N-substituted benzoyl cyclic lactam and preparation method thereof

Abstract

The invention discloses N-substituted benzoyl cyclic lactam and a preparation method thereof.The preparation method comprises the steps that N-substituted benzyl cyclic lactam in the formula is used as a raw material, N-hydroxyphthalimide is used as a catalyst, oxygen is used as an oxygen source, and a binary mixed solvent containing electrolyte is used as electrolyte; and performing electrochemical oxidation in an environment with the current density of 0.14-3mA / cm < 2 > and sufficient oxygen to obtain the N-substituted benzoyl cyclic lactam as shown in the formula. The preparation method of N-substituted benzoyl cyclic lactam provided by the invention has the advantages of simple synthesis process, mild reaction conditions, no transition heavy metal and the like.

Description

Technical Field

[0001] The present invention belongs to the field of compounds, and more particularly, relates to N-substituted benzoyl cyclic lactam and a preparation method thereof. Background Art

[0002] Benzimide is a common structural motif found in natural products, pharmaceutical molecules, and agrochemicals. Compounds containing this structural motif not only serve as multifunctional intermediates with significant application value in organic synthesis but also have a wide range of uses in pharmaceuticals and agrochemicals. Therefore, efficiently constructing the benzoimide skeleton has always been a core goal of organic synthesis research. Typically, aniracetam, represented by Formula (III) below, can selectively act on the central nervous system through the blood-brain barrier and be used as a brain function-enhancing drug. Fumaridine precursors, represented by Formula (IV) below, can be used to synthesize fumarate, which has anti-acetylcholinesterase, anti-allergic, analgesic, gastrointestinal function-regulating, and anthelmintic activities. Rebeccamycin, represented by Formula (V) below, exhibits significant antitumor properties against mouse B16 melanoma cells and P388 leukemia cells in vitro. It is an antitumor antibiotic and intercalator that can intercalate into DNA to interfere with its replication and transcription, and is used in the development of antitumor drugs. Zafirlukast, represented by the following formula (VI), is a synthetic, selective polypeptide leukotriene receptor antagonist that selectively and competitively antagonizes leukotrienes D4 and E4, blocks the binding of cysteinyl leukotrienes to the CysLT1 receptor, reduces airway constriction, lung mucus accumulation, and respiratory tract inflammation, inhibits bronchospasm caused by various stimuli (such as sulfur dioxide, exercise, and cold air), and reduces early and late inflammatory responses induced by antigens. Gliquidone, represented by the following formula (VII), belongs to the second generation of sulfonylurea oral hypoglycemic drugs. Alternatively, benzoyl caprolactam and its analogs can be used as odor absorbers. Furthermore, benzimides also have certain bactericidal effects, such as against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus.

[0003]

[0004]

[0005] Furthermore, N-benzyl-2-pyrrolidone represented by the following formula (IV) is a typical multifunctional intermediate, which is widely used in organic synthesis. It can be used as a solvent and reagent to catalyze oxidation reactions, hydrogenation reactions, and reduction reactions.

[0006] Over the past decade, researchers have developed a variety of synthetic strategies for benzimide derivatives, including acylation reactions of amides with activated carboxylic acid derivatives, carboxylation coupling reactions of aryl halides with amides, and α-oxidation reactions of amides. Among these, direct oxidation reactions of aliphatic C-H bonds have attracted considerable attention due to their operational simplicity and streamlined pathways. However, these methods suffer from harsh reaction conditions, limited substrate compatibility, the need for toxic heavy metals, and the use of stoichiometric oxidants, which have limited their scalable application.

[0007] Therefore, it is of great research significance to develop new methods for synthesizing benzimides using readily available substrates as raw materials. Summary of the Invention

[0008] Technical issues

[0009] The first object of the present invention is to provide a method for preparing N-substituted benzoyl cyclic lactams that can be sustainably synthesized with good selectivity.

[0010] At the same time, the present invention provides a new structure of N-substituted benzoyl cyclic lactam compound.

[0011] Technical Solution

[0012] In order to solve the above problems, the technical solutions adopted by the present invention are as follows:

[0013] The first aspect of the present invention provides a method for preparing an N-substituted benzoyl cyclic lactam, comprising the steps of:

[0014] The N-substituted benzyl cyclic lactam shown in formula (I) is used as substrate, N-hydroxyphthalimide is used as catalyst, oxygen is used as oxygen source, and a binary mixed solvent containing electrolyte is used as electrolyte. 2 Electrochemical oxidation is performed under a current density of 1000 nm and an oxygen-sufficient environment to obtain an N-substituted benzoyl cyclic lactam represented by formula (II);

[0015]

[0016] Wherein, the Z1 ring is one of a spiro[4,5]heterocyclic group and a C6-C7 heterocyclic group;

[0017] R is selected from one of hydrogen, halogen, C1-C3 alkyl, C1-C3 alkoxy, and cyano.

[0018] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the Z1 ring is a spiro[4,5]heterocyclic group;

[0019] The R is selected from one of halogen, C1-C3 alkyl, and C1-C3 alkoxy.

