CN106810430B - A kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives - Google Patents

Abstract

The invention relates to a preparation method of 2-trifluoromethyl-1,4-naphthoquinone derivatives. Copper catalyst, alkali and togni reagent are dissolved in an organic solvent, and benzaldehyde compounds substituted by aryl alkynone are added to form The reaction system, the reaction system is reacted at 60° C. for 10 hours, and the 2-trifluoromethyl-1,4-naphthoquinone derivative is obtained after post-treatment. The invention realizes the synthesis of 2-trifluoromethyl-1,4-naphthoquinone derivatives in one step, the synthesis efficiency is significantly improved, the reaction conditions are mild, the operation is simple, the substrate is suitable for a wide range, and the functional group compatibility is good. Cuprous as a catalyst has good application prospects.

Description

A kind of preparation method of 2-trifluoromethyl-1,4-naphthoquinone derivative

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of a 2-trifluoromethyl-1,4-naphthoquinone derivative.

Background technique

1,4-Naphthoquinone compounds are widely found in nature, and many natural and non-natural molecules with physiological or pharmacological activities contain this fragment:

At the same time, 1,4-naphthoquinone compounds are also an important class of fine chemical intermediates, which have been widely used in pharmaceuticals, pesticides, plasticizers, fragrances, dyes and other industries. Studies have found that 1,4-naphthoquinones The compound has excellent antiseptic, bactericidal, anti-UV, anti-inflammatory and anti-cancer activities.

On the other hand, the introduction of trifluoromethyl (CF ₃ ) into organic compounds can significantly change its acidity, dipole moment, polarity, affinity, etc. due to its strong electron-withdrawing, lipophilic, and stable CF bonds. Lipidity as well as chemical and metabolic stability, therefore, the introduction of trifluoromethyl has become one of the hot spots in organic chemistry and medicinal chemistry research in recent years. However, the introduction of trifluoromethyl groups on naphthoquinones is rare. The traditional synthesis method of 2-trifluoromethyl-1,4-naphthoquinone needs to be synthesized through a five-step reaction (reduction, hydroxyl protection, bromination, trifluoromethylation, oxidation). This multi-step synthesis route atom The economy is low, the synthesis efficiency is low, and the method requires 1,4-naphthoquinone as a raw material. In fact, there are few types of commercial 1,4-naphthoquinone, resulting in an unsatisfactory substrate applicability. 1 The traditional synthetic method of 2-trifluoromethyl-1,4-naphthoquinone:

In 2013, Szabó and Wang Jianbo et al. successively reported copper-catalyzed direct C-H activated trifluoromethylation of 1,4-naphthoquinone rings, realizing a new 2-trifluoromethyl-1,4-naphthoquinone. The synthetic method of the compound:

However, these reactions are all designed based on 1,4-naphthoquinone as the raw material. Like the above methods, they are also limited by the limited number of commercial 1,4-naphthoquinones, and it is difficult to realize the diversity of product structures. Therefore, it is of great significance to develop a one-step synthesis method of 2-trifluoromethyl-1,4-naphthoquinone without using 1,4-naphthoquinone as raw material.

SUMMARY OF THE INVENTION

The invention provides a copper-catalyzed CF radical _- induced trifluoromethylation/cyclization series reaction of aryl alkynone-substituted benzaldehyde, which can construct 2-trifluoromethyl-1 in only one step, 4-naphthoquinone skeleton, and the structural diversity synthesis of 2-trifluoromethyl-1,4-naphthoquinone derivatives can be realized by changing the substituents (R ¹ and R ² ) on the aromatic ring, and the reaction yield is good , the operation is simple, and it has good application value for the synthesis of 2-trifluoromethyl-1,4-naphthoquinone natural products or drug molecules.

