A process for the preparation of a 1,2,4-triazole-3-ketone compound

Abstract

This invention discloses a method for preparing a 1,2,4-triazol-3-one compound, comprising the following steps: mixing compound 1, compound 2, an additive, an oxidant, and a solvent to react and obtain the 1,2,4-triazol-3-one compound; wherein the structural formulas of compound 1, compound 2, and the 1,2,4-triazol-3-one compound are as follows: wherein, R 1 and R 2 Selected independently from C 1～10 Alkyl, substituted or unsubstituted C 6～20 The aryl group. The preparation method of this invention has high atom utilization and can efficiently synthesize functionalized 1,2,4-triazol-3-one compounds. It has the advantages of simple synthesis steps, safe operation, and good compatibility of the synthesis method with functional groups. It yields 1,2,4-triazol-3-one compounds with very high added value, with a yield of up to 85% and a purity of 99%, which greatly saves experimental or production costs and is easy to synthesize industrially.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing a 1,2,4-triazol-3-one compound. Background Technology

[0002] 1,2,4-Triazol-3-ones are an important class of five-membered nitrogen heterocyclic compounds with a variety of biological activities. These special N-heterocyclic compounds have been successfully applied in various fields and have significant biological activities. For example, 2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones with an acidic biphenylsulfonamide moiety have been used as dual AT1 / AT2 receptor antagonists with enhanced affinity.

[0003] The synthetic routes for 1,2,4-triazol-3-ones have received considerable attention over the past few decades. Although numerous synthetic methods for producing 1,2,4-triazol-3-ones have been reported, most conventionally developed strategies suffer from several drawbacks, such as substrate pre-activation, multi-step procedures, harsh reaction conditions, low efficiency, or the generation of undesirable byproducts. Given the urgent need for environmental friendliness and sustainability, green synthesis has become a mainstream alternative to conventional synthetic routes.

[0004] Therefore, it is necessary to develop a safe, environmentally friendly, low-cost, efficient, and simple method for the effective synthesis of 1,2,4-triazol-3-one compounds and their derivatives. Summary of the Invention

[0005] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the first aspect of the present invention provides a method for preparing a 1,2,4-triazol-3-one compound.

[0006] The method for preparing the 1,2,4-triazol-3-one compound according to the first aspect of the present invention includes the following steps:

[0007] Compound 1, compound 2, base, oxidant and solvent were mixed and reacted to obtain 1,2,4-triazol-3-one compound;

[0008] The structural formulas of compounds 1, 2, and 1,2,4-triazol-3-one are as follows:

[0009]

[0010] Among them, R 1 and R 2 Selected independently from C 1～10 Alkyl, substituted or unsubstituted C 6～20 Aryl groups.

[0011] The preparation method according to embodiments of the present invention has at least the following beneficial effects:

[0012] The preparation method of this invention has high atom utilization and can efficiently synthesize functionalized 1,2,4-triazole-3-one compounds. It has the advantages of simple synthesis steps, safe operation, and good compatibility of the synthesis method with functional groups. It yields 1,2,4-triazole-3-one compounds with very high added value, with a yield of up to 85% and a purity of 99%, which greatly saves experimental or production costs and is easy to synthesize industrially.

[0013] According to some embodiments of the present invention, R 1 and R 2 Selected independently from C 1～6 Alkyl, phenyl, C 1～6 alkyl, C 1～6 alkoxy, halogen, C 1～6 Halogenated alkoxy groups and nitro-substituted phenyl groups.

[0014] According to some embodiments of the present invention, the molar ratio of compound 1 to compound 2 is 1:(1 to 3).

[0015] According to some embodiments of the present invention, the molar ratio of compound 1, base and oxidant is 1:(0.8-1.5):(1-1.5).

[0016] According to some embodiments of the present invention, the base is selected from at least one of lithium acetate, sodium acetate, cesium acetate, and tetrabutylammonium iodide.

[0017] According to some embodiments of the present invention, the oxidant is selected from at least one of copper acetate, iodobenzene acetate, iodobenzene iodoacetate, tert-butanol hydroperoxide, and di-tert-butyl peroxide.

