A method for synthesizing diaryl sulfoxide derivatives

Abstract

The present invention provides a method for synthesizing a diaryl sulfoxide derivative. The present invention belongs to the technical field of organic synthesis. The diaryl sulfoxide derivative has a structure of Formula 1, and the synthesis method comprises the following steps: a Grignard reagent B, a zinc reagent, and dichlorothionyl react in a solvent M; the Grignard reagent B has a structure represented by Formula 2, and the solvent M is an organic solvent. The synthesis method provided by the present invention can achieve unexpectedly high yield and high purity in a reaction of a scale of 3 kilograms or more, and the reaction raw materials and reagents are simple and easy to obtain. The diaryl sulfoxide derivative synthesized by the method of the present invention can obtain a high-yield, high-purity final product through simple post-treatment, and the post-treatment is simple, low-cost, repeatable, and suitable for large-scale production, and has high practical value.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing a sulfoxide derivative, in particular to a method for synthesizing a diaryl sulfoxide derivative. Background Art

[0002] Diaryl sulfoxide derivatives are important intermediates for the synthesis of electronic materials. Therefore, it is of great significance to develop efficient and economical methods to synthesize these aromatic compounds.

[0003] In the prior art (Chem. Eur. J. 2022, 28, e202202564), Jordan Berreur et al. disclosed a synthesis method: , which only discloses that the Grignard reagent directly reacts with dithionyl chloride to generate diaryl sulfoxide derivatives, and the reaction yield is low. It is not suitable for commercial application after purification by column chromatography. It does not provide any teaching on improving the reaction system of Grignard reagent and dithionyl chloride, nor does it provide any teaching on first introducing a zinc reagent into the reaction system of Grignard reagent and dithionyl chloride to improve the yield and simplify the purification process.

[0004] The applicant's previous research and development work found that diaryl sulfoxide compounds have important application prospects in the field of electronic materials, but the methods in the prior art are not suitable for the commercial development of such materials. Therefore, a synthesis method with higher yield, lower cost and more suitable for commercialization needs to be further developed. Summary of the invention

[0005] The present invention aims to provide a method for synthesizing a diaryl sulfoxide derivative to solve at least part of the above problems. The method for synthesizing a diaryl sulfoxide derivative disclosed in the present invention can obtain a high-yield, high-purity final product through simple post-treatment, and the post-treatment is simple, low-cost, repeatable, and suitable for large-scale production, and has high practical value.

[0006] According to one embodiment of the present invention, a method for synthesizing a diaryl sulfoxide derivative is disclosed. The diaryl sulfoxide derivative has a structure shown in Formula 1:

[0007] ,

[0008] The synthesis method comprises the following steps:

[0009] The Grignard reagent B, the zinc reagent, and the dichlorothionyl react in the solvent M to generate the diaryl sulfoxide derivative;

[0010] The solvent M is an organic solvent;

[0011] The Grignard reagent B has a structure shown in Formula 2:

[0012] ,

[0013] In Formula 2, X is selected from chlorine, bromine or iodine;

[0014] In equation 1 and equation 2,

[0015] Ring A is selected from a heteroaromatic ring having 3 to 30 carbon atoms, an aromatic ring having 6 to 30 carbon atoms, or a combination thereof;

[0016] R A Indicates single substitution, multiple substitution or no substitution;

[0017] R A The group consisting of hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof;

[0018] Adjacent substituent R A Can optionally be linked to form a ring.

[0019] The invention discloses a novel method for synthesizing a diaryl sulfoxide derivative, comprising the key steps of reacting a Grignard reagent B and a zinc reagent in an organic solvent M, and then reacting with dithionyl chloride to generate a diaryl sulfoxide derivative. The synthesis method of the invention can achieve unexpectedly high yield and high purity in a reaction of a scale of 3 kg or more, and the reaction raw materials and reagents are easy to obtain. The diaryl sulfoxide derivative synthesized by the method of the invention can obtain a high-yield and high-purity final product through simple post-treatment, and the post-treatment is simple, low-cost, repeatable, suitable for large-scale production, and has high practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is the liquid chromatogram of the final product obtained in Example 1.

[0021] Figure 2It is the liquid chromatogram of the final product obtained in Example 2.

[0022] Figure 3 It is the liquid chromatogram of the final product obtained in Example 3.

[0023] Figure 4 It is the liquid chromatogram of the final product obtained in Example 4.

[0024] Figure 5 This is a liquid chromatogram of the final product obtained in Comparative Example 1.

[0025] Figure 6 This is a liquid chromatogram of the final product obtained in Comparative Example 2. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0027] Definition of Substituent Terms

[0028] Halogen or halide - as used herein includes fluorine, chlorine, bromine and iodine.

[0029] Alkyl - As used herein, linear and branched alkyl groups are included. The alkyl group may be an alkyl group having 1 to 20 carbon atoms, preferably an alkyl group having 1 to 12 carbon atoms, and more preferably an alkyl group having 1 to 6 carbon atoms. Examples of the alkyl group include methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, neopentyl, 1-methylpentyl, 2-methylpentyl, 1-pentylhexyl, 1-butylpentyl, 1-heptyloctyl, 3-methylpentyl. Among the above, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, neopentyl and n-hexyl are preferred. In addition, the alkyl group may be optionally substituted.

[0030] Cycloalkyl - as used herein includes cyclic alkyl groups. The cycloalkyl group may be a cycloalkyl group having 3 to 20 ring carbon atoms, preferably a cycloalkyl group having 4 to 10 carbon atoms. Examples of cycloalkyl groups include cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 1-adamantyl, 2-adamantyl, 1-norbornyl, 2-norbornyl, and the like. Of the above, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl are preferred. In addition, the cycloalkyl group may be optionally substituted.

[0031] Heteroalkyl - As used herein, a heteroalkyl group comprises one or more carbons in an alkyl chain substituted with a heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, a selenium atom, a phosphorus atom, a silicon atom, a germanium atom and a boron atom. The heteroalkyl group may be a heteroalkyl group having 1 to 20 carbon atoms, preferably a heteroalkyl group having 1 to 10 carbon atoms, and more preferably a heteroalkyl group having 1 to 6 carbon atoms. Examples of heteroalkyl include methoxymethyl, ethoxymethyl, ethoxyethyl, methylthiomethyl, ethylthiomethyl, ethylthioethyl, methoxymethoxymethyl, ethoxymethoxymethyl, ethoxyethoxyethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, mercaptomethyl, mercaptoethyl, mercaptopropyl, aminomethyl, aminoethyl, aminopropyl, dimethylaminomethyl, trimethylgermanylmethyl, trimethylgermanylethyl, trimethylgermanylisopropyl, dimethylethylgermanylmethyl, dimethylisopropylgermanylmethyl, tert-butyldimethylgermanylmethyl, triethylgermanylmethyl, triethylgermanylethyl, triisopropylgermanylmethyl, triisopropylgermanylethyl, trimethylsilylmethyl, trimethylsilylethyl, trimethylsilylisopropyl, triisopropylsilylmethyl, triisopropylsilylethyl. In addition, heteroalkyl may be optionally substituted.

