Method for synthesizing acyl trifluoroborate compound from benzyl borate compound and application of acyl trifluoroborate compound

Abstract

The invention discloses a method for synthesizing acyl trifluoroborate. The method is as shown in a formula I, in a first organic solvent, a benzyl borate compound shown in a formula (1) and N-bromosuccinimide are used as raw materials, azodiisobutyronitrile is added for a reaction to obtain a compound shown in a formula (2), or the benzyl borate compound shown in the formula (1) is used as a raw material and reacts with NBS (N-bromosuccinimide) under the illumination condition to obtain the compound shown in the formula (2); the compound shown in the formula (2) is combined with potassium bifluoride, cesium fluoride and hydrochloric acid, ammonium bifluoride is stirred to react in a mixed solvent of a second organic solvent and water, and compounds shown in a formula (3), a formula (4) and a formula (5) are obtained; the compound shown in the formula (3) or the formula (4) can react with amines to obtain the compound shown in the formula (6). The method is simple to operate, raw materials are easy to obtain, reaction conditions are mild, a reaction system is green and environment-friendly, a product is easy to separate and purify, the method is particularly suitable for large-scale industrial production, and the synthesis method of the acyl trifluoroborate compound is widened. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemistry and relates to a novel method for synthesizing acyl trifluoroborate, more specifically, a method for synthesizing a series of acyl trifluoroborate compounds by a two-step operation method using benzyl borate compounds as starting materials and an application thereof. Background Art

[0002] Organoboron compounds are multifunctional building blocks in organic synthesis and are widely used in chemical sensing, biological probes, materials science, and drug development. Due to their unique reactivity, acyl boron compounds have gradually emerged in many fields and play an important role. In 2010, Molander's group first reported the synthesis of acyl potassium trifluoroborate compounds (KATs). Acyl potassium trifluoroborate compounds (KATs) can react with hydroxylamine to quickly and efficiently construct amide bonds, can be combined with proteins, peptides, polymers, and fluorescent materials, and are widely used in biochemistry and materials chemistry. They can prepare zwitterionic trifluoroborate imines (TIMs) and their derivatives, which can be further converted into biologically active compounds.

[0003] In view of the wide application of KATs, chemists have reported many synthetic strategies to obtain these valuable organometallic reagents in the past decade. In 2010, the Molander group obtained KATs by capturing acyl anion equivalents with electrophilic boron reagents and quenching them with KHF2. This method is the earliest successful report of KATs synthesis. And KATs can react with azides to synthesize a series of amide compounds, which are widely used. In 2012, the Bode group used benzotriazole compounds and organic lithium reagents to be captured by electrophilic boron reagents at low temperature to prepare KATs. The raw material preparation of this strategy is complex, needs to be carried out at low temperature, is difficult to scale up, and has high cost. From 2014 to 2021, the Bode group creatively reported two types of "acyl boron transfer reagents", which can introduce the entire (CO)-B part under transition metal catalysis or transition metal-free conditions. The yield of this method is greatly improved, the operation steps are simplified, and the substrate is compatible with alkyl, aryl and heterocyclic compounds, providing a basis for the application of KATs. In 2019, Ito's group found that KATs can also be prepared by copper-catalyzed borylation of aldehydes and then oxidation of α-hydroxyboron compounds. The raw materials of this method are easily available, the range of aldehydes is wide, it has step economy, and high functional group tolerance. In 2021-2022, Mankad's group and Marder's group used acid derivatives to effectively prepare KATs by nucleophilic borylation under transition metal catalysis. This type of method solves traditional problems such as expensive raw materials, cumbersome steps, and inability to prepare on a large scale.

[0004] Although significant progress has been made in the synthetic preparation of KATs, it is still necessary to explore new and more practical methods. In the above strategies, the boron-containing moiety is usually introduced at the key step, which requires strong bases or special reagents. These prerequisites limit the substrate range, reduce economic benefits, and limit the application of these methods. Direct α-oxidation of borate is the most direct solution to form the KATs moiety. Compared with the reported methods, organic borates are widely available, and directly converting them into KATs will be a more efficient and economical strategy. However, this conversion is still difficult to achieve, probably due to the intolerance of the boron group under oxidative conditions. Therefore, it is necessary to invent new methods with mild reaction conditions, high yields, and good functional group tolerance. Summary of the invention

[0005] In order to solve the deficiencies in the prior art, the purpose of the present invention is to provide a method for synthesizing acyl trifluoroborate compounds from benzyl borate compounds, as shown in the following formula I. The method has the advantages of simple operation, easy availability of raw materials, mild reaction conditions, green reaction system, environmental friendliness, easy separation and purification of products, and is particularly suitable for large-scale industrial production. The present invention can prepare a series of acyl trifluoroborate compounds efficiently and in high yield, and broadens the synthesis method of acyl trifluoroborate compounds.

[0006]

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] Step 1: In a first organic solvent, a benzyl borate compound represented by formula (1) and N-bromosuccinimide (NBS) are used as raw materials, and azobisisobutyronitrile (AIBN) is added to react to obtain a geminal halobenzyl borate compound represented by formula (2); and / or,

[0009] In a first organic solvent, a benzyl borate compound represented by formula (1) is used as a raw material and reacts with N-bromosuccinimide (NBS) under light conditions to produce a photochemical reaction to obtain a geminal halobenzyl borate compound represented by formula (2);

[0010] The reaction process is shown in the following formula A:

[0011]

[0012] Step 2: In a mixed solvent of a second organic solvent and water, the geminal halobenzyl borate compound represented by formula (2) and potassium bifluoride are reacted by stirring in the mixed solvent to obtain a compound represented by formula (3); and / or,

[0013] In a mixed solvent of a second organic solvent and water, the compound represented by formula (2) is reacted with cesium fluoride and hydrochloric acid in a mixed solvent under stirring to obtain a compound represented by formula (4); and / or,

[0014] In a mixed solvent of a second organic solvent and water, the compound represented by formula (2) is reacted with ammonium hydrogen fluoride under stirring in the mixed solvent to obtain a compound represented by formula (5).

