CN109111374B

CN109111374B - Method for synthesizing alpha-oxo-acetamidine by catalyzing aryl ketone with copper salt by using aromatic amine and amide as nitrogen source

Info

Publication number: CN109111374B
Application number: CN201811208642.5A
Authority: CN
Inventors: 刘强; 谢典科; 郭灿城
Original assignee: Yuanjiang Hualong Catalyst Technology Co ltd
Current assignee: Yuanjiang Hualong Catalyst Technology Co ltd
Priority date: 2018-10-17
Filing date: 2018-10-17
Publication date: 2021-03-09
Anticipated expiration: 2038-10-17
Also published as: CN109111374A

Abstract

The invention discloses a method for synthesizing alpha-oxo-acetamidine by catalyzing aryl ketone with copper salt by taking aromatic amine and amide as nitrogen sources, which comprises the following steps of carrying out one-pot reaction on aryl ketone and aryl amine in an oxygen-containing atmosphere in a DMF (dimethyl formamide) solution system containing copper salt/1, 10-phenanthroline catalyst, di-tert-butyl peroxide and organic base compound to obtain an alpha-oxo-acetamidine compound; according to the method, aromatic amine and amide are used as nitrogen sources, under mild reaction conditions, copper salt is used for catalyzing aryl ketone to perform one-pot reaction to synthesize alpha-oxo-acetamidine at high yield, and the method has the advantages of wide and easily-obtained raw material source, environmental friendliness, low price, simplicity in operation and contribution to industrial production.

Description

Method for synthesizing alpha-oxo-acetamidine by catalyzing aryl ketone with copper salt by using aromatic amine and amide as nitrogen source

Technical Field

The invention relates to a synthesis method of amidine derivatives, in particular to a method for synthesizing alpha-oxo-acetamidine by using aromatic amine and amide as nitrogen sources and catalyzing one-pot reaction of alpha-methyl ketone, aromatic amine and amide with copper salt/1, 10-phenanthroline, and belongs to the field of synthesis of organic intermediates.

Background

Amidines and derivatives thereof are compounds having an N-C ═ N structure, are ubiquitous in natural products and bioactive molecules, and have wide applications in the fields of pharmaceutical chemistry, organic synthetic intermediates, catalyst design, material science, supramolecular chemistry, ligand chemistry and the like. The classical Synthesis methods of amidines include ketoxime method, nitrile ammonolysis method, orthoformate method and amide acetal method, and some new advances have been made recently for synthesizing amidine compounds by C-N coupling reaction catalyzed by transition metal, but mainly using amine as nitrogen source (Zhang C, Zhang L, Jiano N&Catalysis.2012,354(7):1293-1300；Liu X X,Wu Z Y,He Y Q,et al.Advanced Synthesis&2385-; Martinez-Ariza G, McConnell N, Hulme C.organic Letters,2016,18(8): 1864-. While only a series of alpha-ketoamides could be synthesized using amides as nitrogen source (Li D-k, Wang L, et al. chem. Commun.2013,49,3640-3642; Mai W-P, Qu L-B, et al. chemical Communication,2012,48, 10117-10119). In 2014, Wang et al reported oxidative coupling of arylmethylamines and N-substituted carboxamides. The reaction is carried out by₂(sp) of/TBHP by arylmethylamine³) Of C-N bonds and N-substituted carboxamides²) Two cleavage of the C-N bond. (Gao L-F, Tang H-M, Wang Z-Y.Chem.Commun.2014,50,4085-4088). Recently, Wu Anxin et al reported various formulas I₂Assisting methyl ketone compound C (sp)³) Cyclization of the-H bond forms the α -oxoacetylcycloamidine derivative (Zhu Y, Fei Z, Liu M, et al. organic Letters,2013,15(2):378-381.Zhang J, Wu X, Gao Q, et al. organic Letters,2017,19(2): 408-411.). However, these methods can only synthesize cyclic amidine compounds, and are not suitable for synthesizing open-chain amidine compounds.

Disclosure of Invention

Aiming at the defects of the existing synthesis method of amidine and derivatives thereof, the invention aims to provide a method for synthesizing alpha-oxo-acetamidine with high yield by using aromatic amine and amide as nitrogen sources and catalyzing alpha-aryl ketone one-pot reaction by copper salt/1, 10-phenanthroline under mild reaction conditions.

In order to achieve the technical purpose, the invention provides a method for synthesizing alpha-oxoacetamidine by catalyzing aryl ketone with copper salt by using aromatic amine and amide as nitrogen sources, which comprises the steps of carrying out one-pot reaction on aryl ketone and aryl amine in a DMF solution system containing copper salt/1, 10-phenanthroline catalyst, di-tert-butyl peroxide and organic base compound in an oxygen-containing atmosphere to obtain an alpha-oxoacetamidine compound;

the aryl ketone has the structure of formula 1:

the arylamine has the structure of formula 2:

the alpha-oxoacetamidine compound has the structure of formula 3:

wherein the content of the first and second substances,

R₁at least one selected from alkyl, halogen substituent, cyano, nitro, amino, alkoxy and alkoxy acyl;

ar is selected from aryl.

