CN117551023A - Preparation method and application of N-thio-phenyl phthalimide compound - Google Patents

Preparation method and application of N-thio-phenyl phthalimide compound Download PDF

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CN117551023A
CN117551023A CN202311350366.7A CN202311350366A CN117551023A CN 117551023 A CN117551023 A CN 117551023A CN 202311350366 A CN202311350366 A CN 202311350366A CN 117551023 A CN117551023 A CN 117551023A
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phthalimide
mmol
thio
alkenyl
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田俊
高文超
常宏宏
张娟
范婧
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Shanxi Booming Health Technology Co ltd
Taiyuan University of Technology
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Shanxi Booming Health Technology Co ltd
Taiyuan University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • 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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
    • C07D233/84—Sulfur atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
    • C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes

Abstract

The invention discloses a preparation method and application of an N-thio-phthalimide compound, wherein the preparation method is as follows: adding 1, 1-diaryl alkene and phthalimide sulfur chloride into an organic solvent, forming an intermediate through the addition reaction of the phthalimide sulfur chloride to the alkene under the promotion effect of acid or hydrochloride, and removing HCl through trans elimination to form the final alkenyl thiophthalimide. And various alkenyl thioether compounds are simply and efficiently prepared by adopting the reagent. The invention designs and prepares the N-thio-phthalimide reagent library, the raw materials are cheap and easy to obtain, and the preparation steps are simple and convenient; under the action of different catalysts, the alkenyl sulfur modules can be transferred into various molecular frameworks through various reaction conditions.

Description

Preparation method and application of N-thio-phenyl phthalimide compound
Technical Field
The invention relates to a preparation method of an N-thio-phenyl phthalimide compound, which is used for synthesizing various alkenyl thioether compounds, and belongs to the technical field of fine chemical synthesis.
Background
Alkenyl sulfur units are favored by researchers because of their unique bond-like advantages and application value. Specifically, in the bond structure, such a skeleton has both rigidity of a double bond and flexibility of heteroatom sulfur: such as organic small molecule 1, 1-diphenylalkenyl sulfide, is a well known group of Aggregation-induced emission (AIE) chromophores [ acie.2020,59,2338]. As shown in fig. 1.
In view of the unique structural characteristics of the alkenyl sulfide skeleton and the important application value thereof, scientific researchers have conducted extensive research on the synthesis method thereof. The ideas reported so far for the preparation of alkenyl sulfides cover two pathways, biosynthesis and chemical synthesis: the biological pathway mainly utilizes cysteine dehydrogenase to realize the decarboxylation of cysteine with high selectivity, and forms cyclic alkenyl thioether under the action of cyclic enzyme [ ACIE.2021,60,1951]; whereas chemical synthetic routes, alkenyl sulfides are generally built using either Thio-yne reactions in Click chemistry to form alkenyl sulfides, or the free radical C-S oxidation to bond, for example, the Ananikov team employs a photocatalytically implemented Thio-yne domino reaction [ acie.2022,61, e2021168], the Wu Jie team employs a photocatalytically facilitated S8 insertion to build up alkenyl sulfides [ jacs.2023,145,10,5846 ], and, in addition, the Jiang Huanfeng team [ acie.2020,59,2338] reports addition elimination of thiol radicals formed by in situ reduction of sodium sulfinate to yield alkenyl sulfides. A summary of the relevant methods is shown in fig. 2.
The method generally needs an effective chemical reaction of alkenyl and thio structures to form an alkenyl thioether structure, however, the whole alkenyl sulfide is taken as a structural unit and is introduced into various complex structural sites, so that the limitation of alkenyl and thio sources is broken through, and the prior art cannot realize; on the other hand, the precursor alkenyl mercaptan of the alkenyl sulfur unit is a compound which cannot exist stably in nature and is not easily obtained, so that it is important how to introduce the alkenyl sulfur unit by adopting a raw material which has a simple structure and is cheap and easily obtained.
Disclosure of Invention
In view of the importance of the alkenyl thioether structure, the prior synthesis technology has poor universality and complex route, and the invention provides a preparation method of the N-thio-alkenyl phthalimide compound, and various alkenyl thioether compounds are efficiently prepared by adopting the compound.
Alkenyl groups are often incompatible with electrophilic thio groups in the same structure, and the compatibility and stability of both can be enhanced by adding a masking group, phthalimide. The invention creatively designs and prepares a reagent library N-thio-alkenyl phthalimide with modularized introduction of an alkenylthio unit, and realizes the purpose of introducing the alkenylthio group at various sites by using the reagent to construct an alkenyl thioether compound.
The invention provides a preparation method of an N-thio-alkenyl phthalimide compound, which comprises the following preparation conditions:
adding 1, 1-diaryl alkene (I) and phthalimide sulfur chloride (II) into an organic solvent, forming an intermediate III through the addition reaction of the phthalimide sulfur chloride to alkene under the promotion effect of acid or hydrochloride, and removing HCl through trans-elimination to form the final alkenyl thiophthalimide IV.
Wherein the structural formula of the 1, 1-diaryl olefin (I) is as follows:
the structural formula of the phthalimide sulfur chloride (II) is as follows:
the structural formula of the alkenyl thiophthalimide IV is as follows:
the general reaction is as follows:
in the above, R 1 、R 2 Respectively one of phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, p-acetylphenyl, p-benzoylphenyl, p-cinnamoyl and dihydrodibenzocycloheptenyl.
In the preparation method of the N-thio-alkenyl phthalimide compound, the relevant process conditions are further described:
the promoter is one of pyridine hydrochloride, triethylamine hydrochloride, pyridine hydrofluoric acid salt, p-chloropyridine hydrochloride, hydrochloric acid and trifluoroacetic acid; preferably, the accelerator is pyridine hydrochloride.
The molar ratio of the reaction raw materials 1, 1-diaryl olefin to phthalimide sulfur chloride to the accelerator is 1: (1-10): (1-10), preferably, the three raw materials are in a molar ratio of 1:1:1.1.
The reaction temperature is 0-50 ℃, preferably 25 ℃.
The organic solvent is one of dichloromethane, ethyl acetate, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile and N, N-dimethylformamide; preferably, the reaction solvent is methylene chloride; the solvent is used in an amount of 0.1 to 1mmol/mL, preferably 0.1mmol/mL, based on the 1, 1-diarylkene substrate.
The invention provides a method for preparing an alkenyl thioether compound by adopting the N-thio-alkenyl phthalimide reagent, which comprises the following steps:
various alkenyl thioether compounds can be constructed by utilizing the alkenyl thiophthalimide IV, and the diaryl alkenyl thioether compounds are synthesized through the coupling reaction of the alkenyl thiophthalimide IV and aryl boric acid under the action of a copper catalyst as shown in the following formulas (2) - (5); coupling reaction with alkyne under the action of copper catalyst to synthesize diaryl alkenyl alkynyl thioether; reacting with beta-keto ester under the catalysis of Lewis base to synthesize alkenyl thioether containing quaternary carbon center; the alkenyl thioether containing amino acid ester is constructed by the carbene insertion reaction of the rhodium catalyst and the azobenzene acetate.
