CN116969864A - Synthesis method of aromatic sulfonyl fluoride compound - Google Patents

Synthesis method of aromatic sulfonyl fluoride compound Download PDF

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Publication number
CN116969864A
CN116969864A CN202310937286.5A CN202310937286A CN116969864A CN 116969864 A CN116969864 A CN 116969864A CN 202310937286 A CN202310937286 A CN 202310937286A CN 116969864 A CN116969864 A CN 116969864A
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bromide
nickel
aromatic
catalyst
alkyl
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郑昌戈
陈锡飞
赵奎
冯瑞龙
洪建权
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Jiangnan University
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Jiangnan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C07C303/18—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by reaction of sulfides with compounds having functional groups with formation of sulfo or halosulfonyl groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
    • B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
    • B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/847—Nickel

Abstract

The invention discloses a synthesis method of an aromatic sulfonyl fluoride compound, belonging to the field of organic chemistry. The method of the invention uses cheap and easily obtained Na respectively 2 S 2 O 4 The nickel acetate tetrahydrate is a nickel source, the applicability of the substrate is wide, the raw materials are simple and easy to obtain, and the economic cost is low; in addition, the method can realize the synthesis of the target product, and the target product can be obtained in a better yield only by reacting for 15 hours, so that the method is more rapid and efficient. The synthesis method of the invention converts the beta-arylvinyl bromide or benzyl bromide which is easy to obtain into aromatic sulfonyl fluoride under a simpler condition, realizes sulfonyl fluorination of the beta-arylvinyl bromide or benzyl bromide by a one-pot method, and the target compound is used in new drug development and new materialsThe method has wide application in the fields of material synthesis and the like.

Description

Synthesis method of aromatic sulfonyl fluoride compound
Technical Field
The invention particularly relates to a synthesis method of an aromatic sulfonyl fluoride compound, belonging to the field of organic chemistry.
Background
In recent years, as sulfonyl fluoride compounds are receiving increasing attention from the academy and industry, research and application thereof in the fields of chemical biology, drug design, biochemistry and the like have been widely conducted. The sulfonyl fluoride group is introduced to not only enhance the drug effect, but also endow the molecule with good biological activity, and the research value and the application prospect are great. Correspondingly, the synthesis method of the sulfonyl fluoride compound also becomes a leading edge and hot spot field of the current synthesis chemistry. The traditional synthesis method of the sulfonyl fluoride compound is mainly based on fluorine-chlorine exchange reaction, and new synthesis methods such as oxidative fluorination of low-valence sulfur compounds and free radical fluorosulfonylation are reported in succession in recent years, so that the synthesis method of the compound is greatly enriched. In addition, the rapid and structural diversity construction of the molecular library resources can be realized by adopting the synthetic building blocks containing sulfonyl fluoride groups or the multi-connectivity molecules.
Disclosure of Invention
The invention develops a novel method for synthesizing aromatic sulfonyl fluoride. According to the invention, beta-arylvinyl bromide or benzyl bromide reacts with a sulfur dioxide source under the catalysis of a catalyst, and finally, an aromatic sulfonyl fluoride compound is synthesized under the action of N-fluoro bis-benzenesulfonyl imine (NFSI), so that dehalogenation sulfonyl fluorination of aryl halides is realized conveniently, rapidly and efficiently.
The invention aims to provide a synthesis method of aromatic sulfonyl fluoride, which comprises the steps of firstly reacting an aromatic brominated substrate shown in a formula (1) and a sulfur dioxide source for a period of time under the action of a catalyst and a ligand in an organic solvent, then adding NFSI to continue to react, and synthesizing to obtain an aromatic sulfonyl fluoride compound shown in a formula (2);
wherein R isOr->
R 1 Selected from H, C C1-C8 alkyl, C1-C8 haloalkyl, aryl, halo (F, cl, br, I), cyano, trifluoromethylthio, C1-C8 alkoxy, acyl, and amido; r is R 2 And R is 3 Selected from H, C C4 alkyl and aryl;
R 4 selected from H, C C1-C8 alkyl, C1-C8 haloalkyl, aryl, halo (F, cl, br, I), cyano, trifluoromethylthio, C1-C8 alkoxy, acyl, and amido;
in one embodiment of the invention, the method comprises the steps of performing functionalization reaction on beta-arylvinyl bromide shown in a formula (1 a) or benzyl bromide shown in a formula (1 b), a sulfur dioxide source and NFSI serving as reactants under the action of a catalyst, and synthesizing an aromatic sulfonyl fluoride compound shown in a formula (2 a) or a formula (2 b) correspondingly;
in one embodiment of the invention, the sulfur dioxide source is sodium dithionite Na 2 S 2 O 4 。
In one embodiment of the invention, the ligand is any one or more of the following:
in one embodiment of the invention, aryl includes a substituted or unsubstituted benzene ring, naphthalene ring; the substitution may be one to three; the substituted groups being selected from halogen, C 1 -C 8 Alkyl, C 1 -C 8 An alkoxy group.