The conjugated system of the benzene ring in the aryl ketone can form p-pi conjugation with carbonyl, can obviously increase the reaction activity of alpha-methyl, and has a relative ratio of R to R₁When the substituent group is selected from alkyl and the like, the yield of the target product is obviously improved. Aryl ketones are more commonly phenyl or substituted phenyl. The benzene ring of the substituted phenyl group contains 1 substituent. The position of the substituent is not limited, and may be ortho, meta or para. The selection of the type of the substituent on the benzene ring has little influence on the synthesis of the target product, and has a wide selection range, such as can be selected from alkyl (such as C)₁～C₅Such as, in particular, methyl, ethyl, propyl, isopropyl, isobutyl, etc.), halogen substituents (such as fluorine, chlorine, bromine or iodine), cyano, nitro, amino, alkoxy (such as C)₁～C₅Short-chain alkoxy groups) or alkoxyacyl groups (e.g., methoxycarbonyl, ethoxyacyl). Most preferred aryl ketones include: acetophenone, 2-methylacetophenone, 3-methylacetophenone, 4-methylacetophenone, 3-fluoroacetophenone, 4-chloroacetophenone, 4-iodoacetophenone, 4-nitrileacetophenone, 4-nitroacetophenone, 4-aminoacetophenone, 4-methoxyacetophenone, methyl 4-acetylbenzoate, 4-ethoxyacetophenone.

In the arylamine of the present invention, Ar is selected from aryl groups which may theoretically be phenyl, substituted phenyl, condensed ring groups (such as naphthalene and naphthalene derivatives), and the like. The substituted phenyl group can comprise 1-2 substituents, and the substituents can be selected from at least one of alkyl, halogen substituents, alkoxy and nitro. Preferably, it contains a substituent. The position of the substituent is not limited, but is preferably para-position and meta-position, which can reduce steric hindrance. The choice of the substituent on the benzene ring has a relatively large influence on the synthesis of the desired product, and is preferably an electron donating group or a weakly electron withdrawing group, which may be selected from alkyl (e.g. C)₁～C₅Such as, in particular, methyl, ethyl, propyl, isopropylPropyl, isobutyl, etc.), halogen substituents (e.g. fluorine, chlorine, bromine or iodine), alkoxy groups (e.g. C)₁～C₅Such as methoxy, ethoxy) or the like, or a strong electron withdrawing group such as nitro, but the yield of the target product is significantly reduced when the nitro substituent is selected relative to the alkyl, alkoxy, or other substituent. Most preferred arylamines include: 2-methylaniline, 3-methylaniline, 4-methylaniline, 3-chloroaniline, 3-bromoaniline, 3-iodoaniline, 3, 5-dimethoxyaniline, 4-fluoroaniline, 4-chloroaniline, 4-bromoaniline, 4-iodoaniline, 4-isopropylaniline or 4-nitroaniline.

In a preferred embodiment, the organic alkali compound comprises at least one of sodium benzoate, potassium ethoxide, sodium methoxide, and potassium methoxide. Sodium benzoate is more preferred.

In a preferable scheme, the mol ratio of the alpha-methyl ketone to the organic base compound is 1: 1.5-2.5; more preferably 1:1.8 to 2.2.

In a preferred embodiment, the molar ratio of the alpha-methyl ketone to the copper salt is 1: 0.2-0.3.

In a preferable scheme, the molar ratio of the alpha-methyl ketone to the di-tert-butyl peroxide initiator is 1: 2-4.

In a preferable scheme, the molar ratio of copper salt to 1, 10-phenanthroline in the copper salt/1, 10-phenanthroline catalyst is 1: 0.5-1.5; most preferably 1:1. Preferred copper salts include at least one of copper chloride, cuprous chloride, copper acetate, and copper acetylacetonate. The most preferred copper salt is copper chloride. The catalytic activity of copper salt can be obviously improved by introducing a proper amount of 1, 10-phenanthroline ligand into the catalyst

The reaction conditions are as follows: reacting for 24-42 h at 100-130 ℃ in air or oxygen atmosphere. In a more preferred embodiment, the reaction conditions are as follows: reacting for 28-38 h at 115-125 ℃ in air or oxygen atmosphere.

The oxygen-containing atmosphere in the present invention may be air or a pure oxygen atmosphere, and is preferably a pure oxygen atmosphere.

The DMF solution system mainly contains N, N-dimethylformamide which is a benign reaction solvent and one of important nitrogen sources in the amidine synthesis process, other solvents cannot be replaced, the reaction system can contain organic solvents such as dimethyl sulfoxide, toluene and the like, and the reaction effect is obviously poorer than that of the single DMF solvent.