In the above, R 1 、R 2 Respectively one of phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, p-acetylphenyl, p-benzoylphenyl, p-cinnamoyl and dihydrodibenzocycloheptenyl; r is R 3 Is one of phenyl, p-tolyl, p-tert-butylphenyl, p-methoxyphenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-cyanophenyl, p-nitrophenyl, 2,4, 6-trimethylphenyl, 1-naphthyl and N-methylimidazole; r is R 4 Is p-methoxyphenyl.
In the reaction formula (2), the diaryl alkenyl phenyl sulfide compound is synthesized through the coupling reaction of the diaryl alkenyl phenyl sulfide compound and phenylboronic acid under the action of a copper catalyst;
the reaction catalyst is one of cuprous bromide, cuprous chloride, cupric bromide and cupric sulfate, and preferably the catalyst is cupric bromide; the reaction ligand is one of 1, 10-azophenanthrene, 1-bipyridine and 2,2' -biquinoline, and preferably the reaction ligand is 2, 2-bipyridine; the reaction base is one of potassium carbonate, sodium carbonate, cesium carbonate and lithium carbonate, and preferably the reaction base is potassium carbonate; the reaction temperature is 0-100 ℃, preferably 60 ℃; the reaction solvent is one of tetrahydrofuran, 1, 2-dimethoxyethane, acetonitrile and toluene, preferably tetrahydrofuran; the molar ratio of the reaction raw material sulfur reagent, boric acid, reaction catalyst, ligand and reaction alkali is 1 (0.5-2): (0.1-1): (0.1-1): (1-3), preferably, the raw material molar ratio is 1:1:0.1:0.2:2; the reaction solvent is used in an amount of 0.1 to 1mmol/mL (based on the N-thioalkenyl phthalimide reagent), and preferably the solvent is used in an amount of 0.1mmol/mL.
In the reaction formula (3), the diaryl alkenyl alkynyl thioether is synthesized through the coupling reaction of alkyne and copper catalyst; the reaction catalyst is copper acetonitrile hexafluorophosphate, the reaction ligand is 2, 2-bipyridine, the solvent is 1, 1-dichloroethane, and the reaction temperature is 80 ℃; the reaction solvent is used in an amount of 0.1 to 1mmol/mL (based on the N-thioalkenyl phthalimide reagent), and preferably the solvent is used in an amount of 0.1mmol/mL.
In the reaction formula (4), catalyzing a C-S bond formation reaction with beta-keto ester by using Lewis base as a catalyst to synthesize alkenyl thioether containing a quaternary carbon center;
the Lewis base catalyst is 4-dimethylaminopyridine DMAP, triethylenediamine DABCO, diazabicyclo DBU, triethylamine Et 3 Any one of N, tetramethylguanidine TMG, cinchona alkaloid derivatives and trimethylamine, preferably, the reaction catalyst is 4-dimethylaminopyridine; the molar amount of the catalyst is 1-100mol% of the beta-keto ester, preferably 20mol%; the reaction solvent is one of dichloromethane, 1-dichloromethane, tetrahydrofuran and toluene, preferably, the reaction solvent is dichloromethane; the solvent dosage is 0.1-1mmol/mL (tested with N-thioalkenyl phthalimideThe agent is based on the total amount of the solvent), preferably 0.2mmol/mL.
In the above reaction formula (5), the carbene insertion reaction with azobenzene acetate under the action of rhodium catalyst is carried out to construct alkenyl thioether containing amino acid ester.
The reaction catalyst is one of rhodium diacetate and rhodium difluoroacetate, and preferably the catalyst is rhodium diacetate; the catalyst is used in an amount of 1 to 10mol% (based on the N-thioalkenyl phthalimide reagent), preferably 1mol%; the reaction solvent is one of toluene, n-hexane and 1, 2-dichloroethane, preferably, the reaction solvent is n-hexane; the solvent is used in an amount of 0.1 to 1mmol/mL (based on the N-thioalkenyl phthalimide reagent), preferably 0.1mmol/mL; the reaction temperature is 60-100 ℃, preferably 80 ℃.
The invention has the beneficial effects that:
the invention designs and prepares the N-thio-phthalimide reagent library, the raw materials are cheap and easy to obtain, and the preparation steps are simple and convenient; under the action of different catalysts, the alkenyl sulfur modules can be transferred into various molecular frameworks through various reaction conditions.
Drawings
FIG. 1 is a schematic diagram showing aggregation-induced emission of small organic molecule 1, 1-diphenylalkenyl sulfide.
FIG. 2 is a schematic representation of the synthesis of an alkenyl sulfide of the prior art.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, to which the present invention is not limited. Variations and advantages that would occur to one skilled in the art are included in the invention without departing from the spirit and scope of the inventive concept, and the scope of the invention is defined by the appended claims. The procedures, conditions, reagents, experimental methods, etc. for carrying out the present invention are common knowledge and common knowledge in the art, except for those specifically mentioned below, and the present invention is not particularly limited. The data presented in the examples below include specific operations and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
Example 1: synthesis of Compound IVa
1, 1-diphenylethylene (1 mmol,0.18 g) and phthalimidothiochloride (1 mmol,0.22 g) were added to 10mL of methylene chloride, pyridine hydrochloride (1 mmol,0.115 g) was added as an accelerator, and reacted at 25℃for 12 hours, the obtained solution was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=5:1), and the objective product fraction was collected and concentrated under reduced pressure to give a white solid product (292 mg, 82%). TLC, R f ＝0.30(PE:EtOAc＝5:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.85(s,2H),7.70(s,2H),7.32(dd,J＝18Hz,J＝6.8Hz,5H),7.15(s,3H),7.10(s,2H),6.38(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ167.6,141.2,140.4,138.1,134.7,134.3,132.1,129.5,128.6,128.4,128.3,127.8,127.4,124.7,124.0,123.6.HRMS(ESI)m/zcalcd.for C 22 H 15 NO 2 SNa[M+Na] + :380.0716,found:380.0721。
