CN113603619B - Method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as raw material - Google Patents
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- 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
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
Abstract
The invention relates to a method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material, which synthesizes the aryl sulfonyl fluoride by a method of taking the aryl hydrazine hydrochloride as the raw material and adding a sulfur dioxide source and a fluorination reagent under the conditions of copper salt catalysis and alkali promotion through a strategy of 'free radical sulfur dioxide insertion fluorination'. Compared with the prior art, the aryl sulfonyl fluoride is synthesized under the oxidation condition, and the influence of air on the reaction is not obvious in the experiment; the reaction synthesis method is simple, has good selectivity, excellent yield, mild reaction conditions and short reaction time, has universality on various aryl hydrazine hydrochloride substrates, and provides a new idea for synthesis of aryl sulfonyl fluoride.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material.
Background
The sulfonyl fluoride compound can be used as a protein irreversible covalent inhibitor, can be used for selectively and covalently modifying protein, can be used as a reaction probe, and has wide application in the fields of biochemistry, medicinal chemistry and the like [ J.Am.chem.Soc.,2017,139,680; angew.chem.int.ed.,2019,58,957; RSC med. Chem.,2020,11,10. As the application of sulfonyl fluoride compounds becomes more and more extensive, the preparation method thereof is also diversified, and particularly, with the proposal and wide application of the sulfur-fluorine exchange method (SuFEx) of the new development of the click chemistry [ angelw.chem.int.ed., 2014,53,9430 ], sulfonyl fluoride compounds are receiving more and more attention.
Conventional methods for preparing arylsulfonyl fluoride compounds are mostly converted from arylsulfonyl chlorides, sulfonyl hydrazides, sulfonic acids, sulfonates, thiols, thioethers, and aryl halides, etc. [ eur.j.org.chem.,2018, 3648 ].
In recent years, it has been reported in the literature that vinylsulfonyl fluoride (ESF) participates in sulfonyl fluorination reactions on various substrates. The Qin group, using ESF dimerization, synthesized a new highly selective SuFEx click chemistry center compound, but-3-ene-1, 3-disulfonyl difluoro (BDF), which has three active sites selectively involved in quaternary, five-membered, six-membered cyclic sulfonamides with aliphatic sulfonyl fluoride moieties [ chem.
In 2017, a "radical sulfur dioxide insertion fluorination" strategy was reported using Ag (O) 2 CCF 2 SO 2 F) Simultaneously, the activated olefin is used as a trifluoromethylation reagent and a sulfur dioxide source to realize trifluoromethylation fluorosulfonyl of the non-activated olefin [ Angew.]The synthetic route is as follows:
in 2020, radical sulfur dioxide insertion fluorination of aromatic diazonium salts into fluorosulfonylation under reducing conditions was reported [ org.lett.,2020,22,2281; chi.j.chem., 2020,38,1107 ], the synthetic route is as follows:
most of the reported methods for synthesizing sulfonyl fluoride are carried out under reducing conditions, the reaction is easily affected by oxygen in the air, the reaction system needs to be deoxygenated, the reaction conditions are harsh, the operation is complex, and the method is difficult to apply to actual production. Therefore, it is of great significance to study a method for synthesizing sulfonyl fluoride compounds which are insensitive to oxygen.
Disclosure of Invention
The invention aims to provide a method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material, solves the problems that in the prior art, a sulfonyl fluoride compound is easily influenced by oxygen in a synthesis process, is complicated to operate and the like, and provides a new idea for synthesizing sulfonyl fluoride under mild conditions.
The purpose of the invention can be realized by the following technical scheme:
the invention provides a method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material, which specifically comprises the following steps:
taking aryl hydrazine hydrochloride as a raw material, adding a sulfur dioxide source and a fluorination reagent under the catalysis of copper salt and the promotion of alkali, and reacting in a reaction solvent to obtain a target product.
Furthermore, the aryl hydrazine hydrochloride is phenylhydrazine hydrochloride or heterocyclic aryl hydrazine hydrochloride containing an electron-withdrawing substituent or an electron-donating substituent.
