CN110372628B - Internal sulfonamide compound and preparation method thereof - Google Patents

Internal sulfonamide compound and preparation method thereof Download PDF

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CN110372628B
CN110372628B CN201910616230.3A CN201910616230A CN110372628B CN 110372628 B CN110372628 B CN 110372628B CN 201910616230 A CN201910616230 A CN 201910616230A CN 110372628 B CN110372628 B CN 110372628B
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sulfonamide
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CN110372628A (en
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刘文博
钟大猷
刘卫
吴笛
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Wuhan University WHU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring

Abstract

The invention provides an internal sulfonamide compound and a preparation method thereof. Adding a catalyst C, a sulfamide B and an oxidant D into an organic solvent for reaction, and separating and purifying to obtain an internal sulfamide compound E, or adding an oxidant F into the mixture for reaction after the reaction to be detected is finished, and separating and purifying to obtain an internal sulfimide compound G. The catalyst required by the method is an iron complex which is cheap, easy to obtain and low in toxicity. When the sulfamide H is used, the one-pot synthesis of the internal sulfimide compound is realized under the condition that another oxidant F is additionally added after the reaction is finished according to the method. The prepared internal sulfamide and internal sulfimide compounds are widely applied to the fields of pharmaceutical chemistry, material chemistry and organic synthesis.

Description

Internal sulfonamide compound and preparation method thereof
Technical Field
The invention relates to the technical field of organic synthesis, in particular to an internal sulfonamide compound and a preparation method thereof.
Background
The sulfonamide skeleton is widely existed in some drug macromolecules with broad-spectrum antibacterial activity, is a very important structural segment, and plays an important role in the synthesis of new drugs. It is particularly noted that the structures of the lactam class have good water solubility and stability, are considered to be lactam backbone equivalents, and are widely used for structural modification of drugs (as shown in fig. 3), and thus have received wide attention from scientists in the field of pharmaceutical chemistry [ a) Mustafa, a.chem.rev.1954,54,195-223. b) Inagaki, m.; tsuri, t.; jyoyama, h.; ono, t.; yamada, k.; kobayashi, m.; hori, y.; arimura, a.; yasui, k.; ohno, k.; kakudo, s.; koizumi, k.; suzuki, r.; kato, m.; kawai, s.; matsumoto, s.j.med. chem.2000,43,2040-2048. c) Donkor, i.o.curr.med.chem.2000,7,1171-1188. d) Wells, g.j.; tao, m.; josef, k.a.; bihovsky, R.J.Med.chem.2001,44, 3488-; gallet, s.; fluquet, n.; carto, p.; pfeiffer, b.; renard, p.; leonce, S.; pierre, a.; covatte, p.; berthelot, p.j.med.chem.2005,48,7363-7373. f) Lad, n.p.; kulkarni, s.; sharma, r.; mascarenhas, M.; kulkarni, m.r.; pandit, s.s. piolongumine, eur.j.med.chem.2017,126, 870-878 ], and such structures can also be applied to the total synthesis of certain heterocyclic compounds and natural products [ a) Davison, e.c.; fox, m.e.; holmes, a.b.; roughley, s.d.; smith, c.j.; williams, g.m.; davies, j.e.; raithby, p.r.; adams, j.p.; forbes, i.t.; press, n.j.; thompson, m.j.j.chem.soc., Perkin trans.12002, 12, 1494-1514. b) Storer, r.i.; takemoto, t.; jackson, p.s.; brown, d.s.; baxendale, i.r.; ley, S.V.chem.Eur.J.2004,10, 2529-2547 ]. The current methods for synthesizing such structures mainly include (1) Diels-Alder cyclization reaction [ a) rassad, v.a.; grosheva, d.s.; tomashevski, a.a.; sokolov, v.v.chem.heterocyl.comp.2013, 49, 39-65. b) Greig, i.r.; tozer, M.J.; wright, P.T.org.Lett.2001,3, 369-; (2) (ii) cyclic olefin metathesis (RCM) [ a) McReynolds, m.d.; dougherty, j.m.; hanson, p.r.chem.rev.2004, 104,2239-2258. b) Karsch, s.; freitag, d.; schwab, P.Metz, P.Synthesis 2004, 1696-; (3) radical cyclization [ Ueda, m.; miyabe, h.; nishimura, a.; miyata, o.; takemoto, y.; naito, T.org.Lett.2003,5, 3835-; (4) intramolecular Heck reaction [ a) Khalifa, a.; conway, l.; geoghegan, k.; evans, p.tetrahedron lett.2017,58, 4559-4562. b) Laha, j.k.; sharma, s.; kirar, s.; banerjee, U.C.J.org.chem.2017, 82, 9350-9359 et al.
At present, the catalytic synthesis method of the internal sulfonamide skeleton is only reported, and is limited to the synthesis of the structural skeleton of the benzsulfamide through intramolecular amination of a benzenesulfonyl azide substrate. With the rapid development of enzyme catalysis reaction in recent years, the Arnold, Fasan and Hartwig task groups successively report that aryl sulfonyl azide substrates undergo intramolecular amination under enzyme catalysis to obtain rigid benzo-endocarbazide structures, and the benzo-endocarbazide structures have good chemoselectivity and enantioselectivity [ a) McIntosh, J.A.; coelho, p.s.; farwell, c.c.; wang, z.j.; lewis, j.c.; brown, r.; arnold, f.h.angelw.chem., int.ed.2013,52,9309-9312. b) Hyster, t.k.; farwell, c.c.; burler, a.r.; McIntosh, j.a.; arnold, f.h.j.am.chem.soc.2014, 136,15505-15508. c) Prier, c.k.; zhang, r.k.; burler, a.r.; Brinkmann-Chen, S.; arnold, f.h.nat.chem.2017,9,629-634. d) Singh, r.; bordeaux, M.; fasan, r. ACS catal.2014,4,546-552. e) Singh, r.; kolev, j.n.; sutera, p.a.; fasan, r.acs cat.2015, 5,1685-1691. f) Dydio, p.; key, h.m.; hayashi, h.; clark, d.s.; hartwig, J.F. J.am.chem.Soc.2017,139, 1750-1753. The metal catalyst porphyrin cobalt and iridium imine compound can also catalyze the intramolecular reaction of aryl sulfonamide to synthesize benzo-lactam [ Ruppel, J.V.; kamble, r.m.; zhang, x.p. org.lett.2007,9, 4889-; ichino, m.; suematsu, h.; yasutomi, y.; nishioka, y.; uchida, t.; katsuki, T.Angew.chem., Int.Ed.2011, 50, 9884-. In conclusion, the methods have the defects of complex catalyst structure, difficult acquisition, high price and the like, and more importantly, the reaction substrates of the methods are limited to aryl sulfonyl azide substrates and can only be used for synthesizing rigid benzo-lactam products.
