A manganese complex Mn-L and its preparation method and application

Abstract

The invention discloses a manganese complex Mn-L and a preparation method and application thereof. The preparation process of the manganese complex Mn-L of the invention is as follows: under an argon atmosphere, a bidentate ligand with an imidazole-thiophene skeleton is reacted with Mn(CO)5Br to prepare the manganese complex Mn-L, and the manganese complex Mn-L is used as a catalyst to prepare an α-alkyl substituted aromatic acetonitrile derivative by hydrogen borrowing reaction of alcohol and nitrile. The invention adopts a limited self-made manganese complex Mn-L as a catalyst, uses alcohol as an alkylating agent to prepare an α-alkyl substituted aromatic acetonitrile derivative, and generates water as the only by-product, which conforms to the concept of atomic economy and environmental friendliness. At the same time, the method has the advantages of using a catalytic amount of base, short reaction time, and economy. In the formula, R 1 R is selected from C2-C8 straight-chain or branched alkyl, phenyl or heterocyclic aromatic group; 2 , R 3 are independently H or C1-C3 alkyl, R 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

Description

Technical Field

[0001] The invention belongs to the technical field of organic and pharmaceutical synthesis, and specifically relates to a manganese complex Mn-L and a preparation method thereof and application thereof in the preparation of α-alkyl substituted aromatic acetonitrile derivatives. Background Art

[0002] Traditionally, the method for obtaining α-alkyl nitrile derivatives is mainly the substitution reaction of nitrile compounds with halogen-containing compounds. However, the halogen-containing compounds themselves are highly toxic and pose safety risks. At the same time, this process will produce a large amount of wastewater in industry, and the amount of three wastes is large.

[0003] In recent years, metal-catalyzed hydrogen borrowing reactions have flourished. Using alcohols as alkylating agents to construct CC bonds through hydrogen borrowing strategies has become a very important method with high atom economy and strong practicality. However, in the field of hydrogen borrowing, the expensive ruthenium catalyst used to synthesize α-alkyl-substituted aromatic acetonitrile derivatives from alcohols and nitriles through hydrogen borrowing strategies has increased the cost to a certain extent. However, the method of constructing α-alkyl-substituted aromatic acetonitrile derivatives in one step through a phosphine-free metal catalyst has not been reported so far. Summary of the invention

[0004] In view of the above technical problems existing in the prior art, the object of the present invention is to provide a manganese complex Mn-L and a preparation method thereof and an application thereof in the preparation of α-alkyl substituted aromatic acetonitrile derivatives, that is, the present invention uses a method for efficiently preparing α-alkyl substituted aromatic acetonitrile derivatives by catalyzing the hydrogen borrowing reaction of aromatic acetonitrile and primary alcohol using cheap metallic manganese.

[0005] The present invention defines a manganese complex Mn-L, whose structural formula is shown in formula (Mn-L):

[0006]

[0007] In the formula, R 2 , R 3 are independently H or C1-C3 alkyl, R 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

[0008] Furthermore, the present invention further defines the manganese complex Mn-L, whose structural formula is any one of the formulas (Mn-L1 to L6):

[0009]

[0010] Furthermore, the present invention also defines a method for preparing the manganese complex Mn-L, which is specifically: in an argon atmosphere, Mn(CO)5Br and a bidentate ligand having an imidazole-thiophene skeleton as shown in formula (IV) are added to toluene for reflux reaction, and an orange manganese complex Mn-L is obtained after concentration. The reaction route is as follows:

[0011]

[0012] In formula (IV) and formula (Mn-L), R 2 , R 3 are independently H or C1-C3 alkyl, R 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

[0013] Furthermore, the present invention also defines the use of the manganese complex Mn-L as a catalyst in the preparation of α-alkyl substituted aromatic acetonitrile derivatives.

[0014] Furthermore, the present invention also defines a method for preparing an α-alkyl substituted aromatic acetonitrile derivative based on the manganese complex Mn-L of the present invention as a catalyst, comprising the following process: in an argon atmosphere, the aromatic acetonitrile shown in formula (II) and the primary alcohol shown in formula (III), the catalyst manganese complex Mn-L, the alkaline substance and the solvent are sequentially added into a pressure-resistant sealed tube, reacted at 110 to 150° C. for 2 to 24 hours, and then concentrated under reduced pressure to remove the solvent, and the residue is separated by column chromatography to obtain the α-alkyl substituted aromatic acetonitrile derivative shown in formula (I), and the reaction route is as follows:

[0015]

[0016] Ar in formula (II) is phenyl, substituted aryl, heterocyclic aryl or naphthyl; R in formula (III) is 1 Selected from C2-C8 straight chain or branched alkyl, phenyl or heterocyclic aromatic group.

[0017] Furthermore, the present invention also specifies that the alkaline substance in the preparation method of the α-alkyl substituted aromatic acetonitrile derivative is selected from one or a mixture of two or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, potassium carbonate, and cesium carbonate.

[0018] Furthermore, the present invention also defines that the solvent in the method for preparing the α-alkyl substituted aromatic acetonitrile derivative is one or a mixture of two or more of toluene, xylene, tert-butanol and tert-amyl alcohol.

[0019] Furthermore, the present invention also defines the molar ratio of the aromatic acetonitrile represented by formula (II), the primary alcohol represented by formula (III), the alkaline substance, and the metal Mn-L catalyst in the preparation method of the α-alkyl substituted aromatic acetonitrile derivative as 1:1-2:0.1-0.5:0.005-0.02.

[0020] Furthermore, the present invention also defines that the substituent in the substituted aromatic group in the preparation method of the α-alkyl substituted aromatic acetonitrile derivative is halogen, C1~C3 alkyl or C1~C3 alkoxy.

