A method for preparing 2,3-dihydro-5,6-diaryloxathiin

Abstract

The present invention discloses a preparation method of 2,3-dihydro-5,6-diaryloxathiin, comprising the following steps: (1) performing an oxidation reaction on 1-arylacetone and an oxidant in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2,2-dihydroxyacetone; (2) performing a substitution reaction on 1-aryl-2,2-dihydroxyacetone and an aniline derivative in toluene under a protective atmosphere to obtain diarylacetone; (3) performing a cyclization reaction on diarylacetone and mercaptoethanol in the presence of a water-soluble acid and a solvent to obtain the 2,3-dihydro-5,6-diaryloxathiin. The above preparation method has a wide substrate scope and can be used for synthesizing compounds with different molecular structures. Moreover, the reaction of the above synthesis method is mild, with few side reactions. The post-treatment of the product is simple, the yield is high, and the obtained product has high purity, which is beneficial to the industrial production and application of this kind of compound.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and specifically relates to a method for preparing 2,3-dihydro-5,6-diaryloxathiin. Background Art

[0002] 2,3-Dihydro-5,6-diaryl-1,4-oxathiin is a class of compounds with a unique structure. The double bond in the ring can react with oxidants or oxygen under conditions such as light. Therefore, this class of compounds has attracted extensive interest and attention in the fields of light technology such as light absorbers, light emitters, and photochemical caches (WO 01 / 44811A2; Angew.Chem.Int.Ed.2022, 61, e202211767; Angew.Chem.Int.Ed.2022, 61, e202201630; CN112500434A; CN 115947711 A). So far, there are few reports on the synthesis of this class of compounds. Its synthesis mainly includes the following steps: oxidizing arylacetone to 1-aryl-2,2-dihydroxyacetone, then preparing diarylglycolic ketone from 1-aryl-2,2-dihydroxyacetone, and finally reacting diarylglycolic ketone with mercaptoethanol to obtain the final target product. However, the above preparation method currently has the disadvantage of low synthesis efficiency in the second and third steps.

[0003] There are two common methods for preparing diarylglycolic ketone from 1-aryl-2,2-dihydroxyacetone in the above second step: one is the reaction of 1-aryl-2,2-dihydroxyacetone compounds with Grignard reagents prepared from arylamine compounds. Presumably, due to the high activity of Grignard reagents and the product being a benzoin compound containing an active structure, the Grignard reagent will react with the active structure to produce side reactions. Therefore, the yield of the target product prepared by the above method is relatively low, only 50% (WO 0144811 A2); the other is the Friedel-Crafts reaction of 1-aryl-2,2-dihydroxyacetone compounds with arylamine compounds to synthesize diarylglycolic ketone. For example, the prior art (Singh, S.; Ullman, E.F.Syn Comm, 2003, 34:451) reported that the above reaction was carried out in solvent benzene, but the yield of the product obtained after reacting for 3 days at room temperature was only 57%. Further increasing the reaction temperature, it was found that although the reaction rate increased to some extent, there were a large number of by-products in the reaction products. For example, the desired product could be obtained with a yield of 37% by reacting for 3 hours at 80 degrees, but at the same time, by-products of secondary Friedel-Crafts arylation would be produced, and the yield of the by-products was as high as 19%.

[0004] The third step above is to react diaryl ethanol ketone with mercaptoethanol to obtain the final target product. The use of a catalyst is required in this process. In the prior art (WO 01 / 44811A2; Angew. Chem. Int. Ed. 2022, 61, e202211767; Angew. Chem. Int. Ed. 2022, 61, e202201630; CN 112500434A; CN 115947711A), trimethylchlorosilane is used as a catalyst to promote the occurrence of the cyclization reaction. The following problems exist in this reaction system: on the one hand, the usage amount of trimethylchlorosilane (TMSCl) is more than equivalent; and trimethylchlorosilane will react with the hydroxyl group in diaryl ethanol ketone to generate by-products, thus increasing the difficulty of post-treatment and reducing the yield of the target product. The yields reported in the current technology are mostly in the range of 50% - 60%, and only a few reach 60% - 65%; in addition, using trimethylchlorosilane as a catalyst, the post-treatment of its reaction products requires the use of a relatively large amount of water, so that the system containing the product is prone to emulsification and difficult to separate, and the post-treatment is complex and not suitable for industrial production.

[0005] Based on this, in order to improve the synthesis efficiency of 2,3-dihydro-5,6-diaryloxathiin and reduce the cost, there is an urgent need for a preparation method with simple post-treatment and capable of effectively improving the yield, which is suitable for industrial production and promotes its practical application. Summary of the Invention

[0006] The present invention provides a method for preparing 2,3-dihydro-5,6-diaryloxathiin, mainly by improving the second step and the third step of synthesizing 2,3-dihydro-5,6-diaryloxathiin in the prior art, effectively improving the synthesis yield of the target compound and having simple post-treatment of the product, which is suitable for industrial production.

