Method for synthesizing hydroxyl-protected alpha-hydroxy aldehyde compound by electrically reducing aromatic ketone

Abstract

The invention provides a method for synthesizing a hydroxyl-protected alpha-hydroxy aldehyde compound by electrically reducing aromatic ketone, which comprises the following steps of: adding aromatic ketone, a formylation reagent, an additive and electrolyte into a reaction electrolytic tank, adding a reaction solvent in an inert gas atmosphere, tightly covering a plug with an electrode, and carrying out electrolytic reaction to obtain the hydroxyl-protected alpha-hydroxy aldehyde compound. And separating and purifying to obtain the hydroxyl-protected alpha-hydroxy aldehyde compound. Clean electrons are used as a reducing reagent, no transition metal residues exist, raw materials are simple and easy to obtain, reaction conditions are mild, and the method has wide substrate universality and high operability, is a green and economical synthesis method, has extremely high potential industrial prospects and has high commercial application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of α-hydroxy aldehyde compounds, and in particular relates to a method for electro-reducing aromatic ketones to synthesize hydroxy-protected α-hydroxy aldehyde compounds. Background Art

[0002] α-Hydroxy aldehyde is an important multi-functional synthetic building block, which can be converted into various new structures through simple reactions. For example, α-hydroxy aldehyde can be converted into α-hydroxy alcohol, α-hydroxy carboxylic acid, α-hydroxy ester, α-hydroxy nitrile, etc. In addition, through benzoin rearrangement, α-hydroxy aldehyde can also be converted into new products, which provide key raw materials for the synthesis of drugs and active molecules ((a) J. Am. Chem. Soc. 2014, 136, 13971-13974; (b) Synlett 2018, 29, 2015-2018; (c) J. Org. Chem. 2019, 84, 16003-16012; (d) Org. Lett. 2020, 22, 5041-5045; (e) ACS Omega 2020, 5, 25199-25208; (f) Org. Lett. 2021, 23, 1516-1520.).

[0003] For the synthesis of α-hydroxy aldehydes, traditional methods involve pre-preparing formyl anion equivalents, then adding them to carbonyl compounds, and finally removing the formyl protecting group to obtain α-hydroxy aldehydes ((a) J. Chem. Soc., Chem. Commun. 1989, 1256-1258; (b) Tetrahedron Lett. 1989, 30, 6657-6660; (c) Tetrahedron Lett. 1993, 34, 3907-3910; (d) Angew. Chem. Int. Ed. 2007, 46, 4176-4179.). Similar methods include attacking protected formyl ketones with nucleophiles and then deprotecting to obtain α-hydroxy aldehydes ((a) Chem. Lett. 1978, 7, 1253-1256; (b) J. Am. Chem. Soc. 1984, 106, 2943-2948; (c) Synthesis 1984, 1984, 1025-1027; (d) J. Org. Chem. 2001, 66, 2484-2486.). Additionally, α-hydroxy aldehydes can also be prepared by adding cyanide anions to carbonyl compounds followed by hydrolysis (Tetrahedron 1994, 50, 2821.). Furthermore, Ramana reported a method for the oxidative rearrangement of alkenes in the presence of stoichiometric oxidants to prepare α-hydroxy aldehydes (ACS Omega 2020, 5, 25199-25208;). The above methods have drawbacks such as long reaction routes, low atom economy, poor functional group compatibility, the need to use highly toxic reagents, and stoichiometric oxidants.

[0004] Therefore, it is highly necessary to design a simple, mild, and atom-economical method for the synthesis of α-hydroxy aldehydes. Summary of the Invention

[0005] The present invention mainly overcomes the deficiencies in the prior art and provides a method for electrochemically reducing aromatic ketones to synthesize hydroxy-protected α-hydroxy aldehyde compounds. In this method, aromatic ketones, formylating reagents, additives, and electrolytes are added to a reaction electrolytic cell, and a reaction solvent is added under an inert gas atmosphere. The stopper equipped with the electrode is tightened, and an electrolytic reaction is carried out. After separation and purification, hydroxy-protected α-hydroxy aldehyde compounds are obtained. The present invention uses clean electrons as reducing reagents, has no transition metal residues, the raw materials are simple and easily available, the reaction conditions are mild, it has a wide substrate generality, strong operability, is a green and economical synthesis method, has extremely high potential for industrialization, and has high commercial application value.