[0020] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the Z1 ring is selected from one of C6 to C7 heterocyclic groups;

[0021] The R is selected from one of hydrogen, C1-C3 alkoxy and cyano.

[0022] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the Z1 ring is a spiro[4,5]heterocyclic group, and the R is selected from one of halogen, methyl, and methoxy.

[0023] According to the method for preparing an N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the N-substituted benzoyl cyclic lactam is selected from any one of the following:

[0024] 2-(4-methylbenzoyl)-2-aza[4.5]decan-3-one,

[0025] 2-(4-methoxybenzoyl)-2-aza[4.5]decan-3-one,

[0026] 2-(4-chlorobenzoyl)-2-aza[4.5]decan-3-one,

[0027] 2-(4-bromobenzoyl)-2-aza[4.5]decan-3-one,

[0028] 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one,

[0029] N-(4-methoxybenzoyl)azepine -2-ketone,

[0030] N-(3-cyanobenzoyl)azepine -2-ketone,

[0031] N-(2-chlorobenzoyl)azepine -2-ketone,

[0032] N-(4-Methoxybenzoyl)azoctan-2-one

[0033] N-benzoylpiperidin-2-one,

[0034] N-Benzoyl-azepine -2-ketone,

[0035] N-(4-chlorobenzoyl)azepine -2-ketone,

[0036] N-(4-bromobenzoyl)azepine -2-ketone,

[0037] N-(4-Fluorobenzoyl)azepine -2-ketone.

[0038] According to the preparation method of N-substituted benzoyl cyclic lactam provided in any embodiment of the first aspect of the present invention, the electrolyte includes any one, two or more of 2,4,6-triethylpyridine perchlorate, 2,6-dimethylpyridine perchlorate, tetra-n-butylammonium tetrafluoroborate (Bu4NBF4), tetra-n-butylammonium hexafluorophosphate (Bu4NPF6), and tetra-n-butylammonium bromide (Bu4NBr).

[0039] Preferably, the electrolyte comprises 2,6-lutidine perchlorate.

[0040] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the binary mixed solvent includes any one of a binary mixed solvent of acetone and water and a binary mixed solvent of acetonitrile and water;

[0041] Wherein, the volume ratio of acetone to water is (1-3):1; the volume ratio of acetone to water is preferably (2-3):1;

[0042] The volume ratio of the acetonitrile to water is (1-3):1; the volume ratio of the acetonitrile to water is preferably (2-3):1;.

[0043] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the concentration of the substrate N-substituted benzyl cyclic lactam represented by formula (I) in the binary mixed solvent is 0.04 to 0.13 mol / L.

[0044] Preferably, the concentration of the substrate N-substituted benzyl cyclic lactam represented by formula (I) in the binary mixed solvent is 0.5 to 0.13 mol / L.

[0045] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the amount of the catalyst used is 20 to 30 mol%, calculated based on the total amount of N-substituted benzyl cyclic lactam represented by formula (I).

[0046] Preferably, the amount of the catalyst used is 20 to 25 mol%, calculated based on the total amount of the N-substituted benzyl cyclic lactam represented by formula (I).

[0047] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the amount of the electrolyte used is 5 to 20 mol%, calculated based on the total amount of N-substituted benzyl cyclic lactam represented by formula (I).

[0048] Preferably, the amount of the electrolyte used is 5 to 15 mol % based on the total amount of the N-substituted benzyl cyclic lactam represented by formula (I).

[0049] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, at 0.14-2.1 mA / cm 2 Electrochemical oxidation was carried out at a current density of .

[0050] Preferably, the range is 0.14 to 1.5 mA / cm 2 Electrochemical oxidation was carried out at a current density of .

[0051] According to the method for preparing N-substituted benzoyl cyclic lactam provided by any embodiment of the first aspect of the present invention, the anode is graphite and the cathode is nickel.

[0052] The second aspect of the present invention provides an N-substituted benzoyl cyclic lactam as shown in formula (II), wherein the N-substituted benzoyl cyclic lactam can be prepared according to the method for preparing N-substituted benzoyl cyclic lactam provided in any embodiment of the first aspect of the present invention;

[0053]

[0054] wherein the Z1 ring is selected from a spiro[4,5]heterocyclic group and a C6-C7 heterocyclic group;

[0055] R is selected from one of hydrogen, halogen, C1-C3 alkyl, C1-C3 alkoxy, and cyano.

[0056] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam provided, the Z1 ring is a spiro [4,5] heterocyclic group;

[0057] The R is selected from one of halogen, C1-C3 alkyl, and C1-C3 alkoxy.

[0058] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam is provided, wherein the Z1 ring is selected from one of the C6-C7 heterocyclic groups;

[0059] The R is selected from one of hydrogen, C1-C3 alkoxy and cyano.

[0060] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam provided, the Z1 ring is a spiro [4,5] heterocyclic group, and the R is selected from one of halogen, methyl, and methoxy.