In one embodiment of the invention, the acyl group is-C (O) R ', R' is selected from C1-C8 alkyl.
In one embodiment of the invention, the amide group is-C (O) -NR a R b ，R a 、R b Independently selected from C1-C8 alkyl, or-NR a R b Is thatn=1 or 2.
In one embodiment of the invention, aryl includes a substituted or unsubstituted benzene ring, naphthalene ring; the substitution may be one to three; the substituted groups being selected from halogen, C 1 -C 8 Alkyl, C 1 -C 8 An alkoxy group.
In one embodiment of the present invention, the organic solvent includes any one or more of methanol and ethanol. Methanol is preferred.
In one embodiment of the invention, the catalyst is one or more of palladium acetate, palladium dichloride, tetraphenylphosphine palladium, and phosphine ligand-containing palladium catalysts, bis (triphenylphosphine) nickel chloride, nickel acetate or a hydrate thereof, nickel sulfate, nickel bromide, nickel carbonate, nickel, phosphine ligand-containing nickel catalysts.
In one embodiment of the invention, the method further comprises adding additives, namely: the aromatic bromination substrate shown in the formula (1) and the sulfur dioxide source react for a period of time under the action of a catalyst, a ligand and an additive, then NFSI is added for continuous reaction, and the aromatic sulfonyl fluoride compound shown in the formula (2) is synthesized. The additive is any one or more of triethylamine, sodium acetate, 1, 8-diazabicyclo undec-7-ene, potassium carbonate, potassium tert-butoxide, acetic acid, ammonium acetate, tetrabutylammonium bromide, tetrabutylammonium fluoride and lithium hydroxide monohydrate. Sodium acetate is preferred.
In one embodiment of the invention, the molar ratio of aromatic bromination substrate (. Beta. -arylvinyl bromide or benzyl bromide) to catalyst is 1 (0-1). Specifically, the ratio of the raw materials is 1:0.1.
In one embodiment of the invention, the molar feed ratio of aromatic bromination substrate (β -arylvinyl bromide or benzyl bromide) to sulfur dioxide source is 1: (0.5-2.0); preferably 1: (0.9-1.5); specifically, 1:1.2 is selected.
In one embodiment of the invention, the molar ratio of aromatic bromination substrate (. Beta. -arylvinyl bromide or benzyl bromide) to ligand is 1 (0.1-1.1). Specifically selectable 1:0.2
In one embodiment of the invention, the molar ratio of aromatic brominated substrate (. Beta. -arylvinyl bromide or benzyl bromide) to NFSI is 1 (1.0-3.0). Specifically, the ratio of the two components is 1:2.
In one embodiment of the invention, the molar ratio of aromatic bromination substrate (. Beta. -arylvinyl bromide or benzyl bromide) to additive is 1 (0.0-2.0). Specifically selectable 1:1
In one embodiment of the invention, the aromatic bromination substrate (. Beta. -arylvinyl bromide or benzyl bromide) is reacted at a concentration of 0.05 to 5mmol/mL. Specifically, 0.1mmol/mL is preferred.
In one embodiment of the invention, the reaction is carried out under an inert atmosphere. Such as: nitrogen (N) 2 ) Atmosphere.
In one embodiment of the invention, an aromatic bromination substrate (beta-arylvinyl bromide or benzyl bromide), na 2 S 2 O 4 The molar ratio of NFSI, catalyst, ligand, additive is specifically selected to be 1:1.2:2:0.1:0.2:1.
In one embodiment of the invention, the process is carried out by first reacting at 30-100 ℃ for 0.5-15 hours, then returning to room temperature and adding NFSI for further reaction for 2-5 hours.
