Method for synthesizing hydroxamic acid ester through reaction of isoxazolone and alcohol under synergistic catalysis of copper acetate and light

Abstract

The invention discloses a method for synthesizing hydroxamic acid ester by synergistically catalyzing isoxazolone and alcohol to react by using copper acetate and light, which comprises the following steps of: stirring and reacting at normal temperature and under illumination by using copper acetate as a catalyst without adding expensive ligands to obtain the product hydroxamic acid ester. The method has the advantages of low cost, mild reaction conditions, high product selectivity and the like, avoids the use of precious metals such as rhodium, iridium, palladium and the like, has good substrate universality, can be well compatible with active functional groups such as halogens, double bonds, ester groups and the like, and is suitable for reaction of different substituted isoxazolone derivative substrates and alcohol.

Description

Technical Field

[0001] The present invention belongs to the technical field of transition metal and photocatalytic technology, and particularly relates to a method for selectively synthesizing hydroxamic acid esters by the co-catalysis of copper acetate and light in the reaction of isoxazolone and alcohol. Background Art

[0002] Hydroxamic acid esters widely exist in drugs and bioactive inhibitors. Yang Ke-wu et al. (CN117466776A; European Journal of Medicinal Chemistry 265(2024)116055; Chem Biol Drug Des.2022,99:362–372.) reported an antibacterial drug with dual inhibitory properties against MβLs and SβLs and the bacteria mediated by them and its preparation method. The general structural formula is: Wherein, R l is phenyl, an alkyl group having 1 to 5 carbon atoms, cyclopentyl, cyclohexyl, naphthyl, nitro-phenyl, nitro-benzyl, halo-benzyl, an alkyl group having 1 to 5 carbon atoms substituted by phenyl or an alkyl group having 1 to 5 carbon atoms substituted by cyclohexyl; R2 is phenyl, an alkyl group having 1 to 5 carbon atoms, cyclopentyl, cyclohexyl, indolyl, pyridyl, an alkyl group having 1 to 5 carbon atoms substituted by phenyl, an alkyl group having 1 to 5 carbon atoms substituted by cyclohexyl or an alkyl group having 1 to 5 carbon atoms substituted by cyclopentyl. The preparation method of this kind of compound is to dissolve the corresponding acid of R l in anhydrous tetrahydrofuran, add N,N′-carbonyldiimidazole and stir at room temperature for 1 h, then add hydroxylamine hydrochloride and stir overnight to obtain the corresponding amide substance. Dissolve the amide substance in anhydrous tetrahydrofuran, add pyridine at low temperature, stir and slowly dropwise add the corresponding chloroformate of R2 until the reaction is complete to obtain the target product. This kind of antibacterial drug has good inhibitory properties against both MβLs and SβLs. When meropenem or cefazolin is used as the substrate, the inhibition percentages of the inhibitor of the present invention at 20 μΜ against MβLs, NDM-1, IMP-I and SβLs OXA-48, KPC-2 are as high as over 90%, and its half-inhibitory concentration (IC 50 value) is as low as 0.64 μΜ and 0.57 μΜ respectively at the lowest. And the cytotoxicity evaluation shows that when the concentration of these inhibitors is as high as 200 μΜ, more than 80% of the tested cells still maintain viability, indicating that these inhibitors have low cytotoxicity. However, the existing synthesis methods of this kind of antibacterial drugs mainly use acid as the raw material. First, the corresponding hydroxamic acid is prepared, and then it reacts with acyl chloride to generate isoxamic acid ester substances. This process mainly adopts a multi-step synthesis method. It reduces the generality and yield of the substrate. In addition, a large amount of toxic elements such as hydrogen chloride will be generated in the reaction, which greatly limits the large-scale preparation of this reaction. SUMMARY OF THE INVENTION

[0003] The object of the present invention is to provide a method for synthesizing hydroxamic acid esters by the reaction of isoxazolone with alcohol under the synergistic catalysis of copper acetate and light irradiation.

