Method for photocatalytic synthesis of phosphorylated thiophene compound

Abstract

The invention discloses a method for photocatalytic synthesis of phosphorylated thiophene compounds, and belongs to the technical field of organic synthesis. Carbon quantum dots are used as a photosensitizer, phosphine oxide, thiophene and derivatives thereof are used as raw materials, 2-methyltetrahydrofuran and water are used as solvents, the temperature is controlled to be 25-30 DEG C, reaction is performed for 12-24 h under visible light irradiation, and then column chromatography separation is performed to obtain the phosphorylated thiophene compound. The cheap and easily available carbon quantum dots are used for replacing a noble metal catalyst, so that the method has the advantages of mild reaction conditions, easiness in preparation of the catalyst, green and environment-friendly solvent system, energy consumption reduction, high product yield and the like, and a green synthesis path is provided for phosphorylated thiophene compounds.

Description

Technical Field

[0001] The invention relates to a method for synthesizing phosphonylated thiophene compounds, in particular to a method for photocatalytically synthesizing phosphonylated thiophene compounds, and belongs to the technical field of organic synthesis. Technical Background

[0002] Phosphonylated thiophene compounds are important synthetic intermediates, widely used in the synthesis of medicines, pesticides and materials, and as ligands for transition metal catalytic reactions (CN 106831870A; Synth. Met., 2024, 301, 117538; Eur. J. Org. Chem., 2014, 2694-2702), as shown below.

[0003]

[0004] Traditional synthesis methods for phosphonylated thiophene compounds include phosphorylation of thiophene iodide or bromide (Green Chem., 2023, 25, 9779-9794), phosphorylation of thiophene boronic acid (Org. Chem., 2014, 34, 1340-1346), coupling of aromatic esters with phosphine oxides (Org. Lett., 2018, 20, 1150-1153), coupling of diaryl iodonium salts with phosphine oxides (J. Org. Chem., 2013, 78, 8176-8183), etc. These traditional methods usually require high temperature conditions and the use of strong bases, and the thiophene precursors need to be functionalized. These methods have problems such as harsh reaction conditions, many by-products, low atom utilization, and high pollution, so it is difficult to achieve green and sustainable production.

[0005]

[0006] Photocatalytic technology has mild reaction conditions, energy saving and environmental protection, and has attracted widespread attention. Therefore, it is very necessary to develop a method for photocatalytic direct phosphorylation of thiophene to prepare phosphonylated thiophene compounds. Literature reports that using chloro(pyridine)cobalt oxime as a photocatalyst, under argon protection and in the presence of triethylamine in dichloromethane, blue light irradiates thiophene and diphenylphosphine oxide to undergo intermolecular hydrogen cross-coupling, which can directly prepare phosphonylated thiophene compounds (Angew.Chem.Int.Ed.,2022,61,e202209293). This reaction can also be carried out electrochemically under manganese catalysis (ACS Catal.,2021,11,4295-4300). Although great progress has been made, these methods still require metal catalysts and toxic organic solvents, and the reaction also requires inert gas protection, which is costly.

[0007] Therefore, developing a new synthetic route for photocatalysis without the involvement of transition metals for this reaction has important application value.

[0008] Summary of the invention

[0009] The present invention aims at the problems existing in the prior art and proposes a preparation method for the synthesis of phosphonylated thiophene compounds. The synthesis method has mild conditions, uses a photosensitizer without transition metal under visible light irradiation, does not require inert gas protection, has the advantages of step economy, and raw materials and catalysts are cheap and easily available, and is an environmentally friendly green synthesis method.

[0010] A method for photocatalytically synthesizing phosphonylated thiophene compounds: using carbon quantum dots as photosensitizers, phosphine oxide, thiophene or thiophene derivatives as raw materials, 2-methyltetrahydrofuran and water as solvents, reacting at room temperature in the presence of a base under visible light irradiation to obtain phosphonylated thiophene compounds.

[0011] The structural formula of the phosphonylated thiophene compound is as follows:

[0012]

[0013] wherein R is hydrogen, methyl, ethyl, methoxy, phenyl, p-methylphenyl, p-chlorophenyl, fluorine, chlorine, bromine or aldehyde;

[0014] R 1 are independently methyl, phenyl, p-tolyl, p-chlorophenyl or p-bromophenyl.

