CN114349612B - Preparation method of aryl ketone compound - Google Patents

Abstract

The invention provides a preparation method of aryl ketone compounds, which belongs to the technical field of compound synthesis. The method includes reacting an aryl internal alkyne of the formula 1 structure in a solvent at 60°C to 120°C for 12 to 48 hours under the action of a silver catalyst and water. After the reaction is completed, the product is separated and purified to obtain a single aryl alkyne of the formula I structure. Aryl ketones. The raw materials of the present invention are easy to obtain, the experimental operation is simple, the yield of single aryl ketone compounds prepared is good, and gram-scale experiments can be carried out.

Description

A kind of preparation method of aryl ketone compounds

Technical field

The invention belongs to the technical field of compound synthesis, and specifically relates to a preparation method of aryl ketone compounds.

Background technique

As fundamental building blocks in organic synthesis, alkynes are widely used by organic chemists, biochemists, and materials scientists. Alkynes have promoted the development of various synthetic methods. Among these important applications, hydration of alkynes is a simple, effective and practical strategy for the synthesis of carbonyl compounds (M. Rubina, M. Conley and V. Gevorgyan, J. Am. Chem. Soc., 2006, 128, 5818.). Traditional methods are usually carried out in aqueous sulfuric acid solutions using toxic mercury (II) salts as catalysts, and their application in laboratories and industries is limited (Kutscheroff, M.Ber.Dtsch.Chem.Ges., 1881, 14, 1540-1542 .). Therefore, it is highly feasible to develop alternative catalysts to overcome the toxicity of mercury salts.

Despite successes in the regioselective hydration of terminal alkynes, the transformation of internal C-C triple bonds, especially asymmetric internal alkynes, in a regiospecific manner has so far remained elusive, despite some notable precedents. The mid-region selectivity has been improved to about 90/10 (Rzhevskiy, S.A.; Philippova, A.N.; Chesnokov, G.A.; Ageshina, A.A.; Minaeva, L.I.; Topchiy, M.A.; Nechaev, M.S.; Asachenko, A.F., Chemical Communications. 2021, 57 ,5686-5689). To solve this problem, some pioneer studies employed additional directing groups, which forced additional synthetic routes and limited the substrate range. To achieve more efficient regiospecific systems without acidic factors as well as to enable more efficient regiospecific systems with various alkyl groups Diversification of alkyne precursors with aryl termini remains challenging and highly desirable.

However, judging from previous literature reports, the hydration of aryl internal alkynes catalyzed by monometallic Ag requires acidic additives to prepare aryl ketones. The inventors used CO ₂ promoted AgOAc to catalyze the hydration of propargyl alcohol and AgNO ₃ to catalyze the hydration of alkynyl phosphonates to prepare aryl ketones (H.He, C.Qi, X.Hu, Y.Guana ,H.Jianga,GreenChem.2014,16;Xiang,N.Yi,R.Wang,L.Lu,H.Zou,Y.Pan,W.He,Tetrahedron,2015,71,694-699), but its reaction system Additional additives and harsh reaction conditions are required.

Contents of the invention

The purpose of the present invention is to provide a preparation method for aryl ketone compounds in order to solve the problem that the existing preparation methods for aryl ketone compounds require additional additives and regioselectivity.

The invention provides a method for preparing aryl ketone compounds, which method includes:

Under the action of silver catalyst and water, the aryl internal alkyne of formula 1 is reacted in a solvent at 70°C to 120°C for 38 to 48 hours. After the reaction is completed, the product is separated and purified to obtain the aryl ketone compound of formula I. ;

In Formula 1 and Formula I, R ¹ is naphthyl, thienyl, biphenyl, substituted or unsubstituted phenyl, and the substituent group is alkyl, alkoxy, amino or halogen;

R ² is an alkyl group, a hydrogen atom, a substituted or unsubstituted phenyl group, and the substituent group is an alkyl group, an alkoxy group, a cyano group or a halogen.

Preferably, R ¹ is p-methoxyphenyl, and R ² is a hydrogen atom.

Preferably, R ¹ is biphenyl and R ² is methyl.

Preferably, the silver catalyst is AgSbF ₆ , AgOAc, AgBr, CF ₃ COOAg or AgOTf.

Preferably, the molar ratio of the silver catalyst to the aryl internal alkyne having the structure of Formula 1 is (0.05-0.2):1.