[0004] For the above object, the technical solution adopted by the present invention is: Mix the isoxazolone derivative shown in formula I or II or III, copper acetate, methanol or ethanol, and chloroform uniformly, and react at room temperature for 10 to 24 hours under light irradiation. After the reaction is completed, quench the reaction with hydrochloric acid, and separate and purify the product to obtain the hydroxamic acid ester shown in formula I' or II' or III' accordingly.

[0005]

[0006] In the formula, Ar represents any one of phenyl, naphthyl, thienyl, furyl, or Ar represents phenyl mono-substituted or di-substituted with any one of trifluoromethyl, C1-C4 alkyl, fluorine, chlorine, nitro, C1-C2 ester group; R represents methyl or ethyl.

[0007] In the above synthesis method, preferably, the addition amount of copper acetate is 3% to 10% of the molar amount of isoxazolone.

[0008] In the above synthesis method, preferably, the addition amount of methanol or ethanol is 40 to 60 times the molar amount of isoxazolone.

[0009] In the above synthesis method, preferably, the volume ratio of methanol or ethanol to chloroform is 1:3 to 6.

[0010] In the above synthesis method, preferably, react at room temperature for 10 to 24 hours under the irradiation of 40-100W green LEDs.

[0011] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0012] The present invention uses a copper acetate and photocatalytic system for the synthesis of hydroxamic acid esters. The catalyst used is commercially available, environmentally friendly, low-cost, the synthesis method is simple and green, the reaction conditions are mild, the operation is simple, has good substrate generality, is applicable to various isoxazolones, and can also be well compatible with some active functional groups such as halogens, double bonds, ester groups, etc. The target product has high selectivity, and using isoxazolone as the nitrogen source improves the reaction safety. DETAILED DESCRIPTION OF THE INVENTION

[0013] The following further details the present invention in conjunction with examples, but the protection scope of the present invention is not limited to these examples.

[0014] Example 1

[0015] Synthesize compound 1 with the following structural formula

[0016]

[0017] 40.0 mg (0.25 mmol) of phenylisoxazolone, 2.3 mg (0.012 mmol) of copper acetate, 0.5 mL (12.4 mmol) of methanol, and 2 mL of chloroform were mixed uniformly and reacted at room temperature for 12 h under irradiation with a 50 W green LED lamp. After the reaction was complete, the reaction was quenched with 0.1 mL of hydrochloric acid, concentrated under vacuum, and the concentrated product was purified by column chromatography (dichloromethane:ethyl acetate = 5:1) to obtain 42.4 mg of yellow solid compound 1 with a yield of 88%.

[0018] The spectral data of the obtained compound 1 were as follows: 1 H NMR (400 MHz, CDCl3) δ 11.31 (bs, 1H), 8.78 (d, J = 8.0 Hz, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 2H), 7.87 - 7.81 (m, 3H), 7.53 - 7.64 (m, 4H); 13 C NMR (100 MHz, CDCl3) δ: 165.8, 139.3, 138.2, 133.3, 133.2, 131.4, 129.1, 128.4, 127.9, 127.0, 125.8, 118.8, 113.0.

[0019] Example 2

[0020] Synthesize the structural formula as compound 2

[0021]

[0022] In this example, 3-methylphenylisoxazolone in an equimolar amount was used to replace phenylisoxazolone in Example 1, and the other steps were the same as in Example 1 to obtain compound 2 with a yield of 64%.

[0023] The spectral data of the obtained compound 2 were as follows: 1 H NMR (400 MHz, CDCl3) δ 9.69 (s, 1H), 7.61 (s, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 3.91 (s, 3H), 2.35 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 167.2, 155.5, 138.9, 133.7, 130.3, 128.8, 128.3, 124.6, 56.6, 21.4.

