CN110240533B - Preparation method of N, N-dimethyl sulfonamide derivative - Google Patents

Preparation method of N, N-dimethyl sulfonamide derivative Download PDF

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CN110240533B
CN110240533B CN201910622055.9A CN201910622055A CN110240533B CN 110240533 B CN110240533 B CN 110240533B CN 201910622055 A CN201910622055 A CN 201910622055A CN 110240533 B CN110240533 B CN 110240533B
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nitrophenyl
aromatic ring
tert
dimethylsulfonamide
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CN110240533A (en
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车志平
田月娥
陈根强
刘圣明
姜佳
林晓民
杨进明
孙迪
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Henan University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
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    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
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Abstract

The invention discloses a preparation method of N, N-dimethyl sulfonamide derivatives, and belongs to the technical field of synthesis of medicinal compounds. The invention comprises the following components in a molar ratio of (1.0-2.0): (1.2-4.0): (1.5-6.0) Giantreed alkali, a reactant with sulfonyl chloride group and an alkaline substance, and a solvent CH2Cl2、CH3COCH3、CH3CN is reacted at a temperature of-15-80 ℃ for 24-48 h to obtain the N, N-dimethyl sulfonamide derivative simply, efficiently and inexpensively, and the yield reaches 70-98%.

Description

Preparation method of N, N-dimethyl sulfonamide derivative
Technical Field
The invention relates to a preparation method of N, N-dimethyl sulfonamide derivatives, belonging to the technical field of pesticide preparation.
Background
Giantreed alkali (N, N-dimethylamino-3-methylindole) widely exists in plants such as barley, is an alkaloid with allelopathy generated in the plant evolution process, and has certain effect of inhibiting the growth of environmental plants, insects and microorganisms.
Sulfonamides exhibit a wide range of biological activities, e.g. nematicidal, bacteriostatic (oomycete, fungal, bacterial), anticonvulsant, 5-HT6Receptor antagonists, and the like. There are generally two methods for synthesizing the currently reported N, N-dimethylarylsulfonamide derivatives: first, sulfonamide intermediate is synthesized and further reacted with methyl iodide ("Design and synthesis of sulfonamide as novel cardiac myosin activator", Manickam M., Jalani H.B., Pilaiyar T., Boggu P.R., Sharma N.., Venkatesvarao E., Lee Y.J., Jeon E.S., Son M.J., Woo S.H., Jung S.H., Eur.J.Med.Chem., 2018, Vol.143, p.1869-. Second, Sulfonyl chlorides were directly reacted with N, N-dimethylamino to give ("8-sulfomethylated tetrahydro-1H-pyrido [4,3-b ]]indoles as 5-HT6 receptor antagonists”，Ivachtchenko A.V.，Mitkin O.D.，Tkachenko S.E.，Okun I.M.，Kysil V.M，Eur.J.Med.Chem.2010,45,782-789)。
However, the above-mentioned production method has problems of expensive raw materials, complicated process and low yield.
Disclosure of Invention
The invention aims to provide a preparation method of N, N-dimethyl sulfonamide derivatives, which aims to solve the problems of expensive raw materials, complex process and low yield in the prior art.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a preparation method of N, N-dimethyl sulfonamide derivatives comprises the following steps:
(1) reacting arundoin, a reactant with sulfonyl chloride groups, an alkaline substance and a solvent to obtain a reaction solution; the solvent is CH2Cl2、CH3COCH3、CH3Any one of CN; the Giantreed alkali is a reactant with sulfonyl chloride groups, and the molar ratio of alkaline substances is (1.0-2.0): (1.2-4.0): (1.5-6.0); the reaction temperature is-15 DEG CThe reaction time is 24-48 h at the temperature of-80 ℃;
(2) and (2) separating the reaction liquid in the step (1) to obtain the N, N-dimethyl sulfonamide derivative.
The invention selects the giantreed alkali and the reactant with sulfonyl chloride group as raw materials, and selects the alkaline substance and CH2Cl2、CH3COCH3、CH3Any one of CN is used as a solvent, the reaction time is 24-48 h at the reaction temperature of-15-80 ℃, and the N, N-dimethyl sulfonamide derivative can be obtained after separation; the Giantreed alkali is a reactant with sulfonyl chloride groups, and the molar ratio of an alkaline substance to a solvent is (1.0-2.0): (1.2-4.0): (1.5-6.0).