[0018] According to some embodiments of the present invention, the temperature of the reaction is 0°C to 80°C.

[0019] According to some embodiments of the present invention, the reaction temperature is 40°C to 80°C.

[0020] According to some embodiments of the present invention, the reaction time is 0.5 to 24 hours.

[0021] According to some embodiments of the present invention, the solvent is selected from at least one of DMSO, THF, acetonitrile, and toluene.

[0022] According to some embodiments of the present invention, the reaction further includes a purification step after completion.

[0023] According to some embodiments of the present invention, the purification is performed using column chromatography.

[0024] Definitions and general terms

[0025] “C 1～6 "alkyl" indicates an alkyl group with a total number of 1-6 carbon atoms, including C64. 1-6 straight-chain alkyl, C 1-6 Branched alkyl groups and C 3-6 The cycloalkyl group can be, for example, a straight-chain alkyl group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; a branched-chain alkyl group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; or a cycloalkyl group with a total of 3, 4, 5, or 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl, etc. Regarding "C 1～10 "alkyl" has a similar interpretation, except that the number of carbon atoms is different.

[0026] “C 1～6 "alkoxy group" refers to an alkoxy group with a total number of 1-6 carbon atoms, including C64 and C64. 1～6 straight-chain alkoxy, C 1～6 Branched alkoxy groups and C 2～6 The cycloalkoxy group can be, for example, a straight-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5 or 6, a branched-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5 or 6, or a cycloalkoxy group with a total number of carbon atoms of 2, 3, 4, 5 or 6, such as methoxy, ethoxy, n-propoxy, isopropoxy, etc.

[0027] “C 1～6 "haloalkoxy" and "C" 1～6 The definition of "alkoxy group" is basically the same, except that any one H atom in the alkoxy group is replaced by any halogen.

[0028] "Halogen" includes any one or more of fluorine, chlorine, bromine, and iodine.

[0029] "Substituted or unsubstituted C" 6～20 "Aryl" indicates an all-carbon monocyclic or fused polycyclic group with a fully conjugated π-electron system; its total number of carbon atoms is 6 to 20. Furthermore, optionally, at least one hydrogen atom in the aryl group is derived from a carbon atom. 1～6 alkyl, C 1～6 alkoxy, halogen, C 1～6 Halogenated alkoxy groups and nitro groups are substituted.

[0030] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0031] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0032] Figure 1 The 1H NMR spectrum of product 3aa obtained in Example 1;

[0033] Figure 2 The carbon NMR spectrum of product 3aa obtained in Example 1;

[0034] Figure 3 The nuclear magnetic resonance fluorine spectrum of product 3aa obtained in Example 1;

[0035] Figure 4 The 1H NMR spectrum of product 3ab obtained in Example 2;

[0036] Figure 5 The image shows the carbon NMR spectrum of product 3ab obtained in Example 2.

[0037] Figure 6 The 1H NMR spectrum of product 3ac obtained in Example 3;

[0038] Figure 7 The nuclear magnetic resonance carbon spectrum of product 3ac obtained in Example 3;

[0039] Figure 8 The 1H NMR spectrum of product 3ad obtained in Example 4;

[0040] Figure 9 The nuclear magnetic resonance carbon spectrum of product 3ad obtained in Example 4;

[0041] Figure 10 The 1H NMR spectrum of product 3ae obtained in Example 5;

[0042] Figure 11 The image shows the carbon NMR spectrum of the product 3ae obtained in Example 5.