[0024] Example 3

[0025] The synthetic structural formula is like that of compound 3

[0026]

[0027] In this example, 4-methylphenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and other steps were the same as those in Example 1, obtaining compound 3 with a yield of 51%.

[0028] The spectral data of the obtained compound 3 are as follows: 1 H NMR(400MHz,CDCl3)δ9.64(s,1H),7.69(d,J=8.2Hz,2H),7.21(d,J=7.9Hz,2H),3.91(s,3H),2.38(s,3H); 13 C NMR(100MHz,CDCl3)δ167.1,155.6,143.7,129.5,127.6,127.5,56.6,21.7.

[0029] Example 4

[0030] Synthesize the following compound 4

[0031]

[0032] In this example, 4-tert-butylphenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and other steps were the same as those in Example 1, obtaining compound 4 with a yield of 72%.

[0033] The spectral data of the obtained compound 4 are as follows: 1 H NMR(400MHz,CDCl3)δ9.48(s,1H),7.75(d,J=8.5Hz,2H),7.45(d,J=8.7Hz,2H),3.93(s,3H),1.32(s,9H); 13 C NMR(100MHz,CDCl3)δ167.1,156.7,155.6,127.5,125.9,56.6,35.2,31.2.

[0034] Example 5

[0035] Synthesize the following compound 5

[0036]

[0037] In this example, 4-fluorophenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and other steps were the same as those in Example 1, obtaining compound 5 with a yield of 74%.

[0038] The spectral data of the obtained compound 5 are as follows: 1 H NMR(400MHz,CDCl3)δ10.02(s,1H),7.81(dd,J=8.8,5.3,2H),7.08(t,J=8.7Hz,2H),3.91(s,3H); 13 C NMR(100MHz,CDCl3)δ166.0,165.6(d,J=235Hz),155.4,130.2(d,J=10Hz),126.5(d,J=3Hz),116.1(d,J=22Hz),56.7; 19 FNMR(376MHz,CDCl3)δ-115.2(s,1F).

[0039] Example 6

[0040] Synthesize compound 6 with the following structural formula

[0041]

[0042] In this example, 3-fluorophenylisoxazolone in equimolar amount was used to replace phenylisoxazolone in Example 1, and other steps were the same as those in Example 1 to obtain compound 6 with a yield of 86%.

[0043] The spectral data of the obtained compound 6 are as follows: 1 H NMR(400MHz,CDCl3)δ10.06(s,1H),7.57(d,J=7.6Hz,1H),7.50(d,J=9.3Hz,1H),7.39(dd,J=13.5,7.9Hz,1H),7.23(t,J=8.3Hz,1H),3.91(s,3H); 13 C NMR(100MHz,CDCl3)δ165.6,162.7(d,J=247Hz),155.2,132.3,130.7(d,J=8Hz),123.2(d,J=4Hz),120.0(d,J=21Hz),115(d,J=23Hz),56.7; 19 FNMR(376MHz,CDCl3)δ-111.0(s,1F).

[0044] Example 7

[0045] Synthesize compound 7 with the following structural formula

[0046]

[0047] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 3-chlorophenyl isoxazolone, and other steps were the same as those in Example 1 to obtain Compound 7 with a yield of 55%.

[0048] The spectral data of the obtained Compound 7 are as follows: 1 H NMR(400MHz,CDCl3)δ9.89(s,1H),7.78(s,1H),7.66(d,J=7.8Hz,1H),7.51(d,J=8.0Hz,1H),7.36(t,J=7.9Hz,1H),3.93(s,3H); 13 C NMR(100MHz,CDCl3)δ165.6,155.3,135.1,133.1,132.0,130.2,127.9,125.7,56.7。

[0049] Example 8

[0050] Synthesize Compound 8 with the following structural formula

[0051]

[0052] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-chlorophenyl isoxazolone, and other steps were the same as those in Example 1 to obtain Compound 8 with a yield of 84%.