[0007] In order to solve the above technical problems, the present invention provides the following technical solutions:

[0008] The present invention provides a method for preparing 2,3-dihydro-5,6-diaryloxathiin, which is characterized by including the following steps:

[0009] (1) Oxidize 1-aryl ethanone shown in formula (I) with an oxidant in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2,2-dihydroxy ethanone shown in formula (II);

[0010] (2) Under a protective atmosphere, react 1-aryl-2,2-dihydroxy ethanone shown in formula (II) prepared in step (1) with an aniline derivative shown in formula (III) in toluene to obtain diaryl ethanol ketone shown in formula (IV);

[0011] (3) Under a protective atmosphere, the diarylethanone shown in formula (IV) prepared in step (2) is subjected to a cyclization reaction with mercaptoethanol in the presence of a water-soluble acid and a solvent to obtain 2,3-dihydro-5,6-diaryloxathiin shown in formula (V);

[0012] The structures of the above formulas (I) to (V) are as follows:

[0013]

[0014] Among them, R 1 is selected from one of hydrogen, halogen, acyl, cyano, nitro, amino, hydroxy, sulfonyl, sulfonic acid group, C1-C22 alkyl group, C2-C22 alkynyl group, C2-C22 ester group, C1-C22 alkoxy group, C1-C24 haloalkyl group, C6-C22 aryl group, C1-C17 heteroaryl group containing O, N or S;

[0015] R 2 and R 3 each independently is selected from one of hydrogen, C1-C22 alkyl group, C1-C22 acyl group, C6-C22 aryl group, C1-C17 heteroaryl group containing O, N or S.

[0016] In the present invention, unless otherwise specified, the terms used have the general meanings known to those skilled in the art.

[0017] The term "halogen" refers to all halogens, namely fluorine, chlorine, bromine or iodine; the term "acyl" refers to the group -COR; the term "cyano" refers to the group -CN; the term "nitro" refers to the group -NO2; the term "hydroxy" refers to the group -OH; the term "amino" refers to the group -NHR 2 or NR 2 R 3 ; the term "sulfonyl" refers to the group -SO3R 2 ; the term "sulfonic acid group" refers to the group -SO3H; the term "ester group" refers to the group -COOR; the above R can be an alkyl group.

[0018] The term "alkane" refers to cycloalkanes, straight-chain alkanes and branched-chain alkanes with the specified number of carbon atoms. The C1-C22 alkyl group in the present invention refers to an alkyl group having 1-22 carbon atoms. The alkyl groups in the present invention include but are not limited to methyl, ethyl, propyl, n-butyl, n-hexyl, cyclohexyl, n-tetradecyl, etc. The alkyl group also includes substituted alkyl groups. The substituted alkyl group means that one or more positions of the alkyl group are substituted, especially 1-2 substituents, and can be substituted at any position.

[0019] The term "alkynyl" refers to a carbon chain containing at least one carbon-carbon triple bond, which can be straight-chain, branched-chain, or a combination thereof. The C1-C22 alkynyl in the present invention refers to an alkynyl having 1-22 carbon atoms, including but not limited to ethynyl.

[0020] The term "alkoxy" refers to cycloalkanes, straight-chain alkanes, and branched-chain alkanes with a specified number of carbon atoms where a carbon is replaced by oxygen. In certain specific embodiments, the number of oxygen atoms is 1-3, for example, the number of oxygen atoms is 1.

[0021] The term "haloalkyl" refers to a straight-chain, branched-chain, or cyclic saturated aliphatic haloalkyl group. The C1-C24 haloalkyl in the present invention refers to a haloalkyl having 1-22 carbon atoms, where the haloalkyl includes monohaloalkyl and polyhaloalkyl.

[0022] The term "aryl" refers to an aromatic group having a monocyclic, polycyclic, or polycondensed ring structure, having 6-22 carbon atoms and 1-4 rings, especially monocyclic and bicyclic groups. In certain specific embodiments, the aryl has 6-14 carbon atoms. Aryl includes simple aryl and substituted aryl, such as unsubstituted aryls like phenyl, naphthyl, and biphenyl. Substituted aryl refers to an aryl in which one or more hydrogens are substituted, especially 1-3 substituents, which can be substituted at any position. The substituents on the substituted aryl are halogen, alkyl, acyl, sulfonate, sulfonyl, hydroxyl, cyano, amino, or any combination of the above groups.