The technical scheme adopted in the present invention is:

A preparation method of 2-trifluoromethyl-1,4-naphthoquinone, comprising the steps:

Dissolve the copper catalyst, the base and the togni reagent represented by the structural formula III in an organic solvent, and add the aryl alkynone substituted benzaldehyde represented by the structural formula II to form a reaction system, and the reaction system is reacted at 60 ° C for 10 hours. 2-trifluoromethyl-1,4-naphthoquinone derivatives represented by structural formula I;

The togni reagent is 1-(trifluoromethyl)-1,2-phenyliodoyl-3(1H)-one, and the structure is shown in formula III:

Described aryl alkynone substituted benzaldehyde is shown as formula II:

The structure of the 2-trifluoromethyl-1,4-naphthoquinone derivative is shown in formula I:

In formula I and II, R ¹ is hydrogen atom, chlorine or fluorine, and R ² is selected from hydrogen atom, 4-fluoro, 4-chloro, 4-tert-butyl, 2-methyl, 2-methoxy, 3 -One of phenoxy, 2,6-dimethyl, 3,4-dimethoxy, 3,4,5-trimethoxy;

The alkali is potassium carbonate, the catalyst is cuprous bromide, and the organic solvent is acetonitrile.

The molar ratio of the copper catalyst, the base, the togni reagent and the compound represented by the structural formula II is 0.2:1:2:1.

The reaction was carried out at 60°C, and the optimal reaction time was 10 hours.

The reaction scheme of the preferred conditions is as follows:

After the reaction is complete, post-processing is carried out by techniques such as quenching by adding water, extraction, washing of the organic phase, drying, and separation by column chromatography, so as to obtain a high-purity product.

Said extraction can use ethyl acetate as extractant.

Said washing can be washed with saturated brine.

The condition of the described column chromatography separation is: silica gel 300-400 mesh, eluent: the volume ratio of petroleum ether/ethyl acetate is 10/1.

Compared with the prior art, the present invention has the following advantages: 1. The synthesis of 2-trifluoromethyl-1,4-naphthoquinone derivatives is realized in one step, the synthesis efficiency is significantly improved, and the atom and step economy is high; 2. Using 1,4-naphthoquinone as raw material, the structural diversity synthesis of 2-trifluoromethyl-1,4-naphthoquinone derivatives can be realized by changing the aromatic ring substituents (R ¹ and R ² ). The substrates are suitable for The scope is greatly improved; 3. The reaction conditions are mild, the operation is simple, the substrate is suitable for a wide range, and the functional group compatibility is good. Using cheap cuprous bromide as a catalyst, it has good application prospects; 4. This reaction is a relatively rare hexaldehyde group. One of the examples of trapping carbon radicals to synthesize carbonyl compounds. Therefore, the present invention has great theoretical innovation value and practical value.

Detailed ways

Example 1

Take a dry reaction tube, weigh cuprous bromide (5.7mg, 0.04mmol), potassium carbonate (27.6mg, 0.2mmol), 1-(trifluoromethyl)-1,2-phenyliodoyl-3 (1H)-ketone (126.4 mg, 0.4 mmol), evacuated with nitrogen, replaced three times, and then added 2-(3-phenylpropynoyl)benzaldehyde 1a (46.8 mg, 0.2 mmol) dissolved in 2 mL of dry acetonitrile . The reaction was stirred at 60 °C for 10 h, quenched by adding 10 mL of water, extracted three times with ethyl acetate (10 mL), combined, washed with saturated edible water, and dried over anhydrous sodium sulfate. The organic phase was concentrated and separated by silica gel (300-400 mesh) column chromatography (eluent: petroleum ether/ethyl acetate in a volume ratio of 10/1) to obtain 33.2 mg of yellow liquid 3a with a yield of 55%. Product Spectroscopy ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.20 (dd, J ₁ =7.8 Hz, J ₂ =1.2 Hz, 1H), 8.12 (dd, J ₁ =7.8 Hz, J ₂ =1.2 Hz, 1H), 7.86-7.80 (m, 2H), 7.50-7.45 (m, 3H), 7.24-7.23 (m, 2H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.7, 180.9, 149.5, 134.9, 134.6, 132.8 (q, J = 27.2 Hz), 131.9, 131.4, 131.3, 129.8, 128.7 (q, J = 1.6 Hz), 128.0, 127.2, 126.8, 121.7 (q, J = 277.8 Hz); ¹⁹ F NMR ( 565MHz, CDCl ₃ ), δ: -56.29; HRMS (ESI) (m/z): calcd for C ₁₇ H ₉ F ₃ O ₂ ([M+H] ⁺ ), 303.0627; found303.0626.