Further, the copper salt is any one of basic copper carbonate, copper hydroxide, tetraacetonitrile copper tetrafluoroborate, cuprous chloride, cupric chloride, cuprous bromide, cuprous oxide or cupric acetate, and is preferably basic copper carbonate.
Further, the alkali is any one of pyridine, sodium carbonate, sodium bicarbonate, potassium bifluoride, potassium fluoride, potassium hydroxide or potassium carbonate, and is preferably pyridine.
Further, the sulfur dioxide source is any one of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO), 4- (dimethylamino) pyridin-1-ium-1-sulfinate, potassium metabisulfite, sodium metabisulfite or sodium hydrosulfite, and is preferably 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO).
Further, the fluorine source is any one of N-fluoro-bis-benzenesulfonamide (NFSI), selective fluorinating agent (Selectfluor), 1-fluoropyridine tetrafluoroborate or 1-fluoro-2, 4, 6-trimethylpyridine boron tetrafluoride, and is preferably N-fluoro-bis-benzenesulfonamide (NFSI).
Further, the solvent is any one or a mixture of more of acetonitrile, 1, 2-dichloroethane, dichloromethane, ethyl acetate, N-hexane, ethanol, tert-butanol, toluene, acetone, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, chlorobenzene or chloroform, and preferably acetonitrile.
Further, the molar ratio of the aryl hydrazine hydrochloride, the copper salt, the fluorinating reagent, the sulfur dioxide source and the alkali is (1).
Further, the gas atmosphere of the reaction is air or inert gas.
Further, the reaction temperature is 20 to 100 ℃, preferably 40 ℃.
Further, the reaction time is 1-12h.
Further, the structure of the arylsulfonyl fluoride is shown as follows:
wherein, the aryl in the structure of the aryl sulfonyl fluoride is a benzene ring or a heterocyclic compound containing single substituent or multiple substituents;
the R group in the structure of the aryl sulfonyl fluoride is selected from any one or more of straight-chain or branched-chain alkyl containing C1-C4 carbon chains, F, cl, br, I, methoxy, nitro, cyano, sulfonyl, methyl acyl and the like.
Further, the synthetic route of the aryl sulfonyl fluoride is as follows:
the method is different from the method for generating sulfonyl fluoride under reducing condition reported in the literature, and the method leads aryl hydrazine hydrochloride to form aryl free radical under oxidizing condition, combines sulfur dioxide provided by a sulfur dioxide source to obtain aryl sulfonyl free radical, and then carries out insertion fluorination by a fluorinating reagent to finally synthesize aryl sulfonyl fluoride. The method has the advantages of mild reaction conditions, simple operation, short reaction time, insignificant influence of air on the reaction in the experiment, and better compatibility for various aryl substrates, and provides a novel complementary strategy for synthesizing sulfonyl fluoride. The invention provides a brand new method for synthesizing sulfonyl fluoride by starting from an aromatic hydrazine compound which is convenient and easy to obtain to synthesize important aryl sulfonyl fluoride, and provides support for research of certain biological medicines or materials.
The invention is directed to process conditions during the reaction, e.g.Reaction temperature, reaction time and addition amount of raw materials Ratio of (A to B)However, the reaction proceeds smoothly to obtain the sulfonyl fluoride compound, but the yield is lowered, unless the conditions are outside the scope of the claims of the present invention.
Compared with the prior art, the method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material has the following advantages:
1) The aryl sulfonyl fluoride is synthesized under the oxidation condition, the influence of air on the reaction is not obvious in the experiment, the reaction condition is mild, the reaction time is short, and the operation is simple;
2) The method for synthesizing the aryl sulfonyl fluoride has better selectivity and excellent yield;
2) The method for synthesizing the aryl sulfonyl fluoride has better compatibility for various aryl substrates, and provides a brand-new method for synthesizing the aryl sulfonyl fluoride.
