WO2015135438A1 - Halogenated sulfur compound and preparation method and use thereof - Google Patents

Halogenated sulfur compound and preparation method and use thereof Download PDF

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WO2015135438A1
WO2015135438A1 PCT/CN2015/073736 CN2015073736W WO2015135438A1 WO 2015135438 A1 WO2015135438 A1 WO 2015135438A1 CN 2015073736 W CN2015073736 W CN 2015073736W WO 2015135438 A1 WO2015135438 A1 WO 2015135438A1
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structural formula
sulfur compound
halogenated sulfur
compound
halogenated
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PCT/CN2015/073736
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Chinese (zh)
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赖玉龙
胡俊铎
高峰
郭群震
虞小华
蔡国平
江海
毛文聪
陈邦池
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泸州东方农化有限公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/80—Two oxygen atoms, e.g. hydantoin with hetero atoms or acyl radicals directly attached to ring nitrogen atoms
    • C07D233/82—Halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to the synthesis of organosulfur compounds, especially the synthesis of halogenated sulfur compounds, and their reaction in the preparation of sulfonamides of aromatic sulfonyl chlorides, heteroaromatic sulfonyl chloride compounds with aromatic amines and heteroaromatic amine compounds. Catalytic applications.
  • a method for producing a sulfonamide by reacting an aromatic sulfonyl chloride or a heteroaromatic sulfonyl chloride compound with an aromatic amine or a heteroaromatic amine compound and in many cases, a satisfactory effect cannot be obtained because of its slow reaction and poor yield.
  • aromatic sulfonyl chlorides, heteroaromatic sulfonyl chloride compounds, aromatic amines, and heteroaromatic amine compounds contain one or two ortho substituents, the results are often unsatisfactory due to the stereoscopic electronic effect of the ortho substituent. .
  • WO 98/21178 discloses a class of N-arylsulfilimine compounds and uses them for the catalytic reaction of aromatic sulfonyl chloride compounds with aromatic amine compounds to prepare N-arylsulfonamide compounds. Although the method can shorten the reaction time and improve the yield, the chlorine gas is needed in the preparation process of the catalyst, and there is a great risk in production.
  • the invention includes a class of halogenated sulfur compounds (I):
  • X represents Cl, Br, I
  • R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group
  • R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group
  • R 1 and R 2 together represent a C 2 -C 5 methylene group
  • n 0-4; wherein n is 1, the halogenated sulfur compound (I) is not structural formula (L):
  • Y is Cl, Br, I.
  • the invention also discloses a preparation method of the compound of the formula (I), characterized in that the compound of the formula (II)
  • the organic solvent may preferably be one of dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene or xylene.
  • the molar ratio of the compound (II) to the compound (III) is preferably between 1:1 and 3:1.
  • the invention further discloses an application of the halogenated sulfur compound (I') for preparing the sulfonate of the following formula (IV) Amide method:
  • the sulfonamide of the formula (IV) is obtained by reacting at -50 ° C to 100 ° C in an organic base or an organic solvent system.
  • W represents C 1 -C 4 alkyl, aryl, heteroaryl
  • G represents C 1 -C 4 alkyl, aryl, heteroaryl
  • X represents Cl, Br, I
  • R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group
  • R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group
  • R 1 and R 2 together represent a C 2 -C 5 methylene group
  • n 0-4;
  • Y is Cl, Br, I
  • halogenated sulfur compound may be any one or more of the compounds of formula (I');
  • the sulfonyl chloride compound (V) may be methylsulfonyl chloride, 2-(2,2-difluoroethoxy)-6-(trifluoromethyl)-phenylsulfonyl chloride, 5-ethoxy-7- Fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, 5-methoxy-8-fluoro-[1,2,4]triazole-[1,5 , c] pyrimidine-2-sulfonyl chloride, 5-methyl-[1,2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride, 5,7-dimethoxy-[1 , 2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride;
  • the organic amine compound (VI) may be 2,6-dichloroaniline, 2,6-difluoroaniline, 2-amino-3-chloro-benzoic acid methyl ester, 2,6-dichloro-3-methyl Aniline, 2,4-dichloro-5-(4-difluoromethyl-3-methyl-5-oxo-4,5-dihydro-1,2,4-triazole) aniline, 5,8- Dimethoxy-[1,2,4]triazole-[1,5-c]pyrimidin-2-amine.
  • the process produces a sulfonamide of the formula (IV) by reacting an organic amine compound (VI) with a sulfonyl chloride compound (V) in the presence of an organic base and a catalytic amount of the above halogenated sulfur compound (I').
  • the base used in the method may be an alkylamine (e.g., a tertiary amine base or the like), pyridine, picoline, nicotinamide, quinoline or the like, and is usually used in an amount of from 1 to 2 equivalents of the sulfonyl chloride.
  • the amount of the catalyst is between 1% and 30% by mole of the sulfonyl chloride compound.
  • the reaction temperature of the process is between -50 ° C and 100 ° C, and the preferred temperature is between 0 ° C and 40 ° C.
  • the organic solvent of the present process is generally an organic solvent which is inert to the reaction of the sulfonamide (IV), the sulfonyl chloride compound (V), and the halogenated sulfur compound (I'). It may be usually dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene, xylene, etc., or a mixture thereof.
  • the present invention relates to a halogenated sulfur compound such as N-[(1-halo)-thiocyclobutyl]-succinimide and a process for the preparation thereof, and discloses the reaction of such a compound with a sulfonyl chloride and an organic amine.
  • Catalytic applications in the preparation of sulfonamides The catalytic reaction of the sulfonamide prepared by the halogenated sulfur compound disclosed in the present invention requires mild reaction conditions, short reaction time and high yield.
  • the invention does not need to use a relatively dangerous chlorine gas, is safe and environmentally friendly, and has Great application value.
  • N-chlorosuccinimide 13 g was dissolved in 50 ml of dichloromethane, stirred and cooled to 15 ° C, and 8.8 g of tetrahydrothiophene was added to the reaction system. The reaction was stirred for 30 minutes, the solvent was evaporated, and then dried to give the title compound N-[(1-chloro)-thiocyclobutyl]-succinimide about 17.5 g.
  • N-bromosuccinimide 17.8 g was dissolved in 50 ml of a mixed solvent of dichloromethane (10 ml) and dichloroethane (40 ml), stirred and cooled to 15 ° C, and 8.8 g of four was added to the reaction system. Hydrogenthiophene was stirred for 30 min, and the solvent was evaporated to give the title compound N-[(1-chloro)-thiocyclobutyl]-succinimide 22.5 g.