Further, when R isAnd then the reaction is carried out for 0.5 to 1 hour under 55 to 100 hours, and then the reaction is carried out for 2 to 5 hours after the reaction is carried out at room temperature by adding NFSI. Specifically, the reaction is carried out for 0.5h at 65 ℃, then the reaction is carried out at room temperature, NFSI is added, and the reaction is continued for 3h.
When R isWhen the reaction is carried out, firstly, the reaction is carried out for 10 to 15 hours at the temperature of 30 to 50 ℃, then the reaction is carried out at room temperature, and NFSI is added for continuous reaction for 2 to 5 hours. Specifically, the reaction is carried out for 12 hours at 35 ℃ and then the recovery is carried outNFSI was added to room temperature and the reaction continued for 3h.
In one embodiment of the invention, a novel green economical synthesis method comprises the following steps:
with beta-arylvinyl bromide or benzyl bromide and Na 2 S 2 O 4 Adding a catalyst, a ligand and an additive into the raw materials, stirring the mixture at the temperature of between 30 and 100 ℃ for reacting for a period of time to obtain a crude product of the aromatic sulfonyl fluoride compound or benzyl bromide, and then filtering, washing, distilling under reduced pressure and separating by column chromatography to obtain the pure aromatic sulfonyl fluoride compound.
In one embodiment of the present invention, the separation is performed by flash column chromatography to obtain the final aromatic sulfonyl fluoride compound.
In one embodiment of the invention, the method is preferably carried out as follows: beta-arylvinyl bromide or benzyl bromide, na 2 S 2 O 4 Adding the catalyst, the ligand and the additive into a reaction vessel containing a methanol solvent according to the molar ratio of 1:1.2:0.1:0.2:1, stirring for 12 hours at 60-80 ℃, then returning to room temperature, adding 2 equivalents of NFSI, continuously reacting for 3 hours, separating and purifying to obtain the target product.
In one embodiment of the invention, the reaction mechanism of the invention is as follows: under the catalysis of copper, beta-arylvinyl bromide or benzyl bromide coordinates with nickel, sodium dithionite is homolyzed to generate sulfur dioxide negative free radical, nickel is reduced, one molecule of sulfur dioxide is generated, sulfur dioxide is inserted between metal and carbon atoms, one molecule of aryl sulfite is finally removed to form, and NFSI is finally added to react with the sulfur dioxide to obtain a final product.
In one embodiment of the present invention, the use of the resulting β -arylvinylsulfonyl fluoride compound represented by formula (2 a) comprises:
(a) Beta-arylvinylsulfonyl fluoride compounds per se as reactive small molecules; such as: the document (JOURNAL OF ENZYME INHIBITION AND MEDICINAL chemistry.2018,33 (1), 1266-1270) reports that β -arylvinylsulfonyl fluoride compounds have certain telomerase TERT inhibitory activity and are useful as TERT inhibitors; the literature (European Journal of Medicinal chemistry.2019,162, 364-377) reports that the beta-arylvinyl sulfonyl fluoride compound has certain antibacterial activity and can be used as an antibacterial drug; and literature (Bioorganic chemistry.2019,89,103015) reports that β -arylvinylsulfonyl fluoride compounds have better antioxidant and anti-inflammatory activity.
(b) The beta-arylvinyl sulfonyl fluoride compound can be further synthesized into medicines/fine chemical products as an intermediate; such as: the synthesis of β -arylvinylsulfonyl fluoride compounds as starting materials with HPPh2 to give a chiral phosphine is reported in literature (Journal of Organometallic chemistry.2019,899, 120912). Chiral phosphines play an important role in pharmaceutical and fine chemical production. Typically, these optically active compounds participate in the manufacturing process as ligands in organic catalysts or metal-mediated catalytic systems to induce asymmetry.
In one embodiment of the present invention, the use of the resulting aryl methylsulfonyl fluoride compound of formula (2 b) includes:
useful as serine protease inhibitors, see chem. Sci.2015,6,2650-2659.
Vinyl sulfonyl fluoride can be used in a "one-pot click" reaction to directly convert the product to aryl substituted β -sultams. These compounds were found to be selectively addressable amphiphilic reagents for sulfur (vi) fluorine exchange (safex) click chemistry, where the vinyl moiety or sulfonyl fluoride group may be a specific site for nucleophilic attack.