[0061] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam is selected from any one of the following:

[0062] 2-(4-methylbenzoyl)-2-aza[4.5]decan-3-one,

[0063] 2-(4-methoxybenzoyl)-2-aza[4.5]decan-3-one,

[0064] 2-(4-chlorobenzoyl)-2-aza[4.5]decan-3-one,

[0065] 2-(4-bromobenzoyl)-2-aza[4.5]decan-3-one,

[0066] 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one,

[0067] N-(4-methoxybenzoyl)azepine -2-ketone,

[0068] N-(3-cyanobenzoyl)azepine -2-ketone,

[0069] N-(2-chlorobenzoyl)azepine -2-ketone,

[0070] N-(4-Methoxybenzoyl)azoctan-2-one

[0071] N-benzoylpiperidin-2-one,

[0072] N-Benzoyl-azepine -2-ketone,

[0073] N-(4-chlorobenzoyl)azepine -2-ketone,

[0074] N-(4-bromobenzoyl)azepine -2-ketone,

[0075] N-(4-Fluorobenzoyl)azepine -2-ketone.

[0076] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam is selected from any one of the following:

[0077] 2-(4-methylbenzoyl)-2-aza[4.5]decan-3-one,

[0078] 2-(4-methoxybenzoyl)-2-aza[4.5]decan-3-one,

[0079] 2-(4-chlorobenzoyl)-2-aza[4.5]decan-3-one,

[0080] 2-(4-bromobenzoyl)-2-aza[4.5]decan-3-one,

[0081] 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one,

[0082] N-(4-methoxybenzoyl)azepine -2-ketone,

[0083] N-(3-cyanobenzoyl)azepine -2-ketone,

[0084] N-(2-chlorobenzoyl)azepine -2-ketone,

[0085] N-(4-methoxybenzoyl)azoctan-2-one.

[0086] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam is selected from any one of the following:

[0087] 2-(4-methylbenzoyl)-2-aza[4.5]decan-3-one,

[0088] 2-(4-methoxybenzoyl)-2-aza[4.5]decan-3-one,

[0089] 2-(4-chlorobenzoyl)-2-aza[4.5]decan-3-one,

[0090] 2-(4-bromobenzoyl)-2-aza[4.5]decan-3-one,

[0091] 2-(4-Fluorobenzoyl)-2-aza[4.5]decan-3-one.

[0092] According to any embodiment of the second aspect of the present invention, the N-substituted benzoyl cyclic lactam is selected from any one of the following:

[0093] N-(3-cyanobenzoyl)azepine -2-ketone,

[0094] N-(2-chlorobenzoyl)azepine -2-ketone,

[0095] N-(4-methoxybenzoyl)azoctan-2-one.

[0096] The third aspect of the present invention provides use of the N-substituted benzoyl cyclic lactam provided in any embodiment of the second aspect of the present invention in inhibiting Escherichia coli or Staphylococcus aureus.

[0097] A fourth aspect of the present invention provides use of an N-substituted benzoyl cyclic lactam as provided in any embodiment of the second aspect of the present invention in the preparation of a fungicide for inhibiting Escherichia coli or Staphylococcus aureus.

[0098] 3. Beneficial effects

[0099] Benzimide

[0100] Compared with the prior art, the present invention has the following beneficial effects:

[0101] (1) Compared with the preparation method using traditional chemical oxidants, the preparation method of N-substituted benzoyl cyclic lactam provided by the present invention has a simple synthesis process, mild reaction conditions, small amount of chemical reagents, no transition heavy metals, and oxygen is the only oxygen source. The process can be sustained and excellent.

[0102] (2) Taking the preparation of 1-benzoyl-2-pyrrolidone as an example, the content of N-benzylsuccinimide in the product of 1-benzoyl-2-pyrrolidone prepared by direct electrochemical oxidation using 1-benzyl-2-pyrrolidone as a substrate and NHPI as an oxidant is close to or even exceeds that of the target product 1-benzoyl-2-pyrrolidone. That is, compared with the preparation of N-substituted benzoyl cyclic lactams by direct electrochemical oxidation using N-substituted benzyl cyclic lactams containing nitrogen heterocyclic alkyl as a substrate and NHPI as an oxidant, the preparation method of N-substituted benzoyl cyclic lactams provided by the present invention preferably uses N-substituted benzyl cyclic lactams containing spiro[4,5]heterocyclic group as a substrate and NHPI as an oxidant to directly electrochemically oxidize N-substituted benzoyl cyclic lactams, thereby improving the selectivity of the target product N-substituted benzoyl cyclic lactam.

[0103] (3) N-substituted benzoyl cyclic lactam added to a heterocyclic group. The N-substituted benzoyl cyclic lactam with a spirocyclic structure provided by the present invention has better water solubility, lipophilicity, and advantageous conformation, and can increase the activity of the compound and improve the bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0104] Figure 1 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one1 H NMR;

[0105] Figure 2 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one 13 C NMR;

[0106] Figure 3 This is a high-resolution mass spectrum of 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one; DETAILED DESCRIPTION

[0107] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains; the term "and / or" used herein includes any and all combinations of one or more of the associated listed items.

[0108] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents or instruments used, if the manufacturer is not specified, are commercially available conventional products.

[0109] As used herein, the term "about" is used to provide flexibility and imprecision associated with a given term, measurement, or value. One skilled in the art can readily determine the degree of flexibility for a particular variable.

