Method for preparing cyclopropyl formaldehyde derivative by electrically promoting condensation of alkenyl cyclobutanol

Abstract

The invention provides the method for preparing the cyclopropyl formaldehyde derivative from the alkenyl cyclobutanol through electrically-promoted ring shrinkage, and the method does not need to use a precious metal catalyst, and is mild in reaction condition, short in reaction time, wide in substrate range, simple and convenient in post-treatment, green and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to medicinal chemistry, and in particular to a method for preparing cyclopropylcarboxaldehyde derivatives from alkenylcyclobutanol by electrocatalytic ring contraction. Background Art

[0002] Cyclopropylcarboxaldehyde and its derivatives are important pharmaceutical and chemical intermediates and are commonly used reagents for introducing cyclopropyl groups into drug molecules. The three-membered ring structure of the anti-AIDS drug Efavirenz is introduced by cyclopropylacetylene, and cyclopropylcarboxaldehyde is an important raw material for synthesizing cyclopropylacetylene. In addition, Chinese patent CN 114591192A discloses a method for preparing N-cyclopropylmethylaniline using cyclopropylcarboxaldehyde; Chinese patent CN110028423A discloses a method for preparing an important intermediate of the diamide insecticide cyclopropylsulfuronidone by reacting a boron reagent with cyclopropylcarboxaldehyde with a substituted aniline in a trifluoroacetic acid system; Chinese patent CN101115743A discloses a method for preparing the drug elaprilin for acute bacterial skin infections using cyclopropylcarboxaldehyde. Therefore, the synthesis research of cyclopropylcarboxaldehyde and its derivatives is of great importance. Summary of the invention

[0003] The invention provides a method for preparing a cyclopropylcarboxaldehyde derivative by electro-promoted ring contraction of alkenylcyclobutanol. The method does not require the use of a precious metal catalyst, has mild reaction conditions, a short reaction time, a wide substrate range, and a simple and green post-treatment, and is suitable for industrial production.

[0004] To achieve the above object, the technical solution of the present invention is:

[0005] A method for preparing cyclopropylcarboxaldehyde derivatives by electrocatalytic ring contraction of alkenylcyclobutanol, characterized in that the cyclopropylcarboxaldehyde derivatives are prepared by electrocatalysis of alkenylcyclobutanol compound of formula I and reagents, and the reaction scheme is as follows:

[0006]

[0007] R 1 is aryl, heterocyclic or alkyl; R 2 It is hydroxy, halogen, azido, or C1-C6 alkoxy.

[0008] The reagent is selected from triethylamine trihydrogen halide, trimethylsilyl azide, C1-C6 alcohol or water.

[0009] In the above method, when the reagent is water, R 2 is hydroxyl group;

[0010] When the reagent is a C1-C6 alcohol, R 2 is a C1-C6 alkoxy group;

[0011] When the reagent is triethylamine trihalide, R2 is a halogen;

[0012] When the reagent is azidotrimethylsilane, R 2 It is an azido group.

[0013] According to one embodiment of the present invention, the electrocatalytic electrolyte is tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate, tetraethylammonium hexafluorophosphate or lithium tetrafluoroborate; further, the amount of the electrolyte is 1-3 equivalents (compared to the compound of formula I).

[0014] According to one embodiment of the present invention, the electrocatalytic electrolyte is added with a proton additive, and the proton additive is selected from hexafluoroisopropanol, p-toluenesulfonic acid, trifluoroacetic acid or trifluoroethanol; further, the amount of the proton additive is 1-3 equivalents (compared to the compound of formula I)

[0015] According to one embodiment of the present invention, the electrocatalytic anode is RVC, graphite felt, graphite sheet or carbon paper, and the cathode is a foam nickel sheet or a platinum sheet.

[0016] According to one embodiment of the present invention, the organic solvent used in the above-mentioned electrocatalytic reaction is one or a combination of methanol, N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile; preferably, the organic solvent used in the reaction is a mixture of acetonitrile and methanol, wherein the volume ratio of acetonitrile:methanol is 1-9:1.

[0017] According to one embodiment of the present invention, the current used in the above electrocatalytic reaction is 5-12 mA, and the reaction time is 3-6 hours.

[0018] According to one embodiment of the present invention, the electrocatalytic reaction temperature is 15-45°C, preferably room temperature.