[0015] The reaction process is shown in the following formula B:

[0016]

[0017] Step 3: reacting the compound represented by formula (3) or formula (4) with an amine in a third organic solvent to obtain a compound represented by formula (6);

[0018] The reaction process is shown in the following formula C:

[0019]

[0020] In Formula A, Formula B, and Formula C,

[0021] Ar is aryl, substituted aryl, heteroaryl, substituted heteroaryl, etc. 1 , R 2 are independently selected from the same or different alkyl groups, or form a ring.

[0022] In step 1, when azobisisobutyronitrile (AIBN) is added to a first organic solvent to react with a benzyl borate compound of formula (1) and N-bromosuccinimide (NBS) as raw materials to obtain a geminal halobenzyl borate compound of formula (2), the first organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of more than one thereof; preferably, 1,2-dichloroethane, chloroform, or carbon tetrachloride; more preferably, 1,2-dichloroethane (DCE);

[0023] The amount of the first organic solvent used is 1-10 ml; preferably, 2.5 ml.

[0024] The reaction temperature is 0°C-80°C; preferably, 80°C;

[0025] The reaction time is 1-12 hours; preferably, 4 hours.

[0026] The molar ratio of the benzyl borate compound, the N-bromosuccinimide and the azobisisobutyronitrile is (1-1.2):(2-4):(0.05-0.20); preferably, it is 1:2.3:0.05.

[0027] In step 1, when the benzyl borate compound represented by formula (1) is used as a raw material in a first organic solvent and reacts with N-bromosuccinimide (NBS) under light conditions to produce a photochemical reaction to obtain the geminal halobenzyl borate compound represented by formula (2), the first organic solvent is selected from any one or a mixture of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents; preferably, 1,2-dichloroethane, chloroform, and carbon tetrachloride; more preferably, 1,2-dichloroethane (DCE);

[0028] The amount of the first organic solvent used is 1-10 ml; preferably, 2.5 ml.

[0029] The reaction temperature is 0°C-60°C; preferably, 30°C;

[0030] The reaction time is 1-12 hours; preferably, 2 hours.

[0031] The molar ratio of the benzyl borate compound to the N-bromosuccinimide is (1-1.2):(2-4); preferably, it is 1:2.3.

[0032] The illumination condition of the reaction is visible light (400-700nm); preferably, blue light (400-500nm).

[0033] In step 2, the second organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of more thereof; preferably, methanol, ethanol, or hexafluoroisopropanol; more preferably, hexafluoroisopropanol (HFIP).

[0034] The volume ratio of the second organic solvent to the water is (5-10):(1-2); preferably, 5:1; the water can be used to dissolve compounds such as potassium bifluoride, cesium fluoride, ammonium bifluoride, etc., and is miscible with the second organic solvent;

[0035] In step 2, the molar ratio of the geminal halobenzyl borate compound represented by formula (2) to the potassium bifluoride is (1-1.2):(4-12); preferably, it is 1:6.

[0036] In step 2, the molar ratio of the geminal halobenzyl borate compound represented by formula (2) to the cesium fluoride is (1-1.2):(4-12); preferably, 1:6. The molar ratio of the cesium fluoride to the hydrochloric acid is (6-12):(1-5); preferably, 6:1.3;

[0037] In step 2, the molar ratio of the geminal halobenzyl borate compound represented by formula (2) to the ammonium hydrogen fluoride is (1-1.2):(4-12); preferably, it is 1:6.

[0038] In step 2, the reaction temperature is 0°C-80°C; preferably, 60°C;

[0039] The reaction time is 1-8 hours; preferably, 2 hours.

[0040] In step 3, the third organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of more thereof; preferably, acetonitrile, N,N-dimethylformamide, 1,4-dioxane; more preferably, acetonitrile.

[0041] In step 3, the amine includes a secondary amine; preferably, tetrahydropyrrole.

[0042] The molar ratio of the compound represented by formula (3) or formula (4) to the amine is (1-1.2):(1-3); preferably, it is 1:1.2.

[0043] In step 3, the reaction temperature is 0°C-60°C; preferably, 35°C;

[0044] The reaction time is 1-12 hours; preferably, 4 hours.

[0045] Step 1 also includes a reaction solution post-treatment step, wherein the reaction solution post-treatment method is: after the reaction is completed, the reaction solution is diluted with petroleum ether or a mixture of petroleum ether and ethyl acetate, filtered through diatomaceous earth, and the solvent is evaporated under reduced pressure to obtain the halogenated benzyl borate compound shown in formula (2).

[0046] Step 2 also includes a reaction solution post-treatment step, wherein the reaction solution post-treatment method is as follows: after the reaction is completed, the reaction solution is subjected to reduced pressure rotary evaporation to remove low-boiling point compounds, the obtained solid is dissolved in acetone and filtered through diatomaceous earth, the filtrate is collected and rotary evaporated again to remove the solvent, and the obtained solid is washed with dichloromethane to obtain the acyl trifluoroborate compound represented by formula (3), formula (4) or formula (5).