[0023] The term "heteroaryl" refers to a monocyclic, polycyclic, or polycondensed ring group containing 1-4 heteroatoms. The C1-C17 heteroaryl containing O, N, or S in the present invention refers to a heteroaryl having 1-17 carbon atoms, where the heteroatoms are O, N, or S. Heteroaryl includes unsubstituted heteroaryl and substituted heteroaryl. The substituents on the substituted heteroaryl are halogen, alkyl, acyl, sulfonate, sulfonyl, hydroxyl, cyano, amino, or any combination of the above groups.

[0024] Here, in the present invention, the selected groups in the definitions of each substituent can be combined with each other to form a new substituent that conforms to the bonding rules.

[0025] Furthermore, the 2,3-dihydro-5,6-diaryloxathiin can be selected from one of the structures shown in the following V-1 to V-18:

[0026]

[0027]

[0028] Further, in step (1), the oxidant is preferably dimethyl sulfoxide, and the solvent is preferably dimethyl sulfoxide; specifically, the molar ratio of 1-aryl ethanone shown in formula (I) to dimethyl sulfoxide and hydrobromic acid is preferably 1:4 - 12:0.2 - 1.5, such as 1:6:6.

[0029] Further, in step (1), the reaction temperature of the oxidation reaction is preferably 60 - 110 °C, more preferably 90 °C, and the reaction time is preferably 2 - 10 h, more preferably 3 - 6 h.

[0030] In some preferred embodiments of the present invention, step (1) further includes a post-treatment process, specifically: after the oxidation reaction is completed, alkali is added to the system for neutralization, then water is added and stirred until a solid precipitates, and after filtration, it is washed with petroleum ether to obtain 1-aryl-2,2-dihydroxyethanone shown in formula (II).

[0031] Further, in step (2), the molar ratio of 1-aryl-2,2-dihydroxyethanone shown in formula (II) to the aniline derivative shown in formula (III) is preferably 1:0.8 - 2, such as 1:1.

[0032] Further, in step (2), the temperature of the substitution reaction is preferably 40 - 70 °C, more preferably 45 - 65 °C, such as 60 °C; the reaction time is preferably 8 - 24 h.

[0033] In some preferred embodiments of the present invention, step (2) further includes a post-treatment process, specifically: after the substitution reaction is completed, column chromatography separation and purification are carried out, and elution is carried out using a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 2 - 10:1 to obtain diaryl ethanone shown in formula (IV).

[0034] In the process of preparing diaryl ethanone from 1-aryl-2,2-dihydroxyethanone and aniline derivative in the second step of the present invention, it was unexpectedly found that when the solvent in the reaction system is toluene, by controlling the reaction temperature, the yield of diaryl ethanone in the reaction product can be effectively increased, while the amount of by-products is reduced, facilitating the separation of the current product in the post-treatment.

[0035] Further, in step (3), the water-soluble acid is selected from one or more of hydrochloric acid, sulfuric acid, sodium bisulfate, potassium bisulfate, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, and is more preferably trifluoromethanesulfonic acid.

[0036] Further, in step (3), the solvent is preferably toluene or 1,4-dioxane.

[0037] Further, in step (3), the temperature of the cyclization reaction is preferably 90 - 130 °C, more preferably 110 °C; the reaction time is preferably 2 - 24 h.

[0038] In some preferred embodiments of the present invention, step (3) further includes a post-treatment process, specifically: after the cyclization reaction is completed, alkali addition for neutralization, water washing, drying, solvent removal under vacuum, and column chromatography separation and purification are carried out in sequence. When performing column chromatography, a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 50 - 150:1 is used for elution to obtain the target product 2,3-dihydro-5,6-diaryloxathiin.

[0039] In the process of the present invention for preparing the target product 2,3-dihydro-5,6-diaryloxathiin by the cyclization reaction of diaryl ethanedione and mercaptoethanol in the third step, using a water-soluble acid as a catalyst can effectively improve the yield of the target product and is convenient for post-treatment, enabling the product to obtain a product with a purity of over 99% after simple post-treatment.

[0040] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0041] The present invention optimizes the method for preparing 2,3-dihydro-5,6-diaryloxathiin in the prior art, mainly optimizing the second step for preparing diaryl ethanedione and the third step of cyclization reaction, specifically as follows: The present invention unexpectedly discovers that by regulating the solvent and temperature of the second-step reaction system, the yield of the target product can be effectively improved and the content of by-products in the product can be reduced. For example, when the solvent of the second-step reaction system is toluene and the reaction is carried out at 60 °C for 12 h, a product with a yield of 75% of diaryl ethanedione and a by-product yield < 1% can be obtained; in addition, the present invention unexpectedly discovers during the experiment that when using a water-soluble acid to replace trimethylchlorosilane in the prior art, the reaction efficiency of the third-step cyclization reaction can be effectively improved, the yield of the target product is high, and it is easy to separate and purify. A product with a purity of over 99% can be obtained after simple column chromatography separation. The present invention improves the synthesis method of 2,3-dihydro-5,6-diaryloxathiin. The improved preparation process has the advantages of mild reaction conditions, easy regulation, short production cycle, and high yield, and is suitable for the industrial production of 2,3-dihydro-5,6-diaryloxathiin. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 1H NMR spectrum of the product V-1 prepared in Example 1;

[0043] Figure 2 HPLC chart of the product V-1 prepared in Example 1;

[0044] Figure 3 1H NMR spectrum of the product V-2 prepared in Example 2;

[0045] Figure 4HPLC chromatogram of product V-2 prepared in Example 2. Detailed implementation mode

[0046] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs. The terms used in the description of this invention herein are for the purpose of describing specific embodiments only and are not intended to limit the invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items. The "including" or "comprising" described in this invention means that in addition to the components described, other components may also be included or comprised. The "including" or "comprising" described in this invention may also be replaced by the closed "consisting of" or "consisting of...".

[0047] The present invention will be further described below in conjunction with specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the specific embodiments cited are not intended to limit the present invention.

[0048] Example 1

[0049] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiacyclohexadiene shown in formula V-1, and the specific process is as follows:

[0050] (1) Accurately weigh acetophenone (60 g, 500 mmol) and 250 mL of DMSO into a 500 mL three-necked reaction flask, install a reflux condenser and a constant pressure dropping funnel, place the reaction flask in an 80 °C oil bath, stir at this temperature and slowly add hydrobromic acid (30 mL, 40% aq). After the addition, continue to stir for 1 hour, then turn off the heating and let it cool naturally. When the oil bath temperature returns to room temperature, neutralize with sodium hydroxide aqueous solution to neutrality, then cool the reaction system to 5 °C, stir until a solid precipitates, filter and wash the filter cake with petroleum ether (PE) to obtain a solid, which does not need to be further purified, and dry to obtain 65.4 g of 2,2-dihydroxyacetophenone, with a yield of 86%. The product is a pale yellow solid (the purer the higher the color). The 2,2-dihydroxyacetophenone and its derivatives used in subsequent examples are all obtained by this method.

[0051] (2) Transfer 60.8 g (400 mmol) of 2,2-dihydroxyacetophenone prepared in step (1) to a reaction flask, add the raw material N,N-dimethylaniline (48.5 g, 400 mmol), add 400 mL of toluene as the reaction solvent, and react in a 60 °C oil bath under the protection of an inert gas. After reacting for 12 hours, turn off the heating and let it cool naturally, then concentrate to obtain a crude product and directly carry out column chromatography separation (ethyl acetate: petroleum ether = 1:5, Rf ≈ 0.4) to obtain 76.6 g The yield is 75%.

[0052] (3) Transfer 76.6 g (300 mmol) of the product prepared in step (2) to a reaction flask, add mercaptoethanol (30.5 g, 390 mmol), add 300 mL of toluene as the solvent, and add trifluoromethanesulfonic acid (4.5 g, 30 mmol) as the catalyst. The reaction is carried out at 110 °C under the protection of an inert gas. After 12 hours of reaction, turn off the heating and let it cool naturally. Then add sodium hydroxide solution to neutralize to neutrality, wash with water, dry, and concentrate to obtain the crude product, which is directly subjected to column chromatography separation (ethyl acetate: petroleum ether = 1:100, Rf ≈ 0.6) to obtain 81.2 g of compound IV1 with a yield of 91%. The product is a pale yellow solid. The product is characterized by NMR and high performance liquid chromatography, and the characterization results are as follows:

[0053] 1 H NMR (400 MHz, CCl3D) δ 7.26 - 7.22 (m, 2H), 7.19 - 7.13 (m, 5H), 6.60 (d, J = 8 Hz, 2H), 4.53 (t, J = 4 Hz, 2H), 3.25 (t, J = 4 Hz, 2H), 2.95 (s, 6H);

[0054] The purity is 99.94%.

[0055] In addition, for the above step (2), this example studied the effects of solvent types and reaction temperatures on the reaction products, as shown in Table 1 below:

[0056] Table 1

[0057] Group Solvent Reaction Temperature Reaction Time Yield of IV (%) Yield of IVA (%) 1 Toluene 40℃ 24 hours 62％ <1％ 2 Toluene 50℃ 12 hours 69％ <1％ 3 Toluene 60℃ 12 hours 75％ <1％ 4 Toluene 65℃ 12 hours 82％ 2％ 5 Toluene 70℃ 6 hours 79％ 5％ 6 Chlorobenzene 65℃ 12 hours 65％ 2％ 7 Benzotrifluoride 65℃ 12 hours 59％ 1％ 8 Xylene 65℃ 12 hours 67％ 3％ 9 DMSO 65℃ 12 hours 31％ <1％ 10 DMF 65℃ 12 hours 23％ <1％ 11 1,4-Dioxane 65℃ 12 hours 52％ 12％ 12 Tetrahydrofuran 65℃ 12 hours 47％ 15％ 13 1,2-Dichloroethane 65℃ 12 hours 45％ <1％ 14 Ethanol 65℃ 12 hours <5％ <1％

[0058] In the table, IV is IVA is

[0059] As can be seen from Table 1, when the solvent of the reaction system is toluene, a high yield of compound IV can be obtained within 12 hours. And in this reaction system, the reaction rate increases with the increase of the reaction temperature, but the reaction temperature should not be too high. When the reaction temperature > 60 °C, the yield of by-product IVA increases significantly.

[0060] Example 2

[0061] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown by formula V-2, and the specific process is as follows:

[0062] (1) It is the same as step (1) in Example 1;

[0063] (2) Transfer 60.8 g (400 mmol) of 2,2-dihydroxyacetophenone prepared in step (1) to a reaction flask, add (194.2 g, 400 mmol), add 400 mL of toluene as the reaction solvent. The reaction is carried out under the protection of an inert gas and placed in an oil bath at 60 °C. After reacting for 12 hours, turn off the heating and let it cool naturally. Then concentrate to obtain the crude product and directly perform column chromatography separation (ethyl acetate: petroleum ether = 1:5, Rf≈0.5) to obtain 190.8 g The yield is 77%.

[0064] (3) Transfer 185.9 g (300 mmol) of prepared in step (2) to a reaction flask, and add mercaptoethanol (30.5 g, 390 mmol). Add 300 mL of toluene solvent to dissolve it, and add trifluoromethanesulfonic acid (4.5 g, 30 mmol) as a catalyst. The reaction is carried out under the protection of an inert gas at 110 °C. After reacting for 12 hours, turn off the heating and let it cool naturally. Then add sodium hydroxide solution to neutralize to neutral, wash with water, dry, concentrate to obtain the crude product and directly perform column chromatography separation (ethyl acetate: petroleum ether = 1:150, Rf≈0.5) to obtain 174.6 g The yield is 88%, and the product is a pale yellow oily substance; the product is characterized by NMR and high performance liquid chromatography, and the characterization results are as follows:

[0065] 1 H NMR (400 MHz, CCl3D) δ 7.21 - 7.19 (m, 2H), 7.14 - 7.08 (m, 3H), 7.02 (d, J = 8 Hz, 2H), 6.43 (d, J = 8 Hz, 2H), 4.48 (t, J = 4 Hz, 2H), 3.22 - 3.15 (m, 6H), 1.55 - 1.47 (m, 4H), 1.32 - 1.22 (m, 44H), 0.88 (t, J = 8 Hz, 6H);

[0066] The purity is 99.796%.

[0067] Example 3

[0068] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin, shown in formula V-3, and the specific process is as follows:

[0069] (1) It is the same as step (1) in Example 1;

[0070] (2) Transfer 60.8 g (400 mmol) of 2,2-dihydroxyacetophenone prepared in step (1) to a reaction flask, add triphenylamine (98.1 g, 400 mmol), add 400 mL of toluene as the reaction solvent, and react under the protection of an inert gas and in an oil bath at 60 °C. After reacting for 12 hours, turn off the heating and let it cool naturally. Then concentrate to obtain the crude product and directly perform column chromatography separation (ethyl acetate: petroleum ether = 1:5, Rf ≈ 0.45) to obtain 119.9 g The yield is 79%.

[0071] (3) Transfer 113.8 g (300 mmol) of the product prepared in step (2) to a reaction flask, add 2-mercaptoethanol (30.5 g, 390 mmol), dissolve it in 300 mL of toluene solvent, and add trifluoromethanesulfonic acid (4.5 g, 30 mmol) as a catalyst. React under the protection of an inert gas at 110 °C. After reacting for 12 hours, turn off the heating and let it cool naturally. Then add sodium hydroxide solution to neutralize to neutral, wash with water, dry, concentrate to obtain the crude product and directly perform column chromatography separation (ethyl acetate: petroleum ether = 1:120, Rf ≈ 0.5) to obtain 106.2 g The yield is 84%, and the product is a pale yellow solid. The NMR characterization of the product is as follows:

[0072] 1 H NMR (400 MHz, CCl3D) δ 7.27 - 7.12 (m, 9H), 7.11 - 6.95 (m, 8H), 6.88 (d, J = 8 Hz, 2H), 4.53 (t, J = 4 Hz, 2H), 3.25 (t, J = 4 Hz, 2H).

[0073] Example 4

[0074] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin represented by formula V-4. The synthesis method is the same as that in Example 2, using 4-bromoacetophenone to replace acetophenone in Example 2 to prepare the target compound V-4. The yield of the second step is 82%; the yield of the product in the third step is 83%. The product is a pale yellow oil; the NMR characterization data is as follows: 1 H NMR (400 MHz, CCl3D) δ 7.52 (d, J = 8 Hz, 2H), 7.23 (d, J = 8 Hz, 2H), 7.03 (d, J = 8 Hz, 2H), 6.45 (d, J = 8 Hz, 2H), 4.50 (t, J = 4 Hz, 2H), 3.24 - 3.16 (m, 6H), 1.56 - 1.48 (m, 4H), 1.34 - 1.23 (m, 44H), 0.88 (t, J = 8 Hz, 6H).

[0075] Example 5

[0076] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-5. The synthesis method is the same as that in Example 2, using 4-nitroacetophenone to replace acetophenone in Example 2 to obtain the target compound V-5. The yield of the second step is 70%; the yield of the product in the third step is 79%. The product is a yellow solid; the NMR characterization data is as follows: 1 HNMR(400MHz,CCl3D)δ8.12(d,J=8Hz,2H),7.56(d,J=8Hz,2H),7.10(d,J=8Hz,2H),6.51(d,J=8Hz,2H),4.56(t,J=4Hz,2H),3.29-3.20(m,6H),1.57-1.47(m,4H),1.36-1.24(m,44H),0.89(t,J=8Hz,6H).

[0077] Example 6

[0078] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-6. The synthesis method is the same as that in Example 2, using 4-phenylacetophenone to replace acetophenone in Example 2 to obtain the target compound V-6. The yield of the second step is 83%; the yield of the product in the third step is 85%. The product is a light yellow solid; the NMR characterization data is as follows: 1 H NMR(400MHz,CCl3D)δ7.72-7.49(m,9H),7.23(d,J=8Hz,2H),7.01(d,J=8Hz,2H),6.40(d,J=8Hz,2H),4.52(t,J=4Hz,2H),3.22-3.14(m,6H),1.56-1.45(m,4H),1.33-1.22(m,44H),0.87(t,J=8Hz,6H).

[0079] Example 7

[0080] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-7. The synthesis method is the same as that in Example 2, using 4-(1-isoquinolyl)acetophenone to replace acetophenone in Example 2 to obtain the target compound V-7. The yield of the second step is 71%; the yield of the product in the third step is 77%. The product is a yellow solid; the NMR characterization data is as follows: 11H NMR (400 MHz, CCl3D) δ 8.39 (d, J = 8 Hz, 1H), 8.11 (d, J = 8 Hz, 2H), 7.65 - 7.50 (m, 7H), 7.06 (d, J = 8 Hz, 2H), 6.41 (d, J = 8 Hz, 2H), 4.50 (t, J = 4 Hz, 2H), 3.21 - 3.13 (m, 6H), 1.55 - 1.44 (m, 4H), 1.32 - 1.21 (m, 44H), 0.89 (t, J = 8 Hz, 6H).

[0081] Example 8

[0082] This example provides the preparation of 2,3 - dihydro - 5,6 - diaryloxathiin shown in Formula V - 8. The synthesis method is the same as that in Example 2, using 4-(2 - 1,10 - phenanthrolinyl)-acetophenone to replace acetophenone in Example 2 to prepare the target compound V - 8. The yield of the second step is 69%; the yield of the product in the third step is 76%. The product is a yellow solid; the NMR characterization data is as follows: 1 1H NMR (400 MHz, CCl3D) δ 8.75 - 9.69 (m, 3H), 8.23 - 8.10 (m, 3H), 7.71 - 7.52 (m, 4H), 7.07 (d, J = 8 Hz, 2H), 6.46 (d, J = 8 Hz, 2H), 4.52 (t, J = 4 Hz, 2H), 3.24 - 3.14 (m, 6H), 1.56 - 1.46 (m, 4H), 1.36 - 1.24 (m, 44H), 0.88 (t, J = 8 Hz, 6H).

[0083] Example 9

[0084] This example provides the preparation of 2,3 - dihydro - 5,6 - diaryloxathiin shown in Formula V - 9. The synthesis method is the same as that in Example 2, using 4-(6 - phenanthridinyl)acetophenone to replace acetophenone in Example 2 to prepare the target compound V - 9. The yield of the second step is 69%; the yield of the product in the third step is 73%. The product is a yellow solid; the NMR characterization data is as follows: 1 1H NMR (400 MHz, CCl3D) δ 8.19 - 8.10 (m, 3H), 7.81 - 7.65 (m, 9H), 7.22 (d, J = 8 Hz, 2H), 7.04 (d, J = 8 Hz, 2H), 6.42 (d, J = 8 Hz, 2H), 4.50 (t, J = 4 Hz, 2H), 3.23 - 3.15 (m, 6H), 1.54 - 1.45 (m, 4H), 1.34 - 1.22 (m, 44H), 0.88 (t, J = 8 Hz, 6H).

[0085] Example 10

[0086] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-10. The synthesis method is the same as that in Example 3, using 4-bromoacetophenone to replace acetophenone in Example 3 to prepare the target compound V-10. The yield of the second step is 76%; the yield of the product in the third step is 80%. The product is a pale yellow solid; the NMR characterization data are as follows: 1 H NMR(400MHz,CCl3D)δ7.56(d,J=8Hz,2H),7.32-7.12(m,6H),7.10-6.95(m,8H),6.89(d,J=8Hz,2H),4.55(t,J=4Hz,2H),3.26(t,J=4Hz,2H).

[0087] Example 11

[0088] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-11. The synthesis method is the same as that in Example 3, using 4-fluoroacetophenone to replace acetophenone in Example 3 to prepare the target compound V-11. The yield of the second step is 70%; the yield of the product in the third step is 82%. The product is a pale yellow solid; the NMR characterization data are as follows: 1 HNMR(400MHz,CCl3D)δ7.53(d,J=8Hz,2H),7.30-7.12(m,6H),7.11-6.95(m,8H),6.88(d,J=8Hz,2H),4.54(t,J=4Hz,2H),3.26(t,J=4Hz,2H).

[0089] Example 12

[0090] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-12. The synthesis method is the same as that in Example 3, using 4-cyanoacetophenone to replace acetophenone in Example 3 to prepare the target compound V-12. The yield of the second step is 72%; the yield of the product in the third step is 81%. The product is a pale yellow solid; the NMR characterization data are as follows: 1 H NMR(400MHz,CCl3D)δ7.83(d,J=8Hz,2H),7.35-7.16(m,6H),7.12-6.97(m,8H),6.91(d,J=8Hz,2H),4.55(t,J=4Hz,2H),3.25(t,J=4Hz,2H).

[0091] Example 13

[0092] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-13. The synthesis method is the same as that in Example 3, using 4-trifluoromethylacetophenone to replace acetophenone in Example 3 to obtain the target compound V-13. The yield of the second step is 82%; the yield of the product in the third step is 86%. The product is a pale yellow solid; the NMR characterization data is as follows: 1 HNMR(400MHz,CCl3D)δ7.31-7.17(m,8H),7.13-6.97(m,8H),6.89(d,J=8Hz,2H),4.56(t,J=4Hz,2H),3.26(t,J=4Hz,2H).

[0093] Example 14

[0094] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-14. The synthesis method is the same as that in Example 3, using 4-ethynylacetophenone to replace acetophenone in Example 3 to obtain the target compound V-14. The yield of the second step is 56%; the yield of the product in the third step is 70%. The product is a yellow solid; the NMR characterization data is as follows: 1 H NMR(400MHz,CCl3D)δ7.33-7.14(m,8H),7.12-6.97(m,8H),6.89(d,J=8Hz,2H),4.52(t,J=4Hz,2H),3.24(t,J=4Hz,2H),3.01(s,1H).

[0095] Example 15

[0096] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-15. The synthesis method is the same as that in Example 3, using methyl 4-acetylbenzoate to replace acetophenone in Example 3 to obtain the target compound V-15. The yield of the second step is 82%; the yield of the product in the third step is 75%. The product is a yellow solid; the NMR characterization data is as follows: 1 HNMR(400MHz,CCl3D)δ7.69-7.57(m,4H),7.31-7.16(m,6H),7.12-6.94(m,6H),6.89(d,J=8Hz,2H),4.52(t,J=4Hz,2H),3.86(s,1H),3.24(t,J=4Hz,2H).

[0097] Example 16

[0098] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-16. The synthesis method is the same as that in Example 3, using 4-acetylbiphenyl to replace acetophenone in Example 3 to obtain the target compound V-16. The yield of the second step is 84%; the yield of the third-step product is 82%. The product is a yellow solid; the NMR characterization data is as follows: 1 HNMR(400MHz,CCl3D)δ7.61-7.45(m,5H),7.27-7.14(m,8H),7.12-6.95(m,8H),6.89(d,J=8Hz,2H),4.55(t,J=4Hz,2H),3.24(t,J=4Hz,2H).

[0099] Example 17

[0100] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-17. The synthesis method is the same as that in Example 3, using 4-(4-pyridyl)acetophenone to replace acetophenone in Example 3 to obtain the target compound V-17. The yield of the second step is 68%; the yield of the third-step product is 77%. The product is a light yellow solid; the NMR characterization data is as follows: 1 H NMR(400MHz,CCl3D)δ8.65(d,J=8Hz,2H),7.61-7.52(m,6H),7.23-7.14(m,4H),7.12-6.97(m,8H),6.89(d,J=8Hz,2H),4.54(t,J=4Hz,2H),3.25(t,J=4Hz,2H).