The reaction formula is as follows:

Example 2

Except for replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted with aryl alkynone shown in Structural Formula 1b, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 50%, yellow solid, melting point 103-105 °C; ¹ H NMR (400 MHz, CDCl ₃ ), δ: 8.21 (dd, J ₁ =7.6 Hz, J ₂ =1.6 Hz, 1H), 8.14 (dd, J ₁ = 6.8 Hz, J ₂ =2.0 Hz, 1H), 7.90-7.82 (m, 2H), 7.28-7.24 (m, 2H), 7.20-7.16 (m, 2H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.6, 180.7, 163.8 (d, J=250.7Hz), 148.5, 135.0, 134.7, 133.1 (q, J=27.2Hz), 131.9, 131.3, 131.0, 127.1, 126.9, 121.6 (q, J=279.4Hz) ), 115.4, 115.3; ¹⁹ FNMR (565MHz, CDCl ₃ ), δ: -56.25, -110.69; HRMS (ESI) (m/z): calcd for C ₁₇ H ₈ F ₄ O ₂ ([M+H] ⁺ ), 321.0533; found 321.0531.

The reaction formula is as follows:

Example 3

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the aryl alkynone-substituted benzaldehyde shown in Structural Formula 1c, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 52%, yellow solid, melting point 69-71°C; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.19 (dd, J ₁ =7.8 Hz, J ₂ =1.2 Hz, 1H), 8.12 (dd, J ₁ = 7.2 Hz, J ₂ =1.6 Hz, 1H), 7.87-7.81 (m, 2H), 7.46-7.44 (m, 2H), 7.18-7.17 (m, 2H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.4, 180.6, 148.3, 136.2, 135.1, 134.8, 133.1 (q, J=27.2Hz), 131.8, 131.2, 130.2, 129.6, 128.4, 127.2, 126.9, 121.6 (q, J=279.4Hz); ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -56.24; HRMS (ESI) (m/z): calcd for C ₁₈ H ₁₁ F ₃ O ₃ ([M+H] ⁺ ), 337.0238; found 337.0233.

The reaction formula is as follows:

Example 4

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the aryl alkynone-substituted benzaldehyde shown in Structural Formula 1d, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 60%, yellow liquid; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.19 (dd, J ₁ =7.2 Hz, J ₂ =1.2 Hz, 1H), 8.12 (dd, J ₁ =7.2 Hz, J ₂ =1.2 Hz, 1H), 7.84-7.80(m, 2H), 7.48(d, J=8.4Hz, 2H), 7.19(d, J=8.4Hz, 2H), 1.37(s, 9H); ¹³ CNMR( 151MHz, CDCl ₃ ), δ: 183.8, 180.9, 153.0, 149.5, 134.7, 134.4, 132.5 (q, J=27.2Hz), 131.8, 131.3, 128.7 (q, J=1.5Hz), 128.1, 127.1, 126.6, 124.8, 121.7 (q, J=279.4 Hz), 34.9, 31.2; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: 56.20; HRMS (ESI) (m/z): calcd for C ₂₁ H ₁₇ F ₃ O ₂ ([M+H] ⁺ ), 359.1253; found 359.1253.