Example 2: synthesis of Compound IVb
1, 1-bis (4-chlorophenyl) ethylene (0.1 mmol,25 mg) and phthalimide sulfur chloride (1 mmol,0.22 g) were added to 10mL of ethyl acetate, pyridine hydrofluoric acid salt (0.11 mmol,11 mg) was added as an accelerator, reacted at 0℃for 18 hours, the resulting solution was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=5:1), the target product fraction was collected, and concentrated under reduced pressure to give a white solid product (33.2 mg, 78%). TLC, R f ＝0.20(PE:EtOAc＝5:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.94(q,J＝3.2Hz,2H),7.81(q,J＝3.2Hz,2H),7.41(d,J＝8.4Hz,2H),7.31(d,J＝8.4Hz,2H),7.22(d,J＝8.8Hz,2H),7.08(d,J＝8.8Hz,2H),6.47(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ167.4,138.1,138.5,136.0,134.9,134.6,134.0,132.0,130.9,129.1,128.6,128.6,128.5,127.1,125.8,124.1.HRMS(ESI)m/zcalcd.for C 22 H 14 Cl 2 NO 2 S[M+H] + :426.0117,found:426.0100。
Example 3: synthesis of Compound IVc
1, 1-bis (4-bromophenyl) ethylene (0.1 mmol,34 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL of dichloroethane, triethylamine hydrochloride (0.2 mmol,27 mg) was further added as an accelerator, the resultant solution was reacted at 50℃for 18 hours, the solution was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=5:1), the objective product fraction was collected, and concentrated under reduced pressure to give a pale yellow solid (41.9 mg 82%). TLC, R f ＝0.20(PE:EtOAc＝5:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.93(q,J＝3.2Hz,2H),7.80(q,J＝3.2Hz,2H),7.55(d,J＝8.4Hz,2H),7.37(d,J＝8.8Hz,2H),7.24(d,J＝8.4Hz,2H),7.01(d,J＝8.4Hz,2H),6.48(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ167.4,138.9,138.7,136.4,134.9,134.8,132.1,132.0,131.6,131.5,131.2,128.9,127.4,126.0,124.1,122.8,122.2.HRMS(ESI)m/zcalcd.for C 22 H 13 Br 2 NO 2 SNa[M+Na] + :535.8926,found:537.8901。
Example 4: synthesis of Compound IVd
1, 1-bis (4-methylphenyl) ethylene (0.1 mmol,20 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL of acetonitrile, pyridine hydrochloride (0.1 mmol,11 mg) was further added as an accelerator, the resultant solution was reacted at 25℃for 10 hours, the resultant solution was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=5:1), and the objective product fraction was collected, concentrated under reduced pressure to give a pale yellow solid (26.9 mg, 70%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.84(q,J＝3.2Hz,2H),7.69(q,J＝2.8Hz,2H),7.18～7.12(m,4H),6.97(q,J＝8.4Hz,4H),6.31(s,1H),2.30(s,3H),2.22(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ167.6,141.5,138.2,137.8,137.7,135.3,134.7,132.1,129.5,129.3,129.0,127.4,124.0,123.1,21.4,21.2.HRMS(ESI)m/z calcd.for C 24 H 19 NO 2 SNa[M+Na] + :408.1029,found:408.1018。
Example 5: synthesis of Compound IVe
1, 1-bis (4-methoxyphenyl) ethylene (0.1 mmol,24 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mLN, N-dimethylformamide, pyridine hydrochloride (0.1 mmol,11 mg) was further added as an accelerator, the resultant solution was reacted at 25℃for 10 hours, the solution was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=5:1), and the objective product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (27.9 mg, 67%). TLC, R f ＝0.20(PE:EtOAc＝3:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.93(q,J＝3.2Hz,2H),7.78(q,J＝3.2Hz,2H),7.30(dt,J＝8.8Hz,J＝2Hz,2H),7.11(dt,J＝8.8Hz,J＝3.2Hz,2H),6.95(dt,J＝8.8Hz,J＝2.8Hz,2H),6.77(dt,J＝9.2Hz,J＝2.8Hz,2H),6.32(s,1H),3.85(s,3H),3.77(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ167.7,159.6,159.4,141.4,134.7,133.4,132.1,130.9,130.6,128.8,124.0,121.5,113.9,113.6,55.3.HRMS(ESI)m/zcalcd.for C 24 H 20 NO 4 S[M+H] + :418.1108,found:418.1112。
Example 6: synthesis of Compound IVf
1-chloro-4 (1-p-tolenyl) benzene (0.1 mmol,22 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Adding pyridine hydrochloride (0.1 mmol,11 mg) as promoter, reacting at 25deg.C for 20 hr, concentrating under reduced pressure, purifying by column chromatography (PE: etOAc=5:1), collecting target product fraction, and concentrating under reduced pressure to obtain whiteColor solid (34.3 mg, 85%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz)(isomer ratio3:2):δ7.96(q,J＝2.8Hz,2H),7.82(q,J＝3.6Hz,2H),7.42(d,J＝8.4Hz,1H),7.35(d,J＝8.4Hz,1H),7.28～7.21(m,3H),7.15～7.05(m,3H),6.46(d,J＝15.2Hz,1H),2.41(s,1.2H),2.33(s,1.8H). 13 C NMR(CDCl 3 ,100MHz):δ167.5,140.5,139.8,139.0,138.6,138.1,137.3,136.6,134.8,134.2,133.6,132.1,131.0,129.5,129.4,129.1,128.9,128.7,128.4,127.2,124.9,124.0,123.9,21.4,21.1.HRMS(ESI)m/zcalcd.for C 23 H 16 ClNO 2 SNa[M+Na] + :428.0482,found:428.0470。
Example 7: synthesis of Compound IVg
1-bromo-4- (1-p-tolenyl) benzene (0.1 mmol,22 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, the reaction was carried out at 25℃for 15 hours, the resulting solution was concentrated under reduced pressure, and the resultant was purified by column chromatography (PE: etOAc=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (33 mg, 74%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz)(isomer ratio1:1):δ7.96(q,J＝2.8Hz,2H),7.82(q,J＝3.2Hz,2H),7.58(d,J＝8.4Hz,1H),7.39(d,J＝8.8Hz,1H),7.30(d,J＝6.8Hz,3H),7.08～7.06(m,3H),6.48(s,0.5H),6.45(s,0.5H),2.42(s,1.5H),2.33(s,1.5H). 13 C NMR(CDCl 3 ,100MHz):δ167.5,140.5,139.8,139.5138.6,138.1,137.2,137.1,134.8,134.8,134.6,132.1,132.1,131.8,131.4,131.3,129.5,129.4,129.1,129.0,127.2,125.0,124.1,123.9,122.5,121.8,21.4,21.1.HRMS(ESI)m/z calcd.for C 23 H 16 BrNO 2 SNa[M+Na] + :471.9977,found:473.9943。
Example 8: synthesis of Compound IVh