[0101] Example 18

[0102] This example provides the preparation of 2,3-dihydro-5,6-diaryloxathiin shown in Formula V-18. The synthesis method is the same as that in Example 3, using 4-quinolylacetophenone to replace acetophenone in Example 3 to obtain the target compound V-18. The yield of the second step is 71%; the yield of the third-step product is 78%. The product is a light yellow solid; the NMR characterization data is as follows: 1 H NMR(400MHz,CCl3D)δ8.69(s,1H),7.75-7.61(m,4H),7.29-7.15(m,9H),7.13-6.96(m,8H),6.89(d,J=8Hz,2H),4.54(t,J=4Hz,2H),3.25(t,J=4Hz,2H).

[0103] The above-described embodiments are only preferred embodiments given to fully illustrate the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present invention are all within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. A method for preparing 2,3-dihydro-5,6-diaryloxathiin, characterized in that, It includes the following steps: (1) Oxidize the 1-arylacetone shown in formula (I) with an oxidant in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2,2-dihydroxyacetone shown in formula (II); the oxidant is dimethyl sulfoxide; (2) Under a protective atmosphere, carry out a substitution reaction between the 1-aryl-2,2-dihydroxyacetone shown in formula (II) prepared in step (1) and the aniline derivative shown in formula (III) in toluene to obtain diarylacetol shown in formula (IV); (3) Under a protective atmosphere, carry out a cyclization reaction between the diarylacetol shown in formula (IV) prepared in step (2) and mercaptoethanol in the presence of a water-soluble acid and a solvent to obtain 2,3-dihydro-5,6-diaryloxathiin shown in formula (V); the water-soluble acid is trifluoromethanesulfonic acid; The structures of the above formula (I) to formula (V) are as follows: ， wherein, R 1 is selected from the group consisting of hydrogen, halogen, cyano, nitro, C2-C22 alkynyl, C1-C24 haloalkyl, C6 aryl, and C1-C17 N-containing heteroaryl; R 2 and R 3 each independently selected from one of C1-C22 alkyl groups and C6 aryl groups.

2. The preparation method according to claim 1, wherein The 2,3-dihydro-5,6-diaryloxathiin is one of the structures shown in the following V-1 to V-14, V-16 to V-18: ， ， ， 。 3. The preparation method according to claim 1, wherein In step (1), the solvent is dimethyl sulfoxide.

4. The preparation method according to claim 3, characterized in that, The molar ratio of the 1-arylacetone shown in formula (I) to dimethyl sulfoxide and hydrobromic acid is 1:4 - 12:0.2 - 1.

5.

5. The preparation method according to claim 1, characterized in that, In step (1), the reaction temperature of the oxidation reaction is 60 - 110 °C, and the reaction time is 2 - 10 h.

6. The preparation method according to claim 1, characterized in that, In step (2), the reaction temperature of the substitution reaction is 40 - 70 °C, and the reaction time is 8 - 24 h.

7. The preparation method according to claim 1, characterized in that, In step (3), the molar ratio of the diarylacetol shown in formula (IV) to mercaptoethanol and the water-soluble acid is 1:1 - 3:0.1 - 1.

5.

8. The preparation method according to claim 1, characterized in that, In step (3), the solvent is toluene and / or 1,4-dioxane.

9. The preparation method according to claim 1, characterized in that, In step (3), the reaction temperature of the cyclization reaction is 90 - 130 °C, and the reaction time is 2 - 24 h.

10. A method for preparing 2,3-dihydro-5,6-diaryloxathiin, characterized in that, It includes the following steps: (1) Oxidize the 1-arylacetone shown in formula (I) with an oxidant in the presence of hydrobromic acid and a solvent to obtain 1-aryl-2,2-dihydroxyacetone shown in formula (II); the oxidant is dimethyl sulfoxide; (2) Under a protective atmosphere, carry out a substitution reaction between the 1-aryl-2,2-dihydroxyacetone shown in formula (II) prepared in step (1) and the aniline derivative shown in formula (III) in toluene to obtain diarylacetol shown in formula (IV); (3) Under a protective atmosphere, carry out a cyclization reaction between the diarylacetol shown in formula (IV) prepared in step (2) and mercaptoethanol in the presence of a water-soluble acid and a solvent to obtain 2,3-dihydro-5,6-diaryloxathiin shown in formula (V); the water-soluble acid is trifluoromethanesulfonic acid; The structures of the above formula (I) to formula (V) are as follows: ， 。

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