Method for preparing S-(1H-pyrrole-2-yl) substituted phosphorothioate compound

Abstract

The invention provides a method for efficiently and highly selectively synthesizing S-(1H-pyrrole-2-yl) substituted phosphorothioate compounds containing different substituted functional groups, which comprises the following steps: by taking cuprous chloride as a catalyst and taking 2-(2-oxo-2-arylethyl) malononitrile, phosphorus pentasulfide and an alcohol compound as reaction substrates, synthesizing the S-(1H-pyrrole-2-yl) substituted phosphorothioate compounds containing the different substituted functional groups by using a one-pot method, thereby obtaining the S-(1H-pyrrole-2-yl) substituted phosphorothioate compounds containing the different substituted functional groups. An organic solvent is added into a reaction system. The method has the advantages that the catalyst and the phosphorus-sulfur acylation reagent are cheap and easy to obtain; the substrate applicability is high; reaction conditions are mild, safe and reliable; the selectivity of the obtained target product is close to 100%, and the yield is high. The method overcomes the defects of poor reaction selectivity, tedious reaction steps, low yield, high cost, need of reagents harmful to the environment and the like in traditional synthesis of the S-(1H-pyrrole-2-yl) substituted phosphorothioate compound, and has a good industrial application prospect.

Description

Technical Field

[0001] The invention relates to the field of catalytic synthesis of organic thiophosphate compounds, and in particular to a synthesis method for preparing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds by cyclization-tandem reaction of 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and alcohol compounds under copper catalysis. Background Art

[0002] Thiophosphates are an important class of organic synthesis intermediates, which are widely used in pharmaceutical intermediates, pesticides, biological agents, optoelectronic materials, high-efficiency flame retardants and catalyst ligands.

[0003] From the analysis of the types and basic properties of phosphating agents, tetracoordinated organophosphorus reagents can be transformed into tricoordinated organophosphorus compounds through intramolecular tautomerism during the phosphating reaction, that is, the high-energy phosphoryl group (P=O) and the PH bond are converted into a P-OH bond. During the reaction process, tricoordinated organophosphorus reagents often use pentacoordinated phosphorus compounds as intermediates or transition states. It is precisely because of the mutual conversion between compounds with different coordination numbers that organophosphorus reagents are widely used in organic synthesis and become an important part of organophosphorus chemistry, especially organic synthetic chemistry. Phosphorus pentasulfide is an important inorganic chemical raw material and is widely used in various fields. With the increasing awareness of environmental protection, the application of phosphorus pentasulfide has gradually attracted people's attention. The traditional organic conversion process of phosphorus pentasulfide has the defects of low phosphorus resource utilization, large environmental pollution, and low selectivity, which can no longer meet the production requirements of contemporary green phosphorus chemical industry.

[0004] The methods for synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds reported in the literature mainly include: (1) (oxidative) dehydrogenation coupling reaction: first, the NH bond of the pyrrole compound is protected by a protecting group, and then a transition metal (iron, copper, nickel, palladium, etc.), an organic ligand (phosphine, nitrogen, carbene, etc.) and (or) an oxidant catalyzes a dehydrogenation coupling reaction between the P(S)-SH compound and the protected pyrrole compound, and finally a deprotection reaction is performed to obtain the corresponding target product; (2 ) Cross-coupling reaction: P(S)-SH compounds are used to catalyze the cross-coupling reaction with 2-halopyrrole compounds or 2-boronic acid pyrrole compounds in the presence of transition metals (iron, copper, nickel, palladium, etc.), organic ligands (phosphine, nitrogen, carbene, etc.) and bases; (3) Nucleophilic substitution reaction: First, the NH bond of the 2-halopyrrole compound is protected by a protecting group, and then the 2-halopyrrole compound undergoes a nucleophilic substitution reaction with the P(S)-SH compound under the synergistic effect of the transition metal and the base to obtain the corresponding target product. However, the above methods generally use special reaction reagents (difficult to prepare, expensive, etc.), special ligands (phosphine ligands, ferrocene ligands, carbene ligands, etc.), and also have the disadvantages of complicated experimental steps (pre-protection and deprotection strategies, etc.), expensive and difficult to recycle catalysts, harsh reaction conditions, cross-substrate applicability, low yield and high environmental pollution.

[0005] So far, the efficient synthesis of S-(1H-pyrrol-2-yl) substituted thiophosphate compounds has several problems, such as raw material quality, production safety (P-SH compounds have strong corrosiveness and physiological toxicity, poor safety and stability of oxidants, etc.), and product stability and purity. The synthesis technology is quite difficult. Currently, only a few companies in the United States, Germany, the United Kingdom and Japan are producing them. At present, my country's high-end or special organic phosphonate products mainly rely on imports.

[0006] In view of the shortcomings of the existing synthesis process of heterocyclic substituted thiophosphate compounds, the industry is focusing on developing a new method for synthesizing the corresponding S-(1H-pyrrol-2-yl) substituted thiophosphate compounds using stable, cheap and readily available phosphorus pentasulfide as a phosphating agent by using inexpensive catalysts or auxiliary agents for efficient catalysis. Summary of the invention

[0007] The purpose of the present invention is to provide a new method for efficiently and selectively synthesizing corresponding S-(1H-pyrrol-2-yl) substituted thiophosphate compounds by using cheap and readily available 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and alcohol compounds as raw materials through a cyclization-tandem reaction, so as to overcome the above-mentioned defects in the prior art.

[0008] The present invention comprises the following steps: taking a reaction amount of 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide, a catalyst and an organic solvent, placing them in a reaction container under air atmosphere for mixing, and stirring and reacting at 25-100° C. for 3-12 hours to obtain the corresponding S-(1H-pyrrol-2-yl) substituted thiophosphate compounds containing different substituted functional groups; the specific reaction formula is as follows:

[0009]

[0010] Wherein, the catalyst is cuprous chloride and the organic solvent is acetonitrile;

[0011] Ar is selected from phenyl, 4-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 3-methylphenyl, 2-hydroxyphenyl, 3,4-dimethoxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-nitrophenyl, 3-chlorophenyl, 3-bromophenyl, 3-nitrophenyl, 2-fluorophenyl, 2-cyanophenyl, 4-phenylphenyl, 2-naphthyl, 2-furanyl;

[0012] R is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-isopropyl-5-methylcyclohexyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2,3-dichloropropyl, 1,3-dichloroisopropyl, 3-butenyl, 5-hexenyl, 3-butynyl, phenethyl, 3-phenylpropyl, 4-methylphenethyl, 4-methoxyphenethyl, 4-fluorophenethyl, 4-bromophenethyl.

[0013] In the above method for synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds from 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and an alcohol compound, 2-(2-oxo-2-arylethyl)malononitrile is selected from 2-(2-oxo-2-phenyl)malononitrile, 2-(2-oxo-2-(4-methylphenyl))malononitrile, 2-(2-oxo-2-(4-ethylphenyl))malononitrile, 2-(2-oxo-2-(4-ethylphenyl))malononitrile, 2-(2-oxo-2-(4-methoxyphenyl))malononitrile, 2-(2-oxo-2-(4-hydroxyphenyl))malononitrile, 2-(2-oxo-2-(3-methylphenyl))malononitrile, 2-(2-oxo-2-(2-hydroxyphenyl))malononitrile, 2-(2-oxo-2-(3,4-dimethoxyphenyl))malononitrile, 2-(2-oxo-2-(3-methoxyphenyl))malononitrile, 2-(2-oxo-2-(4-hydroxyphenyl))malononitrile, 2-(2-oxo-2-(3-methylphenyl))malononitrile, 2-(2-oxo-2-(2-hydroxyphenyl))malononitrile, 2-(2-oxo-2-(3,4-dimethoxyphenyl))malononitrile, 2-(2-oxo-2-(3-methoxyphenyl))malononitrile, -(2-oxo-2-(4-fluorophenyl))malononitrile, 2-(2-oxo-2-(4-chlorophenyl))malononitrile, 2-(2-oxo-2-(4-bromophenyl))malononitrile, 2-(2-oxo-2-(4-trifluoromethylphenyl))malononitrile, 2-(2-oxo-2-(4-cyanophenyl))malononitrile, 2-(2-oxo-2-(4-nitrophenyl))malononitrile, 2-(2-oxo-2-(3-chlorophenyl))malononitrile , 2-(2-oxo-2-(3-bromophenyl))malononitrile, 2-(2-oxo-2-(3-nitrophenyl))malononitrile, 2-(2-oxo-2-(2-fluorophenyl))malononitrile, 2-(2-oxo-2-(2-cyanophenyl))malononitrile, 2-(2-oxo-2-(4-phenylphenyl))malononitrile, 2-(2-oxo-2-(2-naphthyl))malononitrile, 2-(2-oxo-2-(2-furyl))malononitrile.

[0014] In the above method for synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds from 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and an alcohol compound, the alcohol compound is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, isopentanol, cyclobutanol, cyclopentanol, cyclohexanol, menthol, 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 2,3-dichloropropanol, 1,3-dichloroisopropanol, 3-butene-1-ol, 5-hexene-1-ol, 3-butyn-1-ol, phenylethanol, 3-phenylpropanol, 4-methylphenylethanol, 4-methoxyphenylethanol, 4-fluorophenylethanol, and 4-bromophenylethanol.

[0015] In the method for synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds from 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and alcohol compounds, the molar ratio of 2-(2-oxo-2-arylethyl)malononitrile to phosphorus pentasulfide-based alcohol compounds is 1:[1.0-3.0]:[4.0-12.0]; the molar ratio of 2-(2-oxo-2-arylethyl)malononitrile to cuprous chloride is 1:[0.1-0.3].

[0016] The present invention provides a method for efficiently and selectively synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds from 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide and alcohol compounds under copper catalytic reaction conditions. The reaction process is mild and easy to control. While obtaining a high yield and 100% selectivity, the method is simple and easy to operate, and the auxiliary agents used are cheap and easily available, the preparation is simple, and the method has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the single crystal diffraction analysis diagram of the target product in Example 31. DETAILED DESCRIPTION

[0018] The present invention will be further described below in conjunction with embodiments of the present invention:

[0019] 1. Testing and Analysis

[0020] The structural analysis of the reaction products in the following examples of the present invention was performed using a gas phase-mass spectrometer GC / MS (6890N / 5973N) equipped with an HP-5MS capillary chromatographic column (30m×0.45mm×0.8μm) produced by Agilent and a BrukerAvance-III 500 nuclear magnetic resonance analyzer produced by Bruker. The selectivity and yield of the target product were analyzed using a BrukerAvance-III 500 nuclear magnetic resonance analyzer produced by Bruker.

[0021] 2. Embodiment

[0022] Example 1

[0023] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.

[0024] Example 2

[0025] 39.6 mg (0.2 mmol) of 2-(2-oxo-2-(4-methylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 82%.

[0026] Example 3

[0027] 42.4 mg (0.2 mmol) of 2-(2-oxo-2-(4-ethylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 88%.

[0028] Example 4

[0029] 48.0 mg (0.2 mmol) of 2-(2-oxo-2-(4-tert-butylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.

[0030] Example 5

[0031] 42.8 mg (0.2 mmol) of 2-(2-oxo-2-(4-methoxyphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0032] Example 6

[0033] 40.0 mg (0.2 mmol) of 2-(2-oxo-2-(4-hydroxyphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 88%.

[0034] Example 7

[0035] 39.6 mg (0.2 mmol) of 2-(2-oxo-2-(3-methylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.

[0036] Example 8

[0037] 40.0 mg (0.2 mmol) of 2-(2-oxo-2-(2-hydroxyphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.

[0038] Example 9

[0039] 48.8 mg (0.2 mmol) of 2-(2-oxo-2-(3,4-dimethoxyphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.

[0040] Example 10

[0041] 42.8 mg (0.2 mmol) of 2-(2-oxo-2-(3-methoxyphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 85%.

[0042] Embodiment 11

[0043] 40.4 mg (0.2 mmol) of 2-(2-oxo-2-(4-fluorophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 88%.

[0044] Example 12

[0045] 43.6 mg (0.2 mmol) of 2-(2-oxo-2-(4-chlorophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.

[0046] Embodiment 13

[0047] 52.6 mg (0.2 mmol) of 2-(2-oxo-2-(4-bromophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 90%.

[0048] Embodiment 14

[0049] 50.4 mg (0.2 mmol) of 2-(2-oxo-2-(4-trifluoromethylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0050] Embodiment 15

[0051] 41.8 mg (0.2 mmol) of 2-(2-oxo-2-(4-cyanophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 83%.

[0052] Example 16

[0053] 45.8 mg (0.2 mmol) of 2-(2-oxo-2-(4-nitrophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 82%.

[0054] Embodiment 17

[0055] 43.6 mg (0.2 mmol) of 2-(2-oxo-2-(3-chlorophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.

[0056] Embodiment 18

[0057] 52.6 mg (0.2 mmol) of 2-(2-oxo-2-(3-bromophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0058] Embodiment 19

[0059] 45.8 mg (0.2 mmol) of 2-(2-oxo-2-(3-nitrophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.

[0060] Embodiment 20

[0061] 40.4 mg (0.2 mmol) of 2-(2-oxo-2-(2-fluorophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 83%.

[0062] Embodiment 21

[0063] 41.8 mg (0.2 mmol) of 2-(2-oxo-2-(2-cyanophenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.

[0064] Embodiment 22

[0065] 52.0 mg (0.2 mmol) of 2-(2-oxo-2-(4-phenylphenyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 79%.

[0066] Embodiment 23

[0067] 46.8 mg (0.2 mmol) of 2-(2-oxo-2-(2-naphthyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 80%.

[0068] Embodiment 24

[0069] 34.8 mg (0.2 mmol) of 2-(2-oxo-2-(2-furyl))malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 92 mg (2.0 mmol) of ethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0070] Embodiment 25

[0071] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 64 mg (2.0 mmol) of methanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 43%.

[0072] Embodiment 26

[0073] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 120 mg (2.0 mmol) of n-propanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 78%.

[0074] Embodiment 27

[0075] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 120 mg (2.0 mmol) of isopropanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 82%.

[0076] Embodiment 28

[0077] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 148 mg (2.0 mmol) of n-butanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.

[0078] Embodiment 29

[0079] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 148 mg (2.0 mmol) of isobutyl alcohol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0080] Embodiment 30

[0081] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 176 mg (2.0 mmol) of isoamyl alcohol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 73%.

[0082] Embodiment 31

[0083] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 144 mg (2.0 mmol) of cyclobutanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 82%.

[0084] Embodiment 32

[0085] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 172 mg (2.0 mmol) of cyclopentanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0086] Embodiment 33

[0087] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 200 mg (2.0 mmol) of cyclohexanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 78%.

[0088] Embodiment 34

[0089] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 312 mg (2.0 mmol) of menthol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 76%.

[0090] Embodiment 35

[0091] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 200 mg (2.0 mmol) of 2,2,2-trifluoroethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 79%.

[0092] Embodiment 36

[0093] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 298.8 mg (2.0 mmol) of 2,2,2-trichloroethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 84%.

[0094] Embodiment 37

[0095] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 258 mg (2.0 mmol) of 2,3-dichloropropanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.

[0096] Embodiment 38

[0097] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 258 mg (2.0 mmol) of 1,3-dichloroisopropanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 76%.

[0098] Embodiment 39

[0099] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 144 mg (2.0 mmol) of 3-butene-1-ol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 83%.

[0100] Embodiment 40

[0101] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 200 mg (2.0 mmol) of 5-hexen-1-ol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 77%.

[0102] Embodiment 41

[0103] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 140 mg (2.0 mmol) of 3-butyn-1-ol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 85%.

[0104] Embodiment 42

[0105] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 244 mg (2.0 mmol) of phenylethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 76%.

[0106] Embodiment 43

[0107] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 272 mg (2.0 mmol) of 3-phenylpropanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 83%.

[0108] Embodiment 44

[0109] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 272 mg (2.0 mmol) of 4-methylphenylethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 79%.

[0110] Embodiment 45

[0111] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 304 mg (2.0 mmol) of 4-methoxyphenylethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 78%.

[0112] Embodiment 46

[0113] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 280 mg (2.0 mmol) of 4-fluorophenylethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.

[0114] Embodiment 47

[0115] 36.8 mg (0.2 mmol) of 2-(2-oxo-2-phenyl)malononitrile, 22.2 mg (0.1 mmol) of phosphorus pentasulfide, 402 mg (2.0 mmol) of 4-bromophenylethanol and 4.0 mg (0.04 mmol) of cuprous chloride were added to a Schlenk tube under air, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 60° C. for 3 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 77%.

[0116] As can be seen from the above examples, the method of preparing the corresponding S-(1H-pyrrol-2-yl) substituted thiophosphate compounds containing different substituted functional groups by efficiently reacting 2-(2-oxo-2-arylethyl) malononitrile with phosphorus pentasulfide and alcohol compounds adopted in the present invention has the advantages of mild reaction conditions, cheap and easy to obtain catalysts, and simple preparation. In addition, the method also has the advantages of wide substrate applicability and high yield, and provides a method for efficiently synthesizing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds containing different substituted functional groups.

[0117] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing S-(1H-pyrrol-2-yl) substituted thiophosphate compounds, characterized in that: The method comprises the following steps: taking a reaction amount of 2-(2-oxo-2-arylethyl)malononitrile, phosphorus pentasulfide, a catalyst and an organic solvent, placing them in a reaction container under air atmosphere for mixing, and stirring and reacting at 25-100° C. for 3-12 hours to obtain the corresponding S-(1H-pyrrol-2-yl) substituted thiophosphate compounds containing different substituted functional groups; the specific reaction formula is as follows: Wherein, the catalyst is cuprous chloride and the organic solvent is acetonitrile; Ar is selected from phenyl, 4-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 3-methylphenyl, 2-hydroxyphenyl, 3,4-dimethoxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-nitrophenyl, 3-chlorophenyl, 3-bromophenyl, 3-nitrophenyl, 2-fluorophenyl, 2-cyanophenyl, 4-phenylphenyl, 2-naphthyl, 2-furanyl; R is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-isopropyl-5-methylcyclohexyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2,3-dichloropropyl, 1,3-dichloroisopropyl, 3-butenyl, 5-hexenyl, 3-butynyl, phenethyl, 3-phenylpropyl, 4-methylphenethyl, 4-methoxyphenethyl, 4-fluorophenethyl, 4-bromophenethyl.

2. The method according to claim 1, characterized in that The 2-(2-oxo-2-arylethyl)malononitrile is selected from 2-(2-oxo-2-phenyl)malononitrile, 2-(2-oxo-2-(4-methylphenyl))malononitrile, 2-(2-oxo-2-(4-ethylphenyl))malononitrile, 2-(2-oxo-2-(4-tert-butylphenyl))malononitrile, 2-(2-oxo-2-(4-methoxyphenyl))malononitrile, 2-(2-oxo-2-(4-tert-butylphenyl))malononitrile, 2-(2-oxo-2-(3,4-dimethoxyphenyl))malononitrile, 2-(2-oxo-2-(3-methoxyphenyl))malononitrile, 2-(2-oxo-2-(4-fluorophenyl))malononitrile, 2-(2-oxo-2-(3,4-dimethoxyphenyl))malononitrile, 2-(2-oxo-2-(3-methoxyphenyl))malononitrile, 2-(2-oxo-2-(4-fluorophenyl))malononitrile, 2-(2-oxo-2 2-(2-oxo-2-(4-trifluoromethylphenyl))malononitrile, 2-(2-oxo-2-(4-cyanophenyl))malononitrile, 2-(2-oxo-2-(4-nitrophenyl))malononitrile, 2-(2-oxo-2-(3-chlorophenyl))malononitrile, 2-(2-oxo-2-(3-bromophenyl))malononitrile, phenyl))malononitrile, 2-(2-oxo-2-(3-nitrophenyl))malononitrile, 2-(2-oxo-2-(2-fluorophenyl))malononitrile, 2-(2-oxo-2-(2-cyanophenyl))malononitrile, 2-(2-oxo-2-(4-phenylphenyl))malononitrile, 2-(2-oxo-2-(2-naphthyl))malononitrile, 2-(2-oxo-2-(2-furyl))malononitrile.

3. The method according to claim 1, characterized in that The alcohol compound is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, isopentanol, cyclobutanol, cyclopentanol, cyclohexanol, menthol, 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 2,3-dichloropropanol, 1,3-dichloroisopropanol, 3-butene-1-ol, 5-hexene-1-ol, 3-butyn-1-ol, phenylethyl alcohol, 3-phenylpropanol, 4-methylphenylethyl alcohol, 4-methoxyphenylethyl alcohol, 4-fluorophenylethyl alcohol, and 4-bromophenylethyl alcohol.

4. The preparation method according to claim 1, characterized in that: The molar ratio of the 2-(2-oxo-2-arylethyl)malononitrile to phosphorus pentasulfide and the alcohol compound is 1:[1.0-3.0]:[4.0-12.0]; the molar ratio of the 2-(2-oxo-2-arylethyl)malononitrile to cuprous chloride is 1:[0.1-0.3].

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