[0019] According to one embodiment of the present invention, when the reagent is a C1-C6 alcohol, the above method comprises the following steps: adding an alkenyl cyclobutanol derivative, a C1-C6 alcohol, an electrolyte, a proton additive, and an organic solvent under nitrogen, and stirring the reaction at room temperature to obtain the target compound. When the reagent is methanol, the preparation route is as follows:

[0020]

[0021] According to one embodiment of the present invention, when the reagent is water, the above method comprises the following steps: adding alkenyl cyclobutanol derivatives, water, electrolytes, proton additives, and organic solvents under nitrogen, and stirring the reaction at room temperature to obtain the target compound. The preparation route is as follows:

[0022]

[0023] According to one embodiment of the present invention, when the reagent is triethylamine trihydrogen halide, the above method comprises the following steps: under nitrogen, adding alkenyl cyclobutanol derivative, triethylamine trihydrogen halide, electrolyte, proton additive, organic solvent, and stirring the reaction at room temperature to obtain the target compound. When the reagent is triethylamine trihydrogen fluoride, the preparation route is as follows:

[0024]

[0025] According to one embodiment of the present invention, when the reagent is azidotrimethylsilane, the above method comprises the following steps: adding alkenyl cyclobutanol derivatives, azidotrimethylsilane, electrolyte, proton additive, and organic solvent under nitrogen, and stirring the reaction at room temperature to obtain the target compound. The preparation route is as follows:

[0026]

[0027] According to one embodiment of the present invention, the above-mentioned cyclopropylcarboxaldehyde derivative formula II is selected from the compounds shown in Table 1

[0028] Table 1 Compounds of Formula II

[0029]

[0030]

[0031]

[0032] Beneficial effects:

[0033] The invention provides a method for preparing a cyclopropylcarboxaldehyde derivative by electro-promoted ring contraction of alkenylcyclobutanol. The method does not require the use of a precious metal catalyst, has mild reaction conditions, a short reaction time, a wide substrate range, and a simple and green post-treatment, and is suitable for industrial production. DETAILED DESCRIPTION

[0034] The present invention is described in detail below by specific examples. It is pointed out that the following examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above invention content. Unless otherwise specified, the parts described in the present invention are all weight parts, and the percentages are all mass percentages. The raw materials and reagents used in the present invention are all commercially available products.

[0035] Example 1

[0036] The preparation of 1-(methoxy(phenyl)methyl)cyclopropane-1-carboxaldehyde, the reaction route is as follows:

[0037]

[0038] Specific operation steps: In a 10 mL beaker-type electrolytic cell equipped with a stirring bar, the bottle was filled with a graphite sheet (10 mm × 15 mm × 1.0 mm) and a nickel foam sheet electrode (10 mm x 15 mm × 1 mm), 1 (0.2 mmol, 1.0 equivalent), Bu 4 NBF 4 (0.5 mmol, 0.125 M), TFA (0.4 mmol, 2.0 equiv) in CH 3 CN:CH 3 A solution of 4 mL of 1H 2 O (3:1) was stirred under a nitrogen atmosphere and electrolyzed at a constant current of 10 mA for 3.5 hours at room temperature. The aqueous solution was extracted with ethyl acetate (3×15 mL), and the combined extracts were washed with anhydrous Na 2 SO 4 Dry. Remove the solvent by rotary evaporation under reduced pressure. Then, obtain pure product 1a by silica gel flash column chromatography (eluent: EA / PE=1:60). The product can be stained with 2,4-dinitrophenylhydrazine.

[0039] Table 2. Effects of different electrodes on product preparation

[0040]

[0041] It can be seen from Table 2 that when the anode material is a graphite sheet and the cathode material is a platinum sheet, the yield of the product can achieve relatively good results.

[0042] Table 3. Effect of different electrolytes on product preparation

[0043]

[0044] It can be seen from Table 3 that when the electrolyte is tetrabutylammonium tetrafluoroborate, the yield of the product can achieve relatively good results.

[0045] Table 4. Effect of the amount of electrolyte on product preparation

[0046]

[0047] It can be seen from Table 4 that when the amount of the electrolyte is 0.6 mmol of tetrabutylammonium tetrafluoroborate, the yield of the product can achieve relatively good results.

[0048] Table 5. Effects of different proton additives on product preparation

[0049]

[0050] As shown in Table 5, when the proton additive is trifluoroacetic acid, the yield of the product can achieve relatively good results.

[0051] Table 6. Effect of the amount of proton additive on product preparation

[0052]

[0053] It can be seen from Table 6 that when the amount of the proton additive trifluoroacetic acid is 0.4 mmol, the yield of the product can achieve relatively good results.

[0054] Table 7. Effect of different solvents on product preparation

[0055]

[0056] As shown in Table 7, when the solvent is a mixture of acetonitrile and methanol, the yield of the product can achieve relatively good results.

