CN114950558B - Bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst and method for catalyzing hydrocarbon molecule benzyl site selective oxidation by using same - Google Patents

Bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst and method for catalyzing hydrocarbon molecule benzyl site selective oxidation by using same Download PDF

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CN114950558B
CN114950558B CN202110197817.2A CN202110197817A CN114950558B CN 114950558 B CN114950558 B CN 114950558B CN 202110197817 A CN202110197817 A CN 202110197817A CN 114950558 B CN114950558 B CN 114950558B
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bipiperidine
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manganese catalyst
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CN114950558A (en
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李超群
周继梅
贾敏贤
马建伟
肖建良
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Shaanxi Normal University
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Abstract

The invention discloses a bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst and a method for catalyzing hydrocarbon molecule benzyl site selective oxidation, wherein the bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst is prepared by heating and stirring a cheap and nontoxic trifluoro manganese methane sulfonate serving as a manganese source and 1,1 '-bis (3, 5-dimethylpyridine) -2,2' -bipiperidine serving as a ligand, and the preparation method is simple. The invention relates to a tetradentate manganese catalyst and H in a bipiperidine framework 2 O 2 Under the action of an oxidant, selective catalytic oxidation of benzyl positions of various hydrocarbon organic compounds is realized by adding organic carboxylic acid, so that the aromatic ketone with various functional groups, five-membered and six-membered cyclic imines and the pharmaceutically active molecules with aromatic ketone functional groups are synthesized. Compared with the prior method, the invention has the advantages of easily available raw materials and substrates for catalytic reactionWide range, good compatibility of functional groups, less catalyst consumption, mild reaction conditions, simple operation, environmental protection, no waste generation, good selectivity, high yield and low production cost.

Description

Bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst and method for catalyzing hydrocarbon molecule benzyl site selective oxidation by using same
Technical Field
The invention belongs to the technical field of hydrocarbon bond selective oxidation in hydrocarbon, and in particular relates to a hydrocarbon four-tooth nitrogen-containing manganese catalyst in a bipiperidine skeleton and H 2 O 2 As an oxidizing agent, the corresponding aryl ketone and cyclic imine with various functional groups are generated.
Background
Aryl ketones are a wide variety of natural products and active functional groups of active drug molecules and synthetic unit components. For example: the aryl ketone is: hypericin, acetosyringone, oxcarbazepine, daidzein, sitaxsentan, radicicol, epicatechin gallate, lu Kapa Ni, leucine-rich repeat kinase-2 (LRRK 2), and other key structural units. In addition, such carbonyl compounds are also widely used in advanced materials and are intermediates in the synthesis of many fine chemicals.
Cyclic imines are nitrogen-containing heterocyclic organic compounds, which are the building blocks for the synthesis of many natural products or drug molecules, as well as the active functional groups of some drug molecules. The cyclic imine can be obtained by asymmetric reduction to obtain chiral nitrogen-containing heterocyclic amine, and can be used for synthesizing medicaments (such as tramadol, procyclodine, fluoxetine, trihexyphenyl and atropine) and natural products and analogues thereof through conversion. Cyclic imines are also commonly used in several organic name reactions, the scope of which involves the formation of carbocycles and heterocycles (Diels-Alder and Fischer reactions), electrophilic aromatic substitution (Friedel-Crafts reactions), multicomponent reactions (Mannich, betti and Ugi reactions), nucleophilic addition (Henry, strecker, reformatsky and Pudovik reactions) and ketene cycloaddition (Staudinger reactions).
Aryl ketones are often used to synthesize complex organic molecules. The most predominant methods for the synthesis of aryl ketones are Friedel-Crafts acylation and transition metal catalyzed coupling reactions, which are poor in selectivity, require severe reaction conditions, produce large amounts of waste after reaction with large amounts of toxic or expensive metal salts, andand can be limited to the synthesis of some simple functionalized aryl ketones. Thus, for hydrocarbon benzyl C (sp 3 ) Mild, green, inexpensive, selective direct oxidation of-H is an ideal method for synthesizing aryl ketones, however, literature reports are often used for carbon-hydrogen bonds C (sp 3 ) The oxidizing agent for oxidation of H benzyl is CrO 3 、Na 2 CrO 4 、KMnO 4 、MnO 2 、m-CPBA、 t BuOOH, hypervalent iodine reagent, isodose oxidant; and the reaction produces a large amount of waste, such as potassium permanganate or chromic acid derivatives, which is not friendly to the environment, and the large amount of metal residues produced not only requires huge cost in large-scale application, but also causes huge damage to the environment because the produced waste is a potential carcinogen. Therefore, the development of a less toxic, inexpensive, environmentally friendly catalytic oxidation system is the goal of our development.
Disclosure of Invention
The invention aims to provide a bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst which is low in cost, nontoxic and simple to prepare, and a method for synthesizing aryl ketone, cyclic imine and pharmaceutically active molecules with various functional groups by selectively catalyzing oxidation of carbon-hydrogen bond benzyl positions by the catalyst.
In view of the above, the structural formula of the bipiperidine framework tetradentate manganese catalyst used in the invention is as follows:
the bipiperidine skeleton in the structural formula of the manganese catalyst represents any one of (meso) -2,2 '-bipiperidine, (rac) -2,2' -bipiperidine, (R, R) -2,2 '-bipiperidine and (S, S) -2,2' -bipiperidine; OTf represents the coordinating ion triflate anion. The preparation method of the manganese catalyst comprises the following steps: adding the manganese triflate and the 1,1 '-bis- (2-methylpyridine) -2,2' -bipiperidine manganese into acetonitrile according to the mol ratio of 1:1, stirring for 8 hours at 80 ℃ in a nitrogen atmosphere, and removing acetonitrile to obtain a light yellow solid, namely the bipiperidine skeleton tetradentate nitrogen-containing manganese catalyst.
The manganese catalyst is used for catalysisThe method for synthesizing aryl ketone by hydrocarbon molecule benzyl site selective oxidation comprises the following steps: adding hydrocarbon and manganese catalyst with different functional groups shown in formula I into a reaction bottle containing acetonitrile and acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the acetonitrile into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain aryl ketone with different functional groups shown in a formula II; the reaction equation is shown below:
wherein FG represents C 1 ～C 4 Any one of alkyl, aryl, carboxyl, acyl, amido, acyloxy, sulfonyloxy, cyano, azido, alkynyl, protected primary amine, protected secondary amine, protected amino acid; r represents hydrogen, halogen or C 1 ～C 4 Any one of alkyl and nitro, and n=0 to 6.
In the method for synthesizing aryl ketone by catalytic oxidation of hydrocarbon molecule benzyl site with the manganese catalyst, the addition amount of the manganese catalyst is 0.1-10% of the molar amount of hydrocarbon with different functional groups shown in the formula I, preferably the addition amount of the manganese catalyst is 1-5% of the molar amount of hydrocarbon with different functional groups shown in the formula I; the H is 2 O 2 The addition amount of the catalyst is 5 to 8 times of the molar amount of the hydrocarbon with different functional groups shown in the formula I, and the addition amount of the acetic acid is 4 to 6 times of the molar amount of the hydrocarbon with different functional groups shown in the formula I.
The method for synthesizing the cyclic imine by using the manganese catalyst to catalyze the selective oxidation of the primary amine hydrocarbon bond benzyl site comprises the following steps: adding a primary amine and manganese catalyst shown in formula III into a reaction bottle containing acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile and dropwise adding the acetonitrile into a reaction bottle through a microinjection pump, and reacting for 10-300 minutes at room temperature, wherein primary amine carbon-hydrogen bond benzyl site is selectively oxidized to generate aryl ketoamine shown in a formula IV, and the aryl ketoamine is condensed under the promotion of acetic acid to generate cyclic imine shown in a formula V; the reaction equation is shown below:
wherein R is 1 Represents hydrogen, halogen, C 1 ～C 4 Any one of alkyl groups, R 2 Represents hydrogen or methyl, R 3 Represents hydrogen, C 1 ～C 4 Alkyl, cyclohexyl, phenyl, C 1 ～C 4 Any one of alkyl substituted phenyl and halogenated phenyl, and m=1 or 2.
In the method for synthesizing the cyclic imine by catalyzing the selective oxidation of the primary amine hydrocarbon bond benzyl site by the manganese catalyst, the addition amount of the manganese catalyst is 0.1-10% of the molar amount of the primary amine shown in the formula III, and preferably the addition amount of the manganese catalyst is 1-5% of the molar amount of the primary amine shown in the formula III; the H is 2 O 2 The addition amount of the catalyst is 4 to 6 times of the mole amount of the primary amine shown in the formula III, and the addition amount of the acetic acid is 45 to 55 times of the mole amount of the primary amine shown in the formula III.