The raw material of the arundoin selected in the preparation method has low price and is easy to obtain the reactant with the sulfonyl chloride group, and the raw material of the arundoin, the reactant with the sulfonyl chloride group, the alkaline substance and the solvent are subjected to simple reaction to obtain the N, N-dimethyl sulfonamide derivative, so that the production process of the N, N-dimethyl sulfonamide derivative is greatly simplified, and the yield reaches 70-98 percent.
In order to further improve the reaction efficiency and the yield, it is preferable that the reactant having sulfonyl chloride group in step (1) is represented by formula 2:
Figure BDA0002125820350000021
in the formula 2, R is a substituent or halogen formed by any one of alkane, alkene, alkyne, aromatic hydrocarbon, substituted alkane, substituted alkene, substituted alkyne and substituted aromatic hydrocarbon;
the structural formula of the obtained NN-dimethyl sulfonamide derivative is shown as a formula 3:
Figure BDA0002125820350000022
in formula 3, R is a substituent composed of any one of alkane, alkene, alkyne, aromatic hydrocarbon, substituted alkane, substituted alkene, substituted alkyne, and substituted aromatic hydrocarbon, or halogen.
In order to further improve the reaction efficiency and the yield, preferably, the alkaline substance in the step (1) is LiOH, NaOH, KOH, Mg (OH)2、Ca(OH)2、Al(OH)3、Li2CO3、Na2CO3、K2CO3、Et3And N is any one of the above.
In order to further improve the reaction efficiency and the yield, preferably, the alkaline substance in the step (1) is NaOH, and a catalyst TEBA is also contained; the molar ratio of the Giantreed alkali, the reactant with sulfonyl chloride group, the alkaline substance and the catalyst TEBA is (1.0-2.0): (1.2-2.4): (1.8-3.6): (0.1 to 0.2); the solvent is CH2Cl2(ii) a The reaction temperature is-15 ℃ to 0 ℃, and the reaction time is 24 to 48 hours.
In order to further improve the reaction efficiency and the yield, it is preferable that the basic substance in the step (1) is K2CO3(ii) a The Giantreed alkali is a reactant with sulfonyl chloride groups, and the molar ratio of alkaline substances is (1.0-2.0): (2.0-4.0): (3.0-6.0); the solvent is CH2Cl2、CH3Any one of CN; the reaction temperature is 25-40 ℃, and the reaction time is 24-48 h.
In order to further improve the reaction efficiency and the yield, it is preferable that the basic substance in the step (1) is Et3N; the reaction temperature is 25-80 ℃, and the reaction time is 24-48 h. Based on the above technical scheme, in order to further improve the yield, it is further preferable that the solvent in the step (1) is CH3CN。
In order to further improve the separation efficiency, it is preferable that, before the separation in the step (2), the reaction solution in the step (1) is further concentrated under reduced pressure, and CH is added2Cl2And water, extracting, washing, drying and concentrating. Based on the above technical scheme, in order to further improve the yield, it is further preferable that the separation in the step (2) is performed by silica gel column chromatography.
To further improve the yield, preferably, the reactant having sulfonyl chloride group in step (1) is represented by formula 2:
Figure BDA0002125820350000031
in the formula 2, R is any one of a single aromatic ring, a substituted single aromatic ring, a fused aromatic ring and a substituted fused aromatic ring; the substituent in the substituted single aromatic ring or the substituted condensed aromatic ring is respectively and independently selected from at least one of methyl, methoxy, ethoxy, tert-butyl, isopropyl, nitro, fluorine, chlorine and bromine;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure BDA0002125820350000032
in the formula 3, R is any one of a single aromatic ring, a substituted single aromatic ring, a fused aromatic ring and a substituted fused aromatic ring; the substituent groups in the substituted single aromatic ring or the substituted condensed aromatic ring are respectively and independently selected from at least one of methyl, methoxy, ethoxy, tert-butyl, isopropyl, nitro, fluorine, chlorine and bromine. Based on the technical scheme, in order to further improve the yield, the single aromatic ring is preferably any one of a benzene ring, a five-membered heterocyclic ring or a six-membered heterocyclic ring; the heteroatom in the five-membered heterocycle or the six-membered heterocycle is at least one of nitrogen, sulfur and oxygen. Based on the above technical scheme, in order to further improve the yield, it is further preferable that the fused aromatic ring is a polycyclic organic compound formed by two or more carbocyclic rings or heterocyclic rings sharing a ring edge, and has aromaticity; the hetero atom in the hetero ring is at least one of nitrogen, sulfur and oxygen.