[0032] Alkenyl - as used herein, encompasses straight chain, branched and cyclic olefin groups. Alkenyl can be an alkenyl containing 2 to 20 carbon atoms, preferably an alkenyl having 2 to 10 carbon atoms. Examples of alkenyl include vinyl, propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl, 1-methylvinyl, styryl, 2,2-diphenylvinyl, 1,2-diphenylvinyl, 1-methylallyl, 1,1-dimethylallyl, 2-methylallyl, 1-phenylallyl, 2-phenylallyl, 3-phenylallyl, 3,3-diphenylallyl, 1,2-dimethylallyl, 1-phenyl-1-butenyl, 3-phenyl-1-butenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cycloheptenyl, cycloheptatrienyl, cyclooctenyl, cyclooctatetraenyl and norbornenyl. Additionally, alkenyl groups may be optionally substituted.

[0033] Alkynyl - As used herein, straight chain alkynyl groups are encompassed. The alkynyl group may be an alkynyl group containing 2 to 20 carbon atoms, preferably an alkynyl group having 2 to 10 carbon atoms. Examples of alkynyl groups include ethynyl, propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3,3-dimethyl-1-butynyl, 3-ethyl-3-methyl-1-pentynyl, 3,3-diisopropyl-1-pentynyl, phenylethynyl, phenylpropynyl, etc. Among the above, ethynyl, propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, phenylethynyl, etc. are preferred. In addition, the alkynyl group may be optionally substituted.

[0034] Aryl or aromatic group - As used herein, both non-fused and fused systems are contemplated. The aryl group may be an aryl group having 6 to 30 carbon atoms, preferably an aryl group having 6 to 20 carbon atoms, and more preferably an aryl group having 6 to 12 carbon atoms. Examples of aryl groups include phenyl, biphenyl, terphenyl, triphenylene, tetraphenylene, naphthalene, anthracene, phenanthrene, phenanthrene, fluorene, pyrene, chrysene, perylene and azulene, preferably phenyl, biphenyl, terphenyl, triphenylene, fluorene and naphthalene. Examples of non-fused aryl groups include phenyl, biphenyl-2-yl, biphenyl-3-yl, biphenyl-4-yl, p-terphenyl-4-yl, p-terphenyl-3-yl, p-terphenyl-2-yl, m-terphenyl-4-yl, m-terphenyl-3-yl, m-terphenyl-2-yl, o-tolyl, m-tolyl, p-tolyl, p-(2-phenylpropyl)phenyl, 4'-methylbiphenyl, 4''-tert-butyl-p-terphenyl-4-yl, o-cumyl, m-cumyl, p-cumyl, 2,3-xylyl, 3,4-xylyl, 2,5-xylyl, mesityl and m-quadrenyl. In addition, the aryl group may be optionally substituted.

[0035] Heterocyclic group or heterocycle - As used herein, non-aromatic cyclic groups are contemplated. Non-aromatic heterocyclic groups include saturated heterocyclic groups having 3-20 ring atoms and unsaturated non-aromatic heterocyclic groups having 3-20 ring atoms, wherein at least one ring atom is selected from the group consisting of nitrogen atoms, oxygen atoms, sulfur atoms, selenium atoms, silicon atoms, phosphorus atoms, germanium atoms and boron atoms, and preferred non-aromatic heterocyclic groups are those having 3 to 7 ring atoms, which include at least one heteroatom such as nitrogen, oxygen, silicon or sulfur. Examples of non-aromatic heterocyclic groups include oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxopentanyl, dioxanyl, aziridinyl, dihydropyrrolyl, tetrahydropyrrolyl, piperidinyl, oxazolidinyl, morpholinyl, piperazinyl, oxepinyl, thiepinyl, azepine and tetrahydrothiolyl. Additionally, the heterocyclyl group may be optionally substituted.

[0036] Heteroaryl - As used herein, non-fused and fused heteroaromatic groups may contain 1 to 5 heteroatoms, wherein at least one heteroatom is selected from the group consisting of nitrogen atom, oxygen atom, sulfur atom, selenium atom, silicon atom, phosphorus atom, germanium atom and boron atom. Heteroaryl also refers to heteroaryl. The heteroaryl may be a heteroaryl having 3 to 30 carbon atoms, preferably a heteroaryl having 3 to 20 carbon atoms, and more preferably a heteroaryl having 3 to 12 carbon atoms. Suitable heteroaryl groups include dibenzothiophene, dibenzofuran, dibenzoselenophene, furan, thiophene, benzofuran, benzothiophene, benzoselenophene, carbazole, indole, carbazole, pyridine, indole, pyrrolopyridine, pyrazole, imidazole, triazole, oxazole, thiazole, oxadiazole, oxatriazole, dioxazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, oxazine, oxathiazine, oxadiazine, indole, benzimidazole, indazole, indenozine, benzoxazole, benzisoxazole, benzothiazole, quinoline, isoquinoline, In some embodiments, the heteroaryl group is substituted with 1,2-azaborine, 1,3-azaborine, 1,4-azaborine, borazole and its aza analogs. In some embodiments, the heteroaryl group is substituted with 1,2-azaborine, 1,3-azaborine, 1,4-azaborine, borazole and its aza analogs. In some embodiments, the heteroaryl group is substituted with 1,2-azaborine, 1,3-azaborine, 1,4-azaborine, borazole and its aza analogs. In addition, the heteroaryl group may be optionally substituted.

[0037] Alkoxy - as used herein, represented by -O-alkyl, -O-cycloalkyl, -O-heteroalkyl or -O-heterocyclyl. Examples and preferred examples of alkyl, cycloalkyl, heteroalkyl and heterocyclyl are the same as described above. The alkoxy group may be an alkoxy group having 1 to 20 carbon atoms, preferably an alkoxy group having 1 to 6 carbon atoms. Examples of the alkoxy group include methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuranyloxy, tetrahydropyranyloxy, methoxypropyloxy, ethoxyethyloxy, methoxymethyloxy and ethoxymethyloxy. In addition, the alkoxy group may be optionally substituted.

[0038] Aryloxy - as used herein, represented by -O-aryl or -O-heteroaryl. Examples and preferred examples of aryl and heteroaryl are the same as above. The aryloxy may be an aryloxy having 6 to 30 carbon atoms, preferably an aryloxy having 6 to 20 carbon atoms. Examples of the aryloxy include phenoxy and biphenyloxy. In addition, the aryloxy may be optionally substituted.

