CN104744325B - A kind of Alpha-hydroxy thioether and preparation method and application - Google Patents

A kind of Alpha-hydroxy thioether and preparation method and application Download PDF

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CN104744325B
CN104744325B CN201310744259.2A CN201310744259A CN104744325B CN 104744325 B CN104744325 B CN 104744325B CN 201310744259 A CN201310744259 A CN 201310744259A CN 104744325 B CN104744325 B CN 104744325B
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methyl
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CN104744325A (en
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李志平
席辉
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Renmin University of China
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Abstract

The invention discloses a kind of α hydroxy thioether and preparation method and application.The general structure of this α hydroxy thioether is shown in formula I.The present invention can directly use raw material of industry phenylmercaptan. and derivant thereof etc. to construct the compound of polysubstituted α hydroxy thioether class formation.The method achieve and use the Ni metal being dirt cheap and simple organic carboxyl acid to do accelerator, directly utilize dioxygen oxidation raw material of industry phenylmercaptan. or derivatives thereof and occur oxidation hydroxylating to generate α hydroxy thioether with alkene.The method oxygen is oxidant, and Atom economy is high, environmental friendliness.The inventive method is easy and simple to handle, only needs a step, it is possible to directly high yield synthesis α hydroxy thioether compounds, product is prone to purification, and the method is initiative, is not available for other traditional organic synthesiss, and application prospect is optimistic.

Description

A kind of Alpha-hydroxy thioether and preparation method and application
Technical field
The present invention relates to a kind of Alpha-hydroxy thioether and preparation method and application.
Background technology
Alpha-hydroxy sulfide compound, English α-hydroxysulfide, it is the important heteroatomic compound of a class, is to have Chemical machine field and life science and the wide variety of compounds of drug world.A lot of medicines is had all to contain Having the skeleton of Alpha-hydroxy thioether, such as bicalutamide (1), it belongs to nonsteroidal antiandrogen medicine, is applied to late The treatment of phase carcinoma of prostate, oral administration absorbs good.Leukotriene C-1(2), it is the inflammation to upper lower respiratory tract There is the effect for the treatment of.
The synthetic method of traditional Alpha-hydroxy thioether mainly has: the ring-opening reaction of (1) epoxide. and (2) utilize thioether etc. As sulfur source and olefine reaction.(3) thiophenol of complex condition and olefine reaction.(Gao, P.;Xu,P.F.;Zhai,H. B.Tetrahedron Lett.2008,49,6536.;Movassagh,B.;Navidi,M.Tetrahedron Lett.2008,49, 6712.;Surendra,K.;Krishnaveni,N.S.;Sridhar,R.;Rao,K.R.J.Org.Chem.2006,71, 5819.) these method limitation are very big, and such as selectivity is bad, and productivity is the lowest, the harshest reaction condition, also Have be exactly in course of reaction a lot of side reaction products uncontrollable.The existing method of these drawbacks limit is at synthesis α-hydroxyl The use of base thioether.
Summary of the invention
It is an object of the invention to provide a kind of Alpha-hydroxy thioether and preparation method and application.
The present invention provide Alpha-hydroxy thioether and derivant, its general structure shown in formula I,
In described Formulas I, R1And R2Alkyl, the ester group of C1-C10, the aryl of C1-C10 and C1-C10 selected from C1-C10 Heterocyclic base at least one；
R3Selected from hydrogen, the alkyl of C1-C10, the thiazolinyl of C1-C10, the alkoxyl of C1-C10, hydroxyl, amino, At least one in the aryl of the acyl group of C1-C10, halogen and C1-C20.
Concrete, described R1And R2Selected from hydrogen, methyl, ethyl, cyclohexyl, ester group, furyl, thienyl, At least one in pyridine radicals, naphthyl and phenyl；
Described R3Selected from methyl, ethyl, vinyl, pi-allyl, acrylic, methoxyl group, ethyoxyl, chloro, bromine At least one in base, acetyl group, benzoyl and phenyl.
More specifically, R1For hydrogen or the alkyl of C1-C5, R2For phenyl or-COOMe, R3For C1-C5 to alkane Base or 2-chloro or 2-bromo；
The most concrete, R1For hydrogen or the alkyl of C1-C3, R2For phenyl or-COOMe, R3For C1-C3 to alkane Base or 2-chloro or 2-bromo；
Most specifically, R1For hydrogen or methyl, R2For phenyl or-COOMe, R3For to methyl or 2-chloro；
Any one during compound is following compound shown in described Formulas I:
The method of compound shown in formula I that the present invention provides, comprise the steps: by compound shown in Formula II, Compound shown in formula III and accelerator mix and carry out mercapto hydroxy reaction in organic solvent, react described in complete obtaining Compound shown in Formulas I；
In described Formula II and formula III, R1、R2And R3Definition the most as hereinbefore；
Described accelerator is selected from copper-containing compound and R4At least one in organic acid shown in-COOH；
Wherein, described R4In-COOH, R4It is selected from hydrogen, the alkyl of C1-C10, phenyl, the alkyl of C1-C10 At least one in substituted-phenyl, the phenyl of halogen substiuted, the alkoxy substituted phenyl of C1-C10 and nitro substituted-phenyl.
In said method, compound concretely styrene shown in described Formula II, α-methyl styrene, α-phenylpropen Acetoacetic ester, 2,4,6-trimethylbenzene styrene, acrylic acid methyl ester., Methyl Methacrylate, isoprene or to methyl Styrene；
The concretely 4-methylbenzene phenyl-sulfhydrate of compound shown in formula III, 4-methoxybenzenethiol, 4-bromo thiophenol, 2,4-bis- Methylbenzene phenyl-sulfhydrate, 2-chlorothio-phenol or 1-thionaphthol；
Described copper-containing compound is mantoquita；Described mantoquita is specially the 1 inorganic mantoquita of valency or the inorganic mantoquita of divalent, more specifically Selected from CuCl2、CuBr2、Cu(OAc)2、CuSO4·5H2O and Cu (OAc) H2At least one in O；
Described R4Organic acid shown in-COOH structural formula is p-Methoxybenzoic acid.
Compound shown in described Formula II is 1:1～4, specially 1:2-4 with the molar ratio of compound shown in formula III；
Compound shown in described Formula II is 10～40:1 with the molar ratio of described copper-containing compound, specially 20-40: 1；
Compound shown in described Formula II and described R4The molar ratio of organic acid shown in-COOH is 1:1～4, specifically For 1:1～2.
In described mercapto hydroxy reactions steps, temperature is 50-100 DEG C, specially 50 DEG C, and the time is 1-5 hour, It is specially 1-3 hour；
The oxygen that reaction atmosphere is 1 atmospheric pressure of described oxidative cyclization reaction or air atmosphere；
Described organic solvent selected from dichloromethane, chloroform, 1,2-dichloroethanes, toluene, acetonitrile, normal hexane and At least one in chlorobenzene.
Additionally, to change shown in the compound insecticide as active component shown in Formulas I that the invention described above provides and this Formulas I Compound application in parasite killing, falls within protection scope of the present invention, wherein, and described worm concretely cotten aphid.
The present invention can directly use raw material of industry phenylmercaptan. and derivant thereof etc. to construct polysubstituted Alpha-hydroxy thioether class knot The compound of structure.The method achieve and use the Ni metal being dirt cheap and simple organic carboxyl acid to do accelerator, directly Connect and utilize dioxygen oxidation raw material of industry phenylmercaptan. or derivatives thereof and alkene to occur oxidation hydroxylating to generate Alpha-hydroxy sulfur Ether.The method oxygen is oxidant, and Atom economy is high, environmental friendliness.The inventive method is easy and simple to handle, only needs One step, it is possible to directly high yield synthesis Alpha-hydroxy thio-ether type compounds, product is prone to purification, and the method is initiative , it is not available for other traditional organic synthesiss, application prospect is optimistic.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further elaborated, but the present invention is not limited to following example.Institute Method of stating is conventional method if no special instructions.Described raw material the most all can be from open commercial sources ?.In the present invention, Me all represents methyl, and Ph all represents phenyl, and Et all represents ethyl.
Compound 1-phenyl-2-(shown in embodiment 1, formula I is to Tolylsulfanvl) ethanol (1-phenyl-2-(p-tolylthio) ethanol)
Under 1 atmospheres oxygen atmosphere, in the dry Schlenk reaction tube of 100mL, add 0.025mmol promote Agent Schweinfurt green Cu (OAc)2, 1mmol accelerator p-Methoxybenzoic acid, then reaction system vacuum pump is pumped into very Sky, is filled with oxygen to 1 atmospheric pressure with oxygen ball, by compound benzene second shown in 0.5mmol Formula II in reaction system Methylbenzene phenyl-sulfhydrate is implanted sequentially instead by compound shown in alkene, 5mL organic solvent 1,2-dichloroethanes and 2mmol formula III Answer system.Above-mentioned mixed liquor is carried out mercapto hydroxyization reaction reaction in 3 hours 50 DEG C of heating and continuous stirrings complete, To yellowish-brown reaction mixture, then described mixed liquor rotary evaporation is concentrated, then separate with acidic silica gel post (silica gel: 200-300 mesh, eluant be volume ratio be the mixed solution of ethyl acetate and the petroleum ether of 1:30), steam Fall solvent, obtain colorless oil net product 1-phenyl-2-(to methylphenyl-sulfanyl) ethanol, productivity is 88%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3443,3030,2920,1693,1493,1452,1288,1055,804,698cm-1;
1H NMR(400MHz,CDCl3)δ7.37-7.25(m,7H),7.15(d,J=7.6Hz,2H),4.69(ddd,J= 9.6Hz,3.6Hz,2.4Hz,1H),3.29(dd,J=13.6Hz,3.6Hz,1H),3.04(dd,J=13.6Hz,9.6Hz, 1H),2.97(d,J=2.4Hz1H)2.36(s,3H);
13C NMR(100MHz,CDCl3)δ142.1,137.1,131.0,129.9,128.5,127.9,125.8,71.4, 44.8,21.0;
HRMS calcd for C15H16NaOS(M+Na)+:267.0820;found:267.08114.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For phenyl, R3For to methyl.
Compound 1-phenyl-2-(shown in embodiment 2, formula I is to Tolylsulfanvl) ethanol (1-phenyl-2-(p-tolylthio) ethanol)
According to the step of embodiment 1, only the consumption of accelerator p-Methoxybenzoic acid is replaced with 0.5mmol, sulfydryl Hydroxylating replaces with 1 hour, and products therefrom is that colorless oil net product 1-phenyl-2-(is to methylphenyl-sulfanyl) second Alcohol, productivity is 65%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3443,3030,2920,1693,1493,1452,1288,1055,804,698cm-1;
1H NMR(400MHz,CDCl3)δ7.37-7.25(m,7H),7.15(d,J=7.6Hz,2H),4.69(ddd,J= 9.6Hz,3.6Hz,2.4Hz,1H),3.29(dd,J=13.6Hz,3.6Hz,1H),3.04(dd,J=13.6Hz,9.6Hz, 1H),2.97(d,J=2.4Hz1H)2.36(s,3H);
13C NMR(100MHz,CDCl3)δ142.1,137.1,131.0,129.9,128.5,127.9,125.8,71.4, 44.8,21.0;
HRMS calcd for C15H16NaOS(M+Na)+:267.0820;found:267.08114.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For phenyl, R3For to methyl.
Embodiment 3: the phenyl-2-(of compound 1-shown in formula I is to Tolylsulfanvl) ethanol (1-phenyl-2-(p-tolylthio) ethanol)
According to the step of embodiment 1, only by accelerator Schweinfurt green Cu (OAc)2Consumption replace with 0.0125mmol, Compound shown in formula III replaces with 1mmol to the consumption of methylbenzene phenyl-sulfhydrate, and the time of mercapto hydroxyization reaction replaces with 1 Hour, products therefrom is that colorless oil net product 1-phenyl-2-(is to methylphenyl-sulfanyl) ethanol, productivity is 56%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3443,3030,2920,1693,1493,1452,1288,1055,804,698cm-1;
1H NMR(400MHz,CDCl3)δ7.37-7.25(m,7H),7.15(d,J=7.6Hz,2H),4.69(ddd,J= 9.6Hz,3.6Hz,2.4Hz,1H),3.29(dd,J=13.6Hz,3.6Hz,1H),3.04(dd,J=13.6Hz,9.6Hz, 1H),2.97(d,J=2.4Hz1H)2.36(s,3H);
13C NMR(100MHz,CDCl3)δ142.1,137.1,131.0,129.9,128.5,127.9,125.8,71.4, 44.8,21.0;
HRMS calcd for C15H16NaOS(M+Na)+:267.0820;found:267.08114.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For phenyl, R3For to methyl.
Embodiment 4: the phenyl-1-(of compound 2-shown in formula I is to Tolylsulfanvl)-2-propanol (2-phenyl-1-(p-tolylthio) propan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with α-methyl styrene 0.5mmol, gained The productivity of product is 98%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3521,3226,2951,1494,1447,808,696,481cm-1;
1H NMR(400MHz,CDCl3)δ7.44(d,J=7.2Hz,2H),7.32(t,J=7.2Hz,2H), 7.26-7.23(m,3H),7.04(d,J=7.2Hz,2H),3.50(d,J=13.2Hz,1H),3.31(d,J=13.2Hz,1H), 2.90(s,1H),2.30(s,3H),1.60(s,3H);
13C NMR(100MHz,CDCl3)δ146.2,136.5,132.7,130.5,129.7,128.2,126.9,124.7, 73.9,50.2,29.3,20.9;
HRMS calcd for C16H18NaOS(M+Na)+:281.0971;found:281.0970.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For to methyl.
Embodiment 5: the p-methylphenyl of compound 1-(shown in formula I)-2-(is to Tolylsulfanvl) ethanol (1-(p-tolyl)-2-(p-tolylthio) ethanol)
According to the step of embodiment 1, only compound shown in Formula II used is replaced with p-methylstyrene 0.5mmol, The productivity of products therefrom is 80%.
The nuclear magnetic data of this compound is as follows:
1H NMR(400MHz,CDCl3)δ7.34(d,J=8.0Hz,2H),7.23(d,J=8.0Hz,2H),7.16(d, J=8.0Hz,2H),7.14(d,J=8.0Hz,2H),4.66(ddd,J=9.6Hz,3.6Hz,2.4Hz,1H),3.26(dd,J =13.6Hz,3.6Hz,1H),3.04(dd,J=13.6Hz,9.6Hz,1H),2.87(d,J=2.4Hz,1H),2.35(s,3H);
13C NMR(100MHz,CDCl3)δ139.2,137.5,136.9,131.0,130.9,129.8,129.1,125.7, 71.3,44.6,21.1,21.0;
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For to first Base phenyl, R3For to methyl.
Embodiment 6: the hydroxyl-2-phenyl-3-(of compound 2-shown in formula I is to Tolylsulfanvl) ethyl propionate (ethyl 2-hydroxy-2-phenyl-3-(p-tolylthio) propanoate)
According to the step of embodiment 1, only compound shown in Formula II is replaced with atropic acid ethyl ester, products therefrom Productivity be 65%.
This compound infrared, nuclear magnetic data is as follows:
IR(KBr):νmax3506,2980,1732,1493,1263,1198,1101,808,696cm-1;
1H NMR(400MHz,CDCl3)δ7.62(d,J=8.0Hz,2H),7.36-7.27(m,5H),7.08(d,J= 8.0Hz,2H),4.15-4.11(m,3H),4.04(s,1H),3.79(d,J=13.2Hz,1H),3.43(d,J=13.2Hz, 1H),2.31(s,3H),1.17(t,J=7.2Hz3H);
13C NMR(100MHz,CDCl3)δ173.3,140.4,136.8,132.5,131.3,129.6,128.3,128.1, 125.5,78.6,62.6,46.0,21.0,13.8;
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For phenyl, R2For-COOEt, R3For to methyl.
Embodiment 7: the trimethyl of compound 1-(2,4,6-shown in formula I) phenyl-2-(is to Tolylsulfanvl) ethanol (1-mesityl-2-(p-tolylthio) ethanol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with 2,4,6-trimethylbenzene styrene, gained The productivity of product is 70%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3745,2920,1610,1490,1449,1302,1037,1016,850,806cm-1;
1H NMR(400MHz,CDCl3)δ7.36(d,J=8.0Hz,2H),7.14(d,J=8.0Hz,2H),6.79(s, 2H),5.06(ddd,J=10.4Hz,3.6Hz,2.0Hz,1H),3.33(dd,J=14.0Hz,3.6Hz,1H),3.15(dd,J =14.0Hz,10.4Hz,1H),2.62(d,J=2.0Hz,1H),2.35(s,3H),2.28(s,6H),2.24(s,3H);
13C NMR(100MHz,CDCl3)δ137.0,136.9,136.2,134.0,131.2,130.8,130.1,129.8, 68.8,41.0,21.0,20.7,20.5;
HRMS calcd for C18H22O5NaOS(M+Na)+:309.12836;found:309.12855.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For 2,4,6- Trimethylphenyl, R3For to methyl.
Embodiment 8: the hydroxyl-3-(of compound 2-shown in formula I is to Tolylsulfanvl) methyl propionate (methyl 2-hydroxy-3-(p-tolylthio) propanoate)
According to the step of embodiment 1, only compound shown in Formula II is replaced with acrylic acid methyl ester., the productivity of products therefrom It is 90%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3479,2953,1743,1492,1439,1313,1091,808cm-1;
1H NMR(400MHz,CDCl3)δ7.32(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),4.36(t,J =4.8Hz,1H),3.61(s,3H),3.33(dd,J=13.8Hz,4.0Hz,1H),3.21(dd,J=13.8Hz,6.0Hz, 1H),2.31(s,3H);
13C NMR(100MHz,CDCl3)δ173.1,137.1,131.4,131.0,129.7,69.3,52.4,39.7, 21.0;
HRMS calcd for C11H14NaO3S(M+Na)+:249.0556;found:249.0556.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For hydrogen, R2For-COOMe, R3For to methyl.
Embodiment 9: the hydroxy-2-methyl-3-(of compound 2-shown in formula I is to Tolylsulfanvl) methyl propionate (methyl 2-hydroxy-2-methyl-3-(p-tolylthio) propanoate)
According to the step of embodiment 1, only compound shown in Formula II is replaced with Methyl Methacrylate, products therefrom Productivity be 50%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3501,2953,1738,1493,1207,1099,808cm-1;
1H NMR(400MHz,CDCl3)δ7.32(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),3.50(s, 3H),3.49(s,1H),3.38(d,J=14.0Hz,1H),3.13(d,J=14.0Hz,1H),2.31(s,3H),1.47(s,3H);
13C NMR(100MHz,CDCl3)δ175.3,136.8,131.7,131.3,129.6,74.5,52.5,45.6,25.3, 21.0;
HRMS calcd for C11H14NaO3S(M+Na)+:249.05559;found:249.05558.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For -COOMe, R3For to methyl.
Embodiment 10: the methyl isophthalic acid of compound 2-shown in formula I-(to Tolylsulfanvl)-3-butene-2-ol (2-methyl-1-(p-tolylthio) but-3-en-2-ol)
According to the step of embodiment 1, only compound shown in Formula II being replaced with isoprene, the productivity of products therefrom is 50%。
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3820,2922,1716,1492,1373,1091,1016,923,804cm-1;
1H NMR(400MHz,CDCl3)δ7.31(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),5.88(dd, J=17.6Hz,10.8Hz,2H),5.31(d,J=17.6Hz1H),5.09(d,J=10.8Hz,1H),3.19(d,J= 13.2Hz,1H),3.07(d,J=13.2Hz1H),2.47(s,1H),2.31(s,3H),1.35(s,3H);
13C NMR(100MHz,CDCl3)δ143.2,136.5,132.9,130.5,129.7,113.2,72.7,48.3, 27.1,21.0,;
HRMS calcd for C12H16NaOS(M+Na)+:231.08141;found:231.08160.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For alkene Propyl group, R3For to methyl.
Embodiment 11: the methoxyphenyl of compound 1-((4-shown in formula I) sulfenyl)-2-phenyl-2-propanol (1-((4-methoxyphenyl) thio)-2-phenylpropan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with α-methyl styrene, formula III shownization Compound replaces with 4-methoxybenzenethiol 2mmol, and the productivity of products therefrom is 78%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax2792,1593,1492,1285,1244,1179,1028,826,698cm-1;
1H NMR(400MHz,CDCl3)δ7.42(d,J=7.6Hz,2H),7.32-7.20(m,5H),6.76(d,J= 7.6Hz,2H),3.76(s,3H),3.46(d,J=13.2Hz,1H),3.25(d,J=13.2Hz,1H),2.97(s,1H), 1.58(s,3H);
13C NMR(100MHz,CDCl3)δ159.0,146.3,133.3,128.2,126.9,124.8,114.6,74.0, 55.3,51.5,29.4;
HRMS calcd for C16H18NaO2S(M+Na)+:297.09197;found:297.09198.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For to methyl.
Embodiment 12: the bromophenyl of compound 1-((4-shown in formula I) sulfenyl)-2-phenyl-2-propanol (1-((4-bromophenyl) thio)-2-phenylpropan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with p-methylstyrene, formula III shownization Compound replaces with 4-bromo thiophenol, and the productivity of products therefrom is 85%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3462,2976,2926,2359,1474,1447,1373,1090,1007,698cm-1;
1H NMR(400MHz,CDCl3)1H NMR(400MHz,CDCl3)δ7.43(d,J=7.6Hz,2H), 7.34-7.24(m,5H),7.17(d,J=7.6Hz,2H),3.51(d,J=13.2Hz,1H),3.31(d,J=13.2Hz,1H), 2.75(s,1H),1.62(s,3H);
13C NMR(100MHz,CDCl3)δ145.9,135.7,131.9,131.4,128.3,127.2,124.7,120.2, 74.0,49.5,29.3;
HRMS calcd for C15H15BrNaOS(M+Na)+:344.99192;found:344.99290.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For to methyl.
Embodiment 13: the 3,5-dimethylphenyl of compound 1-((2,4-shown in formula I) sulfenyl)-2-phenyl-2-propanol (1-((2,4-dimethylphenyl) thio)-2-phenylpropan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with p-methylstyrene, formula III shownization Compound replaces with 2, and 4-thiophenol dimethyl benzene, the productivity of products therefrom is 73%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3466,2972,2924,1447,1373,1055,812,698cm-1;1H
NMR(400MHz,CDCl3)δ7.45(d,J=8.0Hz,2H),7.32(t,J=7.6Hz,2H), 7.26-7.23(m,2H),6.96(s,1H),6.91(d,J=8.0Hz,1H),3.45(d,J=13.2Hz,1H),3.25(d,J= 13.2Hz,1H),2.90(s,1H),2.34(s,3H),2.26(s,3H),1.60(s,3H);
13C NMR(100MHz,CDCl3)δ146.3,138.6,136.6,131.8,131.1,130.8,128.2,127.3, 126.9,124.7,73.9,49.5,29.4,20.8,20.6;
HRMS calcd for C17H20NaOS(M+Na)+:295.11271;found:295.11326.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For 2,4-dimethyl.
Embodiment 14: the chlorphenyl of compound 1-((2-shown in formula I) sulfenyl)-2-phenyl-2-propanol (1-((2-chlorophenyl) thio)-2-phenylpropan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with p-methylstyrene, formula III shownization Compound replaces with 2-chlorothio-phenol, and the productivity of products therefrom is 72%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3460,2976,1450,1431,1115,1034,746,698cm-1;
1H NMR(400MHz,CDCl3)δ7.45(d,J=8.0Hz,2H),7.34-7.29(m,4H),7.23(t,J= 7.2Hz,1H),7.14-707(m,2H),3.54(d,J=13.2Hz,1H),3.31(d,J=13.2Hz,1H),2.86(s,1H), 1.64(s,3H);
13C NMR(100MHz,CDCl3)δ145.9,135.3,134.8,130.9,129.7,128.3,127.4,127.1, 127.0,124.7,73.9,48.3,29.4;
HRMS calcd for C17H14ClOS(M+Na)+:301.04484;found:301.04428.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For 2-chloro.
Embodiment 15: the naphthalene sulfenyl of compound 1-(1-shown in formula I)-2 phenyl-2-propanol (1-(naphthalen-1-ylthio)-2-phenylpropan-2-ol)
According to the step of embodiment 1, only compound shown in Formula II is replaced with p-methylstyrene, formula III shownization Compound replaces with 1-thionaphthol, and the productivity of products therefrom is 87%.
This compound infrared, nuclear-magnetism and mass spectrometric data are as follows:
IR(KBr):νmax3462,3053,2361,1447,1065,770,698cm-1;
1H NMR(400MHz,CDCl3)δ8.37(d,J=8.4Hz,1H),7.83(d,J=8.0Hz,1H),7.72(d, J=8.4Hz,1H),7.58-7.48(m,3H),7.43(d,J=8.4Hz,2H),7.34-7.20(m,4H),3.60(d,J= 13.2Hz,1H),3.38(d,J=13.2Hz,1H),2.90(s,1H),1.63(s,3H);
13C NMR(100MHz,CDCl3)δ146.1,133.9,133.4,133.0,129.7,128.6,128.1,127.8, 127.0,126.5,126.2,125.5,125.1,124.7,74.1,49.9,29.4;
HRMS calcd for C19H18NaOS(M+Na)+:317.09706;found:317.09770.
From the foregoing, it will be observed that this product structure is correct, for target compound shown in Formulas I, wherein, R1For methyl, R2For benzene Base, R3For phenyl.
Embodiment 16: compound biological activity test shown in Formulas I.
With cotten aphid for test object, infusion process test previous embodiment is used to prepare the biology of compound shown in gained Formulas I Activity.
Method of testing: prepare to weigh each sample, be separately added into 2mL dimethyl sulfoxide and 18mL clear water, add 3 emulsifying agent 220I(are purchased from Shanghai insecticide factory) it is made into medicinal liquid, blank sample 2mL dimethyl sulfoxide and 28mL Clear water, adds 3 emulsifying agents and is made into.
Prepare one piece of clean gauze bag, 100 insecticides to be measured are put into wherein, then gauze bag and foodstuff are together soaked In the above-mentioned medicinal liquid prepared, take out after 5s and dry, insecticide and foodstuff are placed in clean vessel, transfer to constant temperature extensive 24h is cultivated in multiple room, verifies insect death situation, calculates mortality rate, and is corrected with Abbott formula.
