CN114478150A - S-deuterated methyl-aryl sulfonyl thioester compound and synthesis method and application thereof - Google Patents

S-deuterated methyl-aryl sulfonyl thioester compound and synthesis method and application thereof Download PDF

Info

Publication number
CN114478150A
CN114478150A CN202210075728.5A CN202210075728A CN114478150A CN 114478150 A CN114478150 A CN 114478150A CN 202210075728 A CN202210075728 A CN 202210075728A CN 114478150 A CN114478150 A CN 114478150A
Authority
CN
China
Prior art keywords
methyl
deuterated
reaction
formula
synthesis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202210075728.5A
Other languages
Chinese (zh)
Other versions
CN114478150B (en
Inventor
陈芬儿
肖霄
黄印秋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang University of Technology ZJUT
Original Assignee
Zhejiang University of Technology ZJUT
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang University of Technology ZJUT filed Critical Zhejiang University of Technology ZJUT
Priority to CN202210075728.5A priority Critical patent/CN114478150B/en
Publication of CN114478150A publication Critical patent/CN114478150A/en
Application granted granted Critical
Publication of CN114478150B publication Critical patent/CN114478150B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C313/08—Sulfenic acids; Derivatives thereof
    • C07C313/18—Sulfenamides
    • C07C313/20—Sulfenamides having sulfur atoms of sulfenamide groups bound to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/22—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of hydropolysulfides or polysulfides
    • C07C319/24—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of hydropolysulfides or polysulfides by reactions involving the formation of sulfur-to-sulfur bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/02—Monothiocarboxylic acids
    • C07C327/16—Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/04—Thiosulfonates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/34—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/32—Esters thereof
    • C07F9/3258—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3264—Esters with hydroxyalkyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention discloses an S-deuterated methyl-arylsulfonyl thioester compound and a synthesis method and application thereof, wherein the synthesis method comprises the steps of forming an intermediate shown in a formula (2) by deuterated methanol shown in a formula (1) and an electrophilic reagent in an organic solvent under the environment of alkali and nitrogen; reacting an intermediate shown in a formula (2) with aryl sodium thiosulfonate shown in a formula (3) under the action of a phase transfer catalyst to obtain an S-deuterated methyl-aryl sulfonyl thioester compound, wherein the reaction process is as follows:
Figure DDA0003483912560000011
wherein R is1Is selected from phenyl, substituted phenyl or condensed ring, and the substituent on the substituted phenyl is methyl, methoxy, tertiary butyl or halogen.The method has the advantages of mild reaction conditions, cheap and easily-obtained raw materials, simple reaction operation, high yield, economy, practicability and environmental friendliness; the reaction efficiency is high after the reaction amplification, and the prepared S-deuterated methyl-arylsulfonyl thioester compound can be used for further synthesizing a deuterated thiomethyl compound containing a C-S, P-S, N-S bond.