[0110] Concentration, content, percentage composition and other numerical data can be presented in range format in this article.Should be understood that such range format is only used for convenience and brevity, and should be flexibly interpreted as not only including the numerical value clearly described as range limit, but also including all independent numerical values or subranges encompassed within the described range, just as each numerical value and subrange are clearly described.For example, the numerical range of about 1 to about 4.5 should be interpreted as not only including the limit value of 1 to about 4.5 clearly described, but also including independent numerals (such as 2,3,4) and subranges (such as 1 to 3,2 to 4 etc.).The same principle is applicable to the scope of only narrating a numerical value, such as "less than about 4.5", which should be interpreted as including all above-mentioned values and scopes.In addition, no matter how the breadth of described scope or feature is, this explanation should be applicable.

[0111] In addition, as described in Table 1, the CAS numbers or synthesis methods of the substrates used in the following examples are shown in Table 1 below.

[0112] Table 1. CAS numbers or synthesis methods of substrates used in the following examples

[0113]

[0114]

[0115] The present invention will be further described below with reference to specific examples. In the following examples, the experimental methods without specific conditions are generally carried out under conventional conditions or conditions recommended by the manufacturer.

[0116] Example 1

[0117] The preparation method of 2-(4-methylbenzoyl)-2-aza[4.5]dec-3-one adopts the following reaction formula:

[0118]

[0119] The specific steps are as follows:

[0120] In a 10 mL electrolysis bottle, 0.4 mmol of 2-(4-methylbenzyl)-2-aza[4.5]decan-3-one as a substrate, the electrolyte 2,6-lutidine perchlorate (0.04 mmol, 10 mol% (electrolyte molar mass / substrate molar mass)*100%=10 mol%, the same as described in this example below), the electrocatalyst NHPI (20 mol% (electrocatalyst molar mass / substrate molar mass)*100%=20 mol%, the same as described in this example below), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence, and a graphite plate as an anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that it remains submerged below the reaction liquid level throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring that the bag is always filled with oxygen throughout the reaction. The reaction is conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is stopped. The reaction solution is concentrated under reduced pressure and separated by silica gel column chromatography to obtain 2-(4-methylbenzoyl)-2-aza[4.5]decan-3-one. A white solid is obtained with a yield of 90%.

[0121] 1 H-NMR (400MHz, CDCl3) δ7.51 (d, J=8.2Hz, 2H, Ar-H), 7.20 (d, J=8.1Hz, 2H, Ar-H), 3.71(s,2H,-N-CH2),2.45(s,2H,-CO-CH2),2.40(s,3H,-CH3),1.60(s,10H,-C5H 10 ).13 C-NMR(100MHz, CDCl3)δ174.25,171.0,141.8 132.8,131.2,129.6,128.7,57.0,46.5,36.6,35.0,26.0,23.0.HRMS(ESI)m / z calcd for C 17 H 22 NO2(M+H) + 272.1645, found 272.1644.

[0122] Example 2

[0123] The preparation method of 2-(4-chlorobenzoyl)-2-aza[4.5]dec-3-one adopts the following reaction formula:

[0124]

[0125] The specific steps are as follows:

[0126] In a 10 mL electrolytic bottle, 0.4 mmol of 2-(4-chlorobenzyl)-2-aza[4.5]decan-3-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence, and a graphite plate as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm) was used. 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that it remains submerged below the reaction liquid surface throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring that the bag is always filled with oxygen throughout the reaction. The reaction is conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is stopped. The reaction solution is concentrated under reduced pressure and separated by silica gel column chromatography. 2-(4-chlorobenzoyl)-2-aza[4.5]decan-3-one is isolated and purified as a white solid in an 86% yield.

[0127] 1H-NMR(400MHz, CDCl3)δ7.56-7.50(m,2H,Ar-H),7.40-7.35(m,2H,Ar-H),3.71(s,2H,-N-CH2)),2.47(s,2H,-CO-CH2),1.63-1.48(m,10H,-C5H 10 ). 13C-NMR (100MHz, CDCl3) δ182.5,173.8,138.2,133.2,130.4,130.0,128.8,128.1,36.2,35.3,33.8,33.3,25.5,23.3,21.0.HRMS(ESI)m / z calcd for C 16 H 19 ClNO2(M+H) + 292.1099, found 292.1100.

[0128] Example 3

[0129] The preparation method of 2-(4-bromobenzoyl)-2-aza[4.5]dec-3-one adopts the following reaction formula:

[0130]

[0131] The specific steps are as follows:

[0132] In a 10 mL electrolytic bottle, 0.4 mmol of 2-(4-bromobenzyl)-2-aza[4.5]decan-3-one (CAS: 1308609-76-8), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that it remains submerged below the reaction liquid surface throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring that the bag is always filled with oxygen throughout the reaction. The reaction is conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is stopped. The reaction solution is concentrated under reduced pressure and separated by silica gel column chromatography. 2-(4-bromobenzoyl)-2-aza[4.5]decan-3-one is isolated and purified as a white solid in 88% yield.