Disclosure of Invention
In order to solve the defects in the prior art, the invention aims to provide an internal sulfonamide compound and a preparation method thereof, namely, a novel method for catalyzing by an iron complex is used for synthesizing the internal sulfonamide and the internal sulfonamide imide compound.
To achieve the above object, an aspect of the present invention provides an internal sulfonamide compound, characterized in that: comprises an internal sulfonamide compound E and an internal sulfonamide compound G;
the molecular structural formula of the internal sulfonamide compound E is as follows:
Figure BDA0002124041400000031
the molecular structural formula of the internal sulfonamide compound G is as follows:
Figure BDA0002124041400000032
wherein R is1、R2、R3、R4、R5Are independent from each other; n is selected from 0, 1 or 2;
the R is1Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is2Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is3Optionally selected from hydrogen, alkyl, alkenyl, aryl;
the R is4Optionally selected from hydrogen, alkyl, alkenyl, aryl;
the R is5Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothio, alkylamino or arylamino.
The invention also provides a preparation method of the internal sulfonamide compound, which is characterized by comprising the following steps: the method comprises the following steps:
adding an iron complex catalyst C, a raw material sulfonamide B and an oxidant D into an organic solvent, stirring for reaction, and separating and purifying after the reaction to obtain an internal sulfonamide compound E; the mass ratio of the iron complex catalyst C, the raw material sulfamide B and the oxidant D is 0.01:1:1 to 0.5:1:5 in terms of the raw material dosage;
the prepared internal sulfonamide compound E takes sulfonamide B as a raw material, and the reaction equation is as follows:
Figure BDA0002124041400000041
or adding the iron complex catalyst C, the raw material sulfonamide H and the oxidant D into an organic solvent, stirring for reaction, adding the oxidant F after the detection reaction is finished, reacting, and separating and purifying to obtain an internal sulfimide compound G; the material amount ratio of the iron complex catalyst C, the raw material sulfamide H, the oxidant D and the oxidant F is 0.01:1:1:1 to 0.5:1:5: 2;
the prepared internal sulfonamide compound G takes sulfonamide H as a raw material, and the reaction equation is as follows:
Figure BDA0002124041400000051
wherein R is1、R2、R3、R4、R5Are independent from each other; n is selected from 0, 1 or 2;
the R is1Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is2Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is3Optionally selected from hydrogen, alkyl, alkenyl, aryl;
the R is4Optionally selected from hydrogen, alkyl, alkenyl, aryl;
the R is5Optionally selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothio, alkylamino or arylamino.
The structure of the oxidant F is Ar2I(OCOCF3)2Wherein Ar is2Optionally selected from phenyl, substituted phenyl, naphthyl, substituted naphthyl;
the iron complex catalyst C is a complex formed by iron salt and a ligand; wherein the iron salt is selected from ferric salt or ferrous salt, and has a formula of Fe (X)2Or Fe (X)3(ii) a X is optionally an anion as follows: cl–、Br–、 I–、AcO–、TfO–、ClO4 –、BF4 –Or SbF6 –(ii) a Wherein the ligand is optionally selected from the following structures:
Figure BDA0002124041400000052
wherein R is6Optionally selected from hydrogen, C1-C6 alkyl, phenyl or substituted phenyl; wherein R is7、R8、R9Are each independently a substituent, the same or different; r7、R8、R9Optionally hydrogen, C1-C6 alkyl or fluorine-containing alkyl, aryl, heteroaryl, alkoxy, alkylamino, arylamino; wherein the ratio of the amount of iron and ligand species is from 1:1 to 1: 3;
the oxidant D is a higher-valent iodide, optionally taken from oxyiodobenzene or Ar1I(OCOR)2(ii) a Wherein Ar is1Optionally selected from phenyl, substituted phenyl, naphthyl or substituted naphthyl; wherein R is selected from C1-C6 alkyl or fluorine-containing alkyl.
Preferably, the ratio of the amounts of iron and ligand species is 1: 2.
Further, the fluoroalkyl group is any one of iodobenzene acetate, iodobenzene trifluoroacetate, iodobenzene pivalate, iodobenzene dimethylmalonate or iodobenzene benzoate.
Further, the temperature of the stirring reaction is 20-120 ℃; the separation and purification is any one of column chromatography, recrystallization or distillation.
Still further, the organic solvent is optionally selected from the following solvents or combinations of solvents: acetonitrile, tert-butanol, 1, 2-dichloroethane, dichloromethane, tetrahydrofuran, methyl tert-butyl ether, dioxane, dimethyl sulfoxide, N, N' -dimethylformamide, trifluoroethanol, benzene, toluene, xylene or chlorobenzene.
Still further, the organic solvent is acetonitrile or 1, 2-dichloroethane.
