CN113620848A - Reaction method of thiophenol and o-diiodobenzene - Google Patents
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Abstract
The invention discloses a method for reacting thiophenol and o-diiodobenzene, which takes the thiophenol and the o-diiodobenzene as substrates to react in a solvent in the presence of metal hydride, so as to complete the reaction of the thiophenol and the o-diiodobenzene and obtain o-iodobenzene thioether. Under the action of NaH, o-diiodobenzene and thiophenol are subjected to nucleophilic reaction to generate an o-iodobenzene thioether product. The method completes C-S bond coupling without transition metal, is simple and convenient to operate, and has no problems of metal reagent residue, pollution and the like; meanwhile, compared with the existing precursor, the o-diiodobenzene has the advantages of low price, convenient preparation and better atom economy; the product, phenylsulfide, has an iodine in the ortho position, and can be conveniently converted to obtain various 1, 2-substituted benzenes, particularly, with excellent yields only requiring 3 equivalents of metal hydride.
Description
Technical Field
The invention belongs to organic synthesis, and particularly relates to a reaction method of thiophenol and o-diiodobenzene.
Background
Thioether is widely present in various active natural medicines and functional materials, and the research on the synthesis of thioether compounds is always the goal of chemists to keep the whole course of the study, which has important significance for the development of innovative medicines and the discovery of novel materials. With the vigorous development of the transition metal catalytic coupling reaction, the C-S cross coupling is conveniently completed in one step, and the process routes of synthesizing some complex drugs are greatly shortened. However, the transition metal is rare and expensive, and the problems of residual metal reagent and pollution after reaction are prominent. Obviously, the synthesis of thioether by metal-free C-S coupling is more interesting to researchers; however, the conventional scheme usually requires severe conditions such as strong alkali/high temperature, strong oxidant, Grignard reagent, etc., or prepares precursors such as diazonium salt, iodonium, sulfonium, etc. in advance, and is troublesome to operate.
Disclosure of Invention
The invention discloses a reaction method of thiophenol and o-diiodobenzene, which is a novel method with easily obtained substrate, mild condition and high atom utilization rate, solves the problem that the coupling reaction without transition metal is difficult to be applied in a large scale, and is an important research direction in the field at present.
The invention adopts the following technical scheme:
a reaction method of thiophenol and o-diiodobenzene is characterized by that the thiophenol and o-diiodobenzene are used as substrate, and reacted in the presence of metal hydride and solvent to implement the reaction of thiophenol and o-diiodobenzene.
In the invention, the chemical structural formula of the thiophenol is as follows:
The chemical structural formula of the o-diiodobenzene is as follows:
the reaction of thiophenol and o-diiodobenzene of the invention obtains o-iodobenzene thioether, the chemical structural formula of which is as follows:
In the above structural formula, R1Hydrogen, an electron withdrawing group or an electron donating group such as halogen, alkyl, haloalkyl, cyano, nitro, alkoxy, phenyl, amino, amido, and the like; furthermore, the number of substituents on the benzene ring in the thiophenol structural formula may be one or more. R2Hydrogen, halogen, alkyl, haloalkyl, haloalkoxy, alkoxy, and the like; furthermore, the number of the substituent groups on the benzene ring in the structural formula of the o-diiodobenzene can be one or more; r3The alkyl group is preferably a C3-10 alkyl group, and the alkyl group may be a branched alkyl group or a linear alkyl group.
The reaction of thiophenol and o-diiodobenzene disclosed by the invention is carried out in a solvent in the presence of metal hydride, and the reaction is carried out for 5-15 hours at room temperature-40 ℃ without other substances, so that the o-iodobenzene thioether serving as a product is obtained and is a single product.
In the present invention, the metal hydride is sodium hydride, potassium hydride, calcium hydride, lithium hydride, or the like; the dosage of the metal hydride is 2 to 6 times of the molar weight of the thiophenol, and preferably 3 times of the molar weight of the thiophenol. Furthermore, the dosage of the o-diiodobenzene is 1-3 times of the molar weight of the thiophenol.
In the invention, the solvent is one or more of dimethylacetamide DMA, tetrahydrofuran THF, acetonitrile CH3CN, ethylene glycol dimethyl ether DME and Toluene Toluene, THF and DMA are preferred, and the volume ratio of the two is preferably (3-8): 1.
The prior art discloses o-iodophenylsulfide, but the methods are very limited. For example, the conventional method using o-iodoaniline as a raw material has complicated steps and requires metal and high temperature conditions; the transition metal catalyzes the o-diiodobenzene to directly react with the thiophenol, so that a disubstituted byproduct is easily generated; for the Grignard reagent to initiate the benzyne process, an additional iodine source is required for reaction quenching. Therefore, the NaH is used for synthesizing the o-iodobenzene thioether product when the o-diiodobenzene is used, transition metal is not needed, an additional iodine source is not needed, and the practical value is high.
Drawings
FIG. 1 is a nuclear magnetic spectrum of Compound 3 a;
FIG. 2 is a nuclear magnetic spectrum of Compound 3 f.
Detailed Description
The invention takes the thiophenol and the o-diiodobenzene as the substrates, can complete the reaction in the presence of metal hydride and solvent, obtains the product with high yield, does not need other substances, and solves the problems of the prior art that a metal catalyst, a format reagent and the like are needed.
The raw materials involved in the invention are all existing products, can be purchased in the market, and can also be prepared according to the existing method.
Nuclear magnetic spectrum1H NMR was measured using Agilent 400 MHz and Bruker 400 MHz instruments,13c NMR was measured using a Bruker 400 MHz instrument and the sample solvent was CDCl3Or deuterated DMSO, in solutionThe agent contains TMS internal standard. The LR-MS mass spectrometer was an ESI source. TLC monitoring uses a thin-layer silica gel plate produced by a tobacco yellow sea chemical plant, and the silica gel used for rapid column chromatography is 200-mesh and 300-mesh. The reagents are all commercially available analytically pure or chemically pure, have no special description and are used directly. The anhydrous solvent is either a redistilled solvent or a commercially available dry solvent (carbofuran).
Example one
NaH (0.9 mmol, 3.0 equiv) was weighed into a reaction flask at room temperature, suspended in anhydrous THF (0.8 mL) under conventional magnetic stirring, thiophenol 1 (0.3 mmol, 1.0 equiv, dissolved in 0.2mL DMA) was added dropwise during stirring, after addition was complete, stirred at room temperature for 2min, diiodobenzene 2 (0.6 mmol, 2.0 equiv, dissolved in 0.2mL THF) was added, stirring was continued at room temperature, and the reaction was monitored by TLC. After the reaction is finished, adding ice water and tetrahydrofuran for quenching reaction, extracting for 3 times by ethyl acetate, combining organic layers, washing by a saturated NaCl solution, drying by anhydrous sodium sulfate, filtering, spin-drying a solvent, adding silica gel powder for sample mixing, separating by fast column chromatography to obtain the product of the o-iodophenyl sulfide 3, and calculating the yield conventionally.
Under the preparation method, the compounds 1 and 2 with different structures are taken as substrates, and products with different substituents are obtained, and the method specifically comprises the following steps:
the yield is the isolated yield, and the time marked is the time for TLC to monitor the completion of the reaction. Note that, the superscript b indicates that the reaction temperature for producing the products 3s, 3z, 3ab is 40 ℃; the superscript c indicates that for the preparation of product 3aa, 5 equivalents of sodium hydride are used. FIG. 1 is a nuclear magnetic spectrum of Compound 3 a; FIG. 2 is a nuclear magnetic spectrum of Compound 3 f. As a general sense, the starting materials used can be deduced from the product structure, for example the two starting materials (diiodobenzene, thiophenol) for the preparation of compound 3b are as follows:
two starting materials (diiodobenzene, thiophenol) for the preparation of compound 3f were as follows:
the rest raw materials are analogized in the same way and are the existing products.
Product data characterization
1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.8 Hz, 1H), 7.38 (dd, J = 14.0, 7.0 Hz, 2H), 7.25 – 7.11 (m, 3H), 6.95 (d, J = 7.9 Hz, 1H), 6.89 (t, J = 7.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 161.98 (d, J = 249.5 Hz), 140.45 (d, J = 1.0 Hz), 139.85, 135.22, 130.90 (d, J = 8.1 Hz), 129.19, 128.94, 127.83, 125.22 (d, J = 4.0 Hz), 121.12 (d, J = 18.2 Hz), 116.46 (d, J = 22.2 Hz), 99.21. 19F NMR (377 MHz, CDCl3) δ -107.08。
1H NMR (400 MHz, CDCl3) δ 7.87 (dd, J = 7.9, 1.3 Hz, 1H), 7.33 – 7.27 (m, 1H), 7.25 – 7.22 (m, 1H), 7.17 (dd, J = 7.9, 1.6 Hz, 1H), 7.10 (m, 1H), 7.02 – 6.90 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 163.19 (d, J = 250.5 Hz), 140.23 (d, J = 15.2 Hz), 137.27 (d, J = 7.1 Hz), 131.62, 130.83 (d, J = 8.1 Hz), 129.14, 128.75, 127.07, 127.04, 118.21 (d, J = 23.2 Hz), 114.78 (d, J = 21.2 Hz), 102.06. 19F NMR (377 MHz, CDCl3) δ -111.38。
IR (KBr): 1530, 1454, 1280, 1006, 741, 528 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 7.8, 1.3 Hz, 1H), 7.48 – 7.42 (m, 2H), 7.19 (td, J = 7.8, 1.4 Hz, 1H), 7.13 – 7.06 (m, 2H), 6.90 – 6.82 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 163.17 (d, J = 250.5 Hz), 142.80, 139.80, 136.04 (d, J = 8.1 Hz), 128.93 (d, J = 4.0 Hz), 128.88, 128.69, 127.43, 117.07 (d, J = 22.2 Hz), 98.39. 19F NMR (377 MHz, CDCl3) δ -112.08。
1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 7.9, 1.3 Hz, 1H), 7.46 (dd, J= 7.7, 1.6 Hz, 1H), 7.27 (m, 2H), 7.19 (td, J = 7.5, 1.6 Hz, 1H), 7.14 (ddd, J = 11.0, 7.8, 1.7 Hz, 2H), 6.97 (td, J = 7.7, 1.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 140.19, 139.30, 135.36, 134.38, 132.42, 131.77, 130.28, 129.18, 128.84, 128.77, 127.65, 102.46。
IR (KBr): 1521, 1453, 1005, 768, 739, 536 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.9 Hz, 1H), 7.38 – 7.29 (m, 4H), 7.23 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.9 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 141.50, 139.98, 134.43, 133.96, 132.94, 130.17, 129.92, 129.02, 128.10, 100.28。
IR (KBr): 1563, 1468, 1006, 747, 642, 531 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.5 Hz, 3H), 7.08 (d, J = 7.8 Hz, 1H), 6.96 (t, J = 7.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 141.23, 140.03, 133.98, 133.76, 132.84, 130.48, 129.06, 128.25, 122.41, 100.65。
1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.8 Hz, 1H), 7.45 (dd, J = 15.0, 8.2 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.00 – 6.91 (m, 2H), 6.88 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 164.59 (q, J = 131.3 Hz), 162.09 (q, J = 130.3 Hz), 140.77, 139.87, 137.18 (q, J = 12.1 Hz), 128.95, 128.23, 127.66, 116.36 (q, J = 23.2 Hz), 112.79 (q, J = 26.3 Hz),105.27 (t, J = 52.5 Hz), 98.10. 19F NMR (377 MHz, CDCl3) δ -101.43, -106.84。
1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J = 7.9, 1.3 Hz, 1H), 7.47 (d, J = 2.2 Hz, 1H), 7.34 – 7.28 (m, 1H), 7.21 – 7.14 (m, 2H), 7.00 (td, J = 7.5, 1.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 140.42, 138.64, 135.74, 133.90, 133.41, 132.70, 132.27, 130.10, 129.35, 129.30, 127.98, 103.02。
1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.9, 1.3 Hz, 1H), 7.47 (dd, J = 8.5, 5.9 Hz, 1H), 7.14 (td, J = 7.9, 1.3 Hz, 1H), 7.06 (dd, J = 9.5, 2.8 Hz, 1H), 6.95 (td, J = 8.3, 2.8 Hz, 1H), 6.82 (td, J = 7.6, 1.5 Hz, 1H), 6.56 (dd, J = 8.0, 1.5 Hz, 1H), 2.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 163.55 (d, J = 251.5 Hz), 145.10 (d, J = 9.1 Hz), 142.50, 139.70, 137.80 (d, J = 9.1 Hz), 128.80, 127.61 (d, J = 3.0 Hz), 126.91, 126.81, 118.14 (d, J = 22.2 Hz), 114.43 (d, J = 21.2 Hz), 96.95, 21.06 (d, J = 1.0 Hz). 19F NMR (377 MHz, CDCl3) δ -111.63。
1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.50 (d, J = 5.3 Hz, 1H), 7.41 (d, J = 13.6 Hz, 2H), 7.22 (s, 1H), 7.12 (d, J = 7.5 Hz, 1H), 6.93 (t, J = 7.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 140.32, 139.99, 136.73, 134.52, 132.05 (d, J = 32.3 Hz), 131.74, 129.64 (d, J = 72.7 Hz), 128.99, 128.01 (q, J = 11.1 Hz), 125.14, 124.43 (q, J = 11.1 Hz), 122.43, 102.20. 19F NMR (377 MHz, CDCl3) δ -62.81。
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.9 Hz, 1H), 7.52 (d, J = 8.1 Hz, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.16 (d, J = 8.2 Hz, 2H), 7.08 (t, J = 7.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 143.78, 140.75, 136.85, 135.03, 132.69, 130.60, 129.61, 128.20, 118.71, 109.52, 106.25。
1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 4.1 Hz, 2H), 7.23 (td, J = 8.4, 4.1 Hz, 1H), 7.15 (t, J= 7.5 Hz, 1H), 6.84 (t, J = 7.4 Hz, 1H), 6.69 (d, J = 7.8 Hz, 1H), 2.38 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 142.30, 141.76, 139.67, 135.15, 132.63, 131.12, 129.37, 128.77, 127.83, 127.26, 126.93, 98.02, 20.76。
IR (KBr): 2918, 1510, 1450, 1003, 735, 522 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 7.7 Hz, 2H), 7.22 (d, J = 7.6 Hz, 2H), 7.16 (t, J = 7.5 Hz, 1H), 6.84 (t, J = 6.5 Hz, 2H), 2.39 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.41, 139.59, 139.05, 134.16, 130.64, 129.92, 128.71, 128.40, 127.00, 98.01。
1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.7 Hz, 1H), 7.46 – 7.36 (m, 4H), 7.17 (t, J = 7.5 Hz, 1H), 6.85 (dd, J = 14.3, 7.5 Hz, 2H), 1.35 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 152.13, 143.29, 139.61, 133.74, 129.96, 128.75, 128.57, 127.06, 126.92, 98.19, 34.87, 31.38。
IR (KBr): 1439, 1009, 748, 525 cm–1. 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.83 (dd, J = 17.3, 6.7 Hz, 4H), 7.54 (d, J = 4.1 Hz, 2H), 7.50 – 7.44 (m, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 4.2 Hz, 1H), 6.89 (t, J= 7.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 142.39, 139.78, 134.03, 132.91, 132.59, 131.30, 130.05, 129.64, 129.45, 128.85, 127.91, 127.81, 127.61, 126.89, 126.83, 99.36。
1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.8 Hz, 2H), 7.31 (s, 8H), 7.26 – 7.20 (m, 2H), 7.10 (d, J = 7.7 Hz, 2H), 6.92 (t, J = 7.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 141.19, 140.03, 135.31, 133.93, 132.90, 131.95, 130.74, 129.05, 128.29, 100.96。
1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.7 Hz, 1H), 7.69 (d, J = 7.4 Hz, 1H), 7.31 (t, J = 7.3 Hz, 1H), 6.99 (t, J = 7.2 Hz, 1H), 1.36 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 140.22, 138.63, 137.76, 130.04, 128.37, 111.92, 49.09, 31.23。
1H NMR (400 MHz, CDCl3) δ 8.45 (ddd, J = 4.8, 1.7, 0.7 Hz, 1H), 7.98 (dd, J = 7.9, 1.3 Hz, 1H), 7.67 (dd, J = 7.7, 1.6 Hz, 1H), 7.49 (td, J = 7.8, 1.9 Hz, 1H), 7.38 (td, J = 7.6, 1.3 Hz, 1H), 7.14 – 6.97 (m, 2H), 6.88 (d, J= 8.1 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 159.79, 150.00, 140.56, 136.99, 136.97, 135.82, 130.42, 129.39, 122.12, 120.44, 107.41。
1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.43 – 7.35 (m, 2H), 7.32 (s, 1H), 7.14 (d, J = 8.6 Hz, 1H), 2.67 (s, 3H), 2.59 (s, 3H), 2.40 (s, 3H), 2.27 (s, 3H).13C NMR (101 MHz, CDCl3) δ 140.87, 139.48, 138.04, 136.70, 135.78, 134.11, 133.86, 131.43, 128.64, 127.86, 127.04, 126.48, 125.17, 124.63, 123.22, 117.47, 29.45, 21.97, 19.08, 17.66。
1H NMR (400 MHz, CDCl3) δ 7.85 – 7.74 (m, 4H), 7.69 (s, 1H), 7.52 – 7.45 (m, 2H), 7.37 (dd, J = 8.6, 1.6 Hz, 1H), 7.04 (s, 1H), 2.21 (s, 3H), 2.10 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 140.69, 138.14, 138.12, 137.25, 134.02, 133.13, 132.45, 129.80, 129.10, 128.53, 127.91, 127.62, 126.71, 126.35, 98.90, 19.51, 19.03。
1H NMR (400 MHz, CDCl3) δ 7.47 (dd, J = 7.8, 1.0 Hz, 1H), 7.29 – 7.25 (m, 1H), 7.24 – 7.17 (m, 3H), 6.67 (m, 2H), 3.90 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.21, 141.67, 136.20, 134.17, 133.51, 130.32, 129.72, 129.14, 127.67, 123.09, 109.07, 93.22, 56.78。
Example two
Taking the reaction of the compound 1a and the compound 2a to prepare the product 3a as an example, the development experiment is carried out, the specific process is the same as above, the change of the conditions and the reaction results are shown in table 1. In the example of group 13, NaH (0.9 mmol, 3.0 equiv) was weighed into a reaction flask at room temperature, suspended in anhydrous THF (0.8 mL) and stirred magnetically as usual, while stirring thiophenol 1a (0.3 mmol, 1.0 equiv, dissolved in 0.2mL DMA) was added dropwise, after addition was completed, stirring was carried out at room temperature for 2min, diiodobenzene 2a (0.6 mmol, 2.0 equiv, dissolved in 0.2mL THF) was then added, stirring was continued at room temperature, and the reaction was monitored by TLC. After the reaction is finished, adding ice water and tetrahydrofuran for quenching reaction, extracting for 3 times by ethyl acetate, combining organic layers, washing by a saturated NaCl solution, drying by anhydrous sodium sulfate, filtering, spin-drying a solvent, adding silica gel powder for mixing samples, and performing rapid column chromatography separation to obtain an o-iodophenyl sulfide product 3a, wherein the yield is 78% by conventional calculation.
In the example of group 8, NaH (0.9 mmol, 3.0 equiv) was weighed into a reaction flask at room temperature, suspended in anhydrous THF (0.8 mL) and magnetically stirred, thiophenol 1a (0.3 mmol, 1.0 equiv, dissolved in 0.2mL THF) was added dropwise during stirring, after addition was completed, stirring was carried out at room temperature for 2min, diiodobenzene 2a (0.6 mmol, 2.0 equiv, dissolved in 0.2mL THF) was then added, stirring was continued at room temperature, and the reaction was monitored by TLC. After the reaction is finished, adding ice water and tetrahydrofuran to quench the reaction, extracting for 3 times by ethyl acetate, combining organic layers, washing by a saturated NaCl solution, drying by anhydrous sodium sulfate, filtering, spin-drying a solvent, adding silica gel powder to mix a sample, and performing rapid column chromatography separation to obtain an o-iodophenyl sulfide product 3a, wherein the yield is 65% by conventional calculation.
TABLE 1 different reaction conditions and results
In the context of table 1, the following, b the separation yield is as follows, c the volume ratio of THF to DMA (or DME) is 5:1, d the volume ratio of THF to DMA is 4: 1.
The method has good universality on various substrates. For halogen and polyhalogen substituted substrate, the yield can be more than medium, and the product can be well tolerated by sensitive functional groups such as nitro and cyano, and can be used as a strong electron-withdrawing group (such as CF)3CN), the reaction speed can be accelerated, the reaction time can be shortened, the yield of the electron-donating group substituted thiophenol can be higher, and the product which can selectively attack SH can be obtained for the proton H-containing p-acetamino thiophenol. Experiments are carried out on various substituted diiodobenzenes, which can react with thiophenol very well to obtain a single product with a yield of more than 80%; it is very interesting to note that if there is a substituent group in the ortho position to the diiodobenzene, the regioselectivity of the reaction can be controlled and finally only a single diphenyl sulfide product is obtained.
EXAMPLE III
Referring to example one, the reaction was scaled up comparably and the amount of starting material was scaled up to the gram scale, indicating that the scaled up charge had little effect on the yield of the reaction. Therefore, the reaction solves the difficult problem of large-scale application of the transition-metal-free coupling, and shows the practicability and the industrial application prospect of the reaction.
Synthesis of dibenzothiophene (8 e):
in N2Under protection, adding iodine-containing phenylsulfide (0.3 mmol, 1.0 equiv), Pd2(dpa)3（0.03 mmol, 10 mol%）, Cu(AcO)2(0.06 mmol, 20 mol%), PivONa (sodium pivalate, 0.9 mmol, 3.0 equiv) were weighed into a high temperature pressure resistant tube, DMF (4 mL) solvent was added, heating was carried out at 60 ℃ for 20 min, then heating was carried out to 150 ℃ for stirring reaction, and the reaction was monitored by TLC for 6 h completion. Cooling the reaction solution to room temperature, filtering to remove insoluble substances, extracting with ethyl acetate for 4 times, washing with water for 2 times, combining organic layers, washing with saturated NaCl solution, drying with anhydrous sodium sulfate, filtering, rotary evaporating solvent, mixing with appropriate amount of silica gel powder, performing flash column chromatography (pure PE) to obtain dibenzothiophene solid product 8e with yield of 72%,1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 1.9 Hz, 1H), 8.14 – 8.04 (m, 1H), 7.90 – 7.78 (m, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.54 (dd, J = 8.5, 1.9 Hz, 1H), 7.51 – 7.43 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 140.12, 138.20, 137.46, 134.55, 129.68, 127.48, 124.78, 124.63, 124.21, 123.00, 121.88, 118.44。
Claims (10)
1. a method for reacting thiophenol and o-diiodobenzene is characterized in that thiophenol and o-diiodobenzene are used as substrates and react in a solvent in the presence of metal hydride to complete the reaction of thiophenol and o-diiodobenzene; the chemical structural formula of thiophenol is as follows:
The chemical structural formula of the o-diiodobenzene is as follows:
2. the method of claim 1, wherein R is selected from the group consisting of1Is hydrogen, an electron withdrawing group or an electron donating group, R2Is one or more of hydrogen, halogen, alkyl, halogen alkoxy and alkoxy; r3Is an alkyl group.
3. The method of claim 2, wherein R is O-diiodobenzene1Is one or more of halogen, alkyl, haloalkyl, cyano, nitro, alkoxy, phenyl, amino and amido; r3In the above formula, the number of carbon atoms in the alkyl group is 3 to 10.
4. The method of claim 1, wherein the reaction of thiophenol with o-diiodobenzene yields o-iodobenzene sulfide having the following chemical formula:
R1Is hydrogen, an electron withdrawing group or an electron donating group, R2Is one or more of hydrogen, halogen, alkyl, halogen alkoxy and alkoxy; r3Is an alkyl group.
5. The method of claim 1, wherein the reaction is carried out in a solvent in the presence of a metal hydride without any additional substance; the reaction is carried out for 5-15 hours at room temperature-40 ℃.
6. The method of claim 1, wherein the metal hydride is one or more of sodium hydride, potassium hydride, calcium hydride, and lithium hydride.
7. The method for reacting thiophenol and ortho-diiodobenzene as claimed in claim 1, wherein the amount of said metal hydride is 2 to 6 times the molar amount of said thiophenol; the dosage of the o-diiodobenzene is 1-3 times of the molar weight of the thiophenol.
8. The method for reacting thiophenol and o-diiodobenzene as claimed in claim 1, wherein the solvent is one or more selected from the group consisting of dimethylacetamide, tetrahydrofuran, acetonitrile, ethylene glycol dimethyl ether and toluene.
9. The product of the process of claim 1 wherein said thiophenol is reacted with ortho-diiodobenzene.
10. The application of metal hydride in the reaction of thiophenol and o-diiodobenzene to obtain o-iodophenyl thioether.
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