The method for synthesizing the drug active molecule by using the manganese catalyst to catalyze the selective oxidation of tertiary amine hydrocarbon bond benzyl site comprises the following steps: adding tertiary amine shown in formula VI and catalyst into a reaction bottle containing acetonitrile and chloroacetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the acetonitrile into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain the pharmaceutically active molecules shown in the formula VII; the reaction equation is shown below:
wherein R is 4 、R 6 Each independently represents hydrogen, halogen, C 1 ～C 4 Any one of alkyl groups, R 5 Represents hydrogen or hydroxy, y=0 or 1.
In the method for synthesizing the drug active molecules by catalyzing the selective oxidation of the tertiary amine hydrocarbon bond benzyl site by the manganese catalyst, the addition amount of the manganese catalyst is 0.1 percent of the molar amount of the tertiary amine shown in the formula VI to be over-extended10%, preferably the addition amount of the manganese catalyst is 1% -5% of the molar amount of the tertiary amine shown in the formula VI; the H is 2 O 2 The addition amount of the catalyst is 5 to 8 times of the molar amount of the tertiary amine shown in the formula VI, and the addition amount of the chloroacetic acid is 9 to 12 times of the molar amount of the tertiary amine shown in the formula VI.
The method for synthesizing the drug active molecule by using the manganese catalyst to catalyze the selective oxidation of the cyclic secondary amine carbon hydrogen bond benzyl site comprises the following steps: adding a cyclic secondary amine of formula VIII and a manganese catalyst into a reaction bottle containing acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the aqueous solution into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain the pharmaceutically active molecule shown in the formula IX; the reaction equation is shown below:
where z=an integer of 1 to 4, and u=an integer of 0 to 4.
In the method for synthesizing the active molecules of the medicine by catalyzing the selective oxidation of the cyclic secondary amine carbon hydrogen bond benzyl site by the manganese catalyst, the addition amount of the manganese catalyst is 0.1-10% of the molar amount of the cyclic secondary amine shown in the formula VIII, and preferably the addition amount of the manganese catalyst is 1-5% of the molar amount of the cyclic secondary amine shown in the formula VIII; the H is 2 O 2 The addition amount of the catalyst is 4 to 6 times of the molar amount of the cyclic secondary amine shown in the formula VIII, and the addition amount of the acetic acid is 45 to 55 times of the molar amount of the cyclic secondary amine shown in the formula VIII.
The beneficial effects of the invention are as follows:
the tetradentate manganese catalyst of the bipiperidine framework is prepared by taking cheap and nontoxic manganese triflate as a manganese source and taking 1,1 '-bis (3, 5-lutidine) -2,2' -bipiperidine with a simple structure as a ligand through stirring at 80 ℃, and has a simple preparation method. The invention relates to a tetradentate manganese catalyst and H in a bipiperidine framework 2 O 2 Under the action of oxidant, through adding organic carboxylic acid, the benzyl site selective catalytic oxidation of various hydrocarbon organic compounds is realized to synthesize aromatic ketone, five-membered and six-membered aromatic ketone with various functional groupsCyclic imines, pharmaceutically active molecules with aromatic ketone functionality. Compared with the existing method, the catalytic reaction substrate has the advantages of easily available raw materials, wide substrate range, less catalyst consumption, mild reaction conditions, simple operation, environmental protection, no waste, good selectivity, high yield and low production cost.
Detailed Description
The invention will be further described in detail with reference to examples, but the scope of the invention is not limited to these examples.
Example 1
1. Synthesis of bipiperidine tetradentate nitrogen-containing ligands
134mg (0.8 mmol,1 equiv) of bipiperidine and 326mg (1.7 mmol,2.1 equiv) of 3, 5-lutidine hydrochloride are weighed in sequence in a reaction tube, 10mL of dichloromethane are added, then 160mg (4 mmol,5 equiv) of sodium hydroxide are weighed, dissolved in 2mL of deionized water and added dropwise to the reaction tube, the reaction is magnetically stirred at 55℃for 5 days, after the reaction is finished the reaction solution is transferred to a 100mL separating funnel, 10mL of deionized water is added first, three times of extraction with dichloromethane are carried out, the organic phases are combined, the organic phases are dried over anhydrous sodium sulfate and dehydrated, then, the crude product is obtained by rotary evaporation on a rotary evaporator, and the crude product is purified by silica gel column chromatography to obtain (rac) -1,1' -bis (3, 5-lutidine) -2,2' -bipiperidine white solid 123mg (yield 38%) and (1, 1' -bis (3, 5-lutidine) as white solid (yield 20 mg) by using a mixture of petroleum ether/ethyl acetate/triethylamine in a volume ratio of 50:0.5-10:1:0.1 as eluent. The (rac) -1,1 '-bis- (3, 5-dimethylpyridine) -2,2' -bipiperidine spectral data were: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.20(s,2H),7.19(s,2H),4.18(d,J＝12.4Hz,2H),3.25(d,J＝12.4Hz,2H),2.63(t,J＝10.8Hz,4H),2.36(s,6H),2.24(s,6H),2.02-1.94(m,4H),1.67-1.64(m,2H),1.47-1.35(m,6H),1.16-1.10(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):154.6,146.6,138.5,132.1,131.0,64.0,59.3,54.3,25.9,24.7,24.5,18.7,17.8；HRMS(ESI)m/z calcd for C 26 H 38 N 4 [M+Na] + 429.2989; found 429.2987; the (meso) -1,1 '-bis- (3, 5-dimethylpyridine) -2,2' -bipiperidine spectral data were: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.16(s,2H),7.21(s,2H),4.17(d,J＝12.4Hz,2H),3.67(d,J＝12.4Hz,2H),2.82(s,2H),2.66-2.59(m,2H),2.32(s,6H),2.32-2.30(m,2H),2.26(s,6H),1.74-1.68(m,2H),1.59-1.53(m,4H),1.25-1.10(m,2H),1.09-1.07(m,2H),0.96-0.93(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):155.5,146.0,138.5,132.7,131.1,58.6,56.0,48.8,21.3,21.1,20.5,18.2,17.8；HRMS(ESI)m/z calcd for C 26 H 38 N 4 [M+Na] + :429.2989；found:429.2988.
2. tetradentate manganese catalyst for synthesizing bipiperidine skeleton
87mg (0.25 mmol,1 equiv) of manganese triflate (Mn (OTf) were weighed out in sequence 2 ) And 89mg (0.25 mmol,1 equiv) (rac) -1,1 '-bis- (3, 5-dimethylpyridine) -2,2' -bipiperidine in a 10mL reaction vessel, N was exchanged 2 Three times, then at N 2 3mL of acetonitrile was added thereto, and the reaction was magnetically stirred at 80℃for 8 hours. After the reaction was stopped, the reaction solution was cooled to room temperature, then transferred to a glove box, solid precipitate was removed by filtration with celite, and then transferred to an external oil pump of the glove box to drain the solvent, to obtain 134mg of (rac) -1,1 '-bis- (3, 5-lutidine) -2,2' -bipiperidine manganese catalyst as a pale yellow solid, with a yield of 97%. HRMS (ESI) m/z calcd for C 27 H 38 F 3 MnN 4 O 3 S[M-OTf] + :610.1997,found:610.1993.
Example 2
Synthesis of 3-benzoyl propionic acid of the formula
7.59mg (0.01 mmol) of (rac) -1,1 '-bis- (3, 5-dimethylpyridine) -2,2' -dipiperidine manganese catalyst and 82mg (0.5 mmol) of 1-phenylbutyric acid were added to the reaction tube, 1.5mL of acetonitrile and 143. Mu.L (2.5 mmol) of acetic acid were added, and 125. Mu.L (2.5 mmol) of H having a mass concentration of 30% were then added 2 O 2 Dissolve in 1.5mL acetonitrile and add dropwise to the reaction flask via a microinjection pump and stir the reaction at room temperature for 60 minutes. After the reaction is finished, adding solid sodium sulfite into the reaction solution to quench the residual H 2 O 2 Suction filtration, ethyl acetate washing, filtrate collection, rotary evaporation of solvent and column chromatography separation to obtain 84mg of white solid 3-benzoyl propionic acid, the yield is 94%, and the spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.99(d,J＝7.2Hz,2H,ArH),7.58(d,J＝7.4Hz,1H,ArH),7.48(t,J＝7.6Hz,2H,ArH),3.32(t,J＝6.6Hz,2H),2.83(t,J＝6.4Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):197.9(ArC＝O),179.1(COOH),136.4,133.4,128.7,128.1,33.2,28.1；HRMS(ESI)m/z calcd for C 10 H 10 O 3 [M+Na] + :201.0522,found:201.0521；IR(KBr,plate),ν(cm -1 ):1738(C＝O),1688(ArC＝O).
example 3
Synthesis of 3- (4-fluorobenzoyl) propionic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4- (4-fluorophenyl) butyric acid, and the other steps were the same as in example 2, to obtain 94mg of 3- (4-fluorobenzoyl) propionic acid in 96% yield, and the spectral data were: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.03-8.00(m,2H,ArH),7.15(t,J＝8.4Hz,2H,ArH),3.29(t,J＝6.4Hz,2H),2.82(t,J＝6.4Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):196.2(ArC＝O),178.0(COOH),165.9(d,J C-F ＝253.6Hz),132.8(d,J C-F ＝3.0Hz),130.7(d,J C-F ＝9.3Hz),115.8(d,J C-F ＝21.8Hz),33.1,27.9；HRMS(ESI)m/z calcd for C 10 H 9 FO 3 [M+Na] + :219.0428,found:219.0430；IR(KBr,plate),ν(cm -1 ):1695(ArC＝O).
example 4
Synthesis of 3- (4-acetylbenzoyl) propionic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4- (4-ethylphenyl) butyric acid, H was used 2 O 2 The same procedures as in example 2 were repeated except for replacing 125. Mu.L (2.5 mmol) with 200. Mu.L (4.0 mmol) to give 97mg of 3- (4-acetylbenzoyl) propionic acid in 88% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.08-8.03(m,4H,ArH),3.34(t,J＝6.4Hz,2H),2.85(t,J＝6.4Hz,2H),2.65(s,3H,CH 3 )； 13 C NMR(100MHz,DMSO-d 6 )δ(ppm):198.9(ArC＝O),198.2(ArC＝O),174.2(COOH),140.4,140.0,128.9,128.6,34.0,28.3,27.5；HRMS(ESI)m/z calcd for C 12 H 12 O 4 [M+Na] + :243.0628,found:243.0623；IR(KBr,plate),ν(cm -1 ):3313,2358,2929(O-H),1727(C＝O),1686(ArC＝O).
example 5
Synthesis of 3- (4-nitrobenzoyl) propionic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4- (4-nitrophenyl) butyric acid, and the other steps were the same as in example 2, yielding 99mg of 3- (4-nitrobenzoyl) propionic acid in 89% yield, as shown in the spectral data: 1 H NMR(400MHz,DMSO-d6)δ(ppm):12.22(brs,1H,COOH),8.34(d,J＝8.8Hz,2H,ArH),8.20(d,J＝8.8Hz,2H,ArH),3.33(t,J＝6.2Hz),2.62(t,J＝6.2Hz,2H)； 13 C NMR(100MHz,DMSO-d6)δ(ppm):198.4(ArC＝O),174.2(COOH),150.5,141.5,129.8,124.4,34.3,28.3；HRMS(ESI)m/z calcd for C 10 H 9 NO 5 [M+Na] + :246.0373,found:246.0346；IR(KBr,plate),ν(cm -1 ):1744(C＝O),1678(ArC＝O).
example 6
Synthesis of 3- (4-methylbenzoyl) propionic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with an equimolar amount of 4- (4-methylphenyl) butyric acid, and the other steps were the same as in example 2, to give 89mg of 3- (4-methylbenzoyl) propionic acid in 93% yield, as shown in the following spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.88(d,J＝8.0Hz,2H,ArH),7.26(d,J＝7.6Hz,2H,ArH),3.30(t,J＝6.6Hz,2H),2.81(t,J＝6.4Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):197.6(ArC＝O),178.8(COOH),144.3,134.0,129.4,128.3,33.2,28.1,21.8；HRMS(ESI)m/z calcd for C 11 H 12 O 3 [M+Na] + :215.0679,found:215.0680；IR(KBr,plate),ν(cm -1 ):1674(ArC＝O).
example 7
Synthesis of 3- (4-fluoro-3-methylbenzoyl) propionic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with an equimolar amount of 4- (4-fluoro-3-methylphenyl) butyric acid, and the other steps were the same as in example 2, to obtain 98mg of 3- (4-fluoro-3-methylbenzoyl) propionic acid in 93% yield, as shown in the following spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.86-7.79(m,2H,ArH),7.07(t,J＝9.0Hz,1H,ArH),3.27(t,J＝6.4Hz,2H),2.81(t,J＝6.4Hz,2H),2.32(s,3H,ArCH 3 )； 13 C NMR(100MHz,CDCl 3 )δ(ppm):196.6(ArC＝O),178.4(COOH),164.6(d,J＝252.3Hz),132.7(d,J C-F ＝3.3Hz),132.0(d,J C-F ＝6.6Hz),128.1(d,J C-F ＝9.3Hz),125.5(d,J C-F ＝17.7Hz),115.4(d,J C-F ＝23.0Hz),33.1,28.1,14.6(d,J C-F ＝3.5Hz)；HRMS(ESI)m/z calcd for C 11 H 11 FO 3 [M+Na] + :233.0584,found:233.0582；IR(KBr,plate),ν(cm -1 ):1678(ArC＝O).
example 8
Synthesis of 7-benzoyl heptanoic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 8-phenyloctanoic acid, and the other steps were the same as in example 2, giving 105mg of 7-benzoylheptanoic acid in a yield of 90%, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.94(dd,J＝8.4,1.2Hz,2H,ArH),7.53(t,J＝7.2Hz,1H,ArH),7.46(t,J＝7.6Hz,2H,ArH),2.97(t,J＝7.4Hz,2H),2.36(t,J＝7.4Hz,2H),1.77-1.64(m,4H),1.43-1.40(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.4(ArC＝O),174.2(COOH),137.1,132.9,128.5,128.0,51.4,38.4,34.0,29.0,24.8,24.1；HRMS(ESI)m/z calcd for C 14 H 18 O 3 [M+Na] + :257.1148；found:257.1144；IR(KBr,plate),ν(cm -1 ):1747(C＝O),1683(ArC＝O).
example 9
Synthesis of 7-benzoyl heptanoic acid of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar methyl 8-phenyloctanoate, and the other steps were the same as in example 2, giving 112mg of methyl 7-benzoylheptanoate in a yield of 90% and spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.95(dd,J＝7.6,1.6Hz,2H,ArH),7.54(t,J＝7.2Hz,1H,ArH),7.45(t,J＝7.6Hz,2H,ArH),3.66(s,3H,OCH 3 ),2.96(t,J＝7.4Hz,2H),2.31(t,J＝7.4Hz,2H),1.76-1.71(m,2H),1.68-1.61(m,2H),1.40-1.37(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.4(ArC＝O),174.2(COOMe),137.1,132.9,128.5,128.0,51.4,38.4,34.0,29.0(overlap),24.8,24.1；HRMS(ESI)m/z calcd for C 15 H 20 O 3 [M+Na] + :271.1305；found:271.1304；IR(KBr,plate),ν(cm -1 ):1774(C＝O),1724(C＝O).
example 10
Synthesis of 7-benzoyl heptanamide of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 8-phenyloctanoyl amide, and the other steps were the same as in example 2, giving 96mg of 7-benzoylheptanamide in 82% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.95(dd,J＝7.6,1.2Hz,2H,ArH),7.57(t,J＝6.8Hz,1H,ArH),7.46(t,J＝6.8Hz,2H,ArH),2.97(t,J＝7.4Hz,2H),2.36(t,J＝7.2Hz,2H),1.77-1.64(m,4H),1.42-1.39(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.4(ArC＝O),179.7(CONH 2 ),137.0,132.9,128.6,128.0,38.4,33.9,28.9,28.8,24.5,24.1；HRMS(ESI)m/z calcd for C 14 H 19 NO[M+Na] + :256.1308；found:256.1306；IR(KBr,plate),ν(cm -1 ):1745(C＝O).
example 11
Synthesis of Phenyloctanone of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar n-octylbenzene, and the other steps were the same as in example 2, giving 87mg of phenyloctanone in 85% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.88(d,J＝8.0Hz,2H,ArH),7.48(t,J＝7.6Hz,1H,ArH),7.38(t,J＝7.2Hz,2H,ArH),2.89(t,J＝7.4Hz,2H),1.77-1.66(m,2H),1.38-1.18(m,8H),0.90-0.80(m,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.7(ArC＝O),137.2,132.9,128.6,128.1,38.7,31.8,29.4,29.2,24.5,22.7,14.2；HRMS(ESI)m/z calcd for C 14 H 20 O[M+Na] + :227.1406；found:227.1405；IR(KBr,plate),ν(cm -1 ):1745(C＝O).
example 12
Synthesis of benzophenone of the following structural formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar diphenylmethane, and the other steps were the same as in example 2, giving 86mg of benzophenone in a yield of 95% and spectral data of: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.82-7.80(m,4H,ArH),7.61-7.57(m,2H,ArH),7.50-7.46(m,4H,ArH)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):196.8(ArC＝O),137.7,132.4,130.1,128.3；HRMS(ESI)m/z calcd for C 13 H 10 O[M+Na] + :205.0624；found:205.0628；IR(KBr,plate),ν(cm -1 ):1652(C＝O).
example 13
Synthesis of 1-phenyl-1, 4-octanedione having the structural formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 1-phenyl-4-octanone, and the other steps were the same as in example 2, giving 96mg of 1-phenyl-1, 4-octanedione in 88% yield, as shown in the spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.98(d,J＝7.6Hz,2H,ArH),7.56(t,J＝7.6Hz,1H,ArH),7.46(t,J＝7.6Hz,2H,ArH),3.28(t,J＝6.2Hz,2H),2.86(t,J＝6.2Hz,2H),2.53(t,J＝7.4Hz,2H),1.65-1.57(m,2H),1.39-1.30(m,2H),0.89(t,J＝7.2Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):209.9(C＝O),198.8(ArC＝O),136.8,133.2,128.5,128.1,42.8,36.3,32.5,26.1,22.4,14.0；HRMS(ESI)m/z calcd for C 14 H 18 O 2 [M+Na] + :241.1199；found:241.1198；IR(KBr,plate),ν(cm -1 ):1747(C＝O),1697(C＝O).
example 14
Synthesis of 3-benzoyl propionitrile of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4-phenylbutyronitrile, and the other steps were the same as in example 2, giving 75mg of 3-benzoylpropionitrile in 94% yield, as the spectrum data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.94(d,J＝7.6Hz,2H,ArH),7.61(t,J＝7.4Hz,1H,ArH),7.49(t,J＝7.8Hz,2H,ArH),3.37(t,J＝7.2Hz,2H),2.77(t,J＝7.2Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):195.4(ArC＝O),135.7,133.9,128.9,128.1,119.3,34.3,11.8；HRMS(ESI)m/z calcd for C 10 H 9 NO[M+Na] + :182.0576,found:182.0576.
example 15
Synthesis of 3-benzoylpropyl azide of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4-phenylbutylazide, and the other steps were the same as in example 2, to give 90mg of 3-benzoylpropylazide in a yield of 95% and spectral data of: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.96(d,J＝7.6Hz,2H,ArH),7.57(t,J＝7.4Hz,1H,ArH),7.47(d,J＝7.6Hz,2H,ArH),3.43(t,J＝6.6Hz,2H),3.09(t,J＝7.0Hz,2H),2.08-2.01(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):199.0(ArC＝O),136.8,133.3,128.7,128.1,51.0,35.3,23.4；HRMS(ESI)m/z calcd for C 10 H 11 N 3 O[M+Na] + :212.0794,found:212.0794；IR(KBr,plate),ν(cm -1 ):2102(N 3 ),1686(C＝O).
example 16
Synthesis of 3-benzoyl propyl methanesulfonate of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 4-phenylbutylmethanesulfonate, and the other steps were the same as in example 2, to give 114mg of 3-benzoylpropylmethanesulfonate in 94% yield, as shown in the spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.97(d,J＝8.0Hz,2H,ArH),7.58(t,J＝7.4,1H,ArH),7.47(d,J＝7.8Hz,2H,ArH),4.36(t,J＝6.1Hz,2H),3.15(t,J＝6.8Hz,2H),3.00(s,3H,SO 2 CH 3 ),2.25-2.18(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.7(ArC＝O),136.7,133.4,128.8,128.1,69.5,37.4,34.1,23.7；HRMS(ESI)m/z calcd for C 11 H 14 O 4 S[M+Na] + :265.0505,found:265.0500；IR(KBr,plate),ν(cm -1 ):2358(OSO 2 Me),1687(C＝O).
example 17
Synthesis of 2-benzoylethyl acetate of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 3-phenylpropyl acetate, and the other steps were the same as in example 2, giving 88mg of 2-benzoylethyl acetate in 92% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.96(d,J＝7.6Hz,2H,ArH),7.59(t,J＝7.4Hz,1H,ArH),7.47(t,J＝7.8Hz,2H,ArH),4.52(t,J＝6.4Hz,2H),3.32(t,J＝6.4Hz,2H),2.03(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):197.1(ArC＝O),171.1(OC＝O),136.6,133.5,128.8,128.1,59.7,37.4,21.0；HRMS(ESI)m/z calcd for C 10 H 12 O 3 [M+Na] + :215.0679,found:215.0676；IR(KBr,plate),ν(cm -1 ):1656(ArC＝O).
example 18
Synthesis of 5-benzoyl-2-pentyne of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar 6-phenyl-2-hexyne, and the other steps were the same as in example 2, giving 64mg of 5-benzoyl-2-pentyne in 74% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.96(d,J＝7.6Hz,2H,ArH),7.56(t,J＝7.4Hz,1H,ArH),7.46(t,J＝7.4Hz,2H,ArH),3.37(t,J＝7.2Hz,2H),2.59-2.54(m,2H),1.76(t,J＝2.5Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.4(ArC＝O),136.7,133.2,78.0,76.2,38.2,13.7,3.5；HRMS(ESI)m/z calcd for C 12 H 12 O[M+Na] + :195.0780,found:195.0777.IR(KBr,plate),ν(cm -1 ):2360(C≡C),1680(C＝O).
example 19
Synthesis of 2- (2-oxoethylbenzene) isoindoline-1, 3-dione of the formula
In example 2, the 4-phenylbutyric acid used was replaced with an equimolar amount of 2-ethylbenzisoindoline-1, 3-dione, and the other steps were the same as in example 2 to give 118mg of 2- (2-oxoethylbenzene) isoindoline-1, 3-dione in a yield of 89% and spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.01(d,J＝7.3Hz,2H,ArH),7.91-7.89(m,2H,ArH),7.76-7.74(m,2H,ArH),7.63(t,J＝7.5Hz,1H,ArH),7.51(t,J＝7.8Hz,2H,ArH),5.14(s,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):191.0(ArC＝O),168.0(C＝O),134.5,134.3,134.2,134.1,132.3,129.0,128.2,123.6,44.3；HRMS(ESI)m/z calcd for C 16 H 11 NO 3 [M+Na] + :288.0631；found:288.0640；IR(KBr,plate),ν(cm -1 ):1721(C＝O),1689(ArC＝O).
example 20
Synthesis of methyl (S) -2- ((tert-Butoxycarbonyl) amino) -4-oxo-4-phenylbutyrate of the formula
In example 2, the 4-phenylbutyric acid used was replaced with equimolar methyl (S) -2- ((tert-butoxycarbonyl) amino) -4-phenylbutyrate, and the other steps were the same as in example 2, to give 143mg of methyl (S) -2- ((tert-butoxycarbonyl) amino) -4-oxo-4-phenylbutyrate in 93% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.95-7.93(m,2H,ArH),7.61-7.57(m,1H,ArH),7.49-7.46(m,2H,ArH),5.63(d,J＝8.3Hz,1H,NH),4.72-4.68(m,1H),3.76-3.71(m,1H),3.74(s,3H,OMe),3.56-3.51(m,1H),1.44(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):197.9(ArC＝O),172.1(COOMe),155.7,136.2,133.8,128.8,128.2,80.1,52.7,49.7,41.0,28.4；HRMS(ESI)m/z calcd for C 16 H 21 NO 5 [M+Na] + :330.1312；found:330.1318；IR(KBr,plate),ν(cm -1 ):1710(C＝O),1685(ArC＝O).
example 21
Synthesizing 5-phenyl-3, 4-dihydropyrrole with the structural formula as follows
11.39mg (0.015 mmol) of (rac) -1,1 '-bis- (2-methylpyridine) -2,2' -bipiperidinium manganese catalyst and 75mg (0.5 mmol) of 4-phenylbutylamine are introduced into the reaction tube, 1.5mL (25 mmol) of acetic acid are introduced into the reaction tube, and 125. Mu.L (2.5 mmol) of H having a mass concentration of 30% are then introduced 2 O 2 Is dissolved in1.5mL of acetonitrile was added dropwise to the flask via a microinjection pump, and the reaction was stirred at room temperature for 60 minutes. After the reaction is finished, adding solid sodium sulfite into the reaction solution to quench the residual H 2 O 2 Suction filtration, ethyl acetate washing, filtrate collection, rotary evaporation of solvent and column chromatography separation to obtain 67mg of 5-phenyl-3, 4-dihydro-pyrrole, wherein the yield is 93%, and the spectrum data are as follows: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.85-7.82(m,2H,ArH),7.41-7.36(m,3H,ArH),4.06(t,J＝7.5Hz,2H,C＝NCH 2 ),2.96-2.90(m,2H),2.07-1.97(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.3(C＝N),134.7,130.3,128.5,127.7,61.6,35.0,22.7；HRMS(ESI)m/z calcd for C 10 H 11 N[M+H] + :146.0964；found:146.0965；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 22
The synthetic structural formula of 5- (4-fluorophenyl) -3, 4-dihydro-pyrrole is exemplified as follows
In example 21, the 4-phenylbutylamine used was replaced with equimolar 4- (4-fluorophenyl) butylamine, and the other steps were the same as in example 21, to give 77mg of 5- (4-fluorophenyl) -3, 4-dihydro-pyrrole in 94% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.85-7.80(m,2H,ArH),7.08(t,J＝8.7Hz,2H,ArH),4.05(t,J＝7.2Hz,2H,C＝NCH 2 ),2.95-2.88(m,2H),2.09-1.98(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):172.2(C＝N),165.9(d,J C-F ＝249.0Hz),130.9,130.4,129.8(d,J C-F ＝9.0Hz),127.7,115.4(d,J C-F ＝22.0Hz),61.7,35.1,22.9；HRMS(ESI)m/z calcd for C 10 H 10 FN[M+H] + :164.0870；found:164.0868；IR(KBr,plate),ν(cm -1 ):1610(C＝N).