[0021] By adopting the above technology, compared with the prior art, the beneficial effects of the present invention are as follows: the present invention provides a manganese complex Mn-L and a preparation method thereof, and uses the prepared manganese complex Mn-L as a catalyst to promote the hydrogen borrowing reaction of aromatic acetonitrile and primary alcohol, and efficiently prepares a method for α-alkyl substituted aromatic acetonitrile derivatives, with a reaction yield of more than 92%. Compared with the prior art, the catalyst preparation process of the present invention is simple and low in cost, and is used as a catalyst for the synthesis of α-alkyl substituted aromatic acetonitrile derivatives, and has the characteristics of high atomic economy, low green pollution, high safety, and easy industrialization. The present invention will play an important role in the discovery of new drugs, the structural modification of existing drugs, and the total synthesis of natural products. DETAILED DESCRIPTION

[0022] The present invention is further described in detail below through specific examples, but the present invention is not limited to the examples.

[0023] The metal Mn-L catalysts used in the embodiments of the present invention are prepared by the following method: Mn(CO)5Br and a bidentate ligand having an imidazole-thiophene skeleton as shown in formula (IV) are refluxed in toluene for 8 hours under an argon atmosphere, and an orange-yellow metal Mn-L catalyst is obtained after concentration; the reaction route is as follows:

[0024]

[0025] The ligand shown in formula (IV), Mn-L, wherein R 2 , R 3 are independently C1-C3 alkyl, R 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

[0026] Example 1: Preparation of Catalyst Mn-L1

[0027]

[0028] (1) 2-Thienylmethylamine a1 (0.5 mmol), imidazole carboxaldehyde b1 (0.5 mol), and 10 mL of methanol were added to a 50 mL two-necked bottle equipped with a magnetic rod, and refluxed and stirred at 80°C for 8 hours. After cooling to room temperature, 10 mL of methanol was added, and sodium borohydride (0.5 mmol) was slowly added, and the mixture was reacted at room temperature for 1 hour. After the reaction was completed, the solvent was removed, the reaction was quenched with 30 mL of water, and extracted with ethyl acetate (20 mL x 3). The organic phases were combined, backwashed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (dichloromethane / methanol = 20:1) to obtain the corresponding product L177 mg, yield: 80%.

[0029] Structural characterization of L1: Yellow solid; 80% yield, 1 H NMR (400MHz, CDCl3) δ7.21 (dd, J=5.2, 1.2Hz, 1H), 6.98 (s, 2H), 6.94 (dd, J=5.2, 3.2Hz,1H),6.92-6.89(m,1H),5.50(s,2H),3.98(d,J=0.8Hz,2H),3.93(s,2H); 13 C NMR(100MHz, CDCl3)δ146.84,142.89,126.86,125.53,124.76,47.84,46.03.; HRMS-ESI(m / z):calcd for C9H 12 N3S + [M+H] + 194.0749, found 194.0747.

[0030]

[0031] (2) Add ligand L1 (0.5 mmol) and metal pentacarbonyl manganese bromide (0.5 mmol) to a 100 mL three-necked flask equipped with a magnetic electron to replace argon gas, add toluene (10 mL) in an argon atmosphere, and then reflux at 110° C. for 8 hours. After the reaction is completed, the solvent is concentrated and recrystallized from tetrahydrofuran and n-hexane to obtain the corresponding product Mn-L1175 mg. Yield: 85%.

[0032] The high resolution mass spectrometry data of manganese complex Mn-L1, i.e. catalyst Mn-L1, are as follows: HRMS-ESI (m / z): calcdfor C 12 H 11 N3O3S + [M+H] + 331.9898, found 331.9896.

[0033] Example 2: Preparation of Catalyst Mn-L5

[0034]

[0035] (1) Add o-phenylenediamine a5 (4 mmol), 6N hydrochloric acid solution (4 mL) and amino acid b5 (6 mmol) to a 100 mL three-necked flask equipped with a magnetic rod, and reflux for 144 hours under argon protection. After the reaction is completed, quench the reaction by adding saturated NH3 aqueous solution until the pH value of the mixture becomes slightly alkaline (pH 8-9). Extract with ethyl acetate (20 mL x 3), combine the organic phases, backwash once with saturated brine (20 mL), dry over anhydrous sodium sulfate, and separate by column chromatography (dichloromethane / methanol = 10:1) to obtain the corresponding product c5771 mg, yield: 75%.

[0036] Structural characterization of c5: Yellow solid; 75% yield, 1 H NMR (400MHz, CDCl3) δ7.58 (dd, J=6.0, 3.2Hz, 2H), 7.25-7.18 (m, 3H), 6.95-6 .87(m,2H),4.26(q,J=6.8Hz,1H),4.04-3.94(m,2H),1.56(d,J=6.8Hz,3H).; 13 C NMR (100MHz, CDCl3) δ157.7,143.2,126.9,125.3,124.6,122.4,52.1,46.6,21.5.; HRMS-ESI(m / z):calcd for C 14 H 16 N3S + [M+H] + 258.1060, found 258.1072.

[0037]

[0038] (2) Add c5 (0.5 mmol), thiophene carboxaldehyde d5 (0.5 mol), and 10 mL of methanol to a 50 mL two-necked bottle equipped with a magnetic rod, and reflux and stir at 80°C for 8 hours. After cooling to room temperature, add 10 mL of methanol, slowly add sodium borohydride (0.5 mmol), and react at room temperature for 1 hour. After the reaction is completed, remove the solvent, quench the reaction with 30 mL of water, extract with ethyl acetate (20 mL x 3), combine the organic phases, backwash once with saturated brine (20 mL), dry over anhydrous sodium sulfate, concentrate, and separate by column chromatography (dichloromethane / methanol = 20:1) to obtain the corresponding product L5102 mg, yield: 80%.

[0039] Structural characterization of L5: Yellow solid; 80% yield, 1 H NMR (400MHz, CDCl3) δ7.58 (dd, J=6.0, 3.2Hz, 2H), 7.25-7.18 (m, 3H), 6.95-6 .87(m,2H),4.26(q,J=6.8Hz,1H),4.04-3.94(m,2H),1.56(d,J=6.8Hz,3H).; 13 C NMR (100MHz, CDCl3) δ157.7,143.2,126.9,125.3,124.6,122.4,52.1,46.6,21.5.; HRMS-ESI(m / z):calcd for C 14 H 16 N3S + [M+H] + 258.1060, found 258.1072.