[0133] 1H-NMR (400MHz, CDCl3) δ7.54(d,J=8.6Hz,2H,Ar-H),7.45(d,J=8.6Hz,2H,Ar-H),3.71(s,2H,-N-CH2),2.46(s,2H,-CO-CH2),1.58(s,10H,-C5H 10 ). 13 C-NMR(100MHz, CDCl3)δ173.6,169.7,133.8,133.3,131.5,130.5,126.7,56.8,45.7,36.2,35.3,25.5,22.7.HRMS(ESI)m / zcalcd for C 16 H 19 BrNO2(M+H) + 336.0594, found 336.0597.

[0134] Example 4

[0135] The preparation method of 2-(4-fluorobenzoyl)-2-aza[4.5]dec-3-one adopts the following reaction formula:

[0136]

[0137] The specific steps are as follows:

[0138] In a 10 mL electrolytic bottle, 0.4 mmol of 2-(4-fluorobenzyl)-2-aza[4.5]decan-3-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that it remains submerged below the reaction liquid level throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring that the oxygen bag is always filled with oxygen throughout the reaction. The reaction is conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is stopped. The reaction solution is concentrated under reduced pressure and separated by silica gel column chromatography to obtain 2-(4-fluorobenzoyl)-2-aza[4.5]decan-3-one. A white solid with a yield of 86% is obtained.

[0139] 1 H-NMR (400MHz, CDCl3) δ7.62 (dd, J=8.6, 5.5Hz, 1H, Ar-H), 7.33 (dd, J=8.5, 5.6Hz, 1H, Ar-H), 7.08 (t, J=8. 6Hz,1H,Ar-H),6.97(t,J=8.7Hz,1H,Ar-H),3.71(s,2H,-N-CH2),2.47(s,2H,-CO-CH2),1.58(s,10H,-C5H 10 ). 13 C-NMR (100MHz, CDCl3) δ182.7,176.0,171.9(d,J=445.2Hz),131.8,130.6(d,J= 8.3Hz),115.3(d,J=54.1Hz),36.4,35.5,33.4,25.7,22.9,22.2.HRMS(ESI)m / z calcd for C 16 H 19 FNO2(M+H) + 276.1394,found276.1401.

[0140] Example 5

[0141] The preparation method of 2-(4-methoxybenzoyl)-2-aza[4.5]dec-3-one adopts the following reaction formula:

[0142]

[0143] The specific steps are as follows:

[0144] In a 10 mL electrolytic bottle, 0.4 mmol of 2-(4-methoxybenzyl)-2-aza[4.5]decan-3-one (CAS: 608532-82-7), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that it remains submerged below the reaction liquid surface throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring that the bag is always filled with oxygen throughout the reaction. The reaction is conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is stopped. The reaction solution is concentrated under reduced pressure and separated by silica gel column chromatography to obtain 2-(4-methoxybenzoyl)-2-aza[4.5]decan-3-one. It is a white solid with a yield of 92%.

[0145] 1 H-NMR (400MHz, CDCl3) δ7.63 (d, J=8.8Hz, 2H, Ar-H), 6.89 (d, J=8.8Hz, 2H, Ar-H), 3.85(s,3H,-OCH3),3.70(s,2H,-N-CH2),2.46(s,2H,-CO-CH2),1.59(s,10H,-C5H 10 ). 13 C-NMR(100MHz, CDCl3)δ173.7,169.7,162.6,131.3,126.0,112.8,55.1,35.9,35.0,25.9,22.4.HRMS(ESI)m / z calcd for C 17 H 22 NO3(M+H) + 288.1594, found 288.1607.

[0146] Example 6

[0147] The preparation method of N-benzoylpiperidin-2-one compound adopts the following reaction formula:

[0148]

[0149] The specific steps are as follows:

[0150] In a 10 mL electrolytic bottle, 0.4 mmol of 1-benzyl-2-piperidone (CAS: 4783-65-7), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution, ensuring it remains submerged throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff air into the reaction solution, ensuring sufficient oxygen throughout the reaction. Continue the reaction in constant current mode (2 mA). Stop the reaction when TLC reveals the disappearance of the product spot. Concentrate the reaction solution under reduced pressure and separate it by silica gel column chromatography to obtain N-benzoylpiperidin-2-one as a white solid in 82% yield.

[0151] 1 H-NMR (400MHz, CDCl3) δ7.58-7.52(m,2H,Ar-H),7.49-7.44(m,1H,Ar-H),7.38(dd,J=8.2,6.8Hz ,2H,Ar-H),3.81(t,J=5.7Hz,2H,-N-CH2),2.63-2.46(m,2H,-CO-CH2),2.05-1.86(m,4H,-C2H4). 13 C-NMR (100MHz, CDCl3) δ174.8,173.6,136.3,131.6,128.3,128.0,46.3,34.8,23.0,21.6.

[0152] Example 7

[0153] N-Benzoylazepine The preparation method of -2-ketone adopts the following reaction formula:

[0154]

[0155] The specific steps are as follows:

[0156] In a 10 mL electrolytic bottle, 0.4 mmol of 1-benzylazacycloheptan-2-one (CAS: 33241-96-2), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence, and a graphite plate as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm) was used. 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-benzoylazepine. -2-ketone. White solid, yield 82%.

