Synthesis method of site-selective diaryl sulfone compound

Abstract

The invention discloses a method for synthesizing a site-selective diaryl sulfone compound, which comprises the following steps of: orderly mixing sodium sulfinate, biaryl lambda 3 bromine salt / chlorine salt, alkali or catalyst and solvent, and stirring at 0 DEG C or 95 DEG C to construct a C-S bond, so that site selectivity control can be realized by adjusting reaction conditions, and the site selectivity of the diaryl sulfone compound is improved. The diversified synthesis of the diaryl sulfone compound is realized. According to the present invention, the synthesis of the diaryl sulfone compound can be efficiently and selectively achieved at the high site, the used starting raw material has characteristics of simple synthesis, diverse structures and low price, the reaction cost is reduced, the post-treatment step of the reaction is simplified, and the construction of the site-selective C-S bond can be achieved. The synthesis reaction operation is simple, the condition is mild, the yield is high, the post-treatment is convenient, the amplification of the reaction and the subsequent conversion of the product can be realized, and the method has wide application prospect and practical value.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, and specifically relates to a biarylλ synthesized under alkaline conditions or metal catalysis. 3 A method for the efficient and site-selective conversion of bromide / chloride salts into diaryl sulfone compounds by reacting with sodium sulfite. Background Technology

[0002] Sulfones are widely found in nature and, due to their diverse biological activities, have become crucial structural units in drug and pesticide molecules. Furthermore, sulfones have the potential to improve material properties in materials science and can serve as multifunctional synthetic intermediates for achieving Julianylation, Ramberg-... A series of classic transformations, including reactions and SMILE rearrangements, have been employed. Given the significant value of sulfones in chemistry and applied sciences, the development of strategies for the efficient synthesis of sulfone derivatives has been a major focus.

[0003] The most classic synthetic method for biaryl sulfones is the direct oxidation of the corresponding sulfide. However, the use of strong oxidizing agents often limits functional group compatibility and produces byproducts, affecting the application scope of this method (J.Org.Chem.2010,75,6208-6213; Green Chem.2012,14,3047-3052). Friedel-Crafts sulfonation is another feasible route, but it requires the use of hazardous sulfonyl chlorides and harsh reaction conditions (Chem.Commun.2001,1696-1697; Tetrahedron Lett.2006,47,6063-6066). Transition metal-catalyzed coupling reactions of sulfonates with arylboronic acids or haloarynes provide an efficient route for the synthesis of biaryl sulfones; gold, iridium, ruthenium, palladium, nickel, copper, and cobalt-catalyzed sulfonation reactions of aromatic C–H bonds have been gradually developed, and various sulfonating agents such as sulfonates, sulfonamides, sulfonyl chlorides, and sulfonyl azides can participate in the reactions (J. Org. Chem. 2025, 90, 3279-3289; Org. Lett. 2017, 19, 5166-5169; Org. Lett. 2018, 20, 760-763; Green). (Chem. 2021, 23, 6322-6329); Multi-component reactions involving SO2 substitutes, represented by DABSO, have further expanded the synthetic pathways (ACSCatal. 2019, 9, 10668-10673; Org. Lett. 2024, 26, 945-949). Following the principles of green chemistry, novel synthetic methods without transition metal involvement are receiving increasing attention as complementary and sustainable solutions (J. Org. Chem. 2019, 84, 3919-3926; J. Org. Chem. 2019, 84, 1372-1378).

[0004] It is noteworthy that in reported transformation reactions, the formation site of the new bond is typically determined by the direct linking site of the functional group (such as boric acid or halogen) or by the directing group. Although arylkynes, as highly reactive intermediates with two potential reaction sites, have been explored for sulfone synthesis via CS bond formation, these methods are mostly limited to symmetrical arylkynes (RSCAdv. 2014, 4, 50208-50211). In contrast, asymmetrical arylkynes typically produce a near 1:1 mixture of regioisomers, limiting their synthetic applications. Therefore, developing regioselective sulfonation strategies with controlled reaction conditions to achieve the efficient synthesis of diverse diaryl sulfone compounds remains a significant research area.