  • N-chlorophthalimide 18.1 g was dissolved in 100 ml of toluene, and 8.8 g of tetrahydrothiophene was added with stirring at room temperature. After the reaction was completed for 1 hour, the solvent was evaporated to give the title compound N-[(1-chloro)-thiocyclobutyl]phthalimide about 22 g.
  • N-chlorophthalimide 36.1 g was dissolved in a mixed solvent of 200 ml of toluene (150 ml) and xylene (50 ml), and 12.5 g of dimethyl sulfide was added with stirring at room temperature. After the reaction was completed for 2 hours, the solvent was evaporated to give the title compound N-[(1-chloro)-thiodimethyl]-phthalimide 40.8 g.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention relates to a halogenated sulfur compound such as N-[(1-halogenated)-thiocyclobutyl]-succinimide and preparation method thereof. Disclosed is a catalytic application of such compounds in the reaction of sulfuryl chloride and organic amine to prepare sulfonamide. The disclosed catalytic reaction for preparing sulfonamide by the halogenated sulfur compounds requires a mild reaction condition and a short reaction time, and has a high yield. The present invention does not need to use hazardous chlorine gas, thus being safe and environmentally friendly, and has great application value.

Description

一种卤代硫化合物及其制备方法和应用Halogenated sulfur compound and preparation method and application thereof 技术领域Technical field
本发明涉及一种有机硫化合物的合成，尤其是卤代硫化合物的合成，以及它们在芳族磺酰氯、杂芳族磺酰氯化合物与芳族胺、杂芳族胺化合物制备磺酰胺反应中的催化应用。The present invention relates to the synthesis of organosulfur compounds, especially the synthesis of halogenated sulfur compounds, and their reaction in the preparation of sulfonamides of aromatic sulfonyl chlorides, heteroaromatic sulfonyl chloride compounds with aromatic amines and heteroaromatic amine compounds. Catalytic applications.
背景技术Background technique
通过芳族磺酰氯、杂芳族磺酰氯化合物与芳族胺、杂芳族胺化合物反应制备磺酰胺的方法，许多情况下因为其反应慢且收率差，不能得到满意的效果。特别是芳族磺酰氯、杂芳族磺酰氯化合物和芳族胺、杂芳族胺化合物含有一个或两个邻位取代基时，由于邻位取代基的立体电子效应，结果往往令人不满意。WO98/21178公开了一类N-芳基硫亚胺化合物并将其用于催化芳族磺酰氯化合物与芳族胺化合物反应制备N-芳基磺酰胺化合物的方法。该方法虽然可以使反应时间有所缩短、收率有所提高，但是催化剂制备过程中需要用到氯气，在生产上存在较大危险性。A method for producing a sulfonamide by reacting an aromatic sulfonyl chloride or a heteroaromatic sulfonyl chloride compound with an aromatic amine or a heteroaromatic amine compound, and in many cases, a satisfactory effect cannot be obtained because of its slow reaction and poor yield. In particular, when aromatic sulfonyl chlorides, heteroaromatic sulfonyl chloride compounds, aromatic amines, and heteroaromatic amine compounds contain one or two ortho substituents, the results are often unsatisfactory due to the stereoscopic electronic effect of the ortho substituent. . WO 98/21178 discloses a class of N-arylsulfilimine compounds and uses them for the catalytic reaction of aromatic sulfonyl chloride compounds with aromatic amine compounds to prepare N-arylsulfonamide compounds. Although the method can shorten the reaction time and improve the yield, the chlorine gas is needed in the preparation process of the catalyst, and there is a great risk in production.
发明内容Summary of the invention
本发明包括公开了一类卤代硫化合物(I)：The invention includes a class of halogenated sulfur compounds (I):
Figure PCTCN2015073736-appb-000001
Figure PCTCN2015073736-appb-000001
式中：In the formula:
X代表Cl、Br、I；X represents Cl, Br, I;
R1代表C1-C5的烷基、C6-C12芳基；R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
R2代表C1-C5的烷基、C6-C12的芳基；R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
或R1和R2一起代表C2-C5的亚甲基；Or R 1 and R 2 together represent a C 2 -C 5 methylene group;
Q代表结构： Q stands for structure:
Figure PCTCN2015073736-appb-000002
Figure PCTCN2015073736-appb-000002
n为0-4；其中n为1时，卤代硫化合物(I)不为结构式(L)：n is 0-4; wherein n is 1, the halogenated sulfur compound (I) is not structural formula (L):
Figure PCTCN2015073736-appb-000003
Figure PCTCN2015073736-appb-000003
或结构：Or structure:
Figure PCTCN2015073736-appb-000004
Figure PCTCN2015073736-appb-000004
或结构：Or structure:
Figure PCTCN2015073736-appb-000005
Figure PCTCN2015073736-appb-000005
Y为Cl，Br，I。Y is Cl, Br, I.
本发明还公开了一种式(I)中的化合物的制备方法，其特征是将式(II)化合物The invention also discloses a preparation method of the compound of the formula (I), characterized in that the compound of the formula (II)
Figure PCTCN2015073736-appb-000006
Figure PCTCN2015073736-appb-000006
与式(III)化合物在有机溶剂中反应，Reacting with a compound of formula (III) in an organic solvent,
X-QX-Q
(III)(III)
其中R1，R2，X，Q的定义与式(I)中的定义相同；有机溶剂可以优选二氯甲烷、二氯乙烷、氯仿、四氯化碳、乙腈、甲苯、二甲苯的一种或多种；化合物(II)与化合物(III)摩尔比优选在1:1-3:1之间。Wherein R 1 , R 2 , X, Q have the same meanings as defined in formula (I); the organic solvent may preferably be one of dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene or xylene. One or more kinds; the molar ratio of the compound (II) to the compound (III) is preferably between 1:1 and 3:1.
本发明还进一步公开了卤代硫化合物(I')的一种应用，用于制备下式(IV)磺 酰胺的方法：The invention further discloses an application of the halogenated sulfur compound (I') for preparing the sulfonate of the following formula (IV) Amide method:
W-SO2NH-GW-SO 2 NH-G
(IV)(IV)
在催化量的卤代硫化合物(I')存在下，In the presence of a catalytic amount of a halogenated sulfur compound (I'),
Figure PCTCN2015073736-appb-000007
Figure PCTCN2015073736-appb-000007
式(V)的磺酰氯化合物Sulfonyl chloride compound of formula (V)
W-SO2ClW-SO 2 Cl
(V)(V)
与式(VI)的胺化合物，With the amine compound of formula (VI),
H2N-GH 2 NG
(VI)(VI)
在有机碱、有机溶剂体系中，-50℃-100℃反应制得式(IV)所述磺酰胺。The sulfonamide of the formula (IV) is obtained by reacting at -50 ° C to 100 ° C in an organic base or an organic solvent system.
