Method for preparing thioether compound by reducing sulfoxide through silane under catalysis of iridium

Abstract

The invention relates to a method for preparing thioether compounds by reducing sulfoxide through silane under the catalysis of iridium, which comprises the following step: in an organic solvent, carrying out reduction reaction on sulfoxide through a silane reagent under the catalysis of an iridium complex to obtain thioether. According to the invention, stable, cheap and easily available commercial sulfoxide is used as a raw material, and is reduced by a silane reagent under the catalysis of a metal complex with very low catalyst loading capacity, so that the thioether compound is efficiently synthesized. According to the present invention, the commercial raw material, the low catalyst loading capacity, the low-price reducing agent and the green solvent from the chemical renewable resource are adopted, and the method has advantages of simple operation step, simple separation, fast reaction rate, good universality, high yield and the like.

Description

Technical Field

[0001] The present invention relates to the field of preparation of sulfide compounds, in particular to a method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis. Background Art

[0002] Sulfide compounds have a wide range of applications in organic synthesis and serve as important intermediates in the synthesis of organic compounds. They are widely present in pharmaceuticals and bioactive natural molecules, including the novel antibacterial drug imipenem (2-1), the atypical antipsychotic quetiapine (2-2), the broad-spectrum anticancer agent nelfinavir (2-3), the antipsychotic thioridazine (2-4), the neuroleptic captodiame (2-5), the enzyme inhibitor T10438 (2-6), the prodrug or drug raw material omeprazole sulfide, lansoprazole sulfide (2-7; 2-9), and the gastric treatment albendazole (2-8). They play an important role in the pharmaceutical, materials, and energy fields. Therefore, the development of an efficient method for the synthesis of sulfides is of great significance in numerous fields.

[0003]

[0004] Sulfide compounds have a wide range of applications in medicine, pesticides, and other fields, and many methods for synthesizing sulfides have been reported to date. The preparation of sulfide compounds by reducing sulfoxides is a common and efficient method, occupying a very important position in the research of synthetic sulfides. The methods for reducing sulfoxides can be roughly divided into the following categories: 1) catalytic hydrogenation, which usually relies on noble metals under harsh reaction conditions; 2) reduction of hydride reagents such as silanes, boron, or sulfur reagents, but it produces excessive stoichiometric byproducts; 3) deoxygenation, which uses strong electrophiles (such as triphenylphosphine and oxalyl chloride) to activate sulfoxides; and 4) low-valent metals combined with reducing agents such as PPh3, silanes, boranes, organosulfur compounds, and alcohols.

[0005] Sulfoxide reduction is a key reaction in organic and pharmaceutical synthesis and a common method for synthesizing sulfides. Despite remarkable progress, reported methods suffer from several drawbacks: 1) harsh reaction conditions, such as H₂ / high pressure or high temperature (>100°C); 2) high catalyst requirements; poor chemoselectivity; 3) the use of specialized laboratory equipment, such as microwave ovens; 4) the use of perfluorinated catalysts, which are prohibited by new EU regulations; and 5) the use of stoichiometric additives, such as PPh₃. Therefore, the development of novel catalytic deoxidation methods for sulfoxides to sulfides that address these challenges is highly desirable, particularly with commercially available reagents, which would facilitate their application. Summary of the Invention

[0006] The object of the present invention is to solve the above problems in the prior art and to provide a method for preparing sulfide compounds in high yield by using readily available sulfoxide as a raw material through a silane reduction reaction under iridium catalysis.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] A method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis:

[0009]

[0010] Among them, R 1 , R 2 It is a C1-C20 alkyl, aryl, heteroaryl, naphthyl and substituted derivatives thereof; [Ir] is an iridium complex, and Si-H is a silane reagent.

[0011] The present invention steps are as follows:

[0012] At 0-100° C., sulfoxide is reduced with a silane reagent in an organic solvent under the catalysis of an iridium complex, and then filtered, concentrated, and purified to obtain a sulfide compound;

[0013] The organic solvent can be selected from C2-C6 ethers, halogenated hydrocarbons, aromatic hydrocarbons, etc., in particular tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, chloroform, dichloroethane or toluene, xylene, etc.;

[0014] The iridium complex is [IrCl(CO)(PPh3)2](Vaska complex), [IrCl(COE)2]2, [IrCl(COD)2]2, etc.

[0015] The silane can be alkoxysilane or alkylsilane, such as (EtO)3SiH (triethoxysilane), Et3SiH (triethylsilane), PMHS (polymethylhydrogensilane), TMDS (1,1,3,3-tetramethyldisiloxane), Et2SiH2 (diethylsilane) or Ph2SiH2 (diphenylsilane).

[0016] The molar ratio of the sulfoxide, the iridium complex catalyst and the silane reagent can be 1:0.000001-0.001:1-4.

[0017] In the step, post-treatment does not require extraction, and the product can be quantitatively obtained after filtering part of the reaction.

[0018] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0019] This invention uses stable, inexpensive, and readily available commercial sulfoxides as raw materials, and uses a silane reagent for reduction under the catalysis of a metal complex with a very low catalyst loading to efficiently synthesize sulfide compounds. This invention utilizes commercial raw materials, low catalyst loadings, an inexpensive reducing agent, and a green solvent derived from chemically renewable resources. It offers advantages such as simple operation steps, simplified separation, rapid reaction rates, good universality, and high yields. DETAILED DESCRIPTION

[0020] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer and more understandable, the present invention is further described in detail below in conjunction with the embodiments.

[0021] Example 1

[0022] Synthesis of diphenyl sulfide (2a)

[0023]

[0024] Diphenyl sulfoxide (202.3 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. The reaction mixture was stirred, filtered, concentrated, and purified to obtain the product 2a as a colorless oil (182.5 mg, 98% yield).

[0025] IR(film) 3058,2964,1783,1579,1474,1438,1024,736,689cm -1 ; 1H NMR(500MHz,Chloroform-d)δ7.35-7.31(m,2H),7.29-7.26(m,2H),7.24-7.20(m,1H); 13 C NMR(126MHz,Chloroform-d)δ135.7,130.9,129.1,126.9; HRMS(ESI)m / z for C 12 H 11 S + ([M+H] + ):187.0576;Found:187.0575.

[0026] Example 2

[0027] Synthesis of di(1-naphthyl)sulfide (2b)

[0028]

[0029] Di(1-naphthyl)sulfoxide (302.4 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. The reaction mixture was stirred, filtered, concentrated, and purified to obtain the brown solid product 2b (277.5 mg, 97% yield).

[0030] Mp180-182℃; IR(film) 3053,2919,1562,1502,1379,1254,969,789,768cm -1 ; 1 H NMR (400MHz, Chloroform-d) δ8.43-8.39(m,2H),7.89-7.85(m,2H),7.78-7.74(m,2H),7.54-7.50(m,4H),7.35-7.28(m,4H); 13 C NMR(101MHz,Chloroform-d)δ134.1,132.6,132.4,129.9,128.6,127.9,126.7,126.4,125.9,125.1; HRMS(ESI)m / z for C 19 H 14 S + ([M+H] + ):274.0811;Found:274.0802.

[0031] Example 3

[0032] Synthesis of methyl (p-tolyl) sulfide (2c)

[0033]

[0034] Methyl (p-tolyl) sulfoxide (154.2 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. The reaction mixture was stirred, filtered, concentrated, and purified to obtain the product 2c as a pale yellow oil (115.5 mg, 93% yield).

[0035] IR(film) 2917,1580,1492,799cm -1 ; 1 H NMR (500MHz, Chloroform-d) δ7.19-7.14(m,2H),7.10-7.06(m,2H),2.44(s,3H),2.29(s,3H); 13 C NMR(126MHz,Chloroform-d)δ135.0,134.7,129.6,127.3,20.9,16.5; HRMS(ESI)m / z for C8H 11 S + ([M+H] + ):139.0576;Found:139.0576.

[0036] Example 4

[0037] Synthesis of tetrahydrothiophene (2d)

[0038]

[0039] Tetramethyl sulfoxide (104.2 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. GC analysis of the crude reaction mixture using tetradecane as an internal standard revealed a calculated yield of 93% for compound 2d. Due to its high volatility, no purification was performed.

[0040] Example 5

[0041] Synthesis of phenyl vinyl sulfide (2e)

[0042]

[0043] Phenyl vinyl sulfoxide (152.2 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. The reaction mixture was stirred, filtered, concentrated, and purified to obtain the product 2e as a colorless oil (118.5 mg, 87% yield).

[0044] IR(film) 3059,1584,1479,1439,1093,1023,956,744,690cm -1 ; 1 H NMR(500MHz,Chloroform-d)δ7.36-7.31(m,2H),7.26-7.22(m,2H),7.19-7.15(m,1H),6.48(dd,J=16.6,9.6Hz,1H),5.32-5.25(m,2H); 13 C NMR(126MHz,Chloroform-d)δ134.1,131.7,130.2,128.9,126.9,115.2; HRMS(ESI)m / z for C8H9S + ([M+H] + ):137.0419;Found:137.0420.

[0045] Example 6

[0046] Synthesis of phenylthiophenyl sulfide (2f)

[0047]

[0048] Phenylthiophenyl sulfoxide (208.3 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) were added at room temperature. The reaction mixture was stirred, filtered, concentrated, and purified to obtain the product 2f as a yellow oil (176.6 mg, 87% yield).

[0049] IR(film) 3072,2924,1582,1476,1439,1402,1217,1080,1023,847,738,688cm -1 ; 1H NMR(500MHz,Chloroform-d)δ7.38(d,J=5.4Hz,1H),7.25(d,J=3.6,1H),7.21-7.15(m,4H),7.12-7.07(m,1H),7.00(dd,J=5.4,3.6Hz,1H); 13 C NMR(126MHz,Chloroform-d)δ138.6,135.9,131.2,131.0,128.9,127.8,127.0,125.9; HRMS(ESI)m / z for C 10 H9S + ([M+H] + ):193.0140;Found:193.0141.

[0050] Example 7

[0051] Synthesis of phenoxathiophene (2g)

[0052]

[0053] Dissolve thiophene 10-oxide (216.3 mg) in THF, and add the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (444 μL) at room temperature. Stir the reaction, filter, concentrate, and purify to obtain 2 g (188.0 mg, 94% yield) of a white solid.

[0054] Mp51-53℃; IR(film) 3072,1586,1449,1259,1224,1081,760,746cm -1 ; 1 H NMR(500MHz,Chloroform-d)δ7.15-7.06(m,4H),7.01-6.97(m,4H); 13 C NMR(126MHz,Chloroform-d)δ152.1,127.7,126.8,124.5,120.1,117.8; HRMS(ESI)m / z for C 12 H9OS + ([M+H] + ):201.0369;Found:201.0372.

[0055] Example 8

[0056] Synthetic drug albendazole (2h)

[0057]

[0058] Albendazole sulfoxide (218.3 mg) was dissolved in THF, and the iridium complex [IrCl(CO)(PPh3)2] (3.2 mg) and the silane TMDS (1,1,3,3-tetramethyldisiloxane) (666 μL) were added. The mixture was heated to reflux (80°C). After stirring, the reaction was filtered, concentrated, and purified to obtain a white solid 2h (191.0 mg, 72% yield).

[0059] Mp201-203℃; IR(film) 3323,1713,2956,1633,1443,1326,1195,1269,1096,958,760cm -1 ; 1 H NMR (400MHz, DMSO-d6) δ7.44(d,J=1.7Hz,1H),7.35(d,J=8.2Hz,1H),7.12-7.10(m,1H),3.77(s,3H ),3.34(s,1H),2.86(t,J=7.1Hz,2H),2.52-2.50(m,1H),1.59-1.50(m,2H),0.95(t,J=7.3Hz,3H); 13 C NMR(101MHz,DMSO-d6)δ154.8,147.8,126.8,124.0,115.7,114.1,52.5,36.7,22.1,13.1; HRMS(ESI)m / z for C 12 H 16 N3O2S + ([M+H] + ):266.0958; Found:266.0957.

Claims

1. A method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis, characterized in that: In an organic solvent, sulfoxide is reduced with a silane reagent under the catalysis of an iridium complex to obtain a sulfide. The synthetic route is as follows: Among them, R 1 and R 2 It is a C1-C20 alkyl, aryl, heteroaryl, naphthyl and substituted derivatives thereof; [Ir] is an iridium complex, and Si-H is a silane reagent.

2. The method for preparing a sulfide compound by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The reduction reaction also includes the steps of filtration, concentration and purification.

3. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The molar ratio of sulfoxide, iridium complex and silane reagent is 1:0.000001-0.001:1-4.

4. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The organic solvent is selected from C2-C6 ethers, halogenated hydrocarbons, and aromatic hydrocarbons.

5. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 4, characterized in that: The organic solvent is selected from at least one of tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, chloroform, dichloroethane, toluene and xylene.

6. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The iridium complex is at least one of [IrCl(CO)(PPh3)2], [IrCl(COE)2]2, and [IrCl(COD)2]2.

7. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The silane is selected from alkoxysilane or alkylsilane.

8. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 7, characterized in that: The silane is selected from at least one of triethoxysilane ((EtO)3SiH), triethylsilane (Et3SiH), polymethylhydrogensilane (PMHS), 1,1,3,3-tetramethyldisiloxane (TMDS), diethylsilane (Et2SiH2) or diphenylsilane (Ph2SiH2).

9. The method for preparing sulfide compounds by reducing sulfoxide with silane under iridium catalysis according to claim 1, characterized in that: The temperature of the reduction reaction is 0 to 100°C.

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