[0005] Given these limitations, developing a mild, efficient, and site-selective strategy would provide a valuable complementary route for the synthesis of diaryl sulfone compounds, with broad application prospects and practical value. Summary of the Invention

[0006] Purpose of the invention: The purpose of this invention is to provide a method for synthesizing site-selective diaryl sulfone compounds.

[0007] Technical solution: A method for synthesizing site-selective diaryl sulfone compounds, characterized in that: sodium sulfite and biaryl λ are used. 3 After the bromide / chloride salt, base or catalyst, and solvent are mixed in an orderly manner, the CS bond is constructed under stirring conditions at 0℃ or 95℃, which can yield a series of site-selective diaryl sulfone compounds.

[0008] The specific steps are as follows:

[0009] Synthesis of meta-diaryl sulfones: Route 1, adding sodium sulfite and biaryl λ to a reaction vessel. 3 Bromine / chloride salts, alkalis, and solvents are stirred and reacted at 0°C. After the reaction is complete, the solvent is removed, and the target product is obtained by simple separation by column chromatography.

[0010] Synthesis of ortho-diaryl sulfones: Route 2, adding sodium sulfite and biaryl λ to the reaction vessel. 3 Bromine / chloride salts, catalysts, additives, and solvents were stirred and reacted at 95°C. After the reaction was complete, the solvent was removed, and the target product was obtained by simple separation by column chromatography.

[0011] The reaction route for this synthesis method is as follows:

[0012]

[0013] Among them, Ar and Ar 1 To replace the benzene ring, Ar 2X is a halogen, where the aryl group is substituted.

[0014] The Lewis base is any one of triethylamine, 1,5,7-triazabicyclo[4.4.0]decen-5-ene, 1,8-diazabispirocyclo[5.4.0]undecen-7-ene, triethylenediamine, sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, potassium dihydrogen phosphate, potassium monohydrogen phosphate, lithium bis(trimethylsilylamine), sodium bis(trimethylsilylamine), potassium bis(trimethylsilylamine), lithium hydride, sodium hydride, and potassium hydride, preferably cesium carbonate;

[0015] Solvent 1 is one of tetrahydrofuran, acetonitrile, N,N-dimethylformamide, toluene, dichloromethane, 1,4-dioxane, dimethyl sulfoxide, and diethyl ether, preferably dichloromethane;

[0016] The solvent 2 is one of tetrahydrofuran, acetonitrile, N,N-dimethylformamide, toluene, dichloromethane, 1,4-dioxane, dimethyl sulfoxide, and diethyl ether, preferably dimethyl sulfoxide;

[0017] The catalyst is one of cuprous chloride, cuprous bromide, cuprous iodide, cuprous trifluoromethanesulfonate, copper powder, copper chloride, copper bromide, copper iodide, and copper oxide, preferably cuprous iodide;

[0018] The additive is one of pyridine, pyridine oxide, N,N-dimethylaminopyridine, L-proline, and sodium L-proline, preferably sodium L-proline.

[0019] Furthermore, the method for site-selective synthesis of diaryl sulfone compounds is characterized in that: the biaryl λ described in route 1 3 The molar ratio of bromide / chloride salt, sodium sulfite, and alkali is 1.0:1.0-2.0:1.0-3.0, preferably 1.0:2.0:3.0.

[0020] Furthermore, the method for site-selective synthesis of diaryl sulfone compounds is characterized in that: the biaryl λ described in route 2 3 The molar ratio of bromide / chloride salt, sodium sulfite, catalyst, and additive is 1.0:1.0-2.0:0.1-0.2:0.1-0.2, preferably 1.0:1.2:0.1:0.2.