[0040]

[0041] (3) Add ligand L5 (0.5 mmol) and metal pentacarbonyl manganese bromide (0.5 mmol) to a 100 mL three-necked flask equipped with a magnetic electron to replace argon, add toluene (10 mL) in an argon atmosphere, and then reflux at 110° C. for 8 hours. After the reaction, the solvent is concentrated and recrystallized from tetrahydrofuran and n-hexane to obtain 194 mg of the corresponding product Mn-L5. Yield: 82%. The high-resolution mass spectrum data of the manganese complex Mn-L5, i.e., catalyst Mn-L5, are as follows: HRMS-ESI (m / z): calcd for C 17 H 15 N3O3S + [M+H] + 396.0209, found 396.0205.

[0042] The preparation method of other ligands L and corresponding manganese complexes Mn-L is the same as that of Example 1 or 2, and only the substituent R in the raw material needs to be replaced by 2 , R 3 , R 4 Just make corresponding replacements.

[0043] The structure of ligand L2 is:

[0044]

[0045] Structural characterization of ligand L2: Colorless oil; (73 mg) 70% yield, 1H NMR (400MHz, CDCl3) δ7.20-7.08(m,1H),6.98-6.82(m,3H),6.75(d,J=1.2Hz,1H),3.95(s,2H),3.79(s,2H),3.57(s,3H),2.63(s,1H).; 13 C NMR(100MHz, CDCl3)δ146.11,143.64,126.97,126.62,125.12,124.50,121.31,47.85,44.61,32.73.; HRMS-ESI(m / z):calcd for C 10 H 14 N3S + [M+H] + 208.0903, found 208.0909.

[0046] The high resolution mass spectrometry data of manganese complex Mn-L2, i.e. catalyst Mn-L2, are as follows: HRMS-ESI (m / z): calcdfor C 13 H 13 N3O3S + [M+H] + 346.0052, found 346.0055.

[0047] The structure of ligand L3 is:

[0048]

[0049] Structural characterization of ligand L3: Colorless oil; (87 mg) 72% yield, 1 H NMR (400MHz, CDCl3) δ7.18-7.10(m,1H),6.92-6.84(m,3H),6.75(d,J=1.2Hz,1H),3.95(s,2H),3.79(s,2H),3.57(s,3H).; 13 C NMR(100MHz, CDCl3)δ146.11,143.64,126.97,126.62,125.12,124.50,121.31,47.85,44.61,32.73.; HRMS-ESI(m / z):calcd for C 13 H 14 N3S + [M+H] + 244.0903, found 244.0906.

[0050] The high resolution mass spectrum data of manganese complex Mn-L3, i.e. catalyst Mn-L3, are as follows: HRMS-ESI (m / z): calcdfor C 16 H 13 N3O3S + [M+H] + 382.0052, found 382.0053.

[0051] The structure of ligand L4 is:

[0052]

[0053] Structural characterization of L4: Colorless oil; (84 mg) 66% yield, 1 H NMR (400MHz, CDCl3) δ7.74-7.70(m,1H),7.36-7.26(m,3H),7.26-7.21(m,2H),6.99-6.94(m,2H),4.12(d,J=3.2Hz,4H),3.80(s,3H).; 13 C NMR (100MHz, CDCl3) δ180.82,141.89,129.56,127.83,124.08,122.24,109.76,47.22,23.59,10.02.; HRMS-ESI(m / z):calcd for C 14 H 16 N3S + [M+H] + 258.1060, found 258.1062.

[0054] The high resolution mass spectrometry data of manganese complex Mn-L4, i.e. catalyst Mn-L4, are as follows: HRMS-ESI (m / z): calcdfor C 17 H 15 N3O3S + [M+H] + 396.0209, found 396.0205.

[0055] The structure of ligand L6 is:

[0056]

[0057] Structural characterization of ligand L6: Colorless oil; (100 mg) 70% yield, 1H NMR (400MHz, CDCl3) δ12.17(s,1H),7.57(d,J=7.2Hz,1H),7.47(d,J=7.2Hz,1 H),7.38(dd,J=5.2,1.2Hz,1H),7.14(q,J=4.0Hz,2H),6.97-6.93(m,1H),6.88 (dd,J=3.6,1.2Hz,1H),3.88(d,J=14.4Hz,1H),3.69-3.56(m,2H),2.73(s,1H ), 2.02(dt,J=13.6,6.8Hz,1H),0.99(d,J=6.8Hz,3H),0.78(d,J=6.8Hz,3H).; 13 C NMR (100MHz, CDCl3) δ157.1,145.3,127.0,127.0,125.1,125.0,124.5,122.0 ,121.3,118.9,111.6,62.2,46.5,33.4,19.9,19.9..; HRMS-ESI(m / z):calcd for C 16 H 20 N3S + [M+H] + 286.1373, found 286.1380

[0058] The high resolution mass spectrum data of manganese complex Mn-L6, i.e. catalyst Mn-L6, are as follows: HRMS-ESI (m / z): calcdfor C 19 H 19 N3O3S + [M+H] + 424.0522, found 424.0526.

[0059] Example 3: Preparation of 2,3-diphenylpropionitrile (Ia)

[0060]

[0061] Under argon atmosphere, to a 10mL pressure-resistant sealed tube, benzyl cyanocyanate Ⅱa (58.5mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-butanol (0.5mL) were added in sequence. The reaction was carried out at 135℃ under high pressure for 12h. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 77mg of 2,3-diphenylpropionitrile (Ⅰa), with a yield of 75%.

[0062] Example 4: Preparation of 2,3-diphenylpropionitrile (Ia)

[0063]

[0064] Under argon atmosphere, benzyl cyanide Ⅱa (58.5 mg, 0.5 mmol), benzyl alcohol Ⅲa (98 mg, 1 mmol), catalyst Mn-L1 (4.6 mg, 0.01 mmol), potassium tert-butoxide (28.0 mg, 0.25 mmol, and tert-amyl alcohol (0.5 mL) were added in sequence to a 10 mL pressure-resistant sealed tube. The reaction was carried out under high pressure at 135 ° C for 12 h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 82 mg of 2,3-diphenylpropionitrile (Ⅰa), with a yield of 80%.