[0047] In a specific embodiment, the method comprises the following steps:

[0048] Step 1: Take 1 equivalent (0.5 mmol) of the benzyl borate compound represented by formula (1) and 2.3 equivalents of N-bromosuccinimide as raw materials, add 0.05 equivalent of azobisisobutyronitrile (AIBN), heat at 80°C in 2.5 ml of 1,2-dichloroethane solvent for four hours, and obtain the compound represented by formula (2) after treatment; or take 1 equivalent (0.5 mmol) of the benzyl borate compound represented by formula (1) as raw material and 2.3 equivalents of N-bromosuccinimide in 1,2-dichloroethane solvent, and react at room temperature for 2 hours under photochemical conditions with blue light (400-500 nm) excitation to obtain the compound represented by formula (2);

[0049] The reaction process is shown in the following formula:

[0050]

[0051] Step 2: The compound represented by formula (2) is used as a raw material, and reacted with 6 equivalents of potassium bifluoride, cesium fluoride or ammonium bifluoride, respectively, and stirred in a hexafluoroisopropanol solvent for reaction. After post-treatment of the reaction solution, acyl trifluoroborate compounds represented by formula (3), formula (4) and formula (5) are obtained respectively.

[0052] The reaction process is shown in the following formula:

[0053]

[0054] Step 3: reacting the compound represented by formula (3) or formula (4) with an amine in acetonitrile to obtain a compound represented by formula (6);

[0055] The reaction process is shown in the following formula:

[0056]

[0057] The present invention provides an acyl potassium trifluoroborate compound, the structure of which is shown below:

[0058]

[0059] Wherein, Ar is an aryl group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group.

[0060] Specifically, the acyl potassium trifluoroborate compound includes:

[0061]

[0062] The present invention provides an acyl cesium trifluoroborate compound, the structure of which is shown below:

[0063]

[0064] Wherein, Ar is an aryl group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group.

[0065] Specifically, the acyl cesium trifluoroborate compound includes:

[0066]

[0067] The present invention provides an acyl trifluoroborate ammonium salt compound, the structure of which is shown below:

[0068]

[0069] Wherein, Ar is an aryl group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group.

[0070] Specifically, the acyl ammonium trifluoroborate salt compound is as follows:

[0071]

[0072] The present invention provides an acyl trifluoroborate ammonium salt compound, the structure of which is shown below:

[0073]

[0074] Wherein, Ar is an aryl group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group.

[0075] Specifically, the acyl ammonium trifluoroborate salt compound is as follows:

[0076]

[0077] The present invention also provides a method for synthesizing the above-mentioned acyl trifluoroborate compounds, or the use of acyl trifluoroborate compounds in scale-up production, synthesis of amide compounds, synthesis of complex compounds by reaction with dye molecules, construction of fluorescent molecular compounds, etc.

[0078] Specifically,

[0079] The invention provides the result of the scale-up of the acyl potassium trifluoroborate compound. The benzyl borate compound is synthesized by benzyl chloride under transition metal catalysis. The compound is subjected to simple post-treatment and is not separated by silica gel column chromatography. The acyl potassium trifluoroborate compound can be directly synthesized by bromination with NBS and then hydrolyzed. The reaction can be scaled up to 100 mmoles, and 18.6 grams of acyl potassium trifluoroborate can be synthesized simply and quickly.

[0080]

[0081] The present invention also provides the application of the acyl potassium trifluoroborate compound in organic synthesis, drug fragments, biomolecules, and materials science. The acyl potassium trifluoroborate compound can react with a tryptamine compound to synthesize a corresponding imine compound, and can be further hydrolyzed to synthesize an amide compound. The acyl potassium trifluoroborate compound can react with a dye molecule to synthesize a complex compound, providing a synthesis method for more natural product drug molecules.

[0082]

[0083] In addition, the acyl potassium trifluoroborate compound can quickly construct fluorescent molecular compounds and molecules required for material chemistry.

[0084]

[0085] The beneficial effects of the present invention include: compared with the prior art, the present invention has the characteristics of simple operation, easy availability of raw materials, easy availability of reagents, mild conditions, green and environmentally friendly reaction system, and easy separation and purification of products. It is suitable for synthesizing various highly functionalized benzyl borate compounds. It is particularly suitable for large-scale industrial production, and can efficiently and high-yield prepare high-purity acyl trifluoroborate compounds, thereby broadening the synthesis method of acyl trifluoroborate compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0086] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without paying any creative work.

[0087] Figure 1 For compound 3a 1 H-NMR nuclear magnetic resonance spectrum.

[0088] Figure 2 For compound 3a 13 C-NMR nuclear magnetic resonance spectrum.

[0089] Figure 3 For compound 3a 19 F-NMR nuclear magnetic resonance spectrum.

[0090] Figure 4 For compound 3a 11 B-NMR nuclear magnetic resonance spectrum.

[0091] Figure 5 For compound 3b 1 H-NMR nuclear magnetic resonance spectrum.

[0092] Figure 6 For compound 3b 13 C-NMR nuclear magnetic resonance spectrum.

[0093] Figure 7 For compound 3b 19 F-NMR nuclear magnetic resonance spectrum.

[0094] Figure 8 For compound 3b 11 B-NMR nuclear magnetic resonance spectrum.

[0095] Fig. 9 For compound 3c 1 H-NMR nuclear magnetic resonance spectrum.

[0096] Fig.10 For compound 3c 13 C-NMR nuclear magnetic resonance spectrum.

[0097] Fig.11 For compound 3c 19 F-NMR nuclear magnetic resonance spectrum.

[0098] Fig.12 For compound 3c 11 B-NMR nuclear magnetic resonance spectrum.

[0099] Fig.13 For compound 3d 1 H-NMR nuclear magnetic resonance spectrum.

