CN114539109B - Beta-ketone sulfosulfone synthesis method - Google Patents

Beta-ketone sulfosulfone synthesis method Download PDF

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CN114539109B
CN114539109B CN202210261087.2A CN202210261087A CN114539109B CN 114539109 B CN114539109 B CN 114539109B CN 202210261087 A CN202210261087 A CN 202210261087A CN 114539109 B CN114539109 B CN 114539109B
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dimethyl sulfur
benzoylmethylene
bromide
sulfur bromide
chloroform
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CN114539109A (en
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曾庆乐
康晓康
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Chengdu Univeristy of Technology
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    • 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, eletriptan, an antimigraine drug, adroquinone, for the treatment of breast cancer, etacoxib, for the treatment of osteoarthritis (ye.s, yang.m, wu.j, chem.commu.2020, 56, 4145-4155), and gamma-secretase inhibitors, for the prevention of alzheimer's disease (i.churcher, d.beer, j.d.best, j.l.castro, e.e.clarke, a.gentry, t.harrison, l.hitzel, e.kay, s.kerrad, h.d.wires, p.m.gutierrez, r.m.smith, p.j.oakley, m.reilly, d.e.shaw, m.s.shearman, m.r.ball, s.williams and j.d.j.wriglg, bioorg.med.chem.lett.,2006,16, 280.) contain sulfone units. In the field of organic pesticides, sulfone compounds have very good antibacterial activity, such as 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, 5626-563.), the insecticides oxycarboxin (k.huster, p.n.moza, a.kettrup, chemosphere.1999,38, 23-3429.). 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, 664-670.). 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) The stevens rearrangement of aryldiazoacetates and thioylides is catalyzed by copper/bipyridine complexes (H.Yuan, T.Nuligoda, 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.thirupathi, c.h.tung, z.xu, j.org.chem.2018,83, 9449-9455.). (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 bifunctional 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 GDA0003886935440000021
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 stirring bar was added phenacylidenedimethylthiobromide (0.6 mmol), S-phenylthiobenzenesulfonate (0.5 mmol, sodium carbonate (4 equiv.), 5mL acetonitrile, and finally the tube was sealed with a rubber stopper.A preheated 80 ℃ oil bath was stirred under nitrogen for 4h, after which the reaction mixture was cooled to room temperature, quenched by the addition of saturated sodium chloride solution (10 mL), extracted 3 times with ethyl acetate (15 mL), and the combined organic layers were extracted with anhydrous MgSO 4 Dried 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 as eluent) to give 1-phenyl-2- (benzenesulfonyl) -2- (phenylthio) ethan-1-one as a white solid in 82% yield after purification.
The structural characterization data for the product 1-phenyl-2- (phenylsulfonyl) -2- (phenylthio) ethan-1-one is as follows:
1 H 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).
13 C 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 C 20 H 16 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 20 H 15 FNaO 3 S 2 + 409.0339; found 409.0370, EXAMPLE III
4- (chloro) benzoylmethylenedimethylsulfur bromide was substituted for the benzoylmethylenedimethylsulfur bromide in example one to give 1- (4-chlorophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethane-1-one as a yellow oil in 75% yield.
1 H 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).
13 C 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 C 20 H 15 ClNaO 3 S 2 + 425.0043; found 425.0060 example four
4- (bromo) benzoylmethylenedimethylsulfur bromide was used in place of the benzoylmethylenedimethylsulfur bromide in example one to give 1- (4-bromophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethane-1-one as a white solid in 75% yield.
1 H 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).
13 C 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 C 20 H 15 BrNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 21 H 15 NNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 20 H 15 NNaO 5 S 2 + 436.0284; found 436.0278 EXAMPLE seven
4- (trifluoromethyl) benzoylmethylenedimethylthio bromide was used in place of the benzoylmethylenedimethylthio bromide in example one to give 61% yield of 2- (phenylsulfonyl) -2- (phenylthio) -1- (4- (trifluoromethyl) phenyl) ethan-1-one as a yellow solid.
1 H 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).
13 C 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 C 21 H 15 F 3 NaO 3 S 2 + 459.0307; found 459.0328. Eight embodiment
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.
1 H 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).
13 C 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 C 21 H 15 F 3 NaO 4 S 2 + 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.
1 H 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).
13 C 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 C 21 H 18 NaO 4 S 2 + 421.0539; 421.0560 found, 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.
1 H 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).
13 C 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 C 26 H 20 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 20 H 15 BrNaO 3 S 2 + 468.9538; found 468.9544, example twelve
3- (chloro) benzoylmethylenedimethylsulfur bromide was used instead of the benzoylmethylenedimethylsulfur bromide in example one to give 1- (3-chlorophenyl) -2- (benzenesulfonyl) -2- (phenylthio) ethane-1-one as a colorless oil in 84% yield.
1 H 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).
13 C 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 C 20 H 15 ClNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 21 H 18 NaO 4 S 2 + 421.0539; found 421.0532. Fourteen examples
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.
1 H 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).
13 C 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 C 21 H 18 NaO 4 S 2 + 421.0539; 421.0538 found, 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.
1 H 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).
13 C 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 C 22 H 20 NaO 5 S 2 + 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.
1 H 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).
13 C 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 C 24 H 18 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 17 H 16 NaO 3 S 2 + 355.0433; 355.0430 found, 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.
1 H 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).
13 C 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 C 18 H 14 NaO 3 S 3 + 396.9997; 396.9978 found in nineteen embodiments
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.
1 H 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).
13 C 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 C 20 H 15 ClNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 21 H 18 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 21 H 18 NaO 4 S 2 + 421.0539; 421.0541 found 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.
1 H 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).
13 C 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 C 20 H 15 FNaO 3 S 2 + 409.0339; found 409.0349, example twenty-three
S-propylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 65% yield of 1-phenyl-2- (phenylsulfonyl) -2- (propylthio) ethan-1-one as a yellow solid.
1 H 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).
13 C 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 C 17 H 18 NaO 3 S 2 + 357.0590; found 357.0590 example twenty-four
S-Butylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, gave 1-phenyl-2- (benzenesulfonyl) -2- (propylthio) ethan-1-one as a white solid in 66% yield.
1 H 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).
13 C 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 C 18 H 20 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 26 H 36 NaO 3 S 2 + 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.
1 H 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).
13 C 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 C 19 H 15 NNaO 3 S 2 + 392.0386; found 392.0381. Twenty-seven of the examples
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.
1 H 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).
13 C 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 C 20 H 16 NaO 3 SSe + 438.9578; found 438.9561 example twenty-eight
S-phenyl-4-methylthiobenzenesulfonate instead of S-phenylthiobenzenesulfonate in example one, a white oil of 1-phenyl-2- (phenylthio) -2-toluenesulfonic acid-1-one in a yield of 80% was obtained.
1 H 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).
13 C 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 C 21 H 18 ClNaO 3 S 2 + 405.0590; found 405.0600, twenty-nine embodiment
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.
1 H 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).
13 C 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 C 20 H 15 FNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 20 H 15 ClNaO 3 S 2 + 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.
1 H 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).
13 C 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 C 20 H 15 BrNaO 3 S 2 + :468.9538；found:468.9549.