[0043] Figure 12 The 1H NMR spectrum of product 3af obtained in Example 6;

[0044] Figure 13 The nuclear magnetic resonance carbon spectrum of product 3af obtained in Example 6;

[0045] Figure 14 The 1H NMR spectrum of the product 3ag obtained in Example 7;

[0046] Figure 15 The nuclear magnetic resonance carbon spectrum of the product 3ag obtained in Example 7;

[0047] Figure 16The 1H NMR spectrum of the product 3hb obtained in Example 8;

[0048] Figure 17 The nuclear magnetic resonance carbon spectrum of the product 3hb obtained in Example 8;

[0049] Figure 18 The 1H NMR spectrum of the product 3hc obtained in Example 9;

[0050] Figure 19 The carbon NMR spectrum of the product 3hc obtained in Example 9;

[0051] Figure 20 The NMR fluorine spectrum of the product 3hc obtained in Example 9;

[0052] Figure 21 The 1H NMR spectrum of the product obtained in Example 10 at 3hd;

[0053] Figure 22 The nuclear magnetic resonance carbon spectrum of the product 3hd obtained in Example 10;

[0054] Figure 23 The 1H NMR spectrum of the product 3he obtained in Example 11 is shown below.

[0055] Figure 24 The nuclear magnetic resonance carbon spectrum of the product 3he obtained in Example 11;

[0056] Figure 25 The 1H NMR spectrum of the product 3hf obtained in Example 12;

[0057] Figure 26 The carbon NMR spectrum of the product 3hf obtained in Example 12;

[0058] Figure 27 The 1H NMR spectrum of the product 3hg obtained in Example 13 is shown below.

[0059] Figure 28 The nuclear magnetic resonance carbon spectrum of the product 3hg obtained in Example 13;

[0060] Figure 29 The 1H NMR spectrum of product 3hh obtained in Example 14 is shown below.

[0061] Figure 30 The image shows the carbon NMR spectrum of product 3hh obtained in Example 14. Detailed Implementation

[0062] The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described in conjunction with the embodiments, but the present invention is not limited to these embodiments.

[0063] Unless otherwise specified, the reagents, methods and equipment used in this invention are all conventional reagents, methods and equipment in this technical field.

[0064] Example 1

[0065] Example 1 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0066]

[0067] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of 4-fluorobenzylamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3aa, with a yield of 61% and a purity of 99%.

[0068] The obtained product 3aa is a pale yellow solid, and its proton, carbon, and fluorine spectra are shown below. Figure 1 and Figure 2 and Figure 3 As shown, the structural characterization data are as follows:

[0069] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR (500MHz, DMSO-d6) δ12.66(s,1H),7.99–7.94(m,2H),7.89–7.83(m,2H),7.41(t,J=8.8Hz,2H),7.30–7.26(m,2H),2.33(s,3H). 13 C NMR (126MHz, DMSO-d6) δ164.8,162.8,153.2,144.3,135.9,134.6,129.9,128.2,128.1,123.3,123.3,118.5,116.8,116.6,21.0. 19 F NMR(471MHz,DMSO-d6)δ-109.73.

[0070] Example 2

[0071] Example 2 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0072]

[0073] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of 4-chlorobenzylamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3ab with a yield of 66% and a purity of 99%.

[0074] The obtained product 3ab is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 4 and Figure 5 As shown, the structural characterization data are as follows:

[0075] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR(500MHz,DMSO-d6)δ12.70(s,

[0076] 1H),7.94–7.90(m,2H),7.88–7.84(m,2H),7.65–7.61(m,2H),7.30–7.26(m,2H),2.33(s,3H). 13 C NMR (126MHz, DMSO-d6) δ153.2,144.2,135.8,135.6,134.7,129.9,129.7,127.5,125.6,118.6,21.0.

[0077] Example 3

[0078] Example 3 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0079]

[0080] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of 2-chlorobenzylamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3ac, with a yield of 86% and a purity of 98%.

[0081] The obtained product 3ac is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 6 and Figure 7 As shown, the structural characterization data are as follows:

[0082] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR(500MHz,DMSO-d6)δ12.47(s,

[0083] 1H),7.87–7.81(m,2H),7.75(dd,J=7.6,1.8Hz,1H),7.66(dd,J=7.9,1.3Hz,1H),7.5 8(td,J=7.7,1.8Hz,1H),7.52(td,J=7.5,1.3Hz,1H),7.30–7.25(m,2H),2.32(s,3H). 13 C NMR (126MHz, DMSO-d6) δ152.9,143.8,135.8,134.7,132.5,132.3,131.6,131.0,129.9,128.1,126.3,118.6,21.0.