[0053] The spectral data of the obtained Compound 8 are as follows: 1 H NMR(400MHz,CDCl3)δ9.89(s,1H),8.06(d,J=8.3Hz,2H),7.85(d,J=8.0Hz,2H),3.93(d,J=1.0Hz,6H); 13 C NMR(101MHz,CDCl3)δ166.27,165.97,155.28,134.31,133.91,130.06,127.75,56.75,52.70。

[0054] Example 9

[0055] Synthesize Compound 9 with the following structural formula

[0056]

[0057] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 2-chlorophenyl isoxazolone, and other steps were the same as those in Example 1 to obtain Compound 9 with a yield of 55%.

[0058] The spectral data of the obtained Compound 9 are as follows: 11H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 1.3 Hz, 1H), 7.42 (d, J = 1.1 Hz, 1H), 7.35 (dd, J = 7.7, 5.0 Hz, 1H), 3.95 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 164.7, 155.0, 132.7, 131.5, 130.9, 130.8, 130.6, 127.3, 56.7.

[0059] Example 10

[0060] Synthesize compound 10 with the following structural formula

[0061]

[0062] In this example, 4-bromophenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and the other steps were the same as those in Example 1 to obtain compound 10 with a yield of 93%.

[0063] The spectral data of the obtained compound 10 are as follows: 1 1H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 8.06 (s, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 3.92 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 165.26, 155.16, 131.25, 130.89, 129.55, 129.46, 124.71, 124.67, 122.16, 56.71.

[0064] Example 11

[0065] Synthesize compound 11 with the following structural formula

[0066]

[0067] In this example, 3-bromophenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and the other steps were the same as those in Example 1 to obtain compound 11 with a yield of 90%.

[0068] The spectral data of the obtained compound 11 are as follows: 11H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 3.89 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 165.2, 155.1, 135.8, 132.1, 130.8, 130.4, 126.2, 122.9, 56.7.

[0069] Example 12

[0070] Synthesize compound 12 with the following structural formula

[0071]

[0072] In this example, equimolar 2-bromophenylisoxazolone was used to replace phenylisoxazolone in Example 1, and the other steps were the same as those in Example 1 to obtain compound 12 with a yield of 60%.

[0073] The spectral data of the obtained compound 12 are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.33 (s, 1H), 7.63 (d, J = 1.2 Hz, 1H), 7.61 (d, J = 1.5 Hz, 1H), 7.41 - 7.32 (m, 2H), 3.95 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 165.5, 155.5, 133.8, 133.3, 132.7, 130.5, 127.7, 120.1, 56.7.

[0074] Example 13

[0075] Synthesize compound 13 with the following structural formula

[0076]

[0077] In this example, equimolar 3-trifluoromethylphenylisoxazolone was used to replace phenylisoxazolone in Example 1, and the other steps were the same as those in Example 1 to obtain compound 13 with a yield of 90%.

[0078] The spectral data of the obtained compound 13 are as follows: 1 1H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 8.06 (s, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 3.92 (s, 3H); 1313C NMR (100 MHz, CDCl3) δ 164.3, 155.2, 131.3 (t, J = 33 Hz), 130.9, 129.6, 129.5 (d, J = 3 Hz), 124.9, 124.7, 122.2 (d, J = 3 Hz), 56.9; 19 19F NMR (376 MHz, CDCl3) δ -62.9 (s, 3F).

[0079] Example 14

[0080] Synthesize compound 14 with the following structural formula

[0081]

[0082] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-trifluoromethylphenyl isoxazolone, and other steps were the same as in Example 1, to obtain compound 14 with a yield of 93%.

[0083] The spectral data of the obtained compound 14 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 8.2 Hz, 2H), 7.92 (d, J = 8.2 Hz, 2H), 3.89 (s, 3H); 13 13C NMR (100 MHz, DMSO-d6) δ 164.0, 155.0, 134.9, 132.6 (d, J = 32 Hz), 128.8, 126.3 (d, J = 4 Hz), 124.2 (d, J = 271 Hz), 56.9; 19 19F NMR (376 MHz, CDCl3) δ -63.1 (s, 3F).