In the above reaction, the yield of the reaction can be improved by adding a molecular sieve, wherein the molecular sieve is optionally selected from
Figure BDA0002124041400000061
Molecular sieve,
Figure BDA0002124041400000062
Molecular sieve,
Figure BDA0002124041400000063
Molecular sieves, preferably
Figure BDA0002124041400000064
A molecular sieve;
the invention has the following advantages and beneficial effects:
(1) the method realizes the synthesis of the internal sulfonamide compound by using the cheap and easily-obtained iron catalyst for the first time, and has the advantages of simple reaction operation, high reaction efficiency and good economy;
(2) the in-situ addition of the oxidant realizes the preparation of the internal sulfimide compound by a one-pot method, and provides a brand new method for the synthesis of the internal sulfimide;
(3) the iron catalyst with low toxicity is used, so that heavy metal residues in the synthesized product and the pollution of the reaction to the environment can be effectively reduced.
Drawings
FIG. 1 is a schematic representation of the reaction equation for the internal sulfonamide compound E of the present invention;
FIG. 2 is a schematic representation of the reaction equation for the sulfonamide compound G of the present invention;
FIG. 3 is a representative bioactive molecular structure containing an internal sulfonamide backbone.
Detailed Description
Further features and advantages of the present invention will be understood from the following detailed description. The examples provided are merely illustrative of the method of the present invention and do not limit the remainder of the disclosure in any way.
Example 1: reaction conditions for iron-catalyzed synthesis of internal sulfonamide by taking benzene sulfonamide as standard substrate
Figure BDA0002124041400000071
Figure BDA0002124041400000072
The study was carried out:
Figure BDA0002124041400000073
wherein, the step a is that the reaction is operated at 60 ℃; footnote b indicates that no molecular sieve was added to the reaction; wherein [ Fe ]]Is ferric salt; the ligand structure is shown as table drawing L1-L7; mol% refers to relative molar weight, equiv refers to equivalent weight, base refers to common inorganic base, solvent refers to organic solvent, and the volume is 2 mL; wherein DMF is N, N' -dimethylformamide, MeCN is acetonitrile, DCE is 1, 2-dichloroethane, 1, 4-dioxane is dioxane, tolumene is toluene. Wherein ligand refers to multidentate nitrogen ligand, oxidant refers to oxidant, and yield refers to internal sulfonamide and internal sulfonyl imideThe total nuclear magnetic yield of (1) takes sym-trimethoxybenzene as an internal standard substance. PhI (OAc)2Is iodobenzene acetate, PhI (OCOCF)3)2Is iodobenzene trifluoroacetate, PhI (DMM) is iodobenzene dimethylmalonate, PhI (OPiv)2Is iodobenzene pivalate.
3-Phenylisothiazolidine-1, 1-dioxide [3-Phenylisothiazolidine 1,1-dioxide ]:
Figure BDA0002124041400000081
a white solid, a solid which is,1H NMR(400MHz,CDCl3)δ7.54–7.31(m,5H),4.76–4.70(m, 2H),3.44–3.29(m,1H),3.20(m,J＝12.6,10.6,7.6Hz,1H),2.80–2.73(m,1H), 2.45–2.34(m,1H).
example 2:
3- (4-methylphenyl) isothiazolidine-1, 1-dioxy [3- (4-Tolyl) isothiazolidine 1,1-dioxide ]:
Figure BDA0002124041400000082
weighing ferrous perchlorate (5.1mg,0.02mmol) and ligand L2(8.2mg,0.04mmol) in a 4mL reaction bottle, adding 1.0mL acetonitrile for dissolving, stirring at room temperature for 30 min, weighing after in-situ complexation is finished
Figure BDA0002124041400000083
Molecular sieve (50.0mg), iodobenzene pivalate (163.8mg,0.4mmol) and p-toluene benzenesulfonamide substrate (42.3mg,0.2mmol) were added to the reaction system, and 1.0mL of acetonitrile was added to dissolve, and the mixture was reacted at 80 ℃ for 2 hours, filtered, the cake was washed with an appropriate amount of saturated sodium bicarbonate, the aqueous phase was extracted with dichloromethane 3 times (3 × 10mL), the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and after removal of the solvent, column chromatography was performed (dichloromethane/petroleum ether ═ 1: 1. dichloromethane), to obtain 3- (4-methylphenyl) isothiazolidine 1,1-dioxide (33.7mg, 80%) as an endopolyamide, and a white solid.1H NMR(400MHz, CDCl3)δ7.29(d,J＝8.1Hz,2H),7.19(d,J＝7.9Hz,2H),4.70(dt,J＝9.0,5.9Hz, 1H),4.43(br s,1H),3.36(ddd,J＝12.1,8.0,3.8Hz,1H),3.21(ddd,J＝12.7,10.3, 7.6Hz,1H),2.75(dtd,J＝11.0,7.0,3.8Hz,1H),2.46–2.37(m,1H),2.35(s,3H).
Example 3:
3- (4-Methoxyphenyl) isothiazolidine-1, 1-dioxide [3- (4-methoxyphenylyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000091
A white solid; the yield is 86%;1H NMR(400MHz,CDCl3)δ7.32(d,J＝8.8Hz 2H), 6.90(d,J＝8.8Hz 2H),4.79–4.63(m,1H),4.50(br s,1H),3.81(s,3H),3.45–3.32 (m,1H),3.25–3.17(m,1H),2.76–2.68(m,1H),2.44–2.34(m,1H)；13C NMR(100 MHz,CDCl3)δ159.8,132.0,127.5,114.5,58.0,55.5,48.5,32.4；HRMS(ESI+) calc’d for C10H13NNaO3S[M+Na]+:250.0508,found 250.0513.
3-Phenylisothiazolidine-1, 1-dioxy [3-Phenylisothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000092
White solid
1H NMR(400MHz,CDCl3)δ7.54–7.31(m,5H),4.76–4.70(m,2H),3.44– 3.29(m,1H),3.20(m,J＝12.6,10.6,7.6Hz,1H),2.80–2.73(m,1H),2.45–2.34(m, 1H).