[0157] 1 H-NMR (400MHz, CDCl3) δ7.55 (d, J=6.8Hz, 2H, Ar-H), 7.50-7.43 (m, 1H, Ar-H), 7.42-7.35 (m, 2H ,Ar-H),4.03-3.92(m,2H,-N-CH2),2.77-2.66(m,2H,-CO-CH2),1.94-1.80(m,6H,,-CH2CH2CH 2- ). 13 C-NMR (100MHz, CDCl3) δ177.6,174.1,136.6,131.3,128.1,127.7,45.2,38.8,29.6,29.21,23.7.

[0158] Example 8

[0159] N-(4-methoxybenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0160]

[0161] The specific steps are as follows:

[0162] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(4-methoxybenzyl)azepan-2-one (CAS: 1956354-75-8), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(4-methoxybenzoyl)azepine. -2-ketone. White solid, yield 90%.

[0163] 1 H-NMR (400MHz, CDCl3) δ7.58 (d, J=8.9Hz, 2H, Ar-H), 6.88 (d, J=8.9Hz, 2H, Ar-H), 3.92 (s ,2H,-N-CH2),3.83(s,3H),2.70(d,J=11.1Hz,2H,-CO-CH2),1.83(s,6H,-CH2CH2CH2-). 3 C-NMR(100MHz, CDCl3)δ177.9,174.1,162.8,130.8,128.7,113.8,55.7,46.0,39.1,30.0,29.6,27.2,24.0.HRMS(ESI)m / z calcd for C 14 H 18 NO3(M+H) + 248.1281,found248.1286.

[0164] Example 9

[0165] N-(4-chlorobenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0166]

[0167] The specific steps are as follows:

[0168] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(4-chlorobenzyl)azepan-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(4-chlorobenzoyl)azepine. -2-ketone. White solid, yield 86%.

[0169] 1 H-NMR (400MHz, CDCl3) δ7.47(d,J=8.6Hz,2H,Ar-H),7.36(d,J=8.6Hz,2H,Ar-H),3.96(s,2H,-N-CH2),2.74-2.64(m,2H,-CO-CH2),1.92-1.79(m,6H,-CH2CH2 CH2-). 13 C-NMR (100MHz, CDCl3) δ177.6,173.1,137.5,135.0,129.1,128.5,45.2,38.8,29.5,29.18,23.7.

[0170] Example 10

[0171] N-(4-bromobenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0172]

[0173] The specific steps are as follows:

[0174] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(4-bromobenzyl)azepan-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(4-bromobenzoyl)azepine. -2-ketone. White solid, yield 85%.

[0175] 1 H-NMR (400MHz, CDCl3) δ7.58-7.47(m,2H,Ar-H),7.44-7.37(m,2H,Ar-H),3.96(s,2H,,-N-CH2),2.69(d,J=5.9Hz,2H,-CO-CH2),1.92 -1.79(m,6H,-CH2CH2 CH2-). 13 C-NMR (100MHz, CDCl3) δ177.9,172.1,136.9,131.1,129.5,126.9,43.5,36.2,29.2,28.87,23.0.

[0176] Example 11

[0177] N-(4-Fluorobenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0178]

[0179] The specific steps are as follows:

[0180] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(4-fluorobenzyl)azepan-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(4-fluorobenzoyl)azepine. -2-ketone. White solid, yield 84%.

[0181] 1 H-NMR (400MHz, CDCl3) δ7.58-7.47(m,2H,Ar-H),7.44-7.37(m,2H,Ar-H),3.96(s,2H, -N-CH2),2.69(d,J=5.9Hz,2H,-CO-CH2),1.92-1.79(m,6H,-CH2CH2CH2-).13C-NMR(10 0MHz, CDCl3) δ177.6,173.1,165.8,163.3(d,J=250.4Hz),132.6(d,J=8.7Hz),132.6, 130.4(d,J=3.3Hz),130.26,115.4(d,J=21.8Hz),115.2,45.4,38.8,29.5,29.2,23.7. 19 FNMR (376MHz,CDCl3)δ-107.6.

[0182] Example 12

[0183] N-(3-cyanobenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0184]

[0185] The specific steps are as follows:

[0186] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(3-cyanobenzyl)azepan-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(3-cyanobenzoyl)azepine. -2-ketone. White solid, yield 90%.

[0187] 1 H-NMR (400MHz, CDCl3) δ7.79-7.68(m,3H,Ar-H),7.51(t,J=7.8Hz,1H,Ar-H),4.05-3.87(m,2H,-N-CH2),2.75-2.64(m,2H,-CO-CH2),1.85(s,6H,-CH2CH2 CH2-). 13 C-NMR(100MHz, CDCl3)δ177.5,171.8,138.1,134.1,131.5,131.0,129.0,118.1,112.5,45.0,38.7,29.4,29.1,23.7.HRMS(ESI)m / z calcd for C 14 H 15 N2O2(M+H) + 243.11280,found243.11274.

