C5-selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone

Abstract

This invention discloses a C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone. The method includes: dissolving 4,5-dichloropyridazinone (Formula I), a photocatalyst, and an organic amine reducing agent in an organic solvent under inert gas protection, and reacting under visible light irradiation to obtain 4-chloropyridazinone (Formula II); wherein R is selected from aryl, heteroaryl, alkyl, benzyl, or acylalkyl; the photocatalyst is disodium eosin Y or tetrabromofluorescein; the organic amine reducing agent is N,N-diisopropylethylamine; the organic solvent is DMF, DMSO, or acetonitrile; and the visible light wavelength is 420-520 nm. This method has advantages such as high regioselectivity, mild reaction conditions, and a wide range of applicable substrates.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 4-chloropyridazinone by highly regioselective C5-position hydrogenation dechlorination under visible light catalysis. Background Technology

[0002] Pyridazin-3(2H)-ones (pyridazinones) are an important class of nitrogen-containing heterocyclic compounds, widely found in drugs, pesticides, and functional materials with various biological activities such as anti-inflammatory, anticancer, antibacterial, and cardiovascular protection. 4,5-Dichloropyridazinones are important intermediates in the synthesis of pyridazinone derivatives. By selectively removing the chlorine atom at the C5 position, 4-chloropyridazinones can be prepared, thereby constructing a diverse library of compounds.

[0003] No direct, catalytic, and highly regioselective C5-position hydrogenation dechlorination method for 4,5-dichloropyridazinone has been reported in the prior art. Existing indirect methods (Lopez-Tapia et al., J. Med. Chem. 2015, 58, 8413) require the use of equivalent amounts of hydrazine and copper sulfate, and only one example has been reported; these methods are cumbersome and have limited applicability. Patents WO2021 / 28362 and WO2022 / 237627 describe a method for reducing 4,5-dibromopyridazinone with NaBH4, but only one example has been reported, and it is ineffective for chlorinated substrates. Therefore, developing a mild, efficient, and highly selective C5-position hydrogenation dechlorination method for 4,5-dichloropyridazinone has significant application value. Summary of the Invention

[0004] This invention aims to provide a selective hydrogenation dechlorination method for 4,5-dichloropyridazinone that features mild reaction conditions, simple operation, high yield, good regioselectivity, and a wide range of applicable substrates, particularly achieving highly selective dechlorination at the C5 position.

[0005] The technical solution of the present invention to solve the above-mentioned technical problems is as follows.

[0006] A C5-selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone includes the following steps: under nitrogen or argon protection, 4,5-dichloropyridazinone (as shown in Formula (I), a photocatalyst, and an organic amine reducing agent are dissolved in an organic solvent and reacted under visible light irradiation with a wavelength of 420-520 nm. After the reaction is completed, post-treatment is performed to obtain the C5-selective hydrogenation dechlorination product—4-chloropyridazinone (as shown in Formula (II)).

[0007]

[0008] Wherein, R is selected from phenyl, C1-C4 alkylphenyl, C1-C4 alkoxyphenyl, halophenyl, trifluoromethylphenyl, cyanophenyl, pyridyl, C1-C6 alkyl, tert-butyl, butynyl, bromobutyl, tetrahydrofuranyl, tetrahydropyranyl, benzyl, C1-C4 alkylbenzyl, cyanobenzyl, benzoylmethyl, halobenzoylmethyl, naphthylmethyl, or difluorobenzoylmethyl; the photocatalyst is disodium eosin Y or tetrabromofluorescein; the organic amine reducing agent is N,N-diisopropylethylamine (DIPEA); and the organic solvent is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or acetonitrile (MeCN).

[0009] Preferably, the wavelength of the visible light is 450-460 nm; the organic solvent is DMF; the reaction time is 2-12 hours, more preferably 8-10 hours; the amount of the photocatalyst is 1-10 mol% of the substrate molar amount, more preferably 5 mol%; and the amount of the organic amine reducing agent is 2-5 times the substrate molar amount, more preferably 3 times.