[0084] Example 4

[0085] Example 4 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0086]

[0087] 0.5 mmol ethyl isocyanate, 0.6 mmol 4-iodobenzylamidine hydrochloride, 0.5 mmol tetrabutylammonium iodide, 0.4 mmol iodobenzene acetate, 0.2 mmol copper acetate, and 1 mL DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3ad, with a yield of 60% and a purity of 98%.

[0088] The obtained product 3ad is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 8 and Figure 9 As shown, the structural characterization data are as follows:

[0089] Rf=0.5(petroleum ether:ethyl acetate=3:1) 1 H NMR(500MHz,DMSO-d6)δ12.67(s,1H),

[0090] 7.92(d,J=8.5Hz,2H),7.85(d,J=8.5Hz,2H),7.68(d,J=8.5Hz,2H),7.27(d,J=8.3Hz,2H),2.32(s,3H).13 C NMR (126MHz, DMSO-d6) δ153.18,144.42,138.36,134.67,129.87,127.47,126.16,119.43,118.55,98.00,20.97.

[0091] Example 5

[0092] Example 5 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0093]

[0094] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of 4-nitrobenzylamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3ae, with a yield of 55% and a purity of 98%.

[0095] The obtained product 3ae is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 10 and Figure 11 As shown, the structural characterization data are as follows:

[0096] 1 H NMR (500MHz, DMSO-d6) δ8.38(d,J=9.0Hz,2H),8.16(d,J=8.9Hz,2H),7.88(d,J=8.5Hz,2H),7.29(d,J=8.6Hz,2H),2.33(s,3H). 13 C NMR (126MHz, DMSO-d6) δ153.8,148.5,144.0,135.8,134.9,132.9,129.9,126.8,124.8,118.7,21.0.

[0097] Example 6

[0098] Example 6 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0099]

[0100] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of cyclopropaneformamide hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3af, with a yield of 52% and a purity of 98%.

[0101] The obtained product 3af is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 12 and Figure 13 As shown, the structural characterization data are as follows:

[0102] 1 H NMR(500MHz,DMSO-d6)δ11.73(s,1H),7.77–7.70(m,2H),7.24–7.18(m,2H),2 .29(s,3H),1.85(tt,J=8.4,5.1Hz,1H),1.01–0.94(m,2H),0.93–0.86(m,2H). 13 C NMR (126MHz, DMSO-d6) δ152.9,149.5,136.0,133.9,129.7,118.1,20.9,7.8,6.9.

[0103] Example 7

[0104] Example 7 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0105]

[0106] 0.5 mmol of p-toluene isocyanate, 0.6 mmol of 4-butamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain 3 ag of product, with a yield of 65% and a purity of 98%.

[0107] The obtained product 3ag is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 14 and Figure 15 As shown, the structural characterization data are as follows:

[0108] 1H NMR(500MHz,DMSO-d6)δ11.81(s,1H),7.78–7.72(m,2H),7.24–7.20(m,2H),2. 47(t,J=7.5Hz,2H),2.30(s,3H),1.66(q,J=7.5Hz,2H),0.94(t,J=7.4Hz,3H). 13 C NMR (126MHz, DMSO-d6) δ153.1,147.9,136.1,133.9,129.8,118.1,28.5,20.9,19.9,13.8.

[0109] Example 8

[0110] Example 8 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0111]

[0112] 0.5 mmol p-chloroisocyanurate, 0.6 mmol benzylamidine hydrochloride, 0.5 mmol tetrabutylammonium iodide, 0.4 mmol iodobenzene acetate, 0.2 mmol copper acetate, and 1 mL DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3hb, with a yield of 70% and a purity of 98%.