[0065] Example 5: Preparation of 2,3-diphenylpropionitrile (Ia)

[0066]

[0067] Under argon atmosphere, to a 10mL pressure-resistant sealed tube, benzyl cyanocyanate Ⅱa (58.5mg, 0.5mmol), benzyl alcohol Ⅲa (49mg, 0.5mmol), catalyst Mn-L2 (2.5mg, 0.005mmol), potassium carbonate (34.5mg, 0.25mmol) and toluene (0.5mL) were added in sequence, and the reaction was carried out at 150℃ under high pressure for 2h. After the reaction, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 72mg of 2,3-diphenylpropionitrile (Ⅰa), with a yield of 70%.

[0068] Example 6: Preparation of 2,3-diphenylpropionitrile (Ia)

[0069]

[0070] Under argon atmosphere, to a 10mL pressure-resistant sealed tube, benzyl cyanocyanate Ⅱa (58.5mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L3 (10.0mg, 0.02mmol), sodium tert-butoxide (24.0mg, 0.25mmol) and xylene (0.5mL) were added in sequence, and the reaction was carried out at 135℃ under high pressure for 12h. After the reaction, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 67mg of 2,3-diphenylpropionitrile (Ⅰa), with a yield of 65%.

[0071] Example 7: Preparation of 2-(4-(tert-butyl)phenyl)-3-phenylpropionitrile (Ib)

[0072]

[0073] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added 4-tert-butylphenylacetonitrile Ⅱb (86.5mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L4 (5.1mg, 0.01mmol), cesium carbonate (32.5mg, 0.1mmol) and tert-amyl alcohol (0.5mL) in sequence. The mixture was reacted at 110℃ under high pressure for 24h. After the reaction, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 113mg of 2-(4-(tert-butyl)phenyl)-3-phenylpropionitrile (Ⅰb), with a yield of 86%.

[0074] Structural characterization of Ⅰb: Colorless oil; 86% yield, 1 H NMR (400MHz, CDCl3) δ7.41–7.36 (m, 2H), 7.30 (dq, J = 6.8, 5.6, 5.2Hz, 3H), 7.2 5–7.17(m,4H),3.97(dd,J=8.8,6.4Hz,1H),3.20–3.08(m,2H),1.32(s,9H).; 13 C NMR (100MHz, CDCl3) δ151.3,136.6,132.3,129.2,128.7,127.4,127.1,126.0,120.6,42.3,39.5,34.6,31.3.; HRMS-ESI(m / z):calcd forC 19 H 22 N[M+H] + 264.1747, found 264.1743.

[0075] Example 8: Preparation of 2-(4-chlorophenyl)-3-phenylpropionitrile (Ic)

[0076]

[0077] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added p-chlorobenzeneacetonitrile Ⅱc (75.8mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L5 (5.1mg, 0.01mmol), potassium hydroxide (28.0mg, 0.5mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135℃ for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 2-(4-chlorophenyl)-3-phenylpropionitrile (Ⅰc) 91mg, yield: 76%.

[0078] Structural characterization of Ⅰc: Colorless oil; 76% yield, 1 H NMR (400MHz, CDCl3) δ7.34–7.25(m,5H),7.19–7.14(m,2H),7.10(dd,J=7.2,2.0Hz,2H),4.01–3.96(m,1H),3.22–3.06(m,2H).; 13 C NMR (100MHz, CDCl3) δ135.8,134.2,133.6,129.3,129.2,128.9,128.7,127.6,120.0,42.0,39.2.; HRMS-ESI(m / z):calcd for C 15 H 13 ClN[M+H] + 242.0731, found 242.0739.

[0079] Example 9: Preparation of 2-(4-methoxyphenyl)-3-phenylpropionitrile (Id)

[0080]

[0081] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added p-methoxyphenylacetonitrile Ⅱd (73.6mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L6 (5.3mg, 0.01mmol), sodium hydroxide (20.0mg, 0.5mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out at 135℃ under high pressure for 12h. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 2-(4-methoxyphenyl)-3-phenylpropionitrile (Ⅰd) 106mg, yield: 90%.

[0082] Structural characterization of Ⅰd: Colorless oil; 90% yield, 1H NMR (400MHz, CDCl3) δ7.31–7.23(m,3H),7.18–7.10(m,4H),6.88–6.84(m,2 H),3.94(dd,J=8.4,6.4Hz,1H),3.79(s,3H),3.12(qd,J=13.6,7.2Hz,2H).; 13 C NMR (100MHz, CDCl3) δ159.4,136.4,129.3,128.7,128.6,127.4,127.2,120.7,114.4,55.4,42.3,39.0.; HRMS-ESI(m / z):calcd for C 16 H 16 NO[M+H] + 238.1227, found 238.1235.

[0083] Example 10: Preparation of 3-phenyl-2-(pyridin-3-yl)propionitrile (Ie)

[0084]

[0085] Under argon atmosphere, 3-pyridylacetonitrile Ⅱe (59.1 mg, 0.5 mmol), benzyl alcohol Ⅲa (98 mg, 1 mmol), catalyst Mn-L1 (4.6 mg, 0.01 mmol), potassium tert-butoxide (28.0 mg, 0.25 mmol) and tert-amyl alcohol (0.5 mL) were added in sequence to a 10 mL pressure-resistant sealed tube. The mixture was reacted under high pressure at 135 ° C for 12 h under argon atmosphere. After the reaction, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 75 mg of 3-phenyl-2-(pyridin-3-yl)propionitrile (Ⅰe), with a yield of 75%.

[0086] Structure characterization of Ⅰe: Colorless oil; 75% yield, 1 H NMR (400MHz, CDCl3) δ8.58 (dd, J=4.8, 1.6Hz, 1H), 8.46 (d, J=2.4Hz, 1H), 7.57 (dt, J=8.0, 2.0Hz, 1H), 7.28(dqt,J=4.0,2.8,1.6Hz,4H),7.14–7.05(m,2H),4.06(dd,J=8.0,6.8Hz,1H),3.25–3.09(m,2H).; 13CNMR(100MHz, CDCl3)δ149.7,148.8,135.4,135.1,131.0,129.3,128.8,127.7,123.8,119.5,41.8,37.2.; HRMS-ESI(m / z):calcd for C 14 H 13 N2[M+H] + 209.1073, found 209.1079.