To further improve the yield, preferably, the reactant having sulfonyl chloride group in step (1) is represented by formula 2:
Figure BDA0002125820350000041
in the formula 2, R is phenyl, p-methylphenyl, o-methylphenyl, m-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, m-methoxyphenyl, p-ethoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, mesitylenyl, 2,4, 6-triisopropylbenzenesulfonyl chloride, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-2-nitrophenyl, 4-chloro-3-nitrophenyl, 3-chloro-2-nitrophenyl, Any one of 4-nitro-2-chlorphenyl, 4-nitro-3-chlorphenyl, 3-nitro-2-chlorphenyl, thienyl, naphthyl and quinolyl;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure BDA0002125820350000042
in the formula 3, R is phenyl, p-methylphenyl, o-methylphenyl, m-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, m-methoxyphenyl, p-ethoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, mesitylenyl, 2,4, 6-triisopropylbenzenesulfonyl chloride, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-2-nitrophenyl, 4-chloro-3-nitrophenyl, 3-chloro-2-nitrophenyl, 4-nitro-2-chlorphenyl, 4-nitro-3-chlorphenyl, 3-nitro-2-chlorphenyl, thienyl, naphthyl and quinolyl.
In order to further improve the yield, so that the yield reaches 76% -98%, preferably, the reactant having sulfonyl chloride group in step (1) is represented by formula 2:
Figure BDA0002125820350000051
in the formula 2, R is any one of phenyl, p-methylphenyl, p-methoxyphenyl, 4-tert-butylphenyl, mesityl, 2,4, 6-triisopropylphenyl, 4-fluorophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-3-nitrophenyl, 2-thienyl, 1-naphthyl and 8-quinolyl;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure BDA0002125820350000052
in the formula 3, R is any one of phenyl, p-methylphenyl, p-methoxyphenyl, 4-tert-butylphenyl, mesityl, 2,4, 6-triisopropylphenyl, 4-fluorophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-3-nitrophenyl, 2-thienyl, 1-naphthyl and 8-quinolyl.
Specifically, the reactant having a sulfonyl chloride group is a compound containing a sulfonyl chloride group. The alkaline substance is a substance that provides an alkaline environment. The N, N-dimethyl sulfonamide derivative with the structural formula shown in formula 3 is respectively numbered as 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 3N and 3o when R is respectively selected from phenyl, p-methylphenyl, p-methoxyphenyl, 4-tert-butylphenyl, mesityl, 2,4, 6-triisopropylphenyl, 4-fluorophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-3-nitrophenyl, 2-thienyl, 1-naphthyl and 8-quinolyl, and the corresponding structural formulas are shown as the following table:
Figure BDA0002125820350000053
Figure BDA0002125820350000061
Figure BDA0002125820350000071
drawings
FIG. 1 is a hydrogen spectrum of N, N-dimethylsulfonamide derivatives 3a according to examples 1 and 16 to 20 of the present invention;
FIG. 2 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3b of example 2 of the present invention;
FIG. 3 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3c according to example 3 of the present invention;
FIG. 4 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3d of example 4 of the present invention;
FIG. 5 is a hydrogen diagram of N, N-dimethylsulfonamide derivative 3e of example 5 of the present invention;
FIG. 6 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3f of example 6 of the present invention;
FIG. 7 is a hydrogen spectrum of 3g of an N, N-dimethylsulfonamide derivative of example 7 of the present invention;
FIG. 8 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative of example 8 for 3 h;
FIG. 9 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3i according to example 9 of the present invention;
FIG. 10 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3j according to example 10 of the present invention;
FIG. 11 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3k according to example 11 of the present invention;
FIG. 12 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3l according to example 12 of the present invention;
FIG. 13 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3m according to example 13 of the present invention;
FIG. 14 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3N according to example 14 of the present invention;
FIG. 15 is a hydrogen spectrum of N, N-dimethylsulfonamide derivative 3o according to example 15 of the present invention.