Description

S-deuterated methyl-aryl sulfonyl thioester compound and synthesis method and application thereof
Technical Field
The invention belongs to the technical field of organic compound synthesis, and particularly relates to an S-deuterated methyl-arylsulfonyl thioester compound, a synthesis method and application thereof, belonging to the technical field of organic compound process application.
Background
Methyl groups are ubiquitous as the simplest functional group in numerous natural products and drugs, and play a crucial role in improving the physical properties and biological activity of compounds. Among them, the compounds having structures of thiomethyl, methyl sulfoxide and methyl sulfone are more important cornerstones of modern pharmaceutical chemistry. Such as thiocolchicine, the antipsychotic agent thioridazine, the tubulin polymerization inhibitor having a thiomethyl structure; the medicine with methyl sulfoxide structure for treating cardiovascular diseases, such as thiamazole and sulindac; a non-steroidal anti-inflammatory drug with a methyl sulfone structure, namely, feloxicib, and a medicine for treating basal cell carcinoma, namely, vismodegib;
Figure BDA0003483912550000011
in addition, deuterium atoms are used as bioisosteres of hydrogen atoms, and can be used as tracer atoms to study the metabolic pathways of drugs in human bodies. However, since the bond dissociation energy of the carbon-deuterium bond is higher than that of the carbon-hydrogen bond, introduction of deuterium atoms to replace hydrogen atoms at the metabolic sites of some drugs may have a significant effect on the pharmacokinetic properties of the drugs. Over the past few decades, various deuterated drug candidates have entered clinical trials, and in 2017, the FDA approved the first deuterated drug, ambitant, for marketing. Besides the application in pharmaceutical chemistry, the deuterated labeled compound is a tool and widely applied to the mechanism research of chemical reaction and the identification research of products, and in view of the importance of the deuterated compound, the development of a preparation method with practicability and strong universality is necessary.
Figure BDA0003483912550000021
In summary, the deuterated thiomethyl structure with the thiomethyl skeleton and the deuterated hydrogen is a group with certain patent drug potential, but in the prior art, the traditional method for constructing the deuterated thiomethyl skeleton on the drug structure is mainly carried out through deuterated iodomethane or deuterated dimethyl sulfate with high toxicity, so that the method is limited because of certain damage to human bodies. The method for introducing the deuterated thiomethyl through the deuterated DMSO or the deuterated sodium borohydride, which is developed in recent years, needs to use a large amount of deuterated reagent as a substrate or a solvent, so that the cost is high, and the application of the deuterated reagent on an industrial scale is limited.
It is therefore of particular importance to find a source of deuterium which is non-toxic and capable of synthesizing a deuterated thiomethylating agent starting at 1 equivalent and to explore the coupling method of the deuterated agent with a nucleophilic product.
Disclosure of Invention
The invention overcomes the defects of the traditional reaction for constructing the deuterated thiomethyl skeleton, and innovatively develops a method for directly obtaining a universal deuterated methyl thiolated reagent by taking deuterated methanol as 1 equivalent under mild conditions through a one-pot method. In view of the above, the invention designs a reaction method for preparing S-deuterated methyl-arylsulfonyl thioester compounds by using electrophilic reagents and base-activated deuterated methanol and aryl sodium thiosulfonate in an organic solvent under the action of a phase transfer catalyst.
An S-deuterated methyl-arylsulfonyl thioester compound has a structural formula shown in formula (4), wherein R is1Selected from phenyl, substituted phenyl or condensed ring, wherein the substituent on the substituted phenyl is methyl, methoxy, tert-butyl or halogen
Figure BDA0003483912550000022
A synthetic method of an S-deuterated methyl-arylsulfonyl thioester compound comprises the following steps:
1) forming an intermediate shown in a formula (2) by using deuterated methanol shown in the formula (1) and an electrophilic reagent in an organic solvent under the environment of alkali and nitrogen;
2) reacting an intermediate shown in a formula (2) with aryl sodium sulfosulfonate shown in a formula (3) under the action of a phase transfer catalyst to obtain a compound shown in a formula (4), wherein the reaction process is as follows:
Figure BDA0003483912550000031
wherein R is1Is selected from phenyl, substituted phenyl or condensed ring, and the substituent on the substituted phenyl is methyl, methoxy, tertiary butyl or halogen.
Further, the condensed ring is a naphthalene ring, and the halogen is fluorine, chlorine or bromine.
Further, the electrophile is trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride or methanesulfonic anhydride, preferably trifluoromethanesulfonic anhydride, and the amount of the electrophile is 1.05 to 5.0 equivalents, preferably 1.1 equivalents, to the deuterated methanol represented by formula (1).
Further, the base is 2, 6-lutidine or triethylamine, preferably 2, 6-lutidine, and the amount of the base is 1.0 to 5.0 equivalents, preferably 1.2 equivalents, of deuterated methanol represented by formula (1).
Further, the organic solvent is N, N-dimethylformamide or acetonitrile, preferably N, N-dimethylformamide.
Further, the amount of the phase transfer catalyst is 2.5 to 100 mol%, preferably 5 mol% of the deuterated methanol represented by the formula (1).
Further, the molar ratio of the deuterated methanol represented by the formula (1) to the aryl thiosulfonate represented by the formula (3) is 1.0:1.0 to 1.0:5.0, preferably 1.0: 1.5.
Further, the reaction temperature of the step 1) is-20-0 ℃, and preferably 0 ℃; the reaction temperature in step 2) is 30 to 100 ℃, preferably 60 ℃.
Further, the reaction time of the step 1) is 1-4h, preferably 1.5 h; the reaction time of the step 2) is 4-12h, preferably 6 h.
An application of S-deuterated methyl-arylsulfonyl thioester compounds, in particular to an application in synthesizing aryl deuterated methyl-thiophenol compounds, an application in synthesizing compounds containing C-S bonds, an application in synthesizing compounds containing P-S bonds, an application in synthesizing compounds containing N-S bonds and an application in synthesizing disulfide compounds.
The invention has the beneficial effects that:
1) 1 equivalent of deuterated methanol is adopted, the deuterated methanol is activated by an electrophilic reagent, and finally the deuterated methanol is coupled with aryl thiosulfonic acid sodium salt under the phase transfer catalysis, and the reaction is carried out at the temperature of 30-100 ℃, so that the adverse conditions that the former reaction condition is harsh, a large amount of deuterium sources are needed to be used and the like are overcome, and the reaction for synthesizing the deuterated thiomethyl reagent is developed more efficiently, greenly and conveniently;
2) the compound preparation realizes gram-scale reaction, has practicability and wide application prospect, and is suitable for industrial scale production.
3) The method has the advantages of high reaction efficiency, high yield, simple and stable preparation, no pungent smell and mild reaction conditions.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited. The data given in the examples below include specific operating and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
A synthetic reaction of S-deuterated methyl-aryl sulfonyl thioester compounds comprises the following steps:
Figure BDA0003483912550000041
example 1
Synthesis of S-deuterated methyl-4-benzenesulfonyl thioester:
Figure BDA0003483912550000042
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (128.6mg,1.2mmol,1.2equiv.) and anhydrous DMF (2.0mL), followed by Tf dropwise addition at 0 deg.C2O (310.3mg,1.1mmol,1.1equiv.), after 90min of reaction, sodium benzenethiosulfonate (293.9mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and purified by column chromatography to give product 4a (151.1mg, 80%, deuteron rate)>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ7.92(d,J＝7.7Hz,2H),7.68–7.62(m,1H),7.61 –7.51(m,2H)；13C NMR(100MHz,CDCl3)δ143.5,133.6,129.2,127.0.HRMS (ESI)for C7H5D3O2S2[M+Na]+calcd 214.0046,found 214.0046.