In the synthesis process of the alpha-oxoacetamidine, aryl ketone and aryl amine react according to an equal molar ratio, and formamide can be used as a solvent and a reaction substrate and can be in large excess.

In the preferred scheme, after the reaction is finished, a product is separated and purified by adopting a column chromatography; the eluent adopted by the column chromatography is a mixed solvent of petroleum ether and ethyl acetate, wherein the volume ratio of the petroleum ether to the ethyl acetate is (20-40): 1.

The invention provides a method for synthesizing alpha-oxoacetamidine, which has the following reaction equation:

the reaction principle of the above reaction is: under weak alkaline environment with Cu²⁺Or Cu⁺As a catalyst, DTBP is used as a free radical initiator, aryl ketone, aromatic amine and formamide are used as raw materials to synthesize the alpha-oxoacetoacetamidine compound through oxidative cross coupling.

Compared with the existing synthesis method and technology, the invention has the following advantages and effects:

1) the invention realizes three C (sp) of methyl in aryl ketone for the first time³) Oxidative cross-coupling of-H direct amidination.

2) The invention adopts common copper salt/1, 10-phenanthroline as the catalyst, avoids using other noble metals or transition metals as the catalyst, has wide sources and low cost, and meets the requirements of environmental protection, economy, saving and the like.

3) The reaction process of the invention is carried out in oxygen-containing atmosphere and at lower temperature, and the reaction condition is mild.

4) The method has higher yield of the synthesized alpha-oxoacetoacetamidine compound.

5) The synthesis process of the invention adopts a one-pot reaction, and has the advantages of few reaction steps and simple operation.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of (E) -N, N-dimethyl-2-oxo-N', 2-diphenylacetamidine.

FIG. 2 is a nuclear magnetic carbon spectrum of (E) -N, N-dimethyl-2-oxo-N', 2-diphenylacetamidine.

Detailed Description

The present invention will be described in further detail with reference to specific examples, but the embodiments of the present invention are not limited thereto, and may be performed with reference to conventional techniques for process parameters not specifically mentioned.

All reactions were performed in Schlenk tubes unless otherwise noted.

All reaction starting solvents were obtained from commercial sources and used without further purification.

The product is separated by a silica gel chromatographic column and silica gel (the granularity is 300-400 meshes).

1H NMR (400MHz) and 13C NMR (100MHz) measurements were carried out using a Bruker ADVANCE III spectrometer with CDCl₃As solvent, TMS as internal standard, chemical shifts in parts per million (ppm) and reference shifts of 0.0ppm tetramethylsilane. The following abbreviations (or combinations thereof) are used to explain the multiplicity: s is singlet, d is doublet, t is triplet, q is quartet, m is multiplet, br is broad. Coupling constant J is in Hertz (Hz). Chemical shifts are expressed in ppm, with the center line for the triplet state referenced to deuterated chloroform at 77.0ppm or the center line for the heptad state referenced to deuterated DMSO at 39.52 ppm.

1. Condition optimization experiment:

for example, the construction of α -oxoacetamidins from acetophenone, N-dimethylformamide and aniline, various factors affecting the selection of catalysts, basic compounds, reaction solvents, initiators and the like, and the selection of conditions such as reaction temperature, time and the like have been studied to find optimal reaction conditions.

The reaction route is as follows:

TABLE 1 results of the reaction of acetophenone with N, N-dimethylformamide and aniline under different conditions

^[a]Reaction conditions of alpha-methyl ketone (0.5mmol), arylamine (0.5mmol), catalyst (0.1mmol), base compound (base) (0.5mmol), initiator (oxidantadditive) and solvent (solvent) (2mL) in O₂Reacting for 36 hours at 120 ℃ under the atmosphere;^[b]yield;^[c]1, 10-phenanthroline monohydrate (0.1mmol).^[d]An air atmosphere;^[e]a nitrogen atmosphere;^[f]reacting for 12 h;^[g]reacting for 24 hours; DTBP ═ di-tert-butyl peroxide, TBHP ═ tert-butyl hydroperoxide, BPO ═ benzoyl peroxide, AIBN ═ 2,2' -azobis (2-methylpropanenitrile), DMSO ═ dimethyl sulfoxide, DMF ═ N, N-dimethylformamide, THF ═ tetrahydrofuran.

1) Selection and amount of catalyst

As can be seen from items 1 and 15-20 in Table 1, the use of a copper salt or cuprous salt catalyst has a great influence on the synthesis process of amidine, and the target product can hardly be obtained without adding a copper salt or cuprous salt catalyst. Various cupric salts and cuprous salts have certain catalytic activity on the reaction, but cuprous chloride and cupric chloride taking anions as chloride ions have the best catalytic effect, and the catalytic effect is far better than that of cupric salts or cuprous salts of anions such as bromine, iodine and the like. Meanwhile, the organic copper salt can also obtain higher yield, but the catalytic effect is slightly worse than that of copper chloride and cuprous chloride. The amount of catalyst used is not so great as to affect the reaction, but the catalytic effect is more prominent at 20% molar relative to the substrate. It is worth to say that when copper salt and cuprous chloride are used as catalysts, a proper amount of 1, 10-phenanthroline is added as a complex, so that the catalytic activity of the copper chloride and the cuprous chloride can be obviously improved, as in item 9.