Detailed Description
The following examples are provided to further illustrate the practice of the invention. In the following examples, Arundina graminis, benzenesulfonyl chloride, p-methylbenzenesulfonyl chloride, p-methoxybenzenesulfonyl chloride, 4-tert-butylbenzenesulfonyl chloride, mesitylenesulfonyl chloride, 2,4, 6-triisopropylbenzenesulfonyl chloride, 4-fluorobenzenesulfonyl chloride, 4-bromobenzenesulfonyl chloride, 2-nitrobenzenesulfonyl chloride, 3-nitrobenzenesulfonyl chloride, 4-chloro-3-nitrobenzenesulfonyl chloride, thiophene-2-sulfonyl chloride, 1-naphthalenesulfonyl chloride, 8-quinolinesulfonyl chloride, CH2Cl2、CH3COCH3、CH3CN、LiOH、NaOH、KOH、Mg(OH)2、Ca(OH)2、Al(OH)3、Li2CO3、Na2CO3、K2CO3、Et3N, TEBA, water, flask, adding, stirring, extracting, washing, drying, concentrating, separating and other equipment and raw materials can be obtained through the conventional commercial channel. Silica gel column chromatography: silica gel is used as 200-mesh and 300-mesh column chromatography silica gel, the column is a 4 x 300cm glass column, and the column is packed by a wet method.
Example 1 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of benzene sulfonyl chloride shown as formula 2a into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000081
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Example 2 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 b:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of p-methylbenzenesulfonyl chloride shown as formula 2b into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000082
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 b.
Example 3 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 c:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of p-methoxybenzenesulfonyl chloride shown as formula 2c into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000091
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 c.
Example 4 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 d:
(1) adding 1mmol of Giantreed alkali N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 4-tert-butylbenzenesulfonyl chloride shown as formula 2d into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000092
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 d.
Example 5 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 e:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of mesitylenesulfonyl chloride shown as formula 2e into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000101
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 e.
Example 6 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 f:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 2,4, 6-triisopropylbenzenesulfonyl chloride shown as formula 2f into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000102
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 f.
Example 7 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 g:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 4-fluorobenzenesulfonyl chloride shown as formula 2g into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000111
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 g.
Example 8 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 h:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 4-bromobenzenesulfonyl chloride shown as formula 2h into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000112
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in formula 3 h.
Example 9 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 i:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 2-nitrobenzenesulfonyl chloride shown as formula 2i into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000113
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 i.
Example 10 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 j:
(1) 1mmol of arundoin shown in formula 1Adding N, N-dimethylamino-3-methylindole and 1.5mmol of 3-nitrobenzenesulfonyl chloride shown as formula 2j into a flask with the volume of 50mL, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000121
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 j.
Example 11 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 k:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 4-nitrobenzenesulfonyl chloride shown as formula 2k into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000122
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 k.
Example 12 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 l:
(1) 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of arundoin shown as formula 2l 4-chloro-3-nitrobenzenesulfonyl chloride, indicated by the formula I, was charged into a 50 mL-capacity flask, 10mL of CH was added3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000131
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 l.
Example 13 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 m:
(1) adding 1mmol of Giantreed base N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of thiophene-2-sulfonyl chloride shown as formula 2m into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000132
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 m.
Example 14 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method of preparing compound 3 n:
(1) adding 1mmol of Giantreed alkali N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 1-naphthalene sulfonyl chloride shown as formula 2N into 50mL of calcined sodaIn a bottle, add 10mL CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000141
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3N.
Example 15 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
Preparation of compound 3 o:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 1.5mmol of 8-quinolinesulfonyl chloride shown as formula 2o into a 50mL flask, and adding 10mL of CH3CN was dissolved completely, 1.5mmol Et was added slowly3N, stirring and reacting for 24 hours at 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000142
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 o.