[0100] Fig.14 For compound 3d 13 C-NMR nuclear magnetic resonance spectrum.

[0101] Fig.15 For compound 3d 19 F-NMR nuclear magnetic resonance spectrum.

[0102] Fig.16 For compound 3d 11 B-NMR nuclear magnetic resonance spectrum.

[0103] Fig.17 For compound 3e 1 H-NMR nuclear magnetic resonance spectrum.

[0104] Fig.18 For compound 3e 13 C-NMR nuclear magnetic resonance spectrum.

[0105] Fig.19 For compound 3e 19 F-NMR nuclear magnetic resonance spectrum.

[0106] Fig. 20 For compound 3e 11 B-NMR nuclear magnetic resonance spectrum.

[0107] Fig.21 For compound 3f 1 H-NMR nuclear magnetic resonance spectrum.

[0108] Fig. 22 For compound 3f 13 C-NMR nuclear magnetic resonance spectrum.

[0109] Fig.23 For compound 3f 19 F-NMR nuclear magnetic resonance spectrum.

[0110] Fig.24 For compound 3f 11 B-NMR nuclear magnetic resonance spectrum.

[0111] Fig.25 For compound 3g 1 H-NMR nuclear magnetic resonance spectrum.

[0112] Fig.26 For compound 3g 13 C-NMR nuclear magnetic resonance spectrum.

[0113] Fig. 27 For compound 3g 19 F-NMR nuclear magnetic resonance spectrum.

[0114] Fig.28 For compound 3g 11 B-NMR nuclear magnetic resonance spectrum.

[0115] Fig.29 For compound 3h 1 H-NMR nuclear magnetic resonance spectrum.

[0116] Fig.30 For compound 3h 13 C-NMR nuclear magnetic resonance spectrum.

[0117] Fig.31 For compound 3h 19 F-NMR nuclear magnetic resonance spectrum.

[0118] Fig.32 For compound 3h 11 B-NMR nuclear magnetic resonance spectrum.

[0119] Fig.33 For compound 3i 1 H-NMR nuclear magnetic resonance spectrum.

[0120] Fig.34 For compound 3i 13 C-NMR nuclear magnetic resonance spectrum.

[0121] Fig.35 For compound 3i 19 F-NMR nuclear magnetic resonance spectrum.

[0122] Fig.36 For compound 3i 11 B-NMR nuclear magnetic resonance spectrum. DETAILED DESCRIPTION

[0123] The present invention is further described in detail with reference to the following specific examples and drawings. The process, conditions, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are all common knowledge and common common sense in the art and are not particularly limited by the present invention.

[0124] Example 1: Preparation of potassium acyl trifluoroborate 3a

[0125] Step 1: AIBN (4.1 mg, 0.025 mmol), NBS (204.7 mg, 1.15 mmol) and benzyl borate (0.5 mmol) were added to an oven-dried 15 mL vial with a magnetic stir bar. The vial was sealed with a polypropylene open-top cap with a PTFE / silicone rubber septum, evacuated and refilled with argon for three cycles, and DCE (2.5 mL) was added via a syringe. The resulting reaction mixture was vigorously stirred at 80°C for 4 hours. After the reaction was cooled to room temperature, the solvent was removed under vacuum. The resulting mixture was filtered through celite, rinsed with petroleum ether (2 mL×3), and concentrated in vacuo. The crude product was used in the next step without further purification.

[0126] Step 2: To an oven-dried 20 mL vial with a magnetic stir bar was added gem-dibromide benzyl borate and HFIP (2.5 mL). 2 (234.3 mg, 3.0 mmol) dissolved in H 2 O (0.5 ml), then added dropwise at ambient temperature. The vial was sealed with a polypropylene cap, and the mixture was stirred at 60 ° C for 2 hours. After the reaction was cooled to room temperature, the volatiles were completely removed under vacuum. The mixture was redissolved in acetone and filtered through diatomaceous earth. The filter cake was rinsed with acetone several times until the filtrate was colorless. The combined filtrate was concentrated in vacuo again. The resulting solid was washed with dichloromethane to obtain the desired product as a white solid in a yield of 90%.

[0127]

[0128] Spectral analysis data 3a:

[0129] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.22(d,J=8.0Hz,2H),7.74(d,J=8.0Hz,2H); 13 CNMR(150MHz,Acetone-d 6 ): δ144.8(br),132.5(q,J=31.8Hz), 129.6(q,J=2.3Hz), 125.6(q,J=3.9Hz), 125.4(q,J=271.5Hz); 19 F NMR (565MHz, Acetone-d 6 ): δ – 63.2, – 145.1 (dd, J = 101.2, 49.0Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=51.0Hz).

[0130] Example 2: Preparation of potassium acyl trifluoroborate 3b

[0131] Same as Example 1, yield 82% (as shown in the following structural formula)

[0132]

[0133] Spectral analysis data 3b:

[0134] 1 H NMR (600 MHz, DMSO-d 6 ): δ8.01(d,J=7.9Hz,2H),7.88(d,J=7.9Hz,2H); 13 CNMR (150MHz, DMSO-d 6 ): δ143.7(br),132.3,128.2(q,J=2.5Hz),118.8,113.0; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.1 (dd, J = 101.1, 49.2Hz); 11 B NMR (193 MHz, DMSO-d 6 ):δ–1.2(q,J=51.7Hz).