[0188] Example 13

[0189] N-(2-chlorobenzoyl)azepine The preparation method of -2-ketone adopts the following reaction formula:

[0190]

[0191] The specific steps are as follows:

[0192] In a 10 mL electrolytic bottle, 0.4 mmol of N-1-(2-chlorobenzyl)azepan-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution and ensure that the electrode is always immersed below the reaction liquid surface during the entire reaction. Connect a gas bag filled with pure oxygen to the reaction bottle and blow air into the reaction solution to ensure that the oxygen bag is always filled with sufficient oxygen during the entire reaction. The reaction is carried out in a constant current mode (2mA). When TLC detection shows that the product spot disappears, the reaction is stopped, the reaction solution is concentrated under reduced pressure, and separated by silica gel column chromatography to obtain N-(2-chlorobenzoyl)azepine. -2-ketone. Colorless oily liquid, yield 80%.

[0193] 1 H-NMR (400MHz, CDCl3) δ7.32 (d, J=3.8Hz, 1H, Ar-H), 7.30 (s, 1H, Ar-H), 7.30-7.28 (m, 1H, Ar-H), 7.26 (d ,J=5.7Hz,1H,Ar-H),4.11-4.03(m,2H,-N-CH2),2.73-2.64(m,2H,-CO-CH2),1.91-1.77(m,6H,-CH2CH2 CH2-). 13 C-NMR(100MHz, CDCl3)δ176.6,169.5,138.1,134.3,130.0,129.3,127.5,126.9,43.7,39.0,29.5,28.0,23.7.HRMS(ESI)m / zcalcd for C 13 H 15 ClNO2(M+H) + 252.0786,found 252.0785.

[0194] Example 14

[0195] The preparation method of N-(4-methoxybenzoyl) azacyclooctan-2-one adopts the following reaction formula:

[0196]

[0197] The specific steps are as follows:

[0198] In a 10 mL electrolytic bottle, 0.4 mmol of 1-(4-methoxybenzyl)azocane-2-one, electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution, ensuring it remains submerged throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring sufficient oxygen throughout the reaction. Operate the reaction in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, stop the reaction, concentrate the reaction solution under reduced pressure, and separate and purify it by silica gel column chromatography to obtain N-(4-methoxybenzoyl)azocane-2-one as a white solid in 82% yield.

[0199] 1 H-NMR (400MHz, CDCl3) δ7.59 -7.48(m,2H,Ar-H),6.93-6.81(m,2H,Ar-H),3.99-3.90(m,2H,-N-CH2),3.83(s,3H,-OCH3),2.66(q,J=6.4 Hz,2H,-CO-CH2),1.90(dp,J=12.5,6.1Hz,4H,-CH2-CH2),1.68-1.62(m,2H,-CH2),1.60-1.53(m,2H,-CH2). 13 C-NMR(100MHz, CDCl3)δ178.8,173.7,162.3,130.4,128.3,112.6,55.4,43.6,35.3,31.69,29.0,26.3,23.8.HRMS(ESI)m / z calcd for C 15 H 20 NO3(M+H) + 262.1438, found 262.1436.

[0200] Example 15

[0201] The preparation method of N-benzoyl-azacyclooctan-2-one adopts the following reaction formula:

[0202]

[0203] The specific steps are as follows:

[0204] In a 10 mL electrolytic bottle, 0.4 mmol of 2-benzyl-2-aza[4.5]decan-3-one (CAS: 116725-67-8), electrolyte 2,6-dimethylpyridine perchlorate (10 mol%), electrocatalyst NHPI (20 mol%), 4 mL of acetonitrile-water binary mixed solvent (volume ratio 3:1 v / v) were added in sequence. A graphite plate was used as the anode (52 mm × 7 mm × 1.5 mm, the depth of the electrode inserted into the liquid surface was 20 mm, and the effective area in contact with the electrode liquid was 1.4 cm). 2 ), nickel plate as cathode (50mm×7mm×1.5mm, the depth of electrode insertion into the liquid surface is 20mm, and the effective area in contact with the electrode liquid is 1.4cm 2 Before the reaction begins, immerse the electrode in the reaction solution, ensuring it remains submerged below the liquid level throughout the reaction. Connect a pure oxygen bag to the reaction flask and puff the air into the reaction solution, ensuring sufficient oxygen throughout the reaction. The reaction is then conducted in constant current mode (2 mA). When TLC analysis reveals the disappearance of the product spot, the reaction is terminated. The reaction solution is then concentrated under reduced pressure and separated by silica gel column chromatography to obtain N-benzoyl-azacyclooctan-2-one in an 85% yield.