example 23
Synthesis of 5- (4-chlorophenyl) -3, 4-dihydro-pyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 4- (4-chlorophenyl) butylamine and the other steps were the same as in example 21, giving 83mg of 5- (4-chlorophenyl) -3, 4-dihydro-pyrrole in 93% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.77(d,J＝8.7Hz,2H,ArH),7.38(d,J＝8.7Hz,2H,ArH),4.09-4.04(m,2H,C＝NCH 2 ),2.95-2.88(m,2H),2.10-1.99(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):172.3(C＝N),136.4,133.2,129.0,128.8,61.7,35.0,22.8；HRMS(ESI)m/z calcd for C 10 H 10 ClN[M+H] + :180.0575,found:180.0573；IR(KBr,plate),ν(cm -1 ):1611(C＝N).
example 24
Synthesis of 5- (4-methylphenyl) -3, 4-dihydro-pyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 4- (4-methylphenyl) butylamine, and the other steps were the same as in example 21, giving 73mg of 5- (4-methylphenyl) -3, 4-dihydro-pyrrole in 92% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.75(d,J＝8.1Hz,2H,ArH),7.22-7.14(m,2H,ArH),4.05(t,J＝6.9Hz,2H,C＝NCH 2 ),2.93(d,J＝8.1Hz,2H),2.38(s,3H,ArCH 3 ),2.08-1.97(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.6(C＝N),140.9,131.7,129.3,127.8,61.3,35.0,22.7,21.6；HRMS(ESI)m/z calcd for C 11 H 13 N[M+H] + :160.1121；found:160.1121；IR(KBr,plate),ν(cm -1 ):1609(C＝N).
example 25
Synthesis of 5- (4-fluoro-3-methyl-phenyl) -3, 4-dihydro-pyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 4- (4-fluoro-3-methyl-phenyl) butylamine, and the other steps were the same as in example 21, giving 80mg of 5- (4-fluoro-3-methyl-phenyl) -3, 4-dihydro-pyrrole in 90% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.74(dd,J＝7.5,1.7Hz,1H,ArH),7.62-7.58(m,1H,ArH),7.02(t,J＝8.9Hz,1H,ArH),4.04(t,J＝7.7Hz,2H,C＝NCH 2 ),2.91(tt,J＝8.5,2.0Hz,2H),2.30(d,J＝1.8Hz,3H),2.07-2.00(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):172.4(C＝N),162.6(d,J＝247.0Hz),130.9(d,J＝5.8Hz),130.5(d,J＝3.6Hz),127.0(d,J＝8.3Hz),125.0(d,J＝247.0Hz),115.0(d,J＝17.6Hz),61.4,34.9,22.7,14.5(d,J＝3.5Hz)；HRMS(ESI)m/z calcd for C 11 H 12 FN[M+H] + :178.1027,found:178.1027；IR(KBr,plate),ν(cm -1 ):1618(C＝N).
example 26
Synthesis of 2-methyl-5-phenyl-3, 4-dihydropyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar amounts of 2-amino-5-phenylpentane, and the procedure was otherwise identical to that of example 21, giving 65mg of 2-methyl-5-phenyl-3, 4-dihydropyrrole in 82% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.85-7.83(m,2H,ArH),7.42-7.39(m,3H,ArH),4.33-4.25(m,1H,C＝NCH),3.10-3.02(m,1H),2.93-2.84(m,1H),2.27-2.22(m,1H),1.60-1.51(m,1H),1.37-1.36(d,J＝6.8Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):171.9(C＝N),134.8,130.3,128.4,127.7,68.5,35.3,30.7,22.2；HRMS(ESI)m/z calcd for C 11 H 13 N[M+H] + :160.1121,found:160.1119；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 27
Synthesis of 2-isopropyl-5-phenyl-3, 4-dihydropyrrole of the structural formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar amounts of 2-methyl-3-amino-6-phenylhexane, and the procedure was otherwise identical to example 21 to give 68mg of 2-isopropyl-5-phenyl-3, 4-dihydropyrrole in 73% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.85-7.83(m,2H,ArH),7.41-7.38(m,3H,ArH),4.13-4.06(m,1H,C＝NCH),2.96-2.89(m,2H),2.10-1.96(m,2H),1.72-1.66(m,1H),1.08-1.06(d,J＝6.7Hz,3H),0.91-0.89(d,J＝6.7Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):172.2(C＝N),134.7,130.3,128.4,127.7,78.9,35.4,33.3,24.9,20.0,18.2；HRMS(ESI)m/z calcd for C 13 H 17 N[M+H] + :188.1434,found:188.1439；IR(KBr,plate),ν(cm -1 ):1616(C＝N).
example 28
Synthesis of 2-cyclohexyl-5-phenyl-3, 4-dihydropyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2-cyclohexyl-4-phenylbutylamine, and the other steps were the same as in example 21, giving 84mg of 2-cyclohexyl-5-phenyl-3, 4-dihydropyrrole in 74% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.85-7.83(m,2H,ArH),7.41-7.39(m,3H,ArH),4.02-3.97(m,1H,C＝NCH),2.99-2.81(m,2H),2.11-2.04(m,1H),1.80-1.62(m,5H),1.62-1.55(m,1H),1.33-1.02(m,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):171.8(C＝N),135.0,130.2,128.4,127.7,78.4,43.8,35.2,30.7,29.1,26.8,26.5,26.4,25.8；HRMS(ESI)m/z calcd for C 16 H 21 N[M+H] + :228.1747,found:228.1742；IR(KBr,plate),ν(cm -1 ):1617(C＝N).
example 29
Synthesizing 2, 5-diphenyl-3, 4-dihydropyrrole with the structural formula as follows
In example 21, the 4-phenylbutylamine used was replaced with equimolar 1, 4-diphenylbutylamine, and the other steps were the same as in example 21, giving 82mg of 2, 5-diphenyl-3, 4-dihydropyrrole in 74% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.96-7.93(m,2H,ArH),7.45-7.41(m,3H,ArH),7.34-7.29(m,4H,ArH),7.26-7.23(m,1H,ArH),5.33-5.29(m,1H,C＝NCH),3.20-3.12(m,1H),3.04-2.95(m,1H),2.63-2.54(m,1H),1.94-1.85(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.7(C＝N),146.7,134.5,130.6,128.5,127.9,126.8,126.6,76.1,35.6,32.5.HRMS(ESI)m/z calcd for C 16 H 15 N[M+H] + :222.1277,found:222.1270；IR(KBr,plate),ν(cm -1 ):1611(C＝N).
example 30
Synthesis of 5-phenyl-2- (2-methylbenzene) -3, 4-dihydropyrrole with the structural formula shown below
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2- (2-methylphenyl) -4-phenylbutylamine, and the other steps were the same as in example 21, to give 85mg of 5-phenyl-2- (2-methylphenyl) -3, 4-dihydropyrrole in 72% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.99-7.97(m,2H,ArH),7.48-7.45(m,3H,ArH),7.19-7.14(m,4H,ArH),5.54-5.51(m,1H,C＝NCH),3.20-3.11(m,1H),3.08-2.99(m,1H),2.68-2.59(m,1H),2.43(s,3H),1.84-1.74(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.7(C＝N),143.0,134.6,134.5,130.6,130.2,128.5,127.9,126.6,126.2,125.6,72.9,35.4,31.3,19.6；HRMS(ESI)m/z calcd for C 17 H 17 N[M+H] + :236.1434,found:236.1432；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 31
Synthesis of 5-phenyl-2- (4-methylbenzene) -3, 4-dihydropyrrole with the structural formula shown below
In example 21, the same procedure as in example 21 was repeated except for using equimolar amount of 2- (4-methylphenyl) -4-phenylbutylamine to give 87mg of 5-phenyl-2- (4-methylphenyl) -3, 4-dihydropyrrole in 74% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.96-7.93(m,2H,ArH),7.46-7.41(m,3H,ArH),7.21-7.19(m,2H,ArH),7.16-7.13(m,2H,ArH),5.31-5.27(m,1H,C＝NCH),3.21-3.13(m,1H),3.05-2.96(m,1H),2.62-2.54(m,1H),2.34(s,3H),1.94-1.85(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.5(C＝N),141.7,136.4,134.6,130.6,129.2,128.5,128.0,126.5,75.9,35.6,32.6,21.2；HRMS(ESI)m/z calcd for C 17 H 17 N[M+H] + :236.1434,found:236.1425；IR(KBr,plate),ν(cm -1 ):1612(C＝N).
