims

1. A method for synthesizing aromatic nitriles by cobalt catalysis using terephthalonitrile as a cyaniding agent, characterized in that: The aromatic compound represented by formula I, terephthalonitrile, cobalt (II), a nitrogen ligand, a reducing agent and a base are added to a solvent, and the mixture is stirred and reacted in a range of room temperature to 100°C under argon gas. After the reaction is completed, the mixture is separated and purified to obtain the aromatic nitrile represented by formula II; In the formula, Ar represents an aryl group or a substituted aryl group, and the substituent in the substituted aryl group is selected from any one or two of hydrogen, halogen, phenyl, triphenylmethyl, C1-C8 alkyl, hydroxyl, C1-C6 alkoxy, phenoxy, amide, vinyl, and benzyl; X represents any one of trifluoromethylsulfonate, 4-methylbenzenesulfonate, methylsulfonate, chlorine, bromine, and iodine; The cobalt (II) is selected from any one of cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetate, cobalt carbonate, and cobalt acetylacetonate; The nitrogen ligand is selected from any one of 2,2-bipyridine, 4,4-dimethyl-2,2-bipyridine, and 4,4-tert-butyl-2,2-bipyridine; The reducing agent is selected from zinc powder; The base is selected from any one of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine.

2. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The reaction was stirred at 50-80°C under argon.

3. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The amount of terephthalonitrile used is 1.0 to 3.0 times the molar amount of the aromatic compound.

4. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The amount of cobalt (II) used is 2% to 20% of the molar amount of the aromatic compound.

5. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The amount of the nitrogen ligand used is 2% to 20% of the molar amount of the aromatic compound.

6. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The amount of the reducing agent used is 0.1 to 2.0 times the molar amount of the aromatic compound.

7. The method for synthesizing aromatic nitriles by using terephthalonitrile as a cyaniding agent and cobalt as claimed in claim 1, characterized in that: The amount of the base used is 0.2 to 3.0 times the molar amount of the aromatic compound.

8. The method for synthesizing aromatic nitriles by cobalt catalysis using terephthalonitrile as a cyaniding agent according to claim 1, characterized in that: The solvent is selected from any one of acetonitrile, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide and N-methylpyrrolidone.

9. The method for synthesizing aromatic nitriles by cobalt catalysis using terephthalonitrile as a cyaniding agent according to claim 1, characterized in that: The reaction time is 6 to 24 hours.

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