4-Acetylphenyl-4' -methylphenyl ethylene (0.1 mmol,24 mg) and phthalimide sulfur chloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, the reaction was carried out at 25℃for 10 hours, the resulting solution was concentrated under reduced pressure, and the resultant was purified by column chromatography (PE: etOAc=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (35.5 mg, 86%). TLC, R f ＝0.20(PE:EtOAc＝3:1)； 1 H NMR(CDCl 3 ,400MHz)(Z-isomer):δ8.01(d,J＝8.4Hz,2H),7.93(m,2H),7.79(m,2H),7.50(d,J＝8.4Hz,2H),7.05(q,J＝5.6Hz,4H),6.52(s,1H),2.64(s,3H),2.31(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ197.6,167.4,143.1,140.6,138.1,137.0,136.6,134.8,134.3,132.0,129.8,129.1,128.6,127.2,124.5,124.0,123.5,26.7,21.1.HRMS(ESI)m/z calcd.for C 25 H 20 NO 3 S[M+H] + :414.1158,found:414.1148。
Example 9: synthesis of Compound IVi
4-benzoylphenyl-4' -methylphenylethylene (0.1 mmol,30 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, the reaction was carried out at 25℃for 10 hours, the resulting solution was concentrated under reduced pressure, and the resultant was purified by column chromatography (PE: etOAc=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (40.4 mg, 85%). TLC, R f ＝0.20(PE:EtOAc＝3:1)； 1 H NMR(CDCl 3 ,400MHz)(isomer ratio 1:3):δ7.96～7.93(m,2H),7.89～7.85(m,3H),7.83～7.79(m,2H),7.78-7.68(m,1H),7.64-7.56(m,1H),7.55～7.44(m,3.7H),7.30-7.26(m,1.3H),7.07(m,3H),6.57-6.52(s,0.25,0.75H),2.40(s,0.75H),2.32(s,2.25H). 13 C NMR(CDCl 3 ,100MHz):δ196.2,167.5,142.5,140.6,138.1,137.4,137.13,137.10,134.8,132.5,132.0,130.4,130.1,130.0,129.6,129.5,129.3,129.1,128.4,128.3,127.4,127.1,124.7,124.1,76.7,21.2.HRMS(ESI)m/z calcd.for C 30 H 22 NO 3 S[M+H] + :476.1315,found:476.1308。
Example 10: synthesis of Compound IVj
2- (4- (p-tolyl) vinylphenyl) ethylene-1, 2-triphenyltriphenylbenzene (0.1 mmol,45 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, the reaction was carried out at 25℃for 10 hours, the resulting solution was concentrated under reduced pressure, and the resultant was purified by column chromatography (PE: etOAc=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (46.8 mg, 75%). TLC, R f ＝0.30(PE:EtOAc＝5:1)； 1 H NMR(CDCl 3 ,400MHz)(isomer ratio 3:2):δ8.00～7.96(m,2H),7.81～7.77(m,2H),7.22(s,2H),7.20～7.02(m,19H),6.94(q,J＝4Hz,2H),6.39(s,0.6H),6.34(s,0.4H),2.38(s,1.8H),2.31(s,1.2H), 13 C NMR(CDCl 3 ,100MHz):δ167.65(167.56),143.8,143.7,143.63(143.56),143.56(143.52),143.26(143.20),141.53,141.2,140.8,140.6,140.4,138.17(138.12),137.58(137.56),136.2,135.0,134.66(134.63),132.11(132.09),131.37(131.31),131.27(131.23),129.4,129.3,128.9,127.7,127.62(127.57),127.3,126.6,126.50(126.45),126.45(126.42),124.0(123.95),123.90,21.3,21.1.HRMS(ESI)m/zcalcd.for C 43 H 31 NO 2 SNa[M+Na] + :648.1968,found:648.1960。
Example 11: synthesis of Compound IVk
4-Paraphthylphenyl-4' -p-cinnamoyl phenylethene (0.1 mmol,32 mg) and phthalimidothiochloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, and the mixture was reacted at 25℃for 16 hours,the resulting solution was concentrated under reduced pressure, purified by column chromatography (PE: etoac=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (26 mg, 52%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 HNMR(CDCl 3 ,400MHz):δ8.08(d,J＝8.4Hz,2H),7.93(q,J＝3.2Hz,2H),7.84(s,1H),7.79(q,J＝3.2Hz,2H),7.67(dd,J＝7.6Hz,J＝4.4Hz,2H),7.59(s,1H),7.54(d,J＝8.4Hz,3H),7.44(dd,J＝4.8Hz,J＝1.6Hz,4H),6.53(s,1H),2.32(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ188.9,167.5,166.5,143.9,141.8,139.6,137.1,136.8,136.0,133.8,133.7,133.3,131.6,131.0,130.0,128.9,128.1,128.0,127.8,127.5,126.3,123.5,123.0,122.6,120.9,21.1.HRMS(ESI)m/z calcd.for C 32 H 23 NO 3 SNa[M+Na] + :524.1291,found:524.1289。
Example 12: synthesis of Compound IVl
5-vinyl-10, 11-dihydro-5H-dibenzo [ a, d ]][7]Heptene (0.1 mmol,21 mg) and phthalimide sulfur chloride (0.1 mmol,22 mg) were added to 1mL CH 2 Cl 2 Pyridine hydrochloride (0.1 mmol,11 mg) was added as an accelerator, the reaction was carried out at 25℃for 16h, the resulting solution was concentrated under reduced pressure, and the resultant was purified by column chromatography (PE: etOAc=5:1), and the desired product fraction was collected and concentrated under reduced pressure to give a pale yellow solid (33 mg, 87%). Yield33.3 mg (87%); time is 15h; yellow solid; TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.82(q,J＝3.2Hz,2H),7.67(q,J＝3.2Hz,2H),7.24～7.12(m,5H),7.10～6.97(m,3H),6.23(s,1H),3.07(s,4H). 13 C NMR(CDCl 3 ,100MHz):δ167.6,143.5,139.2,138.9,138.0,137.8,134.7,132.1,130.0,129.0,128.8,128.1,128.0,127.9,126.3,126.2,126.1,124.0,33.4,32.3.HRMS(ESI)m/z calcd.for C 24 H 17 NO 2 SNa[M+Na] + :406.0872,found:406.0862。
Example 13: synthesis of Compound Va
Sulfur reagent IVa (35.7 mg,0.1 mmol) and 4-methylphenylboronic acid (16.31 mg,0.12 mmol) were weighed in sequence and copper bromide (4.46 mg,0.02 mmol), 2-bipyridine (3.12 mg,0.02 mmol), potassium carbonate (13.82 mg,0.2 mmol) were dissolved in freshly distilled THF (2 mL) under nitrogen atmosphere, reacted at 60℃for 5h, the resulting mixture was concentrated under reduced pressure and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a pale yellow solid (24 mg, 82%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.37～7.33(m,2H),7.29(t,J＝3.2Hz,4H),7.20～7.16(m,6H),7.07(d,J＝7.6Hz,2H),6.75(s,1H),2.27(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ141.5,140.2,139.2,137.0,132.8,130.1,129.9,129.8,128.4,128.3,127.8,127.2,125.3,21.1。
Example 14: synthesis of Compound Vb
Sulfur reagent IVa (356 mg,1 mmol) and 4-tert-butylphenylboronic acid (178 mg,1.2 mmol) were weighed in sequence and copper bromide (44.6 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled THF (10 mL) under nitrogen atmosphere, reacted at 60℃for 5h, the resulting mixture was concentrated under reduced pressure and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plates, and the solution was collected and concentrated under reduced pressure to give a white solid (244 mg, 71%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.34～7.27(m,6H),7.25～7.23(m,2H),7.20～7.11(m,6H),6.75(s,1H),1.22(s,9H). 13 C NMR(CDCl 3 ,100MHz):δ150.2,141.6,140.2,139.3,132.9,129.8,129.8,128.4,128.3,127.7,127.2,126.2,125.1,34.6,31.3。
