Preparation method of visible light catalysis beta-aryl beta-pyridyl thiocyanate compound

Abstract

The invention discloses a preparation method of a B-aryl B-pyridyl thiocyanate compound, which comprises the following steps: in the presence of a photocatalyst and under the condition of blue light irradiation, reacting a compound shown as a formula (1), a compound shown as a formula (2) and a compound shown as a formula (3) to generate a beta-aryl beta-pyridyl thiocyanate compound shown as a formula (4); wherein Ar is selected from substituted or unsubstituted aryl, naphthyl and heteroaryl; the compound in the formula (2) is 4-cyanopyridine; the compound in the formula (3) is thiocyanate, and M is a sodium ion, a potassium ion or an ammonium ion; the photocatalyst is selected from a metal iridium photocatalyst, a metal ruthenium photocatalyst and a carbazole photocatalyst. The preparation method provided by the invention has the advantages of cheap and easily available reaction raw materials, simple reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and can realize industrial production and application. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing beta-aryl beta-pyridyl thiocyanate. Background Art

[0002] Thiocyanate (RSCN) is an important nitrogen-sulfur compound containing a thiocyanate functional group. It has a variety of biological activities, such as inhibiting enzyme activity, insecticidal activity, antimicrobial activity, etc., and has important application value in the fields of medicine and pesticides. In addition, thiocyanate compounds are also widely used in the field of organic synthesis. As an important organic synthesis intermediate, thiocyanate can be converted into a variety of organic sulfides such as thiols, thioethers, isothiocyanates, sulfur-containing heterocycles, etc. through simple transformation. At the same time, it can also be used as a cyaniding agent to participate in the reaction well.

[0003] Heterocyclic rings are a type of structural fragment that is widely found in organic compounds, especially in drug molecules, such as the anticancer drug Ensinco and the anticancer drug Abiraterone. According to statistics, more than 90% of newly approved drugs contain heterocyclic structures, highlighting their important role in medicinal chemistry.

[0004] β-Aryl β-pyridyl thiocyanate compounds have two important functional groups, thiocyanate and heterocycle. Therefore, they are not only widely used in organic synthesis, but also the core skeleton of drug molecules.

[0005] Introducing a thiocyanate group and a heterocycle at both ends of an olefin is a very efficient and simple method for obtaining β-aryl β-pyridyl thiocyanate compounds. However, no patent application has been filed for this type of synthesis method. Summary of the invention

[0006] The present invention provides a method for preparing a β-aryl β-pyridyl thiocyanate compound. The present invention realizes for the first time the synthesis of multiple types of β-aryl β-pyridyl thiocyanate compounds under light-induced conditions by using a simple and readily available thiocyanate as a free radical precursor.

[0007] The technical solution of the present invention is as follows:

[0008] A method for preparing a β-aryl β-pyridyl thiocyanate compound comprises: reacting a compound of formula (1), a compound of formula (2) and a compound of formula (3) in the presence of a photocatalyst and under blue light irradiation to generate a β-aryl β-pyridyl thiocyanate compound of formula (4):

[0009]

[0010] Wherein, Ar is selected from substituted or unsubstituted aryl, naphthyl, heteroaryl;

[0011] The compound of formula (2) is 4-cyanopyridine;

[0012] The compound of formula (3) is thiocyanate, and M is sodium ion, potassium ion, or ammonium ion;

[0013] The photocatalyst is selected from metal iridium photocatalyst, metal ruthenium photocatalyst and carbazole photocatalyst.

[0014] The compound of formula (3) may be ammonium thiocyanate, sodium thiocyanate or potassium thiocyanate.

[0015] Preferably, the compound of formula (1) is selected from:

[0016]

[0017] Preferably, the photocatalyst is selected from:

[0018]

[0019] Preferably, the wavelength of the blue light is 390-440 nm; more preferably 390 nm or 427 nm.

[0020] Preferably, the reaction is carried out in an organic solvent, and the organic solvent is at least one of ethylene glycol dimethyl ether, dimethyl sulfoxide, ethyl acetate, and acetone.

[0021] Preferably, the molar ratio of the compound of formula (1), the compound of formula (2), the compound of formula (3) and the photocatalyst is 1:1.0-2.5:2.0-5.5:0.01-0.05.

[0022] The reaction temperature is room temperature; preferably, the reaction temperature is 25 to 30°C.

[0023] The β-aryl β-pyridyl thiocyanate compound prepared by the present invention is a very important organic synthesis intermediate and can be converted into a variety of organic compounds through various chemical reactions.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] (1) The present invention is the first to achieve the synthesis of multiple types of β-aryl β-pyridyl thiocyanate compounds under photoinduced conditions using simple and readily available thiocyanate as a free radical precursor.

[0026] (2) The preparation method of the present invention has the advantages of cheap and readily available reaction raw materials, simple reaction operation, wide application range of reaction substrates, easy reaction scale-up, mild reaction conditions, etc., and can realize industrial production and application. DETAILED DESCRIPTION

[0027] The present invention will be further described in detail below in conjunction with the examples. It should be pointed out that the examples described below are intended to facilitate the understanding of the present invention and do not have any limiting effect on the present invention.

[0028] The operation methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. Unless otherwise specified, the mol% amount of the photocatalyst in each example is based on Compound 1.

[0029] In the following examples, the photocatalyst is:

[0030]

[0031]

[0032] Example 1: Effect of PC4 on the reaction

[0033]

[0034] In a glove box, weigh PC4 (3 mol%), cyanopyridine (0.2 mmol), and NH4SCN (0.2 mmol) into a 4 mL sample bottle, add the solvent ethylene glycol dimethyl ether (2.0 mL) and styrene (0.1 mmol) in sequence, and tighten the PTFE lid. Take the sample bottle out of the glove box, place it under 440 nm blue light, and react at 25 ° C for 12 hours. After the reaction is completed, remove the solvent on a rotary evaporator to obtain a crude product. Use thin layer chromatography or nuclear magnetic resonance to analyze the conversion rate and yield of the reaction. The experimental results obtained are: the nuclear magnetic yield is 73%.

[0035] Example 2: Effect of PC1 on the reaction

[0036] The only difference from Example 1 is that an equimolar amount of PC1 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 5%.

[0037] Example 3: Effect of PC2 on the reaction

[0038] The only difference from Example 1 is that an equimolar amount of PC2 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 10%.

[0039] Example 4: Effect of PC3 on the reaction

[0040] The only difference from Example 1 is that an equimolar amount of PC3 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 12%.

[0041] Example 5: Effect of PC5 on the reaction

[0042] The only difference from Example 1 is that an equimolar amount of PC5 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 8%.

[0043] Example 6: Effect of PC6 on the reaction

[0044] The only difference from Example 1 is that an equimolar amount of PC6 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 18%.

[0045] Example 7: Effect of PC7 on the reaction

[0046] The only difference from Example 1 is that an equimolar amount of PC7 is used to replace PC4, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 25%.

[0047] Example 8: Effect of 427nm blue light on the reaction

[0048] The only difference from Example 1 is that the wavelength of the blue light is 427 nm, and the rest are the same. The experimental results obtained are: the nuclear magnetic resonance yield is 68%.

[0049] Example 9: Effect of EA solvent on reaction

[0050] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of EA, and the rest is the same. The experimental results obtained are: the NMR yield is 5%.

[0051] Example 10: Effect of DMSO solvent on the reaction

[0052] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of DMSO, and the rest is the same. The experimental results obtained are: the NMR yield is 26%.

[0053] Example 11: Effect of Acetone Solvent on Reaction

[0054] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of acetone, and the rest is the same. The experimental results obtained are: the nuclear magnetic resonance yield is 45%.

[0055] Example 12: Effect of KSCN on the reaction

[0056] The only difference from Example 1 is that NH4SCN is replaced by an equimolar amount of KSCN, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 40%.

[0057] Example 13: Effect of NaSCN on the reaction

[0058] The only difference from Example 1 is that NH4SCN is replaced by an equal molar amount of NaSCN, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 38%.

[0059] Example 14: Investigation of olefin substrates

[0060]

[0061] In a glove box, PC4 (3 mol%), cyanopyridine (0.2 mmol), and NH4SCN (0.2 mmol) were weighed into a 4 mL sample bottle, and solvent ethylene glycol dimethyl ether (2.0 mL) and olefin (0.1 mmol) were added in sequence, and the PTFE lid was screwed tight. The sample bottle was taken out of the glove box, placed under 440 nm blue light, and reacted at 25 ° C for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation to obtain a crude product. The conversion rate and separation yield of the reaction were analyzed by thin layer chromatography or nuclear magnetic resonance. The experimental results are shown in Table 1.

[0062] Table 1 Investigation of olefin reaction substrates

[0063]

[0064]

[0065] The analytical data of compound 5-13 are as follows:

[0066] Analytical data of β-aryl β-pyridyl thiocyanate 5

[0067] 1 H NMR (600MHz, MeOD) δ8.50-8.45 (m, 2H), 7.47-7.43 (m, 2H), 7.36 (d, J=4.4Hz , 4H), 7.29 (dp, J=8.7, 4.7Hz, 1H), 4.42 (t, J=8.1Hz, 1H), 3.87-3.75 (m, 2H).

[0068] 13 C NMR (151MHz, MeOD) δ153.20, 150.48, 141.30, 130.18, 129.08, 128.91, 124.92, 112.93, 52.02, 38.36.

[0069] HRMS (ESI) m / z [M+H] + Calculate for C 14 H 13 N2S: 241.0794, found: 241.0785.

[0070] Analytical data of β-aryl β-pyridyl thiocyanate 6

[0071] 1H NMR (600MHz, MeOD) δ8.54-8.46 (m, 2H), 7.63-7.56 (m, 4H), 7.49-7.45 (m, 2H), 7.44- 7.39 (m, 4H), 7.34-7.29 (m, 1H), 4.45 (t, J=8.1Hz, 1H), 3.82 (qd, J=13.3, 8.2Hz, 2H).

[0072] 13 C NMR (151MHz, MeOD) δ153.11, 150.52, 142.10, 141.67, 140.28, 129.94, 129. 90, 129.57, 128.68, 128.55, 127.95, 127.91, 124.92, 112.96, 51.65, 38.31.

[0073] HRMS (ESI) m / z [M+H] + Calculate for C 18 H 15 N2S: 291.0950, found: 291.0959.

[0074] Analytical data of β-aryl β-pyridyl thiocyanate 7

[0075] 1 H NMR (600MHz, MeOD) δ 8.49-8.45 (m, 2H), 7.44-7.40 (m, 2H), 7.29-7.22 (m, 2H), 6.95-6.88 (m, 2H), 4.36 (t, J=8.2Hz, 1H), 3.83-3.70 (m, 5H).

[0076] 13 C NMR (151MHz, MeOD) δ160.79, 153.58, 150.42, 133.16, 130.16, 124.84, 115.52, 113.01, 55.75, 51.25, 38.62.

[0077] HRMS (ESI) m / z [M+H] + Calculate for C 15 H 15 N2OS: 271.0900, found: 271.0908.

[0078] Analytical data of β-aryl β-pyridyl thiocyanate 8

[0079] 1H NMR (600MHz, MeOD) δ8.49 (s, 2H), 7.47-7.43 (m, 2H), 7.42-7.35 (m, 2H), 7.14-7.05 (m, 2H), 4. 44 (t, J=8.1Hz, 1H), 3.83 (dd, J=13.3, 8.3Hz, 1H), 3.77 (dd, J=13.3, 8.1Hz, 1H), 2.26 (s, 3H).

[0080] 13 C NMR (151MHz, MeOD) δ171.05, 152.94, 151.80, 150.55, 138.88, 130.15, 124.91, 123.42, 112.87, 51.40, 38.27, 20.87.

[0081] HRMS (ESI) m / z [M+H] + Calculate for C 16 H 15 N2O2: 299.0849, found: 299.0853.

[0082] Analytical data of β-aryl β-pyridyl thiocyanate 9

[0083] 1 H NMR (600MHz, MeOD) δ8.51 (s, 2H), 7.45 (d, J=5.2Hz, 2H), 7.43-7.36 (m, 2H), 7.13-7.06 (m, 2H), 4.44 (t, J=8.1Hz, 1H), 3.86-3.74 (m, 2H).

[0084] 13 C NMR (151MHz, MeOD) δ164.52, 162.89, 153.03, 150.55, 137.33, 137.31, 131.07, 131.02, 124.89, 116.90, 116.76, 112.82, 51.27, 38.35.

[0085] 19 F NMR (565MHz, MeOD) δ-116.61.

[0086] HRMS (ESI) m / z [M+H] + Calculate for C 14 H 12 FN2S: 259.0700, found: 259.0705.

[0087] Analytical data of β-aryl β-pyridyl thiocyanate 10

[0088] 1 H NMR (600MHz, MeOD) δ8.60-8.40 (m, 2H), 7.46-7.41 (m, 2H), 7.36 (s, 4H), 4.43 (t, J=8.1Hz, 1H), 3.82 (dd, J=13.3, 8.0Hz, 1H), 3.77 (dd, J=13.3, 8.3Hz, 1H).

[0089] 13 C NMR (151MHz, MeOD) 6152.72, 150.59, 140.06, 134.78, 130.77, 130.21, 124.84, 112.80, 51.35, 38.12.

[0090] HRMS (ESI) m / z [M+H] + Calculate for C 14 H 12 ClN2S: 275.0404, found: 275.0414.

[0091] Analytical data of β-aryl β-pyridyl thiocyanate 11

[0092] 1 H NMR (600MHz, MeOD) δ8.51-8.46(m, 2H), 7.55-7.49(m, 2H), 7.45-7.41(m, 2H), 7.33-7.27( m, 2H), 4.41 (t, J=8.1Hz, 1H), 3.82 (dd, J=13.3, 8.0Hz, 1H), 3.76 (dd, J=13.3, 8.2Hz, 1H).

[0093] 13 C NMR (151MHz, MeOD) δ152.63, 150.60, 140.54, 133.23, 131.08, 124.84, 122.74, 112.79, 51.40, 38.04.

[0094] HRMS: could not be found by ESI source.

[0095] Analytical data of β-aryl β-pyridyl thiocyanate 12

[0096] 1H NMR (600MHz, MeOD) δ8.26 (d, J=5.6Hz, 2H), 7.34 (d, J=8.5Hz, 2H), 7.21 (d, J=5.8Hz, 2H), 7.0 9 (d, J=8.5Hz, 2H), 4.16 (t, J=8.1Hz, 1H), 3.56 (ddd, J=30.6, 13.2, 8.2Hz, 2H), 1.89 (s, 3H).

[0097] 13 C NMR (151MHz, MeOD) δ170.27, 151.85, 149.08, 138.20, 135.35, 128.10, 123.49, 120.24, 111.57, 50.07, 36.96, 22.43.

[0098] HRMS(ESI)m / z[M+H]+calcd for C 16 H 16 N30S: 298.1009, found: 298.1012.

[0099] Analytical data of β-aryl β-pyridyl thiocyanate 13

[0100] 1 H NMR (600MHz, MeOD) δ 8.50-8.45 (m, 2H), 7.89-7.78 (m, 4H), 7.52-7.44 (m, 4H), 7.41 (dd, J=8.5, 1.9Hz, 1H), 4.58 (t, J=8.1Hz, 1H), 3.94-3.85 (m, 2H).

[0101] 13 C NMR (151MHz, MeOD) δ153.07, 150.51, 138.57, 134.96, 134.26, 130.01, 128. 96, 128.68, 127.99, 127.58, 127.40, 126.73, 125.01, 112.98, 52.03, 38.29.

[0102] HRMS (ESI) m / z [M+H] + Calculate for C 18 H 15 N2S: 291.0950, found: 291.0959.

[0103] The embodiments described above provide a detailed description of the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a β-aryl β-pyridyl thiocyanate compound, characterized in that: include: In the presence of a photocatalyst and under the irradiation of blue light, the compound of formula (1), the compound of formula (2) and the compound of formula (3) react to generate a β-aryl β-pyridyl thiocyanate compound of formula (4): Wherein, Ar is selected from substituted or unsubstituted aryl, naphthyl, heteroaryl; The compound of formula (2) is 4-cyanopyridine; The compound of formula (3) is thiocyanate, and M is sodium ion, potassium ion, or ammonium ion; The photocatalyst is selected from metal iridium photocatalyst, metal ruthenium photocatalyst and carbazole photocatalyst.

2. The preparation method according to claim 1, characterized in that: The compound of formula (3) may be ammonium thiocyanate, sodium thiocyanate or potassium thiocyanate.

3. The preparation method according to claim 1, characterized in that: The compound of formula (1) is selected from:

4. The preparation method according to claim 1, characterized in that: The catalyst is selected from:

5. The preparation method according to claim 1, characterized in that: The wavelength of the blue light is 390-440nm.

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