[0084] Example 15

[0085] Synthesize compound 15 with the following structural formula

[0086]

[0087] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-nitrophenyl isoxazolone, and other steps were the same as in Example 1, to obtain compound 15 with a yield of 64%.

[0088] The spectral data of the obtained compound 15 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 9.1 Hz, 2H), 8.05 (d, J = 8.9 Hz, 2H), 3.90 (s, 3H); 1313C NMR (100 MHz, DMSO-d6) δ 163.6, 155.0, 150.3, 136.7, 129.5, 124.5, 57.0.

[0089] Example 16

[0090] Synthesize compound 16 with the following structural formula

[0091]

[0092] In this example, 3-nitrophenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and other steps were the same as those in Example 1, to obtain compound 16 with a yield of 93%.

[0093] The spectral data of the obtained compound 16 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 9.1 Hz, 2H), 8.05 (d, J = 8.9 Hz, 2H), 3.90 (s, 3H); 13 13C NMR (100 MHz, DMSO-d6) δ 163.6, 155.0, 150.3, 136.7, 129.5, 124.5, 57.0.

[0094] Example 17

[0095] Synthesize compound 17 with the following structural formula

[0096]

[0097] In this example, 4-methoxycarbonylphenyl isoxazolone in equimolar amount was used to replace phenyl isoxazolone in Example 1, and other steps were the same as those in Example 1, to obtain compound 17 with a yield of 93%.

[0098] The spectral data of the obtained compound 17 are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 8.06 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.3 Hz, 2H), 3.93 (s, 6H); 13 13C NMR (100 MHz, CDCl3) δ 166.3, 166.0, 155.3, 134.3, 133.9, 130.1, 127.8, 56.8, 52.7.

[0099] Example 18

[0100] Synthesize compound 18 with the following structural formula

[0101]

[0102] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-butoxybenzyl isoxazolone, and the other steps were the same as those in Example 1 to obtain Compound 18 with a yield of 92%.

[0103] The spectral data of the obtained Compound 18 are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.20 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 3.94 (t, J = 6.6 Hz, 2H), 3.89 (s, 3H), 3.60 (s, 2H), 1.79 - 1.72 (m, 2H), 1.48 (dd, J = 15.1, 7.4 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 158.9, 155.1, 130.6, 124.3, 115.2, 67.8, 56.6, 40.0, 31.4, 19.3, 13.9.

[0104] Example 19

[0105] Synthesize Compound 19 with the following structural formula

[0106]

[0107] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-fluorobenzyl isoxazolone, and the other steps were the same as those in Example 1 to obtain Compound 19 with a yield of 80%.

[0108] The spectral data of the obtained Compound 19 are as follows: 1 H NMR (400 MHz, Acetone-d6) δ 11.10 (s, 1H), 7.36 (dd, J = 8.6, 5.5 Hz, 2H), 7.08 (t, J = 8.9 Hz, 2H), 3.84 (s, 3H), 3.57 (s, 2H). 13 C NMR (100 MHz, Acetone-d6) δ 168.4, 162.0 (d, J = 242 Hz), 155.1, 131.2 (d, J = 8 Hz), 115.1 (d, J = 21 Hz), 55.8, 38.1; 19 F NMR (376 MHz, CDCl3) δ -117.5 (s, 3F).

[0109] Example 20

[0110] Synthesize Compound 20 with the following structural formula

[0111]

[0112] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar 4-methoxybenzyl isoxazolone, and other steps were the same as those in Example 1, to obtain Compound 20 with a yield of 71%.

[0113] The spectral data of the obtained Compound 20 are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 7.20 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 3.78 (s, 3H), 3.54 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 169.8, 159.1, 155.1, 130.6, 124.9, 114.5, 56.5, 55.4, 39.5.