Example 15: synthesis of Compound Vc
Sulfur reagent IVa (356 mg,1 mmol) and phenylboronic acid (122 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2' -biquinoline (31.2 mg,0.2 mmol), sodium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled acetonitrile (10 mL) under nitrogen atmosphere, reacted for 5h at 60℃and the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (247 mg, 86%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.36(t,J＝16Hz,4H),7.29(d,J＝8Hz,4H),7.24～7.17(m,7H),6.79(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ141.5,141.1,139.2,136.5,129.8,129.54,129.1,128.4,128.3,128.3,128.2,127.8,127.3,127.2,126.8,124.1。
Example 16: synthesis of Compound Vd
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Sulfur reagent IVa (356 mg,1 mmol) and p-methoxyphenylboronic acid (152 mg,1 mmol) were weighed out sequentially under nitrogen atmosphere and copper sulfate (31 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled toluene (10 mL) were reacted at 60℃for 5h, the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a bright yellow solid (232 mg, 73%). TLC, R f ＝0.20(PE:EtOAc＝97:3)； 1 H NMR(CDCl 3 ,400MHz):δ7.37～7.26(m,8H),7.19～7.14(m,6H),6.81(d,J＝8Hz,2H),6.69(s,1H),3.74(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ159.3,141.5,139.2,132.6,129.8,128.4,128.3,127.7,127.1,127.1,126.8,126.6,114.8,55.4。
Example 17: synthesis of Compound Ve
Sulfur reagent IVa (356 mg,1 mmol) and p-chlorobenzeneboronic acid (156 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled toluene (10 mL) under nitrogen atmosphere, reacted for 5h at 25℃and the resulting mixture was concentrated under reduced pressure and purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (244 mg, 76%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.42～7.28(m,7H),7.24～7.17(m,7H),6.71(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ142.0,141.2,139.0,135.1,132.8,130.7,129.71,129.3,129.1,128.4,128.4,128.2,128.0,127.5,127.2,123.2。
Example 18: synthesis of Compound Vf
Sulfur reagent IVa (356 mg,1 mmol) and p-bromophenylboronic acid (200 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled toluene (10 mL) under nitrogen atmosphere, reacted at 80℃for 5h, the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (290 mg, 80%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.38～7.18(m,14H),6.70(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ142.2,141.2,139.0,135.8,132.2,130.9,129.7,128.5,128.4,128.0,127.6127.3,123.0,120.7。
Example 19: synthesis of Compound Vg
Sulfur reagent IVa (356 mg,1 mmol) and p-trifluoromethylboron are combined under nitrogenAcid (190 mg,1 mmol), copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were weighed in sequence and dissolved in freshly distilled toluene (10 mL), reacted at 100℃for 5h, the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plates, and the solution was collected and concentrated under reduced pressure to give a white solid (234 mg, 66%). TLC, R f ＝0.30(PE)； 1 HNMR(CDCl 3 ,400MHz):δ7.48(d,J＝8.4Hz,2H),7.4(d,J＝8Hz,2H),7.36～7.29(m,3H),7.26～7.16(m,7H),6.76(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ144.0,141.8,141.1,138.9,129.7,128.6,128.5(d,J＝2.7Hz),128.3,128.2,128.0(d,J＝32Hz),127.4,126.0,125.9,125.9(q,J＝4.7Hz),125.4,124.1(q,J＝275.0Hz),122.7,121.0,120.0. 19 F NMR(CDCl 3 ,376MHz):δ-62.4。
Example 20: synthesis of Compound Vh
Sulfur reagent IVa (356 mg,1 mmol) and p-nitrobenzoic acid (156 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled toluene (10 mL) under nitrogen atmosphere, reacted for 5h at 60℃and the resulting mixture was concentrated under reduced pressure and purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a yellow solid (210 mg, 63%). TLC, R f ＝0.30(PE)； 1 HNMR(CDCl 3 ,400MHz):δ8.10(dt,J＝9.2Hz,J＝2.4Hz,2H),7.49～7.29(m,J＝Hz,12H),6.86(s,2H). 13 C NMR(CDCl 3 ,100MHz):δ146.7,146.4,145.7,140.8,138.6,129.6,128.5,128.5,128.4,128.2,127.5,127.3,124.2,118.5。
Example 21: synthesis of Compound Vi
Sulfur reagent IVa (356 mg,1 mmol) and 2,4, 6-trimethylphenylboronic acid (164 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled 1, 2-dimethoxyethane (10 mL) under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (274 mg, 83%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.39～7.29(m,5H),7.17～7.07(m,6H),6.88(s,2H),6.28(s,1H),2.39(s,6H),2.21(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ142.3,141.6,139.4,138.6,138.4,130.4,129.7,129.1,128.4,128.2,127.6,126.8,22.2,21.1。
Example 22: synthesis of Compound Vj
Sulfur reagent IVa (351 mg,1 mmol) and 1-naphthalene boronic acid (172 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled toluene (10 mL) under nitrogen atmosphere, reacted for 5h at 60℃and the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a brown solid (192 mg, 57%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ8.26(d,J＝8Hz,1H),7.8(dd,J＝8Hz,J＝1.6Hz,1H),7.74(s,J＝8.4Hz,1H),7.67(dd,J＝7.2Hz,J＝1.2Hz,H),7.51～7.31(m,9H),7.20～7.14(m,7H),6.73(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ141.5,140.8,139.2,134.1,133.4,132.9,129.8,129.7,128.6,128.5,128.4,128.3,127.9,127.3,127.3,127.2,126.7,126.4,125.7,125.4,125.1.HRMS(ESI)m/z calcd.for C 23 H 16 BrNO 2 SNa[M+Na] + :361.1021,found:361.1021。
Example 23: synthesis of Compound Vk