[0205] Example 16

[0206] The preparation method of N-benzoyl-azacyclooctan-2-one adopts the following reaction formula:

[0207]

[0208] The specific operating steps are the same as those in Example 15, and the reaction conditions are as follows with reference to Table 2:

[0209] Table 2 Effect of different reaction conditions on product separation yield

[0210]

[0211]

[0212] Reaction conditions were explored and optimized, and the results are shown in Table 2. Through a systematic examination of the reaction parameters, the optimal conditions were determined: in an undivided electrolytic cell, N-hydroxyphthalimide (NHPI, 20 mol%) as the electrocatalyst, an acetonitrile-water mixed solvent (volume ratio 3:1, v / v) as the reaction medium, 2,6-lutidine perchlorate (10 mol%) as the electrolyte, a nickel plate as the cathode, and a graphite plate as the anode, under an oxygen atmosphere at room temperature. Under these conditions, the target product, 2-benzoyl-2-azaspiro[4.5]decan-3-one (2a), was isolated in an 85% yield (Table 2, No. 1). Control experiments showed that the reaction did not occur when no current was input, no electrolyte was present, no NHPI was present, or the oxygen atmosphere was replaced by nitrogen (Table 2, Nos. 2-5). Electrode material screening revealed that the combination of a graphite anode and a nickel cathode was the most effective for the oxygenation reaction (Table 2, Nos. 6-9). In addition, the yield decreased significantly when the current intensity deviated from the optimized value (Table 2, Nos. 10-15), the electrolyte type or amount was changed (Table 2, Nos. 16-22), other electrocatalyst types, and NHPI loadings below or above 20 mol% (Table 2, Nos. 23-28). Further studies showed that the optimal reaction efficiency was achieved at room temperature (Table 2, Nos. 29-30), a solvent volume of 4 mL (Table 2, Nos. 31-34), and an acetonitrile-water mixture (Table 2, Nos. 35-41).

[0213] The above description is merely an illustrative description of the present invention and its embodiments, which is not restrictive. The embodiment shown in the embodiment is only one embodiment of the present invention, and the actual embodiment is not limited thereto. Therefore, if a person skilled in the art is inspired by the above description and, without departing from the purpose of the present invention, designs an embodiment and examples similar to the technical solution without creatively designing, they shall fall within the scope of protection of the present invention.

Claims

1. A method for preparing an N-substituted benzoyl cyclic lactam, characterized in that: Including steps, The N-substituted benzyl cyclic lactam shown in formula (I) is used as substrate, N-hydroxyphthalimide is used as catalyst, oxygen is used as oxygen source, and a binary mixed solvent containing electrolyte is used as electrolyte. 2 Electrochemical oxidation is performed under a current density of 1000 nm and an oxygen-sufficient environment to obtain an N-substituted benzoyl cyclic lactam represented by formula (II); Wherein, Z1 is one of spiro[4,5]heterocyclic group and C6-C7 heterocyclic group; R is selected from one of hydrogen, halogen, C1-C3 alkyl, C1-C3 alkoxy, and cyano.

2. The method for preparing an N-substituted benzoyl cyclic lactam according to claim 1, wherein When the Z1 ring is a spiro[4,5]heterocyclic group, the R is selected from one of halogen, C1-C3 alkyl, and C1-C3 alkoxy; Alternatively, when the Z1 ring is selected from one of C6-C7 heterocyclic groups, the R is selected from one of hydrogen, C1-C3 alkoxy, and cyano.

3. The method for preparing N-substituted benzoyl cyclic lactam according to claim 1, wherein The Z1 ring is a spiro[4,5]heterocyclic group, and the R is selected from one of halogen, methyl, and methoxy.

4. The method for preparing an N-substituted benzoyl cyclic lactam according to any one of claims 1 to 3, characterized in that: The electrolyte includes any one, two or more of 2,4,6-triethylpyridine perchlorate, 2,6-lutidine perchlorate, tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium hexafluorophosphate and tetra-n-butylammonium bromide.

5. The method for preparing N-substituted benzoyl cyclic lactam according to claim 4, wherein The binary mixed solvent includes any one of a binary mixed solvent of acetone and water and a binary mixed solvent of acetonitrile and water; Wherein, the volume ratio of acetone to water is (1-3):1; The volume ratio of the acetonitrile to water is (1-3):

1.

6. The method for preparing N-substituted benzoyl cyclic lactam according to claim 4, wherein The concentration of the substrate N-substituted benzyl cyclic lactam represented by formula (I) in the binary mixed solvent is 0.04 to 0.13 mol / L; And / or, based on the total amount of the N-substituted benzyl cyclic lactam represented by formula (I), the amount of the catalyst used is 20 to 30 mol%.

7. The method for preparing N-substituted benzoyl cyclic lactam according to claim 4, wherein The amount of the electrolyte used is 5 to 20 mol % based on the total amount of the N-substituted benzyl cyclic lactam represented by formula (I).

8. The method for preparing an N-substituted benzoyl cyclic lactam according to any one of claims 5 to 7, characterized in that: 0.14~2.1mA / cm 2 Electrochemical oxidation was carried out at a current density of .

9. The method for preparing N-substituted benzoyl cyclic lactam according to claim 8, wherein The anode is graphite, and the cathode is nickel.

10. The N-substituted benzoyl cyclic lactam represented by formula (II) is characterized in that: The N-substituted benzoyl cyclic lactam is prepared according to any one of claims 1 to 9; Wherein, the Z1 ring is a spiro[4,5]heterocyclic group; the R is selected from one of halogen, C1-C3 alkyl, and C1-C3 alkoxy; Alternatively, the Z1 ring is selected from one of C6-C7 heterocyclic groups; and the R is selected from one of hydrogen, C1-C3 alkoxy, and cyano.

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