[0021] Beneficial effects: The specific advantages of this invention are as follows:

[0022] 1. This invention provides a convenient method for the preparation of diaryl sulfone compounds. The reaction conditions are mild, the operation is simple, and the post-processing is convenient. Moreover, site selectivity can be controlled by adjusting the reaction conditions, enabling the diversified synthesis of diaryl sulfone compounds.

[0023] 2. The starting materials used in this invention are simple to synthesize, have diverse structures, and are inexpensive, which not only reduces the cost of the reaction but also facilitates the post-processing of the reaction.

[0024] 3. The synthesis method of the present invention has simple operation, mild conditions, fast reaction and high yield, and can realize the scale-up of the reaction, and has broad application prospects and practical value. Attached Figure Description

[0025] Figure 1 The structure of Example 1 prepared according to the present invention 1 H NMR spectrum.

[0026] Figure 2 The structure of Example 2 prepared according to the present invention 1 H NMR spectrum.

[0027] Figure 3 The structure of Example 3 prepared according to the present invention 1 H NMR spectrum.

[0028] Figure 4 The structure of Example 4 prepared according to the present invention 1 H NMR spectrum.

[0029] Figure 5 The structure of Example 5 prepared according to the present invention 1 H NMR spectrum.

[0030] Figure 6 The structure of Example 6 prepared according to the present invention 1 H NMR spectrum.

[0031] Figure 7 The structure of Example 7 prepared according to the present invention 1 H NMR spectrum.

[0032] Figure 8 The structure of Example 8 prepared according to the present invention 1 H NMR spectrum.

[0033] Figure 9 The structure of Example 9 prepared according to the present invention 1 H NMR spectrum.

[0034] Figure 10 The structure of Example 10 prepared according to the present invention 1 H NMR spectrum. Detailed Implementation

[0035] The technical solutions in the embodiments of the present invention will be clearly and completely described below, so that those skilled in the art can better understand the advantages and features of the present invention, thereby making a clearer definition of the scope of protection of the present invention. The embodiments described in this invention are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0036] Example 1

[0037]

[0038] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (98%). 1 H NMR (400MHz, Chloroform-d) δ 8.07–7.93 (m, 4H), 7.68 (d, J = 8.0Hz, 1H), 7.64–7.50 (m, 5H), 7.39 (t, J = 7.5Hz, 1H), 7.32–7.23 (m, 2H).

[0039] Example 22

[0040]

[0041] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-chlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (94%). 1 H NMR(400MHz,Chloroform-d)δ8.01(t,J=1.8Hz,1H),7.96–7.89(m,3H),7.68(dd,J=8.0,1.1Hz,1H),7.64(dt ,J=7.6,1.5Hz,1H),7.58(t,J=7.7Hz,1H),7.52–7.47(m,2H),7.40(td,J=7.5,1.2Hz,1H),7.32–7.24(m,2H).

[0042] Example 3

[0043]

[0044] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 3-chlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (86%). 1 H NMR(400MHz,Chloroform-d)δ8.03(t,J=1.8Hz,1H),7.96(dt,J=7.7,1.7Hz,2H),7.87(dt,J=7.8,1.4Hz,1H),7.69(dd,J=8.0,1.2Hz,1H),7.65(dt,J=7.7 ,1.5Hz,1H),7.60(t,J=7.7Hz,1H),7.56–7.52(m,1H),7.46(t,J=7.9Hz,1H) ,7.40(td,J=7.5,1.2Hz,1H),7.32(dd,J=7.7,1.8Hz,1H),7.29–7.24(m,1H).

[0045] Example 4

[0046]

[0047] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 2,5-dichlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was complete, the reaction system was concentrated and separated by column chromatography to obtain the target product (72%). 1 H NMR (400MHz, Chloroform-d) δ8.36(t,J=2.2Hz,1H),8.01(d,J=2.0Hz,1H),7.96(d,J=7.9Hz,1H),7.68(d,J =7.8Hz,2H),7.60(td,J=7.8,1.7Hz,1H),7.50(dt,J=8.6,2.3Hz,1H),7.43–7.36(m,2H),7.32–7.24(m,2H).