[0113] The obtained product 3hb is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 16 and Figure 17 As shown, the structural characterization data are as follows:

[0114] 1 H NMR (500MHz, DMSO-d6) δ12.76(s,1H),8.03(d,J=8.9Hz,2H),7.97–7.88(m,2H),7.55(dt,J=6.4,3.2Hz,5H). 13 C NMR (126MHz, DMSO-d6) δ153.3,145.6,137.1,131.2,129.6,129.5,129.2,126.5,125.8,119.9.

[0115] Example 9

[0116] Example 9 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0117]

[0118] 0.5 mmol of p-trifluoromethoxyisocyanate, 0.6 mmol of benzylamidine hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3hc, with a yield of 73% and a purity of 98%.

[0119] The obtained product is a pale yellow solid at 3hc, and its proton and carbon spectra are shown below. Figure 18 and Figure 19 and Figure 20 As shown, the structural characterization data are as follows:

[0120] 1 H NMR (500MHz, DMSO-d6) δ12.78(s,1H),8.17–8.08(m,2H),7.97–7.89(m,2H),7.56(dd,J=5.2,2.0Hz,3H),7.50(d,J=8.5Hz,2H). 13 C NMR (126MHz, DMSO-d6) δ153.4,145.7,145.3,137.3,131.3,129.6,126.5,125.8,122.4,119.9. 19 F NMR(471MHz,DMSO-d6)δ-57.01.

[0121] Example 10

[0122] Example 10 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0123]

[0124] 0.5 mmol of 3,5-dimethylphenyl isocyanate, 0.6 mmol of benzylammonium hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3hd, with a yield of 73% and a purity of 98%.

[0125] The obtained product 3hd is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 21 and Figure 22 As shown, the structural characterization data are as follows:

[0126] 1H NMR (500MHz, DMSO-d6) δ12.66(s,1H),7.92(dd,J=7.6,2.2Hz,2H),7.64(d,J=1.6Hz,2H),7.54(dd,J=5.7,1.7Hz,3H),6.88(s,1H),2.33(s,6H). 13 C NMR (126MHz, DMSO-d6) δ153.5,145.2,138.6,138.3,131.0,129.5,126.8,126.8,125.7,116.2,21.6.

[0127] Example 11

[0128] Example 11 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0129]

[0130] 0.5 mmol of p-ethyl isocyanate, 0.6 mmol of benzylammonium hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3he, with a yield of 78% and a purity of 98%.

[0131] The obtained product 3he is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 23 and Figure 24 As shown, the structural characterization data are as follows:

[0132] 1 H NMR (500MHz, DMSO-d6) δ12.65(s,1H),7.96–7.84(m,4H),7.57–7.50(m,3H),7.35–7.27(m,2H),2.63(q,J=7.6Hz,2H),1.20(t,J=7.6Hz,3H). 13 C NMR (126MHz, DMSO-d6) δ153.3,145.0,141.0,136.1,131.0,129.5,128.7,126.7,125.7,118.7,28.1,16.1.

[0133] Example 12

[0134] Example 12 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0135]

[0136] 0.5 mmol of p-n-butyl isocyanate, 0.6 mmol of benzylammonium hydrochloride, 0.5 mmol of tetrabutylammonium iodide, 0.4 mmol of iodobenzene acetate, 0.2 mmol of copper acetate, and 1 mL of DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3hf, with a yield of 72% and a purity of 98%.

[0137] The obtained product 3hf is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 25 and Figure 26 As shown, the structural characterization data are as follows:

[0138] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR(500MHz,DMSO-d6)δ12.65(s,1H),7.93–7.90(m,2H),7.90–7.86(m,2H),7.57–7.51(m,3H),7.3 0–7.25(m,2H),2.59(t,J=7.7Hz,2H),1.59–1.52(m,2H),1.35–1.26(m,2H),0.90(t,J=7.4Hz,3H). 13 CNMR(126MHz,DMSO-d6)δ153.3,145.0,139.5,136.1,131.0,129.5,129.2,126.7,125.7,118.6,34.7,33.6,22.2,14.2.