[0057] Table 8. Effect of different solvent ratios on product preparation

[0058]

[0059] It can be seen from Table 8 that when the ratio of solvent acetonitrile to methanol is 3:1, the yield of the product can achieve relatively good results.

[0060] Table 9. Effects of different current magnitudes and times on product preparation

[0061]

[0062] It can be seen from Table 9 that when the current and time are 10 mA, 3.5 h, the yield of the product can achieve relatively good results.

[0063] Table 10. Effect of different current sizes on product preparation

[0064]

[0065] It can be seen from Table 10 that when the reaction temperature is room temperature (20°C), the yield of the product can achieve relatively good results.

[0066] With reference to the above examples, the universality of the substrate was investigated and the results are shown in Table 11.

[0067] Table 11. Substrate universality investigation

[0068]

[0069]

[0070]

[0071] Example 2

[0072] The preparation of 1-(hydroxy(phenyl)methyl)cyclopropane-1-carboxaldehyde, the reaction route is as follows:

[0073]

[0074] Specific operation steps: In a 10 mL beaker-type electrolytic cell equipped with a stirring bar, the bottle was filled with a graphite sheet (10 mm × 15 mm × 1.0 mm) and a nickel foam sheet electrode (10 mm x 15 mm × 1 mm), 1 (0.2 mmol, 1.0 equivalent), Bu 4 NBF 4 (0.5 mmol, 0.125 M), TFA (0.4 mmol, 2.0 equiv) in CH 3 CN:H 2 The solution in 4 mL of O (1:1) was stirred under a nitrogen atmosphere and electrolyzed at a constant current of 10 mA for 3.5 hours at room temperature. The aqueous solution was extracted with ethyl acetate (3×15 mL), and the combined extracts were washed with anhydrous Na 2 SO 4 Dry. Remove the solvent by rotary evaporation under reduced pressure. Then, obtain pure product 1b by silica gel flash column chromatography (eluent: EA / PE=1:30). The product can be stained with 2,4-dinitrophenylhydrazine.

[0075] Table 12. Effect of different solvents on product preparation

[0076]

[0077] As shown in Table 12, when the solvent is acetonitrile and water (1:1), the yield of the product can achieve relatively good results.

[0078] Table 13. Effect of solvent ratio on product preparation

[0079]

[0080] It can be seen from Table 13 that when the solvent is acetonitrile and water (1:1), the yield of the product can achieve relatively good results.

[0081] Table 14. Effect of the amount of proton additive on product preparation

[0082]

[0083] It can be seen from Table 14 that when the amount of the proton additive is trifluoroacetic acid is 0.4 mmol, the yield of the product can achieve relatively good results.

[0084] Table 15. Effect of different electrolytes on product preparation

[0085]

[0086] It can be seen from Table 15 that when the electrolyte is tetrabutylammonium tetrafluoroborate, the yield of the product can achieve relatively good results.

[0087] With reference to the above examples, the universality of the substrate was examined and the results are shown in Table 16.

[0088] Table 16. Investigation of substrate universality

[0089]

[0090]

[0091] Example 3

[0092] The preparation of 1-(fluoro(phenyl)methyl)cyclopropane-1-carboxaldehyde, the preparation route is as follows:

[0093]

[0094] Specific operation steps: In a 10 mL beaker-type electrolytic cell equipped with a stirring bar, the bottle was filled with carbon paper (10 mm × 15 mm × 1.0 mm) and a platinum electrode (10 mm x 15 mm × 1 mm), 1 (0.2 mmol, 1.0 equivalent), triethylamine trihydrofluoride 0.2 mL, Bu 4 NBF 4 (0.5 mmol, 0.125 M, TFE (0.2 mmol, 1.0 equiv) in CH 3 The solution in 4 mL of CN was stirred under a nitrogen atmosphere and electrolyzed at a constant current of 10 mA for 1.5 hours at room temperature. The aqueous solution was extracted with ethyl acetate (3×15 mL), and the combined extracts were washed with anhydrous Na 2 SO 4 Dry. Remove the solvent by rotary evaporation under reduced pressure. Then, obtain pure product 1c by silica gel flash column chromatography (eluent: EA / PE=1:30). The product can be stained with 2,4-dinitrophenylhydrazine.

[0095] Table 17. Effect of different electrodes on product preparation

[0096]

[0097] It can be seen from Table 17 that when the anode material is carbon paper and the cathode material is platinum sheet, the yield of the product can achieve relatively good results.

[0098] Table 18. Effects of different currents and reaction times on product preparation

[0099]

[0100] It can be seen from Table 18 that when the current and time are 10 mA, 1.5 h, the yield of the product can achieve relatively good results.