Sulfur reagent IVa (400.5 mg,1 mmol) and 1-methyl-1H-imidazolyl-2-boronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) were dissolved in freshly distilled tetrahydrofuran (10 mL) under nitrogen atmosphere, reacted at 60℃for 2H, the resulting mixture was concentrated under reduced pressure, purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plates, and the solution was collected and concentrated under reduced pressure to give a brown solid (367 mg, 63%). TLC, R f ＝0.30(PE:EA＝0.25)； 1 H NMR(CDCl 3 ,400MHz):7.45～7.33(m,5H),7.25(s,5H),7.11(s,1H),7.05(s,1H),6.95(s,1H),3.58(s,3H). 13 CNMR(CDCl 3 ,100MHz):δ140.9,140.8,140.4,140.0,129.6,128.6,128.26,128.0,127.4,127.2,122.8,121.0,33.4.HRMS(ESI)m/zcalcd.for C 18 H 18 N 2 S[M+H] + :293.1107,found:293.1107。
Example 24: synthesis of Compound Vl
Sulfur reagent IVd (385 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (247 mg, 75%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.33(d,J＝8Hz,2H),7.23(d,J＝2.4Hz,3H),7.14(dd,J＝8Hz,J＝2Hz,4H),7.09(t,J＝8.4Hz,3H),6.735(s,1H),2.39(s,4H),2.33(d,J＝4Hz,7H). 13 C NMR(CDCl 3 ,100MHz):δ139.4,137.8,136.4,135.9,135.7,135.4,132.0,128.8,128.8,128.6,128.0,127.9,126.1,122.5,20.3,20.1,20.0。
Example 25: synthesis of Compound Vm
Sulfur reagent IVe (417 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (297 mg, 75%). TLC, R f ＝0.20(PE:EtOAc＝95:5)； 1 H NMR(CDCl 3 ,400MHz):δ7.35(d,J＝8Hz,2H),7.30(dt,J＝8Hz,J＝4Hz,2H),7.19(dt,J＝8.8Hz,J＝2Hz,2H),7.15(d,J＝4Hz,2H),6.96(dt,J＝8.8Hz,J＝2.8Hz,2H),6.83(dt,J＝8.8Hz,J＝3.2Hz,2H),6.65(s,1H),3.86(s,3H),3.81(s,3H),2.35(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ158.0,157.9,139.1,135.6,133.6,132.2,130.7,130.0,128.8,128.7,127.4,121.0,112.6,112.6,54.3,54.2,20.0.HRMS(ESI)m/zcalcd.for C 23 H 16 BrNO 2 SNa[M+Na] + :385.1233,found:385.1233。
Example 26: synthesis of Compound Vn
Sulfur reagent IVb (425 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (229 mg, 62%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.41(dt,J＝12Hz,J＝2Hz,2H),7.35(d,J＝4Hz,2H),7.29(dt,J＝8.4Hz,J＝2Hz,2H),7.25(dt,J＝8.8Hz,J＝2.4Hz,2H),7.15(dd,J＝12.4Hz,J＝8Hz,4H),6.81(s,1H),2.36(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ139.7,137.5,137.4,137.2,133.8,133.2,132.1,131.1,130.4,130.1,130.0,128.8,128.5,128.3,126.9,118.6,21.1.HRMS(ESI)m/zcalcd.for C 23 H 16 BrNO 2 S[M] + :370.0350,found:370.0344。
Example 27: synthesis of Compound Vo
Sulfur reagent IVc (425 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (271mg, 59%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.55(dt,J＝8.4Hz,J＝2.4Hz,2H),7.39(dt,J＝8.8Hz,J＝2Hz,2H),7.33(d,J＝8.4Hz,2H),7.22(dt,J＝8.8Hz,J＝2Hz,2H),7.16(d,J＝8Hz,2H),7.07(dt,J＝8.8Hz,J＝2.4Hz,2H),6.81(s,1H),2.35(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ140.0,137.6,137.6,137.4,132.0,131.8,131.5,131.5,130.4,130.1,128.7,127.0,122.0,121.4,21.1。
Example 28: synthesis of Compound Vp
Sulfur reagent IVi (470 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed out sequentially and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were added under nitrogen atmosphere,the mixture was concentrated under reduced pressure and purified by column chromatography (PE: etoac=99:1) and the isolation and purification was monitored by TLC plates, and the solution was collected and concentrated under reduced pressure to give a yellow solid (380 mg, 90%). TLC, R f ＝0.20(PE:EtOAc＝1:19)； 1 H NMR(CDCl 3 ,400MHz)(1:2isomer):δ7.80～7.77(m,2.5H),7.78-7.76(m,0.75H),7.71(d,J＝8.0Hz,0.75H),7.62-7.54(m,4H),7.38-7.30(m,3H),7.25(d,J＝8.0Hz,1H),7.19-7.08(m,5H),6.96(s,0.33H),6.84(s,0.67H),2.41(s,1H),2.34(s,3H),2.33(s,2H). 13 C NMR(CDCl 3 ,100MHz):δ196.3(196.1),145.4,143.8,139.2,(138.4)138.3,137.9,137.6,137.43(137.38),137.2,136.5,135.7,135.6132.5,132.42,(132.37),132.27,130.4,130.1,130.1,130.0,129.8,129.6,129.3,129.1,128.3(128.2),127.2,126.7,125.6,21.11(21.08),21.07.HRMS(ESI)m/z calcd.for C 29 H 24 OS[M+Na] + :443.1440,found:443.1440。
Example 29: synthesis of Compound Vq
Sulfur reagent IVh (413 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a yellow solid (297 mg, 83%). TLC, R f ＝0.20(PE:EtOAc＝98:2)； 1 H NMR(CDCl 3 ,400MHz):δ8.02(d,J＝8.4Hz,2H),7.48(d,J＝8.4Hz,2H),7.35(d,J＝8Hz,2H),7.16(d,J＝7.6Hz,2H),7.11(s,4H),6.84(s 1H),2.65(s,3H),2.35(d,J＝4.4Hz,6H). 13 C NMR(CDCl 3 ,100MHz):δ197.7,144.5,139.2,138.2,137.4,137.3,136.2,132.4,130.1,130.1,130.0,129.2,128.5,127.1,125.6,26.7,21.2,21.1.HRMS(ESI)m/zcalcd.for C 23 H 16 BrNO 2 SNa[M+Na] + :381.1284,found:381.1284。
Example 30: synthesis of Compound Vr
Sulfur reagent IVl (383 mg,1 mmol) and 4-methylphenylboronic acid (126 mg,1 mmol) were weighed in sequence and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification was monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (206 mg, 63%). TLC, R f ＝0.30(PE:CH 2 Cl 2 ＝95:5)； 1 H NMR(CDCl 3 ,400MHz):δ7.40～7.38(m,1H),7.34(dd,J＝7.2Hz,J＝1.6Hz,1H),7.31(d,J＝8.4Hz,2H),7.26～7.20(m,2H),7.17(td,J＝7.2Hz,J＝1.6Hz,2H),7.12(d,J＝8.8Hz,2H),7.10(d,J＝2Hz,1H),6.66(s,1H),3.19(s,4H),2.33(s,3H). 13 C NMR(CDCl 3 ,100MHz):δ141.7,140.1,139.2,138.9,137.6,136.8,132.8,130.1,129.8,128.7,128.5,128.4,128.2,127.5,126.4,126.2,125.8,33.8,32.3,21.1.HRMS(ESI)m/zcalcd.for C 23 H 21 S[M+H] + :329.1358,found:329.1357。
Example 31: synthesis of Compound Vs
Sulfur reagent IVa (356 mg,1 mmol) and p-cyanobenzylboronic acid (147 mg,1 mmol) were weighed out sequentially and copper bromide (27 mg,0.2 mmol), 2-bipyridine (31.2 mg,0.2 mmol), potassium carbonate (138.2 mg,2 mmol) dissolved in freshly distilled tetrahydrofuran (10 mL) were reacted under nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure at 60℃and purified by column chromatography (PE: etOAc=99:1), the isolation and purification were monitored by TLC plate, and the solution was collected and concentrated under reduced pressure to give a white solid (187 mg, 60%). TLC, R f ＝0.30(PE)； 1 H NMR(CDCl 3 ,400MHz):δ7.49(dt,J＝8.4Hz,J＝2Hz,2H),7.37～7.17(m,12H),6.741(s,1H). 13 C NMR(CDCl 3 ,100MHz):δ144.6,143.0,139.8,137.6,131.4,128.6,127.4,127.2,127.1,126.8,126.4,118.1,117.7,108.2。
Example 32: synthesis of Compound VI