Example 4:
3- (4-Nitrophenyl) isothiazolidine-1, 1-dioxide [3- (4-Nitrophenyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000101
A white solid; the yield is 52%;1H NMR(400MHz,CDCl3)δ8.25(d,J＝8.7Hz,2H), 7.62(d,J＝8.7Hz,2H),4.85(m,J＝7.9Hz,1H),4.74(br s,1H),3.40(ddd,J＝12.3, 7.3,2.7Hz,1H),3.21(td,J＝12.0,7.6Hz,1H),2.88(ddd,J＝13.8,7.1,4.6Hz,1H), 2.50–2.25(m,1H)；13C NMR(100MHz,CDCl3)δ148.0,147.9,127.0,124.5,57.2, 48.2,32.0；HRMS(ESI+)calc’d for C9H10ClNNaO2S[M+Na]+:265.0253,found 265.0254.
example 5:
3- (3-Methoxyphenyl) isothiazolidine-1, 1-dioxide [3- (3-methoxyphenylyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000111
A white solid; the yield is 66%;1H NMR(400MHz,CDCl3)δ7.30(t,J＝7.9Hz,1H), 6.97(d,J＝8.2Hz,2H),6.87(d,J＝8.2Hz,1H),4.75–4.67(m,1H),4.55(br s,1H), 3.82(s,3H),3.44–3.29(m,1H),3.24–3.16(m,1H),2.81–2.73(m,1H),2.45–2.37 (m,1H)；13C NMR(100MHz,CDCl3)δ160.2,141.9,130.3,118.2,114.0,111.6,58.2, 55.5,48.2,32.2；HRMS(ESI+)calc’d for C10H13NNaO3S[M+Na]+:250.0508,found 250.0513.
example 6:
3- (3-Bromophenyl) isothiazolidine-1, 1-dioxide [3- (3-broylphenyl) isothiazolidine 1,1-dioxide]
Figure BDA0002124041400000112
A white solid; the yield is 74%;1H NMR(400MHz,CDCl3)δ7.56(s,1H),7.46(dd,J＝ 7.9,1.0Hz,1H),7.35(d,J＝7.8Hz,1H),7.30–7.21(m,1H),4.73–4.65(m,2H), 3.43–3.31(m,1H),3.19(m,J＝12.5,11.0,7.6Hz,1H),2.79(m,J＝10.4,7.3,3.4 Hz,1H),2.49–2.28(m,1H)；13C NMR(100MHz,CDCl3)δ142.7,131.7,130.8, 129.2,124.8,123.2,57.5,48.2,32.1；HRMS(ESI+)calc’d for C9H10BrNNaO2S [M+Na]+:297.9508,found 297.9509.
example 7:
3- (2-Methoxyphenyl) isothiazolidine-1, 1-dioxy [3- (2-methoxyphenylyl) isothiazolidine 1,1-dioxide]
Figure BDA0002124041400000121
A white solid; the yield is 77%;1H NMR(400MHz,CDCl3)δ7.45(dd,J＝7.6,1.5Hz, 1H),7.34–7.28(m,1H),7.00–6.97(m,1H),6.90(d,J＝8.2Hz,1H),4.96(dd,J＝8.3,7.0Hz,1H),3.86(s,3H),3.34–3.27(m,1H),3.24–3.16(m,1H),2.84–2.76(m, 1H),2.45–2.35(m,1H)；13C NMR(100MHz,CDCl3)δ156.6,129.5,127.5,127.3, 121.2,110.7,55.5,54.4,48.2,30.4；HRMS(ESI+)calc’d for C10H13NNaO3S [M+Na]+:250.0508,found 250.0505.
example 8:
3- (2-Bromophenyl) isothiazolidine-1, 1-dioxy [3- (2-broylphenyl) isothiazolidine 1,1-dioxide 2h])
Figure BDA0002124041400000122
A white solid; the yield is 61%;1H NMR(400MHz,CDCl3)δ7.73(dd,J＝7.8,1.6Hz, 1H),7.54(dd,J＝8.0,1.1Hz,1H),7.42–7.34(m,1H),7.18(td,J＝7.7,1.7Hz,1H), 5.16(dd,J＝14.8,6.7Hz,1H),4.70(br s,1H),3.33(ddd,J＝12.1,7.1,3.7Hz,1H), 3.23–3.12(m,1H),3.06–2.98(m,1H),2.30–2.20(m,1H)；13C NMR(100MHz, CDCl3)δ139.7,133.1,129.8,128.5,127.6,121.8,57.2,48.0,30.1；HRMS(ESI+) calc’d for C9H10BrNNaO2S[M+Na]+:297.9508,found 297.9505.
example 9:
3- (4-Chlorophenyl) isothiazolidine-1, 1-dioxy [3- (4-chlorophenylene) isothiazolidine 1,1-dioxide]
Figure BDA0002124041400000131
A white solid; the yield is 80%;1H NMR(400MHz,CDCl3)δ7.34–7.32(m,4H),4.71 (t,J＝6.6Hz,1H),4.66(br s,1H),3.36–3.30(m,1H),3.22–3.14(m,1H),2.79– 2.71(m,1H),2.38–2.27(m,1H)；13C NMR(100MHz,CDCl3)δ138.9,134.4,129.3, 127.5,57.6,48.3,32.3；HRMS(ESI+)calc’d for C9H10ClNNaO2S[M+Na]+: 254.0013,found 254.0013.
example 10:
3- (4-Bromophenyl) isothiazolidine-1, 1-dioxide [3- (4-broylphenyl) isothiazolidine 1,1-dioxide]
Figure BDA0002124041400000132
A white solid; the yield is 75%;1H NMR(400MHz,CDCl3)δ7.50(d,J＝8.3Hz,2H), 7.29(d,J＝8.4Hz,2H),4.87–4.59(m,2H),3.35(ddd,J＝10.9,7.6,3.1Hz,1H), 3.26–3.13(m,1H),2.85–2.70(m,1H),2.44–2.25(m,1H)；13C NMR(100MHz, CDCl3)δ139.5,132.3,127.9,122.4,57.6,48.3,32.2；HRMS(ESI+)calc’d for C9H10BrNNaO2S[M+Na]+:297.9508,found 297.9512.