W-SO2NH-GW-SO 2 NH-G
(IV)(IV)
其中：among them:
W代表C1-C4烷基、芳基、杂芳基；W represents C 1 -C 4 alkyl, aryl, heteroaryl;
G代表C1-C4烷基、芳基、杂芳基；G represents C 1 -C 4 alkyl, aryl, heteroaryl;
X代表Cl、Br、I；X represents Cl, Br, I;
R1代表C1-C5的烷基、C6-C12芳基；R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
R2代表C1-C5的烷基、C6-C12的芳基；R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
或R1和R2一起代表C2-C5的亚甲基；Or R 1 and R 2 together represent a C 2 -C 5 methylene group;
Q代表结构：Q stands for structure:
Figure PCTCN2015073736-appb-000008
Figure PCTCN2015073736-appb-000008
n为0-4；n is 0-4;
或结构： Or structure:
Figure PCTCN2015073736-appb-000009
Figure PCTCN2015073736-appb-000009
或结构：Or structure:
Figure PCTCN2015073736-appb-000010
Figure PCTCN2015073736-appb-000010
Y为Cl，Br，I；Y is Cl, Br, I;
其中卤代硫化合物可以是式(I')中的任意一个或多个化合物；Wherein the halogenated sulfur compound may be any one or more of the compounds of formula (I');
其中磺酰氯化合物(V)可以是甲基磺酰氯、2-(2,2-二氟乙氧基)-6-(三氟甲基)-苯基磺酰氯、5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯、5-甲氧基-8-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯、5-甲基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯,5,7-二甲氧基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯；Wherein the sulfonyl chloride compound (V) may be methylsulfonyl chloride, 2-(2,2-difluoroethoxy)-6-(trifluoromethyl)-phenylsulfonyl chloride, 5-ethoxy-7- Fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, 5-methoxy-8-fluoro-[1,2,4]triazole-[1,5 , c] pyrimidine-2-sulfonyl chloride, 5-methyl-[1,2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride, 5,7-dimethoxy-[1 , 2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride;
其中有机胺化合物(VI)可以是2,6-二氯苯胺、2,6-二氟苯胺、2-胺基-3-氯-苯甲酸甲酯、2,6-二氯-3-甲基苯胺、2,4-二氯-5-(4-二氟甲基-3-甲基-5-氧-4,5-二氢-1,2,4-三唑)苯胺、5,8-二甲氧基-[1,2,4]三唑-[1,5-c]嘧啶-2-胺。The organic amine compound (VI) may be 2,6-dichloroaniline, 2,6-difluoroaniline, 2-amino-3-chloro-benzoic acid methyl ester, 2,6-dichloro-3-methyl Aniline, 2,4-dichloro-5-(4-difluoromethyl-3-methyl-5-oxo-4,5-dihydro-1,2,4-triazole) aniline, 5,8- Dimethoxy-[1,2,4]triazole-[1,5-c]pyrimidin-2-amine.
本方法通过将有机胺化合物(VI)和磺酰氯化合物(V)在有机碱和催化量的上述卤代硫化合物(I')存在下反应制得式(IV)所述磺酰胺。The process produces a sulfonamide of the formula (IV) by reacting an organic amine compound (VI) with a sulfonyl chloride compound (V) in the presence of an organic base and a catalytic amount of the above halogenated sulfur compound (I').
本方法中所使用的碱可以是烷基胺(如叔胺碱等)、吡啶、甲基吡啶、烟酰胺、喹啉等，通常用量为磺酰氯的1-2当量。催化剂用量为磺酰氯化合物摩尔数的1％到30％之间。The base used in the method may be an alkylamine (e.g., a tertiary amine base or the like), pyridine, picoline, nicotinamide, quinoline or the like, and is usually used in an amount of from 1 to 2 equivalents of the sulfonyl chloride. The amount of the catalyst is between 1% and 30% by mole of the sulfonyl chloride compound.
本方法的反应温度在-50℃-100℃之间，优选的温度是在0℃到40℃之间。The reaction temperature of the process is between -50 ° C and 100 ° C, and the preferred temperature is between 0 ° C and 40 ° C.
本方法的有机溶剂一般是对磺酰胺(IV)、磺酰氯化合物(V)、卤代硫化合物(I')反应惰性的有机溶剂。通常可以是二氯甲烷、二氯乙烷、氯仿、四氯化碳、乙腈、甲苯、二甲苯等，或其混合物。The organic solvent of the present process is generally an organic solvent which is inert to the reaction of the sulfonamide (IV), the sulfonyl chloride compound (V), and the halogenated sulfur compound (I'). It may be usually dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene, xylene, etc., or a mixture thereof.
本发明涉及一种卤代硫化合物如N-[(1-卤代)-硫代环丁基]-丁二酰亚胺及其制备方法，并公开了此类化合物在磺酰氯与有机胺反应制备磺酰胺中的催化应用。本发明公开的此类卤代硫化合物制备磺酰胺的催化反应，所需的反应条件温和，反应时间短，收率高。该发明无需用到具有较强危险性的氯气，安全，环保，具 有极大的应用价值。The present invention relates to a halogenated sulfur compound such as N-[(1-halo)-thiocyclobutyl]-succinimide and a process for the preparation thereof, and discloses the reaction of such a compound with a sulfonyl chloride and an organic amine. Catalytic applications in the preparation of sulfonamides. The catalytic reaction of the sulfonamide prepared by the halogenated sulfur compound disclosed in the present invention requires mild reaction conditions, short reaction time and high yield. The invention does not need to use a relatively dangerous chlorine gas, is safe and environmentally friendly, and has Great application value.
具体实施方式detailed description
下面的实施例进一步举例说明了本发明的一些特征，但本发明所保护的内容和范围并不受下述实施例的限制。The following examples further illustrate some of the features of the present invention, but the scope and scope of the present invention are not limited by the following examples.
实施例1Example 1
制备N-[(1-氯)-硫代环丁基]-丁二酰亚胺Preparation of N-[(1-chloro)-thiocyclobutyl]-succinimide
将13.3g的N-氯代丁二酰亚胺溶于50ml的二氯甲烷中，搅拌并冷却至15℃，向反应体系中加入8.8g四氢噻吩。搅拌反应30分钟，脱去溶剂，干燥得到标题化合物N-[(1-氯)-硫代环丁基]-丁二酰亚胺约17.5g。13.3 g of N-chlorosuccinimide was dissolved in 50 ml of dichloromethane, stirred and cooled to 15 ° C, and 8.8 g of tetrahydrothiophene was added to the reaction system. The reaction was stirred for 30 minutes, the solvent was evaporated, and then dried to give the title compound N-[(1-chloro)-thiocyclobutyl]-succinimide about 17.5 g.