[0006] To achieve the above technical objectives, the technical solution adopted by the present invention is as follows: A method for synthesizing hydroxy-protected α-hydroxy aldehyde compounds by electro-reducing aromatic ketones, and the reaction process is as follows:

[0007] It includes the following steps: Add the aromatic ketone 1, formylation reagent 2, additive, and electrolyte to the reaction electrolytic cell, and add the reaction solvent under an inert gas atmosphere. Tighten the plug equipped with the electrode, and perform an electrolytic reaction. After separation and purification, the hydroxy-protected α-hydroxy aldehyde compound is obtained; Wherein: R 1 is selected from any one or more of hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy, methylthio, fluorine, chlorine, phenyl, trifluoromethyl, naphthyl; R 2 is selected from any one or more of hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy, methylthio, fluorine, chlorine, phenyl, trifluoromethyl, naphthyl; PO is selected from one of trimethylsilyloxy and triethylsilyloxy.

[0008] Furthermore, the molar ratio of the aromatic ketone 1, formylation reagent 2, additive, and electrolyte is 2:4:6:3.75, and the dosage of the reaction solvent is as follows: when the dosage of the aromatic ketone 1 is 0.2 mol, the concentration of the reaction solvent is 0.04 mol / L, and the dosage is 5 mL.

[0009] Furthermore, the reaction electrolytic cell is non-separable.

[0010] Furthermore, the current of the reaction electrolytic cell is 20 mA; the temperature of the electrolytic reaction is room temperature; the time of the electrolytic reaction is 10 h.

[0011] Furthermore, the anode of the electrolytic cell is selected from tin and magnesium materials; the cathode is selected from any one of metal copper wire, glassy carbon, iron wire, tungsten wire, niobium wire, titanium wire, and cobalt wire.

[0012] Furthermore, the electrolyte is tetrabutylammonium hexafluorophosphate; the additive is any one of trimethylchlorosilane and triethylchlorosilane.

[0013] Furthermore, the formylation reagent 2 is any one of N,N-dimethylformamide and N,N-dimethylacetamide.

[0014] Furthermore, the solvent is any one of N,N-dimethylformamide and N,N-dimethylacetamide.

[0015] Furthermore, the separation and purification adopt column chromatography, recrystallization, thin-layer chromatography, or vacuum distillation.

[0016] Further, the eluent in the column chromatography is ethyl acetate - petroleum ether, ethyl acetate - n - hexane, isopropanol - ether or absolute ethanol - methyl tert - butyl ether; the volume ratio of ethyl acetate - petroleum ether, ethyl acetate - n - hexane, isopropanol - ether or absolute ethanol - methyl tert - butyl ether is 1:1 to 50.

[0017] Beneficial effects Compared with the prior art, the present invention has the following advantages: 1. The present invention uses electrons as reducing agents, and there is no transition metal participating in the reaction and no metal residue, which is a green, economical and sustainable organic electrosynthesis method; 2. Compared with the prior art, the raw materials used in the reaction of the present invention are cheap and easily available, the reaction conditions are mild, the atom economy is higher, and the operability is strong; 3. The method provided by the present invention has a wide substrate scope and can synthesize various types of multi - functionalized hydroxy - protected α - hydroxy aldehyde compounds. Description of the drawings

[0018] Figure 1 It is the synthesis route diagram of the α - hydroxy aldehyde compound in the embodiment of the present invention. Detailed implementation manners

[0019] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0020] The synthesis route diagram is as Figure 1 shown, and the α - hydroxy aldehyde compound is synthesized according to the synthesis route diagram.

[0021] Examples 1 - 24: Take a dry reaction test tube, add a magnetic stir bar into it, add aromatic ketone 1 (0.2 mmol), formylation reagent (0.4 mmol) and additive trimethylchlorosilane (0.6 mmol), then bring it into a glove box filled with argon, add electrolyte (0.375 mmol), solvent (5 mL), install a stopper with an electrode and take it out of the glove box. After stirring until all are dissolved, apply the corresponding current at room temperature for reaction for 4 - 7 hours. After the reaction is completed, the reaction solution is extracted with ethyl acetate after adding water, separated, dried, concentrated, and then passed through column chromatography to obtain the target product hydroxy - protected α - hydroxy aldehyde compound 3, as shown in the following reaction equation.