[0087] Example 11: Preparation of 3-phenyl-2-(thiophen-2-yl)propionitrile (IF)

[0088]

[0089] Under argon atmosphere, 2-thiopheneacetonitrile Ⅱf (61.6 mg, 0.5 mmol), benzyl alcohol Ⅲa (98 mg, 1 mmol), catalyst Mn-L1 (4.6 mg, 0.01 mmol), potassium tert-butoxide (28.0 mg, 0.25 mmol) and tert-amyl alcohol (0.5 mL) were added in sequence to a 10 mL pressure-resistant sealed tube. The mixture was reacted at 135 ° C under high pressure for 12 h. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 3-phenyl-2-(thiophen-2-yl)propionitrile (Ⅰf) 75 mg, yield: 70%.

[0090] Structural characterization of Ⅰf: Colorless oil; 70% yield, 1 H NMR (400MHz, CDCl3) δ7.34–7.26(m,4H),7.17–7.12(m,3H),6.98(dd,J=5.2,1.2Hz,1H),4.11(t,J=7.2Hz,1H),3.16(dd,J=7.2,2.0Hz,2H).; 13 C NMR (100MHz, CDCl3) δ136.3,135.1,129.2,128.7,127.5,127.1,126.4,123.0,120.2,41.1,35.0.; HRMS-ESI(m / z):calcd for C 13 H 12 NS[M+H] + 214.0685, found 214.0680.

[0091] Example 12: Preparation of 2-(naphthalen-2-yl)-3-phenylpropionitrile (Ig)

[0092]

[0093] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added 2-naphthylacetonitrile Ⅱg (83.6mg, 0.5mmol), benzyl alcohol Ⅲa (98mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 2-(naphthalene-2-yl)-3-phenylpropionitrile (Ⅰg) 109mg, yield: 85%.

[0094] Structural characterization of Ⅰg: Colorless oil; 85% yield, 1 H NMR (400MHz, CDCl3) δ7.92–7.81(m,3H),7.77(d,J=1.8Hz,1H),7.55(dt,J=6.4,3.6Hz,2H),7.39(dd,J= 8.4,2.0Hz,1H),7.36–7.28(m,3H),7.23–7.17(m,2H),4.20(dd,J=8.0,6.4Hz,1H),3.37–3.20(m,2H).; 13 CNMR (100MHz, CDCl3) δ136.3,133.2,132.9,132.5,129.3,129.0,128.7,127.9,12 7.8,127.5,126.7,126.7,126.6,125.0,120.4,42.2,40.0.; HRMS-ESI(m / z):calcd for C 19 H 16 N[M+H] + 258.1277, found 258.1282.

[0095] Example 13: Preparation of 3-phenyl-2-(m-tolyl)propionitrile (Ih)

[0096]

[0097] Under argon atmosphere, 3-methylbenzylacetonitrile IIh (65.6 mg, 0.5 mmol), benzyl alcohol IIIa (98 mg, 1 mmol), catalyst Mn-L1 (4.6 mg, 0.01 mmol), potassium tert-butoxide (28.0 mg, 0.25 mmol) and tert-amyl alcohol (0.5 mL) were added in sequence to a 10 mL pressure-resistant sealed tube. The mixture was reacted under high pressure at 135 °C for 12 h under argon atmosphere. After the reaction, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 85 mg of 3-phenyl-2-(m-tolyl)propionitrile (Ih). The yield was 77%.

[0098] Structural characterization of Ⅰh: Colorless oil; 77% yield, 1 H NMR (400MHz, CDCl3) δ7.44–7.31(m,4H),7.27–7.18(m,4H),7.14(dt,J=7.6, 1.6Hz, 1H), 4.02 (dd, J = 8.4, 6.4Hz, 1H), 3.21 (t, J = 7.2Hz, 2H), 2.42 (s, 3H); 13 C NMR (100MHz, CDCl3) δ139.0,136.6,135.3,129.3,129.0,129.0,128.7,128.2,127.5,124.6,120.6,42.3,39.9,21.5; HRMS-ESI(m / z):calcd forC 16 H 16 N[M+H] + 222.1277 found 222.1270.

[0099] Example 14: Preparation of 3-phenyl-2-(o-tolyl)propionitrile (Ii)

[0100]

[0101] Under argon atmosphere, 2-methylbenzylacetonitrile IIi (65.6 mg, 0.5 mmol), benzyl alcohol IIIa (98 mg, 1 mmol), catalyst Mn-L1 (4.6 mg, 0.01 mmol), potassium tert-butoxide (28.0 mg, 0.25 mmol) and tert-amyl alcohol (0.5 mL) were added in sequence to a 10 mL pressure-resistant sealed tube. The reaction was carried out under high pressure at 135 ° C for 12 h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 86 mg of 3-phenyl-2-(o-tolyl)propionitrile (Ii), with a yield of 78%.

[0102] Structural characterization of Ⅰi: Colorless oil; 78% yield, 1 H NMR (400MHz, CDCl3) δ7.54–7.47(m,1H),7.41–7.34(m,3H),7.33–7.28(m,2H), 7.27–7.20(m,3H),4.21(dd,J=8.8,6.0Hz,1H),3.25–3.10(m,2H),2.31(s,3H); 13 C NMR (100MHz, CDCl3) δ136.6,135.1,133.8,131.0,129.2,128.8,128.4,127.7,127.5,127.0,120.9,41.0,36.7,19.1; HRMS-ESI(m / z):calcdfor C 16 H 16 N[M+H] + 222.1277 found 222.1262.

[0103] Example 15: Preparation of 3-(4-methoxyphenyl)-2-phenylpropionitrile (Ij)

[0104]

[0105] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl nitrile Ⅱa (58.5mg, 0.5mmol), p-methoxybenzyl alcohol Ⅲj (138.2mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 3-(4-methoxyphenyl)-2-phenylpropionitrile (Ⅰj) 109mg, yield: 92%.