NMR(CDCl3)δ:1H:1.94(t,4H),2.77(s,4H),2.83(t,4H).NMR (CDCl 3 ) δ: 1 H: 1.94 (t, 4H), 2.77 (s, 4H), 2.83 (t, 4H).
实施例2Example 2
制备N-[(1-溴)-硫代环丁基]-丁二酰亚胺Preparation of N-[(1-bromo)-thiocyclobutyl]-succinimide
将17.8g的N-溴代丁二酰亚胺溶于50ml的二氯甲烷(10ml)和二氯乙烷(40ml)混合溶剂中，搅拌并冷却至15℃，向反应体系中加入8.8g四氢噻吩，搅拌反应30min，脱去溶剂，得到标题化合物N-[(1-氯)-硫代环丁基]-丁二酰亚胺22.5g。17.8 g of N-bromosuccinimide was dissolved in 50 ml of a mixed solvent of dichloromethane (10 ml) and dichloroethane (40 ml), stirred and cooled to 15 ° C, and 8.8 g of four was added to the reaction system. Hydrogenthiophene was stirred for 30 min, and the solvent was evaporated to give the title compound N-[(1-chloro)-thiocyclobutyl]-succinimide 22.5 g.
NMR(CDCl3)δ:1H:2.13(t,4H),2.76(s,4H),3.12(t,4H).NMR (CDCl 3 ) δ: 1 H: 2.13 (t, 4H), 2.76 (s, 4H), 3.12 (t, 4H).
实施例3Example 3
制备N-[(1-溴)-硫代二甲基]-丁二酰亚胺Preparation of N-[(1-bromo)-thiodimethyl]-succinimide
在500ml的三口烧瓶中，加入89g的N-溴代丁二酰亚胺和150ml的二氯甲烷，搅拌并冷却至20℃，向反应体系中加入31g二甲硫醚。搅拌反应1h，脱去溶剂，得到标题化合物N-[(1-氯代)-硫代二甲基]-丁二酰亚胺99.5g。In a 500 ml three-necked flask, 89 g of N-bromosuccinimide and 150 ml of dichloromethane were added, stirred and cooled to 20 ° C, and 31 g of dimethyl sulfide was added to the reaction system. The reaction was stirred for 1 h and the solvent was evaporated to give the title compound N-[(1-chloro)-thiodimethyl]-succinimide 99.5 g.
NMR(CDCl3)δ:1H:2.77(s,4H),2.97(s,6H).NMR (CDCl 3 ) δ: 1 H: 2.77 (s, 4H), 2.97 (s, 6H).
实施例4Example 4
制备N-[(1-氯)-硫代二甲基]-丁二酰亚胺Preparation of N-[(1-chloro)-thiodimethyl]-succinimide
在1000ml的三口烧瓶中，加入133g的N-氯代丁二酰亚胺和400ml的乙腈，搅拌并冷却至20℃，向反应体系中加入62g二甲硫醚。搅拌反应1h，脱去溶剂，得到标题化合物N-[(1-氯代)-硫代二甲基]-丁二酰亚胺167g。In a 1000 ml three-necked flask, 133 g of N-chlorosuccinimide and 400 ml of acetonitrile were added, stirred and cooled to 20 ° C, and 62 g of dimethyl sulfide was added to the reaction system. The reaction was stirred for 1 h, and the solvent was evaporated to ethylamine.
NMR(CDCl3)δ:1H:2.71(s,4H),2.76(s,6H).NMR (CDCl 3 ) δ: 1 H: 2.71 (s, 4H), 2.76 (s, 6H).
实施例5 Example 5
制备1-[(1-氯)-硫代环丁基]-3-氯-5,5-二甲基海因Preparation of 1-[(1-chloro)-thiocyclobutyl]-3-chloro-5,5-dimethylhydantoin
在250ml的三口烧瓶中，加入37g的1,3-二氯-5,5-二甲基海因和100ml的二氯乙烷，搅拌并冷却至20℃，向反应体系中加入17.6g四氢噻吩。搅拌反应30分钟，脱去溶剂，干燥后得到标题化合物1-[(1-氯)-硫代环丁基]-3-氯-5,5-二甲基海因约45g。NMR(CDCl3)δ:1H:1.47(s,6H),1.94(t,4H),2.83(t,4H).In a 250 ml three-necked flask, 37 g of 1,3-dichloro-5,5-dimethylhydantoin and 100 ml of dichloroethane were added, stirred and cooled to 20 ° C, and 17.6 g of tetrahydrogen was added to the reaction system. Thiophene. The reaction was stirred for 30 minutes, and the solvent was evaporated, and then evaporated to give the title compound 1-[(1-chloro)-thiocyclobutyl]-3-chloro-5,5-dimethylhydan. NMR (CDCl 3 ) δ: 1 H: 1.47 (s, 6H), 1.94 (t, 4H), 2.83 (t, 4H).
实施例6Example 6
制备N-[(1-氯)-硫代环丁基]邻苯二甲酰亚胺Preparation of N-[(1-chloro)-thiocyclobutyl]phthalimide
将18.1g的N-氯代邻苯二甲酰亚胺溶于100ml的甲苯中，室温下搅拌加入8.8g的四氢噻吩。加毕反应1小时，脱去溶剂干燥后得到标题化合物N-[(1-氯)-硫代环丁基]邻苯二甲酰亚胺约22g。18.1 g of N-chlorophthalimide was dissolved in 100 ml of toluene, and 8.8 g of tetrahydrothiophene was added with stirring at room temperature. After the reaction was completed for 1 hour, the solvent was evaporated to give the title compound N-[(1-chloro)-thiocyclobutyl]phthalimide about 22 g.
实施例7Example 7
制备N-[(1-氯)-硫代二甲基]-邻苯二甲酰亚胺Preparation of N-[(1-chloro)-thiodimethyl]-phthalimide
将36.1g的N-氯代邻苯二甲酰亚胺溶于200ml的甲苯(150ml)和二甲苯(50ml)的混合溶剂中，室温下搅拌加入12.5g的二甲硫醚。加毕反应2小时，脱去溶剂干燥后得到标题化合物N-[(1-氯)-硫代二甲基]-邻苯二甲酰亚胺40.8g。36.1 g of N-chlorophthalimide was dissolved in a mixed solvent of 200 ml of toluene (150 ml) and xylene (50 ml), and 12.5 g of dimethyl sulfide was added with stirring at room temperature. After the reaction was completed for 2 hours, the solvent was evaporated to give the title compound N-[(1-chloro)-thiodimethyl]-phthalimide 40.8 g.
实施例8Example 8
N-[(1-氯)-硫代环丁基]-丁二酰亚胺催化制备3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯Catalytic preparation of 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazole by N-[(1-chloro)-thiocyclobutyl]-succinimide And [1,5-c]pyrimidin-2-yl)sulfonylamino]benzoic acid methyl ester
将1.33g(0.01mol)的N-氯代丁二酰亚胺溶于150ml的二氯甲烷中，搅拌并冷却至5℃，向反应体系中加入0.88g(0.01mol)四氢噻吩。搅拌反应1h，加入2-胺基-3-氯-苯甲酸甲酯18.5g(0.1mol)，然后再加入吡啶11.85g(0.15mol)。加毕，在体系中加入28g(0.1mol)的5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯，搅拌反应5h。除去溶剂，产品用250ml的甲醇洗涤，干燥后得到3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯36.8g。1.33 g (0.01 mol) of N-chlorosuccinimide was dissolved in 150 ml of dichloromethane, stirred and cooled to 5 ° C, and 0.88 g (0.01 mol) of tetrahydrothiophene was added to the reaction system. The reaction was stirred for 1 h, then 18.5 g (0.1 mol) of 2-amino-3-chloro-benzoic acid methyl ester was added, and then 11.85 g (0.15 mol) of pyridine was further added. After the addition, 28 g (0.1 mol) of 5-ethoxy-7-fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride was added to the system, and the reaction was stirred for 5 hours. . The solvent was removed and the product was washed with 250 mL of methanol to give 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine- Methyl 2-yl)sulfonylamino]benzoate 36.8 g.
NMR(DMSO-d6)δ:1H:1.47(t,3H),3.70(s,3H),4.69(q,2H),7.30-7.75(m,4H),11.03(s,1H).NMR (DMSO- d6 ) δ: 1 H: 1.47 (t, 3H), 3.70 (s, 3H), 4.69 (q, 2H), 7.30-7.75 (m, 4H), 11.03 (s, 1H).
实施例9Example 9
N-[(1-溴)-硫代环丁基]-丁二酰亚胺催化制备3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯 Catalytic preparation of 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazole by N-[(1-bromo)-thiocyclobutyl]-succinimide And [1,5-c]pyrimidin-2-yl)sulfonylamino]benzoic acid methyl ester
将实施例1中制备的化合物N-[(1-溴)-硫代环丁基]-丁二酰亚胺5.32g(0.02mol)投入500ml的烧瓶中，加入250ml的二氯甲烷和二氯乙烷的混合溶剂、23.7g(0.3mol)的吡啶、37g(0.2mol)2-胺基-3-氯-苯甲酸甲酯，搅拌并维持温度在15℃，然后再加入56g(0.2mol)的5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯，搅拌反应4h。除去溶剂，产品用400ml的甲醇洗涤，干燥后得到3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯75g.5.2 g (0.02 mol) of the compound N-[(1-bromo)-thiocyclobutyl]-succinimide prepared in Example 1 was placed in a 500 ml flask, and 250 ml of dichloromethane and dichloride were added. a mixed solvent of ethane, 23.7 g (0.3 mol) of pyridine, 37 g (0.2 mol) of 2-amino-3-chloro-benzoic acid methyl ester, stirred and maintained at a temperature of 15 ° C, and then 56 g (0.2 mol) 5-Ethoxy-7-fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, stirred for 4 h. The solvent was removed and the product was washed with 400 ml of methanol and dried to give 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine- 2-yl)sulfonylamino]benzoic acid methyl ester 75g.
NMR(DMSO-d6)δ:1H:1.47(t,3H),3.70(s,3H),4.69(q,2H),7.30-7.75(m,4H),11.03(s,1H).NMR (DMSO- d6 ) δ: 1 H: 1.47 (t, 3H), 3.70 (s, 3H), 4.69 (q, 2H), 7.30-7.75 (m, 4H), 11.03 (s, 1H).
实施例10Example 10
N-[(1-溴)-硫代二甲基]-丁二酰亚胺催化制备3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯Preparation of 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazole catalyzed by N-[(1-bromo)-thiodimethyl]-succinimide And [1,5-c]pyrimidin-2-yl)sulfonylamino]benzoic acid methyl ester
将实施例2中制备的化合物N-[(1-溴)-硫代二甲基]-丁二酰亚胺3.6g(0.015mol)投入250ml的烧瓶中，加入150ml的二氯甲烷、11.9g(0.15mol)的吡啶、18.5g(0.1mol)2-胺基-3-氯-苯甲酸甲酯，搅拌并维持温度在30℃，然后再加入28g(0.1mol)的5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯，搅拌反应3h。除去溶剂，产品用400ml的甲醇洗涤，干燥后得到3-氯-2-[(5-乙氧基-7-氟-[1,2,4]三唑并[1，5-c]嘧啶-2-基)磺酰氨基]苯甲酸甲酯34.5g.3.6 g (0.015 mol) of the compound N-[(1-bromo)-thiodimethyl]-succinimide prepared in Example 2 was placed in a 250 ml flask, and 150 ml of dichloromethane, 11.9 g was added. (0.15 mol) of pyridine, 18.5 g (0.1 mol) of 2-amino-3-chloro-benzoic acid methyl ester, stirred and maintained at a temperature of 30 ° C, and then 28 g (0.1 mol) of 5-ethoxy- 7-Fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, stirred for 3 h. The solvent was removed and the product was washed with 400 ml of methanol and dried to give 3-chloro-2-[(5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine- Methyl 2-yl)sulfonylamino]benzoate 34.5g.
NMR data(DMSO-d6)δ:1H:1.47(t,3H),3.70(s,3H),4.69(q,2H),7.30-7.75(m,4H),11.03(s,1H).NMR data (DMSO- d6 ) δ: 1 H: 1.47 (t, 3H), 3.70 (s, 3H), 4.69 (q, 2H), 7.30-7.75 (m, 4H), 11.03 (s, 1H).