Preferably, the feeding equivalent of water is 1.0 to 6.0 equiv.

Preferably, the solvent is dichloromethane, chlorobenzene, chloroform or 1,2-dichloroethane.

Preferably, the reaction temperature is 70°C to 120°C, and the reaction time is 12 to 48 hours.

Preferably, the separation and purification uses column chromatography or thin layer chromatography, and the developing agent used in the chromatography is a mixture of petroleum ether and ethyl acetate.

Preferably, the volume ratio of petroleum ether to diethyl ether is 100:1 to 10:1.

Beneficial effects of the invention

The invention provides a method for preparing aryl ketone compounds. The method utilizes silver-catalyzed aryl internal alkyne hydration to synthesize aryl ketone compounds. The reaction principle is that silver ions attack the triple bond of an alkyne and form Ag- Complex B, then Ag-complex B reacts with H ₂ O to give intermediate C via nucleophilic attack by -OH, and is deprotonated to form the more stable intermediate D, which is then protonated to form enol E, which It undergoes ketoenol tautomerism to produce aryl ketones. The method of the present invention is simple, the raw materials are easily available, no additional additives are required during the reaction process, the product prepared has a high yield and can be prepared on a gram scale.

Description of the drawings

Figure 1 is a hydrogen nuclear magnetic resonance spectrum of the product 1,2-bis(4-methoxyphenyl)ethane-1-one prepared in Example 1 of the present invention.

Figure 2 is a nuclear magnetic resonance carbon spectrum of the product 1,2-bis(4-methoxyphenyl)ethane-1-one prepared in Example 1 of the present invention.

Figure 3 is a hydrogen nuclear magnetic resonance spectrum of the product 1-(4-methoxyphenyl)-2-phenylethan-1-one prepared on a gram scale in Example 2 of the present invention.

Figure 4 is a nuclear magnetic resonance carbon spectrum of the product 1-(4-methoxyphenyl)-2-phenylethan-1-one prepared on a gram scale in Example 2 of the present invention.

Detailed ways

The present invention first provides a preparation method of aryl ketone compounds, which method includes:

Under the action of silver catalyst and water without using additives, the aryl internal alkyne of the formula 1 structure is reacted in a solvent at 70°C to 120°C for 12 to 48 hours. After the reaction is completed, the product is separated and purified to obtain the formula Aryl ketone compounds of structure I;

In Formula 1 and Formula I, R ¹ is naphthyl, thienyl, biphenyl, substituted or unsubstituted phenyl, and the substituent group is alkyl, alkoxy, amino or halogen; preferably p-tolyl, m-tolyl, p-methoxyphenyl, o-tolyl, p-aminophenyl, phenyl, p-fluorophenyl, p-bromophenyl or p-chlorophenyl,

R ² is an alkyl group, a hydrogen atom, a substituted or unsubstituted phenyl group, and the substituent group is an alkyl group, an alkoxy group, a cyano group or a halogen, preferably p-tolyl, p-methoxyphenyl, or phenyl , p-cyanophenyl, tert-butyl, methyl, ethyl, n-butyl or hydrogen.

Preferably, the formula I has the following structure:

According to the present invention, the molar ratio of the silver catalyst and the aryl internal alkyne of the formula 1 structure is preferably (0.05-0.2):1; the feed amount of water is preferably 1.0 to 6.0 equiv. , more preferably 3.0equiv.

According to the present invention, the silver catalyst is preferably AgSbF ₆ , AgOAc, AgBr, CF3COOAg or AgOTf, more preferably AgSbF ₆ or AgOTf, and most preferably AgOTf; the solvent is preferably dichloromethane, chlorobenzene, or trichloromethane. Methane or 1,2-dichloroethane, more preferably chlorobenzene.

According to the present invention, the reaction temperature is 70°C to 120°C, preferably 100°C; the reaction time is 12 to 48 hours, preferably 44 hours.

According to the present invention, the separation and purification uses column chromatography or thin layer chromatography. The developing agent used in the chromatography is a mixture of petroleum ether and ethyl acetate. The mixing volume ratio of petroleum ether and ethyl acetate is preferably 100:1. ~10:1, more preferably 30:1.

The above reaction process route is as follows:

The following examples illustrate the present invention in more detail without further limiting the present invention.