Claims (1)

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 a beta-ketone thiosulfone compound in one step; the aryloxymethylene dimethyl sulfur bromide is 2- (methoxy) benzoylmethylene dimethyl sulfur bromide, 4- (methoxy) benzoylmethylene dimethyl sulfur bromide, 2,5- (dimethoxy) benzoylmethylene dimethyl sulfur bromide, 4- (methyl) benzoylmethylene dimethyl sulfur bromide, naphthoylmethylene dimethyl sulfur bromide, dibenzoylmethylene dimethyl sulfur bromide, 4- (trifluoromethyl) benzoylmethylene dimethyl sulfur bromide, 4- (fluoro) benzoylmethylene dimethyl sulfur bromide, 4- (chloro) benzoylmethylene dimethyl sulfur bromide, 4- (bromo) benzoylmethylene dimethyl sulfur bromide, 4- (cyano) benzoylmethylene dimethyl sulfur bromide, 4- (nitro) benzoylmethylene dimethyl sulfur bromide, 4- (trifluoromethoxy) benzoylmethylene dimethyl sulfur bromide, thenoylmethylene dimethyl sulfur bromide, 3- (chloro) benzoylmethylene dimethyl sulfur bromide, 3- (bromo) benzoylmethylene dimethyl sulfur bromide, 3- (methoxy) benzoylmethylene dimethyl sulfur bromide, and cyclopropylformylmethylene dimethyl sulfur bromide; the thiosulfonate is S-phenyl thiobenzenesulfonate, S- (4-chlorphenyl) -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, S-phenyl-4-methylthiobenzenesulfonate, S-phenyl-4-fluorobenzenesulfonate, S-phenyl-4-chlorobenzenesulfonate, S-phenyl-4-bromobenzenesulfonate.
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* Cited by examiner, † Cited by third party
Title
Direct 1,2-Oxosulfenylation of Acetylenic Sulfones with DMSO;Fu, Duo ET AL;《Asian Journal of Organic Chemistry》;20211231;1756-1764 *
Direct and Efficient Synthesis of Sulfonium Acyl Sulfonylmethylide Ylides from Acetylenic Sulfones and Dimethyl Sulfoxide;Fu, Duo ET AL;《Synthesis》;20211231;4086-4096 *
Metal-Free Chemoselective Reaction of Sulfoxonium Ylides and Thiosulfonates: Diverse Synthesis of 1,4-Diketones, Aryl Sulfursulfoxonium Ylides, and β-Keto Thiosulfones Derivatives;Wang, Fei ET AL;《Organic Letters》;20201231;6600-6604 *
Product class 1: sulfur ylides;Aggarwal, V. ET AL;《Science of Synthesis》;20041231;21-104 *

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