[0101] Table 19. Effect of the amount of triethylamine trihydrofluoride on product preparation

[0102]

[0103]

[0104] It can be seen from Table 19 that when the amount of the proton additive trifluoroacetic acid is 0.4 mmol, the yield of the product can achieve relatively good results.

[0105] Table 20. Effects of different proton additives on product preparation

[0106]

[0107] It can be seen from Table 20 that when the proton additive is trifluoroethanol, the yield of the product can achieve relatively good results.

[0108] With reference to the above examples, the universality of the substrate was examined and the results are shown in Table 21.

[0109] Table 21. Substrate universality investigation

[0110]

[0111]

[0112] Example 4

[0113] Preparation of 2-(4-chlorobenzylidene)cyclobutane-1-ol, the preparation route is as follows:

[0114]

[0115] Specific operation steps: In a 10 mL beaker-type electrolytic cell equipped with a stirring bar, the bottle was filled with carbon paper (10 mm × 15 mm × 1.0 mm) and a platinum electrode (10 mm x 15 mm × 1 mm), 1 (0.4 mmol, 2.0 equiv), trimethylsilyl azide (0.2 mmol, 1.0 equiv), Bu 4 NBF 4 (0.4 mmol, 0.1 M, HOAc (0.4 mmol, 2.0 equiv) in CH 3 The solution in 6 mL of CN was stirred under a nitrogen atmosphere and electrolyzed at a constant current of 10 mA for 2 hours at room temperature. The aqueous solution was extracted with ethyl acetate (3×15 mL), and the combined extracts were washed with anhydrous Na 2 SO4 Dry. Remove the solvent by rotary evaporation under reduced pressure. Then, obtain pure product 1d by silica gel flash column chromatography (eluent: EA / PE=1:60). The product can be stained with 2,4-dinitrophenylhydrazine.

[0116] Table 22. Effect of different electrodes on product preparation

[0117]

[0118] It can be seen from Table 22 that when the anode material is carbon paper and the cathode material is platinum sheet, the yield of the product can achieve relatively good results.

[0119] Table 23. Effects of different currents and reaction times on product preparation

[0120]

[0121] It can be seen from Table 23 that when the current and time are 10 mA, 2 h, the yield of the product can achieve relatively good results.

[0122] Table 24. Effects of different proton additives on product preparation

[0123]

[0124] It can be seen from Table 24 that when the proton additive is trifluoroacetic acid, the yield of the product can achieve relatively good results.

[0125] Table 25. Effect of different electrolytes on product preparation

[0126]

[0127] It can be seen from Table 25 that when the electrolyte is tetrabutylammonium tetrafluoroborate, the yield of the product can achieve relatively good results.

[0128] With reference to the above examples, the universality of the substrate was examined and the results are shown in Table 26.

[0129] Table 26. Substrate universality investigation

[0130]

[0131]

[0132]

[0133] The structural analysis data are as follows:

[0134] Compound 1: 1 H NMR (600 MHz, CDCl 3)δ9.07(s,1H),7.27(dd,J=7.3,1.7Hz,2H),7.22(d,J=7.5Hz,2H),7.20(d,J=1.8Hz,1H),4.85( s,1H),3.25(s,3H),1.15–1.13(m,1H),1.11–1.08(m,1H),1.00–0.97(m,1H),0.68–0.65(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.16,138.55,128.48,128.03,127.35,80.35,57.47,36.88,13.17,10.44.

[0135] Compound 2: 1 H NMR (600 MHz, CDCl 3 )δ9.15(s,1H),7.58(td,J=6.9,1.6Hz,4H),7.44(t,J=7.7Hz,2H),7.36(d,J=8.1Hz,3H),4.9 6(s,1H),3.36(s,3H),1.27–1.25(m,1H),1.19(s,1H),1.11–1.08(m,1H),0.84–0.82(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.11,140.93,140.77,137.67,128.93,127.80,127.52,127.21,127.19,80.12,57.53,36.95,13.14,10.51.

[0136] Compound 3: 1 H NMR (600 MHz, CDCl 3 )δ9.07(s,1H),7.89–7.86(m,1H),7.83–7.79(m,2H),7.54–7.46(m,4H),6.03(s,1H),3.4 2(s,3H),1.19(t,J=8.4Hz,2H),0.95(td,J=8.4,5.1Hz,1H),0.14(td,J=8.0,5.1Hz,1H). 13 C NMR (151 MHz, CDCl 3)δ200.92,133.71,133.03,131.51,129.06,128.43,126.50,125.81,12 5.35,123.71,123.07,77.37,76.95,75.60,57.77,36.96,13.80,9.77.