The reaction formula is as follows:

Example 5

Except for replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted with aryl alkynone shown in Structural Formula 1e, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 62%, yellow liquid; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.23 (dd, J ₁ =7.2 Hz, J ₂ =0.6 Hz 1H), 8.12 (dd, J ₁ =7.8 Hz, J ₂ = 1.2 Hz, 1H), 7.87-7.81(m, 2H), 7.38-7.36(m, 1H), 7.30-7.26(m, 2H), 7.02(d, J＝7.2 Hz, 1H), 2.15(s, 3H) ); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.4, 180.7, 150.3, 135.0 (q, J=1.5 Hz), 134.9, 134.7, 133.4 (q, J=27.2 Hz), 132.0, 131.8, 131.4, 130.0, 129.5, 127.5 (q, J=3.0 Hz), 127.2, 127.0, 125.5, 121.6 (q, J=277.8 Hz), 20.1; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -58.03; HRMS (ESI )(m/z): calcd for C ₁₈ H ₁₁ F ₃ O ₂ ([M+H] ⁺ ), 317.0784; found 317.0781.

The reaction formula is as follows:

Example 6

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in the structural formula 1a in the example 1 with the benzaldehyde substituted by the aryl alkynone shown in the structural formula 1f, the remaining operation steps are the same as those in the embodiment 1, and the yield : 63%, yellow solid, melting point 124-126 °C; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.20 (dd, J ₁ =7.2 Hz, J ₂ =1.2 Hz, 1H), 8.12 (dd, J ₁ =7.2Hz, J ₂ =1.2Hz 1H), 7.84-7.78(m, 2H), 7.46-7.43(m, 1H), 7.07-7.04(m, 2H), 6.98(d, J=8.4Hz, 1H) , 3.76 (s, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.0, 180.8, 156.4, 147.7, 134.6, 134.4, 133.6 (q, J=27.2 Hz), 132.0, 131.7, 131.2, 129.4, 127.1, 126.8, 121.7 (q, J=277.8 Hz), 121.1, 120.3, 110.8, 55.8; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -58.56; HRMS (ESI) (m/z): calcd for C ₁₈ H ₁₁ F ₃ O ₃ ([M+H] ⁺ ), 333.0733; found 333.0734.

The reaction formula is as follows:

Example 7

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in Structural Formula 1g, all other operation steps are the same as in Example 1, and the yield is the same as that in Example 1. : 58%, yellow liquid; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.18 (dd, J ₁ =7.8 Hz, J ₂ =1.8 Hz, 1H), 8.12 (dd, J ₁ =7.2 Hz, J ₂ ＝1.2 Hz, 1H), 7.86-7.80(m, 2H), 7.42(t, J＝7.8Hz, 1H), 7.37-7.34(m, 2H), 7.14-7.11 (m, 2H), 7.06(d, J=7.8Hz, 2H), 6.95 (d, J=7.8Hz, 1H), 6.87 (t, J=1.8Hz, 1H); ¹³ C NMR (151MHz, CDCl ₃ ), δ: 183.4, 180.7, 157.0, 156.8, 148.8, 135.0, 134.7, 133.1, 132.8, 131.8, 131.3, 130.0, 129.5, 127.2, 126.9, 123.8, 123.4, 121.6(q, J=277.8Hz), 119.9, 119.3, ^11MHz9 ,.CDCl0; ₃ ), δ: -56.42; HRMS(ESI) (m/z): calcd for C ₂₃ H ₁₃ F ₃ O ₃ ([M+H] ⁺ ), 395.0890; found 395.0887.

The reaction formula is as follows:

Example 8

Except for replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in the structural formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in the structural formula 1h, the remaining operation steps are the same as those in the embodiment 1, and the yield is : 61%, yellow solid, melting point: 85-87°C; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.27 (dd, J ₁ =7.8 Hz, J ₂ =1.2 Hz, 1H), 8.16 (dd, J ₁ = 7.8Hz, J ₂ = 1.2Hz, 1H), 7.90 (dt, J = 1.8Hz, 1H), 7.86 (dt, J = 1.8Hz, 1H), 7.28 (d, J = 7.8Hz, 1H), 7.4 (d, J=7.8 Hz, 2H), 2.12 (s, 6H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.2, 180.4, 150.1, 135.0, 134.7, 134.3, 132.0, 131.6, 131.5, 129.0 , 127.5, 127.3, 127.2, 127.0, 121.6 (q, J=279.4 Hz), 20.2; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -59.93; HRMS (ESI) (m/z): calcd for C ₁₉ H ₁₃ F ₃ O ₂ ([M+H] ⁺ ), 331.0940; found 331.0939. The reaction formula is as follows:

Example 9

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in Structural Formula 1i, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 55%, red liquid; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.17 (dd, J ₁ =7.8 Hz, J ₂ =1.8 Hz 1H), 8.11 (dd, J ₁ =7.2 Hz, J ₂ = 1.2 Hz, 1H), 7.84-7.78(m, 2H), 6.94(d, J=8.4Hz, 1H), 6.84(dd, J1 ₌ 8.4Hz, J2=2.4Hz, 1H ₎ , 6.79(d, J=1.8Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 183.8, 181.1, 150.7, 148.5, 134.8, 134.5, 132.5 (q, J=27.2Hz), 131.9, 131.4, 127.2, 126.7, 123.5, 122.6, 121.8 (q, J=277.8Hz), 112.7, 110.6, 56.08, 56.02; ¹⁹ F NMR (565MHz, CDCl ₃ ), δ: -56.23 ;HRMS(ESI)(m/z):calcd for C ₁₉ H ₁₃ F ₃ O ₄ ([M+H] ⁺ ), 363.0839; found 363.0837.

The reaction formula is as follows:

Example 10

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the aryl alkynone-substituted benzaldehyde shown in Structural Formula 1j, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 72%, red solid, melting point 126-128 °C; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.17 (dd, J ₁ =7.8 Hz, J ₂ =1.8 Hz, 1H), 8.11 (dd, J ₁ = 7.2 Hz, J ₂ =1.8 Hz, 1H), 7.85-7.80 (m, 2H), 6.46 (s, 2H), 3.91 (s, 3H), 3.85 (s, 6H); ¹³ C NMR (151 MHz, CDCl) ₃ ), δ: 183.6, 180.9, 152.9, 149.3, 139.4, 134.9, 134.7, 132.8(q, J=27.2Hz), 131.8, 131.3, 127.2, 126.8, 126.4, 121.7(q, J=277.8Hz), 106.6 , 61.1, 56.3; ¹⁹ FNMR (565MHz, CDCl ₃ ), δ: -56.43; HRMS (ESI) (m/z): calcd for C ₂₀ H ₁₅ F ₃ O ₅ ([M+H] ⁺ ), 363.0944; found 363.0941.

The reaction formula is as follows:

Example 11

Except replacing 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted with aryl alkynone shown in Structural Formula 1k, the remaining operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 61%, yellow liquid; ¹ H NMR (400 MHz, CDCl ₃ ), δ: 8.14 (d, J=8.4 Hz, 1H), 8.07 (d, J=2.0 Hz, 1H), 7.78 (dd, J ₁ = 8.4 Hz, J2=2.4Hz, 1H ₎ , 7.48 (d, J=8.4Hz, 2H), 7.17 (d, J=8.4Hz, 2H), 1.37 (s, 9H); ¹³ C NMR (151 MHz, CDCl) ₃ ), δ: 183.0, 180.1, 153.4, 149.6, 141.7, 134.9, 132.7 (q, J=27.2Hz), 132.5, 130.1, 128.8, 128.6, 127.8, 127.1, 125.0, 121.6 (q, J=277.8Hz) , 35.0, 31.3; ¹⁹ FNMR (565MHz, CDCl ₃ ), δ: -56.19; HRMS (ESI) (m/z): calcd for C ₂₁ H ₁₆ ClF ₃ O ₂ ([M+H] ⁺ ), 393.0864; found 393.0831.

The reaction formula is as follows:

Example 12

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in Structural Formula 11, the remaining operation steps are the same as in Example 1, and the yield is the same as that in Example 1. : 63%, yellow solid, melting point: 91-93°C; ¹ H NMR (600 MHz, CDCl ₃ ), δ: 8.16 (dd, J ₁ =8.4 Hz, J ₂ =0.6 Hz, 1H), 8.07 (d, J =2.4Hz,1H),7.80(dd,J ₁ =8.4Hz,J ₂ =1.8Hz,1H),7.38(dt,J ₁ =7.8Hz,J ₂ =1.8Hz,1H),7.29(m,2H ), 7.01 (dd, J ₁ =7.2 Hz, J ₂ =1.2 Hz, 1H), 2.14 (s, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 182.1, 179.6, 166.5 (d, J= 258.8Hz), 156.4, 147.9, 134.2(d, J=8.3Hz), 133.7(q, J=28.1Hz), 182.4, 179.7, 150.2, 141.8, 135.0, 133.5(q, J=27.2Hz), 132.5, 131.4, 131.0, 130.1, 129.6, 128.8, 127.5, 127.1, 126.4, 125.6, 121.4 (q, J=279.4 Hz), 20.0; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -58.00; HRMS (ESI) ( m/z): calcd for C ₁₈ H ₁₀ ClF ₃ O ₂ ([M+H] ⁺ ), 351.0394; found351.0391.

The reaction formula is as follows:

Example 13

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in Structural Formula 1a in Example 1 with the aryl alkynone-substituted benzaldehyde shown in Structural Formula 1m, the rest of the operation steps are the same as in Example 1, and the yield is the same as in Example 1. : 70%, red solid, melting point: 159-160 ℃; ¹ H NMR (600MHz, CDCl ₃ ), δ: 8.14 (d, J=8.4Hz, 1H), 8.08 (d, J=8.4Hz, 1H), 7.80 (dd, J ₁ =8.4 Hz, J ₂ =1.8 Hz, 1H), 6.45 (s, 2H), 3.93 (s, 3H), 3.66 (s, 6H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 182.8, 180.0, 153.0, 149.3, 141.8, 139.7, 135.1, 132.9 (q, J=28.7Hz), 132.4, 130.1, 128.6, 127.1, 126.0, 121.6 (q, J=279.4 Hz), 106.7, 61.4, 56.4; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -56.41, -100.69; HRMS (ESI) (m/z): calcd for C ₂₀ H ₁₄ ClF ₃ O ₅ ([M+H] ⁺ ), 427.0555 ;found 427.0554.

The reaction formula is as follows:

Example 14

Except that the 2-(3-phenylpropynoyl)benzaldehyde shown in the structural formula 1a in Example 1 is replaced by the benzaldehyde substituted with the aryl alkynone shown in the structural formula 1n, the remaining operation steps are the same as those in the embodiment 1, and the yield : 58%, yellow solid, melting point 96-98°C; ¹ H NMR (400 MHz, CDCl ₃ ), δ: 8.24 (dd, J ₁ =8.8 Hz, J ₂ =5.2 Hz, 1H), 7.76 (dd, J ₁ ) = 8.0 Hz, J ₂ =2.4 Hz, 1H), 7.51-7.47 (m, 3H), 7.17 (d, J=8.4 Hz, 2H), 1.37 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) ,δ: 183.0,179.8,166.5(d,J=259.7Hz),153.4,149.7,133.9(d,J=9.1Hz),132.7(q,J=28.7Hz),130.2(d,J=9.1Hz) , 128.8(q, J＝1.5Hz), 128.5, 127.9, 125.0, 122.2(d, J＝22.7Hz), 121.7(q, J＝277.8Hz), 113.7(d, J＝22.7Hz), 35.0, 31.3 ; ¹⁹ F NMR (565MHz, CDCl ₃ ), δ: -56.15, -100.39; HRMS (ESI) (m/z): calcd for C ₂₁ H ₁₆ F ₄ O ₂ ([M+H] ⁺ ), 377.1159; found 377.1166.