example 11:
3- (4-trifluoromethylphenyl) isothiazolidine-1, 1-dioxide [3- (4- (trifluoromethylphenyl) phenyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000141
A white solid; the yield is 88%;1H NMR(400MHz,CDCl3)δ7.64(d,J＝8.2Hz,2H), 7.54(d,J＝8.2Hz,2H),4.87–4.79(m,2H),3.37(ddd,J＝12.3,7.5,3.2Hz,1H), 3.27–3.14(m,1H),2.84–2.80(m,1H),2.47–2.26(m,1H)；13C NMR(100MHz, CDCl3)δ144.6(q,J＝1.0Hz),130.8(q,J＝32.4Hz),126.5,126.1(q,J＝3.8Hz), 124.0(q,J＝270.5Hz),57.6,48.2,32.1；19F NMR(376MHz,CDCl3)δ–62.61(s)； HRMS(ESI+)calc’d for C10H10F3NNaO2S[M+Na]+:288.0277,found 288.0282.
example 12:
3- (3-methylphenyl) isothiazolidine-1, 1-dioxy [3- (3-Tolyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000142
A white solid; the yield is 89%;1H NMR(400MHz,CDCl3)δ7.30–7.25(m,1H),7.24 –7.12(m,3H),4.72–4.68(m,1H),4.51(br s,1H),3.39–3.33(m,1H),3.25–3.17 (m,1H),2.78–2.73(m,1H),2.46–2.38(m,1H),2.37(s,3H).
example 13:
3- (2-methylphenyl) isothiazolidine-1, 1-dioxy [3- (2-Tolyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000151
A white solid; the yield is 81%;1H NMR(400MHz,CDCl3)δ7.58(d,J＝7.4Hz,1H), 7.30–7.23(m,1H),7.21(dd,J＝7.2,1.2Hz,1H),7.17(d,J＝7.2Hz,1H),4.97(t,J ＝6.8Hz,1H),4.51(br s,1H),3.35(ddd,J＝12.3,7.8,4.3Hz,1H),3.21(ddd,J＝ 12.6,9.8,7.6Hz,1H),2.78(ddd,J＝11.6,10.2,5.8Hz,1H),2.37(s,3H),2.37–2.28 (m,1H).
example 14:
3-phenyl-1, 2-thiazinane-1, 1-dioxy [3-phenyl-1, 2-thiazine 1,1-dioxide ]
Figure BDA0002124041400000152
A white solid; the yield is 70%;1H NMR(400MHz,CDCl3)δ7.43–7.29(m,5H),4.59 (dd,J＝11.9,3.4Hz,1H),4.24(br s,1H),3.33–3.19(m,1H),3.01(td,J＝13.1,5.2 Hz,1H),2.43–2.23(m,2H),2.06(ddd,J＝13.9,5.9,3.0Hz,1H),1.73(ddd,J＝17.1, 13.0,8.5Hz,1H).
example 15:
3-methyl-2, 3-dihydrobenzisothiazolidine-1, 1-dioxy [3-methyl-2, 3-dihydrobenzozo [ d ]]isothiazole 1,1-dioxide]
Figure BDA0002124041400000153
A white solid; the yield is 70%;1H NMR(400MHz,CDCl3)δ7.78(d,J＝7.7Hz,1H), 7.64(t,J＝7.5Hz,1H),7.54(t,J＝7.4Hz,1H),7.40(d,J＝7.7Hz,1H),4.82–4.78 (m,1H),1.63(d,J＝6.4Hz,3H).
example 16:
2, 3-dihydrobenzisothiazolidine-1, 1-dioxy [2, 3-dihydrobenzole [ d ] isothiazole 1,1-dioxide ]
Figure BDA0002124041400000161
A white solid; the yield is 50%;1H NMR(400MHz,CDCl3)δ7.80(d,J＝7.8Hz,1H), 7.62(td,J＝7.6,1.1Hz,1H),7.56–7.51(m,1H),7.40(d,J＝7.7Hz,1H),4.81(br s, 1H),4.54(s,2H).
example 17:
3- ((trimethylsilyl) ethynyl) isothiazolidine-1, 1-dioxide [3- ((trimethylsilyl) ethyl) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000162
A yellow solid; the yield is 53 percent;1H NMR(400MHz,CDCl3)δ4.59–4.22(m,2H), 3.31–3.20(m,1H),3.19–3.14(m,1H),2.86–2.66(m,1H),2.61–2.40(m,1H), 0.17(s,9H)；13C NMR(100MHz,CDCl3)δ102.0,91.2,46.7,46.0,30.9,-0.21； HRMS(ESI+)calc’d for C8H15NNaO2SSi[M+Na]+:240.0485,found 240.0489.
example 18:
3, 3-dimethylisothiazolidine-1, 1-dioxide [3,3-dimethylisothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000171
A white solid; the yield is 68 percent;1H NMR(400MHz,CDCl3)δ4.06(br s,1H),3.23(t,J＝ 7.5Hz,2H),2.29(t,J＝7.5Hz,2H),1.40(s,6H)；13C NMR(100MHz,CDCl3)δ 57.9,48.3,37.0,29.7；HRMS(ESI+)calc’d for C5H11NNaO2S[M+Na]+:172.0403, found 172.0404.
example 19:
3-methylisothiazolidine-1, 1-dioxy [3-methylisothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000172
A white solid; the yield is 74%;
1H NMR(400MHz,CDCl3)δ4.04(br s,1H),3.76–3.68(m,1H),3.26–3.20 (m,1H),3.17–3.09(m,1H),2.55–2.48(m,1H),2.09–1.99(m,1H),1.33(d,J＝ 6.3Hz,3H).