The beneficial effects are that:
the process of the invention is carried out under nitrogen (N) 2 ) In the atmosphere, beta-arylvinyl bromide or benzyl bromide is taken as a substrate, na 2 S 2 O 4 The target compound can be obtained by debrominating sulfonyl fluorination of beta-arylvinyl bromide or benzyl bromide under the action of a catalyst, a ligand and NFSI.
The method of the invention uses cheap and easily obtained Na respectively 2 S 2 O 4 The catalyst is sulfur dioxide source, nickel acetate is used as catalyst, the applicability of the substrate is wide, the raw materials are simple and easy to obtain, and the economic cost is low; in addition, the method of the invention only needs 15 hours of reaction to realize the synthesis of the target productThe target product can be obtained with better yield, and the method is more rapid and efficient.
The synthesis method of the invention converts the beta-arylvinyl bromide or benzyl bromide which is easy to obtain into the aromatic sulfonyl fluoride compound under a simpler condition, realizes sulfonyl fluorination of the beta-arylvinyl bromide or benzyl bromide by a one-pot method, and has wide application in the fields of new drug development, new material synthesis and the like.
Drawings
FIG. 1 is a synthetic route diagram of the method of the present invention.
Detailed Description
The following are specific embodiments of the present invention.
The synthetic route diagram of the embodiment of the invention is shown in fig. 1:
beta-arylvinyl bromide or benzyl bromide, na 2 S 2 O 4 Adding the catalyst, the ligand and the additive into a reaction bottle containing a methanol solvent according to the molar ratio of 1:1.2:0.1:0.2, stirring for 12 hours at 50-100 ℃, then returning to room temperature, adding 2 equivalents of NFSI, continuously reacting for 3 hours, separating and purifying to obtain the target product. The reaction expression is shown in figure 1.
The ligand structure involved is as follows:
example 1: synthesis of 4-methoxystyrylsulfonyl fluoride
Under the protection of nitrogen, 4-methoxystyryl bromide (1 mmol) and Na are respectively added 2 S 2 O 4 (1.2 mmol), sodium acetate (1 mmol), nickel acetate tetrahydrate (0.1 mmol), bis (2-diphenylphosphinophenyl) ether (ligand L7,0.2 mmol) and methanol (10 mL) were added to a 25mL reaction tube equipped with a stirrer, and the reaction was allowed to proceed for 0.5 hour at 65℃and then NFSI (2 mmol) was added to the reaction tube after the temperature was recovered for 3 hours. Cooling to room temperature after the reaction, diluting with ethyl ester, washing with distilled water and saturated sodium chloride solution, vacuum concentrating to remove solvent, and separating and purifying target substance by column chromatography149mg of product was obtained in 69% yield (77% of fluorine spectrum).
1 H NMR(400MHz,CDCl 3 )δ7.75(d,J＝15.4Hz,1H),7.54-7.46(m,2H),7.01-6.90(m,2H),6.70(dd,J＝15.4,2.6Hz,1H),3.87(s,3H). 13 C NMR(101MHz,CDCl 3 )δ163.28(s),148.62(d,J＝2.5Hz),131.11(s),123.61(d,J＝0.9Hz),114.88(s),114.67(d,J＝27.6Hz),55.58(s). 19 FNMR(376MHz,CDCl3)δ63.03(s).
Example 2: synthesis of 4-chlorosulfonyl fluoride
Under the protection of nitrogen, 4-chloro-beta-styryl bromide (1 mmol) and Na are respectively added 2 S 2 O 4 (1.2 mmol), sodium acetate (1 mmol), nickel acetate tetrahydrate (0.1 mmol), bis (2-diphenylphosphinophenyl) ether (ligand L7,0.2 mmol) and methanol (10 mL) were added to a 25mL reaction tube equipped with a stirrer, and the reaction was allowed to proceed for 0.5 hour at 65℃and then NFSI (2 mmol) was added to the reaction tube after the temperature was recovered for 3 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted with ethyl ester as an additive, washed with distilled water and saturated sodium chloride solution, and concentrated in vacuo to remove the solvent, and then the target product was purified by column chromatography to give 154mg of the product in a yield of 70%.
1 H NMR(400MHz,CDCl 3 )δ7.76(d,J＝15.5Hz,1H),7.54-7.41(m,4H),6.86(dd,J＝15.5,2.5Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ147.49(d,J＝2.8Hz),139.00(s),130.30(s),129.88(s),129.53(d,J＝0.9Hz),118.60(d,J＝28.5Hz). 19 F NMR(376MHz,CDCl3)δ62.34(s).