Example 16 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as a formula 1, 1.2mmol of benzene sulfonyl chloride shown as a formula 2a, 1.8mmol of KOH and 0.1mmol of catalyst TEBA into a 50mL flask, adding 10mL of dichloromethane to completely dissolve the materials, and stirring and reacting for 24 hours at-15 ℃ to obtain a reaction solution; the reaction formula is shown as follows:
Figure BDA0002125820350000151
(2) adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Example 17 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1, 2.0mmol of benzenesulfonyl chloride shown as formula 2a and 3.0mmol of Na2CO3Into a 50mL capacity flask, 10mL CH was added3CN is completely dissolved, and the mixture is stirred and reacted for 24 hours at the temperature of 25 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000152
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Example 18 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 2.0mmol of benzene sulfonyl chloride shown as formula 2a into a 50mL flask, adding 10mL of CH2Cl2Dissolve it completely, add 4.5mmol Et slowly3N, stirring and reacting for 24 hours at 40 ℃ to obtain reaction liquid; inverse directionThe formula should be as follows:
Figure BDA0002125820350000153
(2) adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Example 19 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 2.0mmol of benzene sulfonyl chloride shown as formula 2a into a 50mL flask, adding 10mL of CH3CN was dissolved completely, 4.5mmol Et was added slowly3N, stirring and reacting for 24 hours at the temperature of 80 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000161
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Example 20 of the Process for preparing N, N-dimethylsulfonamide derivatives of the invention
A method for preparing compound 3 a:
(1) adding 1mmol of arundoin N, N-dimethylamino-3-methylindole shown as formula 1 and 2.0mmol of benzene sulfonyl chloride shown as formula 2a into a 50mL flask, adding 10mL of CH3COCH3Dissolve it completely, add 4.5mmol Et slowly3N, stirring and reacting for 24 hours at 56 ℃ to obtain reaction liquid; the reaction formula is shown as follows:
Figure BDA0002125820350000162
(2) concentrating the dry reaction solution under reduced pressure, adding CH2Cl2And mixing with water, extracting, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, concentrating, evaporating to remove the solvent, and separating by silica gel column chromatography to obtain the N, N-dimethyl sulfonamide derivative shown in the formula 3 a.
Test example:
melting point and nmr spectrum test runs:
the results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 1 show that: the N, N-dimethyl sulfonamide derivative shown in the formula 3a is yellow oily liquid, the yield is 79 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 2 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3b is yellow oily liquid, the melting point is 79-80 ℃, the yield is 88 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ 7.67(d, J ═ 8.0Hz,2H),7.34(d, J ═ 8.0Hz,2H),2.69(s,6H),2.44(s, 3H); HRMS (ESI) Calcd for C9H14NO2S([M+H]+),200.0740；found,200.0745。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 3 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3c is brown solid, the melting point is 73-74 ℃, the yield is 98 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.70-7.73(m,2H),6.99-7.03(m,2H),3.88(s,3H),2.68(s, 6H); HRMS (ESI) Calcd for C9H14NO3S([M+H]+),216.0689；found,216.0690。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 4 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3d is a white solid, the melting point is 118-119 ℃, the yield is 86 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.68-7.71(m,2H),7.52-7.56(m,2H),2.71(s,6H),1.35(s, 9H); HRMS (ESI) Calcd for C12H20NO2S([M+H]+),242.1209；found,242.1211。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 5 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3e is yellow oily liquid, the yield is 89 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ 6.94-6.95(m,2H),2.73(s,6H),2.61(s,6H),2.30(s, 3H); HRMS (ESI) Calcd for C11H18NO2S([M+H]+),228.1053；found,228.1055。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 6 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3f is a light yellow solid, the melting point is 122-123 ℃, the yield is 76 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.16(s,2H),4.14-4.20(m,2H),2.86-2.93(m,1H),2.75(s,6H),1.23-1.26(m, 18H); HRMS (ESI) Calcd for C17H30NO2S([M+H]+),312.1992；found,312.1995。