example 20:
Figure BDA0002124041400000173
the method comprises the following steps: weighing ferrous perchlorate (5.1mg,0.02mmol) and L1(8.1mg,0.04mmol) in a 4mL reaction bottle, adding 1.0mL acetonitrile for dissolving, stirring at room temperature for 30 min, weighing after in-situ complexation is finished
Figure BDA0002124041400000181
Molecular sieves (50.0mg), iodobenzene dimethylmalonate (167.0mg,0.5mmol) and the corresponding sulfonamide substrate (38.6mg,0.2mmol)) Adding the mixture into a reaction system, adding 1.0mL of acetonitrile for dissolving, reacting at 80 ℃ for 2h, filtering, washing a filter cake with a proper amount of saturated sodium bicarbonate, extracting an aqueous phase with dichloromethane for 3 times (3X 10mL), combining organic phases, washing with saturated saline, drying with anhydrous sodium sulfate, removing a solvent, and performing column chromatography separation (dichloromethane/petroleum ether ═ 1: 1-dichloromethane) to obtain pentabasic internal sulfamide 3-pentylisothiazolidine-1, 1-dioxy and hexabasic internal sulfamide 3-butylisothiazolidine-1, 1-dioxy as 3: 5 (32.6mg, 85%).
The second method comprises the following steps: weighing ferrous perchlorate (5.1mg,0.02mmol) and L6(10.1mg,0.06mmol) in a 4mL reaction bottle, adding 1.0mL acetonitrile for dissolving, stirring at room temperature for 30 min, weighing after in-situ complexation is finished
Figure BDA0002124041400000182
Adding a molecular sieve (50.0mg), dimethylmalonic acid iodobenzene (162.5mg,0.5mmol) and a corresponding sulfonamide substrate (38.6mg,0.2mmol) into a reaction system, adding 1.0mL of acetonitrile for dissolving, reacting at 80 ℃ for 2h, filtering, washing a filter cake with a proper amount of saturated sodium bicarbonate, extracting an aqueous phase for 3 times (3X 10mL) by using dichloromethane, combining organic phases, washing by using saturated saline, drying by using anhydrous sodium sulfate, removing a solvent, and then carrying out column chromatography separation (dichloromethane/petroleum ether is 1: 1-dichloromethane), so as to obtain pentabasic sulfonamide 3-pentylisothiazolidine-1, 1-dioxygen and hexabasic sulfonamide 3-butylisothiazolidine-1, 1-dioxygen with the ratio of 2: 1 (28.6mg, 75%).
3-Pentylisothiazolidine-1, 1-dioxy [ 3-pentathiazolidine 1,1-dioxide ]
Figure BDA0002124041400000183
A colorless liquid;1H NMR(400MHz,CDCl3)δ4.31(br s,1H),3.61–3.53(m,1H), 3.26–3.15(m,1H),3.13–3.06(m,1H),2.59–2.43(m,1H),2.12–1.97(m,1H), 1.64–1.53(m,2H),1.42–1.15(m,6H),0.89(t,J＝6.8Hz,3H)；13C NMR(100 MHz,CDCl3)δ55.4,48.2,36.1,31.6,30.0,25.9,22.6,14.1；HRMS(ESI+)calc’d for C8H17NNaO2S[M+Na]+:214.0872,found 214.0873.
3-butylisothiazolidine-1, 1-dioxy [3-Butyl-1,2-thiazinane 1,1-dioxide ]
Figure BDA0002124041400000191
A colorless liquid;1H NMR(400MHz,CDCl3)δ3.74(br s,1H),3.50–3.43(m,1H), 3.20(dt,J＝13.3,3.5Hz,1H),2.98–2.72(m,1H),2.28–2.12(m,2H),1.84–1.80 (m,1H),1.52–1.14(m,7H),0.90(t,J＝7.0Hz,3H)；13C NMR(100MHz,CDCl3)δ 56.8,49.6,35.6,30.7,27.6,23.2,22.5,14.1.
example 21:
3-Phenyl-1, 2-thiazetidine-1, 1-dioxy [3-Phenyl-1,2-thiazetidine 1,1-dioxide ]
Figure BDA0002124041400000192
MS＝183.04
Example 22:
[Tetrahydro-1H,3H-isothiazolo[4,3-c]isothiazole 2,2,5,5-tetraoxide]
Figure BDA0002124041400000193
MS＝211.99
example 23:
isothiazolidine-1, 1-dioxide [ isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000201
MS＝121.02
Example 24:
3-methyl-6-phenyl-1, 2-isothiazolidine-1, 1-dioxy [3-methyl-6-phenyl-1, 2-thiazine 1,1-dioxide ]
Figure BDA0002124041400000202
MS＝225.08
Example 25:
1, 2-Isothiazinane-1, 1-dioxy [1, 2-thiazine 1,1-dioxide ]
Figure BDA0002124041400000203
MS＝135.04
Example 26:
methyl-3, 4,6,7,8, 9-hexahydro-2-hydronaphthalen [2,3-e ] isothiazolidine-3-carboxy-1, 1-dioxo [ methyl 3,4,6,7,8, 9-hexahydro-2H-naphto [2,3-e ] [1,2] thiazine-3-carboxylate 1,1-dioxide ]
Figure BDA0002124041400000211
MS＝295.09
Example 27:
(E) -5- (3, 5-di-tert-butyl-4-hydroxy-benzylideneisothiazolidine-1, 1-dioxy [ (E) -5- (3,5-di-tert-butyl-4-hydroxybenzylidene) isothiazolidine 1,1-dioxide ]
Figure BDA0002124041400000212
MS＝337.17
Example 28:
methyl isothiazolidine-3-carbonyl-1, 1-dioxide [ methyl isothiazolidine-3-carboxylate 1,1-dioxide ]
Figure BDA0002124041400000213
MS＝179.03
Examples 29 to 42:
weighing ferrous perchlorate (5.2mg,0.02mmol) and ligand L2(8.0mg,0.04mmol) in a 4mL reaction bottle, adding 1.0mL acetonitrile for dissolving, stirring at room temperature for 30 min, weighing after in-situ complexation is finished
Figure BDA0002124041400000221
Adding a molecular sieve (50.0mg), iodobenzene pivalate (163.8mg,0.4mmol) and corresponding sulfonamide H (0.2mmol) into a reaction system, adding 1.0mL of acetonitrile, reacting at 80 ℃ until TLC monitors the reaction is complete, adding iodobenzene trifluoroacetate (103.1mg, 0.24mmol) into the reaction system, reacting at 80 ℃ for 1H, filtering, washing a filter cake with a proper amount of saturated sodium bicarbonate, extracting an aqueous phase with dichloromethane for 3 times (3X 10mL), combining organic phases, washing with saturated saline, drying with anhydrous sodium sulfate, removing a solvent, and performing column chromatography (dichloromethane/petroleum ether is 1: 1-dichloromethane) to obtain the endosulfonamide compound G.