[0039] Aralkyl - As used herein, aryl-substituted alkyl groups are encompassed. The aralkyl group may be an aralkyl group having 7 to 30 carbon atoms, preferably an aralkyl group having 7 to 20 carbon atoms, and more preferably an aralkyl group having 7 to 13 carbon atoms. Examples of aralkyl groups include benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylisopropyl, 2-phenylisopropyl, phenyl tert-butyl, α-naphthylmethyl, 1-α-naphthyl-ethyl, 2-α-naphthylethyl, 1-α-naphthylisopropyl, 2-α-naphthylisopropyl, β-naphthylmethyl, 1-β-naphthyl-ethyl, 2-β-naphthyl-ethyl, 1-β-naphthylisopropyl, 2-β-naphthylisopropyl, p-methylbenzyl, m-methylbenzyl, substituted alkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl, arylalkyl,

[0040] Alkylsilyl - As used herein, alkyl-substituted silicon groups are contemplated. The alkylsilyl group may be an alkylsilyl group having 3 to 20 carbon atoms, preferably an alkylsilyl group having 3 to 10 carbon atoms. Examples of the alkylsilyl group include trimethylsilyl, triethylsilyl, methyldiethylsilyl, ethyldimethylsilyl, tripropylsilyl, tributylsilyl, triisopropylsilyl, methyldiisopropylsilyl, dimethylisopropylsilyl, tri-tert-butylsilyl, triisobutylsilyl, dimethyltert-butylsilyl, methyldi-tert-butylsilyl. In addition, the alkylsilyl group may be optionally substituted.

[0041] Arylsilyl - As used herein, encompasses at least one aryl-substituted silicon group. The arylsilyl group may be an arylsilyl group having 6 to 30 carbon atoms, preferably an arylsilyl group having 8 to 20 carbon atoms. Examples of the arylsilyl group include triphenylsilyl, phenyldibiphenylsilyl, diphenylbiphenylsilyl, phenyldiethylsilyl, diphenylethylsilyl, phenyldimethylsilyl, diphenylmethylsilyl, phenyldiisopropylsilyl, diphenylisopropylsilyl, diphenylbutylsilyl, diphenylisobutylsilyl, diphenyltert-butylsilyl. In addition, the arylsilyl group may be optionally substituted.

[0042] Alkylgermanyl - As used herein, alkyl-substituted germanyl is contemplated. The alkylgermanyl may be an alkylgermanyl having 3 to 20 carbon atoms, preferably an alkylgermanyl having 3 to 10 carbon atoms. Examples of the alkylgermanyl include trimethylgermanyl, triethylgermanyl, methyldiethylgermanyl, ethyldimethylgermanyl, tripropylgermanyl, tributylgermanyl, triisopropylgermanyl, methyldiisopropylgermanyl, dimethylisopropylgermanyl, tri-tert-butylgermanyl, triisobutylgermanyl, dimethyltert-butylgermanyl, methyldi-tert-butylgermanyl. In addition, the alkylgermanyl may be optionally substituted.

[0043] Arylgermanyl - As used herein, germanyl groups substituted with at least one aryl or heteroaryl group are contemplated. The arylgermanyl group may be an arylgermanyl group having 6 to 30 carbon atoms, preferably an arylgermanyl group having 8 to 20 carbon atoms. Examples of arylgermanyl groups include triphenylgermanyl, phenyldibiphenylgermanyl, diphenylbiphenylgermanyl, phenyldiethylgermanyl, diphenylethylgermanyl, phenyldimethylgermanyl, diphenylmethylgermanyl, phenyldiisopropylgermanyl, diphenylisopropylgermanyl, diphenylbutylgermanyl, diphenylisobutylgermanyl, diphenyltert-butylgermanyl. In addition, the arylgermanyl group may be optionally substituted.

[0044] The term "aza" in azadibenzofuran, azadibenzothiophene, etc. means that one or more CH groups in the corresponding aromatic fragment are replaced by a nitrogen atom. For example, azatriphenylene includes dibenzo[f,h]quinoxaline, dibenzo[f,h]quinoline and other analogs having two or more nitrogens in the ring system. Other nitrogen analogs of the above-mentioned aza derivatives can be easily thought of by those of ordinary skill in the art, and all such analogs are determined to be included in the terms described herein.

[0045] In the present disclosure, unless otherwise defined, when any one of the terms in the group consisting of substituted alkyl, substituted cycloalkyl, substituted heteroalkyl, substituted heterocyclyl, substituted aralkyl, substituted alkoxy, substituted aryloxy, substituted alkenyl, substituted alkynyl, substituted aryl, substituted heteroaryl, substituted alkylsilyl, substituted arylsilyl, substituted alkylgermanyl, substituted arylgermanyl, substituted amino, substituted acyl, substituted carbonyl, substituted carboxylic acid, Substituted ester groups, substituted sulfinyl groups, substituted sulfonyl groups, substituted phosphino groups refer to any one of alkyl groups, cycloalkyl groups, heteroalkyl groups, heterocyclic groups, aralkyl groups, alkoxy groups, aryloxy groups, alkenyl groups, alkynyl groups, aryl groups, heteroaryl groups, alkylsilyl groups, arylsilyl groups, alkylgermanyl groups, arylgermanyl groups, amino groups, acyl groups, carbonyl groups, carboxyl groups, ester groups, sulfinyl groups, sulfonyl groups and phosphino groups, which may be substituted by one or more of deuterium, halogen groups, unsubstituted alkyl groups having 1 to 20 carbon atoms, unsubstituted alkyl groups having 1 to 20 carbon atoms, Cycloalkyl having 3-20 ring carbon atoms, unsubstituted heteroalkyl having 1-20 carbon atoms, unsubstituted heterocyclyl having 3-20 ring atoms, unsubstituted aralkyl having 7-30 carbon atoms, unsubstituted alkoxy having 1-20 carbon atoms, unsubstituted aryloxy having 6-30 carbon atoms, unsubstituted alkenyl having 2-20 carbon atoms, unsubstituted alkynyl having 2-20 carbon atoms, unsubstituted aryl having 6-30 carbon atoms , unsubstituted heteroaryl having 3 to 30 carbon atoms, unsubstituted alkylsilyl having 3 to 20 carbon atoms, unsubstituted arylsilyl having 6 to 20 carbon atoms, unsubstituted alkylgermanyl having 3 to 20 carbon atoms, unsubstituted arylgermanyl having 6 to 20 carbon atoms, unsubstituted amino having 0 to 20 carbon atoms, acyl, carbonyl, carboxylic acid, ester, cyano, isocyano, hydroxyl, mercapto, sulfinyl, sulfonyl, phosphino and combinations thereof.

[0046] It should be understood that when a molecular fragment is described as a substituent or otherwise attached to another moiety, its name can be written according to whether it is a fragment (e.g., phenyl, phenylene, naphthyl, dibenzofuranyl) or according to whether it is a whole molecule (e.g., benzene, naphthalene, dibenzofuran). As used herein, these different ways of specifying a substituent or attaching a fragment are considered equivalent.

[0047] In the compounds mentioned in this disclosure, hydrogen atoms may be partially or completely replaced by deuterium. Other atoms such as carbon and nitrogen may also be replaced by their other stable isotopes. The replacement of other stable isotopes in the compounds may be preferred because it enhances the efficiency and stability of the device.

[0048] In the compounds mentioned in the present disclosure, polysubstitution refers to the range including disubstitution up to the maximum number of available substitutions. When a substituent in the compounds mentioned in the present disclosure represents polysubstitution (including disubstitution, trisubstitution, tetrasubstitution, etc.), it means that the substituent can exist in multiple available substitution positions on its connection structure, and the substituent existing in multiple available substitution positions can be the same structure or different structures.