example 32
Synthesis of 5-phenyl-2- (4-tert-butylbenzene) -3, 4-dihydropyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2- (4-tert-butylbenzene) -4-phenylbutylamine, and the other steps were the same as in example 21, to give 104mg of 5-phenyl-2- (4-tert-butylbenzene) -3, 4-dihydropyrrole in 75% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.95-7.93(m,2H,ArH),7.45-7.42(m,3H,ArH),7.37-7.35(m,2H,ArH),7.26-7.23(m,2H,ArH),5.30-5.27(m,1H,C＝NCH),3.22-3.14(m,1H),3.05-2.96(m,1H),2.62-2.53(m,1H),1.99-1.89(m,1H),1.31(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.4(C＝N),149.7,141.6,134.6,130.6,128.5,128.0,126.4,125.4,75.9,35.7,34.5,32.3,31.5；HRMS(ESI)m/z calcd for C 20 H 23 N[M+H] + :278.1903,found:278.1907；IR(KBr,plate),ν(cm -1 ):1609(C＝N).
example 33
Synthesis of 5-phenyl-2- (4-chlorobenzene) -3, 4-dihydropyrrole of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2- (4-chlorophenyl) -4-phenylbutylamine, and the other steps were the same as in example 21, to give 93mg of 5-phenyl-2- (4-chlorophenyl) -3, 4-dihydropyrrole in 73% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.86-7.84(m,2H,ArH),7.37-7.35(m,3H,ArH),7.23-7.21(m,2H,ArH),7.17-7.15(m,2H,ArH),5.21-5.18(m,1H),3.12-3.05(m,1H),2.97-2.88(m,1H),2.56-2.47(m,1H),1.81-1.71(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):174.1(C＝N),143.3,134.4,132.6,130.8,128.6,128.5,128.0,127.9,75.4,35.7,32.5；HRMS(ESI)m/z calcd for C 16 H 14 ClN[M+H] + :256.0888,found:256.0890；IR(KBr,plate),ν(cm -1 ):1612(C＝N).
example 34
Synthesis of 3, 3-dimethyl-5-phenyl-3, 4-dihydropyrrole of the structural formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-4-phenylbutylamine, and the same procedure was followed as in example 21 to give 81mg of 3, 3-dimethyl-5-phenyl-3, 4-dihydropyrrole in 94% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.82-7.79(m,2H,ArH),7.41-7.40(m,3H,ArH),3.79(s,2H),2.79(s,2H),1.18(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):172.9(C＝N),134.9,130.3,128.4,127.4,74.8,50.0,38.5,28.1；HRMS(ESI)m/z calcd for C 12 H 15 N[M+H] + :174.1277,found:174.1278；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 35
Synthesizing 3, 3-dimethyl-5- (4-fluorobenzene) -3, 4-dihydropyrrole with the structural formula as follows
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-4- (4-fluorobenzene) butylamine and the other steps were the same as in example 21 to give 91mg of 3, 3-dimethyl-5- (4-fluorobenzene) -3, 4-dihydropyrrole in 95% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.81-7.78(m,2H,ArH),7.10-7.06(m,2H,ArH),3.78(s,2H),2.76(s,2H),1.18(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):171.8(C＝N),164.2(d,J C-F ＝250.0Hz),131.2(d,J C-F ＝3.0Hz),129.5(d,J＝8.0Hz),115.4(d,J＝22.0Hz),74.7,50.0,38.7,28.1；HRMS(ESI)m/z calcd for C 12 H 14 FN[M+H] + :192.1183,found:192.1193；IR(KBr,plate),ν(cm -1 ):1610(C＝N).
example 36
Synthesizing 3, 3-dimethyl-5- (4-methylbenzene) -3, 4-dihydropyrrole with the structural formula as follows
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-4- (4-methylphenyl) butylamine, and the other steps were the same as in example 21, to give 89mg of 3, 3-dimethyl-5- (4-methylphenyl) -3, 4-dihydropyrrole in 95% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.69(d,J＝8.0Hz,2H,ArH),7.20(d,J＝8.0Hz,2H,ArH),3.78(s,2H),2.77(s,2H),2.38(s,3H),1.17(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):173.1(C＝N),140.7,132.2,129.2,127.5,74.5,50.1,38.5,28.2,21.5；HRMS(ESI)m/z calcd for C 13 H 17 N[M+H] + :188.1434,found:188.1444；IR(KBr,plate),ν(cm -1 ):1610(C＝N).
example 37
Synthesis of 6-phenyl-2, 3,4, 5-tetrahydropyridine of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 5-phenylpentanamine, and the procedure was otherwise identical to that of example 21, to give 64mg of 6-phenyl-2, 3,4, 5-tetrahydropyridine in 80% yield, as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.76-7.42(m,2H,ArH),7.37-7.36(m,3H,ArH),3.83(t,J＝5.4Hz,2H,C＝NCH 2 ),2.64-2.61(m,2H),1.87-1.80(m,2H),1.70-1.64(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):165.6(C＝N),140.4,129.6,128.3,126.0,50.0,27.1,22.0,19.9；HRMS(ESI)m/z calcd for C 11 H 13 N[M+H] + :160.1121,found:160.1119；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 38
Synthesis of 3, 3-dimethyl-6-phenyl-2, 3,4, 5-tetrahydropyridine of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-5-phenylpentanamine, and the procedure was otherwise identical to that of example 21, except that 80mg of 3, 3-dimethyl-6-phenyl-2, 3,4, 5-tetrahydropyridine was obtained in 85% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.80-7.77(m,2H,ArH),7.38-7.36(m,3H,ArH),3.55(s,2H),2.68-2.63(m,2H),1.58(t,J＝6.8Hz,2H),0.95(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):164.8(C＝N),139.8,129.6,128.3,126.0,62.3,32.7,27.6,26.4,25.3；HRMS(ESI)m/z calcd for C 13 H 17 N[M+H] + :188.1434,found:188.1444；IR(KBr,plate),ν(cm -1 ):1616(C＝N).
example 39
Synthesis of 3, 3-dimethyl-6- (4-fluorobenzene) -2,3,4, 5-tetrahydropyridine with the structural formula shown in the specification
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-5- (4-fluorophenyl) -pentylamine in the same manner as in example 21 to give 88mg of 3, 3-dimethyl-6- (4-fluorobenzene) -2,3,4, 5-tetrahydropyridine in 86% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.80-7.77(m,2H,ArH),7.07-7.03(m,2H,ArH),3.54(s,2H),2.65-2.61(m,2H),1.59(t,J＝6.8Hz,2H),0.95(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):163.8(d,J＝247.4Hz),163.7(C＝N),136.0(d,J＝3.1Hz),128.0(d,J＝8.5Hz),115.1(d,J＝21.3Hz),62.2,32.7,27.6,26.4,25.3；HRMS(ESI)m/z calcd for C 13 H 16 FN[M+H] + :206.1340,found:206.1349；IR(KBr,plate),ν(cm -1 ):1615(C＝N).
example 40
Synthesizing 3, 3-dimethyl-6- (4-methylbenzene) -2,3,4, 5-tetrahydropyridine with the following structural formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar 2, 2-dimethyl-5- (4-methylbenzene) -pentylamine, and the other steps were the same as in example 21 to give 87mg of 3, 3-dimethyl-6- (4-methylbenzene) -2,3,4, 5-tetrahydropyridine in 86% yield as spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.68(d,J＝8.0Hz,2H,ArH),7.18(d,J＝8.0Hz,2H,ArH),3.53(s,2H),2.66-2.62(m,2H),2.36(s,3H),1.58(t,J＝6.8Hz,2H),0.95(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):164.5(C＝N),139.5,137.1,128.9,125.9,62.2,32.8,27.6,26.4,25.2,21.3；HRMS(ESI)m/z calcd for C 14 H 19 N[M+H] + :202.1590,found:202.1595；IR(KBr,plate),ν(cm -1 ):1609(C＝N).
example 42
Synthesis of 4- (4- (4-chlorophenyl) -4-hydroxypiperidine-1- (4-fluorophenyl) -1-butanone having the following structural formula
5.69mg (0.0075 mmol) (rac) -1,1 '-bis- (2-methylpyridine) -2,2' -bipiperidine manganese catalyst and 90mg (0.25 mmol) 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine are introduced into a reaction tube, 1.0mL acetonitrile and 236mg (2.5 mmol) chloroacetic acid are added to the reaction tube, and 63. Mu.L (1.25 mmol) of H at a mass concentration of 30% are then added 2 O 2 Dissolve in 1.0mL acetonitrile and add dropwise to the reaction flask via a microinjection pump and stir the reaction at room temperature for 60 minutes. After the reaction is finished, adding solid sodium sulfite into the reaction solution to quench the residual H 2 O 2 Suction filtration, ethyl acetate washing, filtrate collection, rotary evaporation solvent and column chromatography separation are carried out to obtain 84mg of 4- (4- (4-chlorophenyl) -4-hydroxypiperidine-1- (4-fluorophenyl) -1-butanone, the yield is 90%, and the spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.03-8.00(m,2H,ArH),7.38(d,J＝8.4Hz,2H,ArH),7.29(t,J＝8.4Hz,2H,ArH),7.13(t,J＝8.4Hz,2H,ArH),2.99(t,J＝6.8Hz,2H),2.80(d,J＝10.8Hz,2H),2.52-2.43(m,4H),2.05-1.97(m,4H),1.70-1.64(m,3H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.3(C＝O),165.6(d,J C-F ＝252.9Hz),146.9,133.6(d,J C-F ＝3.2Hz),132.7,130.6(d,J C-F ＝9.1Hz),128.3,126.1,115.6(d,J C-F ＝21.6Hz),71.0,57.7,49.3,38.3,36.2,21.8；HRMS(ESI)m/z calcd for C 21 H 23 ClFNO 2 [M+H] + :376.1474,found:376.1475；IR(KBr,plate),ν(cm -1 ):1683(C＝O).