Example 2
Synthesis of S-deuterated methyl-4-methylbenzenesulfonyl thioester:
Figure BDA0003483912550000051
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (128.6mg,1.2mmol,1.2equiv.), and anhydrous DMF (2.0mL) were added dropwise followed by Tf at 0 deg.C2O (310.3mg,1.1mmol,1.1equiv.), after 90min of reaction, 4-methylbenzenesulfonic acid sodium salt (315.4mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then the reaction was quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and column chromatography purification was carried out to obtain a product 4b (172.2mg, 84%, deuteration rate)>99%) (eluent polarity: PE: EA 60: 1).
1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.2Hz,2H),7.35(d,J＝8.2Hz,2H), 2.45(s,3H).13C NMR(100MHz,CDCl3)δ144.9,141.1,129.9,127.3,21.8.MS(EI) m/z 205.03(M+).mp:(56.5–57.4℃).
Example 3
Synthesis of S-deuterated methyl-4-methylbenzenesulfonyl thioester:
Figure BDA0003483912550000052
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (128.6mg,1.2mmol,1.2equiv.), and anhydrous acetonitrile (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (310.3mg,1.1mmol,1.1equiv.), after 90min of reaction, 4-methylbenzenesulfonic acid sodium salt (315.4mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then the reaction was quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and column chromatography purification was carried out to obtain a product 4b (155.8mg, 76%, deuterium substitution rate)>99%) (eluent polarity: PE: EA 60: 1).
1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.2Hz,2H),7.35(d,J＝8.2Hz,2H), 2.45(s,3H).13C NMR(100MHz,CDCl3)δ144.9,141.1,129.9,127.3,21.8.MS(EI) m/z 205.03(M+).mp:(56.5–57.4℃).
Example 4
Synthesis of S-deuterated methyl-4-methylbenzenesulfonyl thioester:
Figure BDA0003483912550000061
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (1.80g,50mmol,1.0equiv.), 2, 6-lutidine (6.42g,60mmol,1.2equiv.), and anhydrous DMF (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (15.51g,55mmol,1.1equiv.), after 90min of reaction, 4-methylbenzenesulfonic acid sodium salt (15.77g,75mmol,1.5equiv.), TBAI (0.92g,2.5mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then the reaction was quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and column chromatography was performed to purify to obtain a product 4b (8.71g, 85%,rate of deuteration>99%) (eluent polarity: PE: EA 60: 1).
1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.2Hz,2H),7.35(d,J＝8.2Hz,2H), 2.45(s,3H).13C NMR(100MHz,CDCl3)δ144.9,141.1,129.9,127.3,21.8.MS(EI) m/z 205.03(M+).mp:(56.5–57.4℃).
Example 5
Synthesis of S-deuterated methyl-4-methoxybenzenesulfonyl thioester:
Figure BDA0003483912550000062
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after 90min of reaction, 4-methoxybenzenethiosulfonic acid sodium salt (338.9mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then the reaction was quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and column chromatography purification was carried out to obtain a product 4c (185.6 mg, 84%, deuteration rate)>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ7.91–7.71(m,2H),7.09–6.85(m,2H),3.87(s, 3H)；13C NMR(100MHz,CDCl3)δ163.5,135.1,129.2,114.2,55.6.HRMS(ESI) for C8H7D3O3S2[M+Na]+calcd 244.0152,found 244.0155.
Example 6
Synthesis of S-deuterated methyl-4-tert-butylbenzene sulfonyl thioester:
Figure BDA0003483912550000071
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD(36.07mg,1.0mmol,1.0equiv.), 2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0mL), followed by addition of Tf dropwise at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after 90min of reaction, 4-tert-butylthiosulfonic acid sodium salt (378.0mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and purified by column chromatography to give product 4d (183.1 mg, 74%, deuteron rate)>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.2Hz,2H),7.54(d,J＝8.1Hz,2H), 1.32(s,9H)；13C NMR(100MHz,CDCl3)δ157.5,140.6,126.7,126.1,35.1,30.8. HRMS(ESI)for C11H13D3O2S2[M+Na]+calcd 270.0672,found 270.0672.
Example 7
Synthesis of S-deuterated methyl-4-fluorobenzenesulfonyl thioester:
Figure BDA0003483912550000072
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after 90min of reaction, 4-fluorobenzothiosulfonic acid sodium salt (320.9mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and purified by column chromatography to give 4e (165.3mg, 79%, deuteration rate)>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ8.07–7.85(m,2H),7.31–7.21(m,2H)；13C NMR(100MHz,CDCl3)δ165.5(d,1JC-F＝1020Hz),139.7(d,4JC-F＝16Hz),129.9 (d,3JC-F＝40Hz),116.5(d,2JC-F＝92Hz)；19F NMR(376MHz,CDCl3)δ 103.0.HRMS(ESI)for C7H4D3FO2S2[M+Na]+calcd 231.9952,found 231.9953.
Example 8
Synthesis of S-deuterated methyl-4-chlorobenzenesulfonyl thioester:
Figure BDA0003483912550000081
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after 90min of reaction, 4-chlorobenzenethiosulfonic acid sodium salt (344.9mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and purified by column chromatography to give 4f (180.6mg, 80%, deuteration rate) as a product>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ7.93–7.80(m,2H),7.59–7.47(m,2H)；13C NMR(100MHz,CDCl3)δ142.1,140.3,129.5,128.4；HRMS(ESI)for C7H4D3ClO2S2[M+Na]+calcd 247.9656,found 247.9655.
Example 9
Synthesis of S-deuterated methyl-4-bromobenzenesulfonyl thioester:
Figure BDA0003483912550000091
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0 m., 1.0 m.)L), followed by dropwise addition of Tf at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after 90min of reaction, 4-chlorobenzenethiosulfonic acid sodium salt (410.8mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) were added to the reaction system and reacted at 60 ℃ for 6 hours, then quenched with water, extracted with ethyl acetate, the organic phase was separated, the solvent was removed under reduced pressure, and purified by column chromatography to obtain 4g (210.8mg, 78%, deuteration rate, deuterium oxide rate) of the product>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ7.78(d,J＝8.7Hz,2H),7.70(d,J＝8.7Hz, 2H)；13C NMR(100MHz,CDCl3)δ142.6,132.5,128.8,128.5.HRMS(ESI)for C7H4D3BrO2S2[M+Na]+ calcd 291.9151,found 291.9155.
Example 10
Synthesis of S-deuterated methyl-2-naphthalenesulfonyl thioester:
Figure BDA0003483912550000092
under nitrogen atmosphere, CD was added to a dry schlenk tube3OD (36.07mg,1.0mmol, 1.0equiv.),2, 6-lutidine (150.0mg,1.4mmol,1.4equiv.), and anhydrous DMF (2.0mL) were added dropwise, followed by Tf at 0 deg.C2O (338.5mg,1.2mmol,1.2equiv.), after reacting for 90min, 2-naphthylthiosulfonyl sodium salt (369.0mg,1.5mmol,1.5equiv.), TBAI (18.47mg,0.05mmol,5 mol%) are added to the reaction system, and after reacting for 6 hours at 60 ℃, the reaction is quenched with water, extracted with ethyl acetate, the organic phase is separated, after removing the solvent under reduced pressure, the product is purified by column chromatography to obtain 4h (185.8mg, 77%, deutero rate)>99%) (eluent polarity: PE: EA 20: 1).
1H NMR(400MHz,CDCl3)δ8.46(s,1H),8.04–7.98(m,2H),7.96–7.88(m, 2H),7.72–7.60(m,2H)；13C NMR(100MHz,CDCl3)δ140.1,135.1,131.6,129.8, 129.5,129.4,128.6,127.9,127.8,121.9.HRMS(ESI)for C11H7D3O2S2[M+Na]+ calcd 262.0203,found 262.0200.
Example 11
[1,1' -Biphenyl]-4-yl (methyl-d)3) Synthesis of thioether:
Figure BDA0003483912550000101
s-deuterated methyl-4-methylbenzenesulfonylthioester (1.64g,8mmol,1equiv.) prepared in example 2, 5a (12mmol,2.38g,1.5equiv.), and absolute methanol (40.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.4mmol,63.8mg,0.05equiv.), NaHCO3(16mmol,1.34g,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting an organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6a (1.40g, 86% deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.59(d,J＝8.2Hz,2H),7.54(d,J＝8.2Hz,2H), 7.48–7.42(m,2H),7.39–7.32(m,3H)；13C NMR(100MHz,CDCl3)δ140.7,138.1, 137.7,128.9,127.6,127.3,127.1,127.0.MS(EI)m/z 203.08(M+).mp:(88.7- 90.1℃).
Example 12
(3- (benzyloxy) phenyl) (methyl-d3) Synthesis of thioether:
Figure BDA0003483912550000102