[0135] Example 3: Preparation of potassium acyl trifluoroborate 3c

[0136] Same as Example 1, yield 96% (as shown in the following structural formula)

[0137]

[0138] Spectral analysis data 3c:

[0139] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.14(d,J=8.2Hz,2H),8.04(d,J=8.4Hz,2H),4.36(q,J=7.1Hz,2H),1.37(t,J=7.1Hz,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ166.6,133.2,129.7,129.0,61.5,14.5; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.6 (dd, J = 95.7, 43.7Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=40.5Hz).

[0140] Example 4: Preparation of potassium acyl trifluoroborate 3d

[0141] Same as Example 1, yield 92% (as shown in the following structural formula)

[0142]

[0143] Spectral analysis data 3d:

[0144] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.19-8.16(m,2H),7.34-7.32(m,2H); 13 C NMR (150 MHz, Acetone-d 6 ): δ151.7,140.8(br),131.2(q,J=2.4Hz),121.3(q,J=255.8Hz),120.8; 19 F NMR (565MHz, Acetone-d 6 ): δ – 58.3, – 144.9 (dd, J = 101.7, 49.1Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=49.0Hz).

[0145] Example 5: Preparation of potassium acyl trifluoroborate 3e

[0146] Same as Example 1, yield 89% (as shown in the following structural formula)

[0147]

[0148] Spectral analysis data 3e:

[0149] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.14-8.12(m,2H),7.13-7.10(m,2H); 13 C NMR (150 MHz, Acetone-d 6 ): δ165.5(d,J=248.5Hz), 139.0(br), 131.8(dq,J=8.7,2.5Hz), 115.2(d,J=21.5Hz); 19 F NMR (565MHz, Acetone-d 6 ): δ – 111.6, – 144.8 (dd, J = 102.6, 50.1Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=51.8Hz).

[0150] Example 6: Preparation of potassium acyl trifluoroborate 3f

[0151] Same as Example 1, yield 80% (as shown in the following structural formula)

[0152]

[0153] Spectral analysis data 3f:

[0154] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.06(d,J=8.2Hz,2H),7.41(d,J=8.5Hz,2H); 13 CNMR(150MHz,Acetone-d 6 ): δ140.7(br),137.3,131.0(q,J=2.5Hz),128.7; 19 F NMR (565MHz, Acetone-d 6 ): δ – 144.9 (dd, J = 101.7, 48.5Hz); 11 B NMR (193MHz, Acetone-d6 ):δ–0.9(q,J=51.7Hz).

[0155] Example 7: Preparation of 3 g of potassium acyl trifluoroborate

[0156] Same as Example 1, yield 91% (as shown in the following structural formula)

[0157]

[0158] Spectral analysis data 3g:

[0159] 1 H NMR (600 MHz, Acetone-d 6 ): δ7.99-7.98(m,2H),7.59-7.57(m,2H); 13 C NMR (150 MHz, Acetone-d 6 ): δ131.8, 131.2 (q, J = 2.3Hz), 126.1; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.0 (dd, J = 101.5, 48.1Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=51.2Hz).

[0160] Example 8: Preparation of potassium acyl trifluoroborate 3h

[0161] Same as Example 1, yield 88% (as shown in the following structural formula)

[0162]

[0163] Spectrum analysis data 3h:

[0164] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.36(s,1H),8.32(d,J=7.7Hz,1H),7.78(d,J=7.7Hz,1H),7.64(t,J=7.8Hz,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ142.2(br),132.6,130.3(q,J=31.9Hz),129.5,128.0(q,J=3.6Hz),125.3(br),125.2(q,J=271.3Hz); 19FNMR (565MHz, Acetone-d 6 ): δ – 63.1, – 145.1 (dd, J = 100.6, 47.7Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=50.1Hz).

[0165] Example 9: Preparation of potassium acyl trifluoroborate 3i

[0166] Same as Example 1, yield 80% (as shown in the following structural formula)

[0167]

[0168] Spectral analysis data 3i:

[0169] 1 H NMR (600 MHz, DMSO-d 6 ): δ8.20(s,1H),8.17(d,J=7.8,1H),7.91(d,J=7.6Hz,1H),7.64(t,J=7.7Hz,1H); 13 C NMR (150 MHz, DMSO-d 6 ): δ141.3(br),134.2,132.0(q,J=3.1Hz),131.5(q,J=2.5Hz),129.5,118.9,111.2; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.1 (dd, J = 100.8, 49.4Hz); 11 B NMR (193 MHz, DMSO-d 6 ):δ–1.2(q,J=47.1Hz).

[0170] Example 10: Preparation of potassium acyl trifluoroborate 3j

[0171] Same as Example 1, yield 89% (as shown in the following structural formula)

[0172]

[0173] Spectral analysis data 3j:

[0174] 1 H NMR (600 MHz, Acetone-d 6): δ7.92(d,J=7.6Hz,1H),7.74-7.72(m,1H),7.45-7.41(m,1H),7.22-7.18(m,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ163.6(d,J=243.8Hz), 144.5(br), 130.5(d,J=7.4Hz), 125.3(br), 118.4(d,J=21.7Hz), 115.0(q,J=2.4Hz), 114.9(q,J=2.1Hz); 19 FNMR (565MHz, Acetone-d 6 ): δ – 115.6 (m), – 145.0 (dd, J = 101.6, 48.0Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=51.8Hz).

[0175] Example 11: Preparation of potassium acyl trifluoroborate 3k

[0176] Same as Example 1, yield 83% (as shown in the following structural formula)

[0177]

[0178] Spectrum analysis data 3k:

[0179] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.19(s,1H),8.05(d,J=7.6Hz,1H),7.61-7.59(m,1H),7.36(t,J=7.8Hz,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ134.5,131.9(q,J=3.1Hz),130.8,128.1(q,J=2.5Hz),122.7; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.0 (dd, J = 101.1, 48.2Hz); 11 BNMR (193MHz, Acetone-d 6 ):δ–1.0(q,J=50.9Hz).