[0137] Compound 4: 1 H NMR (600 MHz, CDCl 3 )δ9.16(s,1H),7.84(ddd,J=8.2,6.4,2.9Hz,3H),7.77(d,J=1.7Hz,1H),7.52–7.47(m,2H),7.39(dd,J=8.5,1.7Hz,1H) ,5.11(s,1H),3.38(s,3H),1.30–1.27(m,1H),1.21–1.16(m,1H),1.10–1.06(m,1H),0.79(ddd,J=9.1,7.1,4.6Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.90,133.70,133.03,131.51,129.05,128.43,126.49,125.81,125.35,123.70,123.07,75.60,57.77,36.96,13.80,9.78.

[0138] Compound 5: 1 H NMR (600 MHz, CDCl 3 )δ9.01(s,1H),7.29(tt,J=1.6,0.6Hz,1H),7.27–7.25(m,2H),7.19–7.17(m,1H),4.88(s,1H),3.31 (s,3H),1.26–1.23(m,1H),1.18–1.15(m,1H),1.10–1.07(m,1H),0.81(ddd,J=9.2,7.1,4.7Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.56,141.21,134.56,129.77,128.21,127.31,125.61,79.36,57.55,36.92,12.72,10.36.

[0139] Compound 6: 1 H NMR (600 MHz, CDCl 3)δ9.13(s,1H),7.39(dd,J=7.7,1.8Hz,1H),7.36(dd,J=7.8,1.4Hz,1H),7.28(td,J=7.5,1.4Hz,1H),7.24 (td,J=7.6,1.9Hz,1H),5.54(s,1H),3.35(s,3H),1.18–1.15(m,1H),1.11–1.08(m,2H),0.45–0.42(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.69,135.53,129.67,129.16,127.76,127.01,76.68,57.73,35.80. Compound 7: 1 H NMR (600 MHz, CDCl 3 )δ9.00(s,1H),7.32(d,J=1.9Hz,1H),7.31(d,J=2.0Hz,1H),7.25–7.24(m,1H),7.23–7.22(m,1H),4.88(s,1H),3.29(s,3H),1.22( ddd,J=9.1,7.2,4.7Hz,1H),1.16(ddd,J=9.7,7.0,4.6Hz,1H),1.06(ddd,J=9.8,7.2,4.7Hz,1H),0.79(ddd,J=9.1,7.1,4.7Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.59,137.45,133.77,129.06,128.72,128.68,128.60,79.31,57.44,36.92,12.56,10.23.

[0140] Compound 8: 1 H NMR (600 MHz, CDCl 3 )δ9.11(s,1H),7.54(d,J=7.9Hz,1H),7.35(d,J=7.7Hz,1H),7.32(t,J=7.5Hz,1H),7.16(td,J=7. 6,1.9Hz,1H),5.51(s,1H),3.34(s,3H),1.17–1.14(m,1H),1.12–1.07(m,2H),0.42–0.37(m,1H). 13 C NMR (151 MHz, CDCl 3)δ200.58,136.94,132.92,129.46,128.01,127.58,124.32,78.75,57.69,35.76,13.84,9.45. Compound 9: 1 H NMR (600 MHz, CDCl 3 )δ8.99(d,J=1.2Hz,1H),7.43(s,1H),7.40(dd,J=7.3,1.8Hz,1H),7.21(q,J=7.7Hz,2H),4.85(s,1H),3.29(s,3H),1.23(ddd, J=8.6,7.0,4.4Hz,1H),1.16(ddt,J=9.9,5.2,2.1Hz,1H),1.07(dtd,J=9.8,5.8,1.7Hz,1H),0.80(ddd,J=8.9,7.0,4.6Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.52,130.60,130.21,130.06,129.91,126.42,126.06,79.30,57.56,36.94,12.72,10.37.

[0141] Compound 10: 1 H NMR (600 MHz, CDCl 3 )δ8.99(s,1H),7.48–7.46(m,2H),7.18(dd,J=8.5,1.8Hz,2H),4.87(s,1H),3.29(s,3H),1.22(dd d,J=9.0,7.2,4.6Hz,1H),1.15(ddd,J=9.7,7.0,4.7Hz,1H),1.07–1.04(m,1H),0.81–0.77(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.55,137.99,131.63,131.51,129.42,129.07,121.91,79.33,77.37,76.95,57.47,57.44,36.87,12.54,10.23.