[0049] In the compounds mentioned in the present disclosure, unless explicitly defined, for example, adjacent substituents can be optionally connected to form a ring, the adjacent substituents in the compound cannot be connected to form a ring. In the compounds mentioned in the present disclosure, adjacent substituents can be optionally connected to form a ring, including both the situation where adjacent substituents can be connected to form a ring and the situation where adjacent substituents are not connected to form a ring. When adjacent substituents can be optionally connected to form a ring, the formed ring can be a monocyclic or polycyclic ring (including spirocyclic rings, bridged rings, condensed rings, etc.), as well as alicyclic rings, heteroalicyclic rings, aromatic rings or heteroaromatic rings. In this statement, adjacent substituents can refer to substituents bonded to the same atom, substituents bonded to carbon atoms directly bonded to each other, or substituents bonded to carbon atoms further away. Preferably, adjacent substituents refer to substituents bonded to the same carbon atom and substituents bonded to carbon atoms directly bonded to each other.

[0050] The expression that adjacent substituents can be optionally linked to form a ring is also intended to be taken to mean that two substituents bonded to the same carbon atom are linked to each other by a chemical bond to form a ring, which can be exemplified by the following formula:

[0051] .

[0052] The expression that adjacent substituents can be optionally linked to form a ring is also intended to be taken to mean that two substituents bonded to carbon atoms directly bonded to each other are linked to each other by a chemical bond to form a ring, which can be exemplified by the following formula:

[0053] .

[0054] The expression that adjacent substituents can be optionally linked to form a ring is also intended to be taken to mean that two substituents bonded to a further distant carbon atom are linked to each other by a chemical bond to form a ring, which can be exemplified by the following formula:

[0055] .

[0056] Furthermore, the statement that adjacent substituents can optionally be linked to form a ring is also intended to be taken to mean that, in the case where one of the two adjacent substituents represents hydrogen, the second substituent is bonded at the position to which the hydrogen atom is bonded, thereby forming a ring. This is exemplified by the following formula:

[0057] .

[0058] According to one embodiment of the present invention, a method for synthesizing a diaryl sulfoxide derivative is disclosed. The diaryl sulfoxide derivative has a structure shown in Formula 1:

[0059] ,

[0060] The synthesis method comprises the following steps:

[0061] The Grignard reagent B, the zinc reagent, and the dichlorothionyl react in the solvent M to generate the diaryl sulfoxide derivative;

[0062] The solvent M is an organic solvent;

[0063] The Grignard reagent B has a structure shown in Formula 2:

[0064] ,

[0065] In Formula 2, X is selected from chlorine, bromine or iodine;

[0066] In equation 1 and equation 2,

[0067] Ring A is selected from a heteroaromatic ring having 3 to 30 carbon atoms, an aromatic ring having 6 to 30 carbon atoms, or a combination thereof;

[0068] R A Indicates single substitution, multiple substitution or no substitution; when there are multiple R on the same ring A A When the R A It can be the same or different;

[0069] R A The group consisting of hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof;

[0070] Adjacent substituent RA Can optionally be linked to form a ring.

[0071] In this context, adjacent substituents R A can be optionally connected to form a ring, which is intended to indicate that any adjacent substituents R A Obviously, any adjacent substituents R A They can also not be connected to form a ring.

[0072] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0073] According to one embodiment of the present invention, the Grignard reagent B is first reacted with the zinc reagent in an organic solvent M for 0.1-5 hours, for example, 0.1 hour, 0.2 hour, 0.3 hour, 0.4 hour, 0.5 hour, 0.6 hour, 0.7 hour, 0.8 hour, 0.9 hour, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, and then reacted with thionyl chloride to generate the diaryl sulfoxide derivative.

[0074] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M for 0.2-4 hours, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0075] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M for 0.3-3 hours, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0076] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M for 0.5-3 hours, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0077] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M for 0.5-2 hours, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0078] According to one embodiment of the present invention, the Grignard reagent B first reacts with the zinc reagent in an organic solvent M for 0.5-1 hour, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative.

[0079] According to one embodiment of the present invention, the zinc reagent is selected from wherein the zinc reagent is selected from zinc salt or zinc complex.

[0080] According to one embodiment of the present invention, the zinc reagent is selected from ZnY2 or LZnY2, wherein Y is selected from chlorine, bromine, iodine or pivalate; and L is selected from ethylenediamine derivatives.

[0081] According to one embodiment of the present invention, the zinc reagent is selected from (N,N,N',N'-tetramethylethylenediamine)zinc dichloride (CAS No.: 28308-00-1).

[0082] According to one embodiment of the present invention, the Grignard reagent B and the zinc reagent react in a solvent M to generate a compound C, which then reacts with thionyl chloride to generate the diaryl sulfoxide derivative;

[0083] The solvent M is an organic solvent;

[0084] The compound C has a structure represented by Formula 4:

[0085] ,

[0086] Ring A is selected from a heteroaromatic ring having 3 to 30 carbon atoms, an aromatic ring having 6 to 30 carbon atoms, or a combination thereof;

[0087] R A Indicates single substitution, multiple substitution or no substitution; when there are multiple R on the same ring A A When the R A It can be the same or different;

[0088] R A The group consisting of hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof;

[0089] Adjacent substituent R A Can optionally be linked to form a ring.

[0090] According to one embodiment of the present invention, the Grignard reagent B is generated by the reaction of compound A and magnesium;

[0091] The compound A has a structure shown in Formula 3:

[0092] ,

[0093] In Formula 3, X is selected from chlorine, bromine or iodine;

[0094] Ring A is selected from a heteroaromatic ring having 3 to 30 carbon atoms, an aromatic ring having 6 to 30 carbon atoms, or a combination thereof;

[0095] R A Indicates single substitution, multiple substitution or no substitution;

[0096] R A The group consisting of hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof;

[0097] Adjacent substituent R A Can optionally be linked to form a ring.

[0098] According to one embodiment of the present invention, ring A is selected from a heteroaromatic ring having 3 to 20 carbon atoms, an aromatic ring having 6 to 20 carbon atoms, or a combination thereof.

[0099] According to one embodiment of the present invention, ring A is selected from a benzene ring, a naphthalene ring, a phenanthrene ring, an azabenzene ring, an azanaphthalene ring, an azaphenanthrene ring, or a combination thereof.

[0100] According to one embodiment of the present invention, the diaryl sulfoxide derivative has a structure shown by Formula 1-1 or Formula 1-2:

[0101] , ,

[0102] Wherein, in Formula 1-1, A1 to A5 are selected from CR Aor N; in formula 1-2, A1 to A7 are selected from CR A or N;

[0103] R A The group consisting of hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof;

[0104] Adjacent substituent R A Can optionally be linked to form a ring.

[0105] According to one embodiment of the present invention, X is selected from bromine.