[0180] Example 12: Preparation of potassium acyl trifluoroborate 31

[0181] Same as Example 1, yield 89% (as shown in the following structural formula)

[0182]

[0183] Spectrum analysis data 3l:

[0184] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.13(d,J=1.8Hz,1H),7.97(dd,J=8.2,1.9Hz,1H),7.59(d,J=8.3Hz,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ141.9(br),135.1,132.4,131.1,131.0(q,J=2.3Hz),128.8(q,J=2.2Hz); 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.1 (dd, J = 99.8, 47.2Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.0(q,J=51.3Hz).

[0185] Example 13: Preparation of potassium acyl trifluoroborate 3m

[0186] Same as Example 1, yield 75% (as shown in the following structural formula)

[0187]

[0188] Spectrum analysis data 3m:

[0189] 1 H NMR (600 MHz, DMSO-d 6 ): δ7.69(t,J=7.1Hz,1H),7.41-7.37(m,1H),7.17(t,J=7.4,Hz,1H),7.09(dd,J=10.9,8.2Hz,1H); 13 C NMR (150 MHz, DMSO-d 6 ): δ159.4(d,J=252.4Hz), 132.3(br), 131.4(d,J=8.3Hz), 130.3(br), 123.6(d,J=3.5Hz), 115.9(d,J=22.3Hz); 19 F NMR (565 MHz, DMSO-d 6): δ–117.0(q,J=5.0Hz),–144.5(dd,J=101.9,51.7Hz); 11 B NMR (193 MHz, DMSO-d 6 ):δ–1.6(q,J=51.6Hz).

[0190] Example 14: Preparation of potassium acyl trifluoroborate 3n

[0191] Step 1: NBS (204.7 mg, 1.15 mmol) and benzyl borate (0.5 mmol) were added to a dried 15 mL vial with a magnetic stirring bar. The vial was sealed with a polypropylene open-top cap with a PTFE / silicone rubber septum, evacuated and refilled with argon (three cycles), and DCE (2.5 mL) was added via a syringe. The reaction mixture was then placed in a parallel photoreactor (WP-TEC-1020HSL, WATTCAS), irradiated with a 3W 455-460 nm LED lamp, stirred and cooled in circulating cold water at room temperature for 2 hours. The reaction mixture was diluted with petroleum ether (8 mL), filtered through diatomaceous earth, rinsed with petroleum ether / ethyl acetate = 10: 1 (2 mL×3), and concentrated in vacuo. The crude product was used in the next step without further purification.

[0192] Step 2: Same as step 2 of Example 1, with a yield of 88%.

[0193]

[0194] Spectral analysis data 3n:

[0195] 1 H NMR (600 MHz, Acetone-d 6 ): δ7.84-7.81(m,1H),7.34-7.28(m,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ131.1(q,J=2.5Hz),130.8,130.6,130.2,126.8; 19 F NMR (565MHz, Acetone-d 6 ): δ – 146.9 (dd, J = 100.8, 49.4Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.4(q,J=50.8Hz).

[0196] Example 15: Preparation of potassium acyl trifluoroborate 3o

[0197] Same as Example 14, yield 93% (as shown in the following structural formula)

[0198]

[0199] Spectral analysis data 3o:

[0200] 1 H NMR (600 MHz, Acetone-d 6 ): δ7.82(d,J=7.5,1H),7.53-7.52(m,1H),7.36-7.33(m,1H),7.23-7.21(m,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ134.1, 131.2 (q, J = 2.6Hz), 130.8, 127.4, 118.2; 19 F NMR (565MHz, Acetone-d 6 ): δ – 146.6 (dd, J = 100.7, 48.8Hz); 11 BNMR (193MHz, Acetone-d 6 ):δ–1.5(q,J=50.7Hz).

[0201] Example 16: Preparation of potassium acyl trifluoroborate 3p

[0202] Same as Example 14, yield 75% (as shown in the following structural formula)

[0203]

[0204] Spectral analysis data 3p:

[0205] 1 H NMR (600 MHz, Acetone-d 6 ): δ7.97(dd,J=8.6,6.5Hz,1H),7.16-7.09(m,2H); 13 C NMR (150 MHz, Acetone-d 6 ): δ163.2(d,J=249.2Hz), 133.7(d,J=2.8Hz), 133.6(dq,J=9.3,2.6Hz), 131.9(d,J=10.3Hz), 118.0(d,J=24.7Hz), 113.8(d,J=20.9Hz); 19 F NMR (565MHz, Acetone-d 6): δ – 112.6, – 146.6 (dd, J = 100.2, 48.7Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.4(q,J=50.4Hz).

[0206] Example 17: Preparation of potassium acyl trifluoroborate 3q

[0207] Same as Example 1, yield 94% (as shown in the following structural formula)

[0208]

[0209] Spectral analysis data 3q:

[0210] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.08(d,J=6.9Hz,2H),7.43-7.36(m,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ131.7, 129.2 (q, J = 2.5Hz), 128.5; 19 F NMR (565MHz, Acetone-d 6 ): δ – 144.7 (dd, J = 103.1, 49.0Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.8(q,J=51.9Hz).

[0211] Example 18: Preparation of potassium acyl trifluoroborate 3r

[0212] Same as Example 1, yield 85% (as shown in the following structural formula)

[0213]

[0214] Spectrum analysis data 3r:

[0215] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.02(d,J=8.1Hz,2H),7.42(d,J=8.6Hz,2H),1.32(s,9H); 13 C NMR (150 MHz, Acetone-d 6 ): δ154.8,140.2(br),129.3(br),125.4,35.4,31.6; 19F NMR (565MHz, Acetone-d 6 ): δ – 144.6 (dd, J = 103.0, 47.8Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.8(q,J=51.4Hz).