[0022]

[0023] The NMR analysis results of compound 3 are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.92 (s, 1H), 7.38 – 7.30 (m, 10H), -0.02(s, 9H) ppm. The electrode, formylation reagent, solvent, electrolyte, current, and reaction yield values of Examples 1 to 18 are shown in Table 1 below: Table 1 Reaction conditions and yield values of Examples 1 to 18

[0024]

[0025] Note: Superscript a indicates that unless otherwise specified, all reactions were carried out using 1a (0.2 mmol), 2a (1.0 mmol), solvent (5 mL) at room temperature for 10 hours, with the corresponding materials as the anode and cathode; superscript b indicates the isolated yield of the product; superscript c indicates no additive TMSCl; superscript d indicates the reaction was carried out without electricity.

[0026] Example 19: Take a dry reaction tube, add a magnetic stir bar to it, add aromatic ketone 1b (0.2 mmol), formylation reagent FR-1 (0.4 mmol) and additive trimethylchlorosilane (0.6 mmol), then transfer it into a glove box filled with argon. Add electrolyte (0.375 mmol), solvent (5 mL), install a stopper with an electrode and take it out of the glove box. Stir until completely dissolved, then apply the corresponding current at room temperature for 10 hours. After the reaction is completed, the reaction solution is extracted with ethyl acetate after adding water, separated, dried, concentrated, and then purified by column chromatography to obtain the target product, the hydroxy-protected α-hydroxy aldehyde compound 4.