实施例11Example 11
N-[(1-氯)-硫代环丁基]-丁二酰亚胺催化制备N-(2,4-二氯-5-(4-二氟甲基-4,5-二氢-3-甲基-5-氧代-1H-1,2,4-三唑-1-基)苯基)甲磺酰胺Preparation of N-(2,4-dichloro-5-(4-difluoromethyl-4,5-dihydro-) catalyzed by N-[(1-chloro)-thiocyclobutyl]-succinimide 3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide
将4g(0.03mol)的N-氯代丁二酰亚胺溶于150ml的二氯乙烷中，搅拌并冷却至15℃，向反应体系中加入2.7g(0.03mol)四氢噻吩。搅拌反应30分钟，加入2,4-二氯-5-(4-二氟甲基-3-甲基-5-氧-4,5-二氢-1,2,4-三唑)苯胺30.9g(0.1mol)，然后再加入吡啶15g(0.19mol)。加毕，在体系中加入13.8g(0.12mol)的甲基磺酰氯，搅拌反应5h。除去溶剂，产品用250ml的乙醇洗涤，干燥后得到N-(2,4-二氯-5-(4-二氟甲基-4,5-二氢-3-甲基-5-氧代-1H-1,2,4-三唑-1-基)苯基)甲磺酰胺20.5g。4 g (0.03 mol) of N-chlorosuccinimide was dissolved in 150 ml of dichloroethane, stirred and cooled to 15 ° C, and 2.7 g (0.03 mol) of tetrahydrothiophene was added to the reaction system. The reaction was stirred for 30 minutes and 2,4-dichloro-5-(4-difluoromethyl-3-methyl-5-oxo-4,5-dihydro-1,2,4-triazole)aniline 30.9 was added. g (0.1 mol), followed by the addition of 15 g (0.19 mol) of pyridine. After the addition, 13.8 g (0.12 mol) of methylsulfonyl chloride was added to the system, and the reaction was stirred for 5 hours. The solvent was removed and the product was washed with 250 ml of ethanol and dried to give N-(2,4-dichloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo- 1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide 20.5 g.
NMR data(DMSO-d6)δ:1H:2.41(s,3H),3.13(s,3H),7.52(t,1H,J＝57Hz),7.70(s, 1H),7.98(s,1H),9.81(s,1H)；MS([M-H]-)：384.8.NMR data (DMSO- d6 ) δ: 1 H: 2.41 (s, 3H), 3.13 (s, 3H), 7.52 (t, 1H, J = 57 Hz), 7.70 (s, 1H), 7.98 (s, 1H) , 9.81 (s, 1H); MS ([MH] - ): 384.8.
实施例12Example 12
N-[(1-氯)-硫代环丁基]-丁二酰亚胺和1-[(1-氯)-硫代环丁基]-3-氯-5,5-二甲基海因混合催化制备2,6-二氟-5-甲基(1,2,4)-三唑并(1,5-a)嘧啶-2-磺酰苯胺N-[(1-chloro)-thiocyclobutyl]-succinimide and 1-[(1-chloro)-thiocyclobutyl]-3-chloro-5,5-dimethyl sea Preparation of 2,6-difluoro-5-methyl(1,2,4)-triazolo(1,5-a)pyrimidine-2-sulfonanilide by mixed catalysis
在500ml的三口烧瓶中，加入200ml的二氯甲烷(100ml)和二氯乙烷(100ml)混合溶剂，加毕，加入0.57g(0.002mol)1-[(1-氯)-硫代环丁基]-3-氯-5,5-二甲基海因和0.66g(0.003mol)N-[(1-氯)-硫代环丁基]-丁二酰亚胺、2,6-二氟苯胺12.9g(0.1mol)，三乙胺16.5g(0.15mol)。加毕，搅拌30分钟，加入23.3g(0.1mol)5-甲基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯，搅拌反应3-5小时。除去溶剂，产品用250ml的甲醇洗涤，干燥后得到2,6-二氟-5-甲基(1,2,4)-三唑并(1,5-a)嘧啶-2-磺酰苯胺24.3g。In a 500 ml three-necked flask, 200 ml of a mixed solvent of dichloromethane (100 ml) and dichloroethane (100 ml) was added, and after adding, 0.57 g (0.002 mol) of 1-[(1-chloro)-thiocyclobutane was added. 3-chloro-5,5-dimethylhydantoin and 0.66 g (0.003 mol) of N-[(1-chloro)-thiocyclobutyl]-succinimide, 2,6-di Fluoraniline 12.9 g (0.1 mol), and triethylamine 16.5 g (0.15 mol). After the addition, the mixture was stirred for 30 minutes, and 23.3 g (0.1 mol) of 5-methyl-[1,2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride was added, and the reaction was stirred for 3-5 hours. The solvent was removed and the product was washed with 250 ml of methanol to give 2,6-difluoro-5-methyl(1,2,4)-triazolo(1,5-a)pyrimidine-2-sulfonanilide 24.3. g.
实施例13Example 13
N-[(1-氯)-硫代环丁基]邻苯二甲酰亚胺催化制备N-(2,6-二氯-3-甲基苯基)-5,7-二甲氧基-1,2,4-三唑[1,5-a]嘧啶-2-磺酰胺Preparation of N-(2,6-dichloro-3-methylphenyl)-5,7-dimethoxy by N-[(1-chloro)-thiocyclobutyl]phthalimide -1,2,4-triazole [1,5-a]pyrimidine-2-sulfonamide
在500ml的三口烧瓶中，加入200ml的甲苯，加毕，加入2.69g(0.01mol)N-[(1-氯)-硫代环丁基]邻苯二甲酰亚胺、2,6-二氯-3-甲基苯胺17.6g(0.1mol)，喹啉19.4g(0.15mol)。加毕，搅拌30分钟，加入27.9g(0.1mol)5,7-二甲氧基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯，搅拌反应3-5小时。除去溶剂，产品用250ml的甲醇洗涤，干燥后得到N-(2,6-二氯-3-甲基苯基)-5,7-二甲氧基-1,2,4-三唑[1,5-a]嘧啶-2-磺酰胺29.2g。In a 500 ml three-necked flask, 200 ml of toluene was added, and after adding, 2.69 g (0.01 mol) of N-[(1-chloro)-thiocyclobutyl]phthalimide, 2,6-di was added. Chloro-3-methylaniline 17.6 g (0.1 mol), quinoline 19.4 g (0.15 mol). After the addition, stirring for 30 minutes, adding 27.9 g (0.1 mol) of 5,7-dimethoxy-[1,2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride, stirring reaction 3 -5 hours. The solvent was removed and the product was washed with 250 ml of methanol and dried to give N-(2,6-dichloro-3-methylphenyl)-5,7-dimethoxy-1,2,4-triazole [1] , 5-a] pyrimidine-2-sulfonamide 29.2 g.