Sulfur reagent IVa (317 mg,1 mmol), p-methoxyphenylacetylene (66 mg,0.5 mmol), potassium carbonate (138 mg,1 mmol), cu (CH) were sequentially added to a reaction flask equipped with a stirrer under a nitrogen atmosphere 3 CN) 4 PF 6 (37 mg,0.1 mmol) and 2,2' -bipyridine (18.7 mg,0.12 mmol) were added ultra-dry 1, 2-dichloroethane (4.0 mL) then reacted at 80℃for 12h after the reaction was completed, cooled to room temperature, concentrated under reduced pressure, and the residue was separated by flash column chromatography (PE/EA=50/1) to give a brown liquid (206 mg, 58%). TLC, R f ＝0.30(PE:EtOAc＝50:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.44～7.37(m,5H),δ7.29～7.22(m,7H),6.85(t,J＝8.4Hz,2H),6.78(s,1H),3.81(s,3H). 13 C NMR(101MHz,CDCl 3 ):δ159.9,141.6,140.6,138.0,133.6,129.6,128.6,128.4,128.3,128.2,127.6,127.1,122.6,115.0,114.0,93.7,55.3.HRMS(APCI)m/z calcd.for C 23 H 19 OS[M+H] + :343.1151；found343.1167。
Example 33: synthesis of Compound VIIa
To a reaction flask containing a magneton was added methyl indenone ketonate (190 mg,1 mmol), sulfur reagent IVa (356 mg,1 mmol), and diazabicyclo (30 mg,0.2 mmol) and methylene chloride (10 mL) in this order under nitrogen. Stirring at 25deg.C for 12 hr, concentrating under reduced pressure after the reaction, purifying the concentrate by column chromatography (PE/EA=10:1), and collecting the target fraction to concentrate to obtain yellow solid (360 mg, 90%). TLC, R f ＝0.23(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.94(d,J＝8Hz,1H),7.72(td,J＝8Hz,4Hz,1H),7.52(dd,J＝12,8Hz，2H),7.44-7.32(m,11H),4.03(d,J＝4Hz,1H),3.94(s,3H),3.28(s,1H)； 13 C{1H}NMR(CDCl 3 ,100MHz,):δ196.3,169.5,150.4,141.7,141.4,138.9,135.6,133.9,129.8,128.3,127.9,127.3,126.2,125.7,120.0,59.2,53.7,39.5。
Example 34: synthesis of Compound VIIb
To a reaction flask containing a magneton was added methyl indenone ketonate (190 mg,1 mmol), sulfur reagent IVc (425 mg,1 mmol), and 4-dimethylaminopyridine (24 mg,0.2 mmol) and 1, 1-dichloromethane (1 mL) in this order under nitrogen. Stirring at 25℃for 12h, concentrating under reduced pressure after the reaction, purifying the concentrate by column chromatography (PE/EA=10:1), and collecting the desired fraction to concentrate as a yellow solid (470 mg, 84%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.83(d,J＝8Hz,1H),7.64(dt,J＝8Hz,4Hz,1H),7.43(q,J＝8Hz,6H),7.21(s,1H),3.94(d,J＝16Hz,1H),3.83(s,3H),3.15(s,1H)； 13 C{1H}NMR(100MHz,CDCl 3 )δ196.2,169.3,150.3,139.9,139.2,137.3,135.8,133.7,131.7,131.4,128.9,128.5,126.2,125.7,122.1,121.6,59.0,53.7,39.4。
Example 35: synthesis of Compound VIIc
To a reaction flask containing a magneton was added methyl indenone ketonate (190 mg,1 mmol), sulfur reagent IVc (425 mg,1 mmol), and triethylenediamine (22 mg,0.1 mmol) and tetrahydrofuran (5 mL) in this order under nitrogen. Stirring at 25deg.C for 24h, concentrating under reduced pressure after the reaction, purifying the concentrate by column chromatography (PE/EA=10:1), and collecting the target fraction and concentrating to obtain yellow solid (400 mg, 86%). TLC, R f ＝0.18(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.87(q,J＝4Hz,1H),7.83(d,J＝8Hz,1H),7.76(q,J＝4Hz,1H),7.62(t,J＝8Hz,1H),7.42(t,J＝8Hz,2H),7.15(q,J＝12Hz,4H),6.89(s,1H),6.80-6.86(m,4H),3.83(s,3H),3.80(d,J＝4Hz,6H)； 13 C{1H}NMR(100MHz,CDCl 3 )δ196.3,169.6,159.1,150.5,141.8,135.6,134.6,134.4,134.0,131.1,128.8,128.3,126.2,125.7,123.7,117.0,113.6,59.5,55.4,53.6,39.6。
Example 36: synthesis of Compound VIId
To a reaction flask containing a magneton was added methyl indenone ketonate (190 mg,1 mmol), sulfur reagent IVc (425 mg,1 mmol), and tetramethylguanidine (115 mg,1 mmol) and toluene (10 mL) in this order under nitrogen. Stirring at 25deg.C for 24h, concentrating under reduced pressure after the reaction, purifying the concentrate by column chromatography (PE/EA=10:1), and collecting the target fraction to concentrate to obtain yellow solid (360 mg, 85%). TLC, R f ＝0.20(PE:EtOAc＝4:1)； 1 H NMR(CDCl 3 ,400MHz):δ7.75(q,J＝4Hz,1H),7.53(t,J＝8Hz,1H),7.26-7.36(m,3H),6.95-7.10(m,7H),6.84(s,1H),3.82(d,J＝4Hz,1H),3.72(s,3H),3.09(d,J＝4Hz,5H)； 13 C{1H}NMR(101MHz,CDCl3)δ196.3,169.5,150.5,143.5,139.9,139.1,138.9,137.2,135.6,135.5,133.9,130.1,129.0,128.7,128.3,128.2,127.5,126.6,126.2,126.2,125.7,125.6,124.7,121.2,59.6,53.6,53.2,52.8,39.7,33.7,32.0,29.7,26.9,22.7,14.2,1.1。
Example 37: synthesis of Compound VIII
Methyl diazophenylacetate (26.4 mg,0.15 mmol) and sulfur reagent IVa (35.7 mg,0.1 mmol) were dissolved in n-hexane (1 mL) under nitrogen, rhodium acetate catalyst (2.8 mg,1 mol%) was added, reacted at 70℃for 12h, after removal of the solvent by rotary evaporation under vacuum, purified by column chromatography (PE: etOAc=3:1), and the solution was collected and concentrated under reduced pressure to give a yellow solid (34 mg, 67%). 1 H NMR(CDCl 3 ,400MHz):δ7.84(dd,J＝5.2Hz,J＝2.4Hz,2H),7.77-7.73(m,4H),7.41-7.39(m,3H),7.32(dd,J＝4.8Hz,J＝2.8Hz,3H),7.17(dd,J＝4.8Hz,J＝2.8Hz,3H),7.11-7.08(m,2H),7.00-6.97(m,2H),6.82(s,1H),3.76(s,3H)； 13 C{1H}NMR(CDCl 3 ,100MHz,):
δ166.5,166.0,142.8,140.3,137.5,133.5,133.3132.6,130.4,128.7,127.8127.7,127.2,127.2,
127.1,126.9,126.3,126.2,122.6,122.6,119.0,76.3,76.0,75.7,52.8.HRMS(ESI)m/z calcd.for
C 31 H 23 NO 4 SNa[M+Na] + :506.1421,found:506.1418。

Claims (10)

1. A preparation method of an N-thio-alkenyl phthalimide compound is characterized by comprising the following steps: the preparation conditions are as follows:
adding 1, 1-diaryl alkene and phthalimide sulfur chloride into an organic solvent, forming an intermediate through the addition reaction of the phthalimide sulfur chloride on the alkene under the promotion effect of promoter acid or hydrochloride, and removing HCl through trans elimination to form the final alkenyl thiophthalimide.