[0048] Example 5

[0049]

[0050] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 2,4-dichlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was complete, the reaction system was concentrated and separated by column chromatography to obtain the target product (75%). 1 H NMR(400MHz,Chloroform-d)δ8.35–8.27(m,1H),7.99(d,J=1.8Hz,1H),7.93(dt,J=7.9,1.5Hz,1H),7.7 0–7.63(m,2H),7.58(t,J=7.7Hz,1H),7.50–7.45(m,2H),7.39(td,J=7.5,1.2Hz,1H),7.32–7.23(m,2H).

[0051] Example 6

[0052]

[0053] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-methylbenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (92%). 1 H NMR(400MHz,Chloroform-d)δ8.01(d,J=1.9Hz,1H),7.94(dd,J=7.7,1.7Hz,1H),7.89–7.84(m,2H),7.67(d,J=8.0Hz,1H ),7.60(d,J=8.1Hz,1H),7.55(t,J=7.7Hz,1H),7.38(t,J=7.4Hz,1H),7.33–7.28(m,3H),7.27–7.23(m,1H),2.40(s,3H).

[0054] Example 7

[0055]

[0056] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-trifluoromethylbenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (82%). 1 H NMR(400MHz,Chloroform-d)δ8.11(d,J=8.2Hz,2H),8.06–8.03(m,1H),7.97(dt,J=7.7,1.6Hz,1H),7.79(d,J= 8.2Hz,2H),7.68(td,J=8.0,1.4Hz,2H),7.60(t,J=7.7Hz,1H),7.40(td,J=7.4,1.2Hz,1H),7.33–7.25(m,2H).

[0057] Example 8

[0058]

[0059] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 3-nitro-4-chlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and an ice bath. After the reaction was complete, the reaction system was concentrated and separated by column chromatography to obtain the target product (69%). 1 H NMR(400MHz,Chloroform-d)δ9.08(d,J=2.4Hz,1H),8.34(dd,J=8.4,2.5Hz,1H),7.95(d,J=1.8Hz,1H),7.92(dd,J=7.7,1.6Hz,1 H),7.70–7.66(m,2H),7.62(t,J=7.7Hz,1H),7.46(d,J=8.4Hz,1H),7.40(td,J=7.5,1.2Hz,1H),7.33–7.26(m,2H),2.62(s,3H).

[0060] Example 9

[0061]

[0062] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 2-thiophene sulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (78%). 1 H NMR(400MHz,Chloroform-d)δ8.07(t,J=1.8Hz,1H),8.00(dt,J=7.7,1.6Hz,1H),7.74(dd,J=3.8,1.3Hz,1H),7.71–7.62(m,3H) ,7.58(t,J=7.7Hz,1H),7.39(td,J=7.5,1.3Hz,1H),7.32(dd,J=7.7,1.8Hz,1H),7.28–7.23(m,1H),7.10(dd,J=5.0,3.8Hz,1H).

[0063] Example 10

[0064]

[0065] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 8-quinoline sulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (76%). 1 H NMR(400MHz,Chloroform-d)δ8.96(dd,J=4.3,1.7Hz,1H),8.74(dd,J=7.5,1.4Hz,1H),8.29( d,J=1.8Hz,1H),8.24–8.16(m,2H),8.08(dd,J=8.2,1.4Hz,1H),7.70(t,J=7.8Hz,1H),7.64(d d,J=8.1,1.2Hz,1H),7.57(dt,J=7.5,1.5Hz,1H),7.51(t,J=7.7Hz,1H),7.45(dd,J=8.3,4.2 Hz, 1H), 7.36 (td, J = 7.4, 1.2 Hz, 1H), 7.30 ( dd, J = 7.7, 1.9 Hz, 1H), 7.22 ( td, J = 7.6, 1.8 Hz, 1H).