Example 3: synthesis of benzylsulfonyl fluorides
Under the protection of nitrogen, benzyl bromide (1 mmol) and Na are respectively added 2 S 2 O 4 (1.2 mmol), sodium acetate (1 mmol), nickel acetate tetrahydrate (0.1 mmol), bis (2-diphenylphosphinophenyl) ether (ligand L7,0.2 mmol) and methanol (10 mL) were added to a 25mL reaction tube equipped with a stirrer, and the reaction was allowed to proceed for 12 hours at 35℃and NFSI (2 mmol) was added after the temperature was returned to room temperature, followed by 3 hours. After the reaction, cooling to room temperature, diluting with ethyl ester as additive, washing with distilled water and saturated sodium chloride solution, vacuum concentrating to remove solvent, andthe target was purified by column chromatography to give 87mg of the product in 50% yield.
1 H NMR(400MHz,CDCl 3 )δ7.71-7.34(m,5H),4.60(d,J＝3.2Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ131.69(s),130.94(s),130.35(s),126.55(s),57.88(d,J＝17.7Hz). 19 F NMR(376MHz,CDCl3)δ51.44(s).
Following the synthesis procedure in example 1, the substrate 4-methoxystyryl bromide was replaced with other unsubstituted styryl bromides having C on the benzene ring 1 -C 8 Alkyl, cyano, trifluoromethylthio, -C (O) R', -C (O) -NR a R b Substituted styryl bromides and the like can obtain the beta-arylvinyl sulfonyl fluoride compound with better yield.
Following the synthesis procedure in example 3, the substrate benzyl bromide is replaced by other C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, trifluoromethylthio, C1-C8 alkoxy, -C (O) R', -C (O) -NR a R b Substituted benzyl bromides also give better yields of aryl methylsulfonyl fluoride compounds.
Example 4 influence of different catalysts
Referring to example 1, the catalyst was replaced with palladium acetate, nickel sulfate, nickel carbonate, respectively, from nickel acetate tetrahydrate, and a set of experiments without any catalyst was additionally performed, and the corresponding 4-methoxystyrylsulfonyl fluoride (2 a) was synthesized under the same conditions. Specific yield results are shown in table 1.
TABLE 1 influence of different catalysts on the synthesis of 4-methoxystyrylsulfonyl fluoride a
Catalyst Yield (%)
Without adding 0
Nickel acetate (example 1) 77
Palladium acetate 25
Nickel (Ni) 55
Nickel sulfate 45
Nickel carbonate 66
a. The yield was fluorine spectrum yield.
The result shows that: the yields obtained for the product obtained without catalyst and with palladium acetate or other nickel-based catalysts were no worse than 70% compared to example 1.
Example 5 Effect of different ligands
Referring to example 1, the ligand was replaced with 2,2' -bipyridine (L2), 1, 10-phenanthroline (L3), triphenylphosphine, tricyclohexylphosphine (L6), 1-binaphthyl-2, 2-bisdiphenylphosphine (L5) from L7, and a set of experiments without adding any ligand was added thereto, and the other conditions were unchanged, to synthesize the corresponding 4-methoxystyrylsulfonyl fluoride (2 a). Specific yield results are shown in table 2.
TABLE 2 influence of different ligands on the synthesis of 4-methoxystyrylsulfonyl fluoride a
Ligand Yield (%)
Without adding 0
Bis (2-diphenylphosphinophenyl) ether (L7, example 1) 77
2,2' -bipyridine (L2) 0
1, 10-phenanthroline (L3) 0
Tricyclohexylphosphine (L6) 0
1, 1-binaphthyl-2, 2-bis-diphenylphosphine (L5) 45
Triphenylphosphine (L9) 65
a. The yield was fluorine spectrum yield.
The result shows that: the choice of ligand is also important, and the target product cannot be obtained effectively by adopting partial ligands such as 2,2' -bipyridine, 1, 10-phenanthroline and tricyclohexylphosphine.
EXAMPLE 6 Effect of different solvents
Referring to example 1, the corresponding β -styrenesulfonyl fluoride (2 a) was synthesized by replacing the solvent with acetonitrile, ethanol, and other conditions, respectively, without change. Specific yield results are shown in Table 3.