example 43
Synthesis of 4- (4- (4-fluorophenyl) piperidine-1-phenyl-1-butanone with the structural formula shown below
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-fluorophenyl) -1- (4-phenylbutyl) piperidine, and the other steps were the same as in example 42 to obtain 74mg of 4- (4- (4-fluorophenyl) piperidine-1-phenyl-1-butanone in 91% yield, and the spectral data was: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.98(d,J＝7.6Hz,2H,ArH),7.56(t,J＝7.6Hz,1H,ArH),7.47(t,J＝7.6Hz,2H,ArH),7.16-7.12(m,2H,ArH),6.96(t,J＝8.4Hz,2H,ArH),3.09(d,J＝11.2Hz,2H),3.03(t,J＝7.2Hz,2H),2.53-2.46(m,3H),2.11(t,J＝11.2Hz,2H),2.05-1.99(m,2H),1.80-1.69(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.0(C＝O),161.3(d,J C-F ＝242.2Hz),141.8,137.1,132.9,128.5,128.1(d,J C-F ＝7.6Hz),128.0,115.1(d,J C-F ＝20.8Hz),57.9,54.0,41.8,36.3,33.2,21.5；HRMS(ESI)m/z calcd for C 21 H 24 FNO[M+H] + :326.1915,found:326.1912；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 44
Synthesis of 4- (4- (4-chlorophenyl) piperidine-1-phenyl-1-butanone with the structural formula shown below
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-chlorophenyl) -1- (4-phenylbutyl) piperidine, and the other steps were the same as in example 42 to obtain 77mg of 4- (4- (4-chlorophenyl) piperidine-1-phenyl-1-butanone in 90% yield, and the spectral data was: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.99(d,J＝7.6Hz,2H,ArH),7.56(t,J＝7.6Hz,1H,ArH),7.47(t,J＝7.6Hz,2H,ArH),7.24(d,J＝8.4Hz,2H,ArH),7.11(d,J＝8.4Hz,2H,ArH),3.02(t,J＝7.2Hz,4H),2.47-2.43(m,3H),2.08-1.95(m,4H),1.78-1.62(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.1(C＝O),145.0,137.3,133.0,131.8,128.6,128.5,128.3,128.2,58.2,54.2,42.2,36.5,33.4,22.0；HRMS(ESI)m/z calcd for C 21 H 24 ClNO[M+H] + :342.1619,found:342.1623；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 45
Synthesis of 4- (4- (4-bromophenyl) piperidine-1-phenyl-1-butanone of the formula
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-bromophenyl) -1- (4-phenylbutyl) piperidine, and the other steps were the same as in example 42 to obtain 85mg of 4- (4- (4-bromophenyl) piperidine-1-phenyl-1-butanone in 88% yield, and the spectral data was: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.99(d,J＝7.6Hz,2H,ArH),7.56(t,J＝7.6Hz,1H,ArH),7.46(t,J＝7.6Hz,2H,ArH),7.39(d,J＝8.4Hz,2H,ArH),7.05(d,J＝8.4Hz,2H,ArH),3.01(t,J＝7.2Hz,4H),2.46-2.41(m,3H),2.07-1.95(m,4H),1.78-1.72(m,2H),1.65(dt,J＝12.4,3.6Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.0(C＝O),145.4,137.2,132.8,131.4,128.6,128.5,126.6,119.7,58.0,54.1,42.1,36.3,33.2,21.9；HRMS(ESI)m/z calcd for C 21 H 24 BrNO[M+H] + :386.1114,found:386.1109；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 46
Synthesis of 4- (4- (4-fluorophenyl) piperidine-1- (4-fluorophenyl) -1-butanone with the following structural formula
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-fluorophenyl) -1- (4- (4-fluorophenyl) butyl) piperidine and the other steps were the same as in example 42 to obtain 73mg of 4- (4- (4-fluorophenyl) piperidine-1- (4-fluorophenyl) -1-butanone in 85% yield, and the spectral data were: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.04-8.00(m,2H,ArH),7.16-7.11(m,4H,ArH),6.99-6.94(m,2H,ArH),3.02-2.97(m,4H),2.45-2.41(m,3H),2.07-1.94(m,4H),1.79-1.75(m,Hz,2H),1.69-1.62(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.4(C＝O),165.6(d,J C-F ＝252.2Hz),161.2(d,J C-F ＝242.9Hz),142.0(d,J C-F ＝2.5Hz),133.6(d,J C-F ＝9.1Hz),130.6(d,J C-F ＝9.1Hz),128.1(d,J C-F ＝7.7Hz),115.5(d,J C-F ＝21.7Hz),115.0(d,J C-F ＝20.8Hz),58.0,54.1,41.9,36.2,33.5,21.8；HRMS(ESI)m/z calcd for C 21 H 23 F 2 NO[M+H] + :344.1820,found:344.1819；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 47
Synthesis of 4- (4- (4-chlorophenyl) piperidine-1- (4-fluorophenyl) -1-butanone having the following structural formula
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) piperidine, and the other steps were the same as in example 42 to obtain 75mg of 4- (4- (4-chlorophenyl) piperidine-1- (4-fluorophenyl) -1-butanone in 83% yield, and the spectral data was: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.06-8.02(m,2H,ArH),7.28-7.26(m,2H,ArH),7.18-7.13(m,4H,ArH),3.05-2.99(m,4H),2.50-2.44(m,3H),2.09-1.98(m,4H),1.80-1.65(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.5(C＝O),165.7(d,J C-F ＝252.9Hz),145.0,133.8(d,J C-F ＝3.1Hz),131.8,130.8(d,J C-F ＝9.1Hz),128.6,128.3,115.7(d,J C-F ＝21.7Hz),58.1,54.2,42.2,36.4,33.5,22.0；HRMS(ESI)m/z calcd for C 21 H 23 ClFNO[M+H] + :360.1525,found:360.1524；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 48
Synthesis of 4- (4- (4-bromophenyl) piperidine-1- (4-fluorophenyl) -1-butanone having the following structural formula
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine was replaced with an equimolar amount of 4- (4-bromophenyl) -1- (4- (4-fluorophenyl) butyl) piperidine, and the other steps were the same as in example 42 to obtain 81mg of 4- (4- (4-bromophenyl) piperidine-1- (4-fluorophenyl) -1-butanone in 80% yield, and the spectral data were: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.03-8.00(m,2H,ArH),7.40(d,J＝8.4Hz,2H,ArH),7.15-7.09(m,2H,ArH),7.05(d,J＝8.4Hz,2H,ArH),3.03-2.97(m,4H),2.46-2.42(m,3H),2.07-1.95(m,4H),1.78-1.76(m,2H),1.69-1.62(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):198.4(C＝O),165.6(d,J C-F ＝252.8Hz),145.3,133.7(d,J C-F ＝3.1Hz),131.4,130.7(d,J C-F ＝9.3Hz),128.6,126.7,119.7,115.6(d,J C-F ＝21.5Hz),58.0,54.1,42.1,36.3,33.2,21.8；HRMS(ESI)m/z calcd for C 21 H 23 BrFNO[M+H] + :404.1020,found:404.1015；IR(KBr,plate),ν(cm -1 ):1684(C＝O).
example 49
Synthesis of 1-phenyl-4- (3-phenyl) piperazine-1-butanone with the structural formula shown below
In example 42, the 4- (4-chlorophenyl) -1- (4- (4-fluorophenyl) butyl) -4-hydroxypiperidine used was replaced with equimolar 3-phenyl-1- (4-phenyl) butyl) piperidine, and the other steps were followedExample 42 was conducted in the same manner as in example 42 to obtain 63mg of 1-phenyl-4- (3-phenyl) piperazine-1-butanone in 82% yield as spectral data 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.99-7.97(m,2H,ArH),7.58-7.53(m,1H,ArH),7.48-7.44(m,2H,ArH),7.33-7.27(m,2H,ArH),7.22-7.18(m,3H,ArH),3.02-2.96(m,4H),2.76-2.70(m,1H),2.46-2.42(m,2H),2.03-1.84(m,5H),1.79-1.73(m,1H),1.70-1.59(m,1H),1.49-1.39(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):200.2(C＝O),144.9,137.3,132.9,128.6,128.4,128.2,127.3,126.4,61.3,58.3,53.8,42.9,36.5,31.6,25.8,21.9；HRMS(ESI)m/z calcd for C 21 H 25 NO[M+H] + :308.2009,found:308.2011；IR(KBr,plate),ν(cm -1 ):1685(C＝O).
Example 50
Synthesis of 1,2,3, 4-tetrahydrobenzo [ b ] azepin-5-one of the formula
In example 21, the 4-phenylbutylamine used was replaced with equimolar amounts of 2,3,4, 5-tetrahydro-1H-2-benzazepine, and the procedure was otherwise identical to that of example 21 to give 1,2,3, 4-tetrahydrobenzo [ b ]]Azepin-5-one 66mg, 82% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):7.80(d,J＝7.6Hz,1H,ArH),7.44(t,J＝7.6Hz,1H,ArH),7.35(t,J＝7.6Hz,1H,ArH),7.24(d,J＝7.6Hz,1H,ArH),4.15(s,2H),3.23(t,J＝6.4Hz,2H),2.95(t,J＝6.4Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ(ppm):203.5(C＝O),142.8,138.7,132.0,128.7,128.5,127.3,51.3,43.4,43.3；HRMS(ESI)m/z calcd for C 10 H 11 NO[M+H] + :162.0913,found:162.0915；IR(KBr,plate),ν(cm -1 ):1663(C＝O).
example 51
Synthesis of 5-acetyl-5, 11-hydrogen-10H-dibenzo [ b, f ] -10-ketone with the structural formula shown in the specification
In example 2, equimolar amounts of 10, 11-hydrogen-5H-dibenzo [ b, f were used for 4-phenylbutyric acid]The procedure was otherwise as in example 2, except for using aza-ethyl ketone as a substitute, to give 5-acetyl-5, 11-hydrogen-10H-dibenzo [ b, f]-10-ketone 117mg in 93% yield, spectral data: 1 H NMR(400MHz,CDCl 3 )δ(ppm):8.11(d,J＝7.9Hz,1H,ArH),7.61-7.57(m,2H,ArH),7.42-7.31(m,5H,ArH),4.35(d,J＝14.6Hz,1H),3.86(d,J＝14.6Hz,1H),2.12(s,3H,COCH 3 )； 13 C NMR(100MHz,CDCl 3 )δ(ppm):191.8(ArC＝O),169.8(NC＝O),142.5,133.9,130.7,130.0,129.1,128.8,128.6,127.7,49.1,23.2；HRMS(ESI)m/z calcd for C 16 H 13 NO 2 [M+Na] + :274.0838；found:274.0846；IR(KBr,plate),ν(cm -1 ):1672(C＝O)。

Claims (8)

1. a method for synthesizing aryl ketone by catalyzing selective oxidation of benzyl position of hydrocarbon molecule by using manganese catalyst is characterized in that: adding hydrocarbon and manganese catalyst with different functional groups shown in formula I into a reaction bottle containing acetonitrile and acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the acetonitrile into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain aryl ketone with different functional groups shown in a formula II; the reaction equation is shown below:
wherein FG represents C 1 ～C 4 Any one of alkyl, aryl, carboxyl, acyl, amido, acyloxy, sulfonyloxy, cyano, azido, alkynyl, protected primary amine, protected secondary amine, protected amino acid; r represents hydrogen, halogen or C 1 ～C 4 Any one of alkyl and nitro, n=an integer of 0 to 6;
the structural formula of the manganese catalyst is shown as follows:
the bipiperidine skeleton in the structural formula of the manganese catalyst represents any one of (meso) -2,2 '-bipiperidine, (rac) -2,2' -bipiperidine, (R, R) -2,2 '-bipiperidine and (S, S) -2,2' -bipiperidine; OTf represents the coordinating ion triflate anion.
2. The method for synthesizing aryl ketone by catalytic benzyl site selective oxidation of hydrocarbon molecules with manganese catalyst according to claim 1, wherein the method comprises the following steps: the addition amount of the manganese catalyst is 0.1-10% of the molar amount of hydrocarbon with different functional groups shown in the formula I, H 2 O 2 The addition amount of the catalyst is 5 to 8 times of the molar amount of the hydrocarbon with different functional groups shown in the formula I, and the addition amount of the acetic acid is 4 to 6 times of the molar amount of the hydrocarbon with different functional groups shown in the formula I.
3. A method for synthesizing cyclic imine by catalyzing selective oxidation of primary amine hydrocarbon bond benzyl site by using a manganese catalyst is characterized by comprising the following steps: adding a primary amine and manganese catalyst shown in formula III into a reaction bottle containing acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile and dropwise adding the acetonitrile into a reaction bottle through a microinjection pump, and reacting for 10-300 minutes at room temperature, wherein primary amine carbon-hydrogen bond benzyl site is selectively oxidized to generate aryl ketoamine shown in a formula IV, and the aryl ketoamine is condensed under the promotion of acetic acid to generate cyclic imine shown in a formula V; the reaction equation is shown below:
wherein R is 1 Represents hydrogen, halogen, C 1 ～C 4 Any one of alkyl groups, R 2 Represents hydrogen or methyl, R 3 Represents hydrogen, C 1 ～C 4 Alkyl, cyclohexyl, phenyl, C 1 ～C 4 Alkyl substituted phenyl or halogenated phenyl, m=1 or 2;
the structural formula of the manganese catalyst is shown as follows:
the bipiperidine skeleton in the structural formula of the manganese catalyst represents any one of (meso) -2,2 '-bipiperidine, (rac) -2,2' -bipiperidine, (R, R) -2,2 '-bipiperidine and (S, S) -2,2' -bipiperidine; OTf represents the coordinating ion triflate anion.
4. The method for synthesizing the cyclic imine by catalyzing selective oxidation of primary amine hydrocarbon bond benzyl positions by using the manganese catalyst according to claim 3, wherein the method comprises the following steps of: the addition amount of the manganese catalyst is 0.1-10% of the molar amount of the primary amine shown in the formula III, and H 2 O 2 The addition amount of the catalyst is 4 to 6 times of the mole amount of the primary amine shown in the formula III, and the addition amount of the acetic acid is 45 to 55 times of the mole amount of the primary amine shown in the formula III.
5. A method for synthesizing a drug active molecule by catalyzing selective oxidation of tertiary amine hydrocarbon bond benzyl positions by using a manganese catalyst is characterized by comprising the following steps of: adding tertiary amine shown in formula VI and catalyst into a reaction bottle containing acetonitrile and chloroacetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the acetonitrile into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain the pharmaceutically active molecules shown in the formula VII; the reaction equation is shown below:
wherein R is 4 、R 6 Each independently represents hydrogen, halogen, C 1 ～C 4 Any one of alkyl groups, R 5 Represents hydrogen or hydroxy, y=0 or 1;
the structural formula of the manganese catalyst is shown as follows:
the bipiperidine skeleton in the structural formula of the manganese catalyst represents any one of (meso) -2,2 '-bipiperidine, (rac) -2,2' -bipiperidine, (R, R) -2,2 '-bipiperidine and (S, S) -2,2' -bipiperidine; OTf represents the coordinating ion triflate anion.
6. The method for synthesizing the drug active molecule by catalyzing selective oxidation of tertiary amine hydrocarbon bond benzyl sites by using the manganese catalyst according to claim 5, wherein the method comprises the following steps of: the addition amount of the manganese catalyst is 0.1-10% of the molar amount of tertiary amine shown in the formula VI, H 2 O 2 The addition amount of the catalyst is 5 to 8 times of the molar amount of the tertiary amine shown in the formula VI, and the addition amount of the chloroacetic acid is 9 to 12 times of the molar amount of the tertiary amine shown in the formula VI.
7. A method for synthesizing a drug active molecule by catalyzing selective oxidation of a cyclic secondary amine carbon-hydrogen bond benzyl site by using a manganese catalyst is characterized by comprising the following steps of: adding a cyclic secondary amine of formula VIII and a manganese catalyst into a reaction bottle containing acetic acid, and then adding H 2 O 2 Dissolving the aqueous solution in acetonitrile, dripping the aqueous solution into a reaction bottle through a microinjection pump, reacting for 10-300 minutes at room temperature, and separating and purifying to obtain the pharmaceutically active molecule shown in the formula IX; the reaction equation is shown below:
wherein z=an integer of 1 to 4, and u=an integer of 0 to 4;
the structural formula of the manganese catalyst is shown as follows:
the bipiperidine skeleton in the structural formula of the manganese catalyst represents any one of (meso) -2,2 '-bipiperidine, (rac) -2,2' -bipiperidine, (R, R) -2,2 '-bipiperidine and (S, S) -2,2' -bipiperidine; OTf represents the coordinating ion triflate anion.
8. The method for synthesizing the pharmaceutically active molecule by catalyzing selective oxidation of cyclic secondary amine carbon-hydrogen bond benzyl sites by using the manganese catalyst according to claim 7, wherein the method comprises the following steps of: the addition amount of the manganese catalyst is 0.1-10% of the molar amount of the cyclic secondary amine shown in the formula VIII, and H 2 O 2 The addition amount of the catalyst is 4 to 6 times of the molar amount of the cyclic secondary amine shown in the formula VIII, and the addition amount of the acetic acid is 45 to 55 times of the molar amount of the cyclic secondary amine shown in the formula VIII.
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