2) Selection and amount of free radical initiator

The invention tries for several common free radical initiators in the field, as can be seen from items 1-4 in table 1, the free radical initiators of di-tert-butyl peroxide, tert-butyl hydroperoxide, benzoyl peroxide, 2 '-azobis (2-methylpropanenitrile), and the like have good reaction effect only when the di-tert-butyl peroxide is used as the free radical initiator, and almost no target product is obtained when the benzoyl peroxide, 2' -azobis (2-methylpropanenitrile), and the like are used as the free radical initiator, while only a small amount of target product is obtained when the tert-butyl hydroperoxide is selected as the free radical initiator. Thus, di-tert-butyl peroxide is the best free radical initiator. The amount of the free radical initiator should be appropriate, the yield of the target product is low due to too little free radical generated by using too little free radical initiator, and the yield of the target product is reduced due to the side reaction caused by too much free radical generated by using too much free radical initiator. Therefore, if the amount of the radical initiator is too much or too little, the yield of the target product is reduced, specifically, items 1 and 5 to 8 in Table 1.

3) Selection of base compounds

A large number of experiments show that the reaction must be carried out under weakly alkaline conditions, but different weakly alkaline compounds have large influence on the reaction, such as items 1 and 21-25 in Table 1. The weakly basic compound is preferably an organic Lewis base selected from organic carboxylates, organic alkoxides and the like, and the reaction proceeds smoothly, but the target product is hardly obtained from inorganic carbonates and the like. Organic Lewis bases work best with alkali metal benzoate salts.

4) Selection of reaction temperature

The reaction temperature is an important factor influencing the chemical reaction process, and the yield of the reaction at different temperatures within the temperature range of 80-140 ℃ is considered in the invention, as shown in items 1 and 31-33 in Table 1. Within the temperature range of 80-120 ℃, the yield of the corresponding target product is increased along with the temperature increase, but when the temperature reaches more than 120 ℃, the reaction yield is properly reduced, so that 120 ℃ is the optimal temperature of the reaction.

5) Selection of reaction solvent

DMF is irreplaceable to other solvents because DMF is used as a reaction substrate and a solvent during the synthesis of dihydropyrane. The solvent of the invention can adopt DMF, and simultaneously can also adopt a mixed solvent of DMF and other solvents, such as DMSO, but the effect is poorer than that of adopting single DMF (such as items 26-30 in Table 1, and the ratio of DMF to other solvents is 1: 1).

6) Selection of reaction atmosphere

As can be seen from items 1, 13 and 14 in Table 1, the reaction must be carried out smoothly in an oxygen-containing atmosphere, the reaction cannot be carried out smoothly in an oxygen-isolated atmosphere, and the higher the oxygen content in an oxygen-containing atmosphere, the more favorable the reaction is, and the more favorable it is to carry out the reaction in a pure oxygen atmosphere.

2. Examples 1 to 29. The following examples were all carried out under optimized conditions:

example 1

Adding 0.5mmol of acetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N, N-dimethyl-2-oxo-N', 2-diphenylacetamidine having the structure shown below:

the compound was a yellow solid in 85% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.78(d,J＝7.6Hz,2H),7.51(t,J＝7.4Hz,1H),7.38(t,J＝7.6Hz,2H),6.99(t,J＝7.6Hz,2H),6.75(t,J＝7.4Hz,1H),6.70(d,J＝7.6Hz,2H),3.03(s,6H).¹³C NMR(101MHz,CDCl₃)δ194.50,156.82,148.65,134.48,134.38,129.23,128.83,128.30,122.61,122.19,37.23.

example 2

Adding 0.5mmol of 2-methylacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N, N-dimethyl-2-oxo-N' -phenyl-2- (o-tolyl) acetamidine structure is shown as follows:

the compound was a yellow solid with a yield of 80% and the nuclear magnetic data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.65(d,J＝7.6Hz,1H),7.31(t,J＝7.4Hz,1H),7.22(t,J＝7.8Hz,1H),7.06(d,J＝7.6Hz,1H),6.96(t,J＝7.4Hz,2H),6.73(t,J＝7.6Hz,1H),6.62(d,J＝7.6Hz,2H),3.06(s,6H),2.32(s,3H).¹³C NMR(101MHz,CDCl₃)δ196.24,158.07,148.89,140.56,133.83,133.14,132.11,131.93,128.15,125.88,122.65,122.03,37.27,21.20.

example 3

Adding 0.5mmol of 3-methylacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N, N-dimethyl-2-oxo-N' -phenyl-3- (m-tolyl) acetamidine structure is shown as follows:

the compound was a yellow solid in 86% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.50(s,2H),7.22(d,J＝7.2Hz,1H),7.18(d,J＝6.8Hz,1H),6.90(t,J＝7.2Hz,2H),6.64(dd,J＝16.4,8.0Hz,3H),2.92(s,6H),2.23(s,3H).¹³C NMR(101MHz,CDCl₃)δ193.61,155.85,147.79,137.65,134.23,133.38,128.36,127.67,127.24,125.76,121.54,121.07,36.34,20.17.

example 4

Adding 0.5mmol of 4-methylacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N, N-dimethyl-2-oxo-N' -phenyl-2- (p-tolyl) acetamidine structure is shown as follows:

the compound was a yellow solid in 89% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.68(d,J＝7.6Hz,2H),7.18(d,J＝7.6Hz,2H),7.00(t,J＝7.4Hz,2H),6.76(d,J＝7.2Hz,1H),6.71(d,J＝7.6Hz,2H),3.01(s,6H),2.35(s,3H).¹³C NMR(101MHz,CDCl₃)δ194.05,156.97,148.83,145.59,132.11,129.59,129.42,128.29,122.61,122.10,37.23,21.85.

example 5

Adding 0.5mmol of 3-fluoroacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (3-fluorophenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 79% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.57(d,J＝7.6Hz,1H),7.44(d,J＝8.8Hz,1H),7.36(dd,J＝13.8,7.2Hz,1H),7.20(t,J＝8.2Hz,1H),7.00(t,J＝7.4Hz,2H),6.76(t,J＝7.2Hz,1H),6.68(d,J＝7.6Hz,2H),3.02(s,6H).¹³C NMR(101MHz,CDCl₃)δ193.44,163.99,161.52,156.23,148.46,136.54,136.48,130.65,130.58,128.41,125.25,125.22,122.54,122.36,121.60,121.38,115.5,115.32,37.32.

example 6

Adding 0.5mmol of 4-fluoroacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-fluorophenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 83% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.85–7.73(m,2H),7.06-6.98(m,4H),6.77(t,J＝7.4Hz,1H),6.69(d,J＝7.6Hz,2H),3.03(s,6H).¹³C NMR(101MHz,CDCl₃)δ192.73,167.66,165.10,156.54,148.37,132.09,131.99,130.96,130.93,128.39,122.56,122.38,116.29,116.07,37.28.

example 7

Adding 0.5mmol of 4-chloroacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-chlorphenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 78% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.71(d,J＝7.6Hz,2H),7.35(d,J＝7.2Hz,2H),7.01(t,J＝7.2Hz,2H),6.77(t,J＝7.2Hz,1H),6.69(d,J＝7.6Hz,2H),3.02(s,6H).¹³C NMR(101MHz,CDCl₃)δ192.22,155.32,147.30,139.96,131.77,129.52,128.25,127.39,121.52,121.39,36.32.

example 8

Adding 0.5mmol of 4-iodoacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-iodophenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 67% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.75(d,J＝8.0Hz,2H),7.47(d,J＝7.6Hz,2H),7.01(t,J＝7.4Hz,2H),6.79(t,J＝7.4Hz,1H),6.69(d,J＝7.6Hz,2H),3.03(s,6H).¹³C NMR(101MHz,CDCl₃)δ192.83,155.23,147.27,137.21,132.59,129.32,127.39,121.51,121.37,102.09,36.28.

example 9

Adding 0.5mmol of 4-nitrile acetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-cyanophenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 82% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.83(d,J＝7.6Hz,2H),7.66(d,J＝7.6Hz,2H),6.99(t,J＝7.4Hz,2H),6.76(t,J＝7.4Hz,1H),6.65(d,J＝7.6Hz,2H),3.03(s,6H).¹³C NMR(101MHz,CDCl₃)δ193.40,155.79,147.80,137.11,132.66,129.37,128.54,122.71,122.55,117.61,117.39,37.49.

example 10

Adding 0.5mmol of 4-aminoacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-aminophenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 63% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.59(d,J＝8.4Hz,2H),7.00(t,J＝7.6Hz,2H),6.77-6.72(m,3H),6.49(d,J＝8.0Hz,2H),4.28(s,2H),2.98(s,6H).¹³C NMR(101MHz,CDCl₃)δ190.79,156.61,151.51,148.13,131.10,127.23,123.80,121.62,120.97,112.79,36.36.

example 11

Adding 0.5mmol of 4-nitroacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N-dimethyl-2- (4-nitrophenyl) -2-oxo-N' -phenylacetamidine is shown as the following formula:

example 12

Adding 0.5mmol of 4-methyl acetylbenzoate, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the methyl-4- (2- (dimethylamino) -2- (phenylimino) acetyl) benzoate is shown as the following formula:

the compound was a yellow solid in 69% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ8.02(d,J＝7.2Hz,2H),7.81(d,J＝7.6Hz,2H),6.97(t,J＝7.2Hz,2H),6.73(t,J＝7.4Hz,1H),6.66(d,J＝7.6Hz,2H),3.90(s,3H),3.03(s,6H).¹³C NMR(101MHz,CDCl₃)δ194.21,165.91,156.37,148.29,137.39,134.84,130.00,129.02,128.41,122.58,122.40,52.55,37.40.

example 13

Adding 0.5mmol of 4-methoxyacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-methoxyphenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.76(d,J＝7.6Hz,2H),7.01(t,J＝7.2Hz,2H),6.84(d,J＝7.6Hz,2H),6.75(dd,J＝19.2,7.6Hz,3H),3.82(s,3H),3.02(s,6H).¹³C NMR(101MHz,CDCl₃)δ192.67,164.53,157.14,148.82,148.82,131.79,128.30,127.65,122.60,122.13,114.14,55.53,37.37.

example 14

Adding 0.5mmol of 4-ethoxyacetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-ethoxyphenyl) -N, N-dimethyl-2-oxo-N' -phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 81% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.68(d,J＝8.0Hz,2H),6.94(t,J＝7.4Hz,2H),6.76(d,J＝8.4Hz,2H),6.68(dd,J＝16.6,7.8Hz,3H),3.97(q,J＝6.8Hz,2H),2.95(s,6H),1.33(t,J＝7.0Hz,3H).¹³C NMR(101MHz,CDCl₃)δ192.70,163.98,157.12,149.00,131.78,128.27,127.48,122.55,122.03,114.52,63.88,37.20,14.61.

example 15

Adding 0.5mmol of 4-tert-butyl acetophenone, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -2- (4-tert-butylphenyl) -N, N-dimethyl-2-oxo-N' -phenylacetamidine is shown as follows:

¹H NMR(400MHz,CDCl₃)δ7.72(d,J＝7.6Hz,2H),7.39(d,J＝8.0Hz,2H),7.01(t,J＝7.2Hz,2H),6.75(dd,J＝16.2,7.2Hz,1H),3.02(s,6H),1.29(s,9H).¹³C NMR(101MHz,CDCl₃)δ192.94,157.32,155.93,147.67,130.92,128.20,127.24,124.81,121.64,121.07,36.14,34.24,29.93.

example 16

Adding 0.5mmol of 3, 3-dimethylbutane-2-one, 0.5mmol of aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N,3, 3-tetramethyl-2-oxo-N' -phenylbutanamidine is shown as the following formula:

the compound was a yellow solid in 53% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.17(t,J＝7.6Hz,2H),6.93(d,J＝7.6Hz,1H),6.78(d,J＝7.6Hz,2H),2.96(s,6H),0.82(s,9H).¹³C NMR(101MHz,CDCl₃)δ211.46,156.71,147.91,127.56,122.29,121.40,41.80,36.35,25.44.

example 17

Adding 0.5mmol of acetophenone, 0.5mmol of 2-methylaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N-dimethyl-2-oxo-2-phenyl-N' - (o-tolyl) acetamidine is shown as the following formula:

the compound was a yellow solid in 77% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.75(d,J＝7.6Hz,2H),7.51(t,J＝7.4Hz,1H),7.38(t,J＝7.4Hz,2H),6.90(d,J＝7.2Hz,1H),6.79(t,J＝7.4Hz,1H),6.68(t,J＝7.4Hz,1H),6.51(d,J＝7.6Hz,1H),3.04(s,6H),2.17(s,3H).¹³C NMR(101MHz,CDCl₃)δ194.61,155.97,146.89,134.69,134.33,130.32,129.74,128.85,128.75,125.65,122.33,121.89,37.21,18.37.

example 18

Adding 0.5mmol of acetophenone, 0.5mmol of 3-methylaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N-dimethyl-2-oxo-2-phenyl-N' - (m-tolyl) acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.78(d,J＝7.6Hz,1H),7.51(t,J＝7.2Hz,1H),7.38(t,J＝7.5Hz,1H),6.86(t,J＝7.6Hz,1H),6.58–6.52(m,1H),6.48(d,J＝7.8Hz,1H),3.01(s,3H),2.11(s,2H).¹³C NMR(101MHz,CDCl₃)δ194.58,156.65,148.56,137.87,134.58,134.30,129.22,128.78,128.06,123.42,122.98,119.51,37.28,21.19.

example 19

Adding 0.5mmol of acetophenone, 0.5mmol of 4-methylaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N-dimethyl-2-oxo-2-phenyl-N' - (p-tolyl) acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.79(d,J＝7.4Hz,1H),7.51(t,J＝7.2Hz,1H),7.38(t,J＝7.4Hz,1H),6.79(d,J＝7.3Hz,1H),6.59(d,J＝7.1Hz,1H),3.00(s,3H),2.10(s,2H).¹³C NMR(101MHz,CDCl₃)δ194.88,156.80,146.02,134.51,134.34,131.32,129.25,128.93,128.82,122.34,37.33,20.67.

example 20

Adding 0.5mmol of acetophenone, 0.5mmol of 3-chloroaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N' - (3-chlorophenyl) -N, N-dimethyl-2-oxo-2-phenylacetamidine having the structure shown in the following formula:

¹H NMR(400MHz,CDCl₃)δ7.76(d,J＝7.6Hz,2H),7.52(t,J＝7.2Hz,1H),7.39(t,J＝7.4Hz,2H),6.89(t,J＝8.0Hz,1H),6.71(s,2H),6.56(d,J＝8.0Hz,2H),3.01(d,J＝91.2Hz,6H).¹³C NMR(101MHz,CDCl₃)δ193.79,157.02,150.25,134.67,134.26,133.66,129.24,129.19,128.99,122.84,122.16,120.84,38.08,36.48.

example 21

Adding 0.5mmol of acetophenone, 0.5mmol of 3-bromoaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (3-bromophenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.76(d,J＝7.6Hz,2H),7.52(t,J＝7.4Hz,1H),7.39(t,J＝7.2Hz,2H),6.83(dd,J＝17.4,8.8Hz,3H),6.60(d,J＝7.2Hz,1H),3.00(d,J＝87.9Hz,6H).¹³C NMR(101MHz,CDCl₃)δ193.75,157.04,150.43,134.69,134.27,129.54,129.18,129.00,125.75,125.02,121.86,121.26,38.04,36.48.

example 22

Adding 0.5mmol of acetophenone, 0.5mmol of 3-iodoaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (3-iodophenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.75(d,J＝7.2Hz,2H),7.52(t,J＝7.4Hz,1H),7.38(t,J＝7.4Hz,2H),7.05(d,J＝13.2Hz,2H),6.68(t,J＝7.6Hz,1H),6.63(d,J＝7.6Hz,1H),2.99(d,J＝93.1Hz,3H).¹³C NMR(101MHz,CDCl₃)δ193.94,156.88,148.63,137.21,134.74,134.17,129.22,129.04,124.90,85.66,37.33,36.48.

example 23

Adding 0.5mmol of acetophenone, 0.5mmol of 4-fluoroaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and then separating and purifying by column chromatography to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (4-fluorophenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 84% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.75(d,J＝7.6Hz,1H),7.51(t,J＝7.3Hz,1H),7.37(t,J＝7.4Hz,1H),6.70–6.58(m,2H),2.97(s,3H).¹³C NMR(101MHz,CDCl₃)δ194.47,159.74,157.35,144.87,144.84,134.57,134.32,129.17,128.93,123.70,123.62,114.97,114.75,37.53.

example 24

Adding 0.5mmol of acetophenone, 0.5mmol of 4-chloroaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N' - (4-chlorophenyl) -N, N-dimethyl-2-oxo-2-phenylacetamidine having the structure shown in the following formula:

the compound was a yellow solid in 87% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.74(d,J＝7.6Hz,2H),7.49(t,J＝7.4Hz,1H),7.36(t,J＝7.4Hz,2H),6.91(d,J＝7.6Hz,2H),6.61(d,J＝7.6Hz,2H),2.98(d,J＝89.6Hz,3H).¹³C NMR(101MHz,CDCl₃)δ194.07,157.07,147.51,134.70,134.20,129.19,129.01,128.30,127.22,123.90,37.95,36.48.

example 25

Adding 0.5mmol of acetophenone, 0.5mmol of 4-bromoaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (4-bromophenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.76(d,J＝7.6Hz,2H),7.53(t,J＝7.2Hz,1H),7.40(t,J＝7.6Hz,2H),7.08(d,J＝8.0Hz,2H),6.57(d,J＝7.6Hz,2H),3.00(d,J＝76.6Hz,3H).¹³C NMR(101MHz,CDCl₃)δ193.03,155.91,146.96,133.65,133.20,130.22,128.19,127.97,123.31,113.98,36.98,35.54.

example 26

Adding 0.5mmol of acetophenone, 0.5mmol of 4-iodoaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (4-iodophenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 76% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.77(d,J＝7.6Hz,2H),7.53(t,J＝7.2Hz,1H),7.39(t,J＝7.4Hz,2H),7.27(d,J＝7.6Hz,2H),6.47(d,J＝7.6Hz,6H),3.00(d,J＝94.0Hz,6H).¹³C NMR(101MHz,CDCl₃)δ193.94,156.88,148.63,137.21,134.74,134.17,129.22,129.04,124.90,85.66,37.33,36.48.

example 27

Adding 0.5mmol of acetophenone, 0.5mmol of 4-isopropyl aniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N' - (4-isopropylphenyl) -N, N-dimethyl-2-oxo-2-phenyl acetamidine is shown as the following formula:

¹H NMR(400MHz,CDCl₃)δ7.76(d,J＝7.2Hz,2H),7.50(t,J＝7.4Hz,1H),7.37(t,J＝7.4Hz,2H),6.83(d,J＝6.8Hz,2H),6.61(d,J＝7.2Hz,2H),3.01(s,6H),2.70-2.63(m,1H),1.06(d,J＝6.8Hz,6H).¹³C NMR(101MHz,CDCl₃)δ194.93,156.80,146.14,142.51,134.65,134.24,129.19,128.75,126.22,122.34,37.20,33.25,23.96.

example 28

Adding 0.5mmol of acetophenone, 0.5mmol of 3, 5-dimethoxyaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating and magnetically stirring at 120 ℃ under an oxygen atmosphere, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) -N' - (3, 5-dimethoxyphenyl) -N, N-dimethyl-2-oxo-2-phenylacetamidine having the structure shown in the following formula:

the compound was a yellow solid in 75% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.79(d,J＝7.6Hz,2H),7.50(t,J＝7.4Hz,1H),7.38(t,J＝7.4Hz,2H),6.39(s,1H),6.32(s,2H),3.00(s,6H),2.05(s,6H).¹³C NMR(101MHz,CDCl₃)δ194.62,156.56,148.44,137.63,134.71,134.24,129.22,128.76,123.97,120.40,37.29,21.10.

example 29

Adding 0.5mmol of acetophenone, 0.5mmol of 4-nitroaniline, 0.1mmol of anhydrous copper chloride, 0.1mmol of 1, 10-phenanthroline, 1mmol of potassium benzoate, 2 mmol of DTBP and 2ml of DMF solvent into a reaction test tube, heating at 120 ℃ under an oxygen atmosphere, magnetically stirring, reacting for 36 hours, cooling to room temperature, concentrating, and performing column chromatography separation and purification to obtain a target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate. (E) The structure of the (E) -N, N-dimethyl-N' - (4-nitrophenyl) -2-oxo-2-phenyl acetamidine is shown as the following formula:

the compound was a yellow solid in 47% yield with the following nuclear magnetic data:

¹H NMR(400MHz,CDCl₃)δ7.87(d,J＝8.8Hz,2H),7.75(d,J＝7.6Hz,2H),7.53(t,J＝7.4Hz,1H),7.39(t,J＝7.8Hz,2H),6.73(d,J＝8.8Hz,2H),3.05(d,J＝102.8Hz,6H).¹³C NMR(101MHz,CDCl₃)δ192.81,156.64,155.94,142.47,135.07,133.82,129.23,129.19,124.44,122.69,38.21,36.53.

Claims

1. a method for synthesizing alpha-oxo-acetamidine by catalyzing aryl ketone with copper salt by using aromatic amine and amide as nitrogen sources is characterized in that: in an oxygen-containing atmosphere, performing one-pot reaction on aryl ketone and aryl amine in a DMF solution system containing copper salt/1, 10-phenanthroline catalyst, di-tert-butyl peroxide and an organic base compound to obtain an alpha-oxoacetyl amidine compound;

the aryl ketone has the structure of formula 1:

the arylamine has the structure of formula 2:

the alpha-oxoacetamidine compound has the structure of formula 3:

wherein the content of the first and second substances,

R₁at least one selected from alkyl, halogen substituent, cyano, nitro, amino, alkoxy and alkoxy acyl; the alkyl group is C₁～C₅Alkyl groups of (a); the halogen substituent is a fluorine substituent, a chlorine substituent, a bromine substituent or an iodine substituent; the alkoxy is C₁～C₅Alkoxy group of (a); the alkoxy acyl is C₁～C₅An alkoxyacyl group of (a);

ar is selected from phenyl or substituted phenyl; the substituted phenyl group contains 1-2 substituents; the substituent is selected from C₁～C₅Alkyl, fluoro, chloro, bromo, iodo, C₁～C₅At least one of alkoxy and nitro of (1);

the copper salt comprises at least one of copper chloride, cuprous chloride, copper acetate and copper acetylacetonate; the organic alkali compound comprises at least one of sodium benzoate, potassium ethoxide, sodium methoxide and potassium methoxide;

the reaction conditions are as follows: reacting for 24-42 h at 100-130 ℃ in air or oxygen atmosphere.

2. The method of claim 1, wherein the synthesis of α -oxoacetamidine from copper salt catalyzed aryl ketone using aromatic amine and amide as nitrogen source is characterized by:

the mol ratio of the alpha-methyl ketone to the organic base compound is 1: 1.5-2.5;

the mol ratio of the alpha-methyl ketone to the copper salt is 1: 0.2-0.3;

the molar ratio of the alpha-methyl ketone to the di-tert-butyl peroxide initiator is 1: 2-4.

3. The method of claim 1, wherein the synthesis of α -oxoacetamidine from copper salt catalyzed aryl ketone using aromatic amine and amide as nitrogen source is characterized by: the molar ratio of the copper salt to the 1, 10-phenanthroline in the copper salt/1, 10-phenanthroline catalyst is 1: 0.5-1.5.