实例14Example 14
N-[(1-氯)-硫代二甲基]-邻苯二甲酰亚胺催化制备N-(2,6-二氯苯基)-5-乙氧基-7-氟-[1,2,4]三唑并[1,5-c]嘧啶-2-磺酰胺Preparation of N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-[1] by N-[(1-chloro)-thiodimethyl]-phthalimide ,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide
将实例7制备的0.49g(0.02mol)N-[(1-氯)-硫代二甲基]-邻苯二甲酰亚胺溶于150ml的乙腈中，搅拌反应30分钟，加入2，6-二氯苯胺16g(0.1mol)，然后再加入吡啶11.85g(0.15mol)。加毕，在体系中加入28g(0.1mol)的5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯，搅拌反应3-5小时。除去溶剂，产品用250ml的甲醇洗涤，干燥后得到N-(2,6-二氯苯基)-5-乙氧基-7-氟-[1,2,4]三唑并[1,5-c]嘧啶-2-磺酰胺约33.7g。 0.49 g (0.02 mol) of N-[(1-chloro)-thiodimethyl]-phthalimide prepared in Example 7 was dissolved in 150 ml of acetonitrile, and the reaction was stirred for 30 minutes, and 2,6 was added. Dichloroaniline 16 g (0.1 mol), followed by the addition of 11.85 g (0.15 mol) of pyridine. After the addition, 28 g (0.1 mol) of 5-ethoxy-7-fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride was added to the system, and the reaction was stirred. -5 hours. The solvent was removed and the product was washed with 250 ml of methanol to give N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5. -c] pyrimidine-2-sulfonamide about 33.7 g.

Claims (14)

  1. 一种卤代硫化合物(I)，其特征在于其结构式如下：A halogenated sulfur compound (I) characterized by the following structural formula:
    Figure PCTCN2015073736-appb-100001
    Figure PCTCN2015073736-appb-100001
    式中：In the formula:
    X代表Cl、Br、I；X represents Cl, Br, I;
    R1代表C1-C5的烷基、C6-C12芳基；R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    R2代表C1-C5的烷基、C6-C12的芳基；R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    或R1和R2一起代表C2-C5的亚甲基；Or R 1 and R 2 together represent a C 2 -C 5 methylene group;
    Q的结构式为：The structural formula of Q is:
    Figure PCTCN2015073736-appb-100002
    Figure PCTCN2015073736-appb-100002
    n为0-4，其中n为1时，卤代硫化合物(I)不为结构式(L)：n is 0-4, wherein when n is 1, the halogenated sulfur compound (I) is not structural formula (L):
    Figure PCTCN2015073736-appb-100003
    Figure PCTCN2015073736-appb-100003
    或Q的结构式为：Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100004
    Figure PCTCN2015073736-appb-100004
    或Q的结构式为：Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100005
    Figure PCTCN2015073736-appb-100005
    Y为Cl、Br、I。Y is Cl, Br, I.
  2. 根据权利要求1所述的一种卤代硫化合物(I)，其特征在于所述的Q的结构式为：
    Figure PCTCN2015073736-appb-100006
    时，所述的卤代硫化合物(I)的结构式为：    A halogenated sulfur compound (I) according to claim 1, wherein the structural formula of Q is:
    Figure PCTCN2015073736-appb-100006
    When the halogenated sulfur compound (I) has the structural formula:
    Figure PCTCN2015073736-appb-100007
    Figure PCTCN2015073736-appb-100007
    其中R1，R2，X，Q，n的定义与权利要求1中的定义相同。Wherein R 1 , R 2 , X, Q, n have the same definitions as defined in claim 1.
  3. 一种卤代硫化合物(I)的制备方法，其特征是将化合物(II)与化合物(III)在有机溶剂中反应得到卤代硫化合物(I)，A method for preparing a halogenated sulfur compound (I), characterized in that a compound (II) and a compound (III) are reacted in an organic solvent to obtain a halogenated sulfur compound (I).
    其中化合物(II)的结构式为：Wherein the structural formula of the compound (II) is:
    Figure PCTCN2015073736-appb-100008
    Figure PCTCN2015073736-appb-100008
    化合物(III)的结构式为：The structural formula of the compound (III) is:
    Figure PCTCN2015073736-appb-100009
    Figure PCTCN2015073736-appb-100009
    其中R1，R2，X，Q的定义与权利要求1中的定义相同。Wherein R 1 , R 2 , X, Q have the same definitions as in claim 1.
  4. 根据权利要求3所述的卤代硫化合物(I)的制备方法，其特征在于所述的化合物(II)与化合物(III)优选摩尔比在1:1-3:1之间。The process for producing a halogenated sulfur compound (I) according to claim 3, characterized in that the compound (II) and the compound (III) are preferably in a molar ratio of from 1:1 to 3:1.
  5. 根据权利要求3所述的卤代硫化合物(I)的制备方法，其特征在于所述的有机溶剂优选二氯甲烷、二氯乙烷、氯仿、四氯化碳、乙腈、甲苯、二甲苯中的一种或多种。The method for producing a halogenated sulfur compound (I) according to claim 3, wherein the organic solvent is preferably dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene or xylene. One or more.
  6. 一种卤代硫化合物的应用，其特征在于应用卤代硫化合物制备磺酰胺(IV)，其中卤代硫化合物的结构式为： The use of a halogenated sulfur compound is characterized in that a sulfonamide (IV) is prepared by using a halogenated sulfur compound, wherein the structural formula of the halogenated sulfur compound is:
    Figure PCTCN2015073736-appb-100010
    Figure PCTCN2015073736-appb-100010
    R1代表C1-C5的烷基、C6-C12芳基；R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    R2代表C1-C5的烷基、C6-C12的芳基；R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    或R1和R2一起代表C2-C5的亚甲基；Or R 1 and R 2 together represent a C 2 -C 5 methylene group;
    Q的结构式为：The structural formula of Q is:
    Figure PCTCN2015073736-appb-100011
    Figure PCTCN2015073736-appb-100011
    n为0-4；n is 0-4;
    或Q的结构式为：Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100012
    Figure PCTCN2015073736-appb-100012
    或Q的结构式为：Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100013
    Figure PCTCN2015073736-appb-100013
    Y为Cl、Br、I；Y is Cl, Br, I;
    磺酰胺(IV)的结构式为：The structural formula of sulfonamide (IV) is:
    Figure PCTCN2015073736-appb-100014
    Figure PCTCN2015073736-appb-100014
    W代表C1-C4烷基、芳基、杂芳基；W represents C 1 -C 4 alkyl, aryl, heteroaryl;
    G代表C1-C4烷基、芳基、杂芳基。G represents a C 1 -C 4 alkyl group, an aryl group, or a heteroaryl group.