[0216] Example 19: Preparation of potassium acyl trifluoroborate 3s

[0217] Same as Example 1, yield 91% (as shown in the following structural formula)

[0218]

[0219] Spectrum analysis data 3s:

[0220] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.12(d,J=8.4Hz,2H),7.13(d,J=8.6Hz,2H),2.27(s,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ169.4,154.1,139.6(br),130.6,121.8,21.0; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.2 (dd, J = 100.0, 42.5Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.8(q,J=52.1Hz).

[0221] Example 20: Preparation of potassium acyl trifluoroborate 3t

[0222] Same as Example 1, yield 62% (as shown in the following structural formula)

[0223]

[0224] Spectral analysis data 3t:

[0225] 1 H NMR (500 MHz, Acetone-d 6 ): δ7.41-7.39(m,2H),6.81(dd,J=8.7,3.1Hz,1H),3.78(s,3H); 13 C NMR (150 MHz, Acetone-d 6): δ159.3, 134.6, 116.8 (q, J = 2.6Hz), 116.2, 108.4, 55.7; 19 FNMR (565MHz, Acetone-d 6 ): δ – 146.5 (dd, J = 100.5, 48.7Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.5(q,J=50.1Hz).

[0226] Example 21: Preparation of potassium acyl trifluoroborate 3u

[0227] Same as Example 1, yield 68% (as shown in the following structural formula)

[0228]

[0229] Spectrum analysis data 3u:

[0230] 1 H NMR (500 MHz, Acetone-d 6 ): δ7.77(d,J=2.6Hz,1H),7.41(dd,J=8.8,2.7Hz,1H),6.94(d,J=8.8Hz,1H),3.75(s,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ157.5, 133.4, 133.2 (q, J = 2.5Hz), 115.3, 112.6, 56.5; 19 F NMR (565MHz, Acetone-d 6 ): δ – 147.3 (dd, J = 100.3, 48.3Hz); 11 BNMR (193MHz, Acetone-d 6 ):δ–1.5(q,J=50.7Hz).

[0231] Example 22: Preparation of potassium acyl trifluoroborate 3v

[0232] Same as Example 14, yield 52% (as shown in the following structural formula)

[0233]

[0234] Spectral analysis data 3v:

[0235] 1 H NMR (600 MHz, Acetone-d 6): δ7.73-7.72(m,1H),7.29-7.26(m,1H),6.96-6.95(m,1H),6.91-6.89(m,1H),3.75(s,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ158.2, 131.5 (q, J = 2.3Hz), 131.4, 120.5, 113.0, 56.2; 19 F NMR (565MHz, Acetone-d 6 ): δ – 146.9 (dd, J = 101.8, 47.8Hz); 11 BNMR (193MHz, Acetone-d 6 ):δ–1.3(q,J=51.7Hz).

[0236] Example 23: Preparation of Potassium Acyl Trifluoroborate 3w

[0237] Same as Example 14, yield 79% (as shown in the following structural formula)

[0238]

[0239] Spectrum analysis data 3w:

[0240] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.07(d,J=8.7Hz,2H),6.90(d,J=8.8Hz,2H),3.83(s,3H); 13 C NMR (150 MHz, Acetone-d 6 ): δ163.1,131.4(q,J=2.2Hz),113.7,55.6; 19 FNMR (565MHz, Acetone-d 6 ): δ – 144.4 (dd, J = 103.1, 47.7Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.8(q,J=53.7Hz).

[0241] Example 24: Preparation of Potassium Acyl Trifluoroborate 3x

[0242] Same as Example 1, yield 83% (as shown in the following structural formula)

[0243]

[0244] Spectral analysis data 3x:

[0245] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.86-8.84(m,1H),8.36(d,J=7.1Hz,1H),7.92(d,J=8.2Hz,1H),7.89-7.85(m,1H),7.52(dd,J=8.2,7.1Hz,1H),7.46-7.42(m,2H); 13 C NMR (150 MHz, Acetone-d 6 ): δ140.8(br),134.8,131.2,131.0(q,J=3.0Hz),130.9,128.8,127.5,127.2,126.2,125.6; 19 F NMR (565MHz, Acetone-d 6 ): δ – 145.2 (dd, J = 102.1, 47.3Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.0(q,J=52.5Hz).

[0246] Example 25: Preparation of potassium acyl trifluoroborate 3y

[0247] Same as Example 14, yield 62% (as shown in the following structural formula)

[0248]

[0249] Spectral analysis data 3y:

[0250] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.96(d,J=2.3Hz,1H),8.16(dd,J=8.2,2.3Hz,1H),7.62(d,J=8.5Hz,1H); 13 C NMR (150 MHz, Acetone-d 6 ): δ152.0 (q, J = 2.8Hz), 144.8, 138.7, 128.6; 19 FNMR (565MHz, Acetone-d 6 ): δ – 145.8 (dd, J = 99.9, 48.9Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–1.0(q,J=50.4Hz).