Drawings
FIG. 1 is a NMR spectrum of a 2,4-dichlorobenzenesulfonyl fluoride compound in example 9 of the present invention;
FIG. 2 is a NMR spectrum of a 2,4-dichlorobenzenesulfonyl fluoride compound in example 9 of the present invention;
FIG. 3 is a NMR carbon spectrum of a 2,4-dichlorobenzenesulfonyl fluoride compound in example 9 of the present invention;
FIG. 4 is a NMR spectrum of a 4- ((pyrrolidin-1-ylsulfonyl) methyl) benzenesulfonyl fluoride compound in example 11 of the present invention;
FIG. 5 is a NMR fluorine spectrum of a 4- ((pyrrolidin-1-ylsulfonyl) methyl) benzenesulfonyl fluoride compound in example 11 of the present invention;
FIG. 6 is a NMR carbon spectrum of a 4- ((pyrrolidin-1-ylsulfonyl) methyl) benzenesulfonyl fluoride compound in example 11 of the present invention;
FIG. 7 is a NMR spectrum of a quinoline-7-sulfonyl fluoride compound of example 12 in the present invention;
FIG. 8 is a NMR spectrum of a quinoline-7-sulfonyl fluoride compound of example 12 in accordance with the present invention;
FIG. 9 is a NMR carbon spectrum of a quinoline-7-sulfonyl fluoride compound of example 12 in accordance with the present invention;
Detailed Description
The present invention is further described in detail by the following specific examples, which are implemented on the premise of the technical solution, but the scope of the present invention is not limited by the following examples.
In the following examples, reagents and techniques used are all conventional commercial products or conventional processing techniques in the art unless otherwise specified.
Example 1:
p-bromophenylhydrazine hydrochloride is selected as a template substrate, DABSO is selected as a sulfur dioxide source, NFSI is a fluorine source, and a solvent is DCE, and the reaction is carried out for 10 hours at the temperature of 60 ℃.
44.7mg (0.2 mmol) of 4-bromophenylhydrazine hydrochloride, 138.7mg (0.44 mmol) of N-fluorobisbenzenesulfonamide (NFSI), 60.1mg (0.25 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added to 10mL of sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 2.0mL of acetonitrile is added under the protection of argon gas, a cover is closed, and the sealed tube is placed in a 60 ℃ oil bath to be stirred and reacted for 10 hours. After the reaction is finished, 4-methoxy trifluoromethoxybenzene is added as an internal standard, and the fluorine spectrum yield is 35% through nuclear magnetic analysis.
Example 2:
in addition, pyridine is added to the reaction in example 1, and the results are as follows:
44.7mg (0.2 mmol) of 4-bromophenylhydrazine hydrochloride, 138.7mg (0.44 mmol) of N-fluorobisbenzenesulfonamide (NFSI), 60.1mg (0.25 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added to 10mL of the sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 31.6mg (0.4 mmol) of pyridine and 2.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in a 60 ℃ oil bath to be stirred and reacted for 10 hours. After the reaction is finished, 4-methoxy trifluoromethoxybenzene is added as an internal standard, and the yield of the fluorine spectrum obtained by nuclear magnetic analysis is 54%.
Example 3:
in addition to the basic copper carbonate, the reaction is carried out in example 2, and the results are as follows:
44.7mg (0.2 mmol) of 4-bromophenylhydrazine hydrochloride, 4.4mg (0.02 mmol) of basic copper carbonate, 138.7mg (0.44 mmol) of N-fluorobisbenzenesulfonamide (NFSI), 60.1mg (0.25 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the sealed tube, the atmosphere in the sealed tube was replaced with argon gas so as to ensure that the system was in an inert gas atmosphere, 31.6mg (0.4 mmol) of pyridine and 2.0mL of acetonitrile were added under the protection of argon gas, the cap was closed, and the sealed tube was placed in a 60 ℃ oil bath and stirred for 10 hours. After the reaction is finished, 4-methoxy trifluoromethoxybenzene is added as an internal standard, and the yield of fluorine spectrum obtained by nuclear magnetic analysis is 70%.
Example 4:
based on the above example (example 3), the conditions of sulfur dioxide source, fluorination reagent, reaction solvent, temperature and time were further screened as shown in table 1.
TABLE 1 screening of reaction conditions
Through the screening of the conditions, the optimal conditions are as follows: substrates (0.2mmol, 1.0 equiv.), DABSO (0.25mmol, 1.25equiv.), NFSI (0.44mmol, 2.2 equiv.), pyridine (0.4mmol, 2.0 equiv.), cu 2 (OH) 2 CO 3 (0.02mmol, 0.1equiv.), meCN (2.0 mL), under an argon atmosphere at 40 ℃ for 2h.
Example 5:
under the optimal reaction conditions obtained in example 4, the environment of the reaction system was changed from "inert gas argon environment atmosphere" to "direct air environment", and other conditions were unchanged, and the results were as follows:
44.7mg (0.2 mmol) of 4-bromophenylhydrazine hydrochloride, 4.4mg (0.02 mmol) of basic copper carbonate, 138.7mg (0.44 mmol) of N-fluorobisbenzenesulfonamide (NFSI), 60.1mg (0.25 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the tube, and 31.6mg (0.4 mmol) of pyridine and 2.0mL of acetonitrile were added without purging, and the tube was placed in an oil bath at 60 ℃ and stirred for 10 hours. After the reaction is finished, 4-methoxy trifluoromethoxybenzene is added as an internal standard, and the fluorine spectrum yield is 70% through nuclear magnetic analysis. The experimental result shows that the reaction can also obtain good yield in the air environment atmosphere.
The experimental results show that in an air atmosphere, the sulfonyl fluoride compound can still be obtained with higher yield by using the method. Thus, the preferred conditions are determined to be: substrate (0.2mmol, 1.0 equiv.), DABSO(0.25mmol,1.25equiv.)，NFSI(0.44mmol,2.2equiv.)，pyridine(0.4mmol,2.0equiv.)，Cu 2 (OH) 2 CO 3 (0.02mmol, 0.1equiv.), meCN (2.0 mL), under air at 40 ℃ for 2h.
The following examples are illustrative of the synthesis of sulfonyl fluoride compounds under optimal conditions from different phenylhydrazine hydrochloride salts.
Example 6
Synthesis of 4-bromobenzenesulfonyl fluoride:
89.4mg (0.4 mmol) of 4-bromophenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added into 10mL of the sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound 4-bromobenzenesulfonyl fluoride through a column chromatography technology, wherein the separation yield is 68%.
1 H NMR(400MHz,CDCl 3 ):δ7.88(d,J＝8.7Hz,2H),7.79(d,J＝8.7Hz,2H)； 19 F NMR(376MHz,CDCl 3 ):δ66.5ppm.GC-MS(EI):m/z＝239.9(M + ).
Example 7
Synthesis of 3-bromobenzenesulfonyl fluoride:
89.4mg (0.4 mmol) of 3-bromophenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added into 10mL of the sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. And after the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating the filtrate, and spin-drying to obtain the target compound 3-bromobenzenesulfonyl fluoride through a column chromatography technology, wherein the separation yield is 70%.
1 H NMR(400MHz,CDCl 3 ):δ8.15(d,J＝1.7Hz,1H),7.94(dd,J＝19.9,8.0Hz,2H),7.53(t,J＝8.0Hz,1H)； 19 F NMR(376MHz,CDCl 3 ):δ66.2ppm.GC-MS(EI):m/z＝239.8(M + ).
Example 8
Synthesis of 2-bromobenzenesulfonyl fluoride:
89.4mg (0.4 mmol) of 2-bromophenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added into 10mL of the sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating the filtrate, spin-drying, and obtaining the target compound 2-bromobenzenesulfonyl fluoride and an off-white solid product through a column chromatography technology, wherein the separation yield is 66%.
1 H NMR(400MHz,CDCl 3 ):δ8.15(dd,J＝7.5,2.0Hz,1H),7.89–7.82(m,1H),7.58(td,J＝7.1,6.7,5.2Hz,2H)； 19 F NMR(376MHz,CDCl 3 ):δ57.9ppm.GC-MS(EI):m/z＝239.9(M + ).
Example 9
Synthesis of 4-methoxybenzenesulfonyl fluoride:
69.9mg (0.4 mmol) of 4-methoxyphenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the sealed tube, the atmosphere in the sealed tube was replaced with argon gas so as to ensure that the system was in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under the protection of argon gas, the cover was closed, and the sealed tube was placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound 4-methoxybenzenesulfonyl fluoride through column chromatography technology, wherein the separation yield is 72 percent.
1 H NMR(400MHz,CDCl 3 ):δ7.94(d,J＝9.0Hz,2H),7.06(d,J＝9.0Hz,2H),3.92(s,3H)； 19 F NMR(376MHz,CDCl 3 ):δ67.3ppm.GC-MS(EI):m/z＝190.0(M + ).
Example 10
Synthesis of 4-trifluoromethoxy benzenesulfonyl fluoride:
91.4mg (0.4 mmol) of 4-trifluoromethoxy phenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluoro-bis-benzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added to a 10mL sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining a target compound 4-trifluoromethoxy benzenesulfonyl fluoride and a yellow liquid product through column chromatography, wherein the separation yield is 49%. The product has low boiling point and is easy to be pumped away in vacuum, and the normal pentane is mixed for many times and is dried in a spinning way without being pumped by a vacuum pump, so that the product is basically ensured not to be lost.
1 H NMR(400MHz,CDCl 3 ):δ8.13–8.06(m,2H),7.46(d,J＝8.5Hz,2H)； 19 F NMR(376MHz,CDCl 3 ):δ66.6,-57.7ppm。GC-MS(EI):m/z＝244.0(M + ).
Example 11
Synthesis of 4-tert-butylbenzenesulfonyl fluoride:
80.3mg (0.4 mmol) of 4-tert-butylbenzohydrazinehydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the sealed tube, the atmosphere in the sealed tube was replaced with argon gas to ensure that the system was in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under the protection of argon gas, the cap was closed, and the sealed tube was placed in an oil bath at 40 ℃ and stirred for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound 4-tert-butylbenzenesulfonyl fluoride and a yellow solid product through a column chromatography technology, wherein the separation yield is 59%.
1 H NMR(400MHz,CDCl 3 ):δ7.94(d,J＝8.5Hz,2H),7.63(d,J＝8.2Hz,2H),1.37(s,9H)； 19 F NMR(376MHz,CDCl 3 ):δ66.2ppm.GC-MS(EI):m/z＝216.0(M + ).
Example 12
Synthesis of 4-nitrobenzenesulfonyl fluoride:
75.8mg (0.4 mmol) of 4-nitrophenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the sealed tube, the atmosphere in the sealed tube was replaced with argon gas so as to keep the system in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under the protection of argon gas, the cap was closed, and the sealed tube was placed in an oil bath at 40 ℃ and stirred for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound 4-nitrobenzenesulfonyl fluoride and a white solid product through a column chromatography technology, wherein the separation yield is 51%.
1 H NMR(400MHz,CDCl 3 ):δ8.49(d,J＝8.6Hz,2H),8.25(d,J＝8.9Hz,2H)； 19 F NMR(376MHz,CDCl 3 ):δ66.3ppm.GC-MS(EI):m/z＝204.9(M + ).
Example 13
2, synthesis of 4, 6-trimethylbenzenesulfonyl fluoride:
74.7mg (0.4 mmol) of 2,4, 6-trimethylphenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to a 10mL sealed tube, the air in the sealed tube was replaced with argon gas to ensure that the system was in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under the protection of argon gas, the cap was closed, and the sealed tube was placed in a 40 ℃ oil bath and stirred for reaction for 2h. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound 2,4, 6-trimethylbenzenesulfonyl fluoride and a white solid product through a column chromatography technology, wherein the separation yield is 57%.
1 H NMR(400MHz,CDCl 3 ):δ7.03(s,2H),2.64(d,J＝1.5Hz,6H),2.35(s,3H)； 19 F NMR(376MHz,CDCl 3 ):δ68.1ppm.GC-MS(EI):m/z＝202.0(M + ).
Example 14
Synthesis of 2, 4-dichlorobenzenesulfonyl fluoride:
85.4mg (0.4 mmol) of 2, 4-dichlorohydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added to 10mL of the tube, the atmosphere in the tube is replaced by argon, the system is kept in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon, the cover is closed, and the tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2h. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating the filtrate, spin-drying, and obtaining the target compound 2, 4-dichlorobenzenesulfonyl fluoride through column chromatography technology, wherein the isolation yield is 55 percent.
The nuclear magnetic resonance hydrogen spectrum, the nuclear magnetic resonance fluorine spectrum and the nuclear magnetic resonance carbon spectrum of the target product are respectively shown in fig. 1 to 3.
1 H NMR(400MHz,CDCl 3 ):δ8.05(d,J＝8.6Hz,1H),7.66(d,J＝1.9Hz,1H),7.49(dt,J＝8.6,1.3Hz,1H)； 19 F NMR(376MHz,CDCl 3 ):δ59.6； 13 C NMR(101MHz,CDCl 3 ):δ142.7,134.7,132.7,132.7,132.3,127.8ppm.HRMS(EI)m/z:[M] + Calcd for C 6 H 3 Cl 2 FO 2 S 227.9215；Found 227.9213.
Example 15
Synthesis of naphthalene-1-sulfonyl fluoride:
77.9mg (0.4 mmol) of 1-naphthylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) were added to 10mL of the sealed tube, the atmosphere in the sealed tube was replaced with argon gas so as to ensure that the system was in an inert gas atmosphere, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under the protection of argon gas, the cap was closed, and the sealed tube was placed in an oil bath at 40 ℃ and stirred for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound naphthalene-1-sulfonyl fluoride and a yellow solid product through a column chromatography technology, wherein the separation yield is 75%.
1 H NMR(400MHz,CDCl 3 ):δ8.55(dd,J＝8.6,2.8Hz,1H),8.37(d,J＝7.4Hz,1H),8.24(d,J＝8.2Hz,1H),8.01(d,J＝8.5Hz,1H),7.83–7.74(m,1H),7.69(t,J＝7.5Hz,1H),7.66–7.58(m,1H)； 19 F NMR(376MHz,CDCl 3 ):δ62.5ppm.GC-MS(EI):m/z＝210.0(M + ).
Example 16
Synthesis of 4- ((pyrrolidin-1-ylsulfonyl) methyl) benzenesulfonyl fluoride:
to a 10mL sealed tube was added 116.7mg (0.4 mmol) of 4- ((pyrrolidin-1-ylsulfonyl) methyl) phenylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO), the atmosphere in the sealed tube was replaced with argon gas to ensure that the system was in an inert gas atmosphere, and 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile were added under argon gas protection, the cap was closed, and the sealed tube was placed in a 40 ℃ oil bath and stirred for reaction for 2h. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining a target compound 4- ((pyrrolidine-1-ylsulfonyl) methyl) benzenesulfonyl fluoride and a white solid product by a column chromatography technology, wherein the separation yield is 25%.
The obtained hydrogen nuclear magnetic resonance spectrum, fluorine nuclear magnetic resonance spectrum, and carbon nuclear magnetic resonance spectrum of the target product are shown in fig. 4 to 6, respectively.
1 H NMR(400MHz,CDCl 3 ):δ8.03(d,J＝8.3Hz,2H),7.68(d,J＝8.3Hz,2H),4.31(s,2H),3.27(t,J＝6.6Hz,4H),1.94–1.87(m,4H)； 19 F NMR(376MHz,CDCl 3 ):δ66.2； 13 C NMR(101MHz,CDCl 3 ):δ131.9,128.8,55.7,48.3,25.9ppm.HRMS(EI)m/z:[M] + Calcd for C 11 H 14 FNO 4 S 2 307.0348；Found 307.0347.