Example 29:
3-phenyl-4, 5-dihydroisothiazole-1, 1-dioxy [3-phenyl-4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000222
A white solid; the yield is 88%;1H NMR(400MHz,CDCl3)δ8.03(dd,J＝8.4,1.2Hz, 2H),7.74–7.61(m,1H),7.53(t,J＝7.7Hz,2H),3.75–3.61(m,2H),3.56–3.35(m, 2H).
example 30:
3- (4-methylphenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4-Tolyl) -4,5-dihydroisothiazole 1,1-dioxide]
Figure BDA0002124041400000223
A white solid;1H NMR(400MHz,CDCl3)δ7.92(d,J＝8.3Hz,2H),7.32(d,J＝ 8.3Hz,2H),3.65(dd,J＝8.2,6.4Hz,2H),3.43(dd,J＝8.1,6.5Hz,2H),2.45(s, 3H).
example 31:
3- (4-Nitrophenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4-Nitrophenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000231
A white solid; the yield is 75%;1H NMR(400MHz,CD3CN)δ8.42–8.28(m,2H), 8.28–8.15(m,2H),3.76(dd,J＝8.0,6.3Hz,2H),3.47(dd,J＝7.9,6.3Hz,2H)；13C NMR(100MHz,CD3CN)δ177.2,151.9,137.5,131.1,124.9,45.4,35.1；HRMS (ESI+)calc’d for C9H8N2NaO4S[M+Na]+:263.0097,found 263.0093.
example 32:
3- (3-Methoxyphenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (3-Methoxyphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000232
A white solid; the yield is 81%;1H NMR(400MHz,CDCl3)δ7.63–7.58(m,1H),7.52 (d,J＝7.7Hz,1H),7.42(t,J＝8.0Hz,1H),7.19(dd,J＝8.2,2.4Hz,1H),3.87(s, 3H),3.75–3.55(m,2H),3.56–3.31(m,2H)；13C NMR(100MHz,CDCl3)δ176.0, 160.1,132.2,130.2,121.6,121.4,113.3,55.7,44.4,33.7；HRMS(ESI+)calc’d for C10H11NNaO3S[M+Na]+:248.0352,found 248.0352.
example 33:
3- (3-Bromophenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (3-broylphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000241
A white solid; the yield is 78%;1H NMR(400MHz,CDCl3)δ8.16(s,1H),8.05–7.90(m, 1H),7.80–7.77(m,1H),7.44–7.40(m,1H),3.64(dd,J＝8.3,6.2Hz,2H),3.46(dd, J＝8.1,6.3Hz,2H)；13C NMR(100MHz,CDCl3)δ174.6,137.5,132.9,132.1,130.8, 127.7,123.5,44.4,33.6；HRMS(ESI+)calc’d for C9H8BrNNaO2S[M+Na]+: 295.9351,found 295.9347.
example 34:
3- (2-Methoxyphenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (2-Methoxyphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000242
A white solid;1H NMR(400MHz,CDCl3)δ8.15(dd,J＝7.9,1.8Hz,1H),7.66– 7.48(m,1H),7.09–7.04(m,1H),7.01(d,J＝8.5Hz,1H),3.93(s,3H),3.82(t,J＝ 7.2Hz,2H),3.35(t,J＝6.8Hz 2H)；13C NMR(100MHz,CDCl3)δ178.0,160.5, 135.8,132.5,121.4,120.1,112.0,55.8,44.2,37.9；HRMS(ESI+)calc’d for C10H11NNaO3S[M+Na]+:248.0352,found 248.0352.
example 35:
3- (2-Bromophenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (2-broylphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000251
A white solid;1H NMR(400MHz,CDCl3)δ7.71(dd,J＝7.8,1.3Hz,1H),7.66 (dd,J＝7.6,1.9Hz,1H),7.46(dd,J＝7.5,1.4Hz,1H),7.43–7.38(m,1H),3.94– 3.68(t,2H),3.45(t,2H)；13C NMR(100MHz,CDCl3)δ178.9,134.6,133.6,133.3, 131.0,128.0,121.2,44.7,37.4；HRMS(ESI+)calc’d for C9H8BrNNaO2S[M+Na]+: 295.9351,found 295.9350.
example 36:
3- (4-Chlorophenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4-chlorophenylyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000252
A white solid; the yield is 85%;1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.6Hz,2H), 7.51(d,J＝8.5Hz,2H),3.82–3.57(t,2H),3.56–3.36(t,2H)；13C NMR(100MHz, CDCl3)δ174.8,141.4,130.5,129.8,129.4,44.5,33.6；HRMS(ESI+)calc’d for C9H8ClNNaO2S[M+Na]+:251.9856,found 251.9860.
example 37:
3- (4-Bromophenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4-broylphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000261
A white solid;1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.6Hz,2H),7.68(d,J＝8.6Hz,2H),3.67–3.60(t,2H),3.50–3.41(t,2H)；13C NMR(100MHz,CDCl3)δ 174.9,132.8,130.5,130.1,129.9,44.4,33.6；HRMS(ESI+)calc’d for C9H8BrNNaO2S[M+Na]+:295.9351,found 295.9353.