[0066] Example 11

[0067]

[0068] In a 10 mL reaction tube, 2-bromobiphenylλ was added 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (86%). 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J=1.9Hz,1H),8.02–7.93(m,3H),7.67(d,J=7.9Hz,1H ),7.64–7.59(m,1H),7.55(t,J=7.6Hz,2H),7.41–7.36(m,1H),7.28(dd,J=11.0,2.9Hz,3H).

[0069] Example 12

[0070]

[0071] In a 10 mL reaction tube, 3-bromobiphenylλ was added 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (83%). 1 H NMR(400MHz,Chloroform-d)δ8.47(d,J=2.2Hz,1H),8.00(dd,J=7.5,1.6Hz,2H),7.71(d,J=8.1Hz,2H),7.66–7 .59(m,1H),7.55(d,J=7.8Hz,2H),7.49(dd,J=8.2,2.3Hz,1H),7.43(dd,J=8.0,6.9Hz,1H),7.32–7.27(m,2H).

[0072] Example 13

[0073]

[0074] In a 10 mL reaction tube, 4-chlorobiphenylλ was added 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (81%). 1 H NMR(400MHz,Chloroform-d)δ7.71–7.66(m,2H),7.66–7.61(m,1H),7.54(dd,J=8.1,1.3Hz,1H),7.4 8–7.42(m,3H),7.42–7.39(m,1H),7.28–7.24(m,1H),7.18–7.13(m,2H),7.07(dd,J=7.5,1.8Hz,1H).

[0075] Example 14

[0076]

[0077] In a 10 mL reaction tube, 3-methylbiphenylλ was added 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (80%). 1 H NMR(400MHz,Chloroform-d)δ8.29(d,J=1.8Hz,1H),7.96–7.87(m,2H),7.70(d,J=8.0Hz,1H ),7.61–7.57(m,1H),7.55–7.52(m,2H),7.42–7.34(m,2H),7.33–7.26(m,3H),2.50(s,3H).

[0078] Example 15

[0079]

[0080] In a 10 mL reaction tube, add biphenyl λ 3 Chlorotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL) were added and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (89%). 1H NMR (400MHz, Chloroform-d) δ7.17(d,J=7.9Hz,2H),7.03–6.88(m,2H),6.30(s,1H),5.47(s,1H),4.42(s,2H),3.72(s,3H),2.33(s,3H),1.40(s,9H).

[0081] Example 16

[0082]

[0083] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with chlorotrifluoromethanesulfonate (0.1 mmol), sodium 4-chlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (80%). 1 H NMR(400MHz,Chloroform-d)δ8.03(d,J=1.8Hz,1H),7.93(dd,J=10.3,7.7Hz,3H),7.68 (d,J=7.7Hz,1H),7.58(t,J=7.8Hz,1H),7.52–7.46(m,3H),7.34(dt,J=5.7,4.4Hz,3H).

[0084] Example 17

[0085]

[0086] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with chlorotrifluoromethanesulfonate (0.1 mmol), sodium 3-chlorobenzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (85%). 1 H NMR(400MHz,Chloroform-d)δ8.05(t,J=1.8Hz,1H),7.98–7.93(m,2H),7.86(dt,J=7.8,1.4Hz,1H),7.71–7 .67(m,1H),7.60(t,J=7.8Hz,1H),7.54(ddd,J=8.0,2.1,1.1Hz,1H),7.51–7.45(m,2H),7.38–7.33(m,3H).

[0087] Example 18

[0088]

[0089] In a 10 mL reaction tube, 2-chlorobiphenylλ was added 3 Chlorotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL) were added and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (83%). 1 H NMR(400MHz,Chloroform-d)δ7.76(d,J=8.8Hz,1H),7.63–7.56(m,2H),7.54–7.45(m,2H),7.35(d, J=2.2Hz,1H),7.32–7.26(m,2H),7.22(td,J=7.6,1.7Hz,1H),7.18–7.12(m,2H),7.06–7.01(m,1H).

[0090] Example 19

[0091]

[0092] In a 10 mL reaction tube, 2-bromobiphenylλ was added 3 Chlorotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL) were added and stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (74%). 1 H NMR(400MHz,Chloroform-d)δ7.70–7.62(m,2H),7.62–7.57(m,2H),7.54–7.48(m,2H),7.32–7. 26(m,2H),7.22(td,J=7.6,1.8Hz,1H),7.15(td,J=8.7,1.6Hz,2H),7.04(dd,J=7.6,1.7Hz,1H).

[0093] Example 20

[0094]

[0095] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (88%). 1 H NMR(400MHz,Chloroform-d)δ8.49–8.42(m,1H),7.67–7.60(m,2H),7.47(tt ,J=6.8,1.8Hz,1H),7.37–7.34(m,1H),7.33–7.25(m,6H),7.25–7.18(m,2H).

[0096] Example 21

[0097]

[0098] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-chlorobenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (80%). 1 H NMR (400MHz, Chloroform-d) δ8.47–8.40(m,1H),7.68–7.60(m,2H),7.42–7.38(m,1H),7.38–7.32(m,2H),7.27–7.19(m,6H).

[0099] Example 22

[0100]

[0101] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 3-bromobenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C for 48 hours under a nitrogen atmosphere. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (70%). 1H NMR (400MHz, Chloroform-d) δ8.48–8.42(m,1H),7.69–7.62(m,2H),7.61–7.56(m,1H),7.42–7.33(m,3H),7.32–7.22(m,4H),7.15(t,J=7.9Hz,1H).

[0102] Example 23

[0103]

[0104] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-methoxybenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (74%). 1 H NMR(400MHz,Chloroform-d)δ8.44–8.39(m,1H),7.64–7.56(m,2H),7.43–7.37 (m,1H),7.37–7.31(m,2H),7.25–7.17(m,4H),6.76–6.68(m,2H),3.82(s,3H).

[0105] Example 24

[0106]

[0107] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium 2-naphthalenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (72%). 1 H NMR(400MHz,Chloroform-d)δ8.55–8.49(m,1H),7.86–7.80(m,1H),7.75(d,J=8.7Hz,1H),7.68–7 .59(m,5H),7.58–7.52(m,1H),7.44(dd,J=8.7,1.9Hz,1H),7.35–7.29(m,2H),7.23–7.13(m,3H).

[0108] Example 25

[0109]

[0110] In a 10 mL reaction tube, add biphenyl λ 3 Chlorotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL) were added and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (75%). 1 H NMR(400MHz,Chloroform-d)δ8.49–8.43(m,1H),7.66–7.60(m,2H),7.46(tt ,J=7.0,1.7Hz,1H),7.31–7.25(m,7H),7.23–7.20(m,1H),7.16–7.12(m,1H).

[0111] Example 26

[0112]

[0113] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with chlorotrifluoromethanesulfonate (0.1 mmol), sodium 4-fluorobenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C for 48 hours under a nitrogen atmosphere. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (65%). 1 H NMR (400MHz, Chloroform-d) δ8.49–8.41(m,1H),7.68–7.60(m,2H),7.35–7.26(m,5H),7.25–7.20(m,1H),7.20–7.15(m,1H),6.92(t,J=8.6Hz,2H).

[0114] Example 27

[0115]

[0116] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with chlorotrifluoromethanesulfonate (0.1 mmol), sodium 3-fluorobenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (60%). 1 H NMR(400MHz,Chloroform-d)δ8.49–8.42(m,1H),7.69–7.61(m,2H),7.35–7. 29(m,3H),7.27–7.22(m,2H),7.20–7.11(m,3H),6.90(dt,J=8.1,2.1Hz,1H).

[0117] Example 28

[0118]

[0119] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with chlorotrifluoromethanesulfonate (0.1 mmol), sodium 4-methylbenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and stirred at 95 °C for 48 hours under a nitrogen atmosphere. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (64%). 1 H NMR (400MHz, Chloroform-d) δ 8.45–8.40 (m, 1H), 7.64–7.58 (m, 2H), 7.31–7.26 (m, 3H), 7.22–7.15 (m, 4H), 7.05 (d, J = 8.1Hz, 2H), 2.36 (s, 3H).

[0120] Example 29

[0121]

[0122] In a 10 mL reaction tube, add biphenyl λ 3 Chlorotrifluoromethanesulfonate (0.1 mmol), sodium 4-methoxybenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL) were added and stirred at 95 °C under a nitrogen atmosphere for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (56%). 1H NMR (400MHz, Chloroform-d) δ 8.46–8.39 (m, 1H), 7.64–7.57 (m, 2H), 7.30 (dd, J = 5.6, 3.4Hz, 3H), 7.23–7.16 (m, 4H), 6.75–6.68 (m, 2H), 3.82 (s, 3H).

[0123] Example 30

[0124]

[0125] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture consisted of bromotrifluoromethanesulfonate (0.1 mmol), sodium 4-trifluoromethylbenzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), sodium L-proline (0.02 mmol), and dimethyl sulfoxide (2.0 mL), and was stirred at 95 °C for 48 hours under a nitrogen atmosphere. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (63%). 1 H NMR(400MHz,Chloroform-d)δ8.52–8.43(m,1H),7.71–7.63(m,2H),7.50(d,J=8.3Hz,2H) ,7.40(d,J=8.2Hz,2H),7.34–7.27(m,3H),7.26–7.21(m,1H),7.11(dd,J=7.1,2.1Hz,1H).

[0126] Example 31

[0127]

[0128] In a 10 mL reaction tube, add biphenyl λ 3 Bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and dichloromethane (2.0 mL) were added and stirred for 6 hours under a nitrogen atmosphere at room temperature. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (69%).

[0129] Example 32

[0130]

[0131] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), potassium carbonate (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere at room temperature. After the reaction was complete, the reaction system was concentrated and separated by column chromatography to obtain the target product (36%).

[0132] Example 33

[0133]

[0134] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), lithium tert-butoxide (0.3 mmol), and dichloromethane (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere at room temperature. After the reaction was complete, the reaction system was concentrated and separated by column chromatography to obtain the target product (27%).

[0135] Example 34

[0136]

[0137] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), bis(trimethylsilylaminolithium) (0.3 mmol), and dichloromethane (2.0 mL), and then stirred for 6 hours under a nitrogen atmosphere at room temperature. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (42%).

[0138] Example 35

[0139]

[0140] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.2 mmol), cesium carbonate (0.3 mmol), and tetrahydrofuran (2.0 mL), and stirred for 6 hours under a nitrogen atmosphere and ice bath. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (73%).

[0141] Example 36

[0142]

[0143] In a 10 mL reaction tube, add biphenyl λ 3The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), pyridine (0.015 mmol), and N,N-dimethylformamide (2.0 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (49%).

[0144] Example 37

[0145]

[0146] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous chloride (0.01 mmol), pyridine (0.015 mmol), and N,N-dimethylformamide (2.0 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (42%).

[0147] Example 38

[0148]

[0149] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), copper trifluoromethanesulfonate (0.01 mmol), pyridine (0.015 mmol), and N,N-dimethylformamide (2.0 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (47%).

[0150] Example 39

[0151]

[0152] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture consisted of bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), pyridine (0.015 mmol), and 1,4-dioxane (2.0 mL), and was stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (48%).

[0153] Example 40

[0154]

[0155] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (0.1 mmol), sodium benzenesulfinate (0.12 mmol), cuprous iodide (0.01 mmol), N,N-dimethylaminopyridine (0.015 mmol), and N,N-dimethylformamide (2.0 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (42%).

[0156] Example 41

[0157]

[0158] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (1 mmol), sodium benzenesulfinate (2 mmol), cesium carbonate (3 mmol), and dichloromethane (20 mL), and then stirred for 6 hours under a nitrogen atmosphere and ice bath conditions. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (90%).

[0159] Example 42

[0160]

[0161] In a 10 mL reaction tube, add biphenyl λ 3 The reaction mixture was prepared with bromotrifluoromethanesulfonate (1 mmol), sodium benzenesulfinate (1.2 mmol), cuprous iodide (0.1 mmol), sodium L-proline (0.2 mmol), and dimethyl sulfoxide (20 mL), and stirred at 95 °C for 48 hours. After the reaction was completed, the reaction system was concentrated and separated by column chromatography to obtain the target product (79%).

Claims

1. A method for synthesizing site-selective diaryl sulfone compounds, characterized in that: Sodium sulfite and biaryl λ 3 After the bromide / chloride salt, base or catalyst, and solvent are mixed in an orderly manner, the CS bond is constructed under stirring conditions at 0℃ or 95℃, which can yield a series of site-selective diaryl sulfone compounds. The specific operating steps are as follows: Synthesis of meta-diaryl sulfones: Route 1, adding sodium sulfite and biaryl λ to a reaction vessel. 3 Bromine / chloride salt, base and solvent 1 were stirred and reacted at 0°C. After the reaction was completed, the solvent was removed and the target product was obtained by simple separation by column chromatography. Synthesis of ortho-diaryl sulfones: Route 2 involves adding sodium sulfite and biaryl λ to a reaction vessel. 3 Bromine / chloride salts, catalysts, additives, and solvent 2 were stirred and reacted at 95°C. After the reaction was completed, the solvent was removed, and the target product was obtained by simple separation by column chromatography. The reaction route for this synthesis method is as follows: Among them, Ar and Ar 1 To replace the benzene ring, Ar 2 X is a halogen, where the aryl group is substituted. The base is any one of triethylamine, 1,5,7-triazabicyclo[4.4.0]decen-5-ene, 1,8-diazabispirocyclo[5.4.0]undecen-7-ene, triethylenediamine, sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, potassium dihydrogen phosphate, potassium monohydrogen phosphate, lithium bis(trimethylsilylamine), sodium bis(trimethylsilylamine), potassium bis(trimethylsilylamine), lithium hydride, sodium hydride, and potassium hydride. Solvent 1 is one of tetrahydrofuran, acetonitrile, N,N-dimethylformamide, toluene, dichloromethane, 1,4-dioxane, dimethyl sulfoxide, and diethyl ether; Solvent 2 is one of tetrahydrofuran, acetonitrile, N,N-dimethylformamide, toluene, dichloromethane, 1,4-dioxane, dimethyl sulfoxide, and diethyl ether; The catalyst is one of cuprous chloride, cuprous bromide, cuprous iodide, copper trifluoromethanesulfonate, copper powder, copper chloride, copper bromide, copper iodide, and copper oxide. The additive is one of pyridine, pyridine oxide, N,N-dimethylaminopyridine, L-proline, and sodium L-proline.

2. The method for site-selective synthesis of diaryl sulfone compounds as described in claim 1, characterized in that: The biaryl λ described in Route 1 3 The molar ratio of bromide / chloride, sodium sulfite, and alkali is 1.0:1.0-2.0:1.0-3.

0.

3. The method for site-selective synthesis of diaryl sulfone compounds as described in claim 1, characterized in that: The biaryl λ described in Route 2 3 The molar ratio of bromide / chloride salt, sodium sulfite, catalyst, and additive is 1.0:1.0~2.0:0.1~0.2:0.1~0.2.

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