[0106] Structure characterization of Ⅰj: Colorless oil; 92% yield, 1 H NMR(400MHz, CDCl3)δ7.37(ddt,J=7.2,5.2,3.6Hz,3H),7.30–7.26(m,2H),7.09–7.05( m,2H),6.88–6.83(m,2H),3.99(dd,J=8.0,6.4Hz,1H),3.82(s,3H),3.17–3.08(m,2H).; 13C NMR (100MHz, CDCl3) δ158.9,135.3,130.3,129.0,128.3,128.2,127.5,120.5,114.0,55.3,41.4,40.1.; HRMS-ESI(m / z):calcdfor C 16 H 16 NO[M+H] + 238.1227, found 238.1229.

[0107] Example 16: Preparation of 3-(naphthalen-1-yl)-2-phenylpropionitrile (Ik)

[0108]

[0109] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl nitrile Ⅱa (58.5mg, 0.5mmol), 1-naphthalene methanol Ⅲk (158.2mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 3-(naphthalene-1-yl)-2-phenylpropionitrile (Ⅰk) 90mg, yield: 70%.

[0110] Structure characterization of Ⅰk: Colorless oil; 70% yield, 1 H NMR (400MHz, CDCl3) δ8.01–7.93(m,2H),7.85(d,J=8.0Hz,1H),7.59(dddd,J=17.2,8. 0,6.8,1.2Hz,2H),7.47–7.34(m,7H),4.21(dd,J=8.8,6.8Hz,1H),3.74–3.61(m,2H).; 13 C NMR (100MHz, CDCl3) δ135.7,134.0,132.3,131.3,129.3,129.2,128.4,128.4,128 .2,127.4,126.6,125.9,125.6,122.7,120.6,39.6,38.9.; HRMS-ESI(m / z):calcd for C 19 H 16 N[M+H] + 258.1277, found 258.1279.

[0111] Example 17: Preparation of 3-(naphthalen-2-yl)-2-phenylpropionitrile (I1)

[0112]

[0113] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl nitrile Ⅱa (58.5mg, 0.5mmol), 2-naphthalene methanol Ⅲl (158.2mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135℃ for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 3-(naphthalene-2-yl)-2-phenylpropionitrile (Ⅰl) 95mg, yield: 74%.

[0114] Ⅰl structural characterization: Colorless oil; 74% yield, 1 H NMR (400MHz, CDCl3) δ7.83 (dddd, J=15.2, 6.8, 4.82.4Hz, 3H), 7.64 (s, 1H), 7.50 (dt, J=7.2, 2.4Hz, 2H), 7.42–7.35 (m,3H),7.32(dt,J=7.2,1.6Hz,2H),7.29–7.25(m,1H),4.13(dd,J=8.4,6.4Hz,1H),3.36(qd,J=13.6,7.6Hz,2H).; 13 C NMR (100MHz, CDCl3) δ135.2,133.8,133.4,132.6,129.1,128.4,128.3,128.2,127 .8,127.7,127.6,127.2,126.3,126.0,120.5,42.4,39.8.; HRMS-ESI(m / z):calcd for C 19 H 16 N[M+H] + 258.1277, found 258.1272.

[0115] Example 18: Preparation of 3-(4-isobutylphenyl)-2-phenylpropionitrile (Im)

[0116]

[0117] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide Ⅱa (58.5mg, 0.5mmol), p-tert-butylbenzyl alcohol Ⅲm (164.2mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out at 135℃ under high pressure for 12h. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 3-(4-isobutylphenyl)-2-phenylpropionitrile (Ⅰm) 117mg, yield: 89%.

[0118] Im structural characterization: Colorless oil; 89% yield, 1 H NMR (400MHz, CDCl3) δ7.38 (tdt, J=7.2, 5.2, 1.6Hz, 3H), 7.30 (dd, J=7.6, 1.6Hz, 2H), 7.15–7.07 (m, 4H), 4.02 (dd, J=8. 4,6.4Hz,1H),3.17(qd,J=13.6,7.2Hz,2H),2.49(d,J=7.2Hz,2H),1.88(dh,J=13.6,6.8Hz,1H),0.94(d,J=6.4Hz,6H); 13 C NMR (100MHz, CDCl3) δ140.9,135.4,133.6,129.4,129.0,129.0,128.2,127.5,120.6,45.1,42.0,40.0,30.3,22.4; HRMS-ESI(m / z):calcdfor C 19 H 22 N[M+H] + 264.1747 found 264.1749.

[0119] Example 19: Preparation of 2-phenyl-3-(m-tolyl)propionitrile (In)

[0120]

[0121] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide Ⅱa (58.5mg, 0.5mmol), 3-methylbenzyl alcohol Ⅲn (122.2mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1: 40) to obtain 83mg of 2-phenyl-3-(m-tolyl)propionitrile (Ⅰn), with a yield of 81%.

[0122] I n structural characterization: Colorless oil; 81% yield, 1 H NMR (400MHz, CDCl3) δ7.49–7.37(m,3H),7.36–7.30(m,2H),7.24(t,J=7.6Hz,1H),7.14(d,J=7.6H z,1H),7.05–6.92(m,2H),4.03(dd,J=8.6,6.4Hz,1H),3.17(qd,J=13.6,7.6Hz,2H),2.37(s,3H); 13 C NMR (100MHz, CDCl3) δ138.3,136.3,135.4,130.0,129.1,128.6,128.3,128.2,127.5,126.3,120.5,42.3,39.9,21.4; HRMS-ESI(m / z):calcd for C 16 H 16 N[M+H] + 222.1277 found 222.1272.

[0123] Example 20: Preparation of 3-(4-chlorophenyl)-2-phenylpropionitrile (Io)

[0124]

[0125] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide Ⅱa (58.5mg, 0.5mmol), p-chlorobenzyl alcohol Ⅲo (142.6mg, 1mmol), catalyst Mn-L1 (4.6mg, 0.01mmol), potassium tert-butoxide (28.0mg, 0.25mmol) and tert-amyl alcohol (0.5mL) in sequence. The reaction was carried out under high pressure at 135℃ for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 3-(4-chlorophenyl)-2-phenylpropionitrile (Ⅰo) 91mg, yield: 76%.