Example 17
Synthesis of quinoline-7-sulfonyl fluoride:
78.2mg (0.4 mmol) of 7-quinolinylhydrazine hydrochloride, 8.8mg (0.04 mmol) of basic copper carbonate, 277.5mg (0.88 mmol) of N-fluorobisbenzenesulfonamide (NFSI), and 120.2mg (0.5 mmol) of 4-diazabicyclo [2.2.2] octane-bis (sulfur Dioxide) Adduct (DABSO) are added to a 10mL sealed tube, the air in the sealed tube is replaced by argon gas to ensure that the system is in an inert gas environment, 63.3mg (0.8 mmol) of pyridine and 4.0mL of acetonitrile are added under the protection of argon gas, the cover is closed, and the sealed tube is placed in an oil bath at 40 ℃ and stirred for reaction for 2 hours. After the reaction is finished, cooling to room temperature, filtering out solid impurities, concentrating and spin-drying the filtrate, and obtaining the target compound quinoline-7-sulfonyl fluoride through a column chromatography technology, wherein the separation yield is 28%.
The obtained hydrogen nuclear magnetic resonance spectrum, fluorine nuclear magnetic resonance spectrum, and carbon nuclear magnetic resonance spectrum of the target product are shown in fig. 7 to 9, respectively.
1 H NMR(400MHz,CDCl 3 ):δ9.12(d,J＝3.1Hz,1H),8.86(s,1H),8.30(d,J＝8.3Hz,1H),8.12–7.99(m,2H),7.65(dd,J＝8.4,4.2Hz,1H)； 19 F NMR(376MHz,CDCl 3 ):δ66.1； 13 C NMR(101MHz,CDCl 3 ):152.9,146.8,136.0,132.2,131.7,130.2,126.4,124.6,123.1ppm.HRMS(EI)m/z:[M] + Calcd for C 9 H 6 FNO 2 S 211.0103；Found 211.0101.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (2)
1. A method for preparing aryl sulfonyl fluoride by taking aryl hydrazine hydrochloride as a raw material is characterized in that the aryl hydrazine hydrochloride is taken as the raw material, a sulfur dioxide source and a fluorination reagent are added under the catalysis of copper salt and the promotion of alkali, and the reaction is carried out in a reaction solvent to obtain a target product;
the aryl hydrazine hydrochloride is 4-bromophenylhydrazine hydrochloride, 3-bromophenylhydrazine hydrochloride, 2-bromophenylhydrazine hydrochloride, 4-methoxyphenylhydrazine hydrochloride, 4-trifluoromethoxy phenylhydrazine hydrochloride, 4-tert-butylbenzhydrazide hydrochloride, 4-nitrophenylhydrazine hydrochloride, 2,4, 6-trimethylphenylhydrazine hydrochloride, 2, 4-dichlorophenylhydrazine hydrochloride, 1-naphthylhydrazine hydrochloride, 4- ((pyrrolidine-1-ylsulfonyl) methyl) phenylhydrazine hydrochloride or 7-quinolinhydrazine hydrochloride;
the copper salt is basic copper carbonate;
the alkali is any one of pyridine, sodium carbonate, sodium bicarbonate or potassium carbonate;
the sulfur dioxide source is any one of 4-diazabicyclo [2.2.2] octane-bis (sulfur dioxide) adduct, potassium metabisulfite, sodium metabisulfite or sodium hydrosulfite;
the fluorination reagent is N-fluoro-bis-benzenesulfonamide and a selective fluorination reagent;
the reaction solvent is any one or mixture of acetonitrile, 1, 2-dichloroethane dichloromethane, ethyl acetate, ethanol, toluene, acetone, chlorobenzene or chloroform;
the molar ratio of the arylhydrazine hydrochloride to the copper salt to the fluorizating reagent to the sulfur dioxide source to the alkali is 1:0.1 (2) - (4) to (0.5) - (2) to (1) - (3).
2. The method for preparing arylsulfonyl fluoride by using the hydrochloride of the arylhydrazine as a raw material according to claim 1, wherein the reaction is carried out in air or an inert gas atmosphere;
the reaction temperature is 20-100 ℃; the reaction time is 1-12h.
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