[0139] Example 13

[0140] Example 13 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0141]

[0142] 0.5 mmol cyclohexyl isocyanate, 0.6 mmol benzylamidine hydrochloride, 0.5 mmol tetrabutylammonium iodide, 0.4 mmol iodobenzene acetate, 0.2 mmol copper acetate, and 1 mL DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain 3 hg of product, with a yield of 80% and a purity of 98%.

[0143] The obtained product, 3 hg, is a pale yellow solid. Its proton and carbon spectra are shown below. Figure 27 and Figure 28 As shown, the structural characterization data are as follows:

[0144] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR (500MHz, DMSO-d6) δ12.18(s,1H),7.79(dd,J=7.9,1.8Hz,2H),7.57–7.29(m,3H),3.95(tt,J=11.7,3.8Hz,1H),1.81(dq,J= 12.3, 4.3, 3.8Hz, 4H), 1.68 (ddd, J=27.6, 14.0, 10.4Hz, 3H), 1.36 (qt, J=13.8, 3.7Hz, 2H), 1.20 (ddt, J=16.3, 13.0, 2.8Hz, 1H). 13 C NMR (126MHz, DMSO-d6) δ154.1,143.7,130.3,129.4,127.3,125.2,53.2,33.8,31.7,25.4,25.4.

[0145] Example 14

[0146] Example 14 provides a method for preparing a 1,2,4-triazol-3-one compound. The synthetic route and steps are as follows:

[0147]

[0148] 0.5 mmol phenethyl isocyanate, 0.6 mmol benzylamidine hydrochloride, 0.5 mmol tetrabutylammonium iodide, 0.4 mmol iodobenzene acetate, 0.2 mmol copper acetate, and 1 mL DMSO were sequentially added to a 25 mL screw-top test tube. The mixture was stirred at 80 °C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature to obtain the crude product. The crude product was purified by column chromatography to obtain product 3an, with a yield of 86% and a purity of 98%.

[0149] The obtained product 3an is a pale yellow solid, and its proton and carbon spectra are shown below. Figure 29 and Figure 30 As shown, the structural characterization data are as follows:

[0150] Rf=0.5(petroleum ether:ethyl acetate=3:1); 1 H NMR(500MHz,DMSO-d6)δ12.19(s,

[0151] 1H),7.84–7.76(m,2H),7.53–7.44(m,3H),7.28(dd,J=8.0,6.8Hz,2H),7.24–7.18(m,3H),3.95(dd,J=8.0,6.7Hz,2H),3.02(t,J=7.3Hz,2H). 13 C NMR (126MHz, DMSO-d6) δ154.7,143.9,138.8,130.5,129.4,129.1,128.8,127.2,126.8,125.3,45.7,34.7.

[0152] The present invention has been described in detail above with reference to the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A method for preparing a 1,2,4-triazol-3-one compound, characterized in that, Includes the following steps: Compound 1, compound 2, base, oxidant and solvent were mixed and reacted to obtain 1,2,4-triazol-3-one compound; The base is selected from tetrabutylammonium iodide; the oxidant is iodobenzene acetate and copper acetate; the solvent is selected from DMSO. The structural formulas of compounds 1, 2, and 1,2,4-triazol-3-one are as follows: ； Among them, R 1 and R 2 Selected independently from C 1~6 Alkyl, phenyl, C 1~6 alkyl, C 1~6 alkoxy, halogen, C 1~6 Halogenated alkoxy groups and nitro-substituted phenyl groups.

2. The method for preparing the 1,2,4-triazol-3-one compound according to claim 1, characterized in that, The molar ratio of compound 1 to compound 2 is 1:(1~3).

3. The method for preparing the 1,2,4-triazol-3-one compound according to claim 1, characterized in that, The reaction temperature is 0℃~80℃.

4. The method for preparing the 1,2,4-triazol-3-one compound according to claim 3, characterized in that, The reaction temperature is 40℃~80℃.

5. The method for preparing the 1,2,4-triazol-3-one compound according to claim 1, characterized in that, The reaction time is 0.5 to 24 hours.

6. The method for preparing the 1,2,4-triazol-3-one compound according to claim 1, characterized in that, The reaction is followed by a purification step.

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