[0126] Structure characterization of Ⅰo: Colorless oil; 76% yield, 1 H NMR (400MHz, CDCl3) δ7.38(qt,J=5.2,2.0Hz,3H),7.31–7.25(m,4H),7.09–7.04(m,2H),4.01(dd,J=8.0,6.4Hz,1H),3.22–3.11(m,2H); 13 C NMR (100MHz, CDCl3) δ134.7,134.6,133.4,130.7,129.1,128.8,128.4,127.5,120.1,41.5,39.6.; HRMS-ESI(m / z):calcd for C 16 H 16 N[M+H] + 242.0731 found 242.0730.

[0127] Example 21: Preparation of α-phenylbutyronitrile (Ip)

[0128]

[0129] Under argon atmosphere, to a 10mL pressure-resistant sealed tube, benzyl cyanide Ⅱa (58.5mg, 0.5mmol), ethanol Ⅲp (0.5mL), catalyst Mn-L1 (4.6mg, 0.01mmol) and potassium tert-butoxide (28.0mg, 0.25mmol) were added in sequence. The reaction was carried out under high pressure at 135℃ for 12h. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 54mg of α-phenylbutyronitrile (Ⅰp), with a yield of 75%.

[0130] Structural characterization of Ⅰp: Colorless oil; 75% yield, 1 H NMR (400MHz, CDCl3) δ7.43-7.38(m,2H),7.38-7.32(m,3H),3.81(dd,J=8.8,6.4Hz,1H),2.00-1.80(m,2H),1.59-1.47(m,2H),0.99(t,J=7.2Hz,3H).; 13 C NMR(100MHz, CDCl3)δ135.8,129.0,128.0,127.3,120.7,38.9,29.2,11.5.; HRMS-ESI(m / z):calcd for C 10 H 12N[M+H] + 146.0964, found 146.0970.

[0131] Example 22: Preparation of 2-phenylvaleronitrile (Iq)

[0132]

[0133] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide IIa (58.5mg, 0.5mmol), n-propanol IIIq (0.5mL), catalyst Mn-L1 (4.6mg, 0.01mmol) and potassium tert-butoxide (28.0mg, 0.25mmol) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 53mg of 2-phenylvaleronitrile (Ⅰq), with a yield of 67%.

[0134] Structural characterization of Ⅰq: Colorless oil; 67% yield, 1 H NMR (400MHz, CDCl3) δ7.30-7.25(m,2H),7.24-7.19(m,3H),3.68(dd,J=8.8,6.4Hz,1H) ,1.86-1.66(m,2H),1.41(dddd,J=11.6,10.0,7.2,6.0Hz,2H),0.86(t,J=7.2Hz,3H).; 13 C NMR(100MHz, CDCl3)δ136.1,129.1,128.0,127.3,120.9,37.9,37.15,20.3,13.4.; HRMS-ESI(m / z):calcd for C 11 H 14 N[M+H] + 160.1121, found 160.1128.

[0135] Example 23: Preparation of 2-phenylhexanenitrile (Ir)

[0136]

[0137] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide Ⅱa (58.5mg, 0.5mmol), n-butanol Ⅲr (0.5mL), catalyst Mn-L1 (4.6mg, 0.01mmol) and potassium tert-butoxide (28.0mg, 0.25mmol) in sequence. The reaction was carried out under high pressure at 135℃ for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 53mg of 2-phenylhexanenitrile (Ⅰr). The yield was 61%.

[0138] Structure characterization of Ⅰr: Colorless oil; 61% yield, 1 H NMR (400MHz, CDCl3) δ7.43-7.38(m,2H),7.37-7.33(m,3H),3.79(dd,J=8.6,6.3Hz,1H),2.01-1.85(m,2H),1.52-1.33(m,4H),0.93(t,J=7.1Hz,3H).; 13 C NMR (100MHz, CDCl3) δ136.1,129.0,128.0,127.2,120.9,37.4,35.6,29.1,22.1,13.8.; HRMS-ESI(m / z):calcd for C 12 H 16 N[M+H] + 174.1277, found 174.1280.

[0139] Example 24: Preparation of 2-phenyldecanenitrile (Is)

[0140]

[0141] Under argon atmosphere, to a 10mL pressure-resistant sealed tube were added benzyl cyanide Ⅱa (58.5mg, 0.5mmol), n-octanol Ⅲs (0.5mL), catalyst Mn-L1 (4.6mg, 0.01mmol) and potassium tert-butoxide (28.0mg, 0.25mmol) in sequence. The reaction was carried out under high pressure at 135°C for 12h under argon atmosphere. After the reaction was completed, the solvent was recovered by concentration under reduced pressure. The residue was separated by column chromatography (n-hexane: acetone = 1:40) to obtain 88mg of 2-phenyldecanenitrile (Ⅰs). The yield was 77%.

[0142] Structural characterization of Ⅰs: Colorless oil; 77% yield, 1H NMR (400MHz, CDCl3) δ7.44-7.38(m,2H),7.38-7.29(m,3H),3.79(dd,J=8.6,6.3Hz,1 H),1.99-1.84(m,2H),1.56-1.45(m,2H),1.38-1.25(m,10H),0.91(t,J=6.8Hz,3H).; 13 C NMR (100MHz, CDCl3) δ136.1,129.0,128.0,127.2,120.9,37.4,35.9,31.8,29.3,29.1,23.0,27.0,22.6,14.1.; HRMS-ESI(m / z):calcdfor C 16 H 24 N[M+H] + 230.1903, found 230.1909.

[0143] Example 25: Preparation of Anipamil

[0144]

[0145] (1) Under nitrogen protection, Mn-L1 (0.1 mmol), K2CO3 (1 mmol), 3-methoxyphenylacetonitrile (10 mmol), dodecanol (20 mmol) and toluene (30 mL) were added in sequence to a pressure-resistant sealed tube (150 mL, equipped with a stirring rod). The mixture was stirred under nitrogen protection and refluxed (oil bath temperature 135° C.) for 8 hours. After the reaction was complete, the solvent was evaporated, and the crude product was purified by silica gel (100-200 mesh) column chromatography using ethyl acetate / cyclohexane (2:98) as an eluent to separate 2.67 g of compound B, with a yield of 80%.