[0142] Compound 11: 1 H NMR (600 MHz, CDCl 3)δ9.23(s,1H),7.40(t,J=7.5Hz,1H),7.28(ddt,J=7.3,5.2,2.0Hz,1H),7.16(td,J=7.5,1.2Hz,1H) ,7.04(ddd,J=9.7,8.3,1.2Hz,1H),5.25(s,1H),3.35(s,3H),1.17–1.12(m,3H),0.73–0.69(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.81,161.54,159.90,129.63,127.98,124.36,115.57,77.37,76.95,74.69,57.68,35.98,13.56,10.32.

[0143] Compound 12: 1 H NMR (600 MHz, CDCl 3 )δ9.16(s,1H),7.16(d,J=1.3Hz,4H),4.87(s,1H),3.31(s,3H),2.34(s,3H) ,1.21–1.18(m,1H),1.16–1.13(m,1H),1.06–1.02(m,1H),0.75–0.71(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.34,137.73,135.41,129.18,129.15,127.61,127.30,80.35,57.38,36.87,21.26,13.22,10.48.

[0144] Compound 13: 1 H NMR (600 MHz, CDCl 3 )δ8.96(s,1H),7.61(d,J=8.1Hz,2H),7.43(d,J=8.1Hz,2H),4.97(s,1H),3.31(s,3H),1.28(d,J=2.9Hz,1 H), 1.18 (ddd, J=9.8, 7.1, 4.7Hz, 1H), 1.09 (ddd, J=9.8, 7.2, 4.8Hz, 1H), 0.83 (ddd, J=9.2, 7.1, 4.8Hz, 1H). 13 C NMR (151 MHz, CDCl 3)δ200.25,143.35,127.70,125.47,125.45,125.42,125.40,79.19,57.58,37.00,12.39,10.26.

[0145] Compound 14: 1 H NMR (600 MHz, CDCl 3 )δ9.12(s,1H),7.27(dd,J=5.0,1.2Hz,1H),7.02(ddd,J=3.5,1.2,0.7Hz,1H),6.99(dd,J=5.0, 3.5Hz,1H),5.03(s,1H),3.35(s,3H),1.41–1.38(m,1H),1.21–1.17(m,2H),1.07–1.04(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ200.65,143.00,126.68,126.24,125.39,77.37,76.95,76.85,57.44,37.12,13.28,11.59. Compound 15: 1 H NMR (600 MHz, CDCl 3 )δ9.14(s,1H),7.31–7.28(m,2H),7.26(s,1H),7.25–7.22(m,2H),4.97(s,1H),3.43(q,J=6.9Hz,2H),1. 19–1.17(m,1H),1.13–1.10(m,1H),1.00(ddd,J=9.7,7.3,4.5Hz,1H),0.70(ddd,J=9.1,7.1,4.5Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.42,139.38,128.39,127.89,127.33,78.44,65.01,36.86,15.40,13.15,10.76.

[0146] Compound 16: 1 H NMR (600 MHz, CDCl 3)δ9.19(s,1H),7.36–7.32(m,2H),7.30–7.27(m,3H),4.97(s,1H),3.39(t,J=6.6Hz,2H),1.59–1.54(m,2H),1.26(q,J=3.1Hz,9H) ,1.23–1.20(m,1H),1.18–1.14(m,1H),1.05(ddd,J=9.7,7.2,4.4Hz,1H),0.88(t,J=7.0Hz,4H),0.78(ddd,J=9.2,7.1,4.4Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.48,139.52,128.37,127.86,127.39,78.61,69.78,36.92,31.97 ,31.58,30.34,29.95,29.54,29.39,26.33,22.79,14.24,13.17,10.90.

[0147] Compound 17: 1 H NMR (600 MHz, CDCl 3 )δ9.14(s,1H),7.30(dd,J=4.9,3.1Hz,1H),7.20(s,1H),7.00–6.98(m,1H),4.93(s,1H),3.34(s,3H),1. 26–1.23(m,1H),1.19–1.16(m,1H),1.11(ddd,J=9.7,7.2,4.4Hz,1H),0.87(ddd,J=9.1,7.0,4.3Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.13,140.51,126.52,126.11,122.60,77.28,57.52,36.53,13.31,11.03.

[0148] Compound 18: 1 H NMR (600 MHz, CDCl 3 )δ8.82(s,1H),7.47–7.45(m,2H),7.23–7.21(m,2H),5.16(s,1H),3.06(s,1H),1.20–1.15(m,3H),0.93–0.89(m,1H). 13 C NMR (151 MHz, CDCl 3)δ201.93,139.29,131.48,128.60,121.87,71.57,37.68,11.99,9.80.