The reaction formula is as follows:

Example 15

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in the structural formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in the structural formula 1o, the remaining operation steps are the same as those in the embodiment 1, and the yield : 61%, yellow solid, melting point 90-92°C; ¹ H NMR (400 MHz, CDCl ₃ ), δ: 8.30 (dd, J ₁ =8.4 Hz, J ₂ =4.8 Hz, 1H), 7.78 (dd, J ₁ =8.4Hz,J ₂ =2.8Hz,1H),7.54(dt,J ₁ =8.0Hz,J ₂ =2.4Hz,1H),7.40(dt,J ₁ =7.6Hz,J ₂ =0.8Hz,1H) , 7.33-7.28 (m, 2H), 7.04 (d, J=7.2Hz, 1H), 2.17 (s, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 182.5, 179.4, 166.6 (d, J ＝259.7Hz), 150.4, 135.0, 134.0(d, J＝7.6Hz), 133.5(q, J＝27.2Hz), 131.4, 130.5, 130.4, 130.1, 129.6, 128.5, 127.5(q, J＝1.5Hz) , 125.6, 122.3 (d, J=22.6 Hz), 121.5 (q, J=277.8 Hz), 113.8 (d, J=2.3 Hz), 20.0; ¹⁹ F NMR (565 MHz, CDCl ₃ ), δ: -57.96, -100.11; HRMS (ESI) (m/z): calcd for C ₁₈ H ₁₀ F ₄ O ₂ ([M+H] ⁺ ), 335.0690; found335.0689.

The reaction formula is as follows:

Example 16

Except replacing the 2-(3-phenylpropynoyl)benzaldehyde shown in the structural formula 1a in Example 1 with the benzaldehyde substituted by the aryl alkynone shown in the structural formula 1p, the rest of the operation steps are the same as those in the embodiment 1, and the yield : 54%, yellow solid, melting point: 142-144 °C; ¹ H NMR (400 MHz, CDCl ₃ ), δ: 8.16 (dd, J ₁ =8.8 Hz, J ₂ =5.2 Hz, 1H), 7.83 (dd, J ₁ = 8.4Hz, J ₂ = 2.4Hz, 1H), 7.49-7.43(m, 2H), 7.08-7.04(m, 2H), 6.98(d, J = 8.4Hz, 1H), 3.76(s, 3H) ; ¹³ C NMR (151 MHz, CDCl ₃ ), δ: 181.7, 179.8, 166.6 (d, J=259.7 Hz), 156.4, 148.0, 134.5 (d, J=7.6 Hz), 133.8 (q, J=27.2 Hz) ,131.3, 130.5(d,J＝9.1Hz),129.4,128.3,121.8(d,J＝22.7Hz),121.5(q,J＝277.8Hz),120.8,120.3,113.5(d,J＝24.2Hz) , 110.8, 55.8; ¹⁹ F NMR (565MHz, CDCl ₃ ), δ: -58.72, -100.20; HRMS (ESI) (m/z): calcd for C ₁₈ H ₁₀ F ₄ O ₃ ([M+H] ⁺ ), 351.0639; found 351.0638.

The reaction formula is as follows:

.

Claims (3)

1. a kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives, it is characterised in that include the following steps:

In organic solvent by the dissolution of togni reagent shown in copper catalyst, alkali and structural formula III, it is added shown in structural formula II The compound of benzaldehyde category that aryl acetylenic ketone replaces forms reaction system, and reaction system is reacted 10 hours at 60 DEG C, post-treated To 2- Trifluoromethyl-1 shown in structural formula I, 4- naphthoquinone derivatives；

In formula I and formula II, R¹For hydrogen atom, chlorine or fluorine, R²Selected from hydrogen atom, 4- fluorine, 4- chlorine, 4- tert-butyl, 2- methyl, 2- first One of oxygroup, 3- phenoxy group, 2,6- dimethyl, 3,4- dimethoxy, 3,4,5- trimethoxy；The copper catalyst is Cuprous bromide, the alkali are potassium carbonate, and the organic solvent is acetonitrile, and the togni reagent is 1- (trifluoromethyl)- 1,2- benzenesulfonyl -3 (1H) -one.

2. according to the method described in claim 1, it is characterized by: the copper catalyst, alkali, togni reagent, structural formula II The molar ratio of compound represented is 0.2:1:2:1.

3. according to the method described in claim 1, it is characterized by: the post-processing includes being quenched, extracting, drying and column layer Analysis.