CN114539109A - Beta-ketosulfolane synthesis method - Google Patents

Beta-ketosulfolane synthesis method Download PDF

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CN114539109A
CN114539109A CN202210261087.2A CN202210261087A CN114539109A CN 114539109 A CN114539109 A CN 114539109A CN 202210261087 A CN202210261087 A CN 202210261087A CN 114539109 A CN114539109 A CN 114539109A
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bromide
phenyl
thiobenzenesulfonate
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chloroform
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CN114539109B (en
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曾庆乐
康晓康
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Chengdu Univeristy of Technology
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides

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Abstract

Sulphone as an important organic intermediate, widely found in drugs such as eletriptan, an anti-migraine drug, adroquinone, for the treatment of breast cancer, etaxib, for the treatment of osteoarthritis, and gamma-secretase inhibitors, drugs used for the prevention of alzheimer's disease, contain sulphone building blocks. The sulfone compounds have good antibacterial activity, so the sulfone compounds are also applied to organic pesticides, such as herbicide cafenstrole and insecticide oxycarboxin. In addition, in the aspect of novel functional materials, the poly diaryl sulfone molecules have special photophysical properties and also have wide application in light-emitting diode materials. The patent develops a simple, convenient and efficient method for synthesizing beta-ketone thiosulfone compounds by one-step reaction of double functionalization of arylformyl methylene dimethyl sulfur bromide and thiosulfonic acid ester, the method obtains products with moderate to good yield, and the method has wide substrate range, high functional group tolerance and good applicability.

Description

Beta-ketosulfolane synthesis method
Technical Field
The patent relates to the research field of organic synthesis, pharmaceutical synthesis and organic chemical industry, in particular to a method for synthesizing beta-ketone thiosulfone compounds in one step by carrying out bifunctional reaction on arylformyl methylene dimethyl sulfur bromide and thiosulfonic acid ester under the action of sodium carbonate.
Background
The sulfone compound is a common organic intermediate, and plays an extremely important role in the fields of medicines, pesticides, novel functional materials and the like. In medicine, for example, etaneropent (ye. s, yang. m, wu. j, chem. comun.2020, 56, 4145-4155) for the treatment of migraine, idoquinone for the treatment of breast cancer, etanerib (ye. s, yang. m, wu. j, chem. comun.2020, 56, 4145-4155) for the treatment of osteoarthritis, and gamma-secretase inhibitors (i.churcher, d.beher, j.d.best, j.l.castro, e.e.clarrr, a.try, t.harrison, l.hitzel, e.kay, s.kerrad, h.d.lewis, p.m.gutierrez, r.m.smith, p.j.oley, m.reily, d.e.w, m.shearman, m.r.terall, s.wil.and j.13. eagle, biogler.j.j.16. biog.16. org. In the field of organic pesticides, sulfone compounds have very good antibacterial activity, for example, the herbicides carfentrazone (G.Mitchell, D.W.Bartlett, T.E.M.Fraser, T.R.Hawkes, D.C.Holt, J.K.Townson, R.A.Wicher, Pest Manag.Sci.2001,57, 120. 128.), isoxaflutole (S.Taylor-Lovell, G.K.Sims, L.M.wax, J.Agr.food.Chem.2002,50, 5626. cozao.563.), the insecticides oxycarboxin (K.Huster, P.N.Moza, A.Kettrup, Chemospere.1999, 38, 3423. 29.). In terms of novel functional materials, the polydiaryl sulfone molecules have special photophysical properties and have wide applications in light emitting diode materials (g.barbarella, l.favaretto, a.zanelli, g.gigli, g.m.mazzeo, m.ani, a.bongini, adv.funct.mater.2005,15, 664. sand 670.). Sulfones are also frequently used as important intermediates for Organic Synthesis (N.S. Simpkins, sulfoxines in Organic Synthesis; Pergamon Press: Oxford, 1993.). Based on the importance, the development of a new synthesis method of the sulfone compound has great value.
The synthesis of beta-ketosulfolane mainly comprises the following methods: (1) stevens rearrangement of aryldiazoacetates and thioylides is catalyzed by copper/bipyridine complexes (H.Yuan, T.Nuligonda, H.Gao, C.H.Tung, Z.xu, org.chem.Front.2018,5, 1371-1374.). (2) Copper catalyses the oxidative trifunctional reaction of olefins (S.Huang, N.Thirouathi, C.H.Tung, Z.xu, J.org.chem.2018,83, 9449-. (3) A series free radical reaction of thiosulfonate and oxysulfide ylide (F.Wang, B.X.Liu, W.Rao, S.Y.Wang, org.Lett.2020,22, 6600-6604.). The various methods for synthesizing the beta-ketosulfolane have the defects of metal catalysis, difficult preparation of raw materials, complex operation and the like, so the development of a novel method for synthesizing the sulfone compound with high efficiency and convenience has great significance.