The aryl alkyne raw materials used in the embodiments of the present invention can be prepared by commercial or documented methods. Specific references: (1) Liu, Y.; Du, H. An Alkene-Promoted Borane-Catalyzed Highly Stereoselective Hydrogenation of Alkynes to Give Z-and E-Alkenes.Chem.Eur.J.2015,21,3495-3501;Li,KKCobalt Catalyzed Stereodivergentsemi-hydrogenation ofAlkynes using H ₂ O as the HydrogenSource.Chem.Commun.2019,55,5663-5666 .

Example 1

1. Reaction formula:

2. The amount and properties of reaction raw materials are shown in Table 1:

Table 1

substance molecular weight millimoles Mass/mg volume 1-p-Tolylhexane-1-yne 158.24 0.3 47.5 H ₂ O 18 0.9 16.2 ikB 256.94 0.03 7.70 PhCl 112.56 - - 2.0mL

3. Preparation is as follows:

Add a magnetic stirrer, 1-p-tolylhexane-1-yne (47.5 mg, 0.3 mmol), and AgOTf (7.70 mg, 0.03 mmol) to the sealed tube, and protect the system with argon. Dissolve water (0.9mmol) in 2mL PhCl, quickly add it to the sealed tube with a 5mL syringe, and then seal the sealed tube. Place the sealed tube in an oil bath on a magnetic stirrer with a heating function, stir the reaction at a constant temperature of 100°C for 44 hours, and monitor the reaction with thin layer chromatography. After cooling to room temperature, concentrate under reduced pressure and then separate by column chromatography to obtain the product 1-(p-tolyl)pentan-1-one (42 mg, 74% yield). The hydrogen nuclear magnetic resonance spectrum and carbon spectrum of the product are as shown in the figure. 1 and 2 shown.

The nuclear magnetic resonance data of the product are: ¹ H NMR (400MHz, CDCl3) δ7.86 (d, J = 7.8Hz, 2H), 7.25 (d, J = 7.8Hz, 2H), 2.93 (t, J = 7.3Hz, 2H), 2.41 (s, 3H), 1.73 (s, 2H), 1.36 (d, J = 2.9Hz, 4H), 0.91 (s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ 200.3 (s ),143.5(s),134.7(s),129.2(s),128.2(s),38.5(s),31.6(s),24.2(s),22.5(s),21.6(s),13.9(s) ).

Figures 1 and 2 fully prove the structure of the obtained product. In its hydrogen spectrum Figure 1, the alkyl chain CH ₃ peaks at 0.91ppm, and the CH ₂ on the alkyl chain peaks at 1.36ppm, 1.73ppm, and 2.91-2.94 respectively. Peaks appear at ppm, CH ₃ on the aromatic ring peaks at 3.06ppm, and aromatic ring hydrogen peaks at 7.24-7.87ppm, which is consistent with the structure. In the carbon spectrum 2, the carbons in the alkyl region have peaks at 38.5, 31.6, 24.2, 22.5, 21.6, and 13.9ppm, the aromatic carbons have peaks at 143.5, 134.7, 129.2, and 128.2ppm, and the carbonyl carbons have peaks at 200.3ppm. The peak is consistent with the structure. Therefore, the structure of this compound is confirmed beyond doubt.

Example 2

1. Reaction formula:

2. The amount and properties of reaction raw materials are shown in Table 2:

Table 2

substance molecular weight millimoles Mass/g volume 1-methoxy-4-(phenylethynyl)benzene 208.08 7 1.45 H ₂ O 18 8.4 0.152 ikB 256.94 0.35 0.0899 PhCl 112.56 - - 10.0mL

3. Preparation is as follows:

Add a magnetic stirrer, 1-p-tolylhexane-1-yne (1.45g, 7mmol), and AgOTf (89.9mg, 0.35mmol) to the sealed tube, and protect the system with argon. Dissolve water (8.4mmol) in 10mL PhCl, quickly add it to the sealed tube with a 20mL syringe, and then seal the sealed tube. Place the sealed tube in an oil bath on a magnetic stirrer with a heating function, stir the reaction at a constant temperature of 100°C for 46 hours, and monitor the reaction with thin layer chromatography. After cooling to room temperature, concentrate under reduced pressure and then separate by column chromatography to obtain the product 1-(4-methoxyphenyl)-2-phenylethan-1-one (1g, 63% yield). The NMR of the product The resonance hydrogen spectrum and carbon spectrum are shown in Figures 3 and 4.