example 38:
3- (4-trifluoromethylphenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4- (trifluoromethylphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000262
A white solid; the yield is 92%;1H NMR(400MHz,CD3CN)δ8.21(d,J＝8.2Hz,2H), 7.87(d,J＝8.3Hz,2H),3.75(t,J＝7.9,6.3Hz,2H),3.53–3.32(t,2H)；13C NMR (100MHz,CD3CN)δ177.7,135.9(q,J＝1.0Hz),135.1(q,J＝32.5Hz),130.6, 126.9(q,J＝3.8Hz),124.7(q,J＝270.2Hz),45.3,34.9；19F NMR(376MHz, CD3CN)δ–63.77(s)；HRMS(ESI+)calc’d for C10H8F3NNaO2S[M+Na]+:286.0120, found 286.0118.
example 39:
3- (4-Methoxyphenyl) -4, 5-dihydroisothiazole-1, 1-dioxy [3- (4-Methoxyphenyl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000271
A white solid; the yield is 78%;1H NMR(400MHz,CDCl3)δ7.99(d,J＝8.9Hz,2H), 7.00(d,J＝8.9Hz,2H),3.90(s,3H),3.74–3.58(t,2H),3.49–3.35(t,2H)；13C NMR(100MHz,CDCl3)δ175.0,164.9,131.6,123.5,114.7,55.8,44.5,33.4；HRMS (ESI+)calc’d for C10H11NNaO3S[M+Na]+:248.0352,found 248.0356.
example 40:
3-Methyl-4, 5-dihydroisothiazole-1, 1-dioxy [3-Methyl-4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000272
A white solid;1H NMR(400MHz,CDCl3)δ3.31–3.24(t,2H),3.23–3.16(t,2H), 2.34(s,3H).
example 41:
methyl-4, 5-dihydroisothiazole-3-carbonyl-1, 1-dioxy [ methyl 4,5-dihydroisothiazole-3-carboxylate 1,1-dioxide ]
Figure BDA0002124041400000281
MS＝177.01
Example 42:
(E) -3- (1-allyl) -4, 5-4, 5-dihydroisothiazole-1, 1-dioxy [ (E) -3- (prop-1-en-1-yl) -4,5-dihydroisothiazole 1,1-dioxide ]
Figure BDA0002124041400000282
MS＝159.04。

Claims (4)

1. A method for preparing an internal sulfonamide compound is characterized in that: the method comprises the following steps:
adding an iron complex catalyst C, a raw material sulfonamide B and an oxidant D into an organic solvent, stirring for reaction, and separating and purifying after the reaction to obtain an internal sulfonamide compound E; in terms of the raw material dosage, the mass ratio of the iron complex catalyst C, the raw material sulfamide B and the oxidant D is 0.01:1:1 or 0.5:1: 5;
the prepared internal sulfonamide compound E takes sulfonamide B as a raw material, and the reaction equation is as follows:
Figure FDA0002937049250000011
or adding the iron complex catalyst C, the raw material sulfonamide H and the oxidant D into an organic solvent, stirring for reaction, adding the oxidant F after the detection reaction is finished, reacting, and separating and purifying to obtain an internal sulfimide compound G; in terms of the amount of the raw materials, the mass ratio of the iron complex catalyst C to the raw material sulfamide H to the oxidant D to the oxidant F is 0.01:1:1 or 0.5:1:5: 2;
the prepared internal sulfonamide compound G takes sulfonamide H as a raw material, and the reaction equation is as follows:
Figure FDA0002937049250000012
wherein R is1、R2、R3、R4、R5Are independent from each other; n is selected from 0, 1 or 2;
the R is1Selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is2Selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the R is3Selected from hydrogen, alkyl, alkenyl, aryl;
the R is4Selected from hydrogen, alkyl, alkenyl, aryl;
the R is5Selected from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenoxy, alkylthio, phenothiyl, alkylamino or arylamino;
the structure of the oxidant F is Ar2I(OCOCF3)2Wherein Ar is2Selected from phenyl, substituted phenyl, naphthyl, substituted naphthyl;
the iron complex catalyst C is a complex formed by iron salt and a ligand; wherein the ferric salt is selected from ferric salt or ferrous salt, and has a structural formula of Fe (X)2Or Fe (X)3(ii) a X is selected from the following anions: cl–、Br–、I–、AcO–、TfO–、ClO4 –、BF4 –Or SbF6 –(ii) a Wherein the ligand is selected from the following structures:
Figure FDA0002937049250000021
Figure FDA0002937049250000022
wherein R is6Selected from hydrogen, C1-C6 alkyl, phenyl or substituted phenyl; it is composed ofIn R7、R8、R9Are each independently a substituent, the same or different; r7、R8、R9Selected from hydrogen, C1-C6 alkyl or fluorine-containing alkyl, aryl, heteroaryl, alkoxy, alkylamino and arylamino; wherein the ratio of the amount of iron and ligand species is from 1:1 to 1: 3;
the oxidant D is any one of iodobenzene acetate, iodobenzene trifluoroacetate, iodobenzene pivalate, iodobenzene dimethylmalonate or iodobenzene benzoate;
the organic solvent is selected from the following solvents or a combination of solvents: acetonitrile, tert-butanol, 1, 2-dichloroethane, dichloromethane, tetrahydrofuran, methyl tert-butyl ether, dioxane, dimethyl sulfoxide, N, N' -dimethylformamide, trifluoroethanol, benzene, toluene, xylene or chlorobenzene.
2. A process for producing an internal sulfonamide compound according to claim 1, characterized in that: the ratio of the amounts of iron and ligand species was 1: 2.
3. A process for producing an internal sulfonamide compound according to claim 1 or 2, characterized in that: the temperature of the stirring reaction is 20-120 ℃; the separation and purification is any one of column chromatography, recrystallization or distillation.
4. A process for producing an internal sulfonamide compound according to claim 3, characterized in that: the organic solvent is acetonitrile or 1, 2-dichloroethane.
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