[0114] Example 21

[0115] Synthesize Compound 21 with the following structural formula

[0116]

[0117] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar thiophene methyl isoxazolone, and other steps were the same as those in Example 1, to obtain Compound 21 with a yield of 72%.

[0118] The spectral data of the obtained Compound 21 are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.72 (s, 1H), 7.22 (d, J = 5.2 Hz, 1H), 6.97 (m, 1H), 6.95 (d, J = 3.3 Hz, 1H), 3.86 (s, 3H), 3.80 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 168.2, 154.9, 134.0, 127.7, 127.4, 125.8, 56.6, 34.2.

[0119] Example 22

[0120] Synthesize Compound 22 with the following structural formula

[0121]

[0122] In this example, phenyl isoxazolone in Example 1 was replaced with equimolar styryl isoxazolone, and other steps were the same as those in Example 1, to obtain Compound 22 with a yield of 68%.

[0123] The spectral data of the obtained compound 22 are as follows: 1 H NMR(400MHz,CDCl3)δ10.23(s,1H),7.75(d,J=15.6Hz,1H),7.49-7.46(m,2H),7.32(d,J=6.7Hz,3H),6.56(d,J=15.5Hz,1H),3.87(s,3H); 13 C NMR(100MHz,CDCl3)δ165.7,155.3,144.2,134.3,130.5,129.0,128.3,115.3,56.6.

[0124] Example 23

[0125] Synthesize compound 23 with the following structural formula

[0126]

[0127] In this example, ethanol in equimolar amount was used to replace methanol in Example 1, and other steps were the same as those in Example 1 to obtain compound 23 with a yield of 63%.

[0128] The spectral data of the obtained compound 23 are as follows: 1 H NMR(400MHz,CDCl3)δ9.50(s,1H),7.81-7.79(m,2H),7.54(t,J=7.3Hz,1H),7.45-7.41(m,2H),4.33(q,J=7.2Hz,2H),1.36(t,J=7.1Hz,3H); 13 C NMR(100MHz,CDCl3)δ166.9,154.8,132.9,130.4,128.9,127.6,66.5,14.2.

Claims

1. A method for synthesizing hydroxamic acid esters by the reaction of isoxazolone with alcohol under the synergistic catalysis of copper acetate and light, which is characterized in that: Mix the isoxazolone derivative represented by Formula I or II or III, copper acetate, methanol or ethanol, and chloroform uniformly, and react at room temperature for 10 to 24 hours under light. After the reaction, quench the reaction with hydrochloric acid and separate and purify the product to obtain the hydroxamic acid ester represented by Formula I′ or II′ or III′ accordingly. In the formula, Ar represents any one of phenyl, naphthyl, thienyl, and furyl, or Ar represents phenyl mono-substituted or di-substituted with any one of trifluoromethyl, C1-C4 alkyl, fluorine, chlorine, nitro, and C1-C2 ester group; R represents methyl or ethyl.

2. The method for synthesizing hydroxamic acid ester by the reaction of isoxazolone and alcohol under the co-catalysis of copper acetate and light according to claim 1, wherein: The addition amount of the copper acetate is 3% to 10% of the molar amount of the isoxazolone.

3. The method for synthesizing hydroxamic acid ester by the reaction of copper acetate and light co-catalyzed isoxazolone and alcohol according to claim 1, wherein: The addition amount of the methanol or ethanol is 40 to 60 times the molar amount of the isoxazolone.

4. The method for synthesizing hydroxamic acid ester by the reaction of isoxazolone and alcohol under the co-catalysis of copper acetate and light according to claim 1 or 3, characterized in that: The volume ratio of the methanol or ethanol to the chloroform is 1:3 to 6.

5. The method for synthesizing hydroxamic acid ester by the reaction of copper acetate and light co-catalyzing isoxazolone and alcohol according to claim 1, characterized in that: React at room temperature for 10 to 24 hours under the irradiation of 40 to 100W green LEDs.

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