TABLE 3 influence of different solvents on the Synthesis of beta-styrenesulfonyl fluoride a
Solvent(s) Yield (%)
MeOH (example 1) 77
EtOH 30
CH 3 CN 0
DMSO tace
DMF tace
MeCN 0
i-PrOH 0
Dioxane 0
H 2 O 0
Toluene 0
Acetone 0
DCE 0
a. The yield was the fluorine spectrum yield; trace means that the trace amount cannot be obtained separately.
Example 7 Effect of different reaction temperatures
Referring to example 1, 4-methoxystyrylsulfonyl fluoride was synthesized by replacing the reaction temperature with 25℃and 55℃and 100℃respectively from 65℃under the same conditions.
Specific yield results are shown in Table 5.
TABLE 5 influence of different reaction temperatures on the synthesis of beta-styrenesulfonyl fluorides a
Temperature (. Degree. C.) Yield (%)
25 0
55 42
100 55
a. The yield was fluorine spectrum yield.
The result shows that: the product yields obtained by substituting 25℃at 55℃at 100℃for 65℃in example 1 were all worse than in example 1 and did not exceed 55%.

Claims (10)

1. The method is characterized in that in an organic solvent, an aromatic bromination substrate shown in a formula (1) and a sulfur dioxide source react for a period of time under the action of a catalyst and a ligand, then NFSI is added for continuous reaction, and an aromatic sulfonyl fluoride compound shown in a formula (2) is synthesized;
wherein R isOr->
R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halo, cyano, trifluoromethylthio, C1-C8 alkoxy, acyl, and amido; r is R 2 And R is 3 Selected from H, C C4 alkyl and aryl;
R 4 selected from H, C C1-C8 alkyl, C1-C8 haloalkyl, aryl, halo, cyano, trifluoromethylthio, C1-C8 alkoxy, acyl, and amido.
2. The method according to claim 1, wherein the method is characterized in that beta-arylvinyl bromide shown in formula (1 a) or benzyl bromide shown in formula (1 b), a sulfur dioxide source and NFSI are used as reactants, and the functionalization reaction is carried out under the action of a catalyst, so that the aromatic sulfonyl fluoride compound shown in formula (2 a) or formula (2 b) is obtained through corresponding synthesis;
3. the method of claim 1, wherein the aryl group comprises a substituted or unsubstituted benzene ring, naphthalene ring; the substitution may be one to three; the substituted groups being selected from halogen, C 1 -C 8 Alkyl, C 1 -C 8 An alkoxy group; acyl is-C (O) R ', R' is selected from C1-C8 alkyl; the amide group being-C (O) -NR a R b ，R a 、R b Independently selected from C1-C8 alkyl, or-NR a R b Is thatn=1 or 2.
4. The method of claim 1, wherein the sulfur dioxide source is Na 2 S 2 O 4 。
5. The method of claim 1, wherein the ligand is any one or more of the following:
6. the method of claim 1, wherein the organic solvent comprises any one or more of methanol and ethanol.
7. The method of claim 1, wherein the catalyst is one or more of palladium acetate, palladium dichloride, tetraphenylphosphine palladium, and phosphine ligand-containing palladium catalysts, bis (triphenylphosphine) nickel chloride, nickel acetate or hydrates thereof, nickel sulfate, nickel bromide, nickel carbonate, nickel, phosphine ligand-containing nickel catalysts.
8. The method of claim 1, wherein the molar ratio of aromatic bromination substrate to catalyst is 1 (0-1); the molar feed ratio of the aromatic bromination substrate to the sulfur dioxide source is 1: (0.5-2.0); the catalyst is used in an amount of 0 to 1 molar equivalent relative to the aromatic bromination substrate; the molar ratio of the aromatic bromination substrate to the ligand is 1 (0.1-1.1); the molar ratio of the aromatic bromination substrate to the NFSI is 1 (1.0-3.0); the reaction concentration of the aromatic bromination substrate is 0.05-5mmol/mL.
9. The method of any one of claims 1-8, further comprising adding an additive; the additive is any one or more of triethylamine, sodium acetate, 1, 8-diazabicyclo undec-7-ene, potassium carbonate, potassium tert-butoxide, acetic acid, ammonium acetate, tetrabutylammonium bromide, tetrabutylammonium fluoride and lithium hydroxide monohydrate.
10. The method of claim 9, wherein the molar ratio of aromatic bromination substrate to additive is 1 (0.0-2.0).
CN202310937286.5A 2023-07-27 2023-07-27 Synthesis method of aromatic sulfonyl fluoride compound Pending CN116969864A (en)

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