The N, N-dimethylsulfonic acid obtained in example 7 was addedThe amide derivatives are subjected to melting point and nuclear magnetic resonance spectrum test tests, and the results show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3g is brown solid, the melting point is 75-76 ℃, the yield is 82 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.82(m,2H),7.20-7.27(m,2H),2.71(s, 6H); HRMS (ESI) Calcd for C8H11FNO2S([M+H]+),204.0489；found,204.0490。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 8 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3h is a white solid, the melting point is 91-92 ℃, the yield is 89 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.67-7.70(m,2H),7.62-7.65(m,2H),2.71(s, 6H); HRMS (ESI) Calcd for C8H11BrNO2S([M+H]+),263.9688；found,263.9693。
The N, N-dimethylsulfonamide derivative obtained in example 9 was subjected to melting point and nmr spectrum test tests, and the yield was 83%, and the results showed that: the N, N-dimethyl sulfonamide derivative shown as the formula 3i is yellow oily liquid, and the nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.94-7.99(m,1H),7.67-7.74(m,2H),7.60-7.63(m,1H),2.91(s, 6H); HRMS (ESI) Calcd for C8H11N2O4S([M+H]+),231.0434；found,231.0435。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 10 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3j is light yellow solid, the melting point is 121-122 ℃, the yield is 96 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 8.62 (t),J＝2.0Hz,1H),8.46-8.48(m,1H),8.10-8.13(m,1H),7.77-7.81(m,1H),2.79(s,6H)；HRMS(ESI):Calcd for C8H11N2O4S([M+H]+),231.0434；found,231.0431。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 11 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3k is light yellow solid, the melting point is 175-176 ℃, the yield is 86 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 8.38-8.42(m,2H),7.96-7.99(m,2H),2.78(s, 6H); HRMS (ESI) Calcd for C8H11N2O4S([M+H]+),231.0434；found,231.0437。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 12 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3l is violet solid, the melting point is 102-103 ℃, the yield is 84 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ 8.25(d, J ═ 2.0Hz,1H),7.92(dd, J ═ 8.4Hz,2.0Hz,1H),7.77(d, J ═ 8.4Hz,1H),2.797(s, 6H); HRMS (ESI) Calcd for C8H10ClN2O4S([M+H]+),265.0044；found,265.0048。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 13 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3m is brown solid, the melting point is 67-68 ℃, the yield is 87 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ:7.63(dd, J ═ 5.2Hz,1.2Hz,1H),7.56(dd, J ═ 3.6Hz,1.2Hz,1H),7.17(dd, J ═ 5.2Hz,4.0Hz,1H),2.75(s, 6H); HRMS (ESI) Calcd for C6H10NO2S2([M+H]+),192.0147；found,192.0148。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 14 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3N is yellow oily liquid, the yield is 90 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ 8.76-8.79(m,1H),8.21(dd, J ═ 7.2Hz,1.2Hz,1H),8.06-8.09(m,1H),7.92-7.94(m,1H),7.53-7.67(m,3H),2.82(s, 6H); HRMS (ESI) Calcd for C12H14NO2S([M+H]+),236.0740；found,236.0745。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 15 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3o is light yellow solid, the melting point is 130-131 ℃, the yield is 82 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: δ 9.08-9.10(m,1H),8.47-8.50(m,1H),8.26(dd, J ═ 8.0Hz,1.6Hz,1H),8.05(dd, J ═ 8.0Hz,1.2Hz,1H),7.61-7.65(m,1H),7.54(q, J ═ 4.4Hz,1H),2.99(s, 6H); HRMS (ESI) Calcd for C11H13N2O2S([M+H]+),237.0692；found,237.0689。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 16 show that: the N, N-dimethyl sulfonamide derivative shown in the formula 3a is yellow oily liquid, the yield is 29 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 17 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3a is yellowA oily liquid, yield 63%, NMR spectrum: (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 18 show that: the N, N-dimethyl sulfonamide derivative shown as the formula 3a is yellow oily liquid, the yield is 51 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 19 show that: the N, N-dimethyl sulfonamide derivative shown in the formula 3a is yellow oily liquid, the yield is 78 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