[0251] Example 26: Preparation of potassium acyl trifluoroborate 3z

[0252] Same as Example 14, yield 83% (as shown in the following structural formula)

[0253]

[0254] Spectral analysis data 3z:

[0255] 1 H NMR (600 MHz, Acetone-d 6 ): δ8.13(d,J=8.5Hz,2H),7.86(d,J=8.8Hz,2H),7.78(d,J=8.5Hz,2H),7.59 (d,J=8.5Hz,2H),7.15(d,J=8.6Hz,2H),7.11(d,J=8.8Hz,2H),1.85(s,6H); 13 C NMR (150 MHz, Acetone-d 6 ): δ194.1, 172.5, 160.4, 153.9, 138.4, 137.6, 132.9, 132.1, 131.5, 130.9 (d, J = 2.8Hz), 129.3, 121.7, 118.3, 80.2, 25.6; 19 F NMR (565MHz, Acetone-d 6 ): δ – 147.7 (dd, J = 102.7, 35.4Hz); 11 B NMR (193MHz, Acetone-d 6 ):δ–0.9(q,J=52.0Hz).

[0256] From the above examples and the measured data, it can be seen that the method for preparing acyl trifluoroborate compounds by the method of the present application is simple and convenient to operate, the required raw materials are cheap and easy to obtain, the synthesis route can be simplified, the production efficiency can be improved, and the scale-up experiment can be carried out during the synthesis process, which is suitable for industrial production. The obtained products can also be further converted into a variety of high value-added chemicals.

[0257] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the present invention, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the attached claims.

Claims

1. A method for synthesizing acyl trifluoroborate compounds by using benzyl borate compounds, It is characterized in that The synthesis method is shown in the following formula I: The following steps are involved: Step 1: In a first organic solvent, a benzyl borate compound represented by formula (1) and N-bromosuccinimide are used as raw materials, and azobisisobutyronitrile is added to react to obtain a geminal halobenzyl borate compound represented by formula (2); and / or, In a first organic solvent, a benzyl borate compound represented by formula (1) is used as a raw material and reacts with N-bromosuccinimide under light conditions to produce a geminal halobenzyl borate compound represented by formula (2); Step 2: In a mixed solvent of a second organic solvent and water, the geminal halobenzyl borate compound represented by formula (2) is reacted with potassium bifluoride, cesium fluoride and hydrochloric acid or ammonium bifluoride in a mixed solvent under stirring to obtain a compound represented by formula (3), formula (4) or formula (5); Step 3: reacting the compound represented by formula (3) or formula (4) with an amine in a third organic solvent to obtain a compound represented by formula (6); Wherein, Ar is aryl, substituted aryl, heteroaryl, substituted heteroaryl; R 1 , R 2 are independently selected from the same or different alkyl groups, or form a ring.

2. The method according to claim 1, It is characterized in that In step 1, when azobisisobutyronitrile is added to a first organic solvent to react with a benzyl borate compound represented by formula (1) and N-bromosuccinimide as raw materials to obtain a halogenated benzyl borate compound represented by formula (2), the first organic solvent is any one or a mixture of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents; the amount of the first organic solvent used is 1-10 ml; The molar ratio of the benzyl borate compound represented by formula (1), the N-bromosuccinimide and the azobisisobutyronitrile is (1-1.2): (2-4): (0.05-0.20); The reaction temperature is 0°C-80°C; the reaction time is 1-12h.

3. The method according to claim 1, It is characterized in that In step 1, in a first organic solvent, a benzyl borate compound represented by formula (1) is used as a raw material to undergo a photochemical reaction with N-bromosuccinimide under light conditions to obtain a geminal halobenzyl borate compound represented by formula (2), wherein the first organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of more than one thereof; the amount of the first organic solvent used is 1-10 ml; The molar ratio of the benzyl borate compound represented by formula (1) to the N-bromosuccinimide is (1-1.2):(2-4); The reaction temperature is 0°C-60°C; the reaction time is 1-12h; The illumination condition is visible light with a wavelength of 400-700nm.

4. The method according to claim 1, It is characterized in that In step 2, the second organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of more thereof; the volume ratio of the second organic solvent to the water is (5-10): (1-2); The molar ratio of the geminal halobenzyl borate compound represented by formula (2) to the potassium bifluoride, the cesium fluoride or the ammonium bifluoride is (1-1.2):(4-12); the molar ratio of the cesium fluoride to the hydrochloric acid is (6-12):(1-5); The reaction temperature is 0°C-80°C; the reaction time is 1-8h.

5. The method according to claim 1, It is characterized in that In step 3, the third organic solvent is selected from any one of alkane solvents, aromatic solvents, alcohol solvents, nitrile solvents, ether solvents, ketone solvents, amide solvents, chloroalkane solvents, and sulfoxide solvents, or a mixture of multiple thereof; The amines include secondary amines; The molar ratio of the compound represented by formula (3) or formula (4) to the amine is (1-1.2): (1-3); The reaction temperature is 0°C-60°C; the reaction time is 1-12h.

6. The acyl trifluoroborate compound prepared by the method according to any one of claims 1 to 5, It is characterized in that The acyl trifluoroborate compounds include acyl trifluoroborate potassium compounds Cesium acyl trifluoroborate compounds Acyl trifluoroborate ammonium salt compounds Wherein, Ar is an aryl group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group.

7. The acyl trifluoroborate compound according to claim 6, It is characterized in that The acyl potassium trifluoroborate compounds include compounds described in the following formula:

8. The acyl trifluoroborate compound according to claim 6, It is characterized in that The acyl cesium trifluoroborate compounds include compounds described in the following formula:

9. The acyl trifluoroborate compound according to claim 6, It is characterized in that The acyl ammonium trifluoroborate salt compound includes a compound described by the following formula:

10. Use of the method according to any one of claims 1 to 5, or the acyl trifluoroborate compound according to any one of claims 6 to 9 in scale-up production, synthesis of amide compounds, synthesis of complex compounds by reaction with dye molecules, and construction of fluorescent molecular compounds.

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