Abbott formula: corrected mortality=[(processing mortality rate-comparison mortality rate)/(1-compares mortality rate)] × 100%
The insecticidal activity of gained 1 to 4 pair of cotten aphid of compound is shown in Table 1.
Table 1, the insecticidal activity of compound 1 to 4
Compound 1 prepares compound 1-phenyl-2-(shown in gained Formulas I to Tolylsulfanvl for embodiment 1) ethanol；
Compound 2 prepares compound 2-hydroxy-2-methyl-3-(shown in gained Formulas I to Tolylsulfanvl for embodiment 9) third Acid methyl ester；
Compound 3 prepares compound 1-((4-bromophenyl shown in gained Formulas I for embodiment 12) sulfenyl)-2-phenyl-2- Propanol；
Compound 4 prepares compound 1-((2-chlorphenyl shown in gained Formulas I for embodiment 14) sulfenyl)-2-phenyl-2- Propanol；
More than test result indicate that, benzothiophenes shown in the Formulas I that the present invention provides has certain parasite killing and lives Property.

Claims (9)

1. a method for compound shown in formula I, comprises the steps:
In described Formulas I, R1And R2Selected from hydrogen, methyl, ethyl, cyclohexyl, ester group, furyl, thienyl, pyrrole At least one in piperidinyl, naphthyl and phenyl；
R3Selected from hydrogen, halogen radical, methyl, ethyl, vinyl, pi-allyl, acrylic, methoxyl group, ethyoxyl, At least one in acetyl group, hydroxyl, amino, benzoyl and phenyl；
Compound shown in compound shown in Formula II, formula III and accelerator are mixed in organic solvent, carries out mercapto hydroxy Change reaction, react complete and obtain compound shown in described Formulas I；
In described Formula II and formula III, R1、R2And R3Definition respectively with R in described Formulas I1、R2And R3Determine Justice is identical；
Described accelerator is selected from copper-containing compound and R4At least one in organic acid shown in-COOH structural formula；
Wherein, described R4In-COOH structural formula, R4It is selected from hydrogen, phenyl, methoxyphenyl, halogen substiuted At least one in phenyl and the substituted phenyl of nitro；
Described copper-containing compound is selected from CuCl2、CuBr2、Cu(OAc)2、CuSO4·5H2O and Cu (OAc) H2O In at least one；
Described organic solvent selected from dichloromethane, chloroform, 1,2-dichloroethanes, toluene, acetonitrile, normal hexane and At least one in chlorobenzene.
Method the most according to claim 1, it is characterised in that: described halogen radical is chloro or bromo.
Method the most according to claim 1 and 2, it is characterised in that: compound shown in described Formulas I is followingization Any one in compound:
Method the most according to claim 1, it is characterised in that: described R4Organic acid shown in-COOH structural formula For p-Methoxybenzoic acid.
Method the most according to claim 1, it is characterised in that: shown in compound shown in described Formula II and formula III The molar ratio of compound is 1:1～4；
Compound shown in described Formula II is 10～40:1 with the molar ratio of described copper-containing compound；
Compound shown in described Formula II is 1:1～4 with the molar ratio of described organic acid.
Method the most according to claim 5, it is characterised in that: shown in compound shown in described Formula II and formula III The molar ratio of compound is 1:2-4；
Compound shown in described Formula II is 20-40:1 with the molar ratio of described copper-containing compound；
Compound shown in described Formula II is 1:1～2 with the molar ratio of described organic acid.
Method the most according to claim 1, it is characterised in that: in described mercapto hydroxy reactions steps, temperature Degree is for 50-100 DEG C, and the time is 1-5 hour.
8. want the method described in 7 according to right, it is characterised in that: in described mercapto hydroxy reactions steps, temperature Being 50 DEG C, the time is 1-3 hour.
Method the most according to claim 1, it is characterised in that: the reaction atmosphere of described oxidative cyclization reaction is 1 The oxygen of individual atmospheric pressure or air atmosphere.
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