s-deuterated methyl-4-methylbenzenesulfonylthioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5b (0.3mmol,68.4mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirred at room temperature for 24 hours, after the reaction was completed, water was added to the reaction system to quench, and extraction was performed with dichloromethane. Collecting the organic phase, reducingThe solvent was removed under reduced pressure and purified by column chromatography to give product 6b (38.7mg, 83%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.47–7.31(m,5H),7.23–7.18(m,1H),6.91– 6.84(m,2H),6.78–6.74(m,1H),5.06(s,2H).13C NMR(100MHz,CDCl3)δ159.2, 140.0,136.9,129.8,128.7,128.1,127.6,119.2,113.2,111.4,70.13.HRMS (ESI-TOF)m/z:[M+H]+ Calcd for C14H12D3OS 234.1032；Found 234.1035.
Example 13
(methyl-d)3) Synthesis of (4- (phenoxy) phenyl) sulfide:
Figure BDA0003483912550000111
s-deuterated methyl-4-methylbenzenesulfonylthioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5c (0.3mmol,64.2mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6c (32.8mg, 75%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.38–7.30(m,2H),7.30–7.24(m,2H),7.15– 7.07(m,1H),7.03–6.98(m,2H),6.98–6.94(m,2H)；13C NMR(100MHz,CDCl3) δ157.4,155.3,132.3,129.9,129.2,123.4,119.7,118.8.HRMS(EI-TOF)m/z Calcd for C13H9D3S 219.0797[M]+,Found 219.0802.
Example 14
(methyl-d)3) Synthesis of (2- (phenoxy) phenyl) sulfide:
Figure BDA0003483912550000112
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5d (0.3mmol,64.2mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6d (31.9mg, 73%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.36–7.30(m,2H),7.29–7.25(m,1H),7.18– 7.11(m,2H),7.11–7.06(m,1H),7.00–6.96(m,2H),6.92–6.88(m,1H).13C NMR(100MHz,CDCl3)δ157.3,153.6,130.8,129.8,126.8,126.0,124.5,123.1, 119.4,118.0.HRMS(EI-TOF)m/z Calcd for C13H9D3S 219.0797[M]+,Found 219.0793.
Example 15
(methyl-d)3) Synthesis of (Naphthalen-2-yl) sulfide:
Figure BDA0003483912550000121
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5e (0.3mmol,51.6mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirred at room temperature for 24 hours, after the reaction was completed, water was added to the reaction system to quench, and extraction was performed with dichloromethane. The organic phase was collected, the solvent was removed under reduced pressure, and the product 6e (28.6mg, 81%, deuteration rate) was purified by column chromatography>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.80(d,J＝8.1Hz,1H),7.76(d,J＝8.4Hz,2H), 7.62(d,J＝1.2Hz,1H),7.52–7.46(m,1H),7.46–7.38(m,2H)；13C NMR(100 MHz,CDCl3)δ136.2,134.0,131.1,128.3,127.8,126.9,126.7,125.8,125.3,123.5. MS(EI)m/z 177.07[M]+.mp:(55.4–56.7)℃
Example 16
(methyl-d)3) Synthesis of (phenanthren-9-yl) sulfide:
Figure BDA0003483912550000122
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5f (0.3mmol,66.6mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6f (32.2mg, 71%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ8.74–8.67(m,1H),8.67–8.60(m,1H),8.43– 8.36(m,1H),7.86–7.79(m,1H),7.74–7.66(m,2H),7.64–7.56(m,3H)；13C NMR(100MHz,CDCl3)δ134.5,132.1,130.6,130.4,129.0,127.7,127.1,127.0, 126.9,126.2,125.0,123.4,123.2,122.7.mp:(91.8–93.7)℃.HRMS(EI-TOF)m/z Calcd for C15H9D3S 227.0848[M]+,Found 227.0844.
Example 17
(methyl-d)3) Synthesis of (pyrene-4-yl) sulfide:
Figure BDA0003483912550000131
drying under nitrogen atmosphereS-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5g (0.3mmol,73.8mg,1.5 equiv.), and absolute methanol (2.0mL) were added to the schlenk tube, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain 6g (35.1mg, 70%, deuteration rate) of the product>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ8.56(d,J＝9.2Hz,1H),8.20–8.09(m,4H), 8.04–7.97(m,4H)；13C NMR(100MHz,CDCl3)δ133.2,131.6,131.2,129.5,129.4, 127.7,127.4,127.0,126.3,125.4,125.2,125.1,124.7,123.9.HRMS(ESI-TOF)m/z: [M+H]+ Calcd for C17H10D3S 252.0926；Found 252.0921.mp:(69.9–71.0)℃.
Example 18
(4-chlorophenyl) (methyl-d)3) Synthesis of thioether:
Figure BDA0003483912550000132
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5h (0.3mmol,46.8mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product of 6h (24.5mg, 76%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.25(d,J＝8.7Hz,2H),7.18(d,J＝8.7Hz,2H)；13C NMR(100MHz,CDCl3)δ137.1,131.0,129.0,128.1.MS(EI)m/z 161.01[M]+
Example 19
(4-bromophenyl) (methyl-d)3) Synthesis of thioether:
Figure BDA0003483912550000141
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5i (0.3mmol,60.0mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6i (29.5mg, 72%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.39(d,J＝8.6Hz,2H),7.11(d,J＝8.6Hz,2H)；13C NMR(100MHz,CDCl3)δ137.8,131.9,128.2,118.7.MS(EI)m/z 204.96[M]+.
Example 20
(4-iodophenyl) (methyl-d)3) Synthesis of thioether:
Figure BDA0003483912550000142
s-deuterated methyl-4-methylbenzenesulfonylthioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5j (0.3mmol,74.3mg,1.5 equiv.) and absolute ethanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting an organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6j (35.4mg, 70%, deuteration rate)>99％)(eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.39(d,J＝8.6Hz,2H),7.11(d,J＝8.6Hz,2H)；13C NMR(100MHz,CDCl3)δ137.8,131.9,128.2,118.7.MS(EI)m/z 204.96[M]+. mp:(34.7–36.2)℃.
Example 21
4- ((methyl-d)3) Thio) synthesis of methyl benzoate:
Figure BDA0003483912550000151
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5k (0.3mmol,54.0mg,1.5 equiv.), and absolute ethanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6k (28.9mg, 78%, deuteration rate)>99%) (eluent polarity: PE: EA: 10/1).
1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.5Hz,2H),7.17(d,J＝8.5Hz,2H), 3.82(s,3H)；13C NMR(100MHz,CDCl3)δ170.0,145.5,130.0,126.4,125.0,52.1. HRMS(ESI-TOF)m/z:[M+H]+ Calcd for C9H8D3O2S 186.0668；Found 186.0666.
Example 22
4- ((methyl-d)3) Thio) synthesis of ethyl benzoate:
Figure BDA0003483912550000152
s-deuterated methyl-4-methylbenzenesulfonylthioester (0.2) prepared in example 2 was added to a dry schlenk tube under a nitrogen atmospheremmol,41.0g,1equiv.), 5l (0.3mmol,58.2mg,1.5 equiv.), and anhydrous methanol (2.0mL), CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain 6l (31.8mg, 80%, deuteration rate) of the product>99%) (eluent polarity: PE: EA: 20/1).
1H NMR(400MHz,CDCl3)δ7.94(d,J＝8.5Hz,2H),7.25(d,J＝8.5Hz,2H), 4.36(q,J＝7.1Hz,2H),1.39(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ 166.5,145.3,130.0,126.8,61.0.MS(EI)m/z 199.07[M]+.
Example 23
(methyl-d)3) Synthesis of (4-nitrophenyl) sulfide:
Figure BDA0003483912550000161
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5m (0.3mmol,50.1mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6m (26.8mg, 78%, deuteration rate)>99%) (eluent polarity: PE: EA: 50/1).
1H NMR(400MHz,CDCl3)δ8.13(d,J＝9.1Hz,2H),7.28(d,J＝9.1Hz, 2H)；13C NMR(100MHz,CDCl3)δ148.9,144.9,125.1,124.0.MS(EI)m/z 172.04 [M]+.mp:(62.4-64.1)℃.
Example 24
3- ((methyl-d)3) Thio) benzonitrile synthesis:
Figure BDA0003483912550000162
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5n (0.3mmol,44.1mg,1.5 equiv.), and absolute ethanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6n (19.8mg, 65%, deuteration rate)>99%) (eluent polarity: PE: EA: 10/1).
1H NMR(400MHz,CDCl3)δ7.47–7.34(m,4H)；13C NMR(100MHz, CDCl3)δ141.0,130.6,129.4,129.0,128.4,118.6,113.3.HRMS(ESI-TOF)m/z:[M +H]+ Calcd for C8H5D3NS 153.0566；Found 153.0560.
Example 25
(4- ((methyl-d)3) Thio) phenyl) methanol synthesis:
Figure BDA0003483912550000171
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5o (0.3mmol,45.6mg,1.5 equiv.), and absolute ethanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain the product 6o (23.4mg, 75%, deuteration rate)>99%) (eluent polarity: PE: EA: 5/1).
1H NMR(400MHz,CDCl3)δ7.29(d,J＝8.5Hz,2H),7.25(d,J＝8.5Hz,2H), 4.65(s,2H),1.68(brs,1H)；13C NMR(100MHz,CDCl3)δ137.9,137.8,127.8, 127.0,65.1.HRMS(EI-TOF)m/z Calcd for C8H7D3OS 157.0641[M]+,Found 157.0638.
Example 26
(2- ((methyl-d)3) Thio) phenyl) methanol synthesis:
Figure BDA0003483912550000172
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5p (0.3mmol,45.6mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6p (23.4mg, 75%, deuteration rate)>99%) (eluent polarity: PE: EA: 4/1).
1H NMR(400MHz,CDCl3)δ7.38–7.34(m,1H),7.29–7.24(m,2H),7.19– 7.14(m,1H),4.74(s,2H),2.43(brs,1H)；13C NMR(100MHz,CDCl3)δ139.0, 136.8,128.5,128.2,126.7,125.6,63.7.HRMS(EI-TOF)m/z Calcd for C8H7D3OS 157.0641[M]+,Found 157.0642.
Example 27
4- ((methyl-d)3) Thio) phenol synthesis:
Figure BDA0003483912550000181
s-deuterated methyl-4-methylbenzenesulfonyl thioester prepared in example 2 was added to a dry schlenk tube under a nitrogen atmosphere(0.2mmol,41.0g,1equiv.), 5q (0.3mmol,41.4mg,1.5 equiv.), and anhydrous methanol (2.0mL) were added to the system with CuSO4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6q (20.8mg, 73%, deuteration rate)>99%) (eluent polarity: PE: EA: 5/1).