The results of melting point and nmr spectrum tests on the N, N-dimethylsulfonamide derivative obtained in example 20 show that: the N, N-dimethyl sulfonamide derivative shown in the formula 3a is yellow oily liquid, the yield is 32 percent, and a nuclear magnetic resonance spectrum (1H NMR, 400MHz) features: substitution of deuterium with CDCl3TMS is an internal standard, where the peak assignments are: delta 7.77-7.80(m,2H),7.53-7.63(m,3H),2.71(s, 6H); HRMS (ESI) Calcd for C8H12NO2S([M+H]+),186.0583；found,186.0585。
Southern root knot nematode killing activity assay:
the N, N-dimethyl sulfonamide derivatives 3a to 3o obtained in the above examples 1 to 20 and a commercial nematicide Emamectin benzoate, namely Emamectin benzoate, were used for activity determination of killing Meloidogyne incognita, the tested nematode was Meloidogyne incognita (Kofold & White) Chitwood, and the determination method employed was the dipping method, and the detailed method was as follows: the poisoning activity of the medicament on the nematode is measured by adopting an immersion method reported by Giannakou et al, and the method is slightly improved and specifically operated as follows:
sucking 2mL of liquid medicine to be detected (N, N dimethyl aromatic sulfonamide derivatives 3 a-3 o with concentration gradients of 0.20mg/L, 0.25mg/L, 0.30mg/L, 0.35mg/L and 0.40mg/L respectively), placing the liquid medicine into surface dishes with diameters of 6cm, respectively picking 50 surface-sterilized adult Meloidogyne incognita J2 into each dish, respectively treating the adult Meloidogyne incognita J2 in a constant-temperature incubator at 25 ℃ for 12h, judging the death and survival condition of the Meloidogyne by using a needle stick touch method under an anatomical lens, and calculating the death rate. Drug treatment was repeated 3 times for each mass concentration, and 2 times distilled water treatment was used as a control. Independent experiments were repeated 3 times and the results are shown in table 2.
Table 2: n, N-dimethyl aryl sulfonamide compound in-vitro activity determination result for killing meloidogyne incognita
Figure BDA0002125820350000211
Figure BDA0002125820350000221
The result shows that the N, N-dimethyl aromatic sulfonamide derivative has obvious effect on preventing the meloidogyne incognita, can be used for preventing and treating the meloidogyne incognita, and can be further used for preparing a novel nematicide.

Claims (7)

1. A preparation method of N, N-dimethyl sulfonamide derivatives is characterized by comprising the following steps:
(1) reacting arundoin, a reactant with sulfonyl chloride groups, an alkaline substance and a solvent to obtain a reaction solution; the solvent is CH2Cl2、CH3COCH3、CH3Any one of CN; the Giantreed alkali is a reactant with sulfonyl chloride groups, and the molar ratio of alkaline substances is (1.0-2.0): (1.2-4.0): (1.5-6.0); the reaction temperature is-15-25 ℃, and the reaction time is 24-48 h;
(2) separating the reaction liquid in the step (1) to obtain N, N-dimethyl sulfonamide derivatives;
in the step (1), the alkaline substance is LiOH, NaOH, KOH, Mg (OH)2、Ca(OH)2、Al(OH)3、Li2CO3、Na2CO3、K2CO3、Et3Any one of N;
the reactant with sulfonyl chloride group in the step (1) is shown as a formula 2:
Figure FDA0003470702070000011
in the formula 2, R is any one of a single aromatic ring, a substituted single aromatic ring, a fused aromatic ring and a substituted fused aromatic ring; the substituent in the substituted single aromatic ring or the substituted condensed aromatic ring is respectively and independently selected from at least one of methyl, methoxy, ethoxy, tert-butyl, isopropyl, nitro, fluorine, chlorine and bromine;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure FDA0003470702070000012
in the formula 3, R is any one of a single aromatic ring, a substituted single aromatic ring, a fused aromatic ring and a substituted fused aromatic ring; the substituent in the substituted single aromatic ring or the substituted condensed aromatic ring is respectively and independently selected from at least one of methyl, methoxy, ethoxy, tert-butyl, isopropyl, nitro, fluorine, chlorine and bromine;
the monocyclic aromatic ring is any one of a benzene ring, a five-membered heterocyclic ring or a six-membered heterocyclic ring; the heteroatom in the five-membered heterocycle or the six-membered heterocycle is at least one of nitrogen, sulfur and oxygen;
the fused aromatic ring is a polycyclic organic compound formed by two or more carbocyclic rings or heterocyclic rings to share a ring edge, and has aromaticity; the hetero atom in the hetero ring is at least one of nitrogen, sulfur and oxygen.
2. The process for producing an N, N-dimethylsulfonamide derivative according to claim 1, wherein the basic substance in the step (1) is NaOH, and further comprises a catalyst TEBA; the molar ratio of the Giantreed alkali, the reactant with sulfonyl chloride group, the alkaline substance and the catalyst TEBA is (1.0-2.0): (1.2-2.4): (1.8-3.6): (0.1 to 0.2); the solvent is CH2Cl2(ii) a The reaction temperature is-15 ℃ to 0 ℃, and the reaction time is 24 to 48 hours.
3. The process for producing N, N-dimethylsulfonamide derivatives according to claim 1, wherein the basic substance in the step (1) is K2CO3(ii) a The Giantreed alkali is a reactant with sulfonyl chloride groups, and the molar ratio of alkaline substances is (1.0-2.0): (2.0-4.0): (3.0-6.0); the solvent is CH2Cl2、CH3Any one of CN; the reaction temperature is 25 ℃, and the reaction time is 24-48 h.
4. The process for producing N, N-dimethylsulfonamide derivatives according to claim 1, wherein the basic substance in the step (1) is Et3N; the reaction temperature is 25 ℃, and the reaction time is 24-48 h.
5. The process for producing an N, N-dimethylsulfonamide derivative according to claim 1, wherein before the separation in the step (2), the reaction solution in the step (1) is concentrated under reduced pressure, methylene chloride and water are added, followed by extraction, and the organic phases are combined, washed, dried and concentrated.
6. The method for preparing N, N-dimethyl sulfonamide derivative according to any one of claims 1 to 5, wherein the reactant having a sulfonyl chloride group in the step (1) is represented by formula 2:
Figure FDA0003470702070000021
in the formula 2, R is phenyl, p-methylphenyl, o-methylphenyl, m-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, m-methoxyphenyl, p-ethoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, mesitylenyl, 2,4, 6-triisopropylbenzenesulfonyl chloride, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-2-nitrophenyl, 4-chloro-3-nitrophenyl, 3-chloro-2-nitrophenyl, Any one of 4-nitro-2-chlorphenyl, 4-nitro-3-chlorphenyl, 3-nitro-2-chlorphenyl, thienyl, naphthyl and quinolyl;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure FDA0003470702070000022
in the formula 3, R is phenyl, p-methylphenyl, o-methylphenyl, m-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, m-methoxyphenyl, p-ethoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, mesitylenyl, 2,4, 6-triisopropylbenzenesulfonyl chloride, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-2-nitrophenyl, 4-chloro-3-nitrophenyl, 3-chloro-2-nitrophenyl, 4-nitro-2-chlorphenyl, 4-nitro-3-chlorphenyl, 3-nitro-2-chlorphenyl, thienyl, naphthyl and quinolyl.
7. The method for preparing N, N-dimethyl sulfonamide derivative according to any one of claims 1 to 5, wherein the reactant having a sulfonyl chloride group in the step (1) is represented by formula 2:
Figure FDA0003470702070000031
in the formula 2, R is any one of phenyl, p-methylphenyl, p-methoxyphenyl, 4-tert-butylphenyl, mesityl, 2,4, 6-triisopropylphenyl, 4-fluorophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-3-nitrophenyl, 2-thienyl, 1-naphthyl and 8-quinolyl;
in the step (2), the structural formula of the obtained N, N-dimethyl sulfonamide derivative is shown as a formula 3:
Figure FDA0003470702070000032
in the formula 3, R is any one of phenyl, p-methylphenyl, p-methoxyphenyl, 4-tert-butylphenyl, mesityl, 2,4, 6-triisopropylphenyl, 4-fluorophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-chloro-3-nitrophenyl, 2-thienyl, 1-naphthyl and 8-quinolyl.
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