  7. 根据权利要求6所述的一种卤代硫化合物的应用，其特征在于所述的磺酰胺(IV)的制备方法为：催化剂卤代硫化合物(I')存在下，磺酰氯化合物(V)与胺化合物(VI)，在有机碱、有机溶剂体系中，-50℃-100℃反应制得磺酰胺(IV)； 其中，磺酰氯化合物(V)的结构式为：The use of a halogenated sulfur compound according to claim 6, characterized in that the sulfonamide (IV) is prepared by a catalyst of a halogenated sulfur compound (I') in the presence of a sulfonyl chloride compound (V). The sulfonamide (IV) is obtained by reacting with the amine compound (VI) in an organic base or an organic solvent system at -50 ° C to 100 ° C; Wherein, the structural formula of the sulfonyl chloride compound (V) is:
    Figure PCTCN2015073736-appb-100015
    Figure PCTCN2015073736-appb-100015
    胺化合物(VI)的结构式为：The structural formula of the amine compound (VI) is:
    Figure PCTCN2015073736-appb-100016
    Figure PCTCN2015073736-appb-100016
    磺酰胺(IV)的结构式为：The structural formula of sulfonamide (IV) is:
    Figure PCTCN2015073736-appb-100017
    Figure PCTCN2015073736-appb-100017
    式中：In the formula:
    W代表C1-C4烷基、芳基、杂芳基；W represents C 1 -C 4 alkyl, aryl, heteroaryl;
    G代表C1-C4烷基、芳基、杂芳基。G represents a C 1 -C 4 alkyl group, an aryl group, or a heteroaryl group.
  8. 根据权利要求6或7所述的卤代硫化合物的应用，其特征在于所述的卤代硫化合物(I')，是如下结构式中的任意一个或多个的组合；The use of the halogenated sulfur compound according to claim 6 or 7, wherein the halogenated sulfur compound (I') is a combination of any one or more of the following structural formulas;
    卤代硫化合物(I')的结构式为：The structural formula of the halogenated sulfur compound (I') is:
    Figure PCTCN2015073736-appb-100018
    Figure PCTCN2015073736-appb-100018
    其中Q的结构式为：The structural formula of Q is:
    Figure PCTCN2015073736-appb-100019
    Figure PCTCN2015073736-appb-100019
    n为0-4；n is 0-4;
    或Q的结构式为：Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100020
    Figure PCTCN2015073736-appb-100020
    或Q的结构式为： Or the structural formula of Q is:
    Figure PCTCN2015073736-appb-100021
    Figure PCTCN2015073736-appb-100021
    Y为Cl、Br、I；Y is Cl, Br, I;
    R1代表C1-C5的烷基、C6-C12芳基；R 1 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    R2代表C1-C5的烷基、C6-C12的芳基；R 2 represents a C 1 -C 5 alkyl group, a C 6 -C 12 aryl group;
    或R1和R2一起代表C2-C5的亚甲基。Or R 1 and R 2 together represent a C 2 -C 5 methylene group.
  9. 根据权利要求6或7的所述的卤代硫化合物的应用，其特征在于所述的Q的结构式为：
    Figure PCTCN2015073736-appb-100022
    时，所述的卤代硫化合物(I')的结构式为：    The use of a halogenated sulfur compound according to claim 6 or 7, characterized in that the structural formula of Q is:
    Figure PCTCN2015073736-appb-100022
    When the halogenated sulfur compound (I') has the structural formula:
    Figure PCTCN2015073736-appb-100023
    Figure PCTCN2015073736-appb-100023
    R1，R2，X，n定义同权利要求6。R 1 , R 2 , X, n are as defined in claim 6.
  10. 根据权利要求6或7的所述的卤代硫化合物的应用，其特征在于所述的磺酰氯化合物(V)是甲基磺酰氯、2-(2,2-二氟乙氧基)-6-(三氟甲基)-苯基磺酰氯、5-乙氧基-7-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯、5-甲氧基-8-氟-[1,2,4]三唑-[1,5,c]嘧啶-2-磺酰氯、5-甲基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯,5,7-二甲氧基-[1,2,4]三唑-[1,5,a]嘧啶-2-磺酰氯。Use of the halogenated sulfur compound according to claim 6 or 7, characterized in that the sulfonyl chloride compound (V) is methylsulfonyl chloride, 2-(2,2-difluoroethoxy)-6 -(trifluoromethyl)-phenylsulfonyl chloride, 5-ethoxy-7-fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, 5-methyl Oxy-8-fluoro-[1,2,4]triazole-[1,5,c]pyrimidine-2-sulfonyl chloride, 5-methyl-[1,2,4]triazole-[1,5 , a] pyrimidine-2-sulfonyl chloride, 5,7-dimethoxy-[1,2,4]triazole-[1,5,a]pyrimidine-2-sulfonyl chloride.
  11. 根据权利要求6或7中的所述的卤代硫化合物的应用，其特征在于所述胺化合物(VI)是2,6-二氯苯胺、2,6-二氟苯胺、2-胺基-3-氯-苯甲酸甲酯、2,6-二氯-3-甲基苯胺、2,4-二氯-5-(4-二氟甲基-3-甲基-5-氧-4,5-二氢-1,2,4-三唑)苯胺、5,8-二甲氧基-[1,2,4]三唑-[1,5-c]嘧啶-2-胺。Use of a halogenated sulfur compound according to claim 6 or 7, characterized in that the amine compound (VI) is 2,6-dichloroaniline, 2,6-difluoroaniline, 2-amino group- Methyl 3-chloro-benzoate, 2,6-dichloro-3-methylaniline, 2,4-dichloro-5-(4-difluoromethyl-3-methyl-5-oxo-4, 5-Dihydro-1,2,4-triazole) aniline, 5,8-dimethoxy-[1,2,4]triazole-[1,5-c]pyrimidin-2-amine.
  12. 根据权利要求6或7所述的卤代硫化合物的应用，其特征在于有机碱是烷基胺、吡啶、甲基吡啶、烟酰胺、喹啉的一种或多种；有机溶剂是二氯甲烷、二氯乙烷、氯仿、四氯化碳、乙腈、甲苯、二甲苯的一种或多种。 The use of the halogenated sulfur compound according to claim 6 or 7, wherein the organic base is one or more of an alkylamine, a pyridine, a picoline, a nicotinamide or a quinoline; and the organic solvent is dichloromethane. One or more of dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene, and xylene.
  13. 根据权利要求6或7所述的卤代硫化合物的应用，其特征在于所述的温度优选在0℃-40℃之间。Use of a halogenated sulfur compound according to claim 6 or 7, characterized in that the temperature is preferably between 0 °C and 40 °C.
  14. 根据权利要求6或7所述的卤代硫化合物的应用，其特征在于所述的卤代硫化合物(I')的用量为磺酰氯化合物(V)摩尔数的1％到30％。 The use of the halogenated sulfur compound according to claim 6 or 7, characterized in that the halogenated sulfur compound (I') is used in an amount of from 1% to 30% by mole based on the mole of the sulfonyl chloride compound (V).
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