1H NMR(400MHz,CDCl3)δ7.21(d,J＝8.6Hz,2H),6.78(d,J＝8.6Hz,2H), 5.04(brs,1H).13C NMR(100MHz,CDCl3)δ154.2,130.5,128.9,116.2.HRMS (EI-TOF)m/z Calcd for C7H5D3OS 143.0484[M]+,Found 143.0482.
Example 28
(4- ((methyl-d)3) Thio) phenyl) carbamic acid tert-butyl ester synthesis:
Figure BDA0003483912550000182
s-deuterated methyl-4-methylbenzenesulfonylthioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5r (0.3mmol,71.1mg,1.5 equiv.) and anhydrous methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6r (41.6mg, 86%, deuteration rate)>99%) (eluent polarity: PE: EA: 10/1).
1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.7Hz,2H),7.25(d,J＝8.7Hz,2H), 6.52(s,1H),1.54(s,9H).13C NMR(100MHz,CDCl3)δ152.8,136.3,131.9,128.7, 119.3,80.7,28.4.HRMS(ESI-TOF)m/z:[M+Na]+ Calcd for C12H14D3NO2S265.1066；Found 265.1063.
Example 29
5- ((methyl-d)3) Thio) benzo [ d][1,3]Synthesis of dioxane:
Figure BDA0003483912550000191
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5S (0.3mmol,49.8mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain the product 6s (28.0mg, 82%, deuteration rate)>99%), (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ6.84–6.73(m,3H),5.94(s,2H).13C NMR (100MHz,CDCl3)δ148.2,146.3,130.6,122.0,109.5,108.9,101.3.HRMS(EI-TOF) m/z Calcd for C8H5D3O2S 171.0433[M]+,Found 171.0434.
Example 30
4- ((methyl-d)3) Thio) dibenzo [ b, d]Furan:
Figure BDA0003483912550000192
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.2mmol,41.0g,1equiv.) prepared in example 2, 5t (0.3mmol,63.6mg,1.5 equiv.), and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.4mmol,33.6mg,2equiv.) and stirred at room temperature for 24h, after the reaction was completed, water was added to the reaction system to quench, extraction was performed with dichloromethane, and the organic phase was collectedPhase separation, solvent removal under reduced pressure, column chromatography purification to give 6t (29.5mg, 68%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.94(d,J＝7.6Hz,1H),7.79(d,J＝7.6Hz,1H), 7.65(d,J＝8.2Hz,1H),7.50–7.44(m,1H),7.40–7.33(m,2H),7.33–7.28(m, 1H).13C NMR(100MHz,CDCl3)δ156.1,154.2,127.4,126.1,124.2,123.4,123.0, 121.5,120.9,118.2,112.1.HRMS(EI)m/z Calcd for C13H7D3OS 217.0644[M]+, Found 217.0641.
Example 31
1, 4-bis ((methyl-d)3) Thio) benzene synthesis:
Figure BDA0003483912550000201
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.35mmol,71.8mg,2.3equiv.) prepared in example 2, 5u (0.15mmol,49.8mg, 1equiv.) and absolute methanol (2.0mL) were added to a dry schlenk tube under a nitrogen atmosphere, and CuSO was added to the system4(0.01mmol,1.6mg,0.05equiv.), NaHCO3(0.3mmol,25.2mg,2equiv.) and stirring at room temperature for 24h, after the reaction is finished, adding water into the reaction system for quenching, extracting with dichloromethane, collecting the organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain 6t (17.9mg, 68%, deuteration rate) of the product>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.20(s,4H).13C NMR(100MHz,CDCl3)δ 135.2,127.8.HRMS(EI-TOF)m/z Calcd for C8H4D6S2 176.0601[M]+,Found 176.0599.
Example 32
2- ((methyl-d)3) Synthesis of thio) -1-oxo-2, 3-dihydro-1H-indene-2-carboxylic acid methyl ester:
Figure BDA0003483912550000202
s-deuterated methyl-4-methylbenzenesulfonylthioester (61.5mg,0.3mmol,1.5equiv.),5v (38.0mg,0.2mmol, 1equiv.), Cs prepared in example 2 were added to a dry schlenk tube under a nitrogen atmosphere2CO3(97.7mg,0.3mmol,1.5equiv.) and 1, 2-dichloroethane (1ml), reacting the reaction system at room temperature for 12 hours, adding water into the reaction system after the reaction is finished, quenching, extracting with dichloromethane, collecting an organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6v (43.0mg, 90%, deuteration rate)>99%) (eluent polarity: PE: EA: 20/1).
1H NMR(400MHz,CDCl3)δ7.83(d,J＝7.8Hz,1H),7.66–7.60(m,1H), 7.46–7.40(m,2H),3.89(d,J＝17.8Hz,1H),3.80(s,3H),3.14(d,J＝17.8Hz,1H). 13C NMR(100MHz,CDCl3)δ196.3,169.9,150.5,135.5,134.0,128.4,126.3,125.7, 58.0,53.4,40.1.HRMS(ESI-TOF)m/z:[M+Na]+ Calcd for C12H9D3O3SNa 262.0588；Found 262.0590.
Example 33
2- ((methyl-d)3) Synthesis of thio) -1-oxo-2, 3-dihydro-1H-indene-2-carboxylic acid tert-butyl ester:
Figure BDA0003483912550000211
s-deuterated methyl-4-methylbenzenesulfonylthioester (61.5mg,0.3mmol,1.5equiv.),5w (46.4mg,0.2mmol, 1equiv.) prepared in example 2, Cs were added to a dry schlenk tube under a nitrogen atmosphere2CO3(97.7mg,0.3mmol,1.5equiv.) and 1, 2-dichloroethane (1ml), reacting the reaction system at room temperature for 12 hours, adding water into the reaction system after the reaction is finished, quenching, extracting with dichloromethane, collecting an organic phase, removing the solvent under reduced pressure, and purifying by column chromatography to obtain a product 6w (53.3mg, 95 percent of deuteration rate)>99%) (eluent polarity: PE: EA: 15/1).
1H NMR(400MHz,CDCl3)δ7.80(d,J＝7.5Hz,1H),7.62–7.58(m,1H), 7.43–7.38(m,2H),3.82(d,J＝17.7Hz,1H),3.08(d,J＝17.7Hz,1H),1.46(s, 9H).13C NMR(100MHz,CDCl3)δ196.8,168.3,150.5,135.2,134.2,128.1,126.2, 125.4,83.2,58.6,40.1,28.0.HRMS(ESI-TOF)m/z:[M+Na]+ Calcd for C15H15D3O3S304.1062；Found 304.1060。
Example 34
S- (methyl-d)3) Synthesis of 4-chlorophenyl thioester:
Figure BDA0003483912550000212
a round-bottomed flask was charged with S-deuterated methyl-4-methylbenzenesulfonylthioester (0.25mmol, 51.2mg, 1.0equiv.) prepared in example 2, 5x (52.5mg,0.375mmol,1.5equiv.) and CH3CN (2.5 mL), followed by the addition of tert-butyl hydroperoxide (0.5mmol,64.5mg,2.0equiv,70 wt.% in H2O), refluxing and stirring the reaction at 82 ℃ for 24 hours, removing the solvent under reduced pressure, and purifying by column chromatography to obtain 6x (33.1 mg, 70%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.91(d,J＝8.6Hz,2H),7.43(d,J＝8.6Hz,2H). 13C NMR(100MHz,CDCl3)δ191.4,139.8,135.5,129.1,128.6.HRMS(EI-TOF) m/z Calcd for C8H4D3ClOS 189.0094[M]+,Found 189.0103.
Example 35
4- ((methyl-d)3) Thio) carbonyl) synthesis of methyl benzoate:
Figure BDA0003483912550000221
into a round-bottom flask were charged S-deuterated methyl-4-methylbenzenesulfonylthioester prepared by example 2 (0.25mmol, 51.2mg, 1.0equiv.),5y (61.5mg,0.375mmol,1.5equiv.), and CH3CN(2.5 mL) Then tert-butyl hydroperoxide (0.5mmol,64.5mg,2.0equiv,70 wt.% in H) was added2O), the reaction was refluxed and stirred at 82 ℃ for 24 hours, the solvent was removed under reduced pressure, and then column chromatography purification was performed to obtain 6y (30.8mg, 58%, deuteration rate)>99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.4Hz,2H),8.02(d,J＝8.4Hz,2H), 3.95(s,3H).13C NMR(100MHz,CDCl3)δ192.1,166.3,140.5,134.2,130.0,127.2, 52.6.HRMS(ESI-TOF)m/z:[M+H]+ Calcd for C10H8D3O3S 214.0617；Found 214.0615.
Example 36
(methyl-d)3) Synthesis of (m-tolylethynyl) sulfane:
Figure BDA0003483912550000222
to a dry schlenk tube under nitrogen atmosphere were added 5z (0.2mmol,23.2mg,1equiv.) and anhydrous tetrahydrofuran (1mL), the reaction tube was placed in an ice bath at-78 ℃, LiHMDs (0.22mL, 1M in THF,1.1equiv.) were slowly added dropwise, after 15 minutes, the S-deuterated methyl-4-methylbenzenesulfonylthioester (0.22mmol,45.1mg,1.1equiv.) prepared in example 2 was dissolved in anhydrous tetrahydrofuran (0.22mL), the solution was added dropwise to the reaction tube, reacting for 15 minutes under the same conditions, then placing the schlenk tube at room temperature for 12 hours, quenching the reaction with saturated ammonium chloride after the reaction is finished, followed by extraction with dichloromethane, collection of the organic phase, removal of the solvent under reduced pressure, and purification by column chromatography to give 6z (30.8mg, 87%, deuteration > 99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.26–7.09(m,4H),2.32(s,3H).13C NMR(100 MHz,CDCl3)δ138.1,132.2,129.1,128.6,128.3,123.3,92.0,80.5,21.3.HRMS (EI-TOF)m/z Calcd for C10H7D3S 165.0692[M]+,Found 165.0688.
Example 37
((4-chlorophenyl) ethynyl) (methyl-d)3) Synthesis of sulfane:
Figure BDA0003483912550000231