[0149] Compound 19: 1 H NMR (600 MHz, CDCl 3 )δ8.91(s,1H),7.53(td,J=7.5,1.8Hz,1H),7.29–7.25(m,1H),7.16(td,J=7.6,1.2Hz,1H),7.01(ddd,J=10.4,8.2,1.2Hz,1 H),5.63(s,1H),3.16(s,1H),1.21(ddd,J=9.8,6.9,4.8Hz,1H),1.18–1.11(m,2H),0.85(dddd,J=8.4,6.5,4.8,1.5Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ202.17,129.57,129.51,128.37,128.34,124.34,124.32,115.29,11 5.15,209.81–-3.69(m),66.20,66.18,37.23,12.55,9.38,9.37,1.16.

[0150] Compound 20: 1 H NMR (600 MHz, CDCl 3 )δ8.92(s,1H),7.23–7.21(m,2H),7.16–7.13(m,2H),5.20(s,1H),2.94( s,1H),2.33(s,3H),1.20–1.13(m,3H),0.90(ddd,J=9.1,6.3,3.7Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ201.16,138.55,128.48,128.03,127.35,80.35,57.47,36.88,13.17,10.44.

[0151] Compound 21: 1 H NMR (600 MHz, CDCl 3)δ9.15(s,1H),7.45–7.43(m,1H),7.37(ddd,J=6.7,2.3,1.3Hz,1H),7.33–7.28(m,2H),6.75(s,0.5H),6.67(s,0.5H),1.29(dq,J=5.0,2.3Hz,2H),1.26(d,J=3.6Hz,1H),0.65–0.61(m,1H). 13 C NMR(151MHz,CDCl 3 )δ199.19,129.88,129.59,127.25,127.18,127.04,124.61,124.12,119.25,88.65,87.50,31.58,30.34,14.51,14.48,10.32,10.29.

[0152] Compound 22: 1 H NMR(600MHz,CDCl 3 )δ9.07(d,J=2.0Hz,1H),7.34(dt,J=1.9,1.0Hz,1H),7.33–7.30(m,2H),7.24–7.21(m,1H),6.04(s,0.5H),5.96(s,0.5H),1.36(tt,J=6.9,2.4Hz,2H),1.30–1.27(m,1H),1.05–1.01(m,1H). 13 C NMR(151MHz,CDCl 3 )δ199.14,139.54,134.70,129.90,128.87,126.16,124.22,91.21,90.04,36.18,13.20,11.32. Compound 23: 1 H NMR(600MHz,CDCl 3 )δ9.06(d,J=2.0Hz,1H),7.37–7.34(m,2H),7.29–7.27(m,2H),6.06(s,1H),5.98(s,1H),1.36–1.32(m,2H),1.29–1.26(m,1H),1.03–0.98(m,1H). 13 C NMR(151MHz,CDCl 3 )δ199.21,135.98,135.83,134.61,128.81,127.46,127.41,91.31,90.14,36.19,36.02,13.03,13.02,11.12,11.09.

[0153] Compound 24: 1 H NMR (600 MHz, CDCl 3 )δ9.05(d,J=2.0Hz,1H),7.52–7.49(m,2H),7.24–7.20(m,2H),6.04(s,0.5H),5.96(s,0.5 H),1.34(ddd,J=7.0,5.6,2.8Hz,2H),1.28–1.26(m,1H),1.01(ddd,J=8.9,7.5,4.8Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ198.01,135.32,135.18,130.58,126.58,126.53,90.15,88.98,34.99,34.82,11.87,9.92.

[0154] Compound 25: 1 H NMR (600 MHz, CDCl 3 )δ8.80(s,1H),7.51–7.48(m,2H),7.22–7.19(m,2H),5.25(s,1H),1.29–1.25(m,1H),1.23–1.21(m,1H),0.98(ddd,J=11.1,6.0,3.9Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ199.13,136.29,131.99,129.26,122.61,77.37,76.95,62.28,36.36,12.01,10.16.

[0155] Compound 26: 1 H NMR (600 MHz, CDCl 3 )δ8.93(s,1H),7.59(dd,J=8.5,6.8Hz,5H),7.45(t,J=7.6Hz,2H),7.39(d,J=8.0Hz,2H),5.34( s,1H),1.32(ddd,J=7.9,6.2,3.9Hz,2H),1.02(ddd,J=10.7,6.0,3.8Hz,1H),0.90–0.86(m,1H). 13 C NMR (151 MHz, CDCl 3)δ199.61,144.68–134.01(m),128.99,128.04,127.53,127.23,77.37,76.95,62.88,36.43,12.50.

[0156] Compound 27: 1 H NMR (600 MHz, CDCl 3 )δ8.83(s,1H),7.31(dd,J=8.5,5.3Hz,2H),7.06(t,J=8.6Hz,2H),5.27(s,1H),1.27–1.25(m,2H),1.00–0.96(m,1H),0.87(d,J=7.1Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ199.29,163.53,161.89,133.05,133.03,129.36,129.31,115.89,115.75,62.27,36.44,12.04,10.18.