We report a double functionalization reaction of arylformyl methylene dimethyl sulfur bromide and thiosulfonic acid ester, and develop a new synthetic method of beta-ketone thiosulfone compounds.
To the best of our knowledge, no literature reports are found which are the same as the present application.
Disclosure of Invention
The invention provides a synthesis method of a beta-ketone thiosulfone compound.
The synthesis method of the beta-ketone thiosulfone compound disclosed by the invention is completed in one step, namely under the condition of acetonitrile solution, sodium carbonate is taken as alkali, arylformyl methylene dimethyl sulfur bromide and thiosulfonic acid ester are subjected to bifunctional reaction to synthesize the beta-ketone thiosulfone compound in one step, and the reaction equation is shown as follows.
Figure BDA0003549057280000021
The present invention is illustrated in more detail by the following examples, which are not to be construed as limiting the scope of the invention.
Detailed Description
Example one
To a 25mL glass test tube equipped with a stir bar was added benzoylmethylidene dimethylbromide sulfide (0.6mmol), S-phenylthiobenzenesulfonate (0.5mmol, sodium carbonate (4 equiv.), 5mL acetonitrile, and finally the tube was sealed with a rubber stopper, the tube was stirred under nitrogen with a pre-heated 80 ℃ oil bath for 4h, after which the reaction mixture was cooled to room temperature, then quenched by the addition of saturated sodium chloride solution (10mL), extracted 3 times with ethyl acetate (15mL), and the combined organic layers were MgSO over anhydrous MgSO4Dried and then adsorbed on a rotary evaporator with basic alumina. The residue was purified by flash column chromatography on silica gel (petroleum ether: ethyl acetate 10: 1-5: 1 as eluent) to give 1-phenyl-2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 82% yield.
The structural characterization data for the product 1-phenyl-2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one is as follows:
1H NMR(400MHz,Chloroform-d)δ8.05–7.97(m,2H),7.91–7.83(m,2H),7.70–7.64(m,1H),7.63–7.57(m,1H),7.57–7.41(m,6H),7.37–7.22(m,3H),5.82(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.3,136.3,135.1,134.5,134.4,133.6,132.1,130.7,129.5,129.4,129.2,128.9,128.7,75.6.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H16NaO3S2 +:391.0433；found:391.0443.
example two
4- (fluoro) benzoylmethylidene dimethyl sulphur bromide was substituted for the benzoylmethylidene dimethyl sulphur bromide in example one to give 88% 1- (4-fluorophenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a white solid.
1H NMR(400MHz,Chloroform-d)δ7.91(d,J＝7.4Hz,2H),7.88–7.81(m,2H),7.59(t,J＝7.5Hz,1H),7.46(t,J＝7.8Hz,2H),7.42–7.36(m,2H),7.22(tq,J＝12.7,6.7,5.9Hz,3H),7.04(t,J＝8.5Hz,2H),5.66(s,1H).
13C NMR(101MHz,Chloroform-d)δ187.8,166.5(d,J＝257.8Hz),136.2,134.6,133.6,132.2(d,J＝9.7Hz),132.0,131.5(d,J＝2.9Hz),130.7,129.5(d,J＝5.5Hz),128.8,116.2(d,J＝22.2Hz),75.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15FNaO3S2 +:409.0339；found:409.0370.
EXAMPLE III
4- (chloro) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 1- (4-chlorophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethane-1-one as a yellow oil in 75% yield.
1H NMR(400MHz,Chloroform-d)δ8.03–7.97(m,2H),7.86–7.81(m,2H),7.72–7.66(m,1H),7.55(t,J＝7.8Hz,2H),7.45(ddd,J＝16.5,7.3,1.5Hz,4H),7.37–7.27(m,3H),5.72(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.2,141.1,136.2,134.6,133.6,133.4,131.9,130.7,129.6,129.5,129.3,128.8,128.6,75.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15ClNaO3S2 +:425.0043；found:425.0060.
Example four
4- (bromo) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 1- (4-bromophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 75% yield.
1H NMR(400MHz,Chloroform-d)δ7.96–7.87(m,2H),7.69–7.63(m,2H),7.62–7.56(m,1H),7.54–7.43(m,4H),7.41–7.35(m,2H),7.22(ddd,J＝12.7,7.9,6.1Hz,3H),5.64(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.4,136.2,134.6,133.8,133.6,132.3,131.8,130.7,130.7,130.0,129.6,129.6,128.8,75.8.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15BrNaO3S2 +:468.9538；found:468.9535
EXAMPLE five
4- (cyano) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 4- (2- (benzenesulfonyl) -2- (phenylthio) acetyl) benzonitrile in 62% yield.
1H NMR(400MHz,Chloroform-d)δ8.03–7.97(m,4H),7.80–7.68(m,3H),7.58(t,J＝7.7Hz,2H),7.47–7.41(m,2H),7.39–7.25(m,3H),5.72(s,1H).
13C NMR(101MHz,Chloroform-d)δ187.2,136.9,135.0,133.8,132.6,131.6,130.5,130.4,129.6,128.7,128.6,127.9,116.6,116.4,74.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H15NNaO3S2 +:416.0386；found:416.0378.
EXAMPLE six
4- (Nitro) Benzylmethylene Dimethylthio Bromide instead of Benzylmethylene Dimethylthio Bromide as in example one, a red solid, 1- (4-nitrophenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one, was obtained in 63% yield.
1H NMR(400MHz,Chloroform-d)δ7.95–7.88(m,2H),7.87–7.81(m,2H),7.59(td,J＝7.3,1.3Hz,1H),7.46(t,J＝7.9Hz,2H),7.41–7.36(m,2H),7.28–7.16(m,3H),7.09–6.99(m,2H),5.67(s,1H).
13C NMR(101MHz,Chloroform-d)δ187.8,167.8,165.2,136.2,134.6,133.6,132.2(d,J＝9.8Hz),132.0,131.5(d,J＝3.0Hz),130.7,129.5(d,J＝5.4Hz),128.8,116.2(d,J＝22.1Hz),75.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15NNaO5S2 +:436.0284；found:436.0278.
EXAMPLE seven
4- (trifluoromethyl) benzoylmethylidene dimethyl sulphur bromide was used instead of benzoylmethylidene dimethyl sulphur bromide in example one to give a yellow solid 2- (phenylsulfonyl) -2- (phenylthio) -1- (4- (trifluoromethyl) phenyl) ethan-1-one in 61% yield.
1H NMR(400MHz,Chloroform-d)δ8.05–7.98(m,4H),7.76–7.67(m,3H),7.57(dd,J＝8.4,7.2Hz,2H),7.50–7.43(m,2H),7.39–7.27(m,3H),5.76(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.5,137.7,136.2,135.5,135.2,134.7,133.6,131.6,130.7,129.7,129.6,128.9,125.98,125.95,125.9,125.9,75.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H15F3NaO3S2 +:459.0307；found:459.0328.
Example eight
4- (trifluoromethoxy) benzoylmethylidene dimethyl sulphur bromide was used instead of benzoylmethylidene dimethyl sulphur bromide in example one to give 2- (phenylsulfonyl) -2- (phenylthio) -1- (4- (trifluoromethoxy) phenyl) ethan-1-one as a white solid in 75% yield.
1H NMR(400MHz,Chloroform-d)δ8.07–7.96(m,4H),7.71(t,J＝7.5Hz,1H),7.58(t,J＝7.8Hz,2H),7.53–7.47(m,2H),7.41–7.27(m,5H),5.78(s,1H).
13C NMR(101MHz,Chloroform-d)δ187.9,153.5(d,J＝1.7Hz),136.2,134.6,133.6,133.1,131.9,131.5,130.7,129.6(d,J＝2.8Hz),128.8,121.5,120.4,119.0,75.9.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H15F3NaO4S2 +:475.0256；found:475.0249.
Example nine
4- (methoxy) benzoylmethylen dimethylthio bromide was used in place of the benzoylmethylen dimethylthio bromide from example one to give 1- (4-methoxyphenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a yellow oil in 64% yield.
1H NMR(400MHz,Chloroform-d)δ8.01–7.96(m,2H),7.91–7.85(m,2H),7.65(d,J＝7.5Hz,1H),7.58–7.44(m,4H),7.35–7.25(m,3H),6.97–6.87(m,2H),5.78(s,1H),3.86(s,3H).
13C NMR(101MHz,Chloroform-d)δ187.6,164.7,136.4,134.4,133.5,132.4,131.9,130.7,129.5,129.3,128.7,128.0,114.2,75.7,55.7.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18NaO4S2 +:421.0539；found:421.0560.
Example ten
4- (phenyl) benzoylmethylen dimethylthio bromide was used in place of the benzoylmethylen dimethylthio bromide from example one to give 1- ([1,1' -biphenyl ] -4-yl) -2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 91% yield.
1H NMR(400MHz,Chloroform-d)δ8.09–8.04(m,2H),8.03–7.97(m,2H),7.74–7.69(m,3H),7.65(dt,J＝8.3,1.9Hz,2H),7.62–7.54(m,4H),7.54–7.48(m,2H),7.47–7.42(m,1H),7.41–7.32(m,3H),5.87(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.8,147.1,139.4,136.3,134.5,133.7,133.6,132.3,130.8,129.9,129.5,129.4,129.1,128.7,128.7,127.5,127.4,75.8.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C26H20NaO3S2 +:467.0746；found:467.0747.
EXAMPLE eleven
3- (bromo) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 1- (3-bromophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 85% yield.
1H NMR(400MHz,Chloroform-d)δ8.01(d,J＝7.5Hz,2H),7.96(t,J＝1.6Hz,1H),7.80(d,J＝7.9Hz,1H),7.75–7.66(m,2H),7.57(t,J＝7.8Hz,2H),7.51–7.47(m,2H),7.40–7.29(m,4H),5.70(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.1,137.2,136.8,136.2,134.7,133.7,132.0,131.7,130.7,130.4,129.7,129.6,128.8,127.8,123.2,75.7.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15BrNaO3S2 +:468.9538；found:468.9544.
Example twelve
3- (chloro) benzoylmethylidene dimethyl sulfur bromide was substituted for the benzoylmethylidene dimethyl sulfur bromide in example one to give 1- (3-chlorophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a colorless oil in 84% yield.
1H NMR(400MHz,Chloroform-d)δ8.01(dd,J＝8.4,1.1Hz,2H),7.81(t,J＝1.8Hz,1H),7.76(dt,J＝7.8,1.3Hz,1H),7.69(tt,J＝7.1,1.2Hz,1H),7.56(td,J＝7.1,6.2,1.6Hz,3H),7.51–7.45(m,2H),7.41(d,J＝7.9Hz,1H),7.39–7.32(m,2H),7.32–7.27(m,1H),5.70(s,1H).
13C NMR(101MHz,Chloroform-d)δ188.2,136.6,136.2,135.3,134.7,134.3,133.7,131.8,130.7,130.2,129.6,129.6,129.1,128.8,127.3,75.7.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15ClNaO3S2 +:425.0043；found:425.0025.
EXAMPLE thirteen
3- (methoxy) benzoylmethylen dimethylthio bromide was used in place of the benzoylmethylen dimethylthio bromide from example one to give 1- (3-methoxyphenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a yellow oil in 63% yield.
1H NMR(400MHz,Chloroform-d)δ8.09–8.01(m,2H),7.69(d,J＝7.4Hz,1H),7.61–7.50(m,4H),7.45(d,J＝7.7Hz,1H),7.42–7.29(m,5H),7.21–7.15(m,1H),5.81(s,1H),3.82(s,3H).
13C NMR(101MHz,Chloroform-d)δ189.1,160.0,136.4(d,J＝0.9Hz),134.5,133.6,132.2,130.8,129.9,129.5,129.4,128.7,121.8,121.3,113.1,75.6,55.5.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18NaO4S2 +:421.0539；found:421.0532.
Example fourteen
2- (methoxy) benzoylmethylen dimethylthio bromide was used in place of the benzoylmethylen dimethylthio bromide from example one to give 1- (2-methoxyphenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 45% yield.
1H NMR(400MHz,Chloroform-d)δ8.07–8.00(m,2H),7.71–7.63(m,2H),7.60–7.46(m,5H),7.33(dd,J＝4.9,1.7Hz,3H),7.02(t,J＝7.5Hz,1H),6.87(d,J＝8.4Hz,1H),6.50(s,1H),3.54(s,3H).
13C NMR(101MHz,Chloroform-d)δ190.2,158.5,137.1,135.3,134.2,133.5,132.6,131.8,130.6,129.2,128.7,128.5,125.8,121.3,111.7,78.2,55.4.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18NaO4S2 +:421.0539；found:421.0538.
Example fifteen
2,5- (dimethoxy) benzoylmethylidene dimethyl sulfur bromide was used in place of the benzoylmethylidene dimethyl sulfur bromide in example one to give 1- (2, 5-dimethoxyphenyl) -2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a yellow oil in 58% yield.
1H NMR(400MHz,Chloroform-d)δ8.05–7.98(m,2H),7.65(tt,J＝6.9,1.2Hz,1H),7.58–7.50(m,4H),7.34–7.29(m,3H),7.21–7.14(m,1H),7.05(dd,J＝9.1,3.3Hz,1H),6.80(d,J＝9.1Hz,1H),6.57(s,1H),3.76(s,3H),3.48(s,3H).
13C NMR(101MHz,Chloroform-d)δ189.7,153.7,153.2,137.1,134.2,133.4,132.6,130.7,129.2,128.7,128.5,125.7,122.5,114.5,113.3,78.0(d,J＝3.5Hz),55.8(d,J＝5.6Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C22H20NaO5S2 +:451.0644；found:451.0638.
Example sixteen
1- (naphthyl) benzoylmethylen dimethyl sulfur bromide was substituted for the benzoylmethylen dimethyl sulfur bromide in example one to give 1- (naphthyl) -2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 64% yield.
1H NMR(400MHz,Chloroform-d)δ8.34(s,1H),8.09–8.02(m,2H),7.95–7.91(m,1H),7.89–7.82(m,3H),7.63(dt,J＝15.9,7.4Hz,2H),7.54(t,J＝7.7Hz,5H),7.38–7.27(m,3H),5.96(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.2,136.4,136.0,134.5,133.8,132.4,132.3,131.7,130.8,130.0,129.6,129.5,129.5,128.9,128.8,127.8,127.2,124.1,75.8.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C24H18NaO3S2 +:441.0590；found:441.0582.
Example seventeen
Cyclopropylformylmethylenedimethylthiobromide was used in place of the benzoylmethylenedimethylthiobromide in example one to give 1-cyclopropyl-2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one as a colorless oil in 68% yield.
1H NMR(400MHz,Chloroform-d)δ8.00–7.94(m,2H),7.68(t,J＝7.5Hz,1H),7.55(t,J＝7.8Hz,2H),7.42–7.37(m,2H),7.33–7.23(m,3H),4.93(s,1H),2.44–2.33(m,1H),1.19–1.07(m,4H).
13C NMR(101MHz,Chloroform-d)δ198.8,136.9,134.6,133.2,131.8,129.8,129.5,129.2,129.0,80.6,20.8,14.1,13.7.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H16NaO3S2 +:355.0433；found:355.0430.
EXAMPLE eighteen
Thienoylmethylenedimethylsulfide bromide was used in place of the benzoylmethylenedimethylsulfide bromide of example one to give a colorless oil of 2- (benzenesulfonyl) -2- (phenylthio) -1- (thiophen-2-yl) ethan-1-one in 65% yield.
1H NMR(400MHz,Chloroform-d)δ8.02–7.96(m,2H),7.74(dd,J＝7.9,4.4Hz,2H),7.67(t,J＝7.5Hz,1H),7.57–7.48(m,4H),7.37–7.27(m,3H),7.16–7.10(m,1H),5.57(s,1H).
13C NMR(101MHz,Chloroform-d)δ181.7,142.1,136.7,136.1,134.8,134.6,133.6,132.4,130.7,129.5,129.4,128.8,128.7,77.4.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H14NaO3S3 +:396.9997；found:396.9978
Example nineteen
S- (4-chlorophenyl) -thiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 2- ((4-chlorophenyl) thio) -1-phenyl-2- (benzenesulfonyl) ethan-1-one as a white solid in 77% yield.
1H NMR(400MHz,Chloroform-d)δ7.98–7.93(m,2H),7.88(dd,J＝8.4,1.1Hz,2H),7.64–7.58(m,1H),7.55–7.49(m,4H),7.49–7.42(m,2H),7.38–7.28(m,3H),5.85(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.3,141.5,135.0 134.6,134.6,133.6,132.4,131.9,129.8,129.6,129.3,129.1,129.0,75.3,75.3.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15ClNaO3S2 +:425.0043；found:425.0046.
Example twenty
S- (4-methylphenyl) -thiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 61% yield of 2- ((4-methylphenyl) thio) -1-phenyl-2- (phenylsulfonyl) ethan-1-one as a white solid.
1H NMR(400MHz,Chloroform-d)δ8.04–7.98(m,2H),7.90–7.84(m,2H),7.67(tt,J＝7.0,1.2Hz,1H),7.64–7.52(m,3H),7.45(td,J＝7.5,1.6Hz,2H),7.40–7.35(m,2H),7.10(d,J＝7.9Hz,2H),5.74(s,1H),2.33(s,3H).
13C NMR(101MHz,Chloroform-d)δ189.3,140.0,136.5,135.1,134.5,134.4,134.2,130.8,130.3,129.2,128.9,128.7,128.4,75.8(d,J＝5.3Hz),21.32(d,J＝6.0Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18NaO3S2 +:405.0590；found:405.0596.
Example twenty one
S- (4-methoxyphenyl) -thiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 2- ((4-methoxyphenyl) thio) -1-phenyl-2- (benzenesulfonyl) ethan-1-one as a white solid in 69% yield.
1H NMR(400MHz,Chloroform-d)δ8.06–8.00(m,2H),7.88–7.83(m,2H),7.67(t,J＝7.5Hz,1H),7.57(dt,J＝21.1,7.5Hz,3H),7.48–7.37(m,4H),6.80(d,J＝8.8Hz,2H),5.68(s,1H),3.78(s,3H).
13C NMR(101MHz,Chloroform-d)δ184.5 156.3,131.9,130.4,129.7,129.6,125.9,124.4,124.2,124.0,117.2,110.2,71.2,50.7.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18NaO4S2 +:421.0539；found:421.0541.
Example twenty two
S- (2-fluorophenyl) -thiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 2- ((2-fluorophenyl) thio) -1-phenyl-2- (benzenesulfonyl) ethan-1-one as a white solid in 60% yield.
1H NMR(400MHz,Chloroform-d)δ7.95(ddd,J＝19.3,8.4,1.1Hz,4H),7.69–7.60(m,2H),7.60–7.48(m,5H),7.40–7.32(m,1H),7.17–7.03(m,2H),6.02(d,J＝0.7Hz,1H).
13C NMR(101MHz,Chloroform-d)δ188.4,162.5,160.0,134.9,134.7,134.2,133.5(d,J＝4.2Hz),130.8(d,J＝8.2Hz),129.5,128.3,127.9,127.7,124.0(d,J＝3.8Hz),117.8(d,J＝17.3Hz),115.2(d,J＝22.6Hz),72.6(d,J＝2.7Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15FNaO3S2 +:409.0339；found:409.0349.
Example twenty three
S-propylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 1-phenyl-2- (phenylsulfonyl) -2- (propylthio) ethan-1-one in 65% yield as a yellow solid.
1H NMR(400MHz,Chloroform-d)δ8.03–7.90(m,4H),7.72–7.58(m,2H),7.55(t,J＝7.8Hz,2H),7.48(t,J＝7.8Hz,2H),5.59(s,1H),2.87(ddd,J＝12.1,8.1,6.5Hz,1H),2.72(ddd,J＝12.1,7.9,7.0Hz,1H),1.57(dt,J＝15.2,7.8Hz,2H),0.92(t,J＝7.3Hz,3H).
13C NMR(101MHz,Chloroform-d)δ189.1,136.3,135.0,134.4,134.4,130.6,129.0,129.0,128.7,70.6(d,J＝6.8Hz),34.7,22.4,13.3.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H18NaO3S2 +:357.0590；found:357.0590.
Example twenty four
S-Butylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 1-phenyl-2- (benzenesulfonyl) -2- (propylsulfanyl) ethan-1-one as a white solid in 66% yield.
1H NMR(400MHz,Chloroform-d)δ8.04–7.92(m,4H),7.63(dt,J＝21.2,7.4Hz,2H),7.54(t,J＝7.8Hz,2H),7.47(t,J＝7.8Hz,2H),5.61(s,1H),2.88(ddd,J＝12.0,8.2,6.5Hz,1H),2.73(ddd,J＝12.0,8.1,7.0Hz,1H),1.60–1.44(m,2H),1.32(h,J＝7.2Hz,2H),0.85(t,J＝7.3Hz,3H).
13C NMR(101MHz,Chloroform-d)δ189.1,136.4,135.0,134.4,134.3,130.6,129.0,128.9,128.7,70.7,32.4,30.9,21.8,13.6.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H20NaO3S2 +:371.0746；found:371.0749.
Example twenty-five
S-dodecylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 2- (dodecylthio) -1-phenyl-2- (phenylsulfonyl) ethan-1-one as a white solid in 65% yield.
1H NMR(400MHz,Chloroform-d)δ8.00(d,J＝7.4Hz,2H),7.96(d,J＝7.4Hz,2H),7.64(dt,J＝21.3,7.4Hz,2H),7.54(t,J＝7.8Hz,2H),7.47(t,J＝7.8Hz,2H),5.60(s,1H),2.87(ddd,J＝12.1,8.1,6.6Hz,1H),2.78–2.68(m,1H),1.58–1.44(m,2H),1.24(t,J＝14.6Hz,18H),0.88(t,J＝6.8Hz,3H).