[0015] In one embodiment, the specific steps are as follows: thiophene or a thiophene derivative, phosphine oxide and a solvent are added to a reaction tube, and then a photocatalyst and a base are added to react at room temperature under visible light irradiation to obtain a phosphonylated thiophene compound, and the general reaction formula is as follows:

[0016]

[0017] In one embodiment, the volume ratio of the 2-methyltetrahydrofuran to water is 1:1 to 1:10.

[0018] In one embodiment, the molar ratio of the phosphine oxide to thiophene or thiophene derivative is 1:1 to 1:5, preferably 1:5.

[0019] In one embodiment, the amount of carbon quantum dots selected is 10 mg to 30 mg per mmol of phosphine oxide, preferably 20 mg.

[0020] In one embodiment, the base includes potassium phosphate, potassium hydrogen phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, potassium acetate, triethylamine or 2,6-lutidine, preferably the base is cesium carbonate.

[0021] In one embodiment, the phosphine oxide includes diphenylphosphine oxide, or diphenylphosphine oxide with methyl, chlorine, bromine, iodine or nitro groups substituted on the benzene ring.

[0022] In one embodiment, the thiophene derivative includes thiophene, or thiophene substituted at the 2, 3, or 4 positions by methyl, ethyl, methoxy, phenyl, p-methylphenyl, p-chlorophenyl, fluorine, chlorine, or bromine.

[0023] In one embodiment, the light source is an LED lamp or an incandescent lamp, preferably a blue LED lamp.

[0024] In one embodiment, the reaction is carried out under air atmosphere.

[0025] Beneficial effects: The method is carried out in the absence of an oxidant and under visible light induction conditions, and the hydrogen atom transfer between the carbon quantum dots excited by visible light and diphenylphosphine oxide generates a P-center free radical, realizes the dehydrogenation phosphonylation of thiophene, and is accompanied by the generation of hydrogen.

[0026] The reaction raw materials and solvents used in the invention are cheap and low-toxic, and the catalyst is easy to prepare. Visible blue light is used as a light source, which saves energy.

[0027] This reaction uses carbon quantum dots that do not contain metal ions as photosensitizers, there is no risk of metal residue, and the catalyst is easy to recover.

[0028] The reaction substrate has good adaptability, short reaction time, simple reaction operation and mild conditions. It can selectively and efficiently construct phosphonylated thiophene compounds in one step, which is conducive to industrial production. DETAILED DESCRIPTION

[0029] It is worth noting that the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0030] Example 1

[0031] This embodiment is the synthesis of (4-methylthiophene-2-yl) diphenylphosphine oxide, using 4-methylthiophene and diphenylphosphine oxide as raw materials, and the reaction formula is as follows:

[0032]

[0033] Experimental steps: 3-methylthiophene (5.0mmol), diphenylphosphine oxide (1.0mmol), carbon quantum dots (20mg), cesium carbonate (1.0mmol) were added to 2-methylfuran / water (volume ratio 1:1, 2ml), and stirred for an appropriate time under blue light irradiation at room temperature. After the reaction was completed (monitored by thin layer chromatography), it was extracted with ethyl acetate (3×10mL), and the organic layer was dried with MgSO4 and concentrated by vacuum distillation. The crude product was purified by column chromatography to obtain the target product (yield 87%).

[0034] Product data: 1 H NMR (CDCl3, 400MHz) δ = 7.91–7.76 (m, 4H), 7.65–7.56 (m, 2H), 7.52–7.46 (m, 4H), 7.29–7.24 (m, 1H), 6.81–6.83 (m, 1H), 2.41 (s, 3H) ppm. 13 C NMR(CDCl3,100MHz)δ=148.36(d,J C-P =4.8Hz),138.56(d,J C-P =9.9Hz),133.1(d,J C-P =110.3Hz),132.88(d,J C-P =2.8Hz),131.77(d,J C-P =10.7Hz),130.70(d,J C-P =115.3Hz),129.68(d,J C-P =12.9Hz),126.90(d,J C-P =12.8Hz),15.32ppm.

[0035] Example 2

[0036] This example is the synthesis of (4-bromothiophene-2-yl)diphenylphosphine oxide, 3-bromothiophene is used instead of 3-methylthiophene in Example 1, and the other steps are the same as Example 1 to obtain a light yellow oily substance with the following structural formula, and the yield is 70%.