The nuclear magnetic resonance data of the product are: 1H NMR (400MHz, CDCl3) δ7.98 (d, J = 8.6Hz, 2H), 7.43–7.14 (m, 5H), 6.91 (d, J = 8.6Hz, 2H), 4.22 (s,2H),3.83(s,3H).13C NMR(101MHz,CDCl3)δ196.15,163.48,134.95,130.88,129.64,129.33,128.57,126.70,113.75,55.39,45.20.

Figures 3 and 4 fully prove the structure of the obtained product. In its hydrogen spectrum Figure 3, the alkoxy CH ₃ peaks at 3.83ppm, the methylene CH ₂ peaks at 4.22ppm, and the aromatic ring hydrogen peaks at 6.91 The peak appears at -7.98ppm, which is consistent with the structure. In the carbon spectrum 4, the carbons in the alkyl region have peaks at 55.39 and 45.20ppm respectively, the aromatic carbons have peaks at 163.48, 134.95, 130.88, 129.64, 129.33, 128.57, 126.70, 113.75ppm, and the carbonyl carbons have peaks at 196.15ppm. The peak is consistent with the structure. Therefore, the structure of this compound is confirmed beyond doubt.

Example 3

1. Reaction formula:

2. When R ¹ and R ² in the reaction formula are different substituents, prepare aryl ketone compounds. The preparation method is the same as Example 1. The results are shown in Table 3:

table 3

The results show that this method has a wide range of applications, and a wider range of substrates can be used to synthesize corresponding compounds.

Example 4

The reaction steps and conditions are the same as in Example 1, except that different reaction solvents are changed. The results are shown in Table 4:

Table 4

Solvent Dichloromethane chlorobenzene Chloroform 1,2-Dichloroethane Product yield (%) 25 83 20 53

Table 4 shows that under the same other conditions, chlorobenzene has the highest yield.

Example 5

The reaction steps and conditions are the same as in Example 1, except that different catalysts are used. The results are shown in Table 5:

table 5

catalyst AgSbF ₆ AHc AgBr CF ₃ COOAg ikB Product yield (%) 37 0 0 0 83

As can be seen from Table 5, other silver catalysts can also catalyze the reaction, but AgOTf has the highest yield.

Example 6

The reaction steps and conditions are the same as in Example 1, except that the equivalents of different water are changed. The results are shown in Table 6:

Table 6

Table 6 shows that under the same other conditions, using 3 equivalents has the highest water yield.

Example 7

In order to select an appropriate developing agent for product separation, a series of experiments were conducted to determine the Rf values of different developing agents, as shown in Table 7:

Table 7

Petroleum ether/diethyl ether volume ratio 100:1 50:1 30:1 20:1 f 0.1 0.5 0.7 0.9

It can be seen from Table 7 that when the developing solvent is petroleum ether/diethyl ether with a volume ratio of 3:1-50:1, it is suitable for column chromatography.

Claims (5)

1. A method for preparing an aryl ketone compound, comprising the steps of:

under the action of a silver catalyst and water, reacting the aryl internal alkyne with the structure shown in the formula 1 in a solvent at 70-120 ℃ for 38-48 hours, and separating and purifying a product after the reaction is finished to obtain an aryl ketone compound with the structure shown in the formula I;

in the formula 1 and the formula I, R ¹ P-tolyl, m-tolyl, p-methoxyphenyl, o-tolyl, p-aminophenyl, phenyl, p-fluorophenyl, p-bromophenyl or p-chlorophenyl;

R ² p-tolyl, p-methoxyphenyl, phenyl, p-cyanophenyl, t-butyl, methyl, ethyl or n-butyl;

the solvent is chlorobenzene;

the silver catalyst is AgOTf;

the water feed equivalent is 3.0equiv.

2. The method for preparing aryl ketone compound according to claim 1, wherein the molar ratio of silver catalyst to aryl internal alkyne of formula 1 is (0.05-0.2): 1.

3. The method for preparing aryl ketone compound according to claim 1, wherein the reaction temperature is 70-120 ℃ and the reaction time is 12-48 hours.

4. The method for preparing aryl ketone compound according to claim 1, wherein the separation and purification use column chromatography or thin layer chromatography, and the developing agent used for chromatography is a mixture of petroleum ether and ethyl acetate.

5. The method for preparing aryl ketone compound according to claim 4, wherein the volume ratio of petroleum ether to diethyl ether is 100:1-10:1.