[0157] Compound 28: 1 H NMR (600 MHz, CDCl 3 )δ8.82(s,1H),7.32–7.30(m,3H),7.21(ddd,J=5.8,3.9,1.7Hz,1H),5.26(s,1H),1.32–1.28(m,2H),1.01–0.98(m,1H),0.89–0.86(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ199.09,137.10(d,J=679.5Hz),130.10,128.81,125.85,62.29,36.41,12.16,10.28.

[0158] Compound 29: 1 H NMR (600 MHz, CDCl 3 )δ8.78(s,1H),7.63(d,J=8.2Hz,2H),7.46(d,J=8.0Hz,2H),5.35(s,1H),1.33–1.30(m,2H),1.00(dt,J=6.6,1.9Hz,1H),0.88(d,J=6.6Hz,1H). 13 C NMR (151 MHz, CDCl 3)δ198.90,141.39,128.01,125.83,125.80,62.27,29.85,11.91,10.21.

[0159] Compound 30: 1 H NMR (600 MHz, CDCl 3 )δ8.81(s,1H),7.36–7.33(m,2H),7.27(d,J=2.1Hz,1H),7.26(s,1H),5.26(s,1 H),1.29–1.25(m,2H),1.22(t,J=3.2Hz,1H),0.98(ddd,J=10.7,5.9,3.8Hz,1H). 13 C NMR (151 MHz, CDCl 3 )δ199.17,135.76,134.48,129.04,128.96,62.24,36.40,12.02,10.17.

[0160] Compound 31: 1 H NMR (600 MHz, CDCl 3 )δ8.92(s,1H),7.18(q,J=8.0Hz,4H),5.25(s,1H),2.35(s,3H),1.20(ddt,J=10.2,6.9,3.6Hz,3H),0.96–0.92(m,1H). 13 C NMR (151 MHz, CDCl 3 )δ199.75,138.42,133.93,129.51,127.50,62.99,36.30,21.24,12.54,10.38.

Claims

1. A method for preparing cyclopropylcarboxaldehyde derivatives by electrocatalyzed ring contraction of alkenylcyclobutanol, characterized in that: Cyclopropylcarboxaldehyde derivatives are prepared by electrocatalysis from alkenylcyclobutanol compounds of formula I and reagents. The reaction route is as follows: R1 is an aryl group, a heterocycle or an alkyl group; R2 is a hydroxyl group, a halogen group, an azido group, or a C1-C6 alkoxy group; and the reagent is selected from triethylamine trihydrogen halide, azidotrimethylsilane, a C1-C6 alcohol or water.

2. The method according to claim 1, characterized in that: When the reagent is water, R2 is a hydroxyl group; when the reagent is a C1-C6 alcohol, R2 is a C1-C6 alkoxy group; when the reagent is triethylamine trihydrohalide, R2 is a halogen; when the reagent is azidotrimethylsilane, R2 is an azido group.

3. The method according to claim 1 or 2, characterized in that: The electrocatalytic electrolyte is tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate, tetraethylammonium hexafluorophosphate or lithium tetrafluoroborate; preferably, the amount of the electrolyte is 1-3 equivalents (compared to the compound of formula I).

4. The method according to claim 1, characterized in that: The electrocatalytic electrolyte is added with a proton additive, wherein the proton additive is selected from hexafluoroisopropanol, p-toluenesulfonic acid, trifluoroacetic acid or trifluoroethanol; further, the amount of the proton additive is 1-3 equivalents (compared to the compound of formula I).

5. The method according to claim 1, characterized in that: The anode of the electrocatalysis is RVC, graphite felt, graphite sheet or carbon paper, and the cathode is nickel foam sheet or platinum sheet.

6. The method according to claim 1, characterized in that: The organic solvent used in the electrocatalytic reaction is one or a combination of methanol, N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile; preferably, the organic solvent used in the reaction is a mixture of acetonitrile and methanol, wherein the volume ratio of acetonitrile:methanol is 1-9:

1.

7. The method according to claim 1, characterized in that: The current used in the electrocatalytic reaction is 5-12 mA, and the reaction time is 3-6 hours.

8. The method according to claim 1, characterized in that: The electrocatalytic reaction temperature is 15-45°C, preferably room temperature.

9. The method according to any one of claims 1 to 8, characterized in that: The cyclopropylcarboxaldehyde derivative formula II is selected from the compounds shown in Table 1 Table 1 Compounds of Formula II

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