to a dry schlenk tube, 5aa (0.2mmol,27.0mg,1equiv.) and anhydrous tetrahydrofuran (1mL) were added under a nitrogen atmosphere, the reaction tube was placed in an ice bath at-78 ℃, LiHMDs (0.22mL, 1M in THF,1.1equiv.) were slowly added dropwise, after 15 minutes, the S-deuterated methyl-4-methylbenzenesulfonylthioester (0.22mmol,45.1mg,1.1equiv.) prepared in example 2 was dissolved in anhydrous tetrahydrofuran (0.22mL), the solution was added dropwise to the reaction tube, reacting for 15 minutes under the same conditions, then placing the schlenk tube at room temperature for 12 hours, quenching the reaction with saturated ammonium chloride after the reaction is finished, extraction with dichloromethane was followed, the organic phase was collected, and after removal of the solvent under reduced pressure, column chromatography purification gave 6aa (25.1mg, 68%, deuteration > 99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.6Hz,2H),7.26(d,J＝8.6Hz, 2H)；13C NMR(100MHz,CDCl3)δ134.1,132.7,128.7,122.0,90.7,82.2.HRMS (ESI-TOF)m/z:[M+H]+Calcd for C9H5D3ClS 186.0224；Found 186.0228.
Example 38
2, 5-dichloro-3- ((methyl-d)3) Thio) thiophene synthesis:
Figure BDA0003483912550000232
under nitrogen atmosphere, a dry Schlenk flask was charged with 5ab (76.5mg,0.5mmol, 1equiv.), and 1mL of THL solution was added and cooled to a suitable temperature. TMPMgCl. LiCl (0.55mL,1M in THF,1.1equiv.) was slowly added dropwise at room temperature and stirred at room temperature for 30 minutes. Then, S-deuterated methyl-4-methylbenzenesulfonylthioester prepared in example 2 (128.1mg,0.625mmol, 1.25equiv.) was added and the reaction was carried outThe mixture was stirred at room temperature for 30 minutes. After the reaction is finished, 50% of NH is used4The reaction mixture was quenched with aqueous Cl and Et2O (3X 10 mL). The combined organic layers were washed with Na2SO4Dried and concentrated in vacuo. Purification by flash column chromatography on silica gel gave 6ab (85.4mg, 85%, deuteration rate)>99%). (eluent polarity: PE)
1H NMR(400MHz,CDCl3)δ6.74(m,1H)；13C NMR(100MHz,CDCl3)δ131.3, 127.2,126.5,123.9.HRMS(EI)m/z Calcd for C5HD3Cl2S2 200.9320[M]+,Found 200.9324.
Example 39
S- (methyl-d)3) Synthesis of diphenyl thiophosphonate:
Figure BDA0003483912550000241
under a nitrogen atmosphere, 5ac (0.2mmol,40.4mg,1equiv.) and anhydrous dichloromethane (2mL) were added to a dry schlenk tube, the reaction tube was placed in an ice bath at-78 ℃, LiHMDs (0.22mL, 1M in THF,1.1equiv.) were slowly added dropwise, after 15 minutes, S-deuterated methyl-4-methylbenzenesulfonyl prepared in example 2 (0.22mmol,45.1mg,1.1equiv.) was added, reaction was further performed under the same conditions for 15 minutes, and then the schlenk tube was placed at room temperature for 12 hours, after completion of the reaction, the reaction was quenched with saturated ammonium chloride, followed by extraction with dichloromethane, collection of an organic phase, removal of the solvent under reduced pressure, and purification gave 6ac (30.1mg, 60%, substitution rate of deuterium > 99%) (polarity: PE EA: eluent 5/1).
1H NMR(400MHz,CDCl3)δ7.91–7.84(m,4H),7.56–7.51(m,2H),7.50– 7.44(m,4H)；13C NMR(100MHz,CDCl3)δ132.8(d,1JC-P＝106.7Hz),132.5(d, 4JC-P＝3.0Hz),131.6(d,3JC-P＝10.5Hz),128.8(d,2JC-P＝13.0Hz)；31P NMR(162 MHz,CDCl3)δ44.30.HRMS(ESI-TOF)m/z:[M+H]+ Calcd for C13H11D3OPS 252.0686；Found 252.0686.
Example 40
S- (methyl-d)3) -synthesis of N, N-diphenylthiohydroxylamine:
Figure BDA0003483912550000242
under nitrogen atmosphere, 5ad (0.15mmol,25.4mg,1equiv.) and anhydrous tetrahydrofuran (1mL) were added to a dried Schlenk tube, the reaction tube was placed in an ice bath at 0 ℃, n-butyllithium (0.165 mmol,2.5M in THF,1.1equiv.) was slowly added dropwise, after 1 hour, the reaction tube was lifted to room temperature and stirred for another 1 hour, then S-deuterated methyl-4-methylbenzenesulfonyl thioester (0.22mmol,45.1mg,1.1equiv.) prepared in example 2 was added, and after 12 hours under the same conditions, the reaction was completed, the reaction was quenched with saturated ammonium chloride, followed by extraction with dichloromethane, collection of an organic phase, and after removal of the solvent under reduced pressure, purification was carried out to give 6ad (16.3mg, 50%, deuteration rate > 99%) (polarity: PE).
1H NMR(400MHz,DMSO)δ7.35–7.29(m,2H),7.16–7.12(m,2H),7.09–7.01(m,1H)；13C NMR(100MHz,CDCl3)δ148.2,129.4,122.9,121.9.HRMS (ESI-TOF)m/z:[M+H]+ Calcd for C13H11D3NS 219.1030；Found 219.1032.
EXAMPLE 41
1-dodecyl-2- (methyl-d)3) Synthesis of disulfanes:
Figure BDA0003483912550000251
s-deuterated methyl-4-methylbenzenesulfonylthioester prepared by example 2 (0.22mmol,45.1mg,1.1equiv.) was dissolved in a dry Schlenk tube under a nitrogen atmosphere, and 1mL of anhydrous dichloromethane was added. Then 5ae (40.5mg,0.2mmol,1equiv.), triethylamine (20.2mg, 28.0. mu.L, 0.2mmol,1equiv.) and 0.5mL of anhydrous dichloromethane were made up into a solution, which was slowly added dropwise to a Schlenk tube. The reaction was stirred at room temperature for 4 hours, and after removal of the solvent under reduced pressure, column chromatography purification gave 6ae (35.6 mg, 71%, deuteration > 99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ2.69(q,J＝8.0Hz,2H),1.73–1.64(m,2H), 1.45–1.34(m,2H),1.27(s,16H),0.88(t,J＝6.8Hz,3H)；13C NMR(100MHz, CDCl3)δ39.3,38.5,32.1,29.8,29.7,29.6,29.5,29.4,29.3,28.7,22.8,14.2.HRMS (ESI-TOF)m/z:[M+H]+ Calcd for C13H26D3S2 252.1899；Found 252.1890.
Example 42
1- ((methyl-d)3) Synthesis of sulfoxide) -4-nitrobenzene:
Figure BDA0003483912550000252
s-deuterated methyl-4-methylbenzenesulfonyl thioester (0.22mmol,45.1mg,1.1equiv.) prepared by example 2 was dissolved in a dried Schlenk tube under a nitrogen atmosphere, 1mL of anhydrous dichloromethane was added, then 5af (31.0mg,0.2mmol,1equiv.), triethylamine (20.2mg,28.0 μ L,0.2mmol, 1equiv.) and 0.5mL of anhydrous dichloromethane were formulated into a solution, and the solution was slowly dropped into the Schlenk tube, stirred at room temperature for 4 hours, and after removing the solvent under reduced pressure, column chromatography purification was performed to obtain 6af (32.6 mg, 80%, deuterium substitution > 99%) (eluent polarity: PE).
1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.0Hz,2H),7.65(d,J＝9.0Hz, 2H).13C NMR(100MHz,CDCl3)δ146.6,146.4,125.9,124.3.HRMS(EI-TOF)m/z Calcd for C7H4D3NO2S2204.0107[M]+,Found 204.0104.
Example 43
4- ((methyl-d)3) Synthesis of sulfonyl) -1,1' -biphenyl:
Figure BDA0003483912550000261
6a (0.2mmol,40.6mg,1equiv.) and m-chloroperoxybenzoic acid (81.2mg, 85% mass concentration) were dissolved in dichloromethane (2.0mL) under an air atmosphere in a Schlenk tube, and the reaction was stirred at room temperature for 12 hours, and after removing the solvent under reduced pressure, column chromatography purification was performed to obtain 7a (43.7mg, 93%, deuteration rate > 99%) (eluent polarity: PE: EA ═ 1: 1).
1H NMR(400MHz,CDCl3)δ8.01(d,J＝8.5Hz,2H),7.77(d,J＝8.5Hz,2H), 7.63–7.59(m,2H),7.52–7.47(m,2H),7.46–7.41(m,1H)；13C NMR(100MHz, CDCl3)δ146.9,139.3,139.2,129.2,128.8,128.1,128.0,127.5.HRMS(ESI-TOF) m/z:[M+H]+ Calcd for C13H10D3O2S 236.0825；Found 236.0823.mp:(132.0– 133.2)℃.
Example 44
4- ((methyl-d)3) Synthesis of sulfoxide) -1,1' -biphenyl:
Figure BDA0003483912550000262
6a (0.2mmol,40.6mg,1equiv.) and sodium periodate (51.3mg,0.24mmol,1.2equiv.) were dissolved in methanol to water to 1:1(2.0mL) in a Schlenk tube under an air atmosphere, and the reaction was heated at 50 ℃ for 6 hours, after completion of the reaction, the solvent was removed under reduced pressure, and column chromatography purification was performed to obtain 7b (36.4 mg, 83%, deuteration > 99%) (eluent polarity: EA).
1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.6Hz,2H),7.70(d,J＝8.6Hz,2H), 7.62–7.58(m,2H),7.49–7.44(m,2H),7.42–7.36(m,1H)；13C NMR(100MHz, CDCl3)δ144.4,144.2,139.8,129.1,128.2,128.1,127.3,124.1.HRMS(ESI-TOF) m/z:[M+H]+ Calcd for C13H10D3OS 220.0875；Found 220.0870.mp:(137.4– 139.0)℃.
Example 45
(Z) -N- ([1,1' -Biphenyl)]-4-yl (methyl-d)3)-λ4-sulfoxide group) cyanamide synthesis:
Figure BDA0003483912550000271
under a nitrogen atmosphere, in a Schlenk tube, 6a (0.1mmol,20.3mg,1.1equiv.), NCNH2(5.0mg,0.12mmol,1.2equiv.),PhI(OAc)2(35.4mg,0.11mmol,1.1equiv.) acetonitrile (2.0mL) was added, the reaction was stirred at 0 ℃ for 12 hours, the solvent was removed under reduced pressure, and column chromatography purification was performed to obtain 7c (21.9mg, 90%, deuteration rate)>99%) (eluent polarity: EA).
1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.6Hz,2H),7.79(d,J＝8.6Hz,2H), 7.60–7.55(m,2H),7.52–7.46(m,2H),7.46–7.40(m,1H)；13C NMR(100MHz, CDCl3)δ146.5,139.0,134.6,129.3,129.0,128.9,127.4,126.7,124.1.HRMS (ESI-TOF)m/z:[M+Na]+ Calcd for C14H9D3N2S266.0802；Found 266.0807。