[0027] The chemical structure of 1b is as follows: ; The yield of the target product 4 is 79%, and the chemical structure is as follows: ; The results of NMR analysis are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.91 (s, 1H), 7.38 – 7.36 (m, 3H), 7.36 –7.29 (m, 4H), 7.25 – 7.17 (m, 2H), 1.93 (s, 3H), 0.03 (s, 9H) ppm. 1313C NMR (100 MHz, CDCl3) δ 197.8, 139.9, 139.4, 139.0, 133.1, 128.8, 128.7, 128.5, 127.9, 127.3, 125.4, 87.6, 21.1, 1.9 ppm. HRMS (ESI) calcd for C 18 H 22 NaO2Si + [M+Na] + 321.1281; found 321.1279. Example 20: Basically the same as Example 19, except that: N,N-dimethylamide compound 1c was used, and its chemical structural formula is as follows: ; The yield of the target product 5 was 78%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 1H NMR (400 MHz, CDCl3) δ 10.0 (s, 1H), 7.50 – 7.46 (m, 1H), 7.39 – 7.25 (m, 8H), 0.004 (s, 9H) ppm. 13 13C NMR (100 MHz, CDCl3) δ 197.4, 139.4, 139.2, 134.0, 131.5, 131.1, 130.1, 128.5, 128.2, 127.9, 126.8, 86.6, 1.87 ppm. HRMS (ESI) calcd for C 17 H 20 ClO2Si + [M+H] + 319.0916; found 319.0908. Example 21: Basically the same as Example 19, except that: N,N-dimethylamide compound 1d was used, and its chemical structural formula is as follows: ; The yield of the target product 6 was 67%, and the structural formula is as follows: ; The results of nuclear magnetic resonance analysis are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.91 (s, 1H), 7.36 – 7.31 (m, 5H), 7.25 –7.22 (m, 1H), 7.14 – 7.13 (m, 3H), 2.33 (s, 3H), -0.021 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.9, 140.9, 140.7, 138.2, 129.1, 128.9,128.5, 128.4, 128.3, 128.28, 125.4, 86.9, 21.7, 1.90 ppm. HRMS (ESI) calcd for C 18 H 22 NaO2Si + [M+Na] + 321.1281; found 321.1278. Example 22: It is basically the same as Example 19, except that: N,N-dimethylamide compound 1e is used, and its chemical structural formula is as follows: ; The yield of the target product 7 is 66%, and the structural formula is as follows: ; The results of nuclear magnetic resonance analysis are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 7.40 – 7.28 (m, 8H), 7.25 –7.22 (m, 1H), -0.01 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.4, 143.0, 140.5, 134.6, 129.7, 128.73,128.66, 128.5, 128.2, 126.3, 86.4, 1.87 ppm. HRMS (ESI) calcd for C 17 H 19 ClNaO2Si + [M+Na] +341.0735; found 341.0739. Example 23: Basically the same as Example 19, except that: N,N-dimethylamide compound 1f was used, and its chemical structural formula is as follows: ; The yield of the target product 8 was 53%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.91 (s, 1H), 7.37 – 7.29 (m, 8H), 7.13 –7.06 (m, 3H), 7.01 – 6.94 (m, 3H), -0.01 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.4, 157.6, 157.0, 142.9, 140.7, 129.9,129.7, 128.6, 128.5, 128.3, 123.6, 123.0, 119.1, 118.8, 118.4, 86.7, 1.91ppm. HRMS (ESI) calcd for C 23 H 25 O3Si + [M+H] + 377.1567; found 377.1569. Example 24: Basically the same as Example 19, except that: N,N-dimethylamide compound 1g was used, and its chemical structural formula is as follows: ; The yield of the target product 9 was 65%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.88 (s, 1H), 7.38 – 7.31 (m, 7H), 7.08 –7.02 (m, 2H), -0.01 (s, 9H) ppm. 1313C NMR (100 MHz, CDCl3) δ 198.7, 162.7 (d, J = 246.3 Hz), 140.7, 136.7 (d, J = 3.0 Hz), 130.2 (d, J = 8.0 Hz), 128.6, 128.5, 128.3, 115.4 (d, J = 21.2 Hz), 86.4, 1.8 ppm. 19 19F NMR (377 MHz, CDCl3) δ -113.7 ppm. HRMS (ESI) calcd for C 17 H 20 FO2Si + [M+H] + 303.1211; found 303.1204. Example 25: Basically the same as Example 19, except that: N,N-dimethylamide compound 1h was used, and its chemical structural formula is as follows: ; The yield of the target product 5 was 55%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 7.37 – 7.30 (m, 9H), 0.003 (s, 9H) ppm. 13 13C NMR (100 MHz, CDCl3) δ 198.5, 140.5, 139.5, 134.4, 129.6, 128.68, 128.67, 128.58, 128.2, 86.4, 1.89 ppm. HRMS (ESI) calcd for C 17 H 19 ClNaO2Si + [M+Na] + 341.0735; found 341.0744. Example 26: Basically the same as Example 19, except that: N,N-dimethylamide compound 1i was used, and its chemical structural formula is as follows: ; The yield of the target product 11 was 64%, and its structural formula is as follows: ; The results of NMR analysis were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.36 – 7.31 (m, 5H), 7.22 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 2.36 (s, 3H), -0.02 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.8, 140.9, 138.2, 137.9, 129.2, 128.5, 128.31, 128.30, 128.26, 86.8, 21.3, 1.92 ppm. HRMS (ESI) calcd for C 18 H 22 NaO2Si + [M+Na] + 321.1281; found 321.1283. Example 27: It was basically the same as Example 19, except that the N,N-dimethylamide compound 1j was used, and its chemical structural formula is as follows: ; The yield of the target product 12 was 70%, and its structural formula is as follows: ; The results of NMR analysis were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.86 (s, 1H), 7.36 – 7.31 (m, 5H), 7.24 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), -0.02 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.7, 159.6, 140.8, 132.9, 129.8, 128.5, 128.28, 128.25, 113.9, 86.6, 55.4, 1.89 ppm. HRMS (ESI) calcd for C 18 H 22 NaO3Si + [M+Na] + 337.1230; found 337.1222. Example 28: Basically the same as Example 19, except that: N,N-dimethylamide compound 1k was used, and its chemical structural formula is as follows: ; The yield of the target product 13 was 49%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 7.63 – 7.59 (m, 4H), 7.47 –7.35 (m, 10H), 0.035 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.7, 141.2, 140.8, 140.5, 139.8, 129.0,128.7, 128.6, 128.4, 128.36, 127.7, 127.24, 127.20, 86.8, 1.95.ppm. HRMS (ESI) calcd for C 23 H 24 NaO2Si + [M+Na] + 383.1438; found 383.1439. Example 29: Basically the same as Example 19, except that: N,N-dimethylamide compound 1l was used, and its chemical structural formula is as follows: ; The yield of the target product 14 was 61%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 11H NMR (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.42 – 7.31 (m, 7H), 7.20 (d, J = 8.0 Hz, 2H), -0.01 (s, 9H) ppm. 13 13C NMR (100 MHz, CDCl3) δ 198.6, 149.1, 140.5, 139.5, 129.8 128.72, 128.67, 128.3, 120.8, 120.5 (q, J = 255.8 Hz), 86.3, 1.84 ppm. HRMS (ESI) calcd for C 18 H 20 F3O3Si + [M+H] + 369.1128; found 369.1117. Example 30: Basically the same as Example 19, except that: N,N-dimethylamide compound 1m was used, and its chemical structural formula is as follows: ; The yield of the target product 15 was 68%, and the structural formula is as follows: ; The results of NMR analysis were as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.86 (s, 1H), 7.34 – 7.30 (m, 5H), 7.24 – 7.20 (m, 4H), 2.47 (s, 3H), -0.02 (s, 9H) ppm. 13 13C NMR (100 MHz, CDCl3) δ 198.6, 140.7, 139.1, 137.5, 128.8, 128.6, 128.4, 128.3, 126.2, 86.6, 15.6, 1.92 ppm. HRMS (ESI) calcd for C 18 H 22 NaO2SSi + [M+Na] + 353.1002; found 353.1007. Example 31: Basically the same as Example 19, except that: N,N-dimethylamide compound 1n is used, and its chemical structural formula is as follows: ; The yield of the target product 16 is 70%, and the structural formula is as follows: ; The results of NMR analysis are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.86 (s, 1H), 7.33 – 7.28 (m, 5H), 6.49 (d,J = 2.4 Hz, 2H), 6.39 – 6.38 (m, 1H), 3.72 (s, 6H), -0.02 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3) δ 198.4, 160.8, 143.1, 140.6, 128.5, 128.4,128.3, 106.4, 99.9, 86.8, 55.5, 1.94 ppm. HRMS (ESI) calcd for C 19 H 24 NaO4Si + [M+Na] + 367.1336; found 367.1332. Example 32: Basically the same as Example 19, except that: N,N-dimethylamide compound 1o is used, and its chemical structural formula is as follows: ; The yield of the target product 17 is 64%, and the structural formula is as follows: ; The results of NMR analysis are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.86 (s, 1H), 7.25 – 7.17 (m, 3H), 7.13 (d,J = 8.0 Hz, 2H), 6.95 – 6.81 (m, 3H), 3.75 (s, 3H), 2.33 (s, 3H), -0.03 (s,9H) ppm. 1313C NMR (100 MHz, CDCl3) δ 198.6, 159.7, 142.4, 138.2, 137.8, 129.4, 129.2, 128.3, 120.6, 114.0, 113.5, 86.7, 55.4, 21.3, 1.9 ppm. HRMS (ESI) calcd for C 19 H 24 NaO3Si + [M+Na] + 351.1387; found 351.1385. Specific Application 1 of Hydroxy-Protected α-Hydroxy Aldehyde Compound 3: Dissolve α-hydroxy aldehyde compound 3 (0.2 mmol) in ethyl acetate (30 mL), add dilute hydrochloric acid (30 mL, 1 M) to the above system, react at room temperature for 5 min, then transfer the reaction mixture to a separatory funnel, separate the layers, extract the aqueous phase with ethyl acetate (3 x 10 mL), combine the organic phases, wash with water and saturated brine, then dry over anhydrous sodium sulfate, concentrate and purify by column chromatography to obtain α-hydroxy aldehyde 18. The chemical structural formula of hydroxy-protected α-hydroxy aldehyde compound 3 is as follows: ; The yield of the derived product 18 is 94%, and its structural formula is as follows: ; The results of NMR analysis are as follows: 1 1H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 7.45 – 7.33 (m, 10H), 4.40 (s, 1H) ppm. 13 13C NMR (100 MHz, CDCl3) δ 198.2, 139.5, 129.0, 128.6, 127.6, 83.6 ppm. 13 13C NMR (100 MHz, CDCl3) δ 198.2, 139.5, 128.9, 128.6, 127.6, 83.6 ppm; Specific Application 1 of α-Hydroxy Aldehyde 18: Under room temperature and air conditions, add the pre-prepared α-hydroxy aldehyde 18 (0.3 mmol), sodium carbonate (0.6 mmol), diethylamine (3 mmol) and 1,2-dichloroethane (1.5 mL) into a round-bottom flask. Heat the reaction system to 80 °C and stir continuously for 16 hours. After the reaction is completed, concentrate under reduced pressure, and then purify the crude product by flash column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to obtain the target compound as a transparent oil 19. The chemical structural formula of α-hydroxy aldehyde 18 is as follows: ; The yield of the derived product 19 is 60%, and its structural formula is as follows: ; The results of NMR analysis are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.48 – 7.46 (m, 4H), 7.34 – 7.32 (m, 6H), 4.33 (t, J = 5.9 Hz, 2H), 2.68 (t, J = 5.9 Hz, 2H), 2.47 (q, J = 7.1 Hz, 4H), 0.95 (t, J = 7.1 Hz, 6H) ppm. In the above Examples 1 to 32 and Specific Application 1, the eluent can also be replaced by isopropanol-ether, ethyl acetate-n-hexane or absolute ethanol-methyl tert-butyl ether; column chromatography can be replaced by recrystallization, thin-layer chromatography or distillation under reduced pressure.

[0028] In summary, the present invention discloses a method for synthesizing hydroxy-protected α-hydroxy aldehyde compounds by electro-reducing aromatic ketones. In this method, an aromatic ketone, a formylating reagent, an additive, and an electrolyte are added to a reaction electrolytic cell, and a reaction solvent is added under an inert gas atmosphere. Then, the stopper equipped with electrodes is tightened, and an electrolytic reaction is carried out. After separation and purification, the hydroxy-protected α-hydroxy aldehyde compounds are obtained; the present invention uses clean electrons as a reducing reagent, has no transition metal residue, the raw materials are simple and easily available, the reaction conditions are mild, has a wide substrate generality, and is highly operable. It is a green and economical synthesis method with extremely high potential for industrialization.

[0029] Finally, it should also be noted that the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements, but also includes other elements not expressly listed, or also includes elements inherent to such process, method, article or device.

[0030] Although the preferred embodiments of the present invention have been described, additional changes and modifications can be made to these embodiments by those skilled in the art once they learn of the basic inventive concept. Therefore, the appended claims are intended to be construed to include the preferred embodiments as well as all changes and modifications that fall within the scope of the present invention.

[0031] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.

Claims

1. A method for synthesizing hydroxy-protected α-hydroxy aldehyde compounds by electro-reducing aromatic ketones, characterized in that, The reaction process of the synthesis method is as follows: ； It includes the following steps: Add aromatic ketone 1, formylation reagent 2, additive, and electrolyte into the reaction electrolytic cell, add the reaction solvent under an inert gas atmosphere, tightly cover the plug equipped with the electrode, and perform electrolytic reaction. After separation and purification, the α-hydroxy aldehyde compound protected by hydroxyl group is obtained; Wherein: R 1 is selected from any one or more of hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy, methylthio, fluorine, chlorine, phenyl, trifluoromethyl, naphthyl; R 2 is selected from any one or more of hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy, methylthio, fluorine, chlorine, phenyl, trifluoromethyl, naphthyl; PO is selected from one of trimethylsilyloxy and triethylsilyloxy.

2. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, wherein The molar ratio of the aromatic ketone 1, formylation reagent 2, additive, and electrolyte is 2:4:6:3.

75. The dosage of the reaction solvent is: when the dosage of the aromatic ketone 1 is 0.2 mol, the concentration of the reaction solvent is 0.04 mol / L, and the dosage is 5 mL.

3. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, characterized in that, The reaction electrolytic cell is non-separable.

4. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, characterized in that, The current of the reaction electrolytic cell is 20 mA; the temperature of the electrolytic reaction is room temperature; the time of the electrolytic reaction is 10 h.

5. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, characterized in that, The anode of the electrolytic cell is selected from tin and magnesium materials; the cathode is selected from any one of metal copper wire, glassy carbon, iron wire, tungsten wire, niobium wire, titanium wire, and cobalt wire.

6. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, characterized in that, The electrolyte is tetrabutylammonium hexafluorophosphate; the additive is any one of trimethylchlorosilane and triethylchlorosilane.

7. The method for synthesizing a hydroxyl-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, characterized in that, The formylation reagent 2 is any one of N,N-dimethylformamide and N,N-dimethylacetamide.

8. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, wherein, The solvent is any one of N,N-dimethylformamide and N,N-dimethylacetamide.

9. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 1, wherein, The separation and purification adopt column chromatography, recrystallization, thin-layer chromatography or vacuum distillation.

10. The method for synthesizing a hydroxy-protected α-hydroxy aldehyde compound by electro-reducing an aromatic ketone as described in claim 9, characterized in that, The eluent in the column chromatography is ethyl acetate - petroleum ether, ethyl acetate - n-hexane, isopropanol - ether or absolute ethanol - methyl tert-butyl ether; the volume ratio of ethyl acetate - petroleum ether, ethyl acetate - n-hexane, isopropanol - ether or absolute ethanol - methyl tert-butyl ether is 1:1~50.

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