13C NMR(101MHz,Chloroform-d)δ189.1,136.4,135.1,134.3,134.3,130.6,129.0,128.9,128.6,70.7,32.8,31.9,29.6,29.5,29.4,29.35,29.1,28.8,28.6,22.7,14.2.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C26H36NaO3S2 +:483.1998；found:483.2004.
Example twenty-six
S-pyridylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate from example one, gave 2- ((4-bromophenyl) sulfonyl) -1-phenyl-2- (pyridin-2-ylthio) ethan-1-one in 50% yield as a red oil.
1H NMR(400MHz,Chloroform-d)δ8.37(ddd,J＝4.9,1.7,0.9Hz,1H),8.14–8.07(m,2H),7.96(dt,J＝8.6,1.7Hz,2H),7.71(s,1H),7.63–7.57(m,1H),7.57–7.50(m,1H),7.50–7.40(m,5H),7.16–7.11(m,1H),7.04(ddd,J＝7.3,4.9,0.9Hz,1H).
13C NMR(101MHz,Chloroform-d)δ189.7,152.9,149.3,137.1,137.0,135.4,134.3,134.2,130.3,129.4,128.8,128.9,122.2,121.2,67.5.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15NNaO3S2 +:392.0386；found:392.0381.
Example twenty-seven
Se-phenylselenophenylsulfonate instead of S-phenylthiobenzenesulfonate in example one gave 35% yield of 1-phenyl-2- (phenylseleno) -2- (phenylsulfonyl) ethan-1-one as a white solid.
1H NMR(400MHz,Chloroform-d)δ8.09–8.03(m,2H),7.80(d,J＝7.4Hz,2H),7.67(t,J＝7.4Hz,1H),7.58(dq,J＝15.6,7.5Hz,5H),7.41(dt,J＝15.5,7.6Hz,3H),7.29(t,J＝7.5Hz,2H),5.82(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.4,137.1,135.8,135.0,134.3,134.2,130.6,129.7,129.5,128.9,128.8,128.7,127.7,68.1.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H16NaO3SSe+:438.9578；found:438.9561.
Example twenty-eight
S-phenyl-4-methylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 1-phenyl-2- (phenylthio) -2-toluenesulfonate-1-one as a white oil in 80% yield.
1H NMR(400MHz,Chloroform-d)δ7.88(dd,J＝7.8,4.4Hz,4H),7.59(d,J＝7.4Hz,1H),7.53–7.48(m,2H),7.44(t,J＝7.8Hz,2H),7.35–7.28(m,5H),5.82(s,1H),2.43(s,3H).
13C NMR(101MHz,Chloroform-d)δ189.5,145.7,135.2,134.4,133.5,133.3,132.3,130.8,129.5,129.4,129.3,129.3,128.9,75.5,21.8.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H18ClNaO3S2 +:405.0590；found:405.0600.
Example twenty-nine
S-phenyl-4-fluorosulphonate instead of S-phenylthiobesylate as in example one gave 2- ((4-fluorophenyl) sulfonyl) -1-phenyl-2- (phenylthio) ethan-1-one as a white solid in 70% yield.
1H NMR(400MHz,Chloroform-d)δ8.03(ddd,J＝10.0,5.1,2.5Hz,2H),7.90–7.84(m,2H),7.64–7.58(m,1H),7.53(dt,J＝6.6,1.5Hz,2H),7.49–7.42(m,2H),7.36–7.28(m,3H),7.26–7.17(m,2H),5.85(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.4,167.7,165.2,135.0,134.6,133.9,133.8,133.5,132.1(d,J＝3.1Hz),131.9,129.6(d,J＝4.4Hz),129.2,129.0,116.2,115.9,75.3.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15FNaO3S2 +:409.0339；found:409.0339.
Example thirty
S-phenyl-4-chlorothiobenzenesulfonate instead of S-phenylthiobenzenesulfonate as in example one, gave 2- ((4-chlorophenyl) sulfonyl) -1-phenyl-2- (phenylthio) ethane-1-one as a yellow oil in 67% yield.
1H NMR(400MHz,Chloroform-d)δ7.95(d,J＝8.5Hz,2H),7.88(d,J＝7.6Hz,2H),7.62(t,J＝7.4Hz,1H),7.57–7.49(m,4H),7.46(t,J＝7.7Hz,2H),7.33(dt,J＝14.1,6.8Hz,3H),5.84(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.3,141.5,135.0,134.6,134.6,133.6,132.3,131.9,129.6,129.6,129.2,129.0,75.3.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15ClNaO3S2 +:425.0043；found:425.0063.
Example thirty one
S-phenyl-4-bromothiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 66% yield of 2- ((4-bromophenyl) sulfonyl) -1-phenyl-2- (phenylthio) ethan-1-one as a white solid.
1H NMR(400MHz,Chloroform-d)δ7.92–7.83(m,4H),7.72–7.67(m,2H),7.63(t,J＝7.4Hz,1H),7.55–7.51(m,2H),7.47(t,J＝7.8Hz,2H),7.38–7.29(m,3H),5.82(s,1H).
13C NMR(101MHz,Chloroform-d)δ189.2,135.1,135.0,134.6,133.6,132.4,132.0,131.9,130.2,129.59,129.55,129.2,129.0,75.4.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H15BrNaO3S2 +:468.9538；found:468.9549.

Claims (3)

1. A method for synthesizing beta-ketosulfolane is characterized in that: under the action of sodium carbonate, arylformyl methylene dimethyl sulfur bromide and thiosulfonic acid ester are subjected to bifunctional reaction to synthesize the beta-ketone thiosulfone compound in one step.
2. The method of claim 1, wherein the aryloxymethylene dimethyl sulfide bromide is 2- (methoxy) benzoyloxymethylene dimethyl sulfide bromide, 4- (methoxy) benzoyloxymethylene dimethyl sulfide bromide, 2,5- (dimethoxy) benzoylmethylene dimethyl sulfide bromide, 4- (methyl) benzoylmethylene dimethyl sulfide bromide, naphthoylmethylene dimethyl sulfide bromide, dibenzoylmethylene dimethyl sulfide bromide, 4- (trifluoromethyl) benzoylmethylene dimethyl sulfide bromide, 4- (fluoro) benzoylmethylidene dimethyl sulfide bromide, 4- (chloro) benzoylmethylidene dimethyl sulfide bromide, 4- (bromo) benzoylmethylidene dimethyl sulfide bromide, 4- (cyano) benzoylmethylidene dimethyl sulfide bromide, sulfur dioxide, sulfur bromide, sulfur dioxide, sulfur bromide, sulfur dioxide, sulfur bromide, sulfur dioxide, sulfur bromide, sulfur dioxide, sulfur bromide, sulfur dioxide, 4- (nitro) benzoylmethylene dimethyl sulphur bromide, 4- (trifluoromethoxy) benzoylmethylene dimethyl sulphur bromide, thiophenecarboxylmethylene dimethyl sulphur bromide, 3- (chloro) benzoylmethylene dimethyl sulphur bromide, 3- (bromo) benzoylmethylene dimethyl sulphur bromide, 3- (methoxy) benzoylmethylene dimethyl sulphur bromide and cyclopropylformylmethylene dimethyl sulphur bromide.
3. The method for synthesizing β -ketosulfolane according to claim 1, wherein the thiosulfonate is S-phenyl thiobenzenesulfonate, S- (4-chlorophenyl) -thiobenzenesulfonate, S- (4-methylphenyl) -thiobenzenesulfonate, S- (4-methoxyphenyl) -thiobenzenesulfonate, S- (2-fluorophenyl) -thiobenzenesulfonate, S-propyl thiobenzenesulfonate, S-butyl thiobenzenesulfonate, S-dodecyl thiobenzenesulfonate, S-pyridyl thiobenzenesulfonate, Se-phenylselenophenylsulfonate, S-phenyl-4-methylthiobenzenesulfonate, S-phenyl-4-fluorobenzenesulfonate, S-phenyl-4-chlorobenzene thiosulfonate, S-phenyl-4-fluorobenzenesulfonate, S-phenyl-thiobenzenesulfonate, S-phenyl-4-chlorobenzene thiosulfonate, S-phenyl-thiobenzenesulfonate, S-phenyl-4-fluorobenzenesulfonate, S-phenyl-benzenesulfonate, S-phenyl-4-phenyl-benzenesulfonate, S-phenyl-4-phenyl-thiobenzenesulfonate, S-phenyl-4-phenyl-thiobenzenesulfonate, S, S-phenyl-4-bromobenzene thiosulfonate.
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FU, DUO ET AL: "Direct 1,2-Oxosulfenylation of Acetylenic Sulfones with DMSO", 《ASIAN JOURNAL OF ORGANIC CHEMISTRY》 *
FU, DUO ET AL: "Direct and Efficient Synthesis of Sulfonium Acyl Sulfonylmethylide Ylides from Acetylenic Sulfones and Dimethyl Sulfoxide", 《SYNTHESIS》 *
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