[0106] According to one embodiment of the present invention, in Formula 1-1, at least one of A1 to A5 is selected from CR A In formula 1-2, at least one of A1 to A7 is selected from CR A ;

[0107] The R A Each is independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted alkyl having 1 to 20 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1 to 20 carbon atoms, substituted or unsubstituted heterocyclyl having 3 to 20 ring atoms, substituted or unsubstituted aralkyl having 7 to 30 carbon atoms, substituted or unsubstituted alkoxy having 1 to 20 carbon atoms, substituted or unsubstituted substituted or unsubstituted aryloxy groups having 6 to 30 carbon atoms, substituted or unsubstituted aryl groups having 6 to 30 carbon atoms, substituted or unsubstituted heteroaryl groups having 3 to 30 carbon atoms, substituted or unsubstituted alkylsilyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylsilanyl groups having 6 to 20 carbon atoms, substituted or unsubstituted alkylgermanyl groups having 3 to 20 carbon atoms, substituted or unsubstituted arylgermanyl groups having 6 to 20 carbon atoms, and combinations thereof.

[0108] According to one embodiment of the present invention, in Formula 1-1 and Formula 1-2, at least one of A1 to A4 is selected from CR A .

[0109] According to one embodiment of the present invention, in Formula 1-1 and Formula 1-2, A2 and / or A4 are selected from CR A .

[0110] According to one embodiment of the present invention, R A Each is independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1-20 carbon atoms, substituted or unsubstituted cycloalkyl having 3-20 ring carbon atoms, substituted or unsubstituted heteroalkyl having 1-20 carbon atoms, substituted or unsubstituted heterocyclyl having 3-20 ring atoms, substituted or unsubstituted aryl having 6-30 carbon atoms, substituted or unsubstituted heteroaryl having 3-30 carbon atoms, substituted or unsubstituted alkylsilyl having 3-20 carbon atoms, substituted or unsubstituted arylsilyl having 6-20 carbon atoms, and combinations thereof.

[0111] According to one embodiment of the present invention, R A Each is independently selected from hydrogen, deuterium, fluorine, methyl, isopropyl, 2-butyl, isobutyl, tert-butyl, pent-3-yl, cyclopentyl, cyclohexyl, 4,4-dimethylcyclohexyl, neopentyl, 2,4-dimethylpent-3-yl, 3,3,3-trifluoro-2,2-dimethylpropyl, 1,1-dimethylsilan-4-yl, cyclopentylmethyl, cyanomethyl, trifluoromethyl, trimethylsilyl, phenyldimethylsilyl, phenyl, 3-pyridyl, or a combination thereof.

[0112] According to one embodiment of the present invention, the diaryl sulfoxide derivative is selected from the group consisting of Compound 1 to Compound 37, and the specific structures of Compound 1 to Compound 37 are shown below:

[0113] , , , ,

[0114] , , , ,

[0115] , , , ,

[0116] , , , , , , ,

[0117] , , , , , , , , , , , ,

[0118] , , ,

[0119] , , .

[0120] According to one embodiment of the present invention, the hydrogen in the structures of Compounds 1 to 37 can be partially or completely replaced by deuterium.

[0121] According to one embodiment of the present invention, the organic solvent M is an aprotic solvent.

[0122] According to one embodiment of the present invention, the organic solvent M is any one of an ether solvent and a hydrocarbon solvent, or a combination of two of them.

[0123] According to one embodiment of the present invention, the organic solvent M is selected from any one of tetrahydrofuran, 2-methyltetrahydrofuran, toluene, n-heptane, and diethyl ether, or a combination of at least two thereof.

[0124] According to one embodiment of the present invention, the organic solvent M is ultra-dry tetrahydrofuran.

[0125] According to one embodiment of the present invention, the step of generating the Grignard reagent B further comprises an organic solvent N.

[0126] According to one embodiment of the present invention, the organic solvent N is an aprotic solvent.

[0127] According to one embodiment of the present invention, the organic solvent N is an ether solvent.

[0128] According to one embodiment of the present invention, the organic solvent N is selected from any one of tetrahydrofuran and 2-methyltetrahydrofuran, or a combination of two thereof.

[0129] According to one embodiment of the present invention, the organic solvent N is ultra-dry tetrahydrofuran.

[0130] According to one embodiment of the present invention, the amount of the zinc reagent is 0.1-10 times the amount of thionyl chloride, for example, 0.2 times, 0.3 times, 0.4 times, 0.5 times, 0.6 times, 0.7 times, 0.8 times, 0.9 times, 1 times, 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 2.0 times, 2. 1 times, 2.2 times, 2.3 times, 2.4 times, 2.5 times, 2.6 times, 2.7 times, 2.8 times, 2.9 times, 3.0 times, 3.1 times, 3.2 times, 3.3 times, 3.4 times, 3.5 times, 3.6 times, 3.7 times, 3.8 times, 3.9 times, 4.0 times, 4.5 times, 5.0 times, 5.5 times, 6.0 times, 6.5 times, 7.0 times, 8.5 times, 9.0 times, 9.5 times.

[0131] According to one embodiment of the present invention, the amount of the zinc reagent is 0.5-5 times the amount of thionyl chloride.

[0132] According to one embodiment of the present invention, the amount of the zinc reagent is 0.5-3 times the amount of thionyl chloride.

[0133] According to one embodiment of the present invention, the amount of the zinc reagent is 0.5-2 times the amount of thionyl chloride.

[0134] According to one embodiment of the present invention, the amount of the zinc reagent is 0.5-1.5 times the amount of thionyl chloride.

[0135] According to one embodiment of the present invention, the amount of the zinc reagent is 0.8-1.5 times the amount of thionyl chloride.

[0136] According to one embodiment of the present invention, the amount of the zinc reagent is 1.0-1.3 times the amount of thionyl chloride.

[0137] According to one embodiment of the present invention, the amount of the zinc reagent is 1.1-1.3 times the amount of thionyl chloride.

[0138] According to one embodiment of the present invention, the amount of the zinc reagent is 1.1 times the amount of thionyl chloride.

[0139] According to one embodiment of the present invention, the amount of compound A is 1-10 times the amount of thionyl chloride, for example, it can be 1 time, 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 2.0 times, 2.1 times, 2.2 times, 2.3 times, 2.4 times, 2.5 times, 2.6 times, 2.7 times, 2.8 times, 2.9 times, 3.0 times, 3.1 times, 3.2 times, 3.3 times, 3.4 times, 3.5 times, 3.6 times, 3.7 times, 3.8 times, 3.9 times, 4.0 times, 4.5 times, 5.0 times, 5.5 times, 6.0 times, 6.5 times, 7.0 times, 8.5 times, 9.0 times, 9.5 times.

[0140] According to one embodiment of the present invention, the amount of the compound A is 1.5-3 times the amount of thionyl chloride.

[0141] According to one embodiment of the present invention, the amount of the compound A is 1.5-2.5 times the amount of thionyl chloride.

[0142] According to one embodiment of the present invention, the amount of the compound A is 2.0-3.0 times the amount of thionyl chloride.

[0143] According to one embodiment of the present invention, the amount of the compound A is 2.0-2.2 times the amount of thionyl chloride.

[0144] According to one embodiment of the present invention, the amount of the compound A is 2.0 times the amount of thionyl chloride.