2. The method for producing an N-thio-phthalimide compound according to claim 1, characterized in that: the structural formula of the 1, 1-diaryl olefin is as follows:
the structural formula of the phthalimide sulfur chloride is as follows:
the structural formula of the alkenyl thiophthalimide is as follows:
in the above, R 1 、R 2 Respectively one of phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, p-acetylphenyl, p-benzoylphenyl, p-cinnamoyl and dihydrodibenzocycloheptenyl.
3. The method for producing an N-thio-phthalimide compound according to claim 1, characterized in that: the promoter is one of pyridine hydrochloride, triethylamine hydrochloride, pyridine hydrofluoric acid, p-chloropyridine hydrochloride, hydrochloric acid and trifluoroacetic acid.
4. The method for producing an N-thio-phthalimide compound according to claim 1, characterized in that: the molar ratio of the reaction raw materials 1, 1-diaryl olefin to phthalimide sulfur chloride to the accelerator is 1: (1-10): (1-10); the reaction temperature is 0-50 ℃.
5. The method for producing an N-thiolylphthalimide compound according to claim 4, characterized in that: the molar ratio of the reaction raw materials 1, 1-diaryl olefin to phthalimide sulfur chloride to the accelerator is 1:1:1.1; the reaction temperature was 25 ℃.
6. The method for producing an N-thio-phthalimide compound according to claim 1, characterized in that: the organic solvent is one of dichloromethane, ethyl acetate, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile and N, N-dimethylformamide; the solvent is used in an amount of 0.1 to 1mmol/mL based on the 1, -diarylkene substrate.
7. A process for producing an alkenyl sulfide compound using the N-thio-phthalimide compound produced by the process as claimed in any one of claims 1 to 6, characterized by comprising the steps of:
coupling reaction with aryl boric acid under the action of copper catalyst to synthesize diaryl alkenyl phenyl sulfide compound;
the reaction catalyst is one of cuprous bromide, cuprous chloride, cupric bromide and cupric sulfate, the reaction ligand is one of 1, 10-azodiphenanthrene, 1-bipyridine and 2,2' -biquinoline, the reaction alkali is one of potassium carbonate, sodium carbonate, cesium carbonate and lithium carbonate, the reaction temperature is 0-100 ℃, the reaction solvent is one of tetrahydrofuran, 1, 2-dimethoxyethane, acetonitrile and toluene, and the molar ratio of the reaction raw materials of sulfur reagent, boric acid, the reaction catalyst, the ligand and the reaction alkali is 1 (0.5-2): (0.1-1): (0.1-1): (1-3); the dosage of the reaction solvent is 0.1-1mmol/mL based on the N-thio-phthalimide reagent.
8. A process for producing an alkenyl sulfide compound using the N-thio-phthalimide compound produced by the process as claimed in any one of claims 1 to 6, characterized by comprising the steps of: under the action of a copper catalyst, performing a coupling reaction with alkyne to synthesize diaryl alkenyl alkynyl thioether; the reaction catalyst is copper acetonitrile hexafluorophosphate, the reaction ligand is 2, 2-bipyridine, the solvent is 1, 1-dichloroethane, and the reaction temperature is 80 ℃; the dosage of the reaction solvent is 0.1-1mmol/mL, based on the N-thio-phenyl phthalimide reagent.
9. A process for producing an alkenyl sulfide compound using the N-thio-phthalimide compound produced by the process as claimed in any one of claims 1 to 6, characterized by comprising the steps of: catalyzing C-S bond formation reaction with beta-keto ester by using Lewis base as a catalyst to synthesize alkenyl thioether containing quaternary carbon center;
the Lewis base catalyst is 4-dimethylaminopyridine DMAP, triethylenediamine DABCO, diazabicyclo DBU, triethylamine Et 3 N, tetramethyl guanidine TMG, cinchona alkaloid derivative and trimethylamine, wherein the molar amount of the catalyst is 1-100mol% of beta-keto ester, the reaction solvent is one of dichloromethane, 1-dichloromethane, tetrahydrofuran and toluene, the solvent amount is 0.1-1mmol/mL, and the catalyst is prepared from N-sulfurAlkenyl phthalimide reagent is used as a reference.
10. A process for producing an alkenyl sulfide compound using the N-thio-phthalimide compound produced by the process as claimed in any one of claims 1 to 6, characterized by comprising the steps of: under the action of rhodium catalyst, the catalyst reacts with carbene insertion of azobenzene acetate to construct alkenyl thioether containing amino acid ester;
the reaction catalyst is one of rhodium diacetate and rhodium difluoroacetate, the catalyst dosage is 1-10mol percent, and the N-thio-phthalimide reagent is taken as a reference; the reaction solvent is one of toluene, normal hexane and 1, 2-dichloroethane, the solvent dosage is 0.1-1mmol/mL, and the N-thio-phthalimide reagent is taken as a reference; the reaction temperature is 60-100 ℃.
CN202311350366.7A 2023-10-18 2023-10-18 Preparation method and application of N-thio-phenyl phthalimide compound Pending CN117551023A (en)

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