[0010] Compared with the prior art, the method provided by the present invention has the following beneficial effects:

[0011] (1) High regioselectivity: It can specifically achieve dechlorination at the C5 position without affecting the chlorine atom at the C4 position, and the product structure is well-defined;

[0012] (2) Mild reaction conditions: The reaction is driven by visible light and carried out at room temperature and pressure, avoiding strong reducing agents or high temperature and high pressure conditions;

[0013] (3) Simple operation: one-pot reaction, no complicated steps required;

[0014] (4) Wide range of substrates: It has good compatibility with different substituents (such as aryl, alkyl, benzyl, heterocyclic groups, etc.) attached to the N atom of pyridazinone, and the yield is moderate to excellent (44%-91%).

[0015] (5) Environmentally friendly: Uses low-toxicity or non-toxic reagents and has high atom economy. Attached Figure Description

[0016] Figure 1 The 1H NMR spectrum of 4-chloro-2-phenylpyridazine-3(2H)-one (IIa), the product of Example 1;

[0017] Figure 2 The carbon NMR spectrum of 4-chloro-2-phenylpyridazine-3(2H)-one (IIa), the product of Example 1;

[0018] Figure 3The 1H NMR spectrum of 4-chloro-2-(but-2-ynyl)pyridazine-3(2H)-one (IIm) is shown below.

[0019] Figure 4 The carbon NMR spectrum of 4-chloro-2-(but-2-ynyl)pyridazine-3(2H)-one (IIm) of the product of Example 13;

[0020] Figure 5 The 1H NMR spectrum of 4-chloro-2-(tetrahydrofuran-2-yl)pyridazine-3(2H)-one (IIo), the product of Example 15;

[0021] Figure 6 The carbon NMR spectrum of 4-chloro-2-(tetrahydrofuran-2-yl)pyridazine-3(2H)-one (IIo), the product of Example 15. Detailed Implementation

[0022] The present invention will be further described below with reference to embodiments, but the scope of protection of the present invention is not limited thereto.

[0023] In the following examples, unless otherwise specified, 0.1 mmol of 4,5-dichloro-2-phenylpyridazine-3(2H)-one (Ia) was used as the substrate, the total reaction volume was 1 mL, and the reaction was carried out under nitrogen protection by irradiation with a 25 W LED lamp for 10 hours. The product yield was determined by GC-MS.

[0024] I. Condition Optimization Experiment

[0025] 1. Photocatalyst screening: The photocatalyst was changed according to Table 1, while other conditions remained the same. The results are shown in Table 1. Eosin Y-Na2 showed the best performance, with a yield of 87%.

[0026] Table 1 Screening of photocatalysts

[0027] Entry Photocatalyst (5 mol%) Yield (%) 1 Tetrabromofluorescein 80 2 disodium eosin Y 87 3 Rhodamine 6G 16 4 Rhodamine B 20 5 phenothiazine 4 6 Riboflavin 13 7 <![CDATA[Ru(bpy)3Cl2·6H2O (2 mol%)]]> 63 8 No photocatalyst 43

[0028] 2. Wavelength selection: Using disodium eosin Y as the photocatalyst, the LED light source wavelength was changed according to Table 2. The results are shown in Table 2, with the highest yield (87%) at wavelengths of 453-457 nm.

[0029] Table 2 Wavelength Selection

[0030] Entry Wavelength (nm) Yield (%) 1 Natural light No response 2 378-382 61 3 393-397 52 4 408-412 42 5 423-427 66 6 453-457 87 7 478-482 82 8 518-522 65

[0031] 3. Solvent selection: The reaction solvent was changed according to Table 3. The results are shown in Table 3. DMF had the best effect (87%).

[0032] Table 3 Solvent Screening

[0033] Entry solvent Yield (%) 1 N,N-Dimethylformamide 87 2 Dimethyl sulfoxide 73 3 Acetonitrile 60 4 1,2-Dichloroethane 10 5 Tetrahydrofuran 4.5 6 Cyclohexane No response 7 ethanol 5.7 8 methanol 1.2 9 1,4-Dioxane 8.3

[0034] 4. Screening of reaction time: The reaction time was changed according to Table 4. The results are shown in Table 4. The yield reached 84% after 10 hours. Further extending the time did not significantly improve the yield.

[0035] Table 4 Screening of reaction time

[0036] Entry Time (h) Yield (%) 1 2 24 2 4 55 3 6 69 4 8 79 5 10 84 6 12 83

[0037] 5. The reaction conditions were changed according to Table 5. The results are shown in Table 5. The reaction hardly proceeded when there was no light, no photocatalyst, or no DIPEA. The yield decreased significantly under air atmosphere, indicating that light, photocatalyst, DIPEA and inert atmosphere are all necessary to obtain high yield.

[0038] Table 5 Control Experiment

[0039] Entry condition Yield (%) 1 <![CDATA[N2 protection]]> 84 2 air atmosphere 72 3 Darkness (no light) No response 4 No DIPEA No response 5 No photocatalyst 43

[0040] Summary: The optimal reaction conditions were determined to be: disodium eosin Y (5 mol%) as photocatalyst, DIPEA (3 equiv) as reducing agent, DMF as solvent, 450-460 nm LED illumination, reaction time of 10 hours, and nitrogen protection.

[0041] II. Substrate Expansion Experiment under Optimal Conditions

[0042] The following examples all use the above-described optimal reaction conditions, only changing the R group in substrate formula (I). Example 1 provides a representative operation at a scale of 1 mmol, while the other examples are at a scale of 0.1 mmol.

[0043] Example 1: Synthesis of 4-chloro-2-phenylpyridazine-3(2H)-one (IIa) (1 mmol scale)

[0044]

[0045] In a 10 mL borosilicate glass tube, 0.24 g (1.0 mmol) of 4,5-dichloro-2-phenylpyridazine-3(2H)-one and disodium eosin Y (34.5 mg, 5 mol%) were added, and the tube was sealed with a rubber stopper. The reaction system was purged with vacuum / nitrogen three times. DIPEA (512 μL, 3 equiv) and DMF (2.0 mL) were injected sequentially. The mixture was stirred and reacted for 10 hours under 25 W LED light (450-460 nm). After the reaction was complete, the mixture was washed with saturated brine, extracted with ethyl acetate, and the organic phase was concentrated. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1-6 / 1) to give a white solid product IIa (0.154 g, 75% yield).1 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 4.4 Hz, 1H), 7.61 (d, J = 1.2 Hz, 1H), 7.59 (d, J = 0.8 Hz, 1H), 7.51–7.46 (m, 2H), 7.45–7.39 (m, 2H) (its 1H NMR spectrum is shown in [reference needed]). Figure 1 ). 13 C10 NMR (100 MHz, CDCl3) δ 157.3, 141.4, 138.4, 135.6, 129.1, 128.9, 128.7 (2C), 125.3 (2C) (its carbon NMR spectrum is shown in...) Figure 2 HRMS(ESI) m / z: [M+H] + Calcd for C 10 H8ClN2O 207.0320; Found 207.0326.

[0046] Example 2: Synthesis of 4-chloro-2-(m-tolyl)pyridazine-3(2H)-one (IIb)

[0047]

[0048] Following the procedure in Example 1, using 4,5-dichloro-2-(m-tolyl)pyridazine-3(2H)-one as a substrate, a yellow solid product IIb was obtained in 80% yield. 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 4.4 Hz, 1H), 7.42 (d,J = 4.4 Hz, 1H), 7.41-7.34 (m, 3H), 7.25-7.19 (m, 1H), 2.41 (s, 3H). 13 C NMR(100 MHz, CDCl3) δ 157.4, 141.3, 139.0, 138.3, 135.5, 129.5, 129.1, 128.7,125.9, 122.4, 21.4. HRMS(ESI) m / z: [M+H] + Calcd for C 11 H 10 ClN2O 221.0476; Found221.0479.

[0049] Examples 3-25: Synthesis of other substituted substrates

[0050] Following the procedures of Examples 1 or 2, only the R group in substrate formula (I) was replaced with the corresponding substituent to prepare compound IIc-IIy. Characterization data are as follows:

[0051] 4-Chloro-2-(p-Tolyl)pyridazin-3(2H)-one (IIc)

[0052]

[0053] White solid, 90% yield. 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 3.2 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 3.6 Hz, 1H), 7.19 (d, J = 7.6 Hz, 2H), 2.32 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 157.3, 138.9, 138.7, 138.1, 135.5,129.4 (2C), 129.1, 125.0 (2C), 21.2. HRMS(ESI) m / z: [M+H] + Calcd forC 11 H 10 ClN2O 221.0476; Found 221.0477.

[0054] 4-Chloro-2-(4-methoxyphenyl)pyridazine-3(2H)-one (IId):

[0055]

[0056] White solid, yield 85%. 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J=4.4Hz, 1H), 7.52 (d, J=8.8Hz, 2H), 7.42 (d, J=4.4Hz, 1H), 6.98 (d, J=9.2Hz, 2H), 3.85 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 159.5, 157.4, 138.2, 135.4, 134.4, 129.0, 126.5(2C), 114.0 (2C), 55.6. HRMS(ESI) m / z: [M+H] + Calcd for C 11 H10 ClN2O2 237.0425;Found 237.0426.

[0057] 4-Chloro-2-(4-fluorophenyl)pyridazine-3(2H)-one (IIe):

[0058]

[0059] White solid, yield 81%. 1 H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 4.4 Hz, 1H), 7.62 – 7.58 (m, 2H), 7.46 (d, J = 4.4 Hz, 1H), 7.16 (t, J = 8.0 Hz, 2H). 13 CNMR (100 MHz, CDCl3) 162.2 (d, 1 J C-F = 247.2 Hz), 157.3, 138.4, 137.3 (d, 4 J C-F =3.1 Hz), 135.7, 129.2, 127.2 (d, 3 J C-F = 8.7 Hz, 2C), 115.8 (d, 2 J C-F = 23.0 Hz, 2C). 19 F NMR (375 MHz, CDCl3) δ -112.2 (s). HRMS(ESI) m / z: [M+H] + Calcd forC 10 H7ClFN2O 225.0225; Found 225.0226.

[0060] 4-Chloro-2-(4-chlorophenyl)pyridazine-3(2H)-one (IIf):

[0061]

[0062] White solid, yield 74%. 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 4.3 Hz, 1H), 7.59 (d, J = 8.7 Hz, 2H), 7.48 – 7.41 (m, 3H). 13C NMR (100 MHz, CDCl3) δ156.2, 138.8, 137.5, 134.8, 133.4, 128.2, 128.0 (2C), 125.6 (2C). HRMS(ESI)m / z: [M+H] + Calcd for C 10 H7Cl2N2O 240.9930; Found 240.9930.

[0063] 4-Chloro-2-(4-trifluorotolyl)pyridazine-3(2H)-one (IIg):

[0064]

[0065] White solid, yield 51%. 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 4.4 Hz, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 4.4 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 157.2, 144.0, 138.7, 136.1, 130.5 (q, 2 J C-F = 32.6Hz), 129.3, 126.0 (q, 3 J C-F = 3.6 Hz, 2C), 125.6 (2C), 123.7 (q, 1 J C-F = 270.6Hz). 19 F NMR (376 MHz, CDCl3) δ -62.6 (s). HRMS(ESI) m / z: [M+H] + Calcd forC 11 H7ClF3N2O 275.0194; Found 275.0199.

[0066] 4-Chloro-2-(2,4-dimethylyl)pyridazine-3(2H)-one (IIh):

[0067]

[0068] Yellow solid, yield 66%. 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 4.4 Hz, 1H), 7.44 (d, J = 4.4 Hz, 1H), 7.15 – 7.09 (m, 3H), 2.37 (s, 3H), 2.11 (s, 3H). 13 CNMR (100 MHz, CDCl3) δ 157.3, 139.5, 138.0 (2C), 135.4, 134.1, 131.7, 129.4,127.6, 126.4, 21.2, 17.4. HRMS(ESI) m / z: [M+H] + Calcd for C 12 H 12 ClN2O 235.0633;Found 235.0635.

[0069] 4-Chloro-2-(2,4-dichlorophenyl)pyridazine-3(2H)-one (IIi):

[0070]

[0071] Yellow solid, yield 70%. 1 H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 4.4 Hz, 1H), 7.57 (d, J = 2.0 Hz, 1H), 7.48 (d, J = 4.0 Hz, 1H), 7.40 (dd, J = 8.4, 2.0Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 156.9, 138.4,137.5, 136.1 (2C), 132.5, 130.4, 129.8, 129.5, 128.2. HRMS(ESI) m / z: [M+H] + Calcd for C 10 H6Cl3N2O 274.9540; Found 274.9539.

[0072] 4-Chloro-2-(pyridin-4-yl)pyridazin-3(2H)-one (IIj):

[0073]

[0074] Yellow solid, yield 44%. 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 6.0 Hz, 2H), 7.89 (d, J = 4.4 Hz, 1H), 7.76 (d, J = 6.4 Hz, 2H), 7.47 (d, J = 4.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 157.0, 150.8 (2C), 148.1, 138.9, 136.5, 129.2,118.7 (2C). HRMS(ESI) m / z: [M+H] + Calcd for C9H7ClN3O 208.0272; Found208.0275.

[0075] 4-Chloro-2-methylpyridazine-3(2H)-one (IIk):

[0076]

[0077] Yellow solid, yield 70%. 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J=4.4Hz, 1H), 7.39 (d, J=4.4Hz, 1H), 3.86 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 158.0, 136.9, 134.8,129.3, 41.2. HRMS(ESI) m / z: [M+Na] + Calcd for C5H5ClN2ONa 166.9983; Found166.9985.

[0078] 4-Chloro-2-tert-butylpyridazine-3(2H)-one (IIl):

[0079]

[0080] Yellow solid, yield 74%. 1 H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 4.4 Hz, 1H), 7.34 (d, J = 4.4 Hz, 1H), 1.67 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 158.0,137.9, 133.1, 128.4, 66.8, 27.8 (3C). HRMS(ESI) m / z: [M+Na] + Calcd for C8H 11 ClN2ONa 209.0452; Found 209.0455.

[0081] 4-Chloro-2-(But-2-ynyl)pyridazine-3(2H)-one (IIm):

[0082]

[0083] Purple solid, yield 57%. 1 ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 4.4 Hz, 1H), 7.38 (d, J = 4.4 Hz, 1H), 4.94 – 4.91 (m, 2H), 1.84 – 1.80 (m, 3H) (its ¹H NMR spectrum is shown in [reference needed]). Figure 3 ). 13 C10 NMR (100 MHz, CDCl3) δ 157.6, 137.1, 134.9, 129.1, 102.3, 65.1, 48.4, 32.2 (its C10 NMR spectrum is shown in [reference needed]). Figure 4 HRMS(ESI) m / z: [M+Na] + Calcd forC8H7ClN2ONa 205.0139; Found 205.0142.

[0084] 4-Chloro-2-(4-bromobutyl)pyridazine-3(2H)-one (IIn):

[0085]

[0086] Yellow solid, 90% yield. 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 4.4 Hz, 1H),7.38 (d, J = 4.4 Hz, 1H), 4.26 (t, J = 6.8 Hz, 2H), 3.59 (t, J = 6.4 Hz, 2H),2.06 – 1.94 (m, 2H), 1.83 (dt, J = 13.4, 6.5 Hz, 2H). 13C NMR (100 MHz, CDCl3)δ 157.7, 137.2, 135.1, 129.1, 52.1, 44.3, 29.4, 25.6. HRMS(ESI) m / z: [M+H] + Calcd for C8H 11 ClBrN2O 264.9738; Found 264.9739.

[0087] 4-Chloro-2-(tetrahydrofuran-2-yl)pyridazine-3(2H)-one (IIo):

[0088]

[0089] Yellow solid, yield 91%. 1 ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 4.0 Hz, 1H), 7.36 (d, J = 4.4 Hz, 1H), 6.70 (dd, J = 6.4, 2.8 Hz, 1H), 4.27 – 4.20 (m, 1H), 4.05 – 4.00 (m, 1H), 2.40 – 2.19 (m, 3H), 2.08 – 1.98 (m, 1H) (its ¹H NMR spectrum is shown in [reference needed]). Figure 5 ). 13 C NMR (100 MHz, CDCl3) δ 157.5, 137.2, 134.9, 129.0, 88.2, 70.3, 31.2, 24.7 (its proton NMR spectrum is shown in [reference needed]). Figure 6 HRMS(ESI) m / z: [M+Na] + Calcd forC8H9ClN2O2Na 223.0245; Found 223.0245.

[0090] 4-Chloro-2-(tetrahydropyran-2-yl)pyridazin-3(2H)-one (IIp):

[0091]

[0092] Yellow solid, yield 69%. 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 4.4 Hz, 1H), 7.37 (d, J = 4.4 Hz, 1H), 6.10 (dd, J = 9.8, 2.0 Hz, 1H), 4.19 – 4.10 (m,1H), 3.76 (td, J = 11.6, 2.4 Hz, 1H), 2.22 – 2.09 (m, 1H), 2.08 – 1.99 (m,1H), 1.80 – 1.70 (m, 3H), 1.64 – 1.53 (m, 1H). 13 C NMR (100 MHz, CDCl3) δ157.1, 137.5, 135.3, 129.1, 84.1, 69.0, 29.1, 24.9, 22.7. HRMS(ESI) m / z: [M+Na] + Calcd for C9H 11 ClN2O2Na 237.0401; Found 237.0401.

[0093] 4-Chloro-2-(1,3-dioxolane-2-yl)pyridazine-3(2H)-one (IIq):

[0094]

[0095] A colorless, oily liquid with a yield of 53%. 1 H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 4.4 Hz,1H), 7.36 (d, J = 4.4 Hz, 1H), 5.00 (t, J = 4.4 Hz, 1H), 4.38 (t, J = 7.2 Hz,2H), 4.02 – 3.93 (m, 2H), 3.90 – 3.81 (m, 2H), 2.21 (td, J = 7.2, 4.4 Hz,2H).

[0096] 13 C NMR (100 MHz, CDCl3) δ 157.6, 137.1, 134.9, 129.1, 102.3, 65.1(2C), 48.4, 32.2. HRMS(ESI) m / z: [M+Na] + Calcd for C9H 11 ClN2O3Na 253.0350;Found 253.0354.

[0097] 2-Benzyl-4-chloropyridazine-3(2H)-one (IIr):

[0098]

[0099] White solid, yield 80%. 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 4.4 Hz, 1H), 7.45 (d, J = 6.4 Hz, 2H), 7.36 – 7.26 (m, 4H), 5.35 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 157.6, 137.3, 135.5, 135.2, 129.2, 129.0 (2C), 128.6 (2C), 128.2,56.4. HRMS(ESI) m / z: [M+H] + Calcd for C 11 H 10 ClN2O 221.0476; Found 221.0477.

[0100] 2-(4-tert-butylbenzyl)-4-chloropyridazine-3(2H)-one (IIs):

[0101]

[0102] White solid, yield 75%. 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 4.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 4.4 Hz, 1H), 5.33 (s, 2H), 1.29 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 157.5, 151.1, 137.3,135.1, 132.5, 129.1, 128.8 (2C), 125.6 (2C), 56.1, 34.5, 31.3 (3C). HRMS(ESI)m / z: [M+Na] + Calcd for C 15 H 17 ClN2ONa 299.0922; Found 299.0924.

[0103] 2-(4-cyanobenzyl)-4-chloropyridazine-3(2H)-one (IIt):

[0104]

[0105] White solid, yield 73%. 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 4.4 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 4.4 Hz, 1H), 5.37 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 157.5, 140.4, 137.6, 135.6, 132.5(2C), 129.6 (2C), 129.5, 118.5, 112.2, 56.0. HRMS(ESI) m / z: [M+Na] + Calcd forC 12 H8ClN3ONa 268.0248; Found 268.0251.

[0106] 4-Chloro-2-(2-phenyl)-2-oxoethyl)pyridazine-3(2H)-one (IIu):

[0107]

[0108] White solid, yield 73%. 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.2 Hz, 2H),7.75 (d, J = 4.4 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H),7.44 (d, J = 4.4 Hz, 1H), 5.65 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 191.1,157.9, 137.3, 135.6, 134.6, 134.1, 129.7, 129.0 (2C), 128.1 (2C), 58.7. HRMS(ESI) m / z: [M+H] + Calcd for C 12 H 10ClN2O2 249.0425; Found 249.0427.

[0109] 4-Chloro-2-(2-(4-chlorophenyl)-2-oxoethyl)pyridazine-3(2H)-one (IIv):

[0110]

[0111] White solid, yield 68%. 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 4.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 4.4 Hz, 1H), 5.60 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 190.0, 157.8, 140.6, 137.2, 135.7,132.9, 129.8, 129.5 (2C), 129.3 (2C), 58.6. HRMS(ESI) m / z: [M+H] + Calcd forC 12 H9Cl2N2O2 283.0036; Found 283.0036.

[0112] 4-Chloro-2-(2-(naphth-2-yl)-2-oxoethyl)pyridazine-3(2H)-one (IIw):

[0113]

[0114] White solid, yield 60%. 1 H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.99 (dd, J =14.8, 8.4 Hz, 2H), 7.90 (dd, J = 13.2, 9.6 Hz, 2H), 7.75 (d, J = 4.4 Hz, 1H), 7.63 (t, J = 6.8 Hz, 1H), 7.58 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 4.4 Hz, 1H), 5.77 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 191.0, 157.9, 137.3, 135.9, 135.6,132.3, 131.9, 130.0, 129.7, 129.7, 129.0, 128.9, 127.9, 127.1, 123.5, 58.7.HRMS(ESI) m / z: [M+ Na] + Calcd for C 16 H 11 ClN2O2Na 321.0401; Found 321.0405.

[0115] 4-Chloro-2-(2-(2,4-difluorophenyl)-2-oxoethyl)pyridazine-3(2H)-one (IIx):

[0116]

[0117] White solid, yield 84%. 1 H NMR (400 MHz, CDCl3) δ 8.08 – 8.02 (m, 1H), 7.72 (d, J = 4.4 Hz, 1H), 7.45 (d, J = 4.8 Hz, 1H), 7.05 – 6.00 (m, 1H), 6.99 –6.93 (m, 1H), 5.53 (d, J = 4.0 Hz, 2H).

[0118] 13 C NMR (100 MHz, CDCl3) δ 187.7 (d, 2 J C-F = 5.5 Hz), 166.6 (dd, 1 J C-F =257.6 Hz, 2 J C-F = 12.5 Hz), 163.3 (dd, 1 J C-F = 255.6 Hz, 2 J C-F = 12.7 Hz), 157.8,137.4, 135.6, 133.1 (dd, 2 J C-F = 10.8, 3 J C-F = 4.4 Hz), 129.8, 119.5 (dd, 2 J C-F=14.1, 3 J C-F = 3.6 Hz), 112.9 (dd, 2 J C-F = 22.4 Hz, 3 J C-F = 3.2 Hz), 104.9 (dd, 2 J C-F = 27.1 Hz, 2 J C-F = 25.3 Hz), 62.3 (d, 2 J C-F = 13.7 Hz). 19 F NMR (376 MHz, CDCl3) δ -99.2 (d, J = 1.6 Hz, 1F) δ -103.3 (d, J = 1.6 Hz, 1F). HRMS(ESI) m / z: [M+Na] + Calcd for C 12 H7ClF2N2O2Na 307.0056; Found 307.0059.

[0119] 4-Bromo-2-phenylpyridazine-3(2H)-one (IIy):

[0120]

[0121] White solid, yield 73%. 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 4.4 Hz, 1H),7.66 (d, J = 4.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.48 (t, J = 7.6 Hz, 2H),7.41 (t, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 157.3, 141.5, 135.7,133.3, 129.9, 128.8, 128.7 (2C), 125.3 (2C). HRMS(ESI) m / z: [M+ Na] + Calcdfor C 10 H7BrN2ONa 272.9634; Found 272.9636.

[0122] The embodiments described above are merely illustrative of the technical solutions of the present invention and are not intended to limit it. Those skilled in the art should understand that, without departing from the concept of the present invention, any combination, substitution, or modification of the technical features can be made, and all such modifications should be covered within the protection scope of the present invention. The protection scope of the present invention should be determined by the claims, and the specification can be used to interpret the claims.

Claims

A C5-selective photocatalytic hydrogenation dechlorination method for 1,4,5-dichloropyridazinone, characterized in that, The method includes: under nitrogen or argon protection, dissolving 4,5-dichloropyridazinone (I), a photocatalyst, and an organic amine reducing agent in an organic solvent, and reacting under visible light irradiation with a wavelength of 420-520 nm to obtain the C5-position hydrogenated dechlorination product—4-chloropyridazinone (II). Wherein, R is selected from phenyl, C1-C4 alkylphenyl, C1-C4 alkoxyphenyl, halophenyl, trifluoromethylphenyl, cyanophenyl, pyridyl, C1-C6 alkyl, tert-butyl, butynyl, bromobutyl, tetrahydrofuranyl, tetrahydropyranyl, benzyl, C1-C4 alkylbenzyl, cyanobenzyl, benzoylmethyl, halobenzoylmethyl, naphthylmethyl, or difluorobenzoylmethyl; the photocatalyst is disodium eosin Y or tetrabromofluorescein; the organic amine reducing agent is N,N-diisopropylethylamine (DIPEA); and the organic solvent is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or acetonitrile (MeCN).

2. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 1, characterized in that, The wavelength of the visible light is 450-460 nm.

3. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 1, characterized in that, The organic solvent is DMF.

4. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 1, characterized in that, The reaction time is 2-12 hours.

5. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 4, characterized in that, The reaction time is 8-10 hours.

6. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 1, characterized in that, The amount of the photocatalyst used is 1-10 mol of the substrate molar amount.

7. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 6, characterized in that, The amount of the photocatalyst used is 5 mol.

8. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 1, characterized in that, The amount of the organic amine reducing agent is 2-5 times the molar amount of the substrate.

9. The C5-position selective photocatalytic hydrogenation dechlorination method for 4,5-dichloropyridazinone according to claim 8, characterized in that, The amount of the organic amine reducing agent used is 3 times.

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