[0145] According to one embodiment of the present invention, the reaction temperature of the Grignard reagent B and the zinc reagent is 0-50 degrees Celsius. For example, the reaction temperature can be 5 degrees Celsius, 10 degrees Celsius, 15 degrees Celsius, 20 degrees Celsius, 21 degrees Celsius, 22 degrees Celsius, 23 degrees Celsius, 24 degrees Celsius, 25 degrees Celsius, 26 degrees Celsius, 27 degrees Celsius, 28 degrees Celsius, 29 degrees Celsius, 30 degrees Celsius, 31 degrees Celsius, 32 degrees Celsius, 33 degrees Celsius, 34 degrees Celsius, 35 degrees Celsius, 36 degrees Celsius, 37 degrees Celsius, 38 degrees Celsius, 39 degrees Celsius, 40 degrees Celsius, 45 degrees Celsius.

[0146] According to one embodiment of the present invention, the compound A and magnesium react at room temperature to 50 degrees Celsius.

[0147] According to one embodiment of the present invention, the compound A and magnesium react at 20-30 degrees Celsius.

[0148] According to one embodiment of the present invention, the compound A and magnesium react at 20-25 degrees Celsius.

[0149] According to one embodiment of the present invention, the compound A and magnesium react at room temperature.

[0150] According to one embodiment of the present invention, in the process of reacting the compound A with magnesium to generate the Grignard reagent B, an initiator Q needs to be added.

[0151] According to one embodiment of the present invention, the initiator Q is selected from halogenated alkanes or halogen elements.

[0152] According to one embodiment of the present invention, the initiator Q is selected from 1,2-dibromoethane or iodine.

[0153] According to one embodiment of the present invention, the initiator Q initiates the Grignard reaction at low temperature.

[0154] According to one embodiment of the present invention, the initiator Q initiates the Grignard reaction at -3-0 degrees Celsius.

[0155] According to one embodiment of the present invention, the yield of the diaryl sulfoxide derivative is greater than 75%, for example, it can be 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%.

[0156] According to one embodiment of the present invention, the yield of the diaryl sulfoxide derivative is greater than 80%.

[0157] According to one embodiment of the present invention, the yield of the diaryl sulfoxide derivative is greater than 81%.

[0158] According to one embodiment of the present invention, after the Grignard reagent B, the zinc reagent, and the dithionyl chloride are completely reacted in the solvent M, the aminocarboxylate complex solution is added.

[0159] According to one embodiment of the present invention, after the Grignard reagent B, the zinc reagent, and the dithionyl chloride are completely reacted in the solvent M, an EDTA salt complex solution is added.

[0160] According to one embodiment of the present invention, after the Grignard reagent B, the zinc reagent, and the dithionyl chloride are completely reacted in the solvent M, a tetrasodium ethylenediaminetetraacetic acid solution is added.

[0161] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0162] In the embodiment of material synthesis, unless otherwise stated, all reactions are carried out under nitrogen protection. All reaction solvents are anhydrous and used as they are from commercial sources. The synthetic product uses one or more equipment conventional in the art (including but not limited to Bruker's nuclear magnetic resonance instrument, Shimadzu's liquid chromatograph, liquid chromatography-mass spectrometer, gas chromatography-mass spectrometer, differential scanning calorimeter, Shanghai Lingguang Technology's fluorescence spectrophotometer, Wuhan Cost's electrochemical workstation, Anhui Bei Yi Ke's sublimator, etc.), and the method well known to those skilled in the art is used to confirm the structure and test the characteristics.

[0163] Example 1: Synthesis of Compound 5

[0164] Step 1: Synthesis of intermediate 1

[0165]

[0166] Under nitrogen protection, ultra-dry tetrahydrofuran (20 mL) and magnesium chips (0.53 g, 22 mmol) were added to a 150 mL three-necked flask, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (0.009 g, 0.05 mmol) and 3,5-difluorobromobenzene (0.19 g, 1 mmol) were added. After the addition was completed, the mixture was stirred at 3-0 o C, and after the Grignard reaction was initiated, 3,5-difluorobromobenzene (3.66 g, 19 mmol) was added dropwise and the temperature was raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 1, which was directly used in the next step without purification.

[0167] Step 2: Synthesis of compound 5

[0168]

[0169] Under nitrogen protection, add ultra-dry tetrahydrofuran (20 mL) to a 250 mL three-necked flask, transfer the Grignard reagent to the flask, add (N,N,N',N'-tetramethylethylenediamine)zinc dichloride (2.77 g, 11 mmol), and stir at 20-25 o C for 1 h, and then cool the three-necked flask to -11 to -7 oC, add thionyl chloride (1.18 g, 10 mmol) dropwise at 20-25 o C for 12 h. After the reaction is complete, add ethylenediaminetetraacetic acid tetrasodium aqueous solution (10%, 20 mL) to the three-necked flask, then add 10 mL of toluene to separate the organic phase; wash the organic phase with sodium chloride solution (10%, 20 mL), filter the organic phase, and wash the filter cake with toluene until it is colorless. The organic phase is spin-dried, and 10 mL of n-heptane is added for 20-25 min. o After stirring at 400 °C for 2 h, the mixture was filtered and the solvent was removed to obtain the target product, compound 5 (2.22 g, yield 81%, purity: 99.3%). The product was confirmed to be the target product with a molecular weight of 274.01.

[0170] The relevant liquid phase experimental data of the target product obtained in Example 1 are shown in Table 1 below:

[0171] Table 1

[0172]

[0173] Example 2: Synthesis of Compound 3

[0174] Step 1: Synthesis of intermediate 2

[0175]

[0176] Under nitrogen protection, ultra-dry tetrahydrofuran (20 mL) and magnesium chips (0.53 g, 22 mmol) were added to a 150 mL three-necked flask, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (0.009 g, 0.05 mmol) and 3-trifluoromethylbromobenzene (0.225 g, 1 mmol) were added. After the addition was complete, the mixture was stirred at 3-0 o C. After the Grignard reaction was initiated, 3-trifluoromethylbromobenzene (4.27 g, 19 mmol) was added dropwise and the temperature was raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 2, which was directly used in the next step without purification.

[0177] Step 2: Synthesis of compound 3

[0178]

[0179] Add ultra-dry tetrahydrofuran (20 mL) to a 250 mL three-necked flask, transfer the Grignard reagent to the flask, add (N,N,N',N'-tetramethylethylenediamine)zinc dichloride (2.77 g, 11 mmol), and stir at 20-25 o C for 1 h, and then cool the three-necked flask to -11 to -7 oC, add thionyl chloride (1.18 g, 10 mmol) dropwise at 20-25 o C for 12 h. After the reaction is complete, add ethylenediaminetetraacetic acid tetrasodium aqueous solution (10%, 20 mL) to the three-necked flask, then add 10 mL of toluene to separate the organic phase; wash the organic phase with sodium chloride solution (10%, 20 mL), filter the organic phase, and wash the filter cake with toluene until it is colorless. The organic phase is spin-dried, and 10 mL of n-heptane is added for 20-25 min. o After stirring at 400 °C for 2 h, the mixture was filtered and the solvent was removed to obtain the target product, compound 3 (2.74 g, yield 81%, purity: 98.6%). The product was confirmed to be the target product with a molecular weight of 338.02.