[0037]

[0038] Product data: 1 H NMR (400MHz, CDCl3) δ=7.85–7.73(m,4H),7.67–7.58(m,2H),7.56–7.47(m,4H),7.33(m,1H),7.21(m,1H)ppm. 13 C NMR (100MHz, CDCl3) δ = 138.59 (d, JC-P =9.5Hz),134.36(d,J C-P =110.5Hz),133.88(d,J C-P =2.7Hz),132.58(d,J C-P =114.8Hz),131.79(d,J C-P =9.5Hz),131.21(d,J C-P =11.7Hz),128.67(d,J C-P =12.9Hz),120.27(d,J C-P =5.1Hz)ppm.

[0039] Example 3

[0040] This example is the synthesis of (4,5-dimethylthiophene-2-yl)diphenylphosphine oxide, 2,3-dimethylthiophene is used instead of 3-methylthiophene in Example 1, and the other steps are the same as Example 1 to obtain a light yellow oily substance with the following structural formula, and the yield is 80%.

[0041]

[0042] Product data: 1 H NMR (400MHz, CDCl3) δ=7.83–7.69(m,4H),7.61–7.46(m,4H),7.46–7.35(m,2H),7.24–7.12(m,1H),2.64(s,3H),2.45(s,3H)ppm. 13 C NMR (100MHz, CDCl3) δ = 146.34 (d, J C-P =4.3Hz),135.56(d,J C-P =10.2Hz),132.5(d,J C-P =114.3Hz),131.71(d,J C-P =2.7Hz),131.38(d,J C-P =11.4Hz),129.40(d,J C-P =117.3Hz),127.50(d,J C-P =12.5Hz),126.50(d,J C-P =11.7Hz),15.68,13.52ppm.

[0043] Example 4

[0044] This example is the synthesis of (5-bromo-4-methylthiophene-2-yl)diphenylphosphine oxide, with 2-bromo-3-methylthiophene replacing the 3-methylthiophene in Example 1. The other steps are the same as those in Example 1, and a light yellow oily substance with the following structural formula is obtained, with a yield of 89%.

[0045]

[0046] Product data: 1 H NMR (400MHz, CDCl3) δ=7.85–7.69(m,4H),7.62–7.47(m,4H),7.45–7.36(m,2H),7.24–7.12(m,1H),2.11(s,3H)ppm. 13 C NMR (100MHz, CDCl3) δ = 132.55 (d, J C-P =4.3Hz),132.36(d,J C-P =10.2Hz),131.77(d,J C-P =114.3Hz),131.12(d,J C-P =2.7Hz),129.40(d,J C-P =11.4Hz),127.35(d,J C-P =117.3Hz),126.90(d,J C-P =12.5Hz),106.80(d,J C-P =11.7Hz),17.44ppm.

[0047] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for photocatalytic synthesis of phosphonylated thiophene compounds, characterized in that: The method uses carbon quantum dots as photosensitizers, phosphine oxide, thiophene or thiophene derivatives as raw materials, 2-methyltetrahydrofuran and water as solvents, and reacts at room temperature under visible light irradiation in the presence of a base to obtain phosphonylated thiophene compounds. The structural formula of the phosphonylated thiophene compound is as follows: wherein R is hydrogen, methyl, ethyl, methoxy, phenyl, p-methylphenyl, p-chlorophenyl, fluorine, chlorine, bromine or aldehyde; R 1 are independently methyl, phenyl, p-tolyl, p-chlorophenyl or p-bromophenyl.

2. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the volume ratio of 2-methyltetrahydrofuran to water is 1:1 to 1:

10.

3. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the molar ratio of phosphine oxide to thiophene or thiophene derivatives is 1:1 to 1:5, preferably 1:

5.

4. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the amount of carbon quantum dots selected is 10 mg to 30 mg per millimole of phosphine oxide, preferably 20 mg.

5. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the base comprises potassium phosphate, potassium hydrogen phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, potassium acetate, triethylamine or 2,6-lutidine, and preferably the base is cesium carbonate.

6. A method for photocatalytically synthesizing phosphonylated thiophene compounds as claimed in claim 1, wherein the phosphine oxide comprises diphenylphosphine oxide, or diphenylphosphine oxide with a methyl, chlorine, bromine, iodine or nitro group substituted on the benzene ring.

7. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the thiophene derivative comprises thiophene, or thiophene substituted at the 2, 3, or 4 positions by methyl, ethyl, methoxy, phenyl, p-methylphenyl, p-chlorophenyl, fluorine, chlorine, or bromine.

8. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the light source is an LED lamp or an incandescent lamp, preferably a blue LED lamp.

9. A method for photocatalytic synthesis of phosphonylated thiophene compounds as claimed in claim 1, wherein the reaction is carried out in an air atmosphere.

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