Claims (10)

1. An S-deuterated methyl-aryl sulfonyl thioester compound is characterized in that the structural formula is shown as a formula (4),
Figure FDA0003483912540000011
wherein R is1Is selected from phenyl, substituted phenyl or condensed ring, and the substituent on the substituted phenyl is methyl, methoxy, tertiary butyl or halogen.
2. A method of synthesizing the S-deuterated methyl-arylsulfonyl thioester compound according to claim 1, comprising the steps of:
1) in an organic solvent, reacting deuterated methanol shown in formula (1) with an electrophilic reagent in an environment of alkali and nitrogen to generate an intermediate shown in formula (2);
2) reacting an intermediate shown in a formula (2) with aryl sodium sulfosulfonate shown in a formula (3) under the action of a phase transfer catalyst to obtain a compound shown in a formula (4), wherein the reaction process is as follows:
Figure FDA0003483912540000012
wherein R is1Is selected from phenyl, substituted phenyl or condensed ring, and the substituent on the substituted phenyl is methyl, methoxy, tertiary butyl or halogen.
3. The method of claim 2, wherein the electrophile is trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride, or methanesulfonic anhydride, and the electrophile is used in an amount of 1.05 to 5.0 equivalents to the deuterated methanol of formula (1).
4. The synthesis method of claim 2, wherein the base is 2, 6-lutidine or triethylamine, and the amount of the base is 1.0 to 5.0 equivalents to the deuterated methanol represented by formula (1).
5. The method of synthesis according to claim 2, wherein the organic solvent is N, N-dimethylacetamide or acetonitrile.
6. The synthesis method of claim 2, wherein the phase transfer catalyst is tetrabutylammonium iodide, and the amount of the phase transfer catalyst is 2.5 to 100 mol% of the deuterated methanol represented by formula (1).
7. The synthesis method of claim 2, wherein the molar ratio of the deuterated methanol of formula (1) to the aryl thiosulfonate of formula (3) is from 1.0:1.0 to 1.0: 5.0.
8. The method of claim 2, wherein the reaction temperature of step 1) is-20 to 0 ℃; the reaction temperature of the step 2) is 30-100 ℃.
9. The synthesis method according to claim 2, wherein the reaction time of step 1) is 1-4 h; the reaction time of the step 2) is 4-12 h.
10. The use of the S-deuterated methyl-arylsulfonyl thioesters of claim 1, wherein the use is in the synthesis of aryl deuterated methyl-thiophenyl ether compounds, in the synthesis of compounds containing C-S bonds, in the synthesis of compounds containing P-S bonds, in the synthesis of compounds containing N-S bonds, and in the synthesis of disulfide compounds.
CN202210075728.5A 2022-01-22 2022-01-22 S-deuterated methyl-aryl sulfonyl thioester compound and synthetic method and application thereof Active CN114478150B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210075728.5A CN114478150B (en) 2022-01-22 2022-01-22 S-deuterated methyl-aryl sulfonyl thioester compound and synthetic method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210075728.5A CN114478150B (en) 2022-01-22 2022-01-22 S-deuterated methyl-aryl sulfonyl thioester compound and synthetic method and application thereof