[0146] Structural characterization of B: White solid, 80% yield, 1 H NMR (400MHz, CDCl3) δ7.36-7.29(m,1H),6.94-6.85(m,3H),3.84(s,3H),3.76(dd,J=8.5,6.3 Hz,1H),2.02-1.77(m,2H),1.59-1.47(m,2H),1.28(d,J=3.6Hz,18H),0.90(d,J=7.0Hz,3H).; 13C NMR (100MHz, CDCl3) δ160.1,137.7,130.2,121.0,119.6,113.4,113.2,55.4,37.5,35 .9,32.0,29.7,29.7,29.6,29.5,29.4,29.1,27.2,22.8,14.2.; HRMS-ESI(m / z):calcd for C 24 H 39 BrNO[M+H] + 316.2635, found 316.2646.

[0147] (2) Under nitrogen protection, catalyst Ru-MACHO (0.05 mmol), K2CO3 (0.5 mmol), 2-(3-methoxyphenyl)tetracarbonitrile (5 mmol), allyl alcohol (7.5 mmol) and toluene (10 mL) were added in sequence to a pressure-resistant sealed tube (38 mL, equipped with a stirring rod). The mixture was stirred under nitrogen protection and refluxed (oil bath temperature 110° C.) for 4 hours. After the reaction was complete, the solvent was evaporated, and the crude product was purified by silica gel (100-200 mesh) column chromatography using ethyl acetate / cyclohexane (20:80) as an eluent to separate 1.92 g of compound C, with a yield of 70%.

[0148] (3) Under nitrogen protection, 2-(3-hydroxypropyl)-2-(3-methoxyphenyl)tetradecanenitrile (0.5 mmol) and toluene (1 mL) were added to a round-bottom flask. After cooling to -5°C, PBr3 (0.6 mmol) was slowly added dropwise to the solution and stirred for 30 minutes. The reaction mixture was then heated to room temperature and heated in an oil bath at 100°C for 2 hours. After the reaction was complete, the reaction mixture was cooled to room temperature and poured into ice. The resulting aqueous solution was extracted with ether (2×10 mL), and the combined organic layer was washed with saturated brine and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation, and the crude product was used directly in the next step.

[0149] (4) The above crude product, [2-(3-methoxyphenyl)ethyl]methylamine (0.3 mmol) and acetonitrile (1 mL) were placed in a round-bottom flask. Freshly ground anhydrous Na2CO3 (0.9 mmol) was added and the reaction mixture was heated in an oil bath at 80°C for 6 hours. After the reaction was complete, the solvent was removed by rotary evaporation and the resulting crude product was dissolved in water (2 mL). The aqueous solution was extracted with ethyl acetate (3×10 mL), the combined organic layer was washed with saturated brine, and dried over anhydrous Na2SO4. After removing the solvent, the crude product was purified by silica gel (100-200 mesh) column chromatography using DCM / MeOH (95:5) as the eluent to isolate 1.48 g of anipamil with a yield of 55%.

[0150] The contents described in this specification are merely an enumeration of implementation forms of the inventive concept, and the protection scope of the present invention should not be regarded as being limited to the specific forms described in the embodiments.

Claims

1. A manganese complex Mn-L, whose structural formula is shown in Formula Mn-L: ， In the formula, R 2 , R 3 R is independently H or C1~C3 alkyl, 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

2. A manganese complex Mn-L according to claim 1, wherein the structural formula thereof is any one of the formulas Mn-L1 to Mn-L6: 。 3. A method for preparing the manganese complex Mn-L according to claim 1 or 2, characterized in that Under an argon atmosphere, Mn(CO)5Br and a bidentate ligand having an imidazole-thiophene skeleton as shown in Formula IV were added to toluene for reflux reaction, and an orange manganese complex Mn-L was obtained after concentration. The reaction route is as follows: ， In Formula IV and Formula Mn-L, R 2 , R 3 R is independently H or C1~C3 alkyl, 2 , R 3 Same or different; R 4 is a hydrogen atom or an aromatic group.

4. Use of the manganese complex Mn-L according to claim 1 or 2 in the preparation of an α-alkyl substituted aromatic acetonitrile derivative, wherein the structural formula of the α-alkyl substituted aromatic acetonitrile derivative is as shown in Formula I: ， Wherein Ar is phenyl, substituted aryl, heterocyclic aryl or naphthyl, R 1 The substituted aryl group is selected from C2~C8 straight chain or branched alkyl, phenyl or heterocyclic aryl, and the substituent in the substituted aryl group is halogen, C1~C3 alkyl or C1~C3 alkoxy.

5. A method for preparing an α-alkyl substituted aromatic acetonitrile derivative, characterized in that The method comprises the following steps: in an argon atmosphere, adding aromatic acetonitrile as shown in formula II, primary alcohol as shown in formula III, catalyst manganese complex Mn-L, alkaline substance and solvent into a pressure-resistant sealed tube in sequence, reacting at 110-150° C. for 2-24 hours, and then concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography to obtain an α-alkyl substituted aromatic acetonitrile derivative as shown in formula I. The reaction route is as follows: ， Ar in formula II is phenyl, substituted aryl, heterocyclic aryl or naphthyl; R in formula III is 1 The substituted aryl group is selected from C2~C8 straight chain or branched alkyl, phenyl or heterocyclic aryl, and the substituent in the substituted aryl group is halogen, C1~C3 alkyl or C1~C3 alkoxy.

6. The method for preparing the α-alkyl substituted aromatic acetonitrile derivative according to claim 5, characterized in that The alkaline substance is selected from one or a mixture of two or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, potassium carbonate and cesium carbonate.

7. The method for preparing an α-alkyl substituted aromatic acetonitrile derivative according to claim 5, characterized in that The solvent is one of toluene, xylene, tert-butyl alcohol and tert-amyl alcohol or a mixture of two or more thereof.

8. The method for preparing an α-alkyl substituted aromatic acetonitrile derivative according to claim 5, characterized in that The molar ratio of the aromatic acetonitrile shown in formula II, the primary alcohol shown in formula III, the alkaline substance, and the catalyst manganese complex Mn-L is 1: 1-2: 0.1-0.5: 0.005-0.02.

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