[0180] The relevant liquid phase experimental data of the target product obtained in Example 2 are shown in Table 2 below:

[0181] Table 2

[0182]

[0183] Example 3: Synthesis of Compound 9

[0184] Step 1: Synthesis of intermediate 3

[0185]

[0186] Under nitrogen protection, ultra-dry tetrahydrofuran (20 mL) and magnesium chips (0.53 g, 22 mmol) were added to a 150 mL three-necked flask, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (0.009 g, 0.05 mmol) and 1,5-dimethylbromobenzene (0.185 g, 1 mmol) were added. After the addition was completed, the mixture was stirred at 3-0 o C, and after the Grignard reaction is initiated, 1,5-dimethylbromobenzene (3.51 g, 19 mmol) is added dropwise and the temperature is raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 3, which was directly used in the next step without purification.

[0187] Step 2: Synthesis of compound 9

[0188]

[0189] Under nitrogen protection, add ultra-dry tetrahydrofuran (20 mL) to a 250 mL three-necked flask, transfer the Grignard reagent to the flask, add (N,N,N',N'-tetramethylethylenediamine) zinc dichloride (2.77 g, 11 mmol), and stir at 20-25 o C for 1 h, and cool the three-necked flask to -11 to -7 oC, add thionyl chloride (1.18 g, 10 mmol) dropwise at 20-25 o C for 12 h. After the reaction is complete, add ethylenediaminetetraacetic acid tetrasodium aqueous solution (10%, 20 mL) to the three-necked flask, then add 10 mL of toluene to separate the organic phase; wash the organic phase with sodium chloride solution (10%, 20 mL), filter the organic phase, and wash the filter cake with toluene until it is colorless. The organic phase is spin-dried, and 10 mL of n-heptane is added for 20-25 min. o After stirring at 400 °C for 2 h, the mixture was filtered and the solvent was removed to obtain the target product, compound 9 (2.2 g, yield 85%, purity: 99.0%). The product was confirmed to be the target product with a molecular weight of 258.11.

[0190] The relevant liquid phase experimental data of the target product obtained in Example 3 are shown in Table 3 below:

[0191] Table 3

[0192]

[0193] Example 4: Synthesis of Compound 1

[0194] Step 1: Synthesis of intermediate 4

[0195]

[0196] Under nitrogen protection, ultra-dry tetrahydrofuran (10.9 L) and magnesium chips (0.29 kg, 12.0 mol) were added to a 50 L reactor, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (4.9 g, 26.2 mmol) and 3,5-bis(trifluoromethyl)bromobenzene (0.16 kg, 0.546 mol) were added. After the addition was completed, the mixture was stirred at -3-0 o C, and after the Grignard reaction is initiated, 3,5-bis(trifluoromethyl)bromobenzene (3.05 kg, 10.4 mol) is added dropwise and the temperature is raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 4, which was directly used in the next step without purification.

[0197] Step 2: Synthesis of compound 1

[0198]

[0199] Under nitrogen protection, add 10 L of ultra-dry tetrahydrofuran to a new 50 L reactor, transfer the Grignard reagent to the 50 L reactor, add (N,N,N',N'-tetramethylethylenediamine) zinc dichloride (1.52 kg, 6.02 mol), and heat for 20-25 min. o C for 1 h, and then cool the three-necked flask to -11 to -7o C, add thionyl chloride (0.646 kg, 5.43 mol) dropwise at 20-25 o C for 12 h. After the reaction is complete, add ethylenediaminetetraacetic acid tetrasodium aqueous solution (10%, 5 L) to the three-necked flask, then add 2 L of toluene to separate the organic phase; wash the organic phase with sodium chloride solution (10%, 5 L), filter the organic phase, and wash the filter cake with toluene until it is colorless. The organic phase is spin-dried and 2 L of n-heptane is added for 20-25 min. o After stirring at 400 °C for 2 h, the mixture was filtered and the solvent was removed to obtain the target product, compound 1 (2.1 kg, yield 81%, purity: 99.9%). The product was confirmed to be the target product with a molecular weight of 473.99.

[0200] The relevant liquid phase experimental data of the target product obtained in Example 4 are shown in Table 4 below:

[0201] Table 4

[0202]

[0203] Comparative Example 1: Synthesis of Compound 5

[0204] Step 1: Synthesis of intermediate 1

[0205]

[0206] Under nitrogen protection, ultra-dry tetrahydrofuran (20 mL) and magnesium chips (0.53 g, 20 mmol) were added to a 150 mL three-necked flask, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (0.009 g, 0.05 mmol) and 3,5-difluorobromobenzene (0.19 g, 1 mmol) were added. After the addition was completed, the mixture was stirred at 3-0 o C, and after the Grignard reaction was initiated, 3,5-difluorobromobenzene (3.61 g, 19 mmol) was added dropwise and the temperature was raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 1, which was directly used in the next step without purification.

[0207] Step 2: Synthesis of compound 5

[0208]

[0209] Under nitrogen protection, add ultra-dry tetrahydrofuran (20 mL) to a 250 mL three-necked flask, transfer the Grignard reagent to the flask and cool to -11 to -7 o C, add thionyl chloride (1.18 g, 10 mmol) dropwise at 20-25 oC for 12 h. After the reaction was complete, 10 mL of water was added to quench the reaction. The aqueous phase was extracted three times with dichloromethane (20 mL). After the organic phases were combined, they were washed with saturated sodium bicarbonate solution (50 mL), dried over anhydrous sodium sulfate, and finally the target product, compound 5 (1.23 g, yield 45%, purity: 88.6%), was obtained by column chromatography. The product was confirmed to be the target product with a molecular weight of 274.01.

[0210] The relevant liquid phase experimental data of the target product obtained in Comparative Example 1 are shown in Table 5 below:

[0211] Table 5

[0212]

[0213] Comparative Example 2: Synthesis of Compound 1

[0214] Step 1: Synthesis of intermediate 4

[0215]

[0216] Under nitrogen protection, ultra-dry tetrahydrofuran (20 mL) and magnesium chips (0.53 g, 20 mmol) were added to a 150 mL three-necked flask, and the nitrogen was replaced three times. Then, 1,2-dibromoethane (0.009 g, 1 mmol) and 3,5-bis(trifluoromethyl)bromobenzene (0.293 g, 1 mmol) were added. After the addition was complete, the mixture was stirred at 3-0 o C. After the Grignard reaction was initiated, 3,5-bis(trifluoromethyl)bromobenzene (5.56 g, 19 mmol) was added dropwise and the temperature was raised to 20-25 o C and stirred for 2 h to obtain a tetrahydrofuran solution of intermediate 4, which was directly used in the next step without purification.

[0217] Step 2: Synthesis of compound 1

[0218]

[0219] Under nitrogen protection, add ultra-dry tetrahydrofuran (20 mL) to a new 250 mL three-necked flask, transfer the Grignard reagent to the flask and cool to -11 to -7 o C, add thionyl chloride (1.18 g, 10 mmol) dropwise at 20-25 o C for 12 h. After the reaction is complete, add ethylenediaminetetraacetic acid tetrasodium aqueous solution (10%, 20 mL) to the three-necked flask, then add 10 mL of toluene to separate the organic phase; wash the organic phase with sodium chloride solution (10%, 20 mL), filter the organic phase, and wash the filter cake with toluene until it is colorless. The organic phase is spin-dried, and 10 mL of n-heptane is added for 20-25 min. oAfter stirring at 40 °C for 2 h, the mixture was filtered and the solvent was removed to obtain the target product, compound 1 (2.04 g, yield 43%, purity: 95.2%). The product was confirmed to be the target product with a molecular weight of 473.99.

[0220] The relevant liquid phase experimental data of the target product obtained in Comparative Example 2 are shown in Table 6 below:

[0221] Table 6

[0222]

[0223] discuss:

[0224] Comparative Example 1 and Comparative Example 2 adopt the prior art Chem. Eur. J. 2022, 28, e202202564l, Jordan Berreur et al. disclosed the synthesis method using Grignard reagent. The difference between Example 4 and Comparative Example 2 is whether (N, N, N', N'-tetramethylethylenediamine) zinc dichloride is added in step 2. Compared with Comparative Example 2, the yield of Example 4 is greatly improved by 88%, and the purity of the final product obtained is further improved on the basis of the high purity of Comparative Example 1. The difference between Example 1 and Comparative Example 1 is whether (N, N, N', N'-tetramethylethylenediamine) zinc dichloride is added in step 2, and the post-treatment method is different. Compared with Comparative Example 1, the yield of Example 1 is greatly improved by 80%, and the purity of the final product is improved by 12%; by adding (N, N, N', N'-tetramethylethylenediamine) zinc dichloride in step 2, a high yield and high purity final product can be obtained by simple post-treatment. These data show that the system with (N,N,N',N'-tetramethylethylenediamine) zinc dichloride has few by-products, and a high-purity, high-yield final product can be obtained through simple post-treatment, and the purification process is simple and low-cost, indicating the unexpected excellence of the synthesis method disclosed in the present invention.

[0225] In Examples 2 and 3, diaryl sulfoxide derivatives with different types of substituents were synthesized, and high yields (yields of 81%-85%) and high purity final products were obtained through simple post-treatment, further demonstrating the excellence and universality of the synthesis method of the present invention. Example 4 is a practical application of the method of the present invention. Using the method of the present invention to conduct kilogram-level experiments, a high yield of 81% and a high purity of 99.9% final product can still be obtained through simple post-treatment.

[0226] In summary, the diaryl sulfoxide derivatives synthesized by the method of the present invention can obtain high-yield and high-purity final products through simple post-treatment, and the post-treatment is simple, low-cost, and repeatable, and has high practical value and industrial application prospects.

[0227] It should be understood that the various embodiments described herein are only examples and are not intended to limit the scope of the present invention. Therefore, as will be apparent to those skilled in the art, the claimed invention may include variations of the specific embodiments and preferred embodiments described herein. Many of the materials and structures described herein may be replaced with other materials and structures without departing from the spirit of the present invention. It should be understood that the various theories about why the present invention works are not intended to be restrictive.

Claims

1. A method for synthesizing a diaryl sulfoxide derivative, wherein: The diaryl sulfoxide derivative has a structure shown in Formula 1: ， The synthesis method comprises the following steps: The Grignard reagent B first reacts with the zinc reagent in an organic solvent M, and then reacts with thionyl chloride to generate the diaryl sulfoxide derivative; The zinc reagent is selected from LZnY2, wherein Y is selected from chlorine, bromine or iodine; L is selected from N,N,N',N'-tetramethylethylenediamine; The organic solvent M is any one of an ether solvent and a hydrocarbon solvent or a combination of two thereof; The Grignard reagent B has a structure shown in Formula 2: ， In Formula 2, X is selected from chlorine, bromine or iodine; In equation 1 and equation 2, Ring A is selected from a benzene ring; R A Indicates single substitution, multiple substitution or no substitution; R A Each is independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1-12 carbon atoms, substituted or unsubstituted cycloalkyl having 4-10 ring carbon atoms, or a combination thereof; the substituted alkyl having 1-12 carbon atoms and the substituted cycloalkyl having 4-10 ring carbon atoms refer to any one of the alkyl and cycloalkyl groups being substituted by one or more deuterium or halogen.

2. The synthesis method as claimed in claim 1, wherein the zinc reagent is selected from (N,N,N',N'-tetramethylethylenediamine)zinc dichloride.

3. The synthesis method according to claim 1, wherein the Grignard reagent B is generated by the reaction of compound A and magnesium; The compound A has a structure shown in Formula 3: ， In Formula 3, X is selected from chlorine, bromine or iodine; Ring A is selected from a benzene ring; R A Indicates single substitution, multiple substitution or no substitution; R A Each is independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 12 carbon atoms, substituted or unsubstituted cycloalkyl having 4 to 10 ring carbon atoms, or a combination thereof.

4. The synthesis method according to claim 1, wherein the diaryl sulfoxide derivative has a structure shown by Formula 1-1: ， in, In Formula 1-1, A1 to A5 are selected from CR A ; R A Each is independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl having 1 to 12 carbon atoms, or a combination thereof.

5. The synthesis method according to claim 1 or 3, wherein X is selected from bromine.

6. The synthesis method according to claim 4, wherein In formula 1-1, at least one of A1 to A5 has R A Each is independently selected from deuterium, halogen, substituted or unsubstituted alkyl having 1 to 12 carbon atoms, or a combination thereof.

7. The synthesis method according to claim 6, wherein In formula 1-1, at least one of A1 to A4 is R A .

8. The synthesis method as claimed in claim 1, wherein R A Each is independently selected from hydrogen, deuterium, fluorine, methyl, isopropyl, 2-butyl, isobutyl, tert-butyl, pent-3-yl, cyclopentyl, cyclohexyl, 4,4-dimethylcyclohexyl, neopentyl, 2,4-dimethylpent-3-yl, 3,3,3-trifluoro-2,2-dimethylpropyl, cyclopentylmethyl, trifluoromethyl, or a combination thereof.

9. The synthesis method according to claim 1, wherein the diaryl sulfoxide derivative is selected from the group consisting of Compound 1 to Compound 17, and the specific structures of Compound 1 to Compound 17 are shown below: ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ； Optionally, hydrogen in the structures of Compounds 1 to 17 can be partially or completely replaced by deuterium.

10. The synthesis method according to claim 1, wherein the organic solvent M is selected from any one of tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and n-heptane, or a combination of at least two thereof.

11. The synthesis method according to claim 1, wherein the amount of the zinc reagent is 0.1-10 times the amount of thionyl chloride.

12. The synthesis method as claimed in claim 1, wherein the reaction temperature of the Grignard reagent B and the zinc reagent is 0-50 degrees Celsius.

13. The synthesis method according to claim 1, wherein the yield of the diaryl sulfoxide derivative is greater than 75%.

Images