Publications (2)

Publication Number Publication Date
CN114478150A true CN114478150A (en) 2022-05-13
CN114478150B CN114478150B (en) 2024-04-09

Family

ID=81473182

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210075728.5A Active CN114478150B (en) 2022-01-22 2022-01-22 S-deuterated methyl-aryl sulfonyl thioester compound and synthetic method and application thereof

Country Status (1)

Country Link
CN (1) CN114478150B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114835615A (en) * 2022-05-26 2022-08-02 南京工业大学 Organic sulfur compound and preparation method thereof
CN115057803A (en) * 2022-07-28 2022-09-16 杭州师范大学 S- (methyl-d) 3 ) Synthetic method and application of phenylether substances

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100197909A1 (en) * 2007-05-24 2010-08-05 Yasumichi Fukuda Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in subtituent at 14-position
US20110306771A1 (en) * 2010-06-10 2011-12-15 Econous Systems Inc. Avoidance of non-specific binding on an acoustic wave biosensor using linker and diluent molecules for device surface modification

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100197909A1 (en) * 2007-05-24 2010-08-05 Yasumichi Fukuda Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in subtituent at 14-position
US20110306771A1 (en) * 2010-06-10 2011-12-15 Econous Systems Inc. Avoidance of non-specific binding on an acoustic wave biosensor using linker and diluent molecules for device surface modification

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
CHENG-MI HUANG等: "Visible-Light-Promoted Cross-Coupling Reactions of Aryldiazonium Salts with S-Methyl-d3 Sulfonothioate or Se-Methyl-d3 Selenium Sulfonate: Synthesis of Trideuteromethylated Sulfides, Sulfoxides, and Selenides", 《ORGANIC LETTERS》, vol. 22, no. 22, pages 12 - 12 *
DRABOWICZ, J.等: "Alkanesulfenic acids and acyclic derivatives", 《SCIENCE OF SYNTHESIS》, no. 39, pages 565 - 566 *
KIYOKO FUJIKI等: "Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides and Related Novel Biscarbonyldisulfides", 《SYNTHESIS》, no. 7, pages 1035, XP001064760, DOI: 10.1055/s-2001-14566 *
NORIO SHIBATA等: "A stereocontrolled synthesis of protected (2R,3R)-3-mercaptoaspartic acid via a β-aspartyl enolate sulfenylation", 《SYNLETT》, no. 6, pages 519 *
RENYI PANG等: "Synthesis of S-monofluoromethyl phosphorothioates from PV -H compounds and PhSO2SCH2F", 《CHINESE CHEMICAL LETTERS》, no. 32, pages 453 - 456 *
SUGURU YOSHIDA等: "A mild and facile synthesis of aryl and alkenyl sulfides via copper-catalyzed deborylthiolation of organoborons with thiosulfonates", 《CHEM COMMUN》, vol. 51, no. 93, pages 16615 - 264 *
宋婷婷等: "基于硫代磺酸酯的亲电硫化反应研究进展", 《中国科学：化学》, vol. 51, no. 06, pages 628 - 650 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114835615A (en) * 2022-05-26 2022-08-02 南京工业大学 Organic sulfur compound and preparation method thereof
CN114835615B (en) * 2022-05-26 2023-08-22 南京工业大学 Organic sulfur compound and preparation method thereof
CN115057803A (en) * 2022-07-28 2022-09-16 杭州师范大学 S- (methyl-d) 3 ) Synthetic method and application of phenylether substances
CN115057803B (en) * 2022-07-28 2023-11-24 杭州师范大学 S- (methyl-d) 3 ) Synthesis method and application of phenyl sulfide substance

Also Published As

Publication number Publication date
CN114478150B (en) 2024-04-09

Similar Documents

Publication Publication Date Title
CN114478150B (en) S-deuterated methyl-aryl sulfonyl thioester compound and synthetic method and application thereof
JP5969759B2 (en) Organoboron compound and method for producing the same
CN109879731B (en) Diaryl methane halogenated olefin derivative and preparation method thereof
Varala et al. Cesium salts in organic synthesis: A Review
CN101565393A (en) 3-(substituted bisulfonyl fluromethane)-1-propylene compound, synthetic method and applications thereof
JP5923823B2 (en) Intermediate for acene dichalcogenophene derivative and synthesis method thereof
CN102863371B (en) Fluoro pyrrolin or fluoro pyrroles
CN110256342B (en) Synthetic method of 2-cyano quinoline derivative
CN102875421A (en) Aziridine compound loop opening method based on p-nitrobenzoic acid
CN114044751B (en) Deuterated difluoromethylthio reagent, preparation method thereof and introduction of SCF (SCF) into drug molecules 2 Method for preparing D group
CN113214118A (en) Large steric hindrance ligand regulated and controlled regioselective addition method of dienamine and phenylboronic acid
CN114634431A (en) Synthetic method of olefin compound containing thioether and sulfone substituent
JP2019536746A (en) Method for producing phenylalanine compound
CN112898285B (en) Trifluoromethyl-containing bisoxazole compound, and synthesis method and application thereof in anti-cancer drugs
CN113666826A (en) Method for methoxylation of aryl or heteroaryl
CN109134351B (en) Synthesis method of S-3- (4-aminophenyl) piperidine
CN109320481B (en) Carboxylic acid NHPI ester decarboxylation alkylation method and application thereof in synthesis of diaryl derivatives
CN114213298B (en) Method for preparing thiosulfonate compound by directly oxidizing thiophenol
TWI576349B (en) Manufacturing method of borinic acid derivatives and novel borinic acid derivatives
CN115490728B (en) Synthesis method of allyl phosphine derivative
US3898285A (en) Novel enaminosulfoxides and a process for their preparation
JP5207518B2 (en) Process for producing 3- (2-hydroxy-5-methylphenyl) -N, N-diisopropyl-3-phenylpropylamine
JP2008221056A (en) Method of producing indole compound and catalyst
CN117551023A (en) Preparation method and application of N-thio-phenyl phthalimide compound
CN106278968B (